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Copyrights ©

Dar Jalees Alzaman for Publishing & Distribution

Jordan - Amman - Queen Rania Street - Opposite the College
of Agriculture Al-Assaf Building - Ground Floor
Tel.: 0096265343052Fax: 0096265356219
Third Edition 2023

The Hashemite Kingdom of Jordan

The Deposit Number at The National Library
(2022/ 7 /3628)

616.3

Al Afeef, Amjad Kamal

Medico Notes Internal Medicine / Amjad Kamal Al Afeef.-
3rd.ed – Amman: Dar Jalees Al-Zaman for Publishing And
Distribution,2022
Descriptors:/ Internal Medicine //Diseases//Therapy/

ISBN:978-9957-81-551-6
The author takes full legal responsibility for the contents of this
book, which do not necessarily reflect the viewpoint of the
National Library or any other government department.

All rights reserved.

No part of this book may be translated, reproduced, stored in a
retrieval system, or transmitted in any form or by any means,
electronic or mechanical, including photocopying and recording,
without the prior written permission of the publisher

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 Disclaimer
The medical advices in this book are
derived from the best practices and
are not considered exhaustive nor
intended to replace local
procedures.
The book is based on my own
personal knowledge and
experience!

Amjad K. AlAfeef

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 ‫تنويه هام‪:‬‬
‫هناك مجموعة من المواد العلمية الداعمة لهذا الكتاب على‬
‫شكل شروحات تفاعلية ومسجلة ودورات تعقد باستمرار‬
‫على مدار العام‪ ,‬كما ويوجد بنك أسئلة يحتوي على االف‬
‫األسئلة المتوقعة في االمتحان وكذلك بطاقات فالش كارد‬
‫تساعدك على دراسة وحفظ المادة العلمية في هذا الكتاب‪.‬‬
‫للتسجيل في الدورات أو الحصول على بنك األسئلة‬
‫والمادة العلمية المكملة للكتاب يرجى التواصل مع المؤلف‬
‫أو فريق عمله‪:‬‬

‫‪Dr. Amjad K. AlAfeef‬‬

‫‪Phone: 00962798843824‬‬
‫‪Email: Afeeef.2005@gmail.com‬‬
‫‪Website: www.MedicoJo.com‬‬

‫‪P a g e |ix‬‬
P a g e |x
Table of content
Copyrights © ......................................................................................... iv
Disclaimer ............................................................................................ viii
Table of content .................................................................................... xi
Table of tables ..................................................................................... xv
Table of Figures ..................................................................................... xx
Nephrology ............................................................................................ 1
The kidney function test (KFT)............................................................ 2
Arterial blood gases ........................................................................... 7
Acute kidney injury (AKI) ................................................................. 11
Introduction to the glomerular diseases ........................................ 19
Disorders of nephrotic syndrome .................................................... 23
Disorders of nephritic syndrome ..................................................... 24
Chronic Kidney disease (CKD) ........................................................ 30
Cystic diseases of the kidney .......................................................... 33
Electrolyte disturbances .................................................................. 35
Inherited defects of the nephron ................................................... 41
HTN .................................................................................................... 44
Endocrinology ...................................................................................... 47
Introduction to the Endocrinology ................................................. 48
The pituitary gland ........................................................................... 49
The Thyroid gland ............................................................................. 56
Parathyroid gland ............................................................................ 62
Adrenal gland .................................................................................. 67
Diabetes mellitus (DM)..................................................................... 72
Hypoglycemia .................................................................................. 83
Other endocrine disorders .............................................................. 85
Pulmonology ........................................................................................ 91

P a g e |xi
 Pulmonary Function Test (PFT) .........................................................92
Obstructive lung diseases ................................................................95
Interstitial lung diseases (ILD) ......................................................... 105
Respiratory infections ..................................................................... 110
Pleural diseases ............................................................................... 119
Other respiratory disorders ............................................................. 122
Cardiology .......................................................................................... 129
Diseases of the heart conduction ................................................. 130
Diseases of the myocardium ......................................................... 143
Diseases of Endocardium .............................................................. 164
Pericardial diseases ........................................................................ 172
Other cardiology problems ........................................................... 175
Gastroenterology ............................................................................... 177
Introduction to gastroenterology .................................................. 178
Disorders of the esophagus ........................................................... 179
Stomach and Small intestine ......................................................... 184
Disorders of the large intestine ...................................................... 200
Hepatology ........................................................................................ 207
Introduction to hepatology ........................................................... 208
Acute liver diseases ........................................................................ 212
Chronic liver diseases ..................................................................... 218
Complications of liver cirrhosis ...................................................... 224
Liver storage diseases .................................................................... 228
Hematology........................................................................................ 231
Introduction to Hematology .......................................................... 232
Blood products and transfusion .................................................... 242
Anemia of reduced RBC production............................................ 245
Anemia of high RBC destruction ................................................... 254

P a g e |xii
 Disorders of primary hemostasis .................................................... 265
Disorders of secondary hemostasis............................................... 270
Myeloproliferative disorders .......................................................... 276
Malignant white cell disorders ...................................................... 279
Rheumatology ................................................................................... 291
Introduction to Rheumatology ..................................................... 292
Raynaud’s disease ......................................................................... 295
Erythema nodosum........................................................................ 296
Stevens-Johnson syndrome (SJS) .................................................. 297
Rheumatoid arthritis (RA) .............................................................. 298
Systemic lupus erythematosus (SLE) ............................................. 302
Antiphospholipid syndrome (APS) ................................................ 305
Systemic sclerosis (SS) .................................................................... 306
Sjögren's syndrome ........................................................................ 307
Mixed connective tissue disease (MCTD) .................................... 308
Spondyloarthropathies .................................................................. 308
Osteoarthritis (OA) ......................................................................... 312
Neuropathic joint (Charcot joint) ................................................. 314
Infective arthritis ............................................................................. 315
Crystal-induced arthropathies ...................................................... 317
Vasculitis ......................................................................................... 320
Dermatomyositis ............................................................................. 323
Fibromyalgia ................................................................................... 324
Neurology........................................................................................... 325
Introduction to neurology ............................................................. 326
Thunderclap headache ................................................................ 331
Headache Syndromes................................................................... 333
Acute stroke ................................................................................... 337

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 Epilepsy............................................................................................ 339
Status Epilepticus ............................................................................ 341
Essential tremor ............................................................................... 341
Dementia ........................................................................................ 342
Parkinson's disease (PD) ................................................................. 344
Alcoholic encephalopathies ......................................................... 345
Neurological autoimmune disorders ............................................ 346
Amyotrophic lateral sclerosis (ALS) ............................................... 349
CNS infections ................................................................................. 350
Organophosphate poisoning ........................................................ 352
Common ENT conditions ............................................................... 354
Infectious diseases ............................................................................. 357
Principles of microbiology .............................................................. 358
Pyrexia of unknown origin (PUO) ................................................... 359
Bacterial infections ......................................................................... 360
Viral infections ................................................................................. 367
Sexually transmitted diseases ........................................................ 372
Common parasites ......................................................................... 375
Clinical pharmacology ...................................................................... 379
Drugs and their antidotes .............................................................. 380
Antibiotics........................................................................................ 380
Drugs used in DM ............................................................................ 386
Common cardiac medications .................................................... 388
GI medications ............................................................................... 392
Analgesics ....................................................................................... 394
Corticosteroids ................................................................................ 395
Cyclosporine ................................................................................... 396

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Table of tables
Table 1: Cockcroft-Gault equation for GFR ........................................ 3
Table 2: Tubular vs Glomerular proteinuria .......................................... 4
Table 3: Serum and urine anion gap ................................................... 9
Table 4: The estimated HCO3 and PaCO2 in gas disorders .............. 10
Table 5: Pre-renal azotemia vs ATN .................................................... 15
Table 6: Summary of Tubular diseases ............................................... 18
Table 7: Primary and secondary glomerular diseases ...................... 19
Table 8: PSGN vs. IgA nephropathy ................................................... 25
Table 9: cANCA vs. pANCA ................................................................ 27
Table 10: WHO classification for lupus nephritis ................................ 29
Table 11: CKD stages according to GFR ........................................... 31
Table 12: Types of renal osteodystrophy............................................ 31
Table 13: Indications for hemodialysis................................................ 32
Table 14: Acute on top of chronic renal failure ................................ 32
Table 15: Acute vs. Chronic renal failure ........................................... 32
Table 16: Water deficit calculation .................................................... 35
Table 17: Sodium deficit calculation.................................................. 37
Table 18: common IV fluids and their compositions per liter ........... 37
Table 19: anti-hyperkalemia protocol................................................ 39
Table 20: Laboratory features of RTA types ....................................... 42
Table 21: Genetic syndromes that affect the renal tubules ............ 43
Table 22: Important points about renal artery stenosis..................... 45
Table 23: The drug of choice for HTN in specific groups .................. 45
Table 24: Features of DIDMOD syndrome.......................................... 54
Table 25: disorders of thyrotoxicosis and their unique features ....... 59
Table 26: Hypothyroidism vs. Hyperthyroidism................................... 60
Table 27: Pseudohypocalcemia and corrected calcium ............... 63
Table 28: Differential diagnosis of parathyroid disorders.................. 66
Table 29: Lab tests in primary hypoadrenalism ................................. 69
Table 30: Comparison between T1DM vs. T2DM ............................... 74
Table 31: Glucose investigations and their ranges ........................... 76
Table 32: Health maintenance for all DM patients ........................... 77
Table 33: DKA vs. HHS .......................................................................... 83
Table 34: Treatment of hypoglycemia in babies .............................. 84

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Table 35: Types of Multiple Endocrine Neoplasia (MEN) ...................85
Table 36 Normal and abnormal values of BMI for adults..................87
Table 37: Obstructive vs. Restrictive lung diseases ............................93
Table 38: causes of high vs. low DLco ................................................94
Table 39: Causes of hypoxia according to the A-a gradient ..........94
Table 40: Asthma classification according to the severity ...............96
Table 41: classification of acute asthma exacerbation ...................98
Table 42: Asthma controllers and relievers medications ................ 100
Table 43: Staging of COPD ................................................................ 100
Table 44: Indications for LTOT ............................................................ 102
Table 45:causes of Upper vs. Lower zone lung fibrosis .................... 105
Table 46: Typical vs. atypical pneumonia ........................................ 111
Table 47: Differential diagnosis of pneumonia ................................ 111
Table 48: CURB65 score for pneumonia prognosis .......................... 112
Table 49: indications for the pneumococcal vaccine ................... 113
Table 50: Mantoux test interpretation .............................................. 117
Table 51: the side effects of Anti-TB medications ............................ 118
Table 52: Causes of Exudative and Transudative pleural effusion . 119
Table 53: Modified lights criteria ....................................................... 120
Table 54: causes of Type 1 vs. Type 2 respiratory failure ................. 125
Table 55: Axis deviation interpretation in ECG ................................ 131
Table 56: ECG changes in different conditions ............................... 132
Table 57: CA2DS2 VAS scoring system ............................................... 135
Table 58: Causes of long QT syndrome and TdP ............................. 138
Table 59: the ECG changes in the different degrees of AV block 140
Table 60: CABG indications and graft used .................................... 145
Table 61: Types and contraindications of stress test ....................... 146
Table 62: Stable vs. Unstable angina................................................ 147
Table 63: TIMI score for UA and NSTEMI ............................................ 151
Table 64: Complications of myocardial infarction .......................... 154
Table 65: BNP rule in the diagnosis of SOB ....................................... 157
Table 66: Heart sounds and their causes ......................................... 169
Table 67: Features and causes of different types of Pulses ............ 170
Table 68: Causes of different types of heart murmurs..................... 170
Table 69: Doses of adrenalin and hydrocortisone in anaphylaxis.. 175

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Table 70: The differential diagnosis of epigastric pain ................... 184
Table 71: Different types of H. pylori tests ........................................ 188
Table 72: Gastric vs. Duodenal ulcer ............................................... 189
Table 73: Rockall Score for risk of death in upper GI bleeding ...... 192
Table 74: The sites for absorption of different nutrients................... 194
Table 75: Causes of bloody vs. non-bloody diarrhea ..................... 196
Table 76: differences between IBD types ........................................ 200
Table 77: Clinical features of CD vs. UC .......................................... 201
Table 78: Extraintestinal manifestations in CD and UC ................... 201
Table 79: Complications of CD vs. UC ............................................. 202
Table 80: Treatment of UC ................................................................ 203
Table 81: treatment of CD ................................................................ 203
Table 82: Alarm symptoms for IBS ..................................................... 205
Table 83: Bilirubin metabolism........................................................... 210
Table 84: General information about hepatitis viruses ................... 212
Table 85: HBV markers interpretation ............................................... 214
Table 86: Poor prognostic factors of FHF ......................................... 217
Table 87: Poor prognostic factors of paracetamol-induced liver
failure .................................................................................................. 217
Table 88: Child-Pugh score for liver cirrhosis .................................... 219
Table 89: PBC vs. PSC ........................................................................ 222
Table 90: Differential diagnosis of ascites ........................................ 224
Table 91: the laboratory tests used in assessing hemostasis........... 233
Table 92: The clotting factors affecting PT and PTT ........................ 233
Table 93: Clotting factors names and numbers .............................. 233
Table 94: Blood film interpretation ................................................... 236
Table 95: Unfractionated vs. LMWH ................................................. 237
Table 96: warfarin-induced skin necrosis ......................................... 238
Table 97: Warfarin drug interactions ................................................ 239
Table 98: Heparin vs. Warfarin .......................................................... 240
Table 99: Causes of anemia according to the MCV ..................... 246
Table 100: The normal dietary allowance of iron............................ 246
Table 101: Expected lab tests in IDA ................................................ 247
Table 102: Vitamins B12 vs. folate ...................................................... 251
Table 103: schilling test interpretation (Low: < 3%, Normal: > 7%).. 254

P a g e |xvii
Table 104: Causes of Intravascular and Extravascular hemolysis .. 254
Table 105: Expected lab results in hemolytic anemia ..................... 255
Table 106: Warm vs. cold AIHA ......................................................... 263
Table 107: Types of HIT syndrome ..................................................... 267
Table 108: Interpretation of the blood test results ........................... 272
Table 109: Virchow's triad (the risk factors for hypercoagulability) 272
Table 110: Difference between normal and thrombosed veins .... 273
Table 111: Well's Criteria, A scoring system for the diagnosis of PE 275
Table 112: Causes of massive splenomegaly .................................. 282
Table 113: Ann-Arbor staging of lymphoma .................................... 285
Table 114: Hodgkin vs. Non-Hodgkin lymphoma ............................ 286
Table 115: Side effects of the lymphomas drugs ............................. 286
Table 116: Common gene translocations in hematology .............. 287
Table 117: Diagnostic criteria for multiple myeloma ....................... 288
Table 118: Classifications of arthritis .................................................. 292
Table 119: Joint aspiration rule in different types of arthritis ........... 292
Table 120: The acute phase reactant; CRP ..................................... 293
Table 121: autoantibodies and their associated disorders ............. 293
Table 122: Types of hypersensitivity................................................... 294
Table 123: different HLA types and the associated disorders ........ 294
Table 124: Raynaud’s Phenomenon ................................................ 296
Table 125: Stevens-Johnson vs. Toxic Epidermis Necrolysis ............. 297
Table 126: The diagnostic criteria for RA .......................................... 298
Table 127: DMARDs and their side effects ....................................... 302
Table 128: antibodies associated with SLE ....................................... 303
Table 129: causes of markedly elevated or markedly low ESR ...... 322
Table 130: the cranial nerves ............................................................ 328
Table 131: UMNL vs. LMNL.................................................................. 330
Table 132: types of deep tendon reflexes and their nerve roots ... 330
Table 133: Differential diagnosis of Thunderclap headache ......... 331
Table 134: The red flags (alarm symptoms) of headache .............. 331
Table 135: Differential diagnosis of Headache syndromes ............ 333
Table 136: ABCD2 score for TIA patients .......................................... 338
Table 137: Antiepileptic drugs (AEDs) and their indications ........... 340
Table 138: The most common causes of meningitis ........................ 350

P a g e |xviii
Table 139: CSF interpretation for meningitis patients ...................... 351
Table 140: Empirical antibiotic treatment in meningitis .................. 351
Table 141: Systemic effects of Organophosphate poisoning ........ 353
Table 142: Species of brucella and their most common sources .. 360
Table 143: WHO recommendations for tetanus vaccine (TV) and
tetanus immunoglobulin administration .......................................... 365
Table 144: Diseases affecting HIV patients ...................................... 374
Table 145: Species of Plasmodium and their characteristics ......... 376
Table 146: Common drugs and their antidotes .............................. 380
Table 147: antibiotics classification and their site of action ........... 381
Table 148: antibiotic classification and their type of action .......... 381
Table 149: cephalosporine generations .......................................... 383
Table 150: the bacterial coverage in cephalosporines ................. 383
Table 151: Antipseudomonal agents ............................................... 385
Table 152: The different types of insulin ........................................... 387

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Table of Figures
Figure 1: Physiology of renin-angiotensin system .................................6
Figure 2: IVP showing Ring shadow ....................................................17
Figure 3: RBC cast in urine consistent with glomerulonephritis .........21
Figure 4: A characteristic rash of HSP .................................................28
Figure 5: ECG changes in Hyperkalemia ...........................................38
Figure 6: Treatment approach for HTN ...............................................46
Figure 7: Example of the negative feedback ....................................49
Figure 8: Diagnostic approach to Cushing's syndrome ....................68
Figure 9: Mnemonics for MEN types....................................................85
Figure 10: The normal lung volumes for a healthy 70 kg male .........93
Figure 11: A stepwise approach to asthma control ..........................97
Figure 12: (a) normal chest X-Ray, (b) Hyperinflated chest............ 101
Figure 13: A chest X-ray showing Air fluid level (Lung abscess) ..... 118
Figure 14: chest X-Ray showing bilateral pleural effusion ............... 120
Figure 15: Different types of Chest deformities ................................ 127
Figure 16: the heart conduction system ........................................... 130
Figure 17: strep rhythm ECG showing sinus tachycardia ................ 133
Figure 18: strep rhythm ECG showing sinus bradycardia ................ 133
Figure 19: strep rhythm ECG showing Sick Sinus Syndrome ............ 134
Figure 20: a strep rhythm ECG showing Atrial fibrillation ................. 134
Figure 21: the approach for Atrial fibrillation treatment ................. 135
Figure 22: a strep rhythm ECG showing Atrial flutter ....................... 136
Figure 23: A strep rhythm ECG showing MAT ................................... 136
Figure 24: A strep rhythm ECG showing SVT..................................... 137
Figure 25: A strep rhythm ECG showing Ventricular tachycardia .. 137
Figure 26: A strep rhythm ECG showing Torsade de points ............ 138
Figure 27: A strep rhythm ECG showing Bigeminy ........................... 138
Figure 28: A strep rhythm ECG showing Ventricular Fibrillation ...... 139
Figure 29: A strep rhythm ECG showing Delta wave ...................... 139
Figure 30: anatomy of the coronary artery ...................................... 150
Figure 31: One beat ECG showing epsilon wave ............................ 162
Figure 32: A sketch showing an Atrial myxoma ............................... 163
Figure 33: a) Osler nodes, B) Janeway lesions, C) Roth spots......... 165
Figure 34: Pericardiocentesis procedure ......................................... 173

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Figure 35: A sketch showing the alimentary tract ........................... 178
Figure 36: A sketch showing achalasia. ........................................... 182
Figure 37: The gastric acid secretion and drugs effect on it.......... 185
Figure 38: The suspensory Ligament of Treitz ................................... 190
Figure 39: The liver and biliary tree ................................................... 208
Figure 40: Bilirubin metabolism and excretion ................................. 210
Figure 41: The coagulation cascade in secondary hemostasis .... 232
Figure 42: The normal hematopoiesis .............................................. 234
Figure 43: Hand Joints deformities in Rheumatoid Arthritis ............. 299
Figure 44: Anatomy of the sacroiliac joint ....................................... 309
Figure 45: Joint X-Ray shows Chondrocalcinosis ............................. 319
Figure 46: Erythema migrans in Lyme disease ................................. 363

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P a g e |xxii
 Nephrology
CHAPTER 1

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 The kidney function test (KFT)
The normal functions of the kidneys are:
- Excretion of waste products and drugs
- Regulation of the body fluid and compositions
- Secretion of erythropoietin, renin, and prostaglandins
- Metabolism of Vitamin D

Urea and creatinine

The serum urea (Ur):
- Urea (Ur) is the product of protein catabolism, filtered by
nephron and 30 – 70% reabsorbed back into the blood
- Blood urea nitrogen (BUN) is the nitrogenous content of
urea; it equals the serum urea divided by 2.14
- Both uremia and azotemia are related to renal impairment.
- Azotemia is the presence of nitrogenous substances in the
blood, while uremia is the presence of urea.
The serum creatinine (Cr):
- Creatinine (Cr) is the product of muscle destruction and is
freely excreted but not reabsorbed by nephron
- A reduction or loss of muscle mass because of advanced
age, liver failure, or malnutrition may cause a relatively lower
serum creatinine concentration. In these scenarios, the
serum creatinine and GFR will overestimate kidney function.
BUN to Creatinine ratio (BUN/Cr):
- The normal BUN to Cr ratio is 20:1
- In dehydration, urea will increase while creatinine remains
normal. Therefore, if the ratio becomes > 20:1, the cause is
pre-renal (renal hypoperfusion)
- If the BUN:Cr ratio is 20:1 or less, intra-renal or post-renal
pathologies are the causes.

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 Glomerular filtration rate (GFR)
- GFR measures the amount of plasma filtered across the
glomerular capillaries.
- The normal daily GFR is 100 – 120 ml/min
- At the high levels of GFR, small changes in serum creatinine
level will reflect a large change in the GFR and vice versa in
the low levels.
- GFR is reduced in acute and chronic renal failure
- Serum urea and creatinine do not rise in the case of renal
failure until a 50 – 60% reduction of GFR, so normal urea and
creatinine do not exclude renal insufficiency
GFR calculation: (there are 3 equations)
- The Cockcroft-Gault equation is the least accurate one
- Modification of Diet in Renal Disease (MDRD) study equation
performs best when GFR is <60 mL/min/1.73 m2
- Chronic Kidney Disease Epidemiology (CKD-EPI)
Collaboration equation performs better at near-normal GFR
values

[(140 – age) * body weight * 0.85 for female] / (72* creatinine mg/dl)
Table 1: Cockcroft-Gault equation for GFR

Urinary protein
Normal and abnormal protein in urine:
- It is normal to excrete a tiny amount of protein (known as
Tamm-Horsfall protein) (normal daily loss of < 150 mg/day)
- Proteinuria indicates tubular or glomerular disease; severe
proteinuria (>1g/day) indicates glomerular diseases.
- When significant proteinuria is encountered, renal biopsy
should be done to determine the etiology
Causes of proteinuria:
- Transient proteinuria:
o Postural or orthostatic proteinuria: occurs in upright
positions only
o Non-postural: (Fever, Vigorous exercise, Seizure, etc.)
- Persistent proteinuria: could be glomerular or tubular causes.

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 Tubular Glomerular
Pathology Low reabsorption High permeability
Amount < 1 gm/ day Can be > 1 gm/ day
Albuminuria Absent Present
Associations Glucosuria, phosphaturia Edema, HTN, hematuria
Table 2: Tubular vs Glomerular proteinuria

Detection:
- Urine dipstick:
o Albumin is the only protein that is detected on
dipstick urinalysis.
o Less sensitive: Reported as (+1: 30 mg/dl), (+2: 100
mg/dl), (+3: 300 mg/dl), (+4: 1000 – 2000 mg/dl).
- 24 hours urine collection: Normal < 150 mg/day:
o Renal function usually varies during the day, and
transient proteinuria is present in 2 – 10% of the
population, so 24 urine collection for protein is more
accurate than spot urinary protein measurement.
o Heavy proteinuria > 1g / day (Glomerular origin)
o Nephrotic range proteinuria > 3.5 g/day
- Urine protein/creatinine ratio (P/Cr ratio):
o Recent evidence indicates that the P/Cr ratio is more
accurate than the 24-hour urine protein
measurement (The P/Cr ratio is easier and faster to
perform)
o The P/Cr ratio is equivalent to the number of grams in
the 24-h collection; a ratio of less than 0.2 is
equivalent to 0.2 g of protein per day, and a ratio of
3.5 is equivalent to 3.5 g of protein per day and is
considered nephrotic range.
- Albumin/creatinine ratio (ACR):
o Measures only the albumin in the urine and is used to
evaluate diabetic kidney disease
o It should be done annually for all diabetic patients
o Early morning specimens should be used
o ACR > 2.5 is considered microalbuminuria
- Urinary immunoelectrophoresis
o It is a urine test that measures the immunoglobulins in
a urine sample
o It is used to detect Bence-Johns Protein (BJP) in case
of multiple myeloma

P a g e |4
 The routine urinalysis
- It has 2 parts (dipstick and microscopic analysis)
- Color: normally yellow, darker if dehydrated, and white if
well hydrated. It also can be red-colored if RBCs, myoglobin,
or Hb are present and can be turbid or green if there is an
infection
- Volume:
o Anuria: if less than 100 ml/day
o Oliguria: if less than 500 ml/day
o Polyuria: if more than 3 liters/day
- Specific gravity: normally 1.002 to 1.025
o Reflects the number of particles in the urine
compared to the water content.
o It will be high in dehydration and DM but low in DI
and chronic renal failure.
- Urinary PH: the normal value is 6
o Urine will be alkaline in Proteus infection
o If early morning urine is alkaline, consider distal RTA
- Urine glucose: usually indicates DM, but it is falsely positive in
pregnancy, vitamin C intake, tetracycline or levodopa use
- Urinary ketones: can present in DKA or due to starvation
- Urine protein: proteinuria indicates a glomerular or tubular
disease
- Findings in the urinary microscopy:
o WBC of > 10 hpf indicates UTI
o For persistent high urine WBCs with negative culture,
consider genitourinary TB.
o RBCs of > 5 hpf indicate hematuria

P a g e |5
Physiology of the renin-angiotensin system
- Whenever there is hypoperfusion to the renal artery, renin
hormone is secreted by the Juxtaglomerular apparatus of
the nephron

Figure 1: Physiology of renin-angiotensin system

P a g e |6
 Arterial blood gases
- Arterial blood gas is a test that estimates the blood PH, CO2,
O2, HCO3-, electrolytes, and many other variants.
- Arterial samples, mostly from the radial artery, should be
tested in a special machine to evaluate ABGs.
Quick points about ABGs reading
- The PH: is an indicator of the blood acidity
o Normal blood PH: 7.35 – 7.45
o PH of less than 7.35 indicates acidosis
o PH of more than 7.45 indicates alkalosis
- The PaCO2: is an acid controlled by the lungs
o Normal value: 35 – 45 mmHg
o Hyperventilation causes a CO2 wash leading to
alkalosis
o Hypoventilation causes CO2 retention leading to
acidosis
- The HCO3-: is an alkaline, metabolically controlled by renal
and GI systems
o Normal value: 22 – 28 meq/L
o Decreased HCO3-will lead to acidosis
o Increased HCO3- will lead to alkalosis
Steps for ABGs Reading:
- Step 1: Look for PH:
o If PH is high (> 7.45), the answer is alkalosis
o If PH is low (< 7.35), the answer is acidosis
- Step 2: Look for PaCO2:
o If it changes in the same direction as PH, it is
metabolic
o If it changes in the opposite direction, it is respiratory
- Step 3: look for compensations and mixed disorders.

P a g e |7
 Respiratory acidosis
- It is defined as the increase in PaCO2 that leads to
decreased blood PH.
Causes: (any cause of hypoventilation)
- Primary lung diseases like COPD, OSA, and life-threatening
asthma.
- Neuromuscular disorders: e.g., myasthenia graves,
kyphoscoliosis
- CNS disorders: opiate overdose, brainstem lesions
- Drug-induced hypoventilation: e.g., opiates

Respiratory alkalosis
- It is defined as CO2wash (Decreased PaCO2) that leads to
elevated blood PH.
Causes: (any cause of hyperventilation)
- Anxiety (hysterical hyperventilation)
- Pain and fever
- Anemia
- Interstitial lung disease
- Pulmonary embolism
- Mild Asthma

In respiratory acidosis and alkalosis, minute ventilation is more

important than the respiratory rate (Minute ventilation equals the
respiratory rate multiplied by the tidal volume)

Hyperventilation syndrome: when a patient is exposed to stress,

he starts to hyperventilate, feeling unwell, then more
hyperventilation develops.
- Respiratory alkalosis is a feature
- A patient may develop symptoms like chest pain,
numbness, and weakness
- Treat the patients by making them breathe into a bag to
reduce the CO2 wash

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 Metabolic acidosis
- It is defined as the reduced plasma PH and Plasma HCO3-
- A high anion gap indicates metabolic acidosis even if PH,
PaCO2, and HCO3- are normal.

The anion gap:

- In metabolic acidosis, always measure the anion gap to
determine the differential diagnosis.
- Serum anion gap = (Na) – (Cl + HCO3-)
- Urine anion gap = urine Na – urine Cl
- A wide anion gap means an anion gap of > 12
- The most important causes of normal anion gap
metabolic acidosis are diarrhea and RTA
- RTA has a positive urine anion gap, but diarrhea has a
negative urine anion gap
Table 3: Serum and urine anion gap

Causes of anion gap metabolic acidosis (MUD PILS):

- Methanol overdose
- Uremia: renal failure
- DKA
- Phosphate, paraldehyde, propylene glycol
- Ischemia
- Lactate: hypotension, hypoperfusion
- Starvation, Salicylate overdose
Causes of non-anion gap metabolic acidosis (HARDASS):
- Hyperalimentation
- Addison’s disease
- Renal tubular acidosis (RTA)
- Diarrhea, ileostomies, fistula.
- Acetazolamide
- Spironolactone
- Saline infusion

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 Metabolic alkalosis
- Defined as elevated PH and serum bicarbonate levels
Causes:
- GI loss of acid: vomiting, NG tube suction
- Increased aldosterone: Conn’s, Cushing’s
- Diuretics and Hypokalemia
- Milk-alkali syndrome: high-volume liquid antacids

ABGs compensation
- Whenever the blood has alkalosis or acidosis, the buffering
system in the body tries to return the PH to its normal range
by a process called compensation.
- Metabolic acidosis and alkalosis are compensated by the
CO2 by changing the respiratory rate, while respiratory
acidosis and alkalosis are compensated by changing HCO3-.
- CO2compensation is rapid, but HCO3 compensation usually
takes up to 48 – 72 hours, so respiratory problems with
metabolic compensation indicate that the etiology is longer
than 48 hours.
When the PH and the HCO3-are reduced in metabolic acidosis,
the lung will hyperventilate to washout CO2and make PH return
to normal.
In pure metabolic acidosis, Winters’ formula predicts that CO2
should be 1.5 times the bicarbonate concentration plus 8 ± 2 mm
Hg.
If the PaCO2 is more than predicted, additional respiratory
acidosis is present, while if the PaCO2 is less than predicted,
additional respiratory alkalosis is present.

Disorder Estimated change (Δ)

Metabolic acidosis PaCO2 = [1.5* HCO3-+8] ± 2
Metabolic alkalosis Δ HCO3-= Δ PaCO2 * 0.7
Acute respiratory acidosis Δ PaCO2 = 10 * Δ in HCO3-
Chronic respiratory acidosis 10* Δ PaCO2 = 3.5 * Δ in HCO3-
Acute respiratory alkalosis Change in PaCO2 = 5* Δ of HCO3-
Chronic respiratory alkalosis Change of PaCO2 = 2 * Δ in HCO3-
Table 4: The estimated HCO3 and PaCO2 in gas disorders

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 Triple acid-base disorder estimation
Delta – Delta:
- Delta – Delta = Δ anion gap/ Δ bicarbonate
- Δ Anion Gap = Anion Gap – 10
- Δ Bicarbonate level = Bicarbonate level – 24
- The normal Delta–Delta is 1 – 2
- If Delta – Delta < 1, consider concurrent normal anion gap
metabolic acidosis
- If Delta – Delta > 2, consider concurrent metabolic alkalosis

Acute kidney injury (AKI)

- Acute renal failure or AKI is an acute reversible deterioration
of renal function that develops within days.
Causes: It can be one of three types:
- Pre-renal type (decreased renal perfusion)
- Parenchymal type (ischemia or toxin affecting kidney tissue):
o Acute tubular necrosis (ATN)
o Acute glomerulonephritis
o Acute interstitial nephritis
o Vascular cause
- Post-renal type (obstruction)
Clinical features:
- There is no pathognomonic physical finding to diagnose AKI
without lab investigations. The patient may have an
asymptomatic increase in urea and creatinine or present
with non-specific symptoms like nausea, vomiting, malaise,
weakness, and shortness of breath.
- Abnormalities of the urine volume (anuria, oliguria, or
polyuria)
- Very severe disease may present with confusion, arrhythmia
due to hyperkalemia, or uremic pericarditis.
- Lab abnormalities:
o Azotemia: the rise of BUN and serum creatinine levels
with the reduction of the GFR
o Electrolyte disturbance (hyperkalemia, hyponatremia,
hyperphosphatemia, and hypocalcemia)

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 Pre-renal AKI
- It is a reversible kidney injury resulting from decreased blood
perfusion to the kidneys
- It is the most common type of acute renal failure (70%)
- It is caused by any cause of decreased renal artery
perfusion, e.g., decreased cardiac output, dehydration,
sepsis, shock, burns, or renal artery stenosis
- If it persists without treatment, intrinsic renal failure occurs
Clinical features:
- History of fluid loss followed by decreased urine output (e.g.,
burn, vomiting, diarrhea, etc.)
- Hypotension, decreased urine output
- Signs and symptoms of the cause.
Diagnosis:
- Serum BUN:Cr ratio > 20: 1
- Urine sodium < 20 mEq/l
- Low Fractional sodium excretion (FENa) < 1%
- Urine osmolality > 500 mOsm/kg
- High specific gravity (concentrated urine)

In pre-renal AKI, there will be:

- Decreased blood pressure → increased aldosterone →
increased sodium reabsorption → decreased urine sodium.
- Decreased intravascular volume → increased ADH →
increase water reabsorption → concentrated urine with
high osmolality > 500 mOsm/kg

Treatment:
- The priority is to restore the renal blood flow with IV fluids
- Correction of the cause to prevent further deterioration
- Maintain electrolytes normal
- Avoid nephrotoxic medications during the illness.

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 Hepatorenal syndrome
- It is a renal failure developed secondary to liver disease
- Two main types: Type 1 (acute) and type 2 (gradual)
- Caused by splanchnic vasodilatation and reduced total
systemic vascular resistance
- Very poor prognosis with high mortality.
Clinical features:
- New onset of renal failure in a patient with severe liver
disease
- Absence of any other explanation for the renal failure
Investigations: goes with pre-renal AKI
- Low urine sodium < 15 mEq/l
- FENa < 1%
- Elevated BUN/Creatinine ratio
Treatment:
- Midodrine and octreotide increase the mean arterial
pressure and reduce the splanchnic vasodilatation
- Noradrenaline to increase the mean arterial pressure
- Transjugular intrahepatic portosystemic shunt (TIPSS) will
provide a short-term benefit
- Renal replacement therapy

Intrinsic Renal AKI

Acute tubular necrosis (ATN)
- It is the most common form of intrinsic renal failure
- It characterized by tubular cell damage
- It can be reversible if appropriate management (tubular
cells can regenerate)
- It may be of ischemic or nephrotoxic types
Causes of ATN:
- Ischemic (if there is no adequate treatment of pre-renal AKI,
it will transform into ATN)
- Drugs: Aminoglycosides, amphotericin, vancomycin,
cisplatin, acyclovir, cyclosporine, NSAIDs
o Slow onset: need 5 – 10 days
o Dose-dependent: the higher the dose, the more injury
o Low Mg level increases the risk of aminoglycoside
and cisplatin toxicity.

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 - Contrast media:
o Rapid effect
o It can be prevented with normal saline hydration (the
best choice)
o N-acetylcysteine and sodium bicarbonate are not
consistently proven benefits.
o Only contrast media present with ATN with low urine
sodium, FENa < 1%, and very high specific gravity.
- Hemoglobin (due to hemolysis), myoglobin (due to
rhabdomyolysis)
- Hyperuricemia (from tumor lysis syndrome)
- Bence-Johns proteins in multiple myeloma.
Clinical picture: There are 4 phases of ATN:
- Pre-oliguric phase (0 – 2 days):
o It starts from the precipitating event until oliguria
occurs
o Symptoms of the primary cause are dominant
o This phase is reversible if circulation is restored early
and completely
- Oliguric phase (8 – 14 days)
o Oliguria or rarely anuria
o Water and electrolyte imbalances occur at this phase
- Diuretic phase (10 days)
o The new epithelium cannot concentrate urine
o Polyuria 3 – 5 liters per day leading to dehydration
- Recovery phase (4 – 6 months): The period from the
stabilization of serum laboratory values until the restoration of
optimal renal function
Diagnosis:
- History of toxin exposure is a clue
- Elevated kidney function test
- Urine chemistry shows high sodium, high FENa, and low
osmolality.
Treatment:
- Treatment of the reversible causes
- Maintenance of hydration and electrolyte balance
- Avoid nephrotoxic medications
- Hemodialysis as indicated

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 - Isosthenuria is a condition in which serum osmolality
equals urinary osmolality. It occurs in ATN because of the
failure of the tubular cells to concentrate urine.
- In contrast to pre-renal azotemia, ATN patients
inappropriately lose sodium and water.
o Urinary sodium will be > 40 mmol/l
o Urine osmolality will be below 300 mOsm/l

The parameter Pre-renal azotemia ATN

Urine sodium < 20 mmol/l > 40 mmol/l
BUN/Creatinine > 20 10 – 15
FENa < 1% > 2%
Fractional urea excretion < 35% > 35%
Urine osmolality (mOsm/kg) > 500 < 350
Specific gravity > 1020 < 1010
Response to fluid replacement Yes no
FENa = (urine Na/plasma Na) / (urine Cr/plasma Cr) x 100
Fractional urea excretion = (urine Ur /blood Ur) / (urine Cr/plasma Cr) x 100
Table 5: Pre-renal azotemia vs ATN

Rhabdomyolysis
- Rhabdomyolysis occurs due to severe destruction or necrosis
of the muscles leading to a release of a large amount of
myoglobin which has a toxic effect on renal tubules.
Precipitants:
- Trauma, Crush injury, Prolonged immobility
- Drugs (e.g., Statins, Cocaine toxicity)
- Convulsions
- Snake Bites
- Heatstroke
Clinical picture:
- History of precipitant
- Myalgia
- Dark urine (myoglobinuria)
- May present with arrhythmias or other electrolyte
disturbance signs and symptoms
- Features of acute tubular necrosis (ATN)

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Diagnosis:
- ECG is the most urgent step to do (to rule out arrhythmia
secondary to hyperkalemia)
- Urinalysis: positive for blood in dipstick, but no cells will be
seen in microscopy.
- Urine myoglobin (most accurate test)
- CPK very high
- Hyperkalemia (released from damaged cells)
- Hyperuricemia (nucleic acid released from broken nuclei
and rapidly metabolized into uric acid)
- Hypocalcemia (calcium binds to phosphate and damaged
muscles)
- Elevated urea and creatinine
Treatment:
- Normal saline
- Mannitol and diuresis (decrease contact time of myoglobin
to tubules)
- Bicarbonates (shift potassium to the intracellular
compartment and prevent precipitation of myoglobin in
tubules)
- No need to treat hypocalcemia in rhabdomyolysis

Acute interstitial nephritis (AIN)

Causes:
- Drugs (70%): penicillin, PPI’s, phenytoin, cephalosporin, sulfa
drugs, rifampicin, NSAIDs, furosemide, quinolones,
streptomycin, or allopurinol.
- Systemic diseases (SLE, sarcoidosis, multiple myeloma,
Sjögren’s syndrome)
- Infections (streptococci, TB, CMV)

Medications that are associated with AIN are the same

medications that are associated with drug allergy and rash,
Steven-Johnson syndrome, toxic epidermal necrolysis, and
hemolysis

Presentation:
- Fever (80%), rash (50%), arthralgia
- Usually, non-oliguric acute renal failure
- History of drug hypersensitivity reaction
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Labs:
- KFT: Deterioration of renal function (BUN:Cr ratio < 20)
- CBC: Eosinophilia
- Urinalysis: High RBC, high WBC, WBC casts, proteinuria,
eosinophiluria
Treatment:
- Supportive treatment of acute renal failure
- Oral or IV cortisone (used if there is no improvement after
removal of precipitating factor)
- Management of ESRD, if it occurs (rarely happens)

- Eosinophiluria is not found in AIN due to NSAIDs.

- Urine osmolality and urine sodium are useless in the
diagnosis of AIN.

Papillary necrosis
- It is ischemic necrosis of the renal papilla, which is usually
bilateral
- The precipitating factors are DM, Sickle cell disease, chronic
alcoholism, and Chronic urinary tract obstruction)

Figure 2: IVP showing Ring shadow

Clinical features:
- Consider a diagnosis of papillary necrosis if a sudden
deterioration of KFT in a patient who uses NSAIDs and has a
precipitating factor.
- Fever, Hematuria, Flank pain
- Acute renal failure with oliguria or anuria
- If chronic urinary tract obstruction, asymptomatic sloughing
of the pyramid, and necrotic tissue are present in the urine

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Diagnosis:
- Sudden deterioration of KFT in a patient with DM or chronic
urinary tract obstruction
- Necrotic tissue in urinalysis
- IVP (intravenous pyelography): ring shadow
- CT scan is the most accurate test

Clinically, Papillary necrosis is very similar to pyelonephritis

Treatment:
- Supportive treatment of acute renal failure
- Treatment of the underlying cause

Analgesic nephropathy
- Prostaglandin causes afferent arteriole dilation, so NSAIDs
inhibit prostaglandin and result in renal vascular insufficiency
- High-dose analgesia can cause ATN, AIN, Membranous
glomerulonephritis, or Vascular insufficiency (Papillary
necrosis)
- Renal impairment with a history of NSAIDs use and the
absence of other possible causes is diagnostic (diagnosis of
exclusion)
- Treatment: stop the offensive medication and supportive
measures

Summary of tubular diseases:

- They are generally acute
- Caused by toxins (drugs, hemoglobin, myoglobin, urate)
- None of them cause Nephrotic syndrome or massive
proteinuria
- A biopsy is not needed for diagnosis
- They are not treated with steroids
- Immunosuppressive drugs are not used for treatment
- Removing the toxin and correcting hypoperfusion is the
only treatment
Table 6: Summary of Tubular diseases

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 Post-renal acute renal failure
- It is a deterioration of renal function due to obstruction of
the urinary tract
- History of previous urinary symptoms (hematuria, renal colic,
etc.)
- Anuria is a common feature of post-renal obstruction
Diagnosis:
- BUN/Cr ≤ 20:1
- Antegrade or retrograde pyelography
- Cystoscopy
- HRCT
Treatment: Relieve the obstruction

Introduction to the glomerular

diseases
- A group of inflammatory diseases that affects the glomerulus
of both kidneys
- They are generally chronic, not caused by toxins or
hypoperfusion, and often treated by steroids and
immunosuppressants
- Renal biopsy is the most accurate test

Primary glomerular diseases Secondary glomerular diseases

- Minimal change disease - SLE, DM
- Membranous - Sarcoidosis
glomerulonephritis - Amyloidosis
- Membranoproliferative - Polyarteritis nodosa
glomerulonephritis - Henoch Schönlein
- IgA nephropathy purpura (HSP)
- Goodpasture syndrome - Malarial nephropathy
- Focal segmental - HUS
glomerulosclerosis - Granulomatosis with
polyangiitis
Table 7: Primary and secondary glomerular diseases

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Pathogenesis: There are two main processes:
- Circulating immune complex deposition
o Viruses (HBV, HCV, EBV, HIV, Measles, Mumps)
o Bacteria (group A beta-hemolytic streptococci,
streptococcus Viridians, staph., salmonella,
Gonococci)
o Parasites (Plasmodium malaria, filariasis,
Schistosomiasis)
o Drugs (penicillamine)
o Host antigen (DNA in SLE, malignant tumors)
- Anti-GBM antibodies 5% (Goodpasture syndrome)

Clinical presentations of glomerular diseases

Sub-nephrotic proteinuria
- Selective proteinuria: Glomerular injury only allows the
passage of albumin, but not larger molecules like globulin
- Non-Selective proteinuria: when Glomerular injury allows the
passage of albumin and the larger molecules like globulin

Nephrotic syndrome
- It results from glomerular damage that allows the passage of
more protein to the urine (proteinuria > 3.5 grams/day)
Clinical features and pathogenesis:
- Hypoalbuminemia:
o Occurs due to protein loss in the urine
o This will result in reduced oncotic pressure and
anasarca (started as puffiness around the eyes)
- Hypercholesterolemia: while the liver tries to compensate for
the low protein levels, it will produce cholesterol.
- Decreased renal perfusion due to decreased plasma
volume → activation of the renin-angiotensin system →
sodium water retention
- Increased risk of infection (due to immunity proteins loss)
- Hypercoagulability occurs due to the following:
o Loss of anti-thrombin III in urine
o Altered levels of protein C and S
o Hyperfibrinogenemia (increased hepatic secretion)
o Increased platelet tendency to aggregate

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Examples of nephrotic diseases:
- Minimal change disease
- Membranous glomerulonephritis
- Focal segmental glomerulosclerosis
- Amyloidosis
- Diabetic nephropathy
- Drugs (penicillamine, Gold, Mercury, cadmium)
- Allergic reaction
General treatment:
- Loop diuretics and a low salt diet for edema.
- HMG-COA reductase inhibitors for dyslipidemia
- Anticoagulation to treat and prevent thrombosis
- Maintain blood pressure and electrolytes within normal
- Albumin infusion with mannitol can induce dieresis in oliguric
renal failure
- Specific treatments (steroids and immunosuppressants)

Nephritic syndrome
- It is also known as glomerulonephritis
- The glomerular damage will lead to the passage of RBCs,
- The inflammatory process and local edema of the nephron
lead to decreased GFR, less proteinuria, and azotemia.
Clinical features and pathogenesis:
- Proteinuria < 3.5 grams /day
- Hypoalbuminemia and edema (more in nephrotic)
- Hematuria with dysmorphic RBCs and RBC casts
- More renin-angiotensin system activation leads to HTN
- Renal dysfunction and azotemia

Figure 3: RBC cast in urine consistent with glomerulonephritis

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Examples of nephritic diseases:
- Anti-GBM antibody disease
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
- Henoch-Schönlein purpura
- IgA nephropathy
- Alport syndrome

Diseases that cause both nephritic and nephrotic:

- Diffuse proliferative GN
- Membranoproliferative GN
- Post-streptococcal GN

Rapidly progressive glomerulonephritis

- RPGN is a clinical syndrome characterized by
glomerulonephritis with progression to renal failure within
weeks.
- Severe damage to the glomerulus allows the larger
molecules (fibrin) to pass through the glomerulus
- Fibrin activates cellular proliferation with macrophage
migration and the formation of a crescent of Bowman’s
capsule.
- Patient end with impaired filtration through the glomerulus,
which lead to uremic syndrome

Nephritic/nephrotic syndrome
- The presence of mixed features between nephrotic and
nephritic syndromes
Causes:
- Diffuse proliferative glomerulonephritis
- Membranoproliferative glomerulonephritis

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 Disorders of nephrotic syndrome
Diabetic nephropathy:
- The most common cause of secondary nephrotic syndromes
- Annual screening of albumin creatinine ratio (ACR) is
indicated for all diabetic patients
- Screening should be started at the time of diagnosis for type
2 DM but after 5 years in Type 1 DM.
- Diabetic nephropathy is diagnosed clinically without the
need for a routine biopsy.
- The treatment of choice is ACE inhibitors or ARBs to protect
the nephrons from further damage.
Minimal change disease:
- The most common cause of primary Nephrotic syndrome in
children (10% of nephrotic diseases in adults)
- The biopsy will be normal under the light microscope but will
show effacement of the foot processes of the podocytes
under the electronic microscope.
- It is the most nephrotic disorder to respond to steroids
- The specific treatment: prednisolone (60mg/day) for 8
weeks. However, if the disease is resistant to steroids, use
cyclophosphamide 3mg/kg for 6 – 8 weeks.
Membranous glomerulonephritis:
- The most common cause of primary Nephrotic syndrome in
white adults (40’s to 50’s age group)
- Secondary causes include (HBV, HCV, malaria, lymphoma,
SLE, NSAIDs, etc.)
- High rate of renal vein thrombosis and coagulopathy.
- 50% associated with colon, lung, or stomach cancer
- The fate:
o One-third: spontaneously recovered within 12 months
o One-third will progress to ESRD
o One-third: remain proteinuric
- Treatment:
o Treat the concomitant HBV infection
o Steroids, azathioprine, chlorambucil, cyclosporine,
cyclophosphamide, or cytotoxic agents for 6 months
Focal segmental glomerulosclerosis:
- It is the most common cause of nephrotic syndrome in
blacks, intravenous drug users, and HIV patients.
- Treatment with prednisolone is the most appropriate
- Cytotoxic agents are used for refractory cases

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 Disorders of nephritic syndrome
Post-streptococcal Glomerulonephritis
- PSGN results from a post-infectious complication of Group-A
beta-hemolytic streptococci (Streptococcus pyogenes) of
the throat or skin. The resulting immune complexes will lead
to glomerular injury
- Post-streptococcal GN usually follows infection by 1 – 3
weeks
Clinical features:
- Picture of nephritic syndrome (hematuria with RBC casts,
oliguria, HTN, high urea and creatinine, low GFR)
- Low complement C3 and C4 but returns to normal after 12
weeks
- Positive ASO titer
- Biopsy: (best) electron microscopy shows subepithelial
HUMPS caused by lumpy immune complex deposits
Treatment:
- Bed rest, Low salt diet
- Treatment as AKI, if present
- Diuretics to reduce HTN and edema
- Antihypertensive medications may be required
- Antibiotics, if the culture is positive

Causes of glomerular diseases with low complement levels:

- Post-streptococcal glomerulonephritis
- Subacure bacterial endocarditis
- Membranoproliferative glomeruloneprhritis
- Cryoglobulinemia

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 IgA Nephropathy
- Also called Berger’s disease or mesangioproliferative
glomerulonephritis
- It is the most common cause of glomerulonephritis
worldwide
- Occur due to IgA deposition in the glomerulus
- Gross Hematuria 1-2 days after an upper respiratory infection
Clinical features:
- Picture of nephritic syndrome (hematuria with RBC casts,
HTN, high urea and creatinine, low GFR)
- Nephrotic range proteinuria is rare (worse prognosis)
- Normal complements
- Serum IgA elevated in 50% of cases
- Histology shows mesangial hypercellularity, positive
immunofluorescence for IgA & C3
Treatment:
- No treatment, usually spontaneous resolution
- If it progresses to ESRD, a renal transplant is indicated
- If severe proteinuria, ACEI, and steroids are the treatment.
Prognosis
- 25% of patients develop ESRF
- Markers of a good prognosis: frank hematuria
- Markers of poor prognosis: male gender, more proteinuria,
HTN, hyperlipidemia

IgA nephropathy PSGN

Timing after URTI 1 – 2 days 1 – 2 weeks
main symptom Hematuria Proteinuria
C3 and C4 Normal Low
Biopsy Mesangial Lumpy subepithelial
hypercellularity immune complex deposits
Table 8: PSGN vs. IgA nephropathy

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 Goodpasture syndrome
- Goodpasture syndrome is a clinical syndrome that
comprises glomerulonephritis and pulmonary hemorrhage
due to injury mediated by Anti-glomerular basement
membrane antibody (Anti-GBM)
- Hemoptysis and hematuria are the main features but no
upper respiratory involvement
- Signs and symptoms of vasculitis are usually absent because
the disease is limited to the lung and kidneys
Clinical features:
- Usually Involves ages of 5 – 40 years and more common in
male
- The onset of the disease may be preceded by URTI in 20 –
60% of cases
- Hemoptysis usually precedes nephritis for weeks to months,
and it is associated with dyspnea
- Nephritis present with features of rapidly progressive
glomerulonephritis
Diagnosis:
- Clinical picture suggestive of the diagnosis
- CBC shows anemia (chronic blood loss)
- CXR shows bilateral infiltration
- High TLCO (due to pulmonary hemorrhage)
- Anti-GBM antibody detection in serum (best initial test)
- Renal biopsy showing linear deposits on GBM is the most
accurate test.
Treatment:
- Steroids
- Cyclophosphamide can be helpful
- Plasmapheresis to remove Anti-GBM

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 Granulomatosis with polyangiitis
- Granulomatosis with polyangiitis was previously called
Wegener’s granulomatosis
- It is a vasculitis of the upper and lower respiratory tract along
with glomerulonephritis leading to necrotizing inflammation
of the glomerulus, nasopharynx, and lungs
Clinical features:
- Systemic non-specific symptoms (fever, weight loss)
- Respiratory symptoms:
o Features of sinusitis, nasal septal perforation, and
saddle nose deformity
o Cough, hemoptysis, dyspnea, Chest X-Ray: cavitary
lesion
- Renal features: hematuria, proteinuria
- Eye: conjunctivitis, scleritis, Episcleritis
- Skin: rash, ulcers, nodules

Look for upper and lower respiratory

involvement with renal insufficiency

Diagnosis:
- Suggestive history of Wegener’s granulomatosis
- High ESR
- Positive serology for ANCA (cANCA 90% and pANCA 10%)
- Chest x-ray: a wide variety of presentations, including
cavitating lesions
- Renal biopsy: crescentic glomerulonephritis
Treatment: Steroids, Cyclophosphamide

cANCA: cytoplasmic antineutrophil cytoplasmic antibody

- Wegener’s granulomatosis
pANCA: perinuclear antineutrophil cytoplasmic antibody
- Churg-Strauss syndrome
- Microscopic polyangiitis
Table 9: cANCA vs. pANCA

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 Churg-Strauss syndrome
- Also known as Eosinophilic granulomatosis with polyangiitis
- It is an ANCA-associated pulmonary-renal syndrome
- It is associated with Asthma and Eosinophilia
- Paranasal sinusitis, mononeuritis multiplex may present
- pANCA positive in 60%
- Treatment: steroid

Henoch Schönlein purpura (HSP)

- HSP is a type of small vessel vasculitis of unknown cause
- It is also known as IgA vasculitis
- More common in male children
Clinical features:
- GI: Abdominal pain, melena
- Skin: Palpable purpura, usually in lower limbs and buttocks
- Joints: Arthralgia
- Renal: Nephritic syndrome and renal insufficiency

Figure 4: A characteristic rash of HSP

Diagnosis:
- Mainly clinical diagnosis
- Biopsy is the most accurate test (leukocytoclastic vasculitis)
Treatment:
- Supportive treatment
- Usually, Full recovery within several weeks
- Steroids are effective in reducing tissue edema, arthralgias,
and abdominal discomfort

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 Alport’s syndrome
- It is an x-linked inherited condition that leads to a congenital
collagen defect
Symptoms:
- Progressive renal failure (glomerular disease)
- Hematuria
- Sensorineural deafness
- Visual disturbances (loss of collagen fibers in the lens of the
eye)

Look for a patient with deafness and renal impairment with a

family history of the same condition in his mother or maternal
uncle.

Treatment:
- No Cure
- ACE inhibitors can slow the progression of the renal disease

SLE nephritis
- SLE can give any degree of renal involvement
- Class IV is the most common and severe form of SLE nephritis
- Biopsy is the most accurate test

Class I Normal kidney

Class II Mesangial glomerulonephritis
Class III Focal (and segmental) proliferative glomerulonephritis
Class IV Diffuse proliferative glomerulonephritis (most common
and most severe form)
Class V Diffuse membranous glomerulonephritis
Class VI Sclerosing glomerulonephritis
Table 10: WHO classification for lupus nephritis

Treatment:
- Treatment based on stage according to biopsy
- Mild inflammatory changes may respond to steroids
- Severe proliferative disease is treated with steroids
combined with cyclophosphamide and mycophenolate.

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 Amyloidosis
- Amyloidosis is an abnormal protein deposition
- In primary amyloidosis, the source of protein is unknown, and
the kidneys are the main target of the protein deposition
Causes:
- Idiopathic (primary amyloidosis)
- Myeloma
- Chronic inflammatory diseases:
o Rheumatoid arthritis
o Inflammatory bowel disease
o Chronic infections
Diagnosis: Biopsy showing green birefringence with Congo red
staining is the most accurate test.
Treatment:
- Treatment of the underlying disease
- Melphalan and prednisolone (for primary or unsuccessful
treatment)

Chronic Kidney disease (CKD)

- It is an irreversible deterioration of the renal function that
persists for more than 3 months
- This will lead to excretory, metabolic, and endocrine
dysfunction of kidneys, and the clinical syndrome of uremia
- The leading cause of death in CKD patients is
cardiovascular disease.
Causes:
- Diabetic and HTN nephropathy are the most common
causes
- Glomerular diseases
- Tubulointerstitial diseases
- Renovasculad diseases (vasculitis)
- Structural diseases (e.g., PKD)

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Stages of CKD:
Stage Severity GFR mL/min Clinical state
Stage I Mild Normal No symptoms
Stage II Mild 60 – 89 No symptoms
Stage III Moderate 30 – 59 Anemia may present
Stage IV Severe 15 – 29 Electrolyte disturbances
Stage V ESRD < 15 Dialysis dependent
Table 11: CKD stages according to GFR
Clinical picture:
- Non-specific symptoms: (Nausea, vomiting, pruritus,
diarrhea, convulsions, coma)
- Features of complications (anemia, uremia, etc.)
- Urinary symptoms: (Oliguria, anuria, nocturia, Polyuria)
- Renal osteodystrophy
- Sensory-motor peripheral neuropathy
- Signs and symptoms of electrolyte disturbance

Renal osteodystrophy:
Osteitis fibrosa cystica:
- High PTH (secondary hyperparathyroidism)
- One year later, x-ray findings of subperiosteal erosions of
terminal phalanges and the lateral end of the clavicle
Adynamic bone disease:
- Chronic illness or aggressive vitamin D treatment will
suppress the PTH
- Increased risk of fractures
- Made worse with bisphosphonates
Osteomalacia:
- Vitamin D deficiency
- Hypocalcemia, bone pains, and fractures
Table 12: Types of renal osteodystrophy

Treatment:
- Dietary modifications (protein, K+, and Na+ restriction)
- Treatment of complications (uremia, HTN, electrolytes)
- Treatment of anemia (erythropoietin injections, target Hb not
more than 11)
- Calcium replacement, 1-alpha
- Regular dialysis typically 2 – 3 times weekly
- Renal transplant (definitive treatment)

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Drug dose adjustments in CKD:
- Many medications need dose adjustment in CKD to prevent
their toxicity and accumulation.
- Usually, they are adjusted based on the estimated GFR or
creatinine clearance but not serum creatinine.
- Dose adjustment may be a reduction of the dose,
lengthening the dosing intervals, or both
- Loading doses usually do not require an adjustment

Indications of dialysis in renal failure

- Uremic symptoms (pericarditis, encephalopathy, platelet
dysfunction, or convulsions)
- Fluid overload
- Refractory hyperkalemia > 7 mEq/l
- Acidosis PH < 7.2
- Serum creatinine > 10 mg/dl
- Serum urea > 200 mg/dl
- Regular hemodialysis for ESRD patients.
Table 13: Indications for hemodialysis

Acute on top of chronic renal failure:

The patient is known to have CKD and presents a new kidney
function deterioration (elevation of the baseline creatinine). The
acute deterioration can be reversible to the baseline with proper
management. However, diagnosis and treatment are just like
that in acute renal failure, and then to manage the patient as
CKD according to its stage.
Table 14: Acute on top of chronic renal failure

Acute renal failure Chronic renal disease

History Previously normal History of abnormal KFT
KFT History of any cause of CKD
CBC Not informative Anemia of chronic disease
Renal U/S Normal size kidney Small size kidneys except in DM,
hydronephrosis, Amyloidosis,
Multiple Myeloma, and PKD.
Baseline Normal baseline High baseline
creatinine
Table 15: Acute vs. Chronic renal failure

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 Cystic diseases of the kidney
Characterized by epithelium-lined cavities filled with fluid or
semisolid debris within the kidneys, they include:
- Simple cysts
- Medullary cystic kidney
- Medullary sponge kidney
- Autosomal dominant polycystic kidney disease (ADPKD)
- Autosomal recessive polycystic kidney disease (ARPKD)
- Acquired cystic kidney disease (in chronic hemodialysis
patients)

Simple renal cyst

- It is the most common renal cystic disease
- At least 50% of the population over 50 years old have a cyst
- Usually asymptomatic and diagnosed during an ultrasound
that is done for another purpose
- Imaging used are CT scan, renal ultrasound, urography, or
angiography)
- In the absence of infection or suspected malignancy, there
is no need to treat simple renal cysts

Adult polycystic kidney disease (ADPKD)

- PKDs are genetic diseases in which kidneys are filled with
hundreds of cysts; kidneys become larger than normal and
lose function over time
- Adult PKD is an autosomal dominant, while infant PKD is an
autosimal recessive
- These cysts are lined by tubular epithelium
- Two types of gene mutations in ADPKD
o PKD1 (more severe and early onset) (code for
polycystin1)
o PKD2 (less severe and later onset) (code for
polycystin2)

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Clinical features:
- Flank pain, abdominal pain, abdominal mass
- HTN (due to compression on blood vessels and activation of
RAS)
- Kidney stones (due to compression on collecting ducts and
urinary stasis)
- Hematuria
- Renal insufficiency and renal failure (manifest in adulthood)

ADPKD is associated with cyst formation in other body parts:

- Liver cysts (most common site outside kidneys)
- Seminal vesicle cysts
- Pancreatic Cysts
- Aortic root dilatation, aortic dissection
- Mitral valve prolapse, Tricuspid incontinence
- Berry aneurysm (risk of Subarachnoid hemorrhage)

Treatment:
- ACEI/ARB for treatment of HTN
- Dialysis, or renal transplant in case of ESRD
- Ursodiol for treatment of cholestasis
- Treatment of portal HTN

Autosomal recessive PKD is caused by a mutation in the PKHD1

gene that codes for fibrocystin protein. It is characterized by
oligohydramnios in-utero and early ESRD.
Prenatal ultrasound will show the oligohydramnios and the cystic
kidney.

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 Electrolyte disturbances
Hypernatremia
- Normal serum sodium is 135 – 145 mEq/l
- Hypernatremia is defined as serum Na > 145 mEq/l
- Occur when there is a loss of free water
- Causes include (6D’s) Diuresis, Dehydration, DI, Doctors
(iatrogenic), Diarrhea, and Disease of kidney
Clinical features:
- Thirst, Dry tongue
- Weakness, Restlessness
- Convulsions
- Changes in the level of consciousness (up to coma)
Treatment:
- Treatment of the cause
- Correction rate ≤ 0.5 mEq/l/h (to prevent brain edema)
- Fluid replacement:
o For hypovolemic patients, start with isotonic 0.9%
NaCl to correct the water deficit
o If euvolemic and asymptomatic, start D5W, 0.45%
NaCl, or enteral fluid
o For hypervolemic hypernatremia (rare), use D5W and
diuretics.

Water deficit calculation:

Free water deficit = TBW * ([Na/140] – 1)
TBW = 0.5 * weight (for female), 0.6 * weight (for male)
Table 16: Water deficit calculation

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 Hyponatremia
- Hyponatremia is defined as serum Na < 135 mEq/l
- There are 3 patterns of hyponatremia according to fluid
status in the body
Hypervolemic hypotonic hyponatremia:
- Hyponatremia with increased extracellular fluid
- Seen in edema-associated conditions (Congestive heart
failure, liver cirrhosis, Nephrotic syndrome, advanced renal
failure).
- Pathogenesis: water retention leads to dilutional
hyponatremia
- Treatment:
o Water restriction
o Diuretics (i.e., loop diuretics)
o Hemodialysis in resistant cases
Hypovolemic hypotonic hyponatremia:
- Hyponatremia with decreased extracellular volume
- Causes: diarrhea, vomiting, dehydration, diuresis,
nephropathy, adrenal insufficiency, burns, sweating, fever …
(These causes also may cause hypernatremia)
Euvolemic hypotonic hyponatremia:
- Hyponatremia with normal extracellular fluid
- Causes: (pseudo-hyponatremia, SIADH, Addison’s disease,
hypothyroidism, psychogenic Polydipsia)
- In SIADH:
o Due to high ADH, the urine is inappropriately
concentrated (high urine osmolality)
o High urine sodium, but uric acid and BUN are low
o High serum ADH (the most accurate test)
- In pseudohyponatremia:
o Hyperglycemia → increased serum osmolarity → free
water shifted to intravascular space → drop in sodium
level.
o Each 100 mg of glucose above the normal level
reduces 1.6 mEq in serum sodium
o No treatment for pseudo-hyponatremia (only correct
the glucose level)

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 The thyroid hormone is needed to excrete water; so, in
hypothyroidism, water excretion is decreased, leading to
hyponatremia

Clinical features of hyponatremia:

- Present with CNS problems (Confusion, lethargy,
disorientation, seizures, coma)
- Symptoms of hyponatremia depend on how fast it occurs
(the more acute the hyponatremia, the more severe the
symptoms)
Treatment of hyponatremia:
- The correction rate should not exceed 8 – 10 mEq/l every
day to avoid osmotic demyelination syndrome
- Asymptomatic: restrict fluids
- Moderate symptoms (minimal confusion): saline and loop
diuretics
- Severe (coma): hypertonic saline is indicated
- Demeclocycline and fludrocortisone may be used (block
the action of ADH)

Sodium deficit calculation:

Sodium deficit = TBW * (desired sodium – serum sodium)
TBW = 0.5 * weight (for female), 0.6 * weight (for male)
Table 17: Sodium deficit calculation

The composition of common IV fluids:

Cl Na K Ca Lactate
Normal saline 154 mEq 154 mEq - - -
½ saline 77 mEq 77 mEq - - -
¼ saline 39 mEq 39 mEq - - -
3% saline 512 mEq 512 mEq - - -
Ringer’s lactate 109 mEq 130 mEq 4 mEq 3mEq 28 mEq
Table 18: common IV fluids and their compositions per liter

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 Hyperkalemia
- It is defined as the serum potassium of more than 5.3 mEq/l
- It is a life-threatening condition that may result in a fatal
arrhythmia
If the lab result came with hyperkalemia:
- The most urgent step is ECG (to rule out arrhythmias)
- The first step is to repeat the test with a new sample to rule
out pseudohyperkalemia.
Causes of pseudohyperkalemia:
- Hemolyzed sample
- Delay in sample analysis
- Tourniquet use when drawing sample
- Extreme leukocytosis or thrombocytosis
Causes of true hyperkalemia
- Oliguric renal failure
- Drugs (Potassium-sparing diuretics, ACE-I/ARB, NSAIDs,
cyclosporine, heparin, Beta-blocker, digoxin)
- Type IV RTA
- Addison’s disease
- Shifting potassium out of cells:
o Acidosis
o Rhabdomyolysis
o After chemotherapy (tumor lysis syndrome)
o Insulin deficiency
Clinical features:
- Cardiac conduction abnormalities on ECG
- Low or absent P, Prolonged PR, Wide QRS, peaked T wave
- Sine wave (severe hyperkalemia)
- Cardiac arrhythmias

Figure 5: ECG changes in Hyperkalemia

- Neuromuscular effect: muscular weakness, flaccid muscle

paralysis, paresthesia of the face, tongue, feet, and hands
- GI: Nausea, Intestinal colic, and diarrhea (in very high levels
of potassium)

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Treatment (Anti-hyperkalemia protocol):
Effect Agent Dose Onset
Membrane Calcium 10 mL, 10% over Immediate
stabilization gluconate 10 minutes
Shifters Insulin 10 u in 50 mL of 20 minutes
50% dextrose
SABA 20 mg nebulized 30 minutes
Excretors Furosemide 40 – 80 mg 15 minutes
NaHCO3 150 mmol/L Hours
Kayexalate 15 – 30 g > 2 hours
Definitive Hemodialysis - Immediate
Table 19: anti-hyperkalemia protocol

Calcium gluconate:
- It stabilizes the cell membrane but does not reduce the
serum potassium level
- It is indicated if there are ECG changes or the serum
potassium is ≥ 7mEq/L
- To avoid acute hypercalcemia, provide calcium
gluconate with 100 mL of D5%W infusion over 20 – 30
minutes
- Hypercalcemia potentiates the cardiac toxicity of digoxin;
hence, it is better to avoid calcium gluconate in digoxin
users
Other notes:
- Cardiac monitoring is the most important in hyperkalemia.
- Sodium bicarbonate is indicated in hyperkalemia in the
presence of acidosis
- Hemodialysis is indicated in refractory hyperkalemia of
more than 7 mEq/L
- Kayexalate “sodium polystyrene sulfate” and Calcium
resonium “calcium polystyrene sulfate” remove potassium
from the GI tract
- Hyperkalemia and hypokalemia do not cause seizures;
hypernatremia causes CNS symptoms, while hyperkalemia
causes muscular and cardiac symptoms

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 Hypokalemia
- It is defined as the serum potassium of less than 3.5 mEq/l
Causes:
- Intracellular shift: Alkalosis, High insulin, Beta-agonist, Barium
intoxication
- Renal loss: diuretics, RTA type I and II, primary
hyperaldosteronism, Cushing’s syndrome, Barter’s syndrome,
and hypomagnesemia
- GI loss: vomiting, diarrhea, Ileostomy, ureterosigmoidostomy
- Poor intake
Clinical features:
- Fatigue, weakness, cramps, paralysis, anorexia, nausea,
vomiting
- Decreased bowel mobility (ileus)
- Hyperglycemia: due to suppressed insulin
- Restless legs
- Rhabdomyolysis
- Arrhythmias
- Hypotension (due to decreased peripheral resistance)
- ECG changes: (high P wave, Depressed ST, broad flat T
wave, U wave)
- Metabolic alkalosis
Treatment:
- Potassium-rich diet (Banana, orange, tomato, potato, milk)
- Potassium supplement (oral or IV, according to the case)
- Correct hypomagnesemia
There are magnesium-dependent potassium channels that open
and spell potassium in urine in case of hypomagnesemia

Kdeficit = (Knormal lower limit − Kmeasured) × Bodyweight × 0.4

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 Hypomagnesemia
- Hypomagnesemia is defined as serum Mg level < 1.5 mEq/l
Causes:
- Decreased Mg intake (malnutrition, malabsorption)
- Increased Mg loss (diuretics, diarrhea, vomiting, alcoholism)
- Others: DKA, pancreatitis
Clinical features:
- Hyperactive reflexes
- Concurrent hypocalcemia: Tetany, Paresthesia, Irritability,
seizures
- Concurrent hypokalemia: Arrhythmias
- ECG: long PR and long QT intervals
Treatment:
- IV or oral supplementation
- Hypokalemia and hypocalcemia will not correct until Mg
corrected

Inherited defects of the nephron

Renal tubular acidosis (RTA)
- Increased acidity of blood due to an impaired renal ability
to maintain acid-base balance
- All types of renal tubular acidosis (RTA) are associated with
hyperchloremic metabolic acidosis with a normal anion gap
Types of RTA:
- Type I RTA (Distal classic type): Failure of distal tubules to
secrete H+ ions and reabsorb HCO3-
- Type II RTA (proximal type): Failure of sodium bicarbonate
reabsorption in proximal tubules
- Type IV RTA: (hyporeninemic hypoaldosteronism)
o It is the most common type of RTA
o Reduced aldosterone leads to sodium loss and
retention of potassium and H+.

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 Type Potassium Urine anion gap Urine pH
Type I Hypokalemia Positive > 5.5
Type II Hypokalemia Normal or negative < 5.5
Type IV Hyperkalemia Positive < 5.5
Table 20: Laboratory features of RTA types

Causes of RTA:
- Type I: SLE, RA, Sjögren’s syndrome, amphotericin B
- Type II: Wilson disease, Fanconi syndrome, tetracycline
- Type IV: hypoaldosteronism, diabetes
Diagnostic tests:
- Type I: Urine PH still > 5.5 after ammonium chloride infusion
- Type II: Urine PH will rise after bicarbonate is given
- Type IV: Persistent high urine sodium despite low sodium diet
Common complications of RTA:
- Type I: Nephrocalcinosis, calcium oxalate renal stones.
- Type II: Osteomalacia
- Type IV: hyperkalemia
Treatment of RTA:
- Type I:
o Always correct potassium before acidemia
o Sodium bicarbonate
- Type II:
o Bicarbonate (will not correct the acidemia alone)
o Thiazide diuretics (induces hypovolemia and reduce
the GFR leading to reduced bicarb loss)
o Potassium-sparing diuretics (will limit potassium loss)
- Type IV:
o Correction of hyperkalemia
o Fludrocortisone and sodium bicarbonate

85 – 90% of bicarbonates are normally reabsorbed in proximal

tubules, so it is easier to control type I RTA than type II RTA

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 Fanconi syndrome
It is a defect in proximal convoluted tubules
This will result in the loss of the following substances in the urine:
- Glucose loss → glucosuria
- Phosphates loss → phosphaturia
- Amino acids loss → aminoaciduria
- Bicarbonate loss → metabolic acidosis
- Water loss → dehydration
- Potassium loss → hypokalemia
- Sodium loss → hyponatremia

Barter, Gitelman, and Liddle syndromes

Barter syndrome Gitelman syndrome Liddle syndrome

Hypotension Hypotension Hypertension
Hypokalemia Hypokalemia Hypokalemia
Hypocalcemia Hypercalcemia Hypernatremia
Hypercalciuria Hypocalciuria Hypoaldosteronism
Normal Mg Hypomagnesemia
All are autosomal recessive disorders
All result in metabolic alkalosis
Bartter syndrome: Salt loss in the thick ascending loop of Henle
Gitelman syndrome: Defect in thiazide-sensitive sodium-chloride
symporter in the distal convoluted tubules
Liddle syndrome: Sodium reabsorption with potassium loss
Table 21: Genetic syndromes that affect the renal tubules

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 HTN
- HTN is defined as BP ≥ 140/90
- It is classified as (Essential "95%" vs. Secondary "5 %")
- It is usually asymptomatic but could present as headaches
or the symptoms of its cause.
Causes of secondary HTN:
- Renal artery stenosis
- Chronic kidney disease, glomerulonephritis
- OSA (obstructive sleep apnea)
- Hormonal (pheochromocytoma, Cushing’s,
hyperaldosteronism, hyperparathyroidism)
- Liddle syndrome.
Normal BP < 120/80:
- If the cuff is small, there will be a false high reading
- If the cuff is large, there will be a false low reading
Stages of elevated blood pressure:
- Pre-hypertension (120-139/80-89) – “this is not a disease; it is a
risk category”
- Stage 1 (140 -159/90 - 99)
- Stage 2 (≥ 160/100)
Other types:
- White-coat HTN: high readings at the clinic but normal at
home (need Home Blood Pressure Monitoring – HBPM)
- Masked HTN: high readings at home but normal at the clinic
- HTN urgency: severe HTN without end-organ damage
- HTN emergency: severe HTN with end-organ damage
Emergency HTN:
- HTN encephalopathy
- Intracranial hemorrhage
- ACS, LV failure
- Acute aortic dissection
- Eclampsia
Risk factors:
- Family history, smoking, CKD, high Salt/Sodium diet, obesity,
increasing age, male sex, and sedentary lifestyle.
Diagnosis: (one of the following is diagnostic)
- Two separate readings, or
- Very high reading ≥ 180 systole, or
- Emergency/Urgency HTN

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Renal artery stenosis:
- The most common cause in elderly is atherosclerosis,
- The most common cause in young patients is
fibromuscular dysplasia
- Suspect it, if deteriorating renal function (> 30% increase in
creatinine) in a patient with HTN and newly put on
ACEI/ARB
- Diagnosis: abdominal bruit (O/E), Doppler U/S,
angiography (best)
- Treatment: angioplasty with stenting
- ACEI is contraindicated in bilateral disease (they lead to
an increase in creatinine)
Table 22: Important points about renal artery stenosis

Approach for treatment of HTN:

- The first step is to Exclude secondary causes (and treat the
cause if present)
- If there is no secondary case, treat it as essential HTN:
o Try lifestyle modifications initially
o Anti-HTN medications if there is no improvement by
lifestyle modifications
- If stage 1 – start treatment with one drug
- If stage 2 – start treatment with 2 drugs, one of them is
diuretics

Associated condition The drug of choice

HTN + DM ACEI or ARBs
HTN + BPH Alpha-blockers
HTN + CAD Beta-blockers and CCBs
HTN in pregnancy Methyldopa, labetalol, Hydralazine
Table 23: The drug of choice for HTN in specific groups

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 Figure 6: Treatment approach for HTN

Important notes about HTN:

- In urgency HTN, do not decrease BP rapidly (increase the
risk of brain edema, and do not use diuretics)
- Complications of HTN include: Retinopathy, Nephropathy,
Encephalopathy, Brain Hemorrhage, and LV failure
- Serum creatinine should be monitored after administration
of ACEI; if it is increasing by more than 30%, stop ACEI and
investigate for renal artery stenosis
- Refractory HTN is an uncontrolled HTN despite treatment
with 3 drugs in the maximum dose, one of which is a
diuretic. It may be caused by the following:
o Non-compliance with medications
o Non-compliance with a low-salt diet
o Secondary cause of HTN

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 Endocrinology
CHAPTER 2

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

P a g e |47
 Introduction to the Endocrinology
Hormone Counterregulation
- It is a hormone that opposes the action of another.
Glucose Counter-regulation:
- The action of insulin is counter-regulated by glucagon,
epinephrine (adrenaline), norepinephrine (noradrenaline),
cortisol, and growth hormone
- These counterregulatory hormones raise the level of glucose
in the blood by promoting glycogenolysis, gluconeogenesis,
ketogenesis, and other catabolic processes.
- For example, the exercise-induced reduction in blood
glucose cause increases in levels of epinephrine,
norepinephrine, cortisol, and growth hormone. This will lead
to the maintenance of adequate blood glucose for muscle
uptake
Blood Pressure Counter-regulation:
- The natriuretic peptide (BNP) counter-regulate against renin,
angiotensin, and aldosterone, which elevate blood pressure.
Hormonal feedback regulatory systems
- The hormonal positive and negative feedback are
fundamental in the endocrine system.
- The examples of the negative feedback are numerous; the
high T4 and T3 will suppress the TSH and TRH secretion.
Another example is when the high cortisol levels will suppress
the ACTH release from the pituitary gland.
- Child feeding stimulates milk production, which causes
further feeding is an example of positive feedback.

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 Figure 7: Example of the negative feedback

The pituitary gland

Basics of the pituitary gland
- The pituitary gland is an endocrine gland located in Sella
turcica
- It is the master gland of the body because it is the most
important gland in the endocrine system.
- It contains two lobes: anterior and posterior
- The anterior pituitary gland secretes the following:
o Growth hormone (GH)
o Luteinizing hormone (LH)
o Follicular stimulating hormone (FSH)
o Thyroid-stimulating hormone (TSH)
o Adrenocorticotropic hormone (ACTH)
o Prolactin (PRL)
- Posterior pituitary stores and releases the following
hypothalamus hormones: (storage function)
o Oxytocin
o Antidiuretic hormone (ADH)

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 Basics of the pituitary tumors
- Pituitary tumors are usually benign (adenomas); primary
malignancy is rare
Clinical features:
- Compression effect of the tumors:
o Visual field defect: (bitemporal hemianopia or upper
temporal quadrantanopia): due to compression on
the optic chiasma
o Lateral extension to cavernous sinus leads to cranial
nerves 3, 4 & 6 dysfunction
o Compression of normal tissue of the pituitary gland
leads to hyposecretion of the gland hormones.
- Secretory effects of the tumors:
o Gigantism or Acromegaly (excessive GH secretion)
o Cushing’s disease (with high ACTH)
o Hyperprolactinemia

Some adenomas are called non-functioning adenomas (no

excessive hormone secretion but can cause compression effect)
Diagnosis:
- Clinical features (compression or secretory effects)
- X-ray skull (lateral view) will show enlarged Sella turcica
- Pituitary function test
- MRI of the pituitary gland for localization

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 Acromegaly
- Acromegaly is a Disease of adult life, characterized by the
growth of bulk but not in the height of bone due to over-
secretion of GH after puberty
- Gigantism is a GH oversecretion that occurs before puberty;
it increases the bulk and height of the bone.
Causes:
- Pituitary adenoma (Most common cause - usually
Macroadenoma)
- May present as a part of MEN type I
- Ectopic GH or GHRH production from lymphoma or
bronchial carcinoid.
Clinical features:
- Effects of adenoma (headache, vomiting, visual field
defect, cranial nerves palsy, hypothyroidism, impotence,
amenorrhea)
- Skeletal changes:
o Large hands and feet
o Prognathism (large protruding jaw), Large spacing
teeth
o Prominent supraorbital ridges and large frontal sinus
o Spinal stenosis (due to overgrowing vertebral bones)
o Increased risk of carpal tunnel syndrome, and OSA
- Metabolic effects:
o Glucose intolerance (effect of insulin-like growth
factor)
o DM may present in 10%
o HTN
o Weight gain
- Other effects:
o Hypogonadism (compression effect and
hyperprolactinemia are the main mechanisms)
o Colonic polyps and skin tags
o Bad body smell (enlarged sweat glands)
o Deep voice
Diagnosis:
- Clinical features and the morphology of the patient
- Fasting serum Insulin-like Growth factor (IGF-1) (the best initial
test)
- GH level 1 hour after ingestion of 70 g glucose (Glucose
suppression test) (most accurate test)

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 - Fasting serum PRL elevated in 30% (in GH-secreting
adenoma, PRL is co-secreted from the adenoma)
- Pituitary function test (some hormones may be deficient due
to compression effect)
- CT, MRI of the pituitary gland (to localize the adenoma)
Treatment:
- Surgical treatment (Transsphenoidal resection):
o It is the initial treatment for most patients
o indicated if the surgical cure is likely or CNS pressure
effects are present.
o Larger adenomas are harder to cure
- Medical:
o Somatostatin analogues (Octreotide acetate)
o GH receptor antagonists (Pegvisomant)
o Dopamine agonists (Cabergoline or bromocriptine)
- Radiotherapy (if not responsive to surgery and medical
therapy)

The efficacy of the treatment is monitored by GH and IGF-I levels

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 Hyperprolactinemia
- It Is an Increased level of PRL hormone
- PRL function is to stimulate the production of milk by breasts
- Physiologically stimulated by stress, lactation, and nipple
stimulation and suppressed by dopamine and dopamine
agonists
Causes:
- Prolactinoma (the most common cause)
- Primary hypothyroidism (high TRH will stimulate PRL secretion)
- Pregnancy (high level but opposed by estrogen)
- Chronic renal failure, liver cirrhosis
- PCOS
- Drugs (OCP, estrogen, TCA, Haldol, metoclopramide,
dopamine antagonists, verapamil)
Clinical picture:
- Galactorrhea and hypogonadism
- Unexplained infertility
- Secondary amenorrhea, oligomenorrhea, or menorrhagia
with infertility
- In men: decreased libido, impotence, decreased pubic and
axillary hair, gynecomastia, but galactorrhea is rare in men.
Diagnosis:
- Plasma PRL level
- TFT, pregnancy test, KFT, LFT
- CT, MRI of the pituitary gland (done after confirmation of
high PRL and excluding secondary causes)
Treatment:
- Treatment is unnecessary if the patient is asymptomatic and
fertility is not desired.
- Dopamine agonists (cabergoline, bromocriptine):
o They are the first line in the treatment of prolactinoma
o Tumor shrinkage and PRL normalization are the signs
of effective treatment
- Transsphenoidal surgical removal (Indicated if no response
to medical treatment)

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 Diabetes insipidus (DI)
- DI results in insufficient (central) or ineffective (nephrogenic)
ADH, leading to high volume water loss in urine
Types:
- Central DI: Any CNS disorder (stroke, tumor, trauma, hypoxia,
infection, histiocytosis) impair the production of ADH in the
hypothalamus or storage in the posterior pituitary gland.
- Nephrogenic DI: less common, characterized by loss of ADH
effect on collecting ducts, caused by (lithium,
demeclocycline, CKD, Hypokalemia, hypercalcemia,
pyelonephritis, renal amyloidosis, Sjögren’s syndrome)

DIDMOD syndrome: is a congenital syndrome characterized by

central diabetes insipidus, Diabetes mellitus, Optic atrophy,
and deafness.
Table 24: Features of DIDMOD syndrome

Clinical features:
- High volume nocturia (first clue of DI)
- Polyuria, Polydipsia
- Severe hypernatremia (CNS symptoms are possible)
Diagnosis:
- High serum sodium and osmolality
- Low urine sodium and osmolality
- ADH is high in nephrogenic type and low in central type
- Water deprivation test (best initial test)
- Desmopressin challenge test (best to differentiate between
the DI types)
Treatment:
- Central DI: vasopressin (DDAVP)
- Nephrogenic DI:
o Potassium and calcium correction
o Stop lithium, demeclocycline, or any possible cause
o If no improvement, use hydrochlorothiazide or NSAIDs

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 Hypopituitarism
- Deficiency of pituitary hormones due to damage in the
pituitary gland
- If all hormones are deficient, it is termed panhypopituitarism
Causes:
- Compressing pituitary adenoma (the most common cause)
- Others: tumors, trauma, radiation, infection, infarction,
hemochromatosis, sarcoidosis, histiocytosis
Clinical features: Depends on which hormone is deficient
- GH loss: lethargy, muscle weakness, short stature (not
obvious in adults)
- LH, FSH: failure of sex hormone production
o Women: no ovulation, no menstruation
o Men: no testosterone or sperms, Gynecomastia,
Impotence
o Both will have: Loss of libido, Scanty axillary and pubic
hair
- TSH loss: (symptoms of hypothyroidism)
- ACTH loss: this leads to a decreased cortisol level
o Hypoglycemia, Hypotension, hyponatremia,
hyperkalemia, Nausea, and vomiting
- Prolactin loss: no symptoms in men, but a lactation failure in
women after birth.
- ADH deficiency: central diabetes insipidus
- Untreated or severe Hypopituitarism may cause a coma
- Melanocyte-stimulating hormone (MSH) loss will lead to
hypopigmentation of the skin
Diagnosis:
- Pituitary function test: Testosterone, ACTH, PRL, FSH, LH, TSH,
T3, T4, and GH stimulating test
- Aldosterone is not affected, so serum potassium will remain
normal.
Treatment:
- Treatment of the underlying cause
- Hormone replacement therapy (cortisone, thyroxine,
testosterone and estrogen, recombinant human growth
hormone)

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 The Thyroid gland
- It is a part of the endocrine system located in the neck
- Composed of two lobes and connected by an isthmus
- Secrets thyroxin, which is responsible for metabolic activity in
the body
- Thyroxin secretion is stimulated by TSH, which secreted by
the pituitary gland

Hypothyroidism
- It is defined as an inability of the thyroid gland to maintain
the body’s requirement of the thyroxin hormone
- It can be primary or secondary, or tertiary
Primary hypothyroidism: (will lead to increased TSH)
- Hashimoto’s thyroiditis (the most common cause)
- Endemic iodine deficiency
- Idiopathic
- Atrophy
- Radioiodine therapy
- Congenital agenesis
- Drug-induced (lithium, amiodarone, anti-thyroid drugs)
Secondary hypothyroidism: Pituitary lesion, which leads to TSH and
thyroxine deficiency
Tartary hypothyroidism: Hypothalamus lesion leads to decreased
TRH, TSH, and thyroxin
Clinical features:
- Delayed reflexes (most important bed-side test in
hypothyroidism)
- Generalized weakness
- Cold intolerance
- Constipation
- Menorrhagia but lately amenorrhea
- Brittle nails and hair
- Peripheral edema (late)
- Weight gain with decreased appetite
- Goiter may be present (the first sign in Hashimoto)
- Thinning of the outer half of eyebrows
- In pediatrics (large tongue, umbilical hernia, mental
retardation)
- ECG: sinus bradycardia with low voltage

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Diagnosis:
- Serum TSH (high in primary but low in secondary)
- Free T4 level (low)
- Anti-thyroid peroxidase or anti-thyroglobulin antibodies in
Hashimoto’s thyroiditis
- Dyslipidemia may present
- Pituitary CT or MRI if secondary hypothyroidism
Subclinical hypothyroidism:
- Elevation of TSH with normal T4
- No symptoms of hypothyroidism
- No need for routine treatment of these cases
Treatment: Thyroxine replacement orally

Indications for treatment in subclinical hypothyroidism:

- TSH of more than double the normal
- Positive anti-thyroid peroxidase (anti-TPO)
- Pregnant patient

Hashimoto’s thyroiditis
- Autoimmune disorder against thyroid gland leading to
hypothyroidism
- It is the most common cause of hypothyroidism
- It may cause thyroid lymphoma as a complication.

10% of patients with Hashimoto thyroiditis may be antibody negative

Clinical features:
- Usually subclinical for years before becoming clinical
- Goiter (the first sign)
- Features of hypothyroidism
Diagnosis:
- Mild hyperthyroidism may present initially, but
hypothyroidism is inevitable
- Thyroid function shows clinical or subclinical hypothyroidism
- Presence of anti-TPO (anti-thyroid peroxidase) and anti-TG
(anti-thyroglobulin) antibodies
- A biopsy may be needed
Treatment:
- Medical thyroxine replacement
- Surgical treatment for large goiter or suspicion of lymphoma

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 Myxedema Coma
- It is a medical emergency caused by hypothyroidism and
precipitated by stress
Clinical features:
- Hypothermia, hypoglycemia, and hyponatremia
- Confusion or coma
Treatment:
- IV T3
- Oxygen, Hydrocortisone, Dextrose water
- Antibiotics
- Gradual re-warming by blankets

Hyperthyroidism
- It is an increased activity of the thyroid gland which leads to
an excessive amount of thyroxin in the body resulting in a
high metabolic rate
- More common in females 5:1
Causes:
- Grave’s disease (most common 75%):
o Caused by thyroid-stimulating antibodies
(autoimmune)
o Will present with diffuse thyroid enlargement and
ophthalmopathy
o Pretibial Myxedema, myopathy may be a feature
- Multi-nodular goiter (Plummer’s disease)
- Autonomously functioning solitary thyroid nodule
- Thyroiditis (sub-acute or postpartum)
- Drugs (e.g., amiodarone) (amiodarone can cause both
hypo or hyperthyroidism)
- Maybe secondary to pituitary adenoma (TSH will be high)
Clinical features:
- Nervousness, sweating, tremor, palpitation, tachycardia,
and angina
- Weight loss with increased appetite, Diarrhea, Heat
intolerance
- Pretibial Myxedema
- Amenorrhea, oligomenorrhea, impotence
- Goiter, Hyperreflexia, Hyperkinetic movement
- Eye signs (only seen in Grave’s disease): Led retraction, Led
lag, Conjunctival injection, Ophthalmoplegia, Exophthalmos

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 Diagnosis Unique features
Graves’ disease Eye signs and skin manifestations
Subacute thyroiditis Tender thyroid gland
Silent thyroiditis Painless, non-tender thyroid gland
Pituitary adenoma High TSH level
Table 25: disorders of thyrotoxicosis and their unique features

Diagnosis:
- Low TSH, high T3, High T4 (high TSH level is seen in
hyperthyroidism secondary to pituitary adenoma)
- Grave’s disease:
o Elevated TSH receptor-stimulating antibody
o Antithyroglobulin and anti-microsomal antibodies
may be high
- Radioactive iodine scan (RAIU):
o Elevated in Graves’ disease
o Low in (subacute thyroiditis, silent thyroiditis,
exogenous thyroxine use)
- Hypercalcemia, high Alkaline Phosphatase
- Low Thyroglobulin level is useful in patients with thyrotoxicosis
caused by surreptitious use of thyroid hormone
Treatment:
- Carbimazole (anti-thyroid agent)
o It can be used in the second or third trimester of
pregnancy
o Less hepatotoxic than PTU
- Propylthiouracil (PTU) (anti-thyroid agent)
o Used in the first trimester of pregnancy
o More hepatotoxic than methimazole
o Better to use in thyroid storm
- Thyroidectomy (surgery)
- Radioactive iodine ablation
- Beta-blockers (symptomatic control, decreases the
conversion of T4 to T3)
- Eye signs are treated with steroids or by surgery if not
responsive.

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 Thyroid storm
- A medical emergency of hyperthyroidism, Precipitated by
stress, infection, trauma
Symptoms:
- Fever, nausea, vomiting, and diarrhea
- Arrhythmias, Tachycardia, HTN, Heart failure
- Coma
Treatment:
- Propranolol:
o Block the target organ effect of thyroxine
o Block the peripheral conversion of T4 to T3
- Propylthiouracil or Methimazole:
o PTU is preferred over methimazole
o Block thyroid hormones production
- Steroids
- Radioactive iodine ablation (for a permanent cure)

Hypothyroidism Hyperthyroidism
Bradycardia Tachycardia, arrhythmia, AF
Constipation Diarrhea
Weight gain with less appetite Weight loss with more appetite
Fatigue, depression, coma Anxiety, restlessness, nervousness
Hyporeflexia Hyperreflexia
Cold intolerance Heat intolerance
Heat preference Cold preference
Hypothermia Fever
Coarse hair, dry skin Fine hair, moist skin
Table 26: Hypothyroidism vs. Hyperthyroidism

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 Sub-Acute thyroiditis (De Quervain’s
thyroiditis)
- Inflammation of the thyroid gland (usually to viral etiology)
- It leads to a release of stored thyroxin and thyrotoxicosis
features, followed by hypothyroidism features due to the
destruction of the thyroid cells.
- Viral infection is the most common cause
Clinical features:
- Painful neck
- Features of hyperthyroidism initially
- Later – features of hypothyroidism
Diagnosis:
- High T3, T4 (initially) then later will be decreased
- High ESR
- Decreased RAIU in all parts of the thyroid
Treatment:
- Steroid, NSAIDs (aspirin)
- Treatment of hyperthyroidism initially
- Later, the patient will remain hypothyroidism and will need
thyroxin

Sick euthyroid syndrome (Nonthyroidal illness)

- Any acute, severe illness can affect the circulating TSH and
thyroid hormones in the absence of any thyroid disease
- Unless a thyroid disorder is strongly suspected, routine thyroid
function testing should be avoided in acutely ill patients.
Lab investigations:
- Low T3 syndrome: Low free T3 with normal T4 and TSH (the
most common pattern)
- Low T4 syndrome: reduced T3 and T4 due to accelerated
consumption.
- TSH may be reduced, normal or increased
Treatment:
- No treatment is needed; the changes are reversible upon
recovery from the systemic illness

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 Parathyroid gland
- There are 4 parathyroid glands that are anatomically
adjacent to the thyroid gland.
- Parathyroid hormone (PTH) regulates the serum calcium
level
Calcium regulation
- PTH affects the serum calcium by the following mechanisms:
o Increase urinary reabsorption of calcium
o Increase intestinal calcium absorption
o Extracts calcium from bones into the blood
- Vitamin D effects on the serum calcium
o Increase urinary reabsorption of calcium
o Increase intestinal calcium absorption
o Increase calcium deposition to the bone
- Calcium effects on PTH:
o High serum calcium will suppress PTH release
o Low serum calcium will stimulate PTH release

Hypercalcemia
- The most common cause of hypercalcemia is primary
hyperparathyroidism
- If hypercalcemia is severe and symptomatic, there is a high
prevalence of malignancy due to PTH-like particles
Causes of hypercalcemia:
- Primary hyperparathyroidism (most common cause)
- Vitamin D intoxication
- Sarcoidosis
- Thiazide diuretics
- Hyperthyroidism
- Malignancy: Multiple Myeloma, or Metastasis to bone
Clinical features:
- Usually asymptomatic
- Psychiatric symptoms (confusion, depression, psychosis)
- GI: Constipation, abdominal pain
- Cardiovascular: short QT syndrome and hypertension
- Renal: nephrolithiasis, DI, renal insufficiency, polyuria

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Treatment:
- I.V normal saline (first line)
- Furosemide (Lasix) – use with caution.
- Calcitonin has a faster effect than Bisphosphonates
- Bisphosphonates (inhibit bone resorption)
- Surgical removal of the adenoma
- Mithramycin (used to treatment of hypercalcemia in
malignancy)
- Steroids (treat hypercalcemia in sarcoidosis)

Hypocalcemia (tetany)
- Tetany: increased excitability of peripheral nerves due to
hypocalcemia or alkalosis
Causes:
- Primary hypoparathyroidism: post-thyroidectomy (most
common cause)
- Hypomagnesemia (magnesium is necessary for PTH release
from the gland; hypomagnesemia leads to increase urinary
loss of calcium)
- Renal failure (kidneys are unable to activate Vitamin D into
1,25 (OH) vitamin D)
- Vitamin D deficiency
- Genetic disorders and fat malabsorption
- Alkalosis (metabolic or respiratory)
- Low albumin status (Pseudohypocalcemia)

Pseudohypocalcemia:
-Normal serum Calcium is 8.4 – 10.6 mg/dL
-Normal serum Albumin is 3.5 – 5.5 g/dL (mean = 4.0)
-Every 1 g/L drop in albumin will result in 0.8 mg/dL drop in
serum calcium.
Example on corrected calcium calculation:
Consider serum albumin is 2.5 g/L, and serum calcium is 7.8 mg/dL.
Corrected calcium = 0.8 * (4.0 – serum albumin) + serum ca.
Corrected calcium = 0.8 * (4 – 2.5) + 7.8 = 9 mg/dL.
So, this is a case of Pseudohypocalcemia, not true hypocalcemia.
Table 27: Pseudohypocalcemia and corrected calcium

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Clinical features:
- In children: (carpopedal spasm, stridor, convulsions)
- In adults: tingling in hands, feet, and around the mouth,
muscle cramps, Psychosis, abdominal cramps
- Special signs:
o Trousseaus sign (carpal spasm after inflation of cuff on
the arm)
o Chvostek's sign (twitching of facial muscles after
facial nerve tapping)
o Peroneal sign (taping on Peroneal nerve results in
dorsiflexion and abduction of the foot)
o Erb's sign (motor nerve can be stimulated by low
current < 5 milliamperes)
o Prolonged QT interval in ECG
Treatment:
- Oral or I.V calcium
- Vitamin D replacement
- For hypomagnesemia, administrate MgSO4
- Correction of alkalosis

Hyperparathyroidism
- It can be primary, secondary
- Primary: adenoma, hyperplasia, or carcinoma of the
parathyroid gland
- Secondary: high PTH in response to low serum calcium (CRF,
malabsorption, rickets…)
Clinical features:
- Primary hyperparathyroidism:
o Features of hypercalcemia
o Bone pain and pathological fractures
- Secondary hyperparathyroidism:
o Features of hypocalcemia
Diagnosis:
- Primary hyperparathyroidism:
o High serum calcium and high PTH
o High Alkaline Phosphatase
o High chloride
o Low serum phosphate
o Imaging to localize the pathology

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 - Secondary hyperparathyroidism:
o Low serum calcium
o High PTH level
o Features of the cause
Treatment:
- Primary type:
o Treat hypercalcemia
o Remove the cause (e.g., adenoma removal)
- Secondary type:
o Treat hypocalcemia
o Correct the cause

Hypoparathyroidism
Causes:
- Postoperative hypoparathyroidism, after thyroid surgery, is
the most common cause
- Idiopathic
- Pseudohypoparathyroidism (tissue resistance to PTH)

Pseudohypoparathyroidism: is a congenital resistance to

parathyroid hormone leading to hypocalcemia,
hyperphosphatemia, high PTH and low IQ, short stature, and short
fourth and fifth metacarpals.
Pseudopseudohypoparathyroidism: will present with the same
morphological features of pseudohypoparathyroidism but with
normal serum calcium, phosphate, and PTH

Clinical features of primary hypoparathyroidism:

- Tetany (in severe cases)
- Features of hypocalcemia

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 Familial hypocalciuric hypercalcemia (FHH)
- It is an autosomal dominant disorder caused by a calcium
sensor defect that increases the set point for the serum
calcium
- It can be diagnosed early in childhood by serum and urinary
calcium concentrations
Pathogenesis:
- Abnormal sensing of the blood calcium by the parathyroid
gland and renal tubule, causing inappropriate secretion of
PTH and excessive reabsorption of calcium in the distal renal
tubules
- This will lead to hypercalcemia and hypocalciuria
Diagnosis:
- Most cases are detected during family screening
- Elevated serum calcium and PTH.
- Low urine calcium
- Low urinary calcium:creatinine ratio
Treatment:
- Usually asymptomatic and needs no treatment
- Total parathyroidectomy can be beneficial
- The condition is not responsive to diuretics or
bisphosphonates
Diagnosis Ca PTH PO4 Additional notes
Primary ↑ ↑ ↓ High urine Ca:creatinine ratio
hyperparathyroidism
Secondary ↓ ↑ ↑ Reduced Ca enhances PTH
hyperparathyroidism
Tertiary ↑ ↑ ↑ History of CKD
hyperparathyroidism
Hypoparathyroidism ↓ ↓ ↑
FHH ↑ ↑ Low urine Ca:creatinine ratio
Vitamin D deficiency ↓ ↑ ↓
Pseudo- ↓ ↑ ↑ Specific morphological
hypoparathyroidism features
Pseudo-pseudo- Normal Specific morphological
hypoparathyroidism features
Table 28: Differential diagnosis of parathyroid disorders

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 Adrenal gland
Anatomy:
- Two adrenal glands, located normally at the upper pole of
both kidneys
- They are composed of cortex and medulla and covered by
a capsule
- The cortex is composed of 3 layers:
o Zona glomerulosa: it secrets aldosterone
o Zona fasciculata: it secrets cortisone
o Zona reticularis: it secrets androgen
- Medulla secrets epinephrine and Norepinephrine

Hypercortisolism (Cushing's)
- Increase secretion of cortisone by adrenal glands
- Cushing's syndrome is used interchangeably with
hypercortisolism
- Cushing's disease is a term used for pituitary overproduction
of the ACTH hormone
Causes:
- Pituitary tumor (ACTH-secreting tumor) – Cushing's disease
(most common 70%)
- Adrenal tumor (decreased ACTH)
- Ectopic ACTH production
- Iatrogenic: steroid administration

Causes of Ectopic ACTH secreting tumors:

- Small cell lung cancer
- Bronchial carcinoid
- Pheochromocytoma
- Medullary thyroid cancer
Clinical features:
- Hypertension, hyperglycemia, hypokalemia
- Fat redistribution: Moon face, weight gain / central obesity,
buffalo hump, thin extremities
- Skin: Thinning of skin, abdominal striae, decreased wound
healing, easy bruising, hirsutism, acne, skin pigmentation
- Muscle weakness (proximal muscle)
- Sexual disturbances, edema, amenorrhea
- Psychiatric symptoms (e.g., depression)

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Diagnosis:
- Low dose (1 mg) dexamethasone suppression test
- ACTH levels
- High dose (8 mg)dexamethasone suppression test
- CT or MRI to localize the pathology
- Petrosal sinus sampling to confirm Cushing's disease when
microadenoma does not show in imaging
- Other labs: hyperglycemia, hyperlipidemia, Hypokalemia,
metabolic alkalosis

Figure 8: Diagnostic approach to Cushing's syndrome

Treatment:
- Pituitary adenoma: transsphenoidal excision
- Adrenal source: adrenalectomy of the affected side
- For Ectopic ACTH secretion: treat the cause
- For iatrogenic: stop steroid use if possible

Petrosal sinus: is the venous drainage of the pituitary gland, if

imaging fails to localize the pituitary adenoma, then
microadenoma is suspected, and petrosal sinus sampling will
confirm the diagnosis.

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 Hypoadrenalism (Addison's disease)
- Chronic primary adrenal insufficiency
- Note that acute adrenal insufficiency is called adrenal crisis
Causes:
- Autoimmune (most common cause 80%)
- Infection (HIV, TB)
- Bilateral adrenalectomy
- Metastatic cancer in adrenal glands
Clinical features:
- Weakness, weight loss, fatigue, vomiting, fever, constipation,
abdominal pain, impotence, syncope, postural hypotension,
loss of axillary hair
- Hyperpigmentation of skin (due to increased MSH), Not
present in secondary adrenal insufficiency
- Hypotension
- Vitiligo (autoimmune process)
Diagnosis:
- Hyperuricemia, hyperkalemia, hypercalcemia
- Hyponatremia, hypoglycemia, metabolic acidosis
- Abdominal CT scan
- Specific tests:
o Serum cortisol (low) and ACTH (high)
o Cosyntropin stimulation test (most specific test)
o Anti-adrenal antibodies 50%
o Low serum aldosterone
Treatment: Hormone replacement
Low High
Sodium Urea
Blood sugar Potassium
Serum cortisol Calcium
Serum aldosterone ACTH
Table 29: Lab tests in primary hypoadrenalism

Secondary hypoadrenalism:
It is caused by hypothalamic or pituitary disease or long-
term steroid suppression; aldosterone remains normal in this
case because it is controlled by the renin-angiotensin
system.

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 Adrenal crisis
- It is a medical emergency caused by sudden and marked
insufficiency of adrenocortical hormones
Precipitating factors:
- Stress (trauma, infection, hemorrhage, surgery, hypotension)
- Sudden withdrawal of chronic high-dose steroid therapy
Clinical features:
- Dehydration, headache, confusion, coma
- Hypotension (shock)
- Hypoglycemia
- Nausea, vomiting, diarrhea, abdominal pain
- Hyponatremia and hyperkalemia
- High urea
Treatment:
- Hydrocortisone injection (first step)
- I.V fluids
- Treatment of hypoglycemia
- Antibiotics
- Shock management

Primary hyperaldosteronism
- Hypersecretion of aldosterone despite low renin and
hypertension
Causes:
- Adrenal adenoma (Conn's syndrome)
- Adrenal hyperplasia
- Adrenal malignancy (rare)
Diagnosis:
- Suspected if HTN + Hypokalemia + metabolic alkalosis
- Aldosterone:renin ratio > 20 (best initial test)
- 24 hours urinary aldosterone
- Localize tumor or hyperplasia by CT or MRI (best)
Treatment:
- Surgery for tumor
- Spironolactone for hyperplasia

Spironolactone (Aldactone) is an anti-androgenic drug, so it

causes gynecomastia and decreased libido

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 Pheochromocytoma
- It is a tumor of the medulla of the adrenal gland that
secretes epinephrine and norepinephrine,
- It can be associated with other conditions like (MEN IIB,
neurofibromatosis, and Von Hippel Lindau syndrome)

10% malignant, 10% bilateral, 10% familial, and 10% extra-adrenal

Clinical features:
- HTN (paroxysmal or persistent)
- Sweating
- Tachycardia
- Weight loss
- Tremor
- Hyperglycemia, hypercalcemia, and erythrocytosis
Diagnosis:
- Free metanephrine level in plasma (initial test)
- 24 hours urinary vanillylmandelic acid
- 24 hours urinary catecholamines
- 24 hours urinary metanephrine (the most accurate test)
- Imaging to localize the tumor
Treatment:
- Phenoxybenzamine (alpha-blocker)
- Non-cardioselective beta-blockers (e.g., propranolol)
- Surgical removal (the definite treatment)

Non-cardioselective beta-blockers should be used if significant

tachycardia occurs after the alpha blockade. Beta-blockers
should not be administered until an adequate alpha blockade is
achieved because unopposed alpha-adrenergic receptor
stimulation can precipitate a hypertensive crisis. However,
cardioselective beta-blockers may be used.

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 Diabetes mellitus (DM)
- DM is a clinical syndrome characterized by hyperglycemia
due to an absolute or relative insulin deficiency.
- There are two common types of DM (Type 1 and type 2)
Metabolism of glucose:
- The blood-brain barrier is not permeable to free fatty acids,
so it depends on glucose as a main source of energy
- Glucose enters circulation by the gut (from food) or by the
liver (gluconeogenesis and glycogenolysis)
- Insulin and glucagon are regulatory hormones of glucose;
they are synthesized and secreted by the pancreas
- Insulin is also responsible for fatty acid metabolism and
causes triglyceride accumulation in the body, while low
insulin levels can activate lipolysis.

Type 1 DM
- An autoimmune disease destroys insulin-secreting β cells in
the pancreas; it will remain asymptomatic until 90% of beta
cells are destroyed and usually starts before 30-35 years old
- Glutamic acid antibodies (GAD antibodies) have a role in
pathogenesis, but it is not useful for diagnosis or screening
- T1DM is also Association with HLA-DR3 or HLA-DR4
- Like any other autoimmune disease, it can be associated
with other autoimmune diseases like Addison's disease,
pernicious anemia, and Vitiligo
- There is 35% concordance between monozygotic twins in
T1DM but 100% concordance between monozygotic twins in
T2DM
- Environmental factors play a role in T1DM, like smoked food,
viral infections, or cow's milk administration in infant life
(bovine serum albumin is implicated in the development of
T1DM)

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Metabolic and clinical features: Features of T1DM do not manifest
until 90% of beta cells are destroyed. Insulin deficiency starts to
manifest, and hyperglycemia results in a toxic effect on the
remaining beta cells and thus more profound, rapidly progressive
insulin deficiency that leads to:
- Lipolysis: weight loss, ketogenesis, and metabolic acidosis
- Hyperglycemia: osmotic polyuria and dehydration
- Dehydration can lead to renal impairment, hyperosmolarity,
polydipsia, and hyperkalemia (shifting of K+ out of cells)

The summary of the T1DM presentation:

- Weight loss
- Metabolic acidosis with ketogenesis (DKA)
- Polyuria, Polydipsia, and polyphagia
- Dehydration and acute renal failure

Treatment:
- Insulin (OHA are not beneficial)
- The target A1C target is < 7%
- Treatment of complications if present (e.g., DKA)

Type 2 DM
- The patient has decreased insulin level, but to a lesser extent
than T1DM, and is usually associated with insulin resistance.
- Environmental and genetic factors are implicated in the
development of T2DM
- Obesity and a sedentary lifestyle (under-activity) are
important risk factors
- T2DM usually affects older ages
Metabolic and clinical features:
- In T2DM, insulin suppresses lipolysis, and thus weight gain is a
prominent feature, while ketosis and metabolic acidosis will
be rare
- Slowly growing hyperglycemia leads to less severe or even
absent symptoms of hyperglycemia
- The patient may present with mild generalized fatigue,
Polyuria, polyphagia, and Polydipsia for a long period

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 The summary of the T2DM presentation:
- Mild fatigue for a long period
- Polyuria, Polyphagia, and Polydipsia
- If a stressful event occurs, increased counterregulatory
hormones will lead to hyperglycemic hyperosmolar
nonketotic coma (HHS)
- DKA is very rare in T2DM

Treatment:
- Lifestyle modifications (initially for 3 months)
- Oral hypoglycemic agents:
o Start if there is no glucose improvement with the
lifestyle modifications for 3 months
o Provide a single agent if the A1C level is less than 9%
o Provide two agents if the A1C level is more than 9%
o A combination of more than OHA is possible with
paying attention to their side effects and interactions.
- Insulin: Used for patients who are not responding or cannot
tolerate OHA

HbA1c target in DM treatment:

- If a young educated patient and easily controlled (on
lifestyle modifications only or lifestyle modifications +
Metformin), an A1C target of less than 6.5% is acceptable
- If the patient is on any drug that can cause hypoglycemia
(e.g., sulfonylurea), the A1C target of less than 7% is
appropriate.

T1DM T2DM
Definition Insulin deficiency Insulin resistance
Onset Childhood Adulthood
Obesity Not related Related
Treatment Insulin dependent Non-insulin dependent
Complication DKA HHS
Table 30: Comparison between T1DM vs. T2DM

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 Prediabetes (Pre-DM)
- It is not a disease but rather a risk category
- These patients are at risk of developing DM later in their lives
Diagnosis of Prediabetes:
- Impaired fasting glucose (IFG): FBS 100-125 mg/dl
- Impaired glucose tolerance (IGT): 2h 75 g OGTT140-199
mg/dl
Management:
- Lifestyle modifications (diet, exercise, stop smoking, control
HTN, control dyslipidemia)
- Metformin especially for:
o Those who are > 60-year-old
o Those with high BMI > 35 kg/m2
o Women with a history of gestational DM

Maturity onset diabetes of the youth (MODY)

- Genetic defect (autosomal dominant) of beta-cell function
leads to decreased insulin secretion.
- The incidence is between 9 and 25 years old.
Criteria for diagnosis:
- Diabetes is diagnosed in 3 generations in the family.
- At least one family member diagnosed under the age of 25
years
Treatment of DM in pediatrics:
- Insulin is the drug of choice for DM in pediatrics

Lab tests and diagnostic criteria

- Urinary glucose level is not a reliable indicator for DM. It may
increase due to a decreased urinary threshold (e.g.,
pregnancy and young people)
- Random blood sugar (RBS) is a test done at a random time
(non-fasting patients)
- Fasting blood sugar (FBS): testing after 8 hours of fasting.
- 2h 75 g OGTT is done 2 hours after administering 75 grams of
sugar to a fasting patient.
- Glycated hemoglobin (HbA1c): reflects glycemic control
over 3 months and is a measure of a patient's long-term
diabetes control

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Lab test Normal range Pre-DM DM
FBS (mg/dL) < 100 100 – 125 ≥ 126
2h-P OGTT (mg/dL) < 140 140 – 199 ≥ 200
HbA1c < 5.6% 5.7 – 6.4% ≥ 6.5%
Table 31: Glucose investigations and their ranges

Diagnostic criteria of DM: any one of the following is diagnostic:

- The presence of DKA is diagnostic for T1DM
- Symptoms of DM + RBS ≥ 200 mg/dl or,
- One of the following On at least two separate occasions:
o FBS ≥ 126 mg/dl
o 2h 75 g OGTT ≥ 200 mg/dl
o RBS ≥ 200 mg/dl
o HbA1c ≥ 6.5%

DM complications
- Patients with T1DM should be assessed for DM complications
5 years after initial diagnosis with DM
- Patients with T2DM should be evaluated at the time of
diagnosis because T2DM remains for many years
undiagnosed and can cause complications at the time of
diagnosis.
Microvascular complications:
- Retinopathy – visual problems (After 5 years of DM)
- Nephropathy – renal impairment (After 10 years of DM)
- Neuropathy – sensory and autonomic can be affected (15
years of DM)
- Diabetic foot – ulceration, infection, and gangrene
Macrovascular complications:
- CAD – Coronary Arterial Disease (the most common cause
of death)
- PAD – Peripheral Arterial Disease
- CVA – Cerebrovascular Accidents
Others:
- Cataract
- Infections (UTI, Pneumonia, soft tissue infections, TB)

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 - To prevent diabetic complications, diabetic control
should be achieved with near-normal glycemic control;
this will reduce deaths and vascular complications
related to DM.
- In the case of nephropathy, consider a cause other than
DM if there is no retinopathy

Health maintenance in DM patients:

- Pneumococcal vaccination for all patients
- Yearly eye examination
- Aspirin to all patients with DM who are > 30 years
old
- Statin in patients with high LDL > 100 mg/dl
- ACEI/ARB for patients with DM + HTN and/or
microalbuminuria.
- Foot examination for neuropathy and ulcers
Table 32: Health maintenance for all DM patients

Diabetic retinopathy
- Screening for retinopathy is recommended to be done
yearly.
- This usually occurs in the first decade of DM development
Stages:
- Non-proliferative stage:
o Retinal vascular microaneurysms
o Blot hemorrhages
o Cottonwool spots
- Proliferative stage:
o Neovascularization in response to hypoxia
o Vitreous hemorrhage due to rupture of the new blood
vessels
- Macular edema:
o It may occur at any stage
o The most common cause of vision loss in DM patients
(25% risk of moderate vision loss in the next 3 years)

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Treatment:
- Prevention is the most effective therapy:
o Intense diabetic control
o Intense blood pressure control
o Temporary paradoxical worsening of retinopathy may
occur within 6 – 12 months of improved glycemic
control
- Proliferative retinopathy: pan-retinal laser photocoagulation
- Macular edema: focal laser photocoagulation

Diabetic nephropathy
- It is the most common cause of renal failure in adults.
- This condition takes up to 10 years of diabetes to develop.
However, high A1c is an independent risk factor for
microalbuminuria.
- Albuminuria in individuals with DM is associated with an
increased risk of cardiovascular disease.
- Individuals with diabetic nephropathy commonly have
diabetic retinopathy as well
- Smoking will accelerate the development and progression
of diabetic nephropathy
Clinical and laboratory features:
- Persistent albuminuria (microalbuminuria)
- HTN, nephrotic syndrome, and renal failure
Stages of diabetic nephropathy: (according to timing)
- In the first year after DM onset:
o Renal hypertrophy and glomerular hyperfiltration
o Results from afferent arteriolar dilatation and efferent
arteriolar vasoconstriction
o Increased GFR up to 140%
- During the first 5 years:
o Mesangial volume expansion (resulted in Kimmelstiel-
Wilson nodules)
o Glomerular basement membrane thickening (more
permeability to proteins)
o Disruption of the podocytes (more protein loss)
o GFR is returning to normal

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 - Persistent albuminuria 30–299 mg/day (Microalbuminuria):
o Occurs after 5 – 10 years after DM onset
o May progress to macroalbuminuria (≥ 300 mg/day)
o It cannot be detected by urinalysis
- Persistent albuminuria ≥ 300 mg/day (Macroalbuminuria)
o Develops over the next 10 years
o Once macroalbuminuria develops, ESRD will occur in
7 – 10 years
o Blood pressure and pathologic renal changes are
likely to be irreversible at this time
Screening: by albumin creatinine ratio (ACR):
- It should be done annually for all patients
- It should be done by an early morning specimen
- ACR > 2.5 is considered microalbuminuria
Management:
- Diabetic control is the most important step in the
management
- Strict blood pressure control (< 140/90)
- ACE inhibitors or ARBs are the treatments of choice to
reduce the progression of the disease and to reduce the
level of microalbuminuria
- Strict control of dyslipidemia

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 Diabetic neuropathy
- Symmetrical sensory polyneuropathy: also called Gloves and
stocking impairment, with loss of tendon reflexes in legs
- Asymmetrical motor neuropathy: thought to be due to an
acute infarction in the lumbosacral plexus. present with
weakness of proximal muscles associated with loss of tendon
reflexes
- Mononeuropathy: motor or sensory, rapid dysfunction of
single peripheral or cranial nerve, most common nerves
affected are 3rd, 6th cranial nerves, sciatic nerve, and
femoral nerve. if more than one nerve is affected, it is called
mononeuritis multiplex
- Autonomic neuropathy: postural hypotension, loss of
bladder control, bradycardia, erectile dysfunction,
constipation, diarrhea, incontinence, gastric atony.

Diabetic ketoacidosis (DKA)

- DKA usually occurs in T1DM, characterized by insulin
deficiency with increasing counterregulatory hormones (GH,
Cortisone, Adrenalin, Glucagon)
- It can present in T2DM, but that is very rare.
Precipitants:
- Stress, infection, trauma
- Non-adherence to insulin therapy
- Expired insulin or bad insulin storage
Pathogenesis:
- Lake of insulin → hyperglycemia → osmotic diuresis →
dehydration → electrolyte disturbance (hyponatremia)
- Lake of insulin → lipolysis → ketone bodies → metabolic
acidosis → deep rapid breathing (for compensation)
- Total body potassium is deficient, but normal serum
potassium due to shifting to extracellular fluids
Clinical features:
- Polyuria, polyphagia, and Polydipsia
- Dehydration
- Kussmaul's breath (deep rapid respiration) with fruity-smelling
breath
- Altered mental status
- Non-specific abdominal pain

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Lab investigations:
- ABGs:
o Metabolic acidosis with a wide anion gap
o Low bicarbonate level (the most accurate measure
of severity of DKA)
- High ketones in urine and plasma
- Hyperkalemia, hypokalemia, or normal serum potassium
may present, but total body potassium is always low
- Hyperglycemia (Must be ≥ 250 mg/dl)
- Pseudo-hyponatremia
Treatment:
Keep NPO, insert Foley’s catheter to monitor urine output
- Fluid (first line):
o 1 liter over ½, 1, 2, 2,4, 4, 6, then 1-liter q8 hours
o The fluid type is normal saline and should be shifted to
D5W whenever the serum glucose level is < 250 mg/dl.
o A slower infusion may be indicated in 18-25 year-old
patients as they are at greater risk of cerebral edema
- Insulin:
o 0.1 unit/kg/hour insulin infusion pump
o Check serum glucose every 1 hour.
- Potassium (KCL):
o Serum K+ > 5.3 mEq/L: stop KCL infusion
o Serum K+ 3.5 - 5.3 mEq/L: give 40 mEq/L
o Serum K+ < 3.5 mEq/L: give > 40 mEq/L under senior
supervision.
o Check serum potassium every 2 – 4 hours
- Sodium bicarbonates indications:
o It is not used routinely as it rapidly reverses acidosis,
impairs cardiac function, reduces tissue oxygenation,
and promotes hypokalemia.
o Sodium bicarbonate use is associated with the risk of
brain edema.
o It is indicated if severe acidosis is present (i.e., arterial
pH < 7.0)
o Dose: 50 mmol/L in 200mL of sterile water with 10
mEq/L KCl per hour for 2 hours until the pH is > 7.0
- Mannitol can be used if cerebral edema present
- Antibiotics for treatment of underlying infection
Serum glucose, electrolytes, KFT, and ABGs, should be checked
regularly to monitor improvement

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 Hyperosmolar Hyperglycemic syndrome (HHS)
- Also called hyperosmolar hyperglycemic nonketotic coma
- Usually, it occurs in T2DM
- Relative or partial insulin deficiency leads to decreased
glucose utilization and increased gluconeogenesis
- Lipolysis can be suppressed by a small amount of insulin, so
there will be no ketone bodies formation
Features:
- Hyperglycemia (Must be > 600 mg/dl)
- Polyuria, polyphagia, Polydipsia
- Dehydration along with electrolytes disturbances
- Hyperosmolarity
- Decreased level of consciousness

Osmolarity = 2(Na+) + serum glucose + serum urea (all in mmol/l)

Treatment:
- Intravenous fluid management:
o 1–3 L of 0.9% normal saline over the first 2 – 3 hours
o Use 0.45% saline if there is hypernatremia (> 15 meq/L)
o After hemodynamic stability is achieved, reverse the
free water deficit (0.45% saline then D5W); the
calculated deficit should be reversed over the next 2
days.
o As in DKA, Glucose should be added to the
intravenous fluid if the RBS is less than 250 mg/dL.
- Potassium repletion as in DKA
- Insulin therapy:
o IV insulin bolus of 0.1 unit/kg; then
o IV insulin infusion constant rate of 0.1 unit/kg/hour.
o Double the insulin dose if serum glucose is not falling
o Reduce insulin infusion to 0.05 u/kg/hour if serum
glucose is less than 250 mg/dL.
o Continue insulin infusion until the patient has resumed
eating and can be transferred to subcutaneous
insulin.

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 Parameter DKA HHS
Age Young patients Elderly patients
Disease type T1DM > T2DM T2DM
Glucose ≥ 250 mg/dl More than 600 mg/dl
Acidosis Present (HCO3-< 18) Not present (HCO3-> 18)
Anion gap Increased Normal
Osmolality > 290 mOsm/kg > 320 mOsm/kg
Dehydration Less than HHS More prominent
Insulin required More Less
Table 33: DKA vs. HHS

Hypoglycemia
General considerations about hypoglycemia
- Hypoglycemia may be postprandial or fasting
- Postprandial hypoglycemia occurs within 5 hours after the
last meal and is a common complication of gastrectomy or
gastric bypass
Whipple's triad: (diagnostic for hypoglycemia)
- Decreased level of consciousness
- Serum glucose < 55 mg/dl
- Improvement after administration of glucose
Causes:
- Surreptitious (Insulin or OHA use)
- Insulinoma
- Chronic disorders (Severe CLD, CKD)
- Hypocortisolism
- Infant of diabetic mother
- Anorexia nervosa
Treatment:
- Oral carbohydrates (for conscious patients)
- Intravenous dextrose (for unconscious patients)
- Intravenous glucagon can be used
- Correct the underlying cause
- For postprandial type, choose small meals containing fat,
high-fibers, and complex carbohydrates

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 - The appropriate dose of intravenous dextrose to treat
hypoglycemia is 0.25 g/kg. this is equivalent for 2.5 ml/kg
of 10% dextrose or 1 ml/kg of D25%.
- Use a central line to administrate dextrose of
concentration of more than 10% to avoid the risk of
thrombophlebitis.
Table 34: Treatment of hypoglycemia in babies

Surreptitious hypoglycemia
- It is the deliberate use of insulin or oral hypoglycemic agents
(OHA) or insulin to induce hypoglycemia
Diagnosis:
- History of access to OHA or insulin
- C-peptide level (during the event):
o It is an indicator of high endogenous insulin
o It will be high in OHA usage
o It will be low in insulin usage
- A urinary toxicology screen for OHA
Treatment:
- Correct the hypoglycemia
- Adjust the dose of insulin or OHA if the patient is taking a
high dose by mistake
- Appropriate reporting as indicated in your country

Insulinoma
- Insulin is a peptide hormone composed of 51 amino acids
- Insulinoma is a benign tumor (usually < 2cm diameter) (few
cases are malignant)
- An insulin-secreting tumor affects beta cells of the pancreas
commonly found in the body and tail.
- It may present as a part of MEN type I
Diagnosis:
- The patient has recurrent unexplained hypoglycemia.
- Hypoglycemia (Whipple's triad)
- C-peptide will be high during the attack
- Insulin levels will be high
- Imaging to locate the tumor
Treatment:
- Treatment of hypoglycemia
- Surgical removal of the tumor

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 Other endocrine disorders
Multiple Endocrine Neoplasia (MEN)
- Inherited (Autosomal dominant) rare syndrome in which
multiple endocrine glands got Neoplasia
- The most common presentation in MEN I is hypercalcemia

MEN Associated tumors

MEN I Pancreatic, Pituitary, Parathyroid tumor
MEN IIa Parathyroid, Pheochromocytoma, Medullary thyroid ca.
MEN IIb Pheochromocytoma, Medullary thyroid cancer,
Neuroma, and Marfanoid features
Table 35: Types of Multiple Endocrine Neoplasia (MEN)

Figure 9: Mnemonics for MEN types

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 Gynecomastia
- It is also called gynecomazia.
- It is defined as glandular breast tissue in males due to an
imbalance between estrogen and androgen.
Causes:
- Idiopathic (25%)
- Physiologic (persistence pubertal gynecomastia) (25%)
- Drug-induced (10-25%): Cimetidine, Digoxin, Spironolactone,
Anti-androgen therapy, and some steroids.
- Hypogonadism (10%)
o Klinefelter's syndrome
o Autoimmune gonadal failure
o Orchitis
o Chemotherapy
o Hypopituitarism
o Kallmann's syndrome (GnRH deficiency)
o Hyperprolactinemia
- Androgen resistance syndromes
- Estrogen excess:
o Liver failure
o Estrogen-secreting tumors (testes, adrenal)
o HCG secreting tumor (testes, lung)
Diagnosis:
- Clinical diagnosis
- A detailed history and Drug history are important
Treatment:
- Remove the cause if possible
- Surgical removal for cosmetic reasons

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 Obesity
- It is defined as the body mass index of ≥ 30 kg/m2
- Obesity increases the rate of mortality and morbidity
because of its association with insulin resistance, DM, HTN,
dyslipidemia, stroke, IHD, peripheral arterial diseases,
Osteoarthritis, GERD, OSA, and many other conditions.
- The body mass index = weight in kg/(height in meters)2

Body mass index (BMI) estimation for adults:

Underweight <18.5 kg/m2
Normal weight 18.5 – 24.9 kg/m2
Overweight 25 – 29.9 kg/m2
Obesity ≥ 30 kg/m2
Table 36 Normal and abnormal values of BMI for adults

Management:
- The reasonable initial goal is the loss of 0.5 – 1 kg of weight
per week
- Combined diet and exercise therapy (exercise is not
effective as monotherapy)
- Pharmacologic therapy like gastric and pancreatic lipase
inhibitors (Orlistat) may be used.
- Bariatric surgeries are indicated if the BMI of > 40 kg/m2 or >
30 kg/m2 in the presence of obesity-related conditions like
(OSA, DM, OA)
o Improves the quality of life and reduces mortality
o Improves glycemic control for DM patients
o Reduce the use of medications

Types of bariatric surgeries:

- Banding procedure: a band is placed around the upper
part of your stomach to create a small pouch to hold food
- Gastric bypass: involves creating a small pouch from the
stomach and connecting the newly created pouch
directly to the small intestine
- Sleeve gastrectomy: removing about 75% of the stomach

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 Dyslipidemia
- It is an abnormal increase in cholesterol or Triglyceride
- LDL is the main cause of atherosclerosis
- HDL is good lipoprotein and does not cause atherosclerosis
Risk factors:
- Endocrine: Hypothyroidism, Cushing’s syndrome, DM,
Obesity
- Renal: CKD, Glomerulonephritis
- Liver disease
- Sedentary lifestyle and alcohol
- Drug use: OCP, Steroid, Diuretic in high dose
Signs:
- Atherosclerosis: blood vessels plaque (CAD, PAD, Renal artery
stenosis)
- Skin manifestations:
o Tendinous xanthoma: associated with familial
hypercholesterolemia
o Eruptive xanthoma: associated with
hypertriglyceridemia
Investigations:
- Fasting Lipid profile (LDL, HDL, Total cholesterol, TG)
- TFT, KFT, LFT, Serum glucose
- Assessment of CAD
Cases in which statin should be used (CAD equivalents):
- Peripheral arterial disease (PAD)
- Carotid disease
- Aortic artery disease
- DM
Management:
- Lifestyle modifications
- Statins (HMG CO-A inhibitors)
o The best treatment for a high LDL level
o The lipid-lowering agent with the strongest mortality
benefit
o They have an antioxidant effect on the endothelial
lining
o E.g., Atorvastatin, Simvastatin, Lovastatin, Rosuvastatin
o Side effects: Myositis, hepatotoxicity, warfarin
potentiation

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- Niacin:
o Excellent drug to add the statin
o Niacin is stronger than statin, exercise, and smoking
cessation to raise HDL
o Associated with Glucose intolerance, elevation of uric
acid, and itching
- Fibrates (lipoprotein lipase stimulators):
o E.g., Gemfibrozil, fenofibrate
o Lower TG level more than statin
o The combination with a statin increases the risk of
Myositis
- Cholestyramine:
o Bile acid Sequestrant
o Has significant interaction with other medications in
the gut (decrease their absorption)
o Side effects include constipation and Flatus.
- Ezetimibe (Cholesterol absorption inhibitor):
o Lowers LDL but with no benefit
o Not better than placebo in the clinical endpoint
- Protein Convertase Subtilisin Kexin type 9 (PCSK9) inhibitors:
o E.g., Evolocumab, Alirocumab
o Injectable medication that can decrease LDL strongly
o Used if the patient is not responsive or cannot tolerate
statin

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 Metabolic syndrome
-Also known as insulin resistance syndrome or syndrome X
-A cluster of metabolic and pathophysiologic disorders
confer increased cardiovascular disease and DM risk.
Components:
- Central obesity (waist circumference)
- High triglycerides (> 1.7 mmol/l)
- Low HDL (< 1.0 mmol/l)
- HTN
- T2DM or impaired glucose tolerance (IGT)

- Women with PCOS are at increased risk of developing

insulin resistance, hyperlipidemia, and metabolic
syndrome
- LDL and total cholesterol may be below average in
patients with metabolic syndrome. Therefore, they do
not exclude CVD risk and are not a part of this cluster.

Management:
- Lifestyle modifications (diet, physical activity)
- Treatment of dyslipidemia
- Blood pressure control
- Diabetic control

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 Pulmonology
CHAPTER 3

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Pulmonary Function Test (PFT)
Spirometry and Lung volumes
-PFT is used to determine the nature of the pulmonary disease
(Obstructive V.S restrictive)
- Spirometry is used to differentiate obstructive vs. restrictive
lung diseases.
Components of Lung volumes and spirometry:
- Tidal volume (TV):
o The volume of respiration at rest
o Normally 20 ml in newborn
o 350 ml in adult female
o 500 ml in adult male
- Residual volume (RV):
o The remaining volume which cannot be exhaled
o Normally 1200 ml in adults
o This volume cannot be measured by the spirometry
- Total Lung Capacity (TLC):
o Equal to FVC + RV = normally 6200 ml
o Increased in case of Emphysema
- Forced Vital capacity (FVC):
o The volume of forced inspiration to forced expiration
o VC = TLC – RV = 5000 ml
o It will be reduced in case of restrictive lung disease
- FEV1:
o Forced expiratory volume in 1 second
o It is significantly reduced in the case of obstructive
lung disease
- FEV1/FVC ratio:
o Significantly reduced in case of obstructive lung
disease
o Normal or increased in restrictive lung disease

Inspiratory capacity (IC) = TV + IRV

Vital capacity (VC) = TV + IRV + ERV
Forced resedual capacity (FRC) = ERV + RV
Total lung capacity (TLC) = RV + ERV + TV + IRVs

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 Figure 10: The normal lung volumes for a healthy 70 kg male
(1- Tidal volume, 2- inspiratory reserved volume, 3- residual volume, 4- expiratory
reserved volume, 5- inspiratory capacity, 6- vital capacity, 7- functional residual
capacity, 8- total lung capacity)

Obstructive diseases Restrictive diseases

FEV1 Significantly reduced Reduced
FVC Reduced or normal Significantly reduced
FEV1/FVC Reduced Normal or increased
Example: Asthma Pulmonary fibrosis,
COPD Asbestosis, Sarcoidosis,
Bronchiectasis ARDS, RDS, Kyphoscoliosis,
Cystic fibrosis Neuromuscular disorders
Table 37: Obstructive vs. Restrictive lung diseases

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 TLCO (DLCO)
- Diffusing capacity or transfer factor of the lung for CO gas
- It describes the rate of gas diffusion from alveoli to blood.
- In COPD, DLco differentiates emphysema from chronic
bronchitis
- In restrictive lung diseases, DLco determines intrinsic vs.
extrinsic restrictive lung diseases.
Causes of increased DLCO Causes of decreased DLCO
- Asthma - Fibrosis
- Polycythemia - Pneumonia
- Pulmonary hemorrhage - PE
- Male gender - Pulmonary edema
- Exercise - Anemia
- Left to right shunt - Emphysema
- Low cardiac output
Table 38: causes of high vs. low DLco

A-a gradient
- It measures the efficacy of gas exchange between alveoli
(A) and the artery (a)
How to calculate:
- A – a gradient = PAO2 – PaO2
- PaO2 is measured by ABGs
- PAO2 = FiO2 * (760 – 47) – (1.25 * PaCO2)
- The normal A-a gradient = 0.3 * age in years
Interpretation:
- An abnormal A-a gradient suggests the lungs as a possible
cause of hypoxemia
- The normal A-a gradient suggests causes external to the
lung as a cause for hypoxemia
Hypoxia with wide Aa gradient Hypoxia with narrow Aa gradient
Pulmonary edema (CHF, ARDS) Hypoventilation
Lobar pneumonia Central nervous system disorders
Atelectasis High altitude
Pulmonary embolism Hemoglobin defect (Anemia)
COPD and Asthma
Pneumothorax
Table 39: Causes of hypoxia according to the A-a gradient

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 Obstructive lung diseases
Asthma
- Asthma is a chronic disease that causes inflammation with
reversible & variable narrowing of the airways (The main
difference between asthma and COPD is reversibility and
variability)
- Asthma is usually associated with a history or family history of
other IgE-related diseases like atopic dermatitis (eczema)
and atopic rhinitis (hay fever)
- 70% of asthmatic patients are sensitive to Aspirin and other
NSAIDs.
- Triggers are: dust, smoking, air pollution, Drugs – NSAID, Beta-
blockers, exercise, emotions, sudden changes in air
temperature
Types of asthma:
- Occupational asthma: chemicals at work worsen asthma,
and the patient is better at weekends.
- Cough variant asthma: asthma presented with cough
exclusively.
- Exercise-induced asthma: asthmatic attack triggered by
exercise.
Pathophysiology:
Exposure to allergen → bronchospasm, airway edema, increased
mucus and goblet cells → airway obstruction → hypoxemia →
hyperventilation → Decreased PaCO2 → respiratory alkalosis →
respiratory muscle fatigue → decreased ventilation → increase CO2
+ respiratory acidosis + respiratory failure
Diagnosis:
- CXR shows a hyperinflated chest:
o Horizontal ribs
o Wide spaces between ribs
o Low set, flat diaphragm
o Vertical heart
o Hyperlucent lung field
- Pulmonary function test (PFT) (The most accurate test):
o Will show decreased FEV1/FVC ratio
o Increase in FEV1 > 12% and 200 ml after use of SABA
(reversibility)
o FEV1 also used for staging
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 - Increased DLCO
- Peak expiratory flow and ABGs (the best initial tests in acute
asthma)
- Other tests:
o CBC: eosinophilia
o Skin testing: to identify the specific allergen
The main clinical features of asthma:
- Symptoms usually worsen at night and vary over time
- Cough (the most common symptom)
- Dyspnea, expiratory wheezing, tachypnea, tachycardia,
chest tightness
- Pulsus paradoxus
- Reversible obstruction on PFT
- Associations:
o Asthma is frequently associated with nasal polyps and
sensitivity to aspirin
o History or family history Eczema and atopic dermatitis
are usually present.

Classification of asthma:
Class of asthma Diurnal attacks Nocturnal attacks FEV1%
Mild intermittent < 2/week < 2/month ≥ 80
Mild persistent > 2/week > 2/month ≥ 80
Moderate persistent Every day > 1 per week 60-80
Severe persistent Every day Every day < 60
Table 40: Asthma classification according to the severity

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 Asthma management
- The following table shows the stepwise approach to treating
asthma
- Step up or step down in medications according to the
patient's symptoms.
- The patient’s compliance with his inhaler and technique
should be checked before changing the medications.

Figure 11: A stepwise approach to asthma control

Short-acting beta-agonist:
- Used as needed (reliever)
- Side effects: hypokalemia, tachycardia, and tremor
- SABA alone has more risk of exacerbation compared to
SABA + ICS use. Therefore, according to the recent
guidelines, ensure the patient will adhere to ICS therapy
before prescribing SABA.
Inhaled corticosteroids (ICS)
- Used as add on if asthma is not controlled on SABA alone
- Example: beclomethasone, fluticasone
- Used as a controller (preventer) but (not used as a reliever in
acute asthma)
- Side effects include dysphonia and oral candidiasis
Long-acting beta 2 agonists (LABA)
- Used as controller, not reliever
- Example: Salmeterol
- Formoterol is a fast-acting LABA used as a reliever.
- it is not used as monotherapy in asthma patients

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Leukotriene receptor antagonist (LTRA)
- Oral medication (not inhaler) is used to control asthma but
not as a reliever
- Example: Montelukast
Long-acting muscarinic antagonist (LAMA)
- Used as controller, not reliever
- Example: Tiotropium
- It can be used alone or in combination as ICS-LABA-LAMA

Acute exacerbation of asthma

- It is also called Status asthmaticus
- it is defined as acute or subacute worsening of symptoms
and lung function in a patient with asthma.
- Asthma exacerbation is classified as moderate, severe, and
life-threatening asthma.

Parameter Moderate Severe Life-threatening

PEFR 50 – 75% 33 – 50% < 33%
General Conscious Conscious Cyanosed
Condition Normal speech Can’t complete Confusion
a sentence Coma
RR < 25/min > 25/min Bradycardia
Pulse < 110/min > 110 Hypotension
Chest Wheezy Wheezy Silent chest
ABGs Resp. alkalosis Resp. alkalosis Resp. acidosis
PaCO2 Low Low Normal or high
O2 sat. ≥ 92% ≥ 92% < 92%
Table 41: classification of acute asthma exacerbation

Assessment of acute asthma exacerbation:

- If the patient has an O2 saturation of < 92%, ABGs test is
mandatory
- Chest x-ray is recommended in the following cases:
o Life-threatening asthma
o When pneumothorax is suspected
o If the patient is not responding to the usual treatment

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Indications for admission:
- All patients with life-threatening asthma
- Severe asthma attack not responding to the initial treatment
- Previous near-fatal asthma attack
- Pregnant women
- An attack despite the use of oral steroids
Treatment:
- The first step:
o Oxygen: For all hypoxic patients, given by venturi
mask
o SABA: 5 – 10 puffs by MDI and spacer (SABA nebulizer
is indicated in severe cases)- can be repeated up to
3 doses in 1 hour.
o Early administration of systemic Steroid (40 – 50 mg
oral prednisolone)
- The second step: Nebulized SAMA (Short-acting muscarinic
antagonists, e.g., Ipratropium)
- The third step: Magnesium sulfate IV (1.2 – 2 g over 30
minutes)
o Not routinely used
o Only if the previous measures fail to improve the
patient
- Intubation and mechanical ventilation should be done in
any patient with life-threatening or near-fatal asthma.
- Early administration of intramuscular adrenaline is
indicated in a patient with acute asthma exacerbation
and anaphylaxis
- Aminophylline and theophylline have poor efficacy and
safety profile, so they are not recommended in the
treatment of acute asthma exacerbation anymore
- High-dose ICS-formoterol combination is similar to SABA in
relieving asthma, but this will need more studies to be
adopted officially.
- Avoid sedatives in asthma exacerbation because they
further suppress respiration and worsen the condition.

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 Asthma controllers (preventers) Asthma relievers
Inhaled steroids (ICS) Oral steroids (OCS)
Oral steroid (OCS) I.V steroids
LTRA, LABA, ICS-formoterol SABA, SAMA, ICS-LABA
Cromoglycate Magnesium sulfate
Ketotifen Atropine, Adrenaline
Ephedrine sulfate
Table 42: Asthma controllers and relievers medications

COPD
- COPD is a chronic obstructive lung disease that causes
progressive inflammation and narrowing of the airways.
- Patients have irreversible and non-variable (fixed) narrowing
of the airways and loss of elasticity of the lungs.
Causes:
- Smoking:
o It is the most common cause
o Tobacco destroys Elastin fibers in the lung
o The most effective mortality benefit is to stop smoking
- Alpha-1-Antitrypsin deficiency:
o The most common cause in young and non-smokers.
- Other causes (pollution, occupational exposure)
Clinical picture: there are two clinical types of COPD:
- Chronic bronchitis:
o Cough and sputum on most days for at least 3
months in 2 consecutive years
o Cyanosis, peripheral edema (due to Cor pulmonale),
prolonged expiration.
- Emphysema:
o Enlargement of distal airway spaces and obstruction
of alveoli, the AP diameter (pigeon chest), and
increased TLC
o Pink skin, barrel chest, hyper-resonant to percussion
o Lung compliance is increased in emphysema

Stage 1 Stage 2 Stage 3 Stage 4

FEV1 80% 50 – 79% 30 – 49% < 30%
FEV1/FVC < 0.7 < 0.7 < 0.7 < 0.7
Table 43: Staging of COPD

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Diagnosis:
- CXR (best initial test)
o Hyperinflation, Bulla, Flat diaphragm, horizontal ribs
(air trapping)
o Increased anteroposterior diameter
- PFT (the most accurate test)
o Low FEV1 and low FVC, low FEV1/FVC ratio (< 70%)
o Rversibility of < 12% and < 200 mL in the FEV1 after
SABA administration.
- DLCO (decreased in emphysema)
- ABGs (for acute exacerbations), hypoxia, and high CO2
- ECG: RVH or MAT may be present
- Echocardiogram: pulmonary HTN, RVH, RAH

Figure 12: (a) normal chest X-Ray, (b) Hyperinflated chest

Complications:
- Polycythemia
- Bulla rupture leading to pneumothorax
- Respiratory failure (Type II in chronic bronchitis but Type I in
emphysema)
- Cor-pulmonale (Right ventricular heart failure)
Treatment:
- Measures to reduce mortality:
o Smoking cessation (the most important)
o H. Influenza and pneumococcal vaccine
o Long-Term Oxygen Therapy (LTOT).
- Measure to reduce symptoms:
o SABA (More rapid onset)
o SAMA (Most effective in COPD but slower than SABA)
o LABA (More sustained effect)
o ICS + LABA (ICS is not used as monotherapy in COPD)

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 - Surgical measures (both morality and symptomatic benefits):
o Volume reduction
o Lung transplant
Treatment of COPD exacerbation:
- O2 therapy:
o O2 saturation target is 88 – 92% until ABGs available
o If there is no CO2 retention, make the target 94 – 98%
- Bronchodilator (SABA+SAMA) with a back-to-back nebulizer
- Give prednisolone 40 mg daily for 5 days
- Oral antibiotics (Amoxicillin, Tetracycline, or clarithromycin)
only if there are purulent sputum

Other important points about COPD:

-The most common bacteria in COPD exacerbation is H.
Influenzae, then streptococcus pneumonia.
- Do not use 100% oxygen (If 100% O2 is used in a patient
with CO2 retention, O2 will inhibit the respiratory center
leading to hypoventilation and respiratory failure)
Indications for LTOT:
- PaO2 < 55 mmHg (resting or exercise)
- O2 saturation < 88% (resting or exercise)
- PaO2 < 60 mmHg with heart disease or polycythemia
- O2 saturation < 90% with heart disease or polycythemia
Instructions for LOTO usage:
- Maintain O2 saturation > 90% and PaO2 > 60 mmHg
- Devices used: Nasal cannula or venturi mask
- Duration: at least 15 hours per day
Signs and symptoms of hypercapnia (CO2 retention):
- Headache
- Tremor (asterixis)
- Large pulse volume
- Warm extremities (due to vasodilatation)
- Papilledema (due to high ICP)
- Decreased LOC
Indications for admission of COPD exacerbation patients:
- Life-threatening exacerbation
- For ventilator support (NIV, or conventional mechanical
ventilator)
Table 44: Indications for LTOT

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 Alpha-1-antitrypsin deficiency
- Deficiency of alpha-1-antitrypsin due to a genetic problem
- Autosomal recessive condition (located on chromosome 14)
o Normally, PiMM
o Homozygous PiSS (50% normal A1AT levels)
o Homozygous PiZZ (10% normal A1AT levels)
- Alpha-1-antitrypsin is a protease inhibitor protein synthesized
by the liver
- A1AT deficiency presents with a combination of COPD and
liver cirrhosis
- COPD (usually emphysema) in young (< 40 years) and non-
smoker patients is considered A1AT deficiency until proven
otherwise
Diagnosis:
- Chest X-Ray: findings of COPD
- Low albumin, high PT time (caused by liver cirrhosis)
- PFT: fixed obstruction
- A1AT level (low)
- Genetic testing
Treatment:
- No smoking
- Intravenous A1AT
- Treat as COPD if it occurs

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 Bronchiectasis
- Dilatation of the airways due to chronic lung infection in
childhood (anatomic defect)
- Usually affects medium-sized airways
- The most common infectious pathogen is Pseudomonas
aeruginosa
Causes:
- Cystic fibrosis is the most common cause of bronchiectasis
- Obstruction: tumor, foreign body
- Chronic or Recurrent Infection
- Kartagener's syndrome (ciliary dysfunction)
- Hypogammaglobulinemia
Symptoms:
- Episodes of lung infection with a high volume of foul-smelling
sputum
- Hemoptysis
- Clubbing
- Recurrent infections
Diagnosis:
- High-resolution CT scan (signet ring appearance)
- Chest X-Ray (tram-track appearance)
- PFT – Obstructive pattern
- Investigations of the cause
Treatment:
- Treatment of the cause
- Antibiotics
- Chest physiotherapy
- ICS

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 Interstitial lung diseases (ILD)
- The main presentation in these patients is progressive
shortness of breath or nonproductive coughs.
- They present with decreased lung compliance, a restrictive
pattern on PFT, hypoxia, and decreased DLco, VC, and TLC.
However, FEV1/FVC ratio is increased or normal.

Classification of ILD

Classification based on the major underlying histopathology:

Inflammatory and fibrotic ILDs Granulomatous ILDs
Idiopathic pulmonary fibrosis Hypersensitivity pneumonitis
Asbestosis Sarcoidosis
Drug-induced Granulomatous with
Radiation-induced polyangiitis
Connective tissue disorders Churg-strauss syndrome

Classification based on the most commonly affected lung zone:

Lower zone fibrosis Upper zone fibrosis
Idiopathic pulmonary fibrosis Silicosis
Drug-induced ILD Hypersensitivity pneumonitis
Asbestosis Ankylosing spondylitis
Most connective tissue diseases Tuberculosis
Sarcoidosis
Table 45:causes of Upper vs. Lower zone lung fibrosis

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 Idiopathic Pulmonary Fibrosis (IPF)
- Also known as cryptogenic fibrosing alveolitis
- An idiopathic progressive disease of an Irreversible process
Symptoms:
- Exertional dyspnea and non-productive cough
- Late expiratory crackles (Velcro-like crepitations)
- Clubbing
Diagnosis:
- Chest x-ray:
o Early: reticulonodular pattern
o Late: honeycombing
- A restrictive pattern on PFT
- High-resolution CT scan (Best): ground glass appearance
- Biopsy (the most accurate but rarely needed)
Treatment:
- Oxygen
- Supportive measures
- Lung transplant for end-stage (definite treatment)

Sarcoidosis
- Unknown etiology usually occurs in young and black
patients
- A multi-system disease characterized by non-caseating
granuloma
- More common in non-smokers
Clinical picture:
- It could be asymptomatic, but cough, SOB, and fatigue may
present
- Facial nerve involvement is the most common neurological
manifestation
- Skin manifestations:
o Erythema nodosum (Good prognosis)
o Lupus pernio (purplish lesion of the facial skin) (poor
prognosis)
- Anterior uveitis
- Hepatosplenomegaly
- Non-deforming arthritis
- Hypercalcemia: (macrophages inside the granulomas
cause an increased conversion of vitamin D to its active
form (1,25-dihydroxycholecalciferol))

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 Syndromes of sarcoidosis:
- Lofgren's syndrome is an acute form of sarcoidosis
characterized by bilateral hilar lymphadenopathy (BHL),
erythema nodosum, fever, and polyarthralgia. It usually
carries an excellent prognosis
- Heerfordt's syndrome (uveoparotid fever) there is parotid
enlargement, fever, uveitis, and facial palsy secondary
to sarcoidosis

Diagnosis:
- Chest x-ray (best initial test)
- Non-specific (high ESR, Hypercalcemia...)
- Bronchoalveolar lavage: increased lymphocytes (T-helper
cells) (CD4/CD8 > 4)
- Spirometry: restrictive pattern
- Biopsy of lung or lymph nodes showing non-caseating
granuloma (the most accurate)

The ACE level may be elevated, but it is not specific, not sensitive,
and has a minor role in diagnosis. However, it can be used for
monitoring the disease activity

Stages of sarcoidosis according to Chest X-Ray:

- Stage 1: Bilateral Hilar Lymphadenopathy (BHL)
- Stage 2: BHL + interstitial infiltrates
- Stage 3: diffuse interstitial infiltrates only
- Stage 4: diffuse fibrosis
Poor prognostic factors in sarcoidosis:
- Insidious onset, symptoms > 6 months
- An absence of erythema nodosum
- Extra-pulmonary manifestations: e.g., lupus pernio,
splenomegaly
- Chest X-Ray: stage III-IV
- Black people and Older ages
Treatment:
- Stages 1&2: spontaneous resolution
- Steroids may be needed If:
o Stages > 2 with progressive symptoms
o Hypercalcemia
o Eye-heart or CNS involvement

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 Extrinsic Allergic Alveolitis (EAA)
- Also known as (hypersensitivity pneumonitis)
- Inhalation of organic substances leads to the destruction of
alveoli and pulmonary fibrosis
- Involves type 3 or type 4 hypersensitivity reaction (Type 3
more prominent)
Examples of EAA:
- Farmer’s Lung (Thermophilic Actinomycetes)
- Bird Breeder’s/Bird Fancier’s Lung (Chlamydia psittaci in bird
droppings)
- Humidifier Lung (Aureobasidium pullulans)
- Sauna Taker’s Lung (Aureobasidium)
Clinical features:
- Acute EAA:
o Dyspnea, cough, fever, chills, malaise (lasting 18-24 h)
o CXR: diffuse infiltrates
o Type III (immune complex) reaction
- Chronic EAA:
o Insidious dyspnea, cough, anorexia, weight loss
o PFT: progressively restrictive
o Chest X-Ray: upper lobe lung fibrosis.
o Type IV (cell-mediated, delayed hypersensitivity)
o Chronic changes are irreversible
Diagnosis:
- Chest x-ray: (Upper zone fibrosis)
- Bronchoalveolar lavage (Lymphocytosis)
- Blood – NO EOSINOPHILIA
Treatment:
- Avoid exposure
- Steroid

Drug and radiation-induced ILD

Drug-induced ILD examples:
Bleomycin, Cyclophosphamide, Amiodarone, Procainamide, Illicit
drugs (heroin, methadone), Antibiotics (nitrofurantoin, penicillin,
sulfonamide), Anti-Inflammatory Agents (methotrexate,
penicillamine), Gold salts, Rituximab, anti-TNF agents (Infliximab,
Etanercept, Adalimumab).

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Radiation-Induced fibrosis:
- Early-onset fibrosis: (before 6 weeks)
- Late-onset fibrosis: (6-12 months post-exposure)
- Infiltrates conform to the shape of the radiation field

Adult Respiratory Distress Syndrome (ARDS)

- ARDS: is a respiratory failure from lung injury or due to
systemic disease
- Presented with Secondary hypoxia + distress + non-
cardiogenic pulmonary edema
- Prognosis is Poor, Mortality 30-40%
Causes: ARDS is idiopathic, but a large number of illnesses and
injuries are associated with alveolar damage; examples are:
- Aspiration
- Sepsis
- Near drowning
- Pneumonia, PE, COVID19
- Burn, Shock, Trauma
Diagnosis:
- Chest X-ray shows bilateral infiltrates and air bronchogram.
- ABGs:
o PaO2/FIO2 < 300: mild ARDS
o PaO2/FIO2 < 200: moderate ARDS
o PaO2/FIO2 < 100: severe ARDS

Note:
on room air, the FiO2 is 21% (0.21), so if the patient has PaO2 of 105
on room air, then the PaO2/FiO2 = 105/0.21 = 500
Example: Patient on 50% oxygen has PaO2 of 80 mmHg, calculate
the PaO2/FiO2 ratio:
PaO2/FiO2 ratio = (80/0.5) = 160 (160 means moderate ARDS)

Treatment:
- Mechanical ventilation with the following settings
o Low Tidal volume 6ml/kg (best support)
o High PEEP to keep alveoli open
- A prone position of the patient's body
- Steroids may be used in the late stage if fibrosis occurs.
- Treatment of the underlying disorder

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 Respiratory infections
Pneumonia
Introduction and classification
- Pneumonia is defined as an infection of the lung, which can
be bacterial, viral, or fungal
Risk factors:
- Low Immunity
- Low ciliary movement (e.g., smoking, CF, and Kartagener's
syndrome)
- Decrease protective mechanisms like gag and cough reflex

Aspiration pneumonia usually presents in the Right middle or

lower lobe, Due to the vertical direction of the right Bronchus

Pneumonia classification:
- Community-acquired (CAP): pneumonia that occurs before
or within 48 hours after hospital admission
o Typical CAP (high fever, productive cough, unwell
toxic patient) usually shows lobar consolidation on
chest X-Ray.
o Atypical CAP is caused by organisms that are not
detectable on gram stain and not culturable on
standard blood agar, usually with milder symptoms
with no sputum and diffuse patchy infiltration on
chest X-Ray.
- Hospital-acquired pneumonia (HAP):
o It started 48 hours after admission.
o Staphylococcus aureus is the most common cause
o Pneumonia developed in the first 48 hours post-
admission is CAP, not HAP.

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 Typical pneumonia Atypical pneumonia
Most common cause Pneumococci Mycoplasma
Presentation Fever, productive Myalgia, arthralgia
cough
Chest x-ray Lobar consolidation Patchy infiltration
Other causes H influenza type B Viruses (e.g., CMV)
Staph aureus Fungi
Pseudomonas Legionella
E coli Chlamydia
Klebsiella
Table 46: Typical vs. atypical pneumonia

Differential diagnoses of pneumonia

The clinical scenario The most likely organism
Typical pneumonia Strep pneumonia (80%)
Pneumonia after recent influenza Staph aureus
Alcoholism and DM. Klebsiella pneumonia
Cavity lesion on chest x-ray.
Poor dentition, aspiration Anaerobic bacteria
Atypical pneumonia Mycoplasma pneumonia
Young, Healthy patients
Associated Cold AIHA
Associated erythema multiform
Contaminated water sources. Legionella
Air conditioning systems.
Diarrhea, Hyponatremia.
HIV positive patients pneumocystis jiroveci (PCP)
Pneumonia in COPD patient Hemophilus influenzae
CF or bronchiectasis patient Pseudomonas
Table 47: Differential diagnosis of pneumonia

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 Typical pneumonia
- The most common cause is streptococcus pneumonia
- Streptococcus pneumonia is characterized by rapid onset,
higher fever, rusty sputum, and the activation of herpes
labialis.
Clinical picture:
- Cough with sputum
- Fever or hypothermia
- Dyspnea (if severe infection)
- Hemoptysis can be a feature
- Pleuritic chest pain
- Signs of consolidation (Bronchial breathing, Egophony)
- Can cause Atrial fibrillation
Diagnosis:
- Chest X-ray (best initial test)
- Leukocytosis (non-specific marker)
- ABGs and Pulse oximeter to assess the severity
- Gram stain and Culture (best to determine etiology)
Treatment:
- Supportive (O2, IV fluids, Analgesia)
- Salbutamol nebulizer or MDI
- Antibiotics
- Hospitalize if needed according to CURB65 criteria (1 point
for each element)

C U R B 65
Confusion Urea > 7 RR >30 BP < 90/60 Age ≥ 65
- 0 - 1 point: Treatment at home
- 2 – 3: admission to the hospital
- 4 – 5: ICU admission
Table 48: CURB65 score for pneumonia prognosis

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The choice of antibiotic in typical pneumonia treatment:
- Outpatient cases:
o If previously healthy with no antibiotic use in the past
3 months, use macrolides (azithromycin or
clarithromycin) or Doxycycline
o If there are comorbidities or use of antibiotics in the
past 3 months, use respiratory fluoroquinolones
(Levofloxacin or Moxifloxacin)
- Inpatient cases:
o Respiratory fluoroquinolone (Levofloxacin or
Moxifloxacin) or
o Ceftriaxone with Azithromycin
Indications for the pneumococcal vaccine:
- Everyone above the age of 65 years
- Chronic (heart, liver, lung, or kidney) diseases
- Functional or anatomical asplenia
- Hematologic malignancies (leukemia, lymphoma)
- Immunosuppression (DM, alcoholics, steroid use, HIV)
- CSF leak and cochlear implantation recipients
If the vaccine was given before the age of 65 for another
condition, it should be repeated 5 years after the first dose
Table 49: indications for the pneumococcal vaccine

Klebsiella pneumonia
- It is classically in alcoholics and DM patients
- Presented with Red-Current jelly sputum (hemoptysis from
necrotizing disease)
- Present with aspiration pneumonia
- A common cause of Lung Abscess and cavitating lesion on
-
chest x-ray
Mycoplasma pneumonia
- The most common cause of atypical pneumonia
- Present with a dry cough, rarely severe
- Associated with:
o Bullous myringitis (eardrum infection)
o Cold agglutinin hemolytic anemia
o Erythema multiform (rash with typical target lesion)
o Splenomegaly
- This bacterium has no cell wall, so it is resistant to antibiotics
that inhibit cell wall like penicillin
- Treatment: Erythromycin, clarithromycin

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 Legionella pneumonia
- Commonly in air-conditioning systems, workers
- Associated with:
o GI symptoms (abdominal pain and diarrhea)
o CNS symptoms (e.g., headache and confusion)
o Hyponatremia
- Lymphopenia is a feature
- Diagnosis by Urine antigen test
- Treatment: Macrolides (e.g., Erythromycin)

Pneumocystis Carinii Pneumonia (PCP)

- It is caused by yeast-like fungus pneumocystis jiroveci
- Usually seen in patients with cancer, chemotherapy, HIV,
and drug abusers
- It is the most common cause of pneumonia in HIV patients
(with CD4 < 200)
- Pneumothorax is a common complication
Clinical features: dyspnea, cough, fever, and Few chest signs
Diagnosis:
- LDH level is always elevated
- The most accurate test is bronchoalveolar lavage
Treatment:
- Cotrimoxazole (best initial for treatment and prophylaxis)
- Steroids are used if hypoxia is present (decrease mortality)
- IV pentamidine for severe cases

Ventilator-associated pneumonia (VAP)

- Mechanical ventilation interferes with normal protective
mechanisms (cough, mucociliary clearance)
- The most common pathogen is Acinetobacter
- Present with fever, new infiltration, and purulent secretions
come from the endotracheal tube
- A sputum culture is the best test
Treatment: (three-drug combination)
- Anti-pseudomonas agent (cephalosporin or penicillin, or
Carbapenem)
- Another antipseudomonal agent (aminoglycoside or
fluoroquinolone)
- MRSA agent (vancomycin, or linezolid)

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 Tuberculosis (TB)
- It is an infection caused by Mycobacterium Tuberculosis (an
Acid-fast bacilli bacterium that can cause caseating
granuloma)
- Can be latent in 95% and primary active disease in 5%, or
secondary active disease (activation of latent infection)
- It can be pulmonary, extrapulmonary, or both.
Transmission of TB
- Airborne (droplet nuclei) that remain suspended in the air for
several hours before inhaled
- TB bacteria invade the immunity, survive and replicate in the
macrophages
Classification:
- Primary infection:
o More common in children and immunocompromised
patients
o Not associated with high-level transmissibility
- Secondary (post-primary) infection:
o More, if the infection is acquired later in life
o Because of the frequent cavitation, it is more often
infectious.

Risk factors for TB reactivation:

- HIV infection (the most potent risk factor)
- Silicosis (silica is toxic to macrophages)
- Chronic renal failure and hemodialysis
- Diabetes mellitus
- Intravenous drug use
- Immunosuppressive treatment
- Smoking

Features of pulmonary TB:

- Primary infection:
o More common in children than adults
o Usually asymptomatic unless progressed or immune-
suppressed patients.
o Cough, hemoptysis, upper lobe consolidation, fever,
and pleuretic chest pain with no response to usual
antibiotics

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 o Constitutional symptoms (night sweating, weight loss,
anorexia)
o Ghon's complex is a lesion seen in the lung caused by
tuberculosis. The lesions consist of a calcified focus of
infection and an associated lymph node
- Post-primary (secondary):
o More common in adults (called Adult-type)
o Mainly in the apical zones (higher oxygen tension
compared to the lower zones)
o The lesion varies from small infiltration to extensive
cavitation
Features of extrapulmonary TB:
- Lymph nodes: the most common (35% of extrapulmonary
cases)
- Genitourinary TB
- TB polyserositis: pleuritis, peritonitis, and pericarditis
- Pott's disease: TB infection of the vertebrae
- Hepatitis, meningitis, osteomyelitis …
- Intestinal TB most commonly occurs in the ileocecal region,
causing intestinal obstruction.
- Adrenal involvement: Hypoadrenalism can manifest.
Features of miliary TB:
- Widespread hematogenous dissemination of TB to the lung,
abdominal organs, CNS, etc.
- The lesions are usually yellowish granulomas of 1 – 2 mm in
diameter
- Fever, night sweats, anorexia, weakness, and weight loss are
presenting symptoms in the majority of cases
Diagnosis of active TB:
- Chest –X-Ray: upper zone lesion, Hilar lymphadenopathy, or
miliary TB.
- Sputum or tissue smear for acid-fast bacilli (AFB)
- Nucleic acid amplification technology
o Rapid to confirm TB in AFB-positive patients
o Real-time nucleic acid amplification technology
simultaneously detects TB and rifampin resistance in
less than 2 hours
- Mycobacterial culture:
o Sputum stain and Culture for acid-fast bacilli (done 3
times to exclude TB)
o Modern cultures require 2 – 3 weeks to confirm the
presence of TB

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Diagnosis of latent TB: PPD test is indicated.
- Tuberculin purified protein derivative (PPD) test
- Also called Mantoux skin test or tuberculin skin test (TST)
- The test measures the response to antigenic stimulation by T
cells that reside in the skin.
- It will not differentiate between active and latent TB
- Once the PPD test is positive, it remains positive for life

Mantoux test is considered positive in the following conditions:

- Induration ≥ 15 mm induration (for any patient)
- Induration ≥ 10 mm induration and one of the following :
o A recent arrival from a high prevalent country
o I.V drug user
o Child < 4 years
- Induration ≥ 5 mm induration and one of the following:
o HIV positive
o Recent contact with TB patient
o Typical TB changes on chest x-ray
o Organ transplant
Table 50: Mantoux test interpretation

Prevention:
- BCG vaccination
- Provided for all infants within 45 days of life
- A booster dose can be provided for those who are traveling
to endemic areas
- Isolation of TB cases should be done
Treatment:
- Rifampin, Isoniazid (INH), Pyrazinamide, Ethambutol (RIPE):
o Give 4 drugs (RIPE) for 2 months, then,
o 2 drugs (RI) for 4 months
- If bacteria are sensitive to all drugs, no need for Ethambutol
- If previously treated, add streptomycin
- For a patient with latent TB, INH for 9 months.
- Treatment is extended to 9 months if (osteomyelitis, miliary
TB, or pregnancy)
- Steroids can decrease neurogenic complications in TB
meningitis.

All Anti-TB are bactericidal except Ethambutol which is a

bacteriostatic

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 Drug Adverse effects Treatment
Rifampicin Red-colored body No need for treatment
secretions
Isoniazid Peripheral Prophylactic with
neuropathy pyridoxine (Vit B6)
Pyrazinamide Hyperuricemia Treat if symptomatic only
Hepatotoxicity
Ethambutol Optic neuritis/ color Adjust dose in renal
vision failure
Streptomycin Ototoxic, Dose adjustment.
nephrotoxic
Table 51: the side effects of Anti-TB medications

Lung abscess
- Localized collection of pus in the lung occuring in patients
with large-volume aspiration not adequately treated
- Predisposing factors are processes that interfere with
swallowing or coughing (e.g., stroke, Intoxication)
Clinical features:
- Cough with a large volume of foul-smelling sputum
- Fever, Weight loss, clubbing fingers
Diagnosis:
- Cavity with Air fluid level appears on imaging
- A lung biopsy is the best to determine the pathogen
- A sputum culture is not beneficial (all people have normal
flora of anaerobes in their mouth)

Figure 13: A chest X-ray showing Air fluid level (Lung abscess)
Treatment:
- Clindamycin or penicillin
- Surgical drainage is used only if failed medical therapy.

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 Pleural diseases
Pleural effusion
- Pleura: is a serous membrane covering the lungs. It has 2
parts: parietal pleura (outer) and visceral pleura (inner)
- Pleural space: is the space between parietal and visceral
pleura and normally contains 25 ml of fluid called serous fluid
- Pleural effusion is an abnormal collection of fluids within the
pleural space
- Pleural fluids can be Transudates or exudates

Pneumothorax: air in the pleural space

Hemothorax: blood in pleural space
Chylothorax: lymphatic fluid in pleural space
Empyema: Pus in the pleural space

Causes:
Transudative Pleural effusion Exudative Pleural effusion
CHF (most common) Infection, Empyema
Liver cirrhosis Malignancy
Nephrotic syndrome Inflammation
Peritoneal dialysis Trauma
Myxoedema Oesophageal perforation
Constrictive pericarditis Asbestosis
Superior vena cava syndrome Meigs' Syndrome
Pulmonary embolism can cause both exudates and transudates
but can cause exudates more often
Table 52: Causes of Exudative and Transudative pleural effusion

Clinical picture:
- Can be asymptomatic
- Dyspnea, chest pain
- Stony Dullness to percussion + Decreased TVF + trachea
shifted away
- Decreased or absent breath sounds, bronchial breathing
above effusion.
- Signs and symptoms of the cause

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Diagnosis:
- Chest X-ray (best initial test)
o PA view will show the effusion if > 250 mL (Loss of
costophrenic angle, meniscus sign)
o A lateral view will show the effusion if > 50 ml in
amount.
o Lateral decubitus will show a shifting of fluids (now
replaced by chest ultrasound and paracentesis)
- CT scan (more informative than chest x-ray)
- Thoracentesis (most accurate test): differentiate exudates
from Transudates

Figure 14: Chest X-Ray showing bilateral pleural effusion

How to differentiate exudate from transudate:

Check for pleural fluid protein:
- If > 30 g/l, consider exudates
- If < 20 g/l, consider transudates
- If 20 – 30 g/l and one of the light's criteria are found,
consider exudates
Modified Light's criteria:
- Pleural/serum protein ratio > 0.5
- Pleural/serum LDH ratio > 0.6
- Pleural fluid LDH > two-thirds the upper limit of normal
serum
Table 53: Modified lights criteria

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Treatment:
- Small effusion needs no treatment
- Treat the cause
- Cardiogenic pleural effusion is highly responsive to diuretics
- Thoracentesis (therapeutic and diagnostic)
- If refractory and recurrent, pleurodesis (intrapleural
bleomycin or talcum powder)
- If empyema develops, a chest tube, antibiotics, and surgical
drainage may be needed

Asbestos-related lung diseases

- Can be asymptomatic for 20 – 30 years (latency period)
- Pleural exudative effusion and hemoptysis may develop
Several diseases occur due to asbestos exposure:
- Pleural plaques are the most common asbestos-related lung
disease (Benign with no malignant transformation)
- Asbestos may cause pleural thickening
- Asbestosis (lower lobe fibrosis)
- Lung cancer: Asbestosis and smoking together increase the
risk by 50 times
- Mesothelioma is a malignant asbestos-related disease of the
pleura
Diagnosis:
- Calcified pleural plaques found on chest x-ray
- Biopsy (best)
Treatment: Extra-pleural pneumonectomy (rarely successful)

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 Other respiratory disorders
Sleep apnea syndromes
- It is defined as a repetitive period of apnea during sleep
leading to distorted sleeping, snoring, daytime sleepiness,
and hypertension
- A period of more than 10 seconds without breathing is
considered an apneic episode
Causes:
- Obstructive sleep apnea (OSA):
o Obesity (the most common cause)
o Other causes include macroglossia, Large tonsils,
Marfan's syndrome, etc.
o The chest wall and abdominal movements are
present during the apneic episode
- Central sleep apnea:
o CNS disorder
o Drug-induced respiratory center suppression
o The chest wall and abdominal movements are
absent during the apneic episode.
- Mixed apnea: both central and obstructive.
Clinical features:
- Daytime somnolence, headache, impaired memory
- Loud snoring (usually noted by a sleep partner)
Diagnosis:
- Epworth Sleepiness Scale (questionnaire by the patient)
- Polysomnography (Sleep study) is the most accurate test: a
pulse oximeter, EEG, airflow, and thoracoabdominal
movements may be monitored during sleep.
- The severity can be determined by the AHI
o Mild: AHI 5 – 14 events per hour
o Moderate: AHI 15 – 29 events per hour
o Severe: AHI ≥ 30 events per hour
- ABGs show compensated respiratory acidosis

Apnea hypopnea index (AHI) is the number of apneas plus

hypopneas per hour of sleep

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Treatment:
- Obstructive sleep apnea:
o Weight loss
o C-PAP (continuous positive airway pressure) (first line)
o Uvulopalatopharyngoplasty (surgical widening of the
airways)
o Intra-oral devices (if C-PAP is not tolerated)
- Central sleep apnea:
o Avoid alcohol and sedatives.
o Acetazolamide may be effective by causing
metabolic acidosis and stimulating respiration
o Medroxyprogesterone (a central respiratory stimulant)
Complications:
- Respiratory failure
- Pulmonary HTN
- Cor-pulmonale

Pulmonary arterial HTN (PAH)

- Mean pulmonary arterial pressure > 25 mmHg at rest or
Systolic pulmonary pressure > 40 mmHg
- The mean arterial pressure (MAP) = systolic + 2(diastolic) / 3
Causes:
- Primary pulmonary HTN, also known as idiopathic pulmonary
arterial HTN (PPH or IPAH)
- Any form of chronic lung disease can cause Pulmonary HTN:
(COPD, Chronic pulmonary emboli, Polycythemia Vera,
Interstitial lung disease, Fibrosis, Hypoxia)
Clinical features:
- Dyspnea, Fatigue, Syncope, Chest pain
- Wide splitting S2 (due to delayed RV emptying), loud S2,
raised JVP, RVH
- Raynaud's phenomenon
- Tricuspid regurgitation
Diagnosis:
- Chest X-Ray (best initial test): the pulmonary arteries will be
dilated proximally and narrowed distally
- Echocardiography: estimates the pulmonary blood pressure
using Doppler ultrasound
- Right heart (Swan-Ganz) catheter (the most accurate test)
- ECG: RAD, right side hypertrophy

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 - CTPA and V/Q scan might show PE if it was the cause
- CBC may show polycythemia (due to hypoxia)
Treatment:
- Treatment of the cause
- Sildenafil, bosentan, or prostacyclin analogs are the best
- CCBs, hydralazine, and nitroglycerin are less effective
- Diuretics for heart failure
- Oxygen slows the progression (especially in COPD)
- Definite treatment: heart-lung transplant

Eosinophilic lung diseases

- Diseases that are associated with increased eosinophils in
bronchoalveolar lavage and lung biopsy
Causes:
- Loffler’s syndrome: pulmonary eosinophilia in response to
parasitic infection (e.g., Ascaris, Strongyloides, Dirofilaria)
- Allergic Bronchopulmonary Aspergillosis (ABPA)
- Eosinophilic pneumonia (can be viral or bacterial)
- Churg-Strauss syndrome (vasculitis)
- Drug-induced (cocaine, Phenytoin, some antibiotics, etc.)

Allergic Bronchopulmonary Aspergillosis (ABPA)

- Hypersensitivity of the lung due to the fungal antigen
(Aspergillus fumigatus)
- Clinical scenario: Patient with asthma or CF presents with
infiltration in routine CXR
- The persistent inflammatory response may lead to
bronchiectasis.
Clinical features: Cough, Wheezing, Hemoptysis
Diagnosis:
- CBC: eosinophilia
- Skin test reactivity to Aspergillus antigen
- High IgE level
- Imaging: CXR, CT scan (pulmonary infiltration)
- Aspergillus fumigatus in blood or sputum
Treatment:
- Prednisolone (regular low dose)
- Itraconazole (An anti-fungal agent) may be used
- If resistant, IgE Monoclonal Antibodies

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 Aspergilloma: forming fungus ball may be asymptomatic or
present with Hemoptysis, treatment by (surgery, Bronchial artery
Embolization)

Respiratory failure
Failure of the respiratory system to maintain normal blood gases
Diagnosis: ABGs
There are two types:
- Type 1: Hypoxia without Hypercapnia
- Type 2: Hypoxia with Hypercapnia
Treatment: Intubation and Treatment of the cause

Hypoxia: PO2 < 60 mmHg, Hypercapnia: PaCO2 > 50 mmHg

Causes of Type 1 Causes of Type 2

Emphysema Chronic bronchitis
Moderate asthma Life-threatening asthma
Neuromuscular disorders Neuromuscular disorders
PE Chest wall deformities
Pneumonia OSA
ARDS Suffocation
High altitude
Right to left shunt
Table 54: causes of Type 1 vs. Type 2 respiratory failure

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 Respiratory neoplasms
Small cell lung cancer
- Also known as Oat cell lung cancer
- Usually central
- Usually, metastatic disease by the time of diagnosis
Management:
- Combination of chemotherapy and radiotherapy
- More extensive disease: palliative chemotherapy
- Surgery has no rule in the treatment

Non-Small Cell lung cancer

- Three main subtypes of non-small cell lung cancer
Squamous cell cancer:
- Typically, central and can cause a cavitary lesion
- Strongly associated with finger clubbing
Adenocarcinoma:
- The most common type of lung cancer in non-smokers,
although the majority of patients who develop lung
adenocarcinoma are smokers
- Typically, peripheral
Large cell lung carcinoma:
- Poorly differentiated tumors with a poor prognosis
- Typically, peripheral

Paraneoplastic features of lung cancers

Small cell cancer:
- ADH secretion: SIADH (hyponatremia)
- ACTH secretion: Cushing's syndrome
- Antibody formation: Lambert-Eaton-myasthenic syndrome
Squamous cell cancer:
- PTHrP secretion: Hypercalcemia
- TSH secretion: Hyperthyroidism
- Hypertrophic pulmonary osteoarthropathy (HPOA)
Adenocarcinoma:
- Gynecomastia
- HPOA

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 - HPOA: a triad of periostitis, digital clubbing, and painful
arthropathy of the large joints.
- Pancoast tumor: is a peripheral tumor that occurs at the
apex of the lung, usually spreads to adjacent tissue,
usually non-small cell lung cancer, traditionally questioned
as a cause of Horner Syndrome
- Horner syndrome: ptosis, myosis, anhidrosis, and
enophthalmos, due to a defect in the sympathetic
nervous system, can be caused by Pancoast tumor.

Chest wall deformities

- Kyphosis: abnormal anterior deviation of the thoracic spine
- Scoliosis: abnormal lateral deviation of the thoracic spine
- Kyphoscoliosis: mixed with Kyphosis and scoliosis
- Pectus excavatum (funnel chest): the lower end of the
sternum is curved backward
- Pectus carinatum: (Pigeon chest): outward protrusion of the
sternum and rips (caused by severe asthma during
childhood)

Figure 15: Different types of Chest deformities

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 Chest X-Ray lesions
Causes of cavitating lesions on chest X-Ray:
- Lung abscess
- Squamous cell lung cancer
- Tuberculosis
- Wegener's granulomatosis
- Pulmonary embolism
- Rheumatoid arthritis
- Sarcoidosis
- Aspergillosis, histoplasmosis, coccidioidomycosis
Causes of Nodular lesions on Chest X-Ray:
- Benign tumors, such as hamartomas
- Infections (TB, histoplasmosis, hydatid cyst)
- Inflammation (RA - Caplan syndrome, Sarcoidosis,
Wegener's granulomatosis)
- Malignant tumors (primary or metastatic lung cancer)
Causes of bilateral hilar lymphadenopathy on Chest X-Ray:
- Sarcoidosis, EAA
- Infection: TB, Fungal infections, mycoplasma
- Malignancy: Lymphoma, carcinoma, mediastinal tumors

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 Cardiology
CHAPTER 4

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Diseases of the heart conduction
The normal Heart conduction
- SA node generates impulses that spread through atria,
delayed at the AV node, spread down through the HIS
bundle, spread to right and left bundle branches, then
reach Purkinje fibers
- Automaticity: cardiac cell's ability to spontaneously
generate an electrical impulse (depolarize) – normally at the
SA node
- SA node typically generates impulses at 60 – 100 per minute.
- AV node typically delays impulse for 0.08 seconds.

Figure 16: the heart conduction system

On ECG:
- P wave: represents atrial depolarization (contraction)
- QRS waves: represents ventricular depolarization
(contraction)
- T wave: represents ventricular repolarization (relaxation)

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 Basic ECG
The essential parts to be assessed on ECG are (Rhythm, Rate, Axis,
intervals, and Chamber enlargement)
Rhythm:
- The normal sinus rhythm of the heart, generated from SA
node, Regular, Each P wave followed by a QRS complex
then T wave
- If the rhythm is irregular, so you have to determine if it is
regularly irregular or irregularly irregular
Rate:
- Normal heart rate is 60 – 100 bpm
- Rate more than 100 bpm is called Tachycardia
- A rate of less than 60 bpm is called bradycardia
- Calculate the rate by dividing 300 by the number of large
squares between each QRS complex
The Axis deviation:
- The normal axis is between -30 and +90 degrees
- Can be determined by examining Leads I, II, And AVF
- Causes of RAD (RALPH-W):
o Right ventricular hypertrophy (RVH)
o Anterolateral MI
o Left Posterior Hemiblock
o WPW syndrome
- Causes of LAD (VILLAH-W):
o Ventricular tachycardia
o Inferior MI
o Left Anterior Hemiblock
o WPW syndrome

Axis deviation Lead I Leads II and AVF

Normal Positive (˄) Positive (˄)
Right axis deviation (RAD) Negative (˅) Positive (˄)
Left Axis Deviation (LAD) Positive (˄) Negative (˅)
Extreme axis deviation Negative (˅) Negative (˅)
Table 55: Axis deviation interpretation in ECG

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The intervals:
- PR interval:
o Normally 120 – 200 ms (3-5 small squires)
o Prolonged in AV block and aortic valve abscess
o Short in WPW syndrome
- The QRS complex:
o Normal Q wave (< 40 ms width and < 2 mm depth)
o The normal QRS complex is < 120 ms (< 3 ss) (Narrow
complex)
o Poor R wave progression from V1 to V6 is a non-
specific sign of infarction
- The QT interval:
o Normal corrected QT (QTc) 380-440 ms (9.5-11 ss)
(QTc = QT/√RR)
Chamber enlargement:
- Left atrial (P mitrale): P wave > 120 ms in lead II
- Right atrial (P pulmonale) P wave > 2.5 mm height in lead II
- Left ventricular: S wave in V1 + R wave in V6 > 35 mm height
- Right ventricular: RAD with R wave in V1 > 7 mm

Condition ECG changes

Hyperkalemia Low or absent P, Prolonged PR interval, Wide
QRS, Peaked T wave, Sine wave (severe)
Hypokalemia High P wave, Depressed ST segment, Broad
flat T wave, U wave
Hypocalcemia Intermittent long QT interval, Long ST
segment, Torsade de points
Hypercalcemia Short QT interval, Short ST segment, Wide flat
T wave, Osborn wave
Hypomagnesemia Tall T wave, ST depression
Hypermagnesemia Long PR, Wide QRS
Hypothermia Long PR, Long QT, Wide QRS, Shivering
artifact, Osborn wave, Low voltage
Bradyarrhythmia, PVCs
Table 56: ECG changes in different conditions

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 Arrhythmias (Abnormal conduction)
Sinus Tachycardia
- Rhythm and rate: regular and fast (HR > 100 bpm)
- Causes: fever, pain, anxiety, pregnancy, exercise,
hyperthyroidism, CO2 retention, and drugs
- Treatment: treat the cause

Figure 17: strep rhythm ECG showing sinus tachycardia

Sinus Bradycardia
- Rhythm: regular and slow (HR < 60 bpm)
- Causes: drugs, Myxoedema, heart block, high ICP,
hypothyroidism, athletes, and jaundice
- Obstructive jaundice is often listed among the causes of
sinus bradycardia. It is usually attributed to the effect of bile
salts on the sinoatrial node.
- Treatment: no need if asymptomatic, atropine if
symptomatic, but Pacemaker is the definitive treatment in
severe cases

Figure 18: strep rhythm ECG showing sinus bradycardia

Sick Sinus Syndrome (SSS)

- It is the most common indication for pacemaker placement
- Sinus node dysfunction, block/pause, common in the
elderly.
- It occurs due to age-related degeneration of the cardiac
conduction system and fibrosis of the SA node (the most
common cause)
- It may be associated with tachyarrhythmia, called (Tachy-
Brady syndrome)
- AF and thromboembolism may occur

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 - Can cause intermittent lightheadedness, syncope, or
sudden cardiac death
- Treatment: if symptomatic, cardiac pacing and
anticoagulants for AF

Figure 19: strep rhythm ECG showing Sick Sinus Syndrome

Atrial fibrillation (AF)

- AF is the most common sustained arrhythmia
- Re-entrant waves within the atria
- More in elderly, DM, HTN, and IHD patients

Figure 20: a strep rhythm ECG showing Atrial fibrillation

Causes: (IHD, pneumonia, HTN, thyrotoxicosis, pericarditis, alcohol)

Types:
- Paroxysmal (less than 7 days, stop spontaneously)
- Persistent (more than 7 days, stopped by medications or
cardioversion)
- Permanent (do not stop)

Signs of instability in cardiac arrhythmias:

- Altered mental status
- Loss of consciousness
- Hypotension (shock)
- Pulmonary edema
- Respiratory distress
- Increasing chest pain

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 Figure 21: the approach for Atrial fibrillation treatment

- The drug of choice for AF with CHF is Digoxin

- Oral anticoagulants are the first-line anticoagulants in
atrial fibrillation patients

CA2DS2 VAS score Points Interpretation

CHF 1 Score 0:
HTN 1 Aspirin or no anticoagulation
Age > 75 2 Score 1:
DM 1 Aspirin or anticoagulation
Stroke or TIA 2
Score 2 or more:
Vascular disease 1
Anticoagulation
Age > 65 1
Sex (female) 1
Table 57: CA2DS2 VAS scoring system

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 Atrial flutter

Figure 22: a strep rhythm ECG showing Atrial flutter

- Large re-entry circuit in Right Atrium
- Atrial rate: 300 BPM
- Ventricular rate: 300 bpm (1:1), 150 (2:1), or 100 (3:1)
- Rhythm: regular or maybe irregular
- P waves: saw-tooth appearance, best seen in leads II, III or
AVF
- QRS: normal (less than 120 ms)
Treatment:
- Same as atrial fibrillation
- Cardioversion guidelines are the same as Atrial fibrillation

Multifocal Atrial Tachycardia (MAT)

- Multiple foci from the atria with re-entrant pathways
- Associated with COPD, Hypoxia
- It may be asymptomatic
ECG:
- At least 3 different P wave morphologies
- Rate > 100 bpm

Figure 23: A strep rhythm ECG showing MAT

Treatment:
- Treat as AF but avoid Beta-blockers if lung disease is present

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 Supraventricular Tachycardia (SVT)
- SVT: regular, no P wave, narrow QRS, and HR > 150 bpm

Figure 24: A strep rhythm ECG showing SVT

Causes: (Hypokalemia, Hyperthyroidism, Excessive alcohol)

Treatment:
- For unstable patients: synchronized cardioversion.
- For stable patients:
o Step 1: Vagal maneuvers: (carotid massage, ocular
massage, Ice on the forehead, Valsalva maneuver)
o Step 2: Adenosine (6, 12, then 12 mg I.V push)
o Step 3: I.V verapamil, Diltiazem, or metoprolol.
o Step 4: synchronized cardioversion (if unresponsive)
- Definitive treatment: catheter ablation.

Important notes about SVT treatment:

- Auscultate for bruits before carotid massage (risk of CVA)
- Adenosine is contraindicated in asthma patients

Ventricular Tachycardia (VT)

Figure 25: A strep rhythm ECG showing Ventricular tachycardia

- VT: Regular, wide QRS (> 120 millisecond), no P wave, no T

wave
- Rate > 100 (usually 140-200)
- Associated with (AV dissociation + capture beats)
- Can be monomorphic or polymorphic
Treatment:
- For unstable patients: DC cardioversion
- For stable patients: amiodarone, Lidocaine, procainamide

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 Torsade de points (TdP)

Figure 26: A strep rhythm ECG showing Torsade de points

- It is also known as (twisting points)

- It is associated with Long QT syndrome
- May result in sudden death
Treatment:
- For unstable patients: cardioversion
- For stable patients: I.V magnesium sulfate
- Always correct the underlying cause.

Hypo- Anti- Others

Hypo-K+ Antiarrhythmics MI
Hypo-Ca++ (amiodarone, sotalol) SAH
Hypo-Mg++ Antidepressants (TCA) Congenital long QT
Hypothermia Antimalarials syndrome (Ex:
Antipsychotic (Haldol) Romano-word-
Antibiotic (erythromycin) syndrome)
Table 58: Causes of long QT syndrome and TdP

Premature ventricular contractions (PVCs)

- Ectopic beats arise from ventricular foci
Causes: Hypoxia, fibrosis, Electrolyte disturbances, heart failure,
HTN, Digoxin toxicity, hypercalcemia, and hyperthyroidism.
Treatment:
- Treat the underlying cause
- Avoid alcohol and caffeine
- If symptomatic, Beta-blockers

Figure 27: A strep rhythm ECG showing Bigeminy

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 Ventricular fibrillation (VF)

Figure 28: A strep rhythm ECG showing Ventricular Fibrillation

Rhythm: irregular + no clear P, QRS, or T waves, no clear pattern

Treatment: DC shock and ACLS protocol

Note: the patient with VF never be stable

Wolff-Parkinson-White syndrome (WPW)

- A congenital defect is characterized by the presence of an
accessory bundle between the atrium and ventricle.
- This bundle is called the "bundle of Kent"
- Type A (Left Side) or type B (Right Side)
- Short PR interval and early ventricular depolarization (Delta
wave)

Figure 29: A strep rhythm ECG showing Delta wave

Treatment:
- Acute arrhythmias (DC shock, amiodarone, or
procainamide)
- Definitive treatment (electrical ablation of the bundle of
Kent)

Beta-blockers, CCB, and digoxin are contraindicated in WPW

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 Heart Block (AV block)
- Also known as AV block (atrioventricular block)
- Decreased or absent conduction through AV node
- It could be first, second, or third-degree
- Maybe due to RCA-mediated ischemia

Types of heart block

First degree AV block: long PR interval > 200ms, asymptomatic,
need no treatment

Second degree AV block (Mobitz type I): progressive

prolongation of the PR interval, followed by failure of conduction
of P wave, no need for a pacemaker.

Second degree AV block (Mobitz type II): prolongation of the PR

interval followed by failure of conduction of P wave, need
Pacemaker

Third-degree AV block (complete AV block): P and QRS waves

are not related to each other, regular P – P intervals and R – R
intervals usually come with bradycardia and need Pacemaker

Table 59: the ECG changes in the different degrees of AV block

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 Important to know:
- Pacemakers (pacer): can be temporary or permanent –
the temporary one can help as a bridge until a
permanent pacer is inserted.
- ICD (implantable cardiac defibrillator): a device
implanted and used to give DC shock if needed, used in
patients who are at risk of sudden cardiac death due to
arrhythmias, and severe Heart failure (EF% < 35%)

Indications for catheter ablation:

- AF: ablation at pulmonary vein bifurcation
- Atrial flutter: ablation of flutter focus at the right atrium
- WPW syndrome: ablation at the accessory bundle (bundle
of Kent)
- Ventricular tachycardia: usually, the focus is within the right
ventricle

CPR in adults
BLS approach:
- Indications for BLS use:
o Cardiac arrest with no pulse
o Bradycardia with poor perfusion
- The sequence of actions of BLS (C-A-B)
o Compression (should be started immediately after no
longer than 10 seconds of assessment)
o Airway (open the airway after 30 compressions)
o Breathing (give mouth-to-mouth breathing)
High-quality CPR:
- Compression quality:
o In adults, use the heel of one hand with one hand on
top of the other.
o Compress over the lower half of the sternum
o The chest should be depressed 5 – 6 cm in depth with
each compression
o The compression rate should be 100 – 120 per minute
o Minimize interruption (less than 10 seconds)
o Rotate compressor every 2 minutes or sooner if
fatigued

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 - Compression to ventilation ratio:
o If there is no advanced airway, the compression
ventilation ratio should be 30:2 regardless of the
number of rescuers.
o If advanced airway is present, continuous
compression with one ventilation every 5 – 6 seconds
o excessive ventilation should be avoided

CPR in suspected or confirmed COVID-19:

- Wear PPE before entering the room
- Consider using a CPR device for adults and adolescents
meeting the height and weight criteria
- Before intubation, use a bag mask with a tight seal and
HEPA filter, if available
- Intubate early (use a cuffed tube, use video laryngoscopy
if available)
- Pause chest compression to intubate
- Minimize closed-circuit disconnection

Shockable vs. non-shockable rhythms:

- Asystole and PEA are non-shockable rhythms: start
compression, give adrenaline every 3 – 5 minutes, reassess
the rhythm every 2 minutes
- Pulseless VT and VF are shockable rhythms: give D/C shock,
start CPR for 2 minutes, then start the following cycle:
o Shock + CPR for 2 minutes with adrenalin
o Shock + CPR for 2 minutes with amiodarone

- In shockable rhythms, no adrenaline or amiodarone is

given after the first shock
- Adrenaline is given after the second shock, but
amiodarone is given after the third shock
- Compression is done for 2 minutes per cycle, and the
patient’s rhythm and pulse should be reassessed in less
than 10 seconds.

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 Diseases of the myocardium
Ischemic Heart Diseases (IHD)
- Diseases of the heart due to ischemia (decreased blood
perfusion)
- Also known as atherosclerotic heart disease or coronary
heart disease
- The main symptom is (typical chest pain)
Typical chest pain:
- Central, retrosternal
- Heavy, dull, squeezing in character, or pressure-like.
- Radiated to neck, jaw, epigastrium, shoulders, or back
- Increased by exercise and relieved by rest or nitrates

Types of IHD: Stable Angina, Unstable angina, NSTEMI, and STEMI

Types of chest pain and differential diagnosis:
- Pain changes with exertion: exertional chest pain (IHD)
- Pain that changes with respiration: pleuritic chest pain (e.g.,
PE, pleuritis)
- Pain that changes with position: positional (e.g.,
pericarditis)
- Pain that changes with palpation: chest wall tenderness
(e.g., costochondritis)

Risk factors of IHD:

- Non-modifiable risk factors: (Old age, male sex, family history
(first-degree relatives), Race)
- Modifiable risk factors:
o Diseases: DM, HTN, Dyslipidemia, obesity
o Lifestyle and habits: (Smoking, Alcohol, sedentary
lifestyle, saturated fatty acid diet)

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Notes:
- Females after menopause will have the same risk as males
for CAD
- Postmenopausal HRT is not protective against CAD
- The worst risk factor for CAD is DM
- The most common risk factor for CAD is HTN
- Only a CAD in a first-degree young family member is a risk
factor
- High LDL is the most dangerous portion of the lipid profile in
terms of risk for CAD
- Smoking cessation has the greatest mortality improvement
in patients with CAD
- The most common cause of non-ischemic chest pain is GI
causes.

Premature CAD: CAD in males < 55 years or females < 65 years old
Diagnostic testing:
- ECG: best initial test for all kinds of chest pain
- Cardiac enzymes: may be elevated in IHD
- ECG stress test: to evaluate chest pain when the cause is
unclear and the ECG is not diagnostic.
- Coronary angiography: used to detect the anatomic
location of CAD.
- 24 hours Holter monitor: for rhythm evaluation.

Stable angina
- Stable angina occurs due to stable obstruction of the
coronary artery
- Cholesterol plaque causes narrowing of the blood vessel
and leads to a decreased blood supply to the heart muscles
(especially during exercise or high demands)
- In this case, there is no infarction to the heart muscles
Symptoms:
- Symptoms will start after 70% stenosis of the coronary artery
- Typical chest pain with exertion and relieved by rest 2 – 10
minutes (Note that ACS pain is 10 – 30 minutes)
Diagnosis:
- Just clinical diagnosis
- Normal cardiac enzymes
- Normal ECG (maybe abnormal during pain only)
- Stress Test
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Treatment:
- Treat risk factors (DM, HTN, Dyslipidemia, obesity) and
- Improve lifestyle (stop smoking, diet, exercise)
- Beta-blockers (the first-line treatment)
- Calcium channel blockers (second-line treatment)
- Nitrates (used in combination with beta-blockers and CCB)
- Ranolazine (if the patient is still symptomatic despite an
optimum dose of beta-blockers, CCB, and nitrates)
- Cardioprotective medications:
o Aspirin: reduce the risk of MI, Stroke
o ACEI: reduce the mortality rate in HF, DM, HTN, and
old MI
o High-intensity statin: reduce the risk of MI and death
- PCI can be done if still symptomatic after drug therapy (not
improve mortality more than drugs)
- CABG (coronary artery bypass graft) may be needed

Coronary Artery Bypass Graft (CABG):

Indications:
- Three vessels disease
- Left main artery disease
- Proximal LAD occlusion with EF% less than 50%
- Chronic disabling angina
Graft used:
- Internal mammary artery (better)
- A reversed segment of great saphenous vein
Table 60: CABG indications and graft used

Terminology:
- ACS: acute coronary syndrome (STEMI, NSTEMI, UA)
- Stable angina is not a part of ACS
- ST-elevation ACS: ST-elevation MI
- Non-ST-elevation ACS: NSTEMI + Unstable angina (UA)
- CABG: coronary artery bypasses grafting
- PCI: percutaneous coronary intervention

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Stress test:
Types of stress tests:
- Exercise ECG stress test
- Pharmacological ECG stress test (using Dobutamine)
- Exercise echocardiogram stress testing
- Pharmacological echocardiogram stress test
Contraindications of ECG stress test:
- Recent myocardial infarction
- High-risk Unstable angina
- Symptomatic severe aortic stenosis
- Uncontrolled arrhythmias causing hemodynamic instability
- Uncompensated heart failure
- Acute pulmonary embolus
- Acute aortic dissection
- Malignant hypertension
Note:
- Beta-blockers, CCB, and nitrates should be held 48 hours
before the stress test
- The stress test is not used for low or high-probability
patients; it is only used for intermediate probability
Table 61: Types and contraindications of stress test

Notes about nitrates:

- Nitrates do not decrease mortality but decrease
symptoms
- Nitrates are contraindicated with Viagra (risk of
hypotension)
- Tolerance to nitrate can occur, so nitrate-free intervals
should present
Notes about beta-blockers:
- Treat with Beta-blockers to target heart rate of 50 – 60/m
- Beta-blockers reduce the heart rate and O2 demands
leading to mortality reduction.
- Non-selective Beta-blockers are contraindicated with
asthma because they can cause bronchospasm
- Beta-blocker should not be given together with verapamil
or diltiazem (risk of cardiac arrest)

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Other notes:
- PCI cannot decrease mortality more than drug therapy in
Stable angina but only improve quality of life and
decrease symptoms
- The most anterior chamber of the heart is the right
ventricle, while the most posterior chamber is the left
atrium.
- Angina equivalent: exertional shortness of breath
- Angina decubitus: angina on changing position occurs
because gravity redistributes bodily fluids. This
redistribution makes the heart work harder.

Unstable angina (UA)

- Unstable angina due to transient obstruction of the coronary
artery
- The plaque ruptured and mobile, causing transient
obstruction of the coronary artery
Symptoms:
- Typical chest pain at rest (central, retrosternal, heavy in
character, radiated to neck –jaw-epigastrium or back)
- Same as stable angina, but the pain comes at rest
- Unstable angina may be preceded by stable angina for
years
Diagnosis:
- Clinical diagnosis
- Normal cardiac enzymes (no muscle necrosis)
- ECG: ST depression or T wave inversion

Stable angina Unstable angina (UA)

Exertional pain Pain at rest or new-onset pain
Crescendo-decrescendo pain Crescendo pain
2 – 10 minutes duration > 10 minutes duration
Table 62: Stable vs. Unstable angina

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 Cardiac enzymes
Myoglobin:
- The first cardiac enzyme to appear after MI (1 – 4 hours)
- Not specific
CPK (creatinine phosphokinase):
- Can be high in conditions other than MI (like a skeletal
muscle injury, IM injections, rhabdomyolysis, CVA, etc.)
- Onset: 4 – 6 hours, and offset at 2 – 3 days post-MI
- CK-MB is useful for diagnosing re-infarction
- Types of CPK include:
o CK-MM (found in skeletal muscles)
o CK-MB (mostly found in the heart)
o CK-BB (mostly found in the brain)
Troponin:
- It is the most sensitive and specific for myocardial damage
- Subtypes include Troponin T, I, and C
- Troponin T and I are sensitive and specific for myocardial
damage
- Onset 4 – 6 hours, offset at 10 – 14 days post-MI
- Causes of positive troponin other than MI are (CKD, sepsis,
pneumonia, pericarditis 50%, pulmonary embolism, heart
failure, atrial fibrillation, rhabdomyolysis with cardiac injury,
myocarditis, cardiac injury, and surgery)
Other cardiac enzymes:
- AST can be released by the myocardium in case of MI
- The last cardiac enzyme to rise and lasts for the longest
period is LDH
NSTEMI
- NSTEMI: infarction of cardiac muscles without ST elevation
- It affects the partial thickness of the myocardium, so it is
called partial thickness MI
Diagnosis:
- Typical chest pain > 30 minutes associated with sweating and
nausea
- High cardiac enzymes
- ST depression or T wave inversion (but not ST elevation)

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 STEMI
- STEMI: complete obstruction of the coronary artery with full-
thickness necrosis of the myocardium, also known as full-
thickness myocardial infarction.
Diagnosis:
- Typical chest pain
- Elevated cardiac enzymes
- ST-elevation
ECG changes in MI:
- Within hours, peaked T wave and ST deviation (elevation or
depression)
- Within 24 hours, T inversion and ST-segment resolution
- Within a few days, pathologic Q wave (> 1/3 the R length or
> 40 ms) (persist in 90% of patients and resolute in 10%)
Infarction Locations and their relation to ECG:
- Inferior MI:
o Affected leads on ECG: II, III, AVF
o Affected artery: Right Coronary artery (RCA)
o Most commonly associated with bradycardia,
hypotension, and High JVP
o High-fluid volume is recommended as this case is
preload dependent (especially in Right V4
involvement)
o Nitrates are contraindicated in this case
- Anterior MI:
o Affected leads: V3 – V4
o Affected artery: left Anterior descending artery (LAD)
- Septal MI:
o Affected leads V1 – V2
o Affected artery: left Anterior descending artery (LAD)
- Lateral MI
o Affected leads: I, AVL, V5 – V6
o Affected artery: left Circumflex artery
o Leads I and AVL are high lateral leads
- Posterior MI:
o ST depression on the anterior and septal leads
o Rarely come isolated (usually associated with inferior
or lateral MI)

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 Arterial supply of the heart:
- Left aortic sinus → left coronary artery (LCA) → LAD and
circumflex
- Right aortic sinus → right coronary artery (RCA) → posterior
descending
- RCA supplies SA node in 60%, AV node in 90%
Venous drainage of the heart:
- The coronary sinus drains into the right atrium
- Thebesian veins (minute veins in the walls of the heart
chambers)

Figure 30: anatomy of the coronary artery

Treatment of ACS
Treatment for all patients with ACS at ER: (MONA-B)
- Morphine IV for pain relief (not suitable to use in inferior MI –
reduce preload).
- Oxygen (only if O2 saturation is less than 94%)
- Nitrates (But contraindicated in inferior MI risk of severe
hypotension)
- Beta-blockers (Metoprolol IV – reduces mortality)
- Anti-platelet and Heparin therapy: as follows:
o Aspirin: for all types of ACS
o If NSTEMI: Ticagrelor or Clopidogrel in addition to
Aspirin + Heparin
o If PCI is planned: ticagrelor or prasugrel with
intravenous GP IIb/IIIa inhibitor

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 o Clopidogrel used if patient ineligible for ticagrelor and
prasugrel
o Prasugrel is contraindicated in those with a history of
stroke/TIA, and a lower dose is recommended for
those > 75-year-old
Reperfusion choice for STEMI:
- If PCI cannot be achieved by 90 minutes in the same hospital
or 120 minutes in the nearest PCI-capable hospital, then do
thrombolysis
- If thrombolysis is contraindicated – do PCI
- If failed thrombolysis, PCI should be done
After reperfusion:
- ACE inhibitors should be used unless contraindicated
- Dual antiplatelet therapy
- Continue Statin therapy
- heparin is indicated during the period of hospitalization

TIMI score for UA and NSTEMI: (score from 0 – 7):

- Age ≥ 65 years old
- ≥ 3 Risk factors for CAD
- Known case of CAD (> 50% stenosis)
- Aspirin used in last week
- ≥ 2 anginal episodes in the previous 24 hours
- ST deviation
- Positive cardiac markers
If the score is ≥ 3, use LMWH, Glycoprotein IIB/IIIa inhibitor, and
early angiography
Table 63: TIMI score for UA and NSTEMI

Signs of successful reperfusion after STEMI:

- Accelerated Idioventricular arrhythmia
o Also known as reperfusion arrhythmia
o Early (within 6 hours), frequent (> 30 per hour), and
repetitive (> 3 consecutive hours)
o Ventricular tachycardia is considered benign if it
appears within 24 hours post-reperfusion therapies. It
needs no treatment.
- Regression of ST-elevation by ≥ 50%

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Contraindications to thrombolytics:
- Absolute contraindications:
o Prior intracranial hemorrhage (ICH)
o Significant closed head trauma or facial trauma
within 3 months
o Intracranial or intraspinal surgery within 2 months
o Known structural cerebral vascular lesion or malignant
intracranial neoplasm
o Ischemic stroke within 3 months
o Suspected aortic dissection
o Active bleeding or bleeding diathesis (excluding
menses)
o Severe uncontrolled hypertension (unresponsive to
emergency therapy)
o For streptokinase, prior treatment within the previous 6
months
- Relative contraindications:
o Traumatic or prolonged (> 10 minutes)
cardiopulmonary resuscitation (CPR) or major surgery
less than 3 weeks previously
o History of prior ischemic stroke not within the last 3
months
o Recent (within 2-4 weeks) internal bleeding
o Pregnancy
o Current use of an anticoagulant (e.g., warfarin) with
INR > 1.7 or PT > 15 seconds

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Notes:
- A stent could be inserted during PCI to keep the coronary
artery patent
- Two types of stents are available (drug-eluting and bare-
metal stents)
- Dual antiplatelet therapy should be used with Aspirin and
Clopidogrel post-MI
- Dual antiplatelet therapy lasts for 1 year in the drug-eluting
stent and 1 month only in bare metal
- The most common cause of re-stenosis post PCI is: non-
compliance to dual antiplatelet therapy
- Nifedipine increases cardiac output and heart rate leading
to increased oxygen demand (should be avoided in ACS)
- Avoid NSAIDs and steroids in periinfarction pericarditis; they
interfere with ventricular healing and remodeling but can
be used in Dressler's syndrome
- Antiplatelet and heparin are NOT reperfusion therapy.
- Reperfusion therapy includes PCI, streptokinase, and TPA

Complications of MI
- 75% of patients will have arrhythmias, the most common
cause of death during the first hour
- 10 – 15% will have AF and A. Flutter during hospitalization (
poor prognosis)
- AF and heart block are more common in inferior MI
- VT and Ventricular fibrillation in the first 24 hours do not affect
prognosis (treated by early DC shock)
- Ventricular fibrillation is the most common arrhythmia post-MI

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Complications of MI Features
Arrhythmias Palpitation, instability, ECG findings
LV free wall rupture Signs of cardiac tamponade -
usually occur during the first week
Papillary muscle rupture Signs of acute Mitral regurgitation
Ventricular septum rupture Signs of VSD
LV aneurysm Persistent ST elevation
Re-occlusion, stent Typical chest pain + high CK-MB
restenosis and/or new ST elevation
Dressler’s syndrome (3P's) 2 – 10 weeks post-MI, pericarditis,
pleuritis, pyrexia treated by NSAIDs
[1] signs of cardiac tamponade: (muffled heart sound + raised

JVP + hypotension +pulsus paradoxus + electrical alternans)

[2] Mitral regurgitation: (soft S1+split S2+ pan-systolic murmur-

blowing in character, hypotension, acute heart failure)

[3] VSD: (pan-systolic murmur - harsh in character)

Table 64: Complications of myocardial infarction

Conditions like MI
Coronary vasospasm (Prinzmetal angina)
- Chest pain at rest usually occurs in a young patient
- Transient ST deviation
- Absent obstruction on angiogram
- It can be triggered by drugs like (cocaine and
methamphetamine)
- Aspirin should be avoided (it can aggravate the ischemic
attack)
- Beta-blockers are contraindicated (they can increase the
vasospasm)
- The treatment of choice is CCB with or without long-acting
nitrates
Takotsubo cardiomyopathy:
- Typical chest pain + ST-elevation + elevated cardiac enzyme
- Associated with stress
- Normal angiogram
- Echocardiogram shows (octopus pot)
- Treatment is supportive
- 95% self-resolution within 7 days

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 Congestive Heart Failure (CHF)
- Impaired heart's diastolic filling or Ejection of blood, almost
any cardiac disease can cause heart failure
Classifications:
- Systolic (HFrEF) vs. Diastolic (HFpEF) heart failure
- Right-Sided vs. Left-sided Heart failure (the most common
cause of right-side HF is left-side HF)
- low output HF vs. High output HF
The severity of HF according to EF%:
- Grade I (EF > 60%) (Normal)
- Grade II (EF = 40-59%)
- Grade III (EF = 21-39%)
- Grade IV (EF ≤ 20%)
NYHA classification of HF:
- Class I: no limitations on ordinary physical activities
- Class II: slight limitation of ordinary physical activities
- Class III: marked limitation of physical activity
- Class IV: symptoms of CHF present at rest

Hyponatremia is an independent predictor of mortality in CHF

Symptoms of HF:
- Symptoms of low cardiac output – left side (hypotension,
syncope, cold extremities…)
- Symptoms of backward congestion are as the following:
o Left-side heart failure: dyspnea, orthopnea, PND,
pulmonary edema, pleural effusion, cardiomegaly,
left side S3/S4 Gallop rhythm.
o Right-side heart failure: peripheral and lower limb
edema, liver congestion, hepatojugular reflux, ascites,
high JVP, right side S3/S4 gallop rhythm.

Terminology:
- Dyspnea: shortness of breath
- Orthopnea: shortness of breath on lying flat
- Paroxysmal nocturnal dyspnea (PND): SOB about a ½ hour
after sleeping.

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Pathology:
Heart insult → decreases heart function → decreases renal
perfusion → activation of the Renin-angiotensin system and the
sympathetic nervous system → leads to sodium water retention →
more load at heart → more cardiomegaly and dilation → More
heart insult.
Diagnosis:
- Echocardiogram measures Ejection fraction and assesses
the valvular condition and wall motion abnormalities.
- Identify risk factors and causes which lead to HF
- ECG, CXR
- Blood workup (CBC, U&Es, KFT, LFT, A1C, LIPID profile, TSH)
Features of CHF on CXR: (ABCDE)
- Alveolar edema (Bat’s wings)
- Kerley B lines (interstitial edema)
- Cardiomegaly
- Dilated prominent upper lobe vessels
- Effusion (pleural)
Treatment of chronic CHF:
- Lifestyle measures: diet, exercise, DM control, smoking
cessation, decrease alcohol consumption, sodium restriction
(no more than 2.4 sodium or 5 grams salt daily)
- ACEI/ARB can reduce the mortality rate (Avoid CCB as it
can worsen the edema)
- Beta-blockers (only: carvedilol or bisoprolol) decrease the
mortality rate (avoid during decompensated heart failure)
- Diuretics (Aldactone – reduce mortality, Furosemide –
symptomatic treatment)
- Digoxin has only symptomatic benefits and no effect on
mortality
- Annual influenza vaccine
- One-time pneumococcal vaccine

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Advanced treatment:
- Sacubitril/Valsartan: Angiotensin Receptor Neprilysin Inhibitor
(ARNI); it is a new drug that provides mortality and
symptomatic benefit for systolic dysfunction
- Ivabradine: inhibits the “Funny channels” used in a patient
with heart failure where heart rate > 70 bpm or when Beta-
blockers are contraindicated
- ICD is indicated if EF < 35% - to decrease the risk of sudden
death
- Left ventricular assist device (LVAD) or Cardiac transplant
(last resort for treatment of HF)

Treatment tips:
- HF treatment with mortality benefits are: ACEI/ARB, Beta-
blockers, Spironolactone, Eplerenone (hydralazine +
Nitrates), ICD, Sacubitril/Valsartan
- Digoxin and Loop Diuretics have no mortality benefits
(only symptomatic)
- CCB may increase the mortality rate and worsen edema
in systolic heart failure but reduces the mortality in isolated
diastolic heart failure
- Digoxin and spironolactone are not beneficial in diastolic
heart failure

Role of BNP:
BNP (brain natriuretic peptide) is an enzyme secreted by heart
muscles due to stretching or infarction of these muscles. It acts as
a diuretic to decrease blood pressure and decrease the load on
the heart; useful to investigate if you are not sure if shortness of
breath is due to a cardiac or respiratory cause
- If BNP level is high (> 500 pg/ml), cardiac cause
- If BNP is not high, non-cardiac cause
Causes of high BNP:
- Heart failure
- Acute MI
- Mitral valve rupture
- Constrictive pericarditis
- Large pulmonary embolus
Table 65: BNP rule in the diagnosis of SOB

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 Pulmonary edema
- Pulmonary edema is a collection of fluids in the interstitium of
the lungs
- It can be caused by increased orthostatic pressure or
decreased oncotic pressure inside the blood vessels leading
to fluid leak to the interstitium.
- Acute pulmonary edema usually presents due to
Decompensated Heart Failure (DHF). (associated with high
BNP)
- Other causes include: renal failure, excessive fluid
replacement, ARDS, decreased albumin (nephrotic
syndrome, liver cirrhosis)
- Late inspiratory crepitations (unchanged with cough)
Treatment of Acute pulmonary edema:
- keep patient in a semi-sitting position
- Oxygen
- Morphine (reduces anxiety and preload)
- High dose furosemide (40-500mg)
- Nitrates
- Non-invasive or mechanical ventilation if indicated.
- Dobutamine or intra-aortic balloon pump can be used in
pulmonary edema and cardiogenic shock.
- Treatment of the precipitating condition (MI, arrhythmia …)

Digoxin and digoxin toxicity

Digoxin is used in the treatment of HF (positive inotropic) & rate
control in the management of atrial fibrillation (rate control)
Action: decrease AV node conduction and increase the force of
cardiac muscle contraction
Features of toxicity:
- Fatigue, nausea & vomiting, anorexia, confusion
- Yellow-green vision
- Arrhythmias: e.g., AV block, bradycardia, short QT interval
Predisposing factors:
- Hypokalemia (Most Common)
- Hyperkalemia (less common)
- Increasing Age
- Renal Failure
- Myocardial Ischemia

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 - Hypomagnesaemia, Hypercalcemia, Hypernatremia,
Acidosis
- Hypoalbuminemia
- Hypothermia
- Hypothyroidism
Treatment:
- Correct arrhythmia
- Correct and monitor potassium
- Digibind (Digifab): is a digoxin-specific antibody used as an
antidote to digoxin in case of toxicity
In digoxin toxicity, calcium gluconate should be avoided; it may
precipitate ventricular fibrillation or ventricular tachycardia.

Myocarditis
- It is an inflammation of the heart muscle that can be acute
or chronic and cause dilated cardiomyopathy.
Causes:
- Could be idiopathic, infectious, toxin, or systemic disease
- Most common infection = viral infection = coxsackie B virus,
other virus: HIV
- Bacterial: diphtheria, clostridia
- Lyme disease
- Autoimmune (SLE, RA...)
- Chagas disease: American trypanosomiasis can be a cause
- Drug-induced: Doxorubicin
Symptoms:
- Fever, chest pain, and SOB may present with sudden death
Diagnosis:
- ECG: Non-specific ST-T changes
- Positive cardiac enzymes
- High WBC
- The lab results of the cause
- Chest X-Ray: dilated heart + silhouette sign
- Echocardiography: hypokinesia, dilated heart chambers
Treatment:
- Supportive
- Treatment of complications like arrhythmias
- Treatment of the cause, if possible
Complications: DCM, Embolic events, Arrhythmias, and sudden
death

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 Cardiomyopathies
Cardiomyopathy is a Primary myocardial disease with no known
cause
The new classification:
- Primary cardiomyopathy:
o Hypertrophic obstructive cardiomyopathy (HOCM)
o Arrhythmogenic Right Ventricular Cardiomyopathy
- Mixed cardiomyopathy:
o Dilated cardiomyopathy
o Restrictive cardiomyopathy
- Acquired cardiomyopathy:
o Peripartum cardiomyopathy
o Takotsubo cardiomyopathy
- Secondary cardiomyopathy:
o Infective (coxsackie B virus, HIV, Chagas disease…)
o Infiltrative (Amyloidosis)
o Storage (Hemochromatosis)
o Toxicity (drugs, Alcohol)
o Inflammatory (sarcoidosis)
o Autoimmune (SLE)

Dilated Cardiomyopathy (DCM)

- It is the most common form of cardiomyopathies
- Dilated heart and systolic +/- diastolic dysfunction
- All 4 chambers affected but LV more than RV
- Absence of congenital, valvular or ischemic heart disease
Causes:
- Most cases are idiopathic
- Post- viral Myocarditis (the most common cause)
- Alcohol or Drugs (e.g., Doxorubicin)
- Radiation
- Chagas disease
Clinical Features:
- Features of Congestive heart failure
- Arrhythmias and sudden death may occur
- Embolization
- Mitral regurgitation

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Treatment:
- Drugs that lower mortality: (ACEI, ARB, Beta-blockers,
spironolactone)
- Digoxin used to control symptoms
- Pacemaker improves both symptoms and survival
- Implantable Cardioverter Defibrillator (ICD) has mortality
benefits in some patients

Hypertrophic obstructive cardiomyopathy

- It is regional hypertrophy of the left ventricle that most
commonly involves the interventricular septum
- HOCM is the most common cause of sudden death in
athletes
- Most cases are inherited as an autosomal dominant disease
- Due to a mutation in the gene encoding β-myosin heavy
chain protein (sarcomere)
Pathogenesis:
- Left ventricular outflow tract obstruction due to septal and
the anterior mitral valve leaflet hypertrophy.
- Factors affecting the degree of obstruction:
o Factors increasing preload and afterload will reduce
the obstruction
o Factors that reduce the ventricular size (e.g.,
dehydration, Inotropes, ACEI, ARBs) will worsen the
obstruction.
Clinical features:
- The condition is usually asymptomatic
- It may present with sudden death
- Chest pain (usually at rest and not related to exercise)
- Syncope (usually arrhythmogenic during exercise)
- Features of CHF (usually diastolic – reduced filling)
Diagnosis:
- ECG:
o Left ventricular and left atrial hypertrophy
o Inverted symmetric T wave in leads V3 – V6 (apical)
- Echocardiogram: (MR SAM ASH)
o Mitral Regurgitation (MR)
o Systolic anterior motion (SAM) of the anterior mitral
valve
o Asymmetric septal hypertrophy (ASH) > 1.5 times the
thickness of the posterior wall.

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Management
- Avoid competitive sports (to prevent sudden death)
- Beta-blockers (first line if ejection fraction ≥ 50%)
- CCB (e.g., verapamil) may be substituted for beta-
blockers
- Warfarin or DOAC, regardless of the CHA2DS2VASc score
- Septal ablation or surgical myomectomy
- Cardioverter-defibrillator for high-risk patients

Digitalis, Nitrates, positive inotropes, ACEI, and ARBs will worsen

the obstruction in HOCM, and they should not be used.

Arrhythmogenic Right ventricular

cardiomyopathy (ARVC)
- Also known as Arrhythmogenic right ventricular dysplasia
- It is the second most common cause of sudden death in
athletes
- An autosomal dominant pattern that may present with
syncope or sudden cardiac death
- The right ventricular myocardium is replaced by fatty and
fibrofatty tissue
- Implantable-Cardioverter-Defibrillator (ICD) is the treatment
of choice and is better than Beta-blockers and other
antiarrhythmic agents
ECG changes:
- T wave inversion in V1- V3.
- An epsilon wave in 50% of cases (a small positive deflection
at the end of the QRS complex)

Figure 31: One beat ECG showing epsilon wave

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 Peripartum cardiomyopathy
Typical develops between the last month of pregnancy and 5
months post-partum
more common in older women, greater parity and multiple
gestation

Cardiac tumors
- The most common primary cardiac tumor is atrial myxoma,
but the most common cardiac tumors are metastatic (e.g.,
melanoma, thymoma)
- The most common site for atrial myxoma is the left atrium
- The most common site for angiosarcoma is the right atrium
Clinical features:
- Constitutional symptoms: fever, anorexia, weight loss
- Digital clubbing, Embolization, atrial fibrillation
- Mid-diastolic murmur
Diagnosis: Echocardiography
Treatment:
- Resection to reduce the risk of embolization and
complications
- Anticoagulation

Figure 32: A sketch showing an Atrial myxoma

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 Diseases of Endocardium
Infective Endocarditis (IE)
- Endocarditis is an inflammation of the endocardium or heart
valves, usually due to bacterial infection.
Risk factors:
- IV drug users – most commonly affect the tricuspid valve
- Previous Endocarditis
- Prosthetic valve
- Congenital heart disease (But not ASD)
- Valvular heart disease (Mitral prolapse...)
- Poor dental hygiene
Most common bacteria causing endocarditis:
- The common cause of Native valve Endocarditis:
o Health-care associated: Staphylococcus aureus.
o Community-acquired: Streptococcus viridans
- The most common cause of prosthetic valve endocarditis:
o In the first 2 months: Coagulase-negative
Staphylococcus epidermidis (CoNS)
o From 2 – 12 months: Staphylococcus aureus
o After 12 months: Streptococcus viridans
- The most common cause in IV drug users:
o Staphylococcus aureus
- The most common cause in patients with colon cancer:
o Streptococcus gallolyticus (S. bovis)
o Clostridium septicum endocarditis
- Streptococcus viridans (most in poor dental hygiene)
- Non-infective endocarditis (sterile vegetation):
o Libman-Sacks: due to SLE
o Marantic endocarditis: due to malignancy
Signs and symptoms:
- Non-specific symptoms: (fever, rigors, general weakness)
- Cardiac: (dyspnea, chest pain, clubbing, new murmur, CHF)
- Embolic phenomena: (petechiae, splinter hemorrhage,
Janeway lesion- at sole and palm, CNS or Renal emboli)
- Immune complex phenomena (Osler's nodes at digits,
Glomerulonephritis, Roth's spots at retina)
- Hemolytic anemia can be caused if there is an infective
Endocarditis in a prosthetic valve

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 Figure 33: a) Osler nodes, B) Janeway lesions, C) Roth spots

Notes:
- Osler nodes are pathognomonic for infective endocarditis
- The most common sign of IE is: fever
- The second most common sign of IE is: Heart murmur

Modified Duke Criteria:

Pathological criteria: (positive Histology or microbiology of
pathological material obtained at autopsy or cardiac surgery)
Major criteria:
- Positive culture "2 cultures, 48 hours apart, and typical
organisms"
- Positive Echo.
Minor criteria:
- Predisposing factors
- Fever > 38.5
- Embolic phenomena
- Immune complex phenomena
- Positive culture but not meeting major criteria
Diagnosis:
- 1 Pathological criterion, or
- 2 major criteria, or
- 3 minor criteria and 1 major, or
- 5 minor criteria

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Treatment:
- Supportive treatment
- Empyrical antibiotics then switch according to culture results

The empirical antibiotics for infective endocarditis:

- Native valve: amoxicillin, ± Low-dose Gentamicin
- Penicillin allergic, MRSA, or severe sepsis: vancomycin +
low-dose gentamicin
- Prosthetic valve: vancomycin + rifampicin + low-dose
gentamicin

Indications for surgery in IE:

- Severe valvular incompetence
- Aortic abscess (often indicated by a lengthening PR interval)
- Infections resistant to antibiotics/fungal infections
- Cardiac failure refractory to standard medical treatment
- Recurrent emboli after antibiotic therapy
Poor prognostic factors:
- Staph aureus infection
- Prosthetic valve (especially early, acquired during surgery)
- Culture-negative Endocarditis
- Low complement levels

Valvular heart diseases

Aortic stenosis
- Progressive degenerative disease of the normal trileaflet
aortic valve is the most common cause (in elderly patients)
- Congenital bicuspid aortic valve usually occurs in 20 – 40
years olf patients
Clinical features:
- Chest pain, dyspnea, syncope (usually exertional)
- Systolic ejection murmur
- S4 and muffled S2
- Narrow pulse pressure and slow rising pulse
- Echocardiogram is the most accurate test

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Treatment:
- If asymptomatic, there is no need for treatment,
- Medical treatment: diuretics, digoxin, and ACE inhibitors
- If symptomatic; valve replacement for elderly or balloon
valvoplasty in young patients

Aortic regurgitation
- Acute AR is mostly caused by aortic dissection and IE
- Chronic AR is caused by aortic dilatation, calcification,
rheumatic disease, and bicuspid aortic valve.
Clinical features:
- Angina, orthopnea, exertional dyspnea
- Early diastolic murmur
- Soft S1 and S2, loud S3
- Wide pulse pressure
Specific signs of AR:
- Water hammer pulse
- Easily palpable popliteal and Dorsalis Pedis pulse
- Hill’s sign: Popliteal systolic blood pressure exceeding
brachial systolic blood pressure by ≥ 60 mmHg (most
sensitive sign for aortic regurgitation)
- Quincke’s sign: capillary pulsations in nail beds
- Corrigan sign: Prominent (jerky) carotid pulsation (dancing
carotid)
- De Musset’s sign: Head nodding in time with the pulse
- Muller’s sign: Pulsation of the uvula in time with the pulse
- Rosenbach’s sign: Hepatic pulsations
- Traube’s sign: Systolic and diastolic sounds heard over the
femoral artery (“pistol shots”)
Treatment:
- Indications for surgical replacement of the valve in AR:
o Acute aortic regurgitation
o Chronic symptomatic AR
o Chronic asymptomatic with LVEF < 50%
- ACEI and CCB are only indicated in symptomatic patients.

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 Mitral stenosis
- The most common cause is RF (Rheumatic mitral stenosis is
more common in women)
- Other causes (congenital, calcification, fibrosis)
Clinical features:
- Pulmonary edema, Pulmonary HTN, hemoptysis
- Malar flush (due to CO2 retention)
- Late-diastolic murmur with opening snap
- Laud S1
- Atrial fibrillation (as a complication)
- Hypoplastic left ventricle
Treatment:
- Surgical repair or replacement
- Diuretics, long-acting nitrates, beta-blockers, and CCB
- Warfarin for all patients with AF and MS regardless of
CHA2DS2VASc score.

Mitral regurgitation
- The most common cause is RF,
- It can be caused by MI, Left ventricular dilatation
- Symptoms: Pulmonary edema, atrial enlargement, Pan-
systolic murmur, soft S1, split S2, and S3 (if severe)
- Treatment:
o Diuretics
o ACEI
o Surgery (may be needed if severe)

Mitral prolapse
- Can be associated with (Marfan's syndrome, Turner
syndrome, Ehlers-Danlos syndrome, polycystic kidney
disease)
- Symptoms: atypical chest pain, palpitation, can cause
sudden death
- Mid-systolic click, late systolic murmur

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 Tricuspid valve abnormalities
Tricuspid stenosis:
- Cause – endocarditis, RF, congenital
- Diastolic murmur
Tricuspid regurgitation:
- Cause – Right Ventricular dilatation, RF, pulmonary-HTN,
- Signs: Pansystolic murmur, pulsatile hepatomegaly

Heart sounds
The first heart sound (S1) is caused by the closure of the Mitral and
Tricuspid valves, while the second heart sound (S2) is due to aortic
and pulmonary valves closure

Heart sound Features

First heart Closure of mitral and tricuspid valves
sound (S1) Soft if mitral regurgitation and Loud in mitral
stenosis
2nd heart Closure of aortic and pulmonary valves
sound (S2) Soft in aortic stenosis
Splitting during inspiration is normal
Fixed splitting is seen in the case of ASD
3rd heart Caused by diastolic filling of the ventricle
sound (S3) Considered normal if < 30 years old (may persist in
women up to 50 years old).
Heard in left ventricular failure (e.g., dilated
cardiomyopathy), constrictive pericarditis, and
severe mitral regurgitation
4th heart Caused by atrial contraction against a stiff
sound (S4) ventricle
It may be heard in aortic stenosis, HOCM,
hypertension
Table 66: Heart sounds and their causes

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 Pulses
Type of pulse Features and causes
Pulsus Greater than the normal (10 mmHg) fall in
paradoxus systolic blood pressure during inspiration
Causes: Severe asthma, COPD, Cardiac
tamponade
Slow rising pulse Aortic stenosis
Collapsing Aortic regurgitation
Patent ductus arteriosus (PDA)
Hyperkinetic (anemia, thyrotoxicosis, fever,
exercise/pregnancy)
Pulsus alternans Regular alternation of the force of the arterial
pulse
Caused by severe LVF
Bisferiens pulse Double pulse - two systolic peaks
Caused by Mixed aortic valve disease
Occasionally occurs in HOCM
Jerky pulse Caused by HOCM
Table 67: Features and causes of different types of Pulses

Murmurs
Murmur type Possible Causes
Ejection systolic Aortic stenosis, Pulmonary stenosis, HOCM,
ASD, Fallout's
Pan-systolic MR/TR (blowing in character)
VSD ('harsh' in character)
Late systolic Mitral valve prolapse
Coarctation of aorta
Early diastolic Aortic regurgitation
Graham-Steel murmur (PR, blowing murmur)
Mid-late diastolic Mitral stenosis ('rumbling' in character)
Austin-Flint murmur (severe AR, rumbling
murmur)
Continuous Patent ductus arteriosus (PDA)
machine-like
murmur
Table 68: Causes of different types of heart murmurs

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 Effects of some maneuvers on Murmurs
Squatting and leg rising:
- Increased venous return
- Increased intensity of all murmurs except Mitral prolapse
and HOCM, which will be decreased
Standing and Valsalva maneuver:
- Decrease venous return to the heart
- Decrease the intensity of all murmurs except for MVP and
HOCM, which are increased.
Handgrip:
- Decrease left ventricular emptying
- Decrease loudness of (AS, MVP, and HOCM) murmurs
- Increase loudness of (AR and MR) murmurs
- No effect on MS
Nitrates:
- Same effect as ACEI on murmurs
- Direct arteriolar vasodilator
- Increased ventricular emptying
- Increase loudness of (AS, MVP, and HOCM) murmurs
- Decrease loudness of (AR and MR) murmurs
- No effect on MS

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 Pericardial diseases
Pericarditis
- Pericarditis is an inflammation of the pericardium
- If pericarditis is associated with extravasation, pericardial
effusion and tamponade can occur
- If chronic pericarditis, fibrosis, and calcification will result in
constrictive pericarditis
Causes:
- Most commonly – idiopathic
- Infection (viral, bacterial, TB, fungal)
o The most common infection is coxsackie B virus
- Inflammation (SLE, RA, Dressler's syndrome)
- Metabolic (uremia)
- Malignancy (Hodgkin's lymphoma, breast cancer, lung
cancer)
Clinical features:
- A friction rub is the earliest sign of pericarditis
- Atypical chest pain (positional; increased by lying back and
decreased by bending forward)
- Fever, General weakness
Diagnosis: Clinical picture + friction rub + ECG changes
- The most specific ECG change is depressed PR interval
(elevated on AVR)
- Other ECG changes: ST elevation in all leads (diffuse ST
elevation) (Depression on AVR)
- Echocardiogram for assessing for pericardial effusion
Treatment:
- Bed-rest, NSAIDs
- Colchicine decreased recurrence
- Steroids for severe or recurrent cases
- Treatment of the underlying disease

Anticoagulant is not safe to use in pericarditis

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 Pericardial effusion
- It defined as Fluid collection within the pericardium
Causes:
- Can be Transudate due to (CHF, hypothyroidism, or
hypoalbuminemia)
- Exudates due to (same causes of pericarditis)
Symptoms:
- It depends on the amount of fluid and May be
asymptomatic
- Dyspnea, cough, signs of pericarditis, elevated JVP and
Ewart's sign, muffled heart sounds
- Best investigation: pericardiocentesis (determine exudates
Vs. Transudate)
Treatment:
- If mild: observation + NSAIDs
- If sever: pericardiocentesis

Ewart’s Sign: Bronchial breathing and dullness to percussion

at the lower angle of the left scapula due to effusion.

Figure 34: Pericardiocentesis procedure

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 Cardiac tamponade
- Rapid or massive accumulation of pericardial effusion, or
blood collection in the pericardial space
- It causes decreased venous return, filling, and stroke volume.
Diagnosis:
- Beck's tirade (hypotension, increased JVP, and muffled
heart sounds)
- Other symptoms: dyspnea, pulsus paradoxus, shock, and
peripheral edema
- Pulsus paradoxus (inspiratory fall in systolic BP > 10 mmHg
during quiet breathing)
- Electrical alternans (high and low voltage of QRS's on ECG
alternatively)
Treatment:
- Best: urgent pericardiocentesis
- Pericardiectomy
- IV fluids (to increase cardiac output)
- Treatment: of the underlying cause

Note: avoid diuretics in cardiac tamponade because

it decreases venous return and worsens the symptoms.

Constrictive pericarditis
Fibrosis, calcification, thickening, and adherence of pericardium
that limit the expansion of the heart
Kussmaul's sign: a paradoxical rise in jugular venous pressure (JVP)
on inspiration, usually present in constrictive pericarditis. (Rarely
present in tamponade).
Best Treatment: Pericardiectomy

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 Other cardiology problems
Anaphylaxis
- Anaphylaxis: IgE mediated severe, life-threatening,
generalized, or systemic hypersensitivity reaction; the patient
must be already sensitized to the antigen
- Anaphylactoid reaction: Non-IgE related (complement-
mediated), similar clinically to anaphylaxis and treated the
same way, does not need preceding sensitization to antigen
- Urticaria: is a part of anaphylaxis (redness of the skin as a
result of exposure to an antigen)
Pathogenesis: Exposure to an antigen → immune system activation
→ IgE binds to Mast cells → histamine, prostaglandins, and
leukotrienes release → vasodilatation → hypotension and shock
Common causes of anaphylaxis
- Food (e.g., Nuts) - the most common cause in children
- Medications
- Bites and stings (e.g., Wasp sting)
Clinical presentation:
- Rash (present in all types of anaphylaxis)
- Hypotension and tachycardia
- Respiratory symptoms (SOB, wheezing, stridor…)
The best investigation is serum tryptase level that remains elevated
for 12 hours post anaphylaxis
Treatment:
- First-line treatment is adrenalin 1/1,000 (best to give IM)
- Hydrocortisone: (its action needs up to 4 hours)
- Chlorphenamine (Allerfrin)
- Nebulized Beta-2 agonist
- Supportive measures (O2, I.V Fluids)
- Emergent airway protection if required (intubation,
cricothyroidotomy)
Doses of adrenalin Doses of hydrocortisone
0.5 ml for adults 25 mg < 6 months
0.3 ml for children > 6 months 50 mg 6 month-6 years
0.15 ml for children < 6 months 100 mg 6 years -12 years
200 mg > 12 years
Table 69: Doses of adrenalin and hydrocortisone in anaphylaxis

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 Syncope
- Sudden impairment of consciousness
- Should be distinguished from seizures
- In syncope, no warning symptoms, no abnormal movements
during the attack, fast and full recovery in less than 2
minutes, and no symptoms after the attack.
Causes:
- Gradual onset syncope:
o Toxic metabolic
o Hypoglycemia
o Anemia
o Hypoxic etiology
- Sudden onset with a sudden return to consciousness
syncope:
o Structural heart disease (e.g., valvular disease)
o Ventricular arrhythmias
o Vasovagal attack
Diagnosis:
- Cardiac and neurological examination:
o If a murmur is present, echocardiography is indicated
o If there is a history of head trauma or focal
neurological deficit, a brain CT scan is indicated
o If normal cardiac exam and still suspected cardiac
cause, Holter monitor is indicated
- ECG, cardiac enzymes
- Serum glucose
- Oximeter
- CBC
- Urine and blood toxicology screen
- Tilt table testing (vasovagal syncope)

Only brain stem stroke can cause syncope (lesion in the

posterior circulation). The Brain stem is responsible for sleep
and awake control

Treatment:
- Treatment of the cause
- Vasovagal syncope treated with beta-blockers
(maintenance) and atropine (for attack)

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 Gastroenterology
CHAPTER 5

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Introduction to gastroenterology
Dysphagia is a Difficulty in swallowing that is present in most
esophageal disorders
- Oropharyngeal dysphagia:
o It is difficulty of initiating swallowing
o Causes (CVA, Parkinson, MG, ALS)
o Diagnosis (Videofluoroscopy with liquid and solid
phases)
- Esophageal dysphagia:
o For solid food: esophageal web, Schatzki ring
o Progressive for solid food: esophageal cancer or
peptic stricture
o For liquid only or liquid and solid food: motility disorder
(e.g., achalasia)
Odynophagia: painful swallowing
Alarm symptoms indicating endoscopy:
- Weight loss
- Blood in stool
- Anemia

Both dysphagia and odynophagia can lead to weight loss

Figure 35: A sketch showing the alimentary tract

(1) pharynx, (2) Esophagus, (3) Stomach, (4) descending colon, (5) Sigmoid, (6)
Rectum, (7) Duodenum, (8) Transverse colon, (9) Ascending colon.

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 Disorders of the esophagus
Gastroesophageal reflux disease (GERD)
- Reflux disease: reflux of gastric acidity to the esophagus.
- Due to inappropriate relaxation of the lower esophageal
sphincter (LES)
- Symptoms of GERD are worsened by alcohol, nicotine,
chocolate, caffeine, late-night meals, Hiatus hernia, and
obesity.
Causes:
- Transient LES relaxation (Most common cause)
- Decrease LES tone (e.g., systemic sclerosis)
- Acid hypersecretion (e.g., Zollinger-Ellison Syndrome)
Clinical picture:
- Heartburn (the most common symptom)
- Gastric content regurgitation
- Chest pain may present, especially with esophagitis present
- Dysphagia is a late symptom
- Cough, wheezes, and aspiration pneumonia
- Hoarseness, metallic taste, and dental caries
Diagnosis:
- The clinical picture with improvement after the Trial of PPI
(Proton pump inhibitor) is usually diagnostic. (if there are no
alarm symptoms)
- 24-hours PH Monitoring (best investigation)
- Endoscopy indicated if:
o Alarm symptoms
o Screening for Barrett's esophagus (after 5-10 years)
Treatment:
- Lifestyle modification:
o Weight loss, no late meals, head elevation in bed
o Avoid coffee, tea, alcohol, and carbonated
beverages
- Medical treatment:
o PPI (the best maintenance therapy)
o H2 blockers (for mild or intermittent symptoms)
o Antacids (On demands)
- Surgical treatment (Nissan's fundoplication) indicated if:
o Failed medical treatment
o Development of complications

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 Stepwise treatment for GERD if there are no Alarm symptoms:
- Order once-daily PPI
- Order twice-daily PPI if there is no improvement
- Do Upper endoscopy of no improvement after 8 weeks if
alarm symptoms appear

Complications:
- Barrett's Esophagus
- Esophagitis: inflammation of the esophagus, ranging from
redness to ulceration and bleeding
- Motility disturbance
- Anemia: IDA (due to bleeding if present)
- Stricture: narrowing of part of the esophagus due to
longstanding esophagitis

Barrette's Esophagus (BE)

- The Squamous lining of the lower esophagus is replaced by
columnar lining due to chronic exposure to acidity due to
GERD (cellular metaplasia)
- This is a pre-malignant condition "0.5%/year risk of malignant
transformation"; it can cause adenocarcinoma of the
esophagus
- Clinically asymptomatic
Diagnosis: biopsy
Treatment: symptomatic treatment and endoscopy.
- For barrette's alone: PPI and endoscopy q3 – 5 years
- For low-grade dysplasia: PPI and endoscopy q6 – 12 months
or endoscopic ablation
- For high-grade dysplasia: endoscopic ablation

Anti-reflux surgery does not prevent the progression of BE to

Adenocarcinoma

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 Esophagitis
- Esophagitis is an inflammation of the esophagus
- The most common presenting symptom is Odynophagia
- The most common cause of infectious esophagitis is
Candida albicans, followed by CMV and HSV.
Esophageal candidiasis:
- Candida albicans: is a normal commensal of mouth
- It can cause oral thrush and esophagitis in immune-
suppressed patients (e.g., DM, Steroid users, HIV)
- In an immunosuppressed patient with oral thrush and
odynophagia, treat for candidiasis without doing an upper
endoscopy.
- The absence of oral thrush does not rule out esophageal
candidiasis
- Treatment:
o Fluconazole or Itraconazole for candidiasis
o Ganciclovir for CMV esophagitis
o Acyclovir for HSV esophagitis
Drug-induced esophagitis:
- Potassium supplements, NSAIDs, tetracycline, and
bisphosphonates are known to induce esophagitis
- Symptoms of severe retrosternal pain with swallowing after
several hours of ingesting the pill are characteristic.
- Treatment is supportive
Eosinophilic Esophagitis (EE):
- The presence of eosinophils in the esophageal biopsy
- Most commonly occurs in children
- Young adults with EE will present with severe dysphagia and
food impaction.
- GERD may be associated with esophageal eosinophilia and
mimic EE
- Treatment: Fluticasone or budesonide swallowing (8 weeks
PPI to rule out GERD induced Eosinophilia)
Corrosive esophageal damage:
- Substances that can cause burns in the mouth, pharynx, and
esophagus
- Seen commonly in suicidal attempts
- Induction of vomiting or NG tube insertion are
contraindicated in corrosive esophageal injuries.

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 Motility disorders of the esophagus
Achalasia
- Achalasia is the most common esophageal motility disorder
- It is caused by degeneration of the myenteric plexus leading
to hypertonic LES that fails to relax during swallowing
- Usually, it presents in the middle ages, about 40-year-old
- Females are more affected than males.
- Achalasia is a premalignant condition; it can result in
squamous cell carcinoma of the esophagus.

Figure 36: A sketch showing achalasia.

(1) Dilated esophagus, (2) hypertonic LES

Causes:
- Failure of local nerve supply (Vagus nerve):
o Weak peristaltic waves of the body of the esophagus
o Failure of LES to relax
- Chagas Disease (Trypanosoma cruzi) is a cause
- Carcinoma, lymphoma. (Pseudoachalasia)
Clinical picture:
- Longstanding, painless, slowly progressive Dysphagia (to
liquid more than solid foods) with periods of remission and
relapse (the most common symptom)
- Some patients developed severe chest pain due to spasms
of the esophagus.
- Non-acidic regurgitation of undigested food
- Heartburn is usually absent
- Pulmonary symptoms (night cough, aspiration pneumonia)

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Diagnosis:
- CXR (wide mediastinum and features of aspiration)
- Barium swallow (best initial test) will show a fluid level with
distal tapering (Bird's beak sign, or rat-tail sign)
- Esophageal manometry (the most accurate test)
- Endoscopy to rule out adenocarcinoma (i.e.,
pseudoachalasia) (in achalasia, mucosa will be normal)

For achalasia testing: start with Barium swallow, then do

manometry to document the absent peristalsis and then
finally do Endoscopy to rule out pseudoachalasia

Treatment:
- Endoscopic pneumatic dilatation of LES (safer than surgery)
- Botulinum toxin injection to LES (high recurrence rate)
- Surgical myotomy (Heller Myotomy) (more effective than
pneumatic dilatation)

Esophageal Spasm
- It is an abnormally forceful non-peristaltic contraction of the
esophagus with normal sphincteric relaxations
- It may be spontaneous or triggered by cold or hot liquids,
stress, or carbonated beverages.
Clinical features:
- Chest pain that is related to food
- Typical chest pain that is relieved by nitrates may present
- Dysphagia to solids and liquids
Diagnosis:
- ECG should be done to rule out Myocardial infarction.
- Barium swallow (Corkscrew appearance)
- Esophageal manometry (the most accurate test)
Treatment:
- Medical treatment: Nitrates, CCB, and anti-reflux measures
- Endoscopic botulinum toxin injection
- Surgery (long esophageomyotomy) (only if refractory)

Nutcracker esophagus (Hypertensive peristalsis): Severe

esophageal spasm with very high pressure on manometry
- The most common symptom is chest pain
- Treatment: nitrates and nifedipine

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 Stomach and Small intestine
Epigastric pain
- Epigastrium is the region just below the xiphoid process
- Pain in the epigastrium is as common as 25% of the
population at some point in their lives
- Non-ulcer dyspepsia is the most common cause of epigastric
pain in patients less than 50-year-old (50-90%)

Epigastric pain features and association Most likely diagnosis

The most important cause Myocardial infarction
The most common cause Non-ulcer dyspepsia
Pain that increased with food Gastric ulcer (GU)
Pain in young with weight loss Gastric ulcer (GU)
Pain improved with food, weight gain Duodenal ulcer (DU)
Pain in elderly with weight loss Gastric cancer
Radiated to the back with tenderness Pancreatitis
Metallic taste, cough, and hoarseness GERD
Diabetes, bloating, early satiety Gastroparesis
Table 70: The differential diagnosis of epigastric pain

Non-ulcer dyspepsia (NUD)

Also called functional dyspepsia (FD)
-
Epigastric pain with no identified etiology
-
It is the most common cause of epigastric pain
-
Diagnosis is made after endoscopy (will be normal)
-
NUD cause is not known (but NSAIDs, antibiotics,
-
bisphosphonates, and potassium supplements may be
implicated)
Treatment:
- Stop all medications that may be the cause (if possible)
- If < 60 years old and no alarm symptoms: Test and treat
approach for H. pylori
- If ≥ 60 years or alarm symptoms: upper endoscopy

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 - Acid suppression:
o Liquid antacids are as effective as H2 blockers
o H2 blockers are effective in 70% of patients with
epigastric pain
o PPI (proton pump inhibitors) (Best initial): have the
best effect on epigastric pain treatment, but no
difference in efficacy between different PPIs

Figure 37: The gastric acid secretion and drugs effect on it

Gastritis (Gastropathy)
- It is an inflammation of the stomach epithelial lining
- Can be acute or chronic, autoimmune, drug-induced, or
infectious
Causes: alcohol, NSAIDs, stress, H. Pylori infection, portal HTN
Clinical features:
- Most chronic gastritis cases are asymptomatic and need no
treatment, but acute cases are usually symptomatic.
- Gastrointestinal bleeding without pain (the most common)
- Epigastric pain in severe erosive gastritis
Diagnosis:
- Test and treat strategy for H. pylori
- Upper endoscopy is the only accurate test
- CBC may show anemia
Treatment:
- H. pylori eradication if positive
- PPI (proton pump inhibitors) have the best effect on
epigastric pain treatment, but no difference in efficacy
between different PPIs

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Autoimmune gastritis:
- Anti-parietal cell antibodies or anti-intrinsic factor antibodies
- It causes mucosal atrophy and loss of the intrinsic factor
leading to B12 deficiency
- It is associated with other autoimmune diseases
- Increase the risk of malignancy

- You cannot distinguish Duodenal ulcer, gastric ulcer,

gastritis, and non-ulcer dyspepsia clinically without
endoscopy.
- NSAIDs have an anti-prostaglandin effect, leading to a loss
of protective mechanisms in the stomach mucosa:
o Decreased Mucous secretion
o Decreased bicarbonate secretion
o Decreased blood flow

Peptic ulcer disease (PUD)

- It is an ulceration of the lower esophagus, stomach, or
duodenum and can occur in the ileum adjacent to Meckel's
diverticulum.
- The most common site of gastric ulcer (GU) is at the lesser
curvature (exactly at the Incisura angularis)
- Blood Group O is a risk factor
Causes:
- H. pylori:
o The most common cause in developing countries
o More common in the duodenum than in the stomach
- NSAIDs: non-selective COX 1&2 inhibitors:
o The most common cause in developed countries
o The 2nd most common cause in developing countries
o Inhibit prostaglandins, thus decreasing mucus
- Stress-induced: any acute illness, RTA, Burn
- Zollinger Ellison syndrome (Gastrinoma)
- Crohn's disease
- Idiopathic

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 - All patients with peptic ulcer disease should be tested for
H. pylori regardless of the use of NSAIDs
- Alcohol and smoking are not causing a peptic ulcer, but
they can delay healing and increase complications
- Incisura angularis: is a part of the lesser curvature of the
stomach. It is the most common site for H. pylori
colonization, atrophy, metaplasia, ulceration, and gastric
carcinoma (routine biopsy is taken from it during
gastroscopy)

Clinical picture:
- Dyspepsia is the most common symptom
- Recurrent episodes of epigastric pain, which is related to
meal
- PUD is the most common cause of UGIB, but most ulcers do
not bleed
- Sometimes vomiting may present
Diagnosis:
- Test all patients for H. pylori infection and treat if positive
- Upper GI endoscopy is the most accurate test:
o If alarm symptoms present
o If onset ≥ 60-year-old
o If no improvement despite adequate treatment
o Biopsy from ulcerated mucosa should be done (for
assessment of H. pylori and to rule out malignancy)
Management:
- Stop smoking and alcohol
- Identify and treat the cause (to prevent recurrence)
- PPI is effective in 95% of cases
- Surgical treatment is rarely required (gastric resection or
vagotomy)

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 H. pylori infection
- It is a gram-negative bacterium that causes peptic ulcers
Diagnosis:
- Serology test (will remain positive in 50% after eradication)
- Urea breath test (Expensive, false-negative with recent
therapy)
- Stool antigen test (cheap and specific)
- Rapid urease test (simple, false-negative with recent
therapy)
- Histology by biopsy (most accurate of all tests)
- Culture (time-consuming, expensive, determines the
antibiotic susceptibility)

H. pylori test Sensitivity Specificity

Serology test > 80% > 90%
Urea breath test > 90% > 90%
Stool antigen test > 90% > 90%
Rapid urease test 80 – 95% 95 – 100%
Histology 80 – 90% > 95%
Table 71: Different types of H. pylori tests

Treatment:
- Triple therapy:
o The first line treatment
o PPI bid, amoxicillin 1g bid, and clarithromycin 500 mg
bid for 7 – 14 days
- Quadruple therapy:
o PPI + metronidazole + tetracycline + bismuth.
o Indicated in the probability of clarithromycin
resistance or penicillin allergy
- Levofloxacin-based therapy: PPI bid + amoxicillin 1g bid +
levofloxacin 500 mg qday for 10 – 14 days.
Follow-up:
- Test for the cure of H. pylori after treatment with stool or
breath tests (not serology test)
- Testing should be done 4 weeks after completion of the
therapy
- Upper endoscopy is indicated if the patient is still
symptomatic after treatment or if the cause is uncertain.

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 Complications of peptic ulcer disease include perforation,
chronicity, bleeding, anemia, malignant transformation, and
gastric outlet obstruction

Gastric ulcer Duodenal ulcer

Pain relation to food Aggravated Relieved
Prevalence Less common More common
Risk of malignancy 4% No risk
Routine biopsy Needed Not needed
Healing confirmation Needed Not needed unless
by endoscopy complicated
The most common Incisura The first part (first 2 cm)
location angularis Anterior duodenal wall
Table 72: Gastric vs. Duodenal ulcer

Notes:
- 25% of gastric cancers will ulcerate
- To avoid false-negative results for H. pylori, stop antibiotics
for 28 days and strop PPI for 2 weeks before testing (or do
histological testing by biopsy)
- Selective COX 2 inhibitors NSAIDs provides NO better
protection than non-selective NSAIDs + PPI

Gastroparesis
- Defective gastric emptying but without obstruction.
- Can be inherited or acquired disorder of the gastric
pacemaker or autonomic disorder
Causes:
- Longstanding diabetes leads to gastric dysmotility
- Systemic sclerosis
- Hypothyroidism
- Anticholinergic drugs and narcotics
Diagnosis:
- Mainly clinical diagnosis
- For acute symptoms: upper endoscopy is indicated to rule
out gastric outlet obstruction
- For chronic symptoms: Nuclear gastric emptying study

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Symptoms: abdominal fullness, vomiting, weight loss, bloating, and
early satiety.
Treatment:
- Erythromycin (for acute gastroparesis)
- Metoclopramide (for chronic gastroparesis)

Notes:
- During testing for gastric emptying, RBS should be < 275
(high glucose can acutely impair gastric emptying)
- Dystonia and tardive dyskinesia are extrapyramidal side
effects of metoclopramide; stop it if any of them appear
to avoid the irreversibility of these side effects.

Upper GI bleeding (UGIB)

- Basic anatomy: ligament of Treitz: the suspensory ligament of
the duodenum
- Upper GI bleeding: is a bleeding proximal to the ligament of
Treitz (75% of GI bleedings)
Causes:
- Duodenal ulcer (the most common cause)
- Gastric Ulcer, gastritis, gastric cancer
- Esophagogastric varices, Esophagitis, Esophageal cancer
- Mallory-Weiss tear
- Aortoenteric fistula
- Coagulopathy (drugs, renal disease, liver disease, DIC)
- Epistaxis

Figure 38: The suspensory Ligament of Treitz

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Clinical features:
- Occult blood in the stool (less severity)
- Melena (Black stool)
- Coffee ground vomiting
- Hematemesis
- Hematochezia (the most severe)
- Hemodynamic instability (according to severity)
o Orthostasis (less severity)
o Tachycardia
o Hypotension (the most severity)

Orthostasis:
When going from lying down to a standing position,
- More than a 10 bpm increase in heart rate is called
orthostatic tachycardia
- More than 20 mmHg drop in systolic BP or > 10 mmHg drop
in diastolic BP is called orthostatic hypotension

Management:
- Stabilize patient (ABC): intravenous lines, fluid resuscitation,
blood, and platelet transfusion, and keep the patient NPO
- NG tube insertion (this will determine UGIB vs. LGIB)
- Intravenous proton pump inhibitors
- Serial HB, KFT, electrolytes, vitals monitoring.
- Upper endoscopy (the best diagnostic and therapeutic)
- Surgery may have a rule if endoscopy fails to stop the
bleeding
- Treatment of the cause:
o Coagulation problems: Vitamin K, FFP, cryoprecipitate
o Thrombocytopenia: platelet transfusion
o Esophageal varices: Octreotide decreases Portal BP

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Rockall Score:
Points 0 1 2 3
Age < 60 60 – 79 ≥80 --
Shock HR < 100 HR > 100 SBP < 100 --
SBP > 100 SBP > 100 -- --
Comorbidities -- -- HF, IHD CKD, CLD,
malignancy
Score 0 and no further evidence of bleeding: discharge home
Score > 0: Refer for urgent upper endoscopy
Table 73: Rockall Score for risk of death in upper GI bleeding

Notes:
- Platelet transfusion indicated if the platelet count is < 50,000
with active bleeding
- Metoclopramide and erythromycin have an action of
increasing gastric emptying; they are useful before
endoscopy to remove clots

Diseases of Malabsorption
Celiac disease (gluten-sensitive enteropathy)
- It is an autoimmune disease due to exposure to gliadin
(gliadin is a product of gluten breakdown) associated with
HLA-DQ2 (chromosome 6) found in 80-90%, HLA-DQ8
- It usually starts at age 6 months when adding food other
than milk (It never manifests at birth)
Pathogenesis:
- Gluten is a protein present in (Rye, Barley, Oats, and Wheat)
- Gluten exposure can cause characteristic changes in the
lining of the small intestine, resulting in malabsorption (Rapid
response and reversible if a gluten-free diet has been taken)
- The proximal part of the small bowel is more affected than
the distal part

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 Celiac disease may be associated with other autoimmune
conditions like T1DM, thyroid diseases, primary biliary
cirrhosis, IgA deficiency, pernicious anemia, IBD, and
myasthenia gravis.

Clinical picture: (These symptoms are reversible when a gluten-free

diet is administrated)
- Bloating and abdominal pain
- Chronic diarrhea (greasy, smelly stool)
- Weight loss, failure to thrive (malabsorption)
- Anemia (folate, B12, and iron malabsorption)
- Symptoms of vitamin deficiency
- Skin manifestation (Dermatitis herpetiformis) (10%)
Diagnosis:
- Anti-gliadin, anti-endomysial, and anti-tissue
transglutaminase antibodies (best initial tests)
- Perform Anti-tTG IgG for patients with IgA deficiency
- Small bowel biopsy (most accurate) (diagnosis of celiac
disease and exclude bowel lymphoma)
- Improvement of symptoms on a gluten-free diet
- Stool fat > 7%
- Measure bone density for all patients diagnosed with Celiac
disease

Notes:
Celiac disease is usually misdiagnosed as IBS, so if a patient
presents with a history of IBS and anemia, do Anti-tTG, biopsy if
positive, and then order a gluten-free diet. However, all patients
should be treated with a gluten-free diet regardless of symptoms,
including those with isolated dermatitis herpetiformis

Treatment:
- Gluten-free diet
- Monitor response by measuring Anti-tTG IgA antibody or by
repeating bowel biopsy
- Vitamin D and calcium for patients with Osteomalacia
Complications: malnutrition, anemia, vitamin deficiency, bleeding
tendency, and small bowel lymphoma or adenocarcinoma.

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 Sites for absorption of nutrients
The site for absorption of different nutrients:
- Stomach: Alcohol.
- Duodenum: Ca, Mg, iron, Vitamins A and D, glucose.
- Jejunum: Fat, sucrose, lactose, fat-soluble vitamins A and
D, water-soluble vitamins, proteins, amino acids, glucose.
- Ileum: Proteins and amino acids, vitamin B12.
- Colon: Water, potassium, sodium chloride, fatty acids from
fiber digestion.
Table 74: The sites for absorption of different nutrients

Diseases of vitamin deficiencies

Beriberi:
- It is caused by thiamin (vitamin B1) deficiency
- Wet beriberi: SOB, lower limb edema, heart failure
- Dry beriberi: (Wernicke’s encephalopathy): Paralysis,
confusion, and nystagmus
Pellagra:
- It is caused by vitamin B3 (Niacin) deficiency
- Features: Dementia, diarrhea, dermatitis, depression, and
death (5Ds)
Scurvy:
- It is caused by vitamin C (ascorbic acid) deficiency
- Features: Gum bleeding, sore legs and arms
Osteomalacia:
- It is caused by vitamin d deficiency
- In pediatrics, it is called Rickets
- This will lead to bone deformities, bone pains, and
pathological fractures
Vitamin K deficiency:
- Vitamin K is also known as phytonadione
- Vitamin K-dependent clotting factors are (X, IX, VII, II, protein
c, and protein S)
- Its deficiency will lead to bleeding tendency and elevated
INR
Vitamin A deficiency:
- Vitamin A is also known as retinoic acid
- Its deficiency will lead to night blindness, dry hyperkeratotic
skin, conjunctival dryness, and corneal ulceration.

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 Diarrhea
- Diarrhea is an increase in stool frequency or loose stool
Diarrhea classification:
- Can be Acute < 14 days vs. Chronic > 14 days
- Inflammatory vs. Non-inflammatory
- Secretory (persist with fasting) vs. Osmotic (stop with fasting)
- Bloody diarrhea vs. Watery diarrhea

Stool electrolytes:
Stool osmolality = 2(Na + K)
If stool osmolality is less than 250 mOsm, the cause is:
- Factitious diarrhea (Laxative use, Adding water to stool)
Stool osmotic gap = 290 – 2(Na + K):
- If > 100 mOsm, osmotic diarrhea is the cause
- If < 50 mOsm, secretory diarrhea is the cause

Osmotic diarrhea:
- Stool osmotic gap > 100 mOsm
- Stops with fasting and never awake patient during sleep
- Usually not leading to dehydration
Secretory diarrhea:
- Stool osmotic gap < 50 mOsm
- Occurs at fasting or during sleep
- Usually high volume > 1 L/day
Causes of infectious diarrhea:
- The most common cause of diarrhea is infection
- Viral (rotavirus is the most common cause)
- Toxin-mediated (Staph. aureus, Clostridium)
- Bacteria (Shigella, Campylobacter, c. difficile, salmonella)
- Protozoa (Giardia, Cryptosporidium, amoebic dysentery)
- Systemic (diverticulitis, sepsis, PID, meningitis, atypical
pneumonia, malaria)
Causes of non-infectious diarrhea:
- GI: (IBD, malignancy, Zollinger-Ellison syndrome)
- Metabolic: (DKA, DM, thyrotoxicosis, uremia, VIPoma)
- Drugs and toxins: (NSAIDs, PPIs, cytotoxic agents, Antibiotics,
laxatives)
- Carcinoid syndrome

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Causes of bloody diarrhea:
- Infectious:
o Bacterial: Enterohemorrhagic E. Coli, Salmonella,
Shigella, Campylobacter, Yersinia, C. difficile (less
often bloody),
o Viruses: CMV
o Parasites: Entamoeba histolytica, Schistosomiasis
- Inflammatory Bowel Disease
- Medications: NSAIDs, chemotherapy
- GI bleeding (AVMs, diverticulosis, brisk UGI bleeds, etc.)
- Others: Ischemic Colitis, Diverticulitis, Cancer, Radiation

Causes of bloody diarrhea Causes of non-bloody diarrhea

Campylobacter jejuni Shigella (diarrhea type)
Enteroinvasive E. coli Enteropathogenic E. coli
Entameba histolytica Salmonella Enterotoxigenic E. coli
Shigella (dysentery type) Vibrio cholera
Yersinia enterolitica Most viral diarrhea
Enterohemorrhagic E. coli Toxin-mediated (Staph aureus,
(Shigella toxin-producing) clostridium botulinum)
Table 75: Causes of bloody vs. non-bloody diarrhea

Clinical picture:
- Fever and Bloody diarrhea indicate colitis
- History < 18 hours indicates toxin-mediated
- History > 5 days indicate protozoal infection
- Symptoms of the systemic causes
- Dehydration may be present (need further assessment)
Diagnosis:
- Stool culture and microscopy (do not order stool culture for
diarrhea less than 1-week duration)
- C. difficile toxin, CBC, KFT, electrolytes
- Colonoscopy (used for most patients with chronic diarrhea)
- 24 hours stool collection for fat (if colonoscopy is not
diagnostic)

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Treatment:
- Fluid and electrolytes replacement (oral is the best, IV if
severe)
- Antibiotics (rarely indicated)
Indications for antibiotics use:
- If a bacterial cause is identified or strongly suspected
(Shigella, Vibrio cholera, C. difficile, Traveller's diarrhea)
- Associated bacterial infection (Otitis, pneumonia)
- Prolonged fever with fecal blood or leukocytes

Melanosis coli: is a benign pigmentation of the colon mucosa; it

results from chronic laxative use

Campylobacteriosis
- Campylobacter is the most common bacterial cause of
infectious intestinal disease
- Diagnosis is made by a positive stool culture but requires
special media and handling
Clinical features:
- Prodrome: headache, myalgia, and fevers (as high as 40°C)
- Abdominal pain
- Watery offensive diarrhea 2 – 4 days, then become bloody
Treatment:
- Usually, supportive treatment is adequate
- Erythromycin or azithromycin can be used when there is a
risk of complications

Traveler’s diarrhea
- Traveler’s diarrhea occurs within 2 weeks of a visit to a
tropical area
- Usually, mild self-limiting diarrhea for less than 72 hours
Causes:
- E. coli is the most common cause
- Other causes: Shigella, Salmonella, Campylobacter, Giardia
lamblia
Treatment: Fluoroquinolones significantly reduce the duration and
severity of traveler’s diarrhea when given for 1 – 3 days.

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 Giardiasis
- It is an infection with the parasite Giardia lamblia
- Giardia lamblia is a flagellate protozoan
- Transmitted through contaminated water, food, surfaces, or
objects. (oral-fecal transmission)
Pathogenesis: Giardia parasite causes non-inflammatory diarrhea
(it does not invade the intestinal mucosa but only covers it
preventing absorption)
Clinical features:
- Giardiasis presents as traveler’s diarrhea with symptoms
lasting more than 10 days
- It can cause both acute or chronic diarrhea (Chronic
diarrhea is most likely to be associated with weight loss)
- Symptoms: bloating, flatulence, abdominal pain, loose stool,
explosive watery diarrhea, weight loss
- Symptoms begin after returning from a travel
Treatment:
- Metronidazole (the most commonly used drug)
- Tinidazole

Pseudomembranous colitis
- Clostridium difficile are gram-positive bacilli
- Clostridium difficile antibiotic-associated colitis is produced
by two toxins, A and B
Pathogenesis:
- Pseudomembranous colitis is diarrhea that occurs as a result
of antibiotic use
- The eradication of the normal flora in the intestine leads to
excessive growth of clostridium difficile that will release toxins
leading to bloody or watery diarrhea
- Possible complications are (toxic megacolon and sepsis)

The most common antibiotics implicated in Clostridium difficile

infections are Clindamycin, Cephalosporins (second and third
generations), Quinolones, Amoxicillin, and Ampicillin)

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Diagnosis:
- Clinical presentation of diarrhea following antibiotics use
- Cytotoxin assay of the stool is the best test to order; it is
sensitive and highly specific
- Colonoscopy would show the classic Pseudomembranes
Treatment:
- If this is the first episode of Clostridium difficile infection
o Oral vancomycin for 10 days (the first-line treatment)
o Oral fidaxomicin (the second line)
o Oral vancomycin and IV metronidazole (the third line)
- If the patient has recurrent episodes:
o Oral vancomycin and IV metronidazole
o Consider surgery
o Consider fecal microbiota transplant (if ≥ 2 episodes)
- If fulminant or complicated disease is not responsive to the
previous treatment, perform a colectomy.

Severe C. difficile infection is defined by any one of the following:

- WBC count > 15,000/ul
- Serum creatinine > 1.5 times the baseline
- Age of more than 60-year-old

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 Disorders of the large intestine
Inflammatory Bowel Diseases (IBD)
- The two main types of inflammatory bowel disease are
Crohn's disease (CD) and Ulcerative colitis (UC).
- They are HLA B27-associated diseases
- They are best diagnosed with endoscopy and biopsy.

Features Crohn’s disease Ulcerative colitis

Male: female Equal for both Male more affected
Most common site Terminal ileum The Rectum.
non-caseating Present Not present
granuloma
Smoking relation Increased by Decreased by
smoking smoking
Serum marker ASCA pANCA

Microscopic involvement of CD and UC:

Features Crohn’s disease Ulcerative colitis
Site Any site from It starts at the rectum and
mouth to anus never spreads beyond the
ileocecal valve
Thickness Transmural Mucosa and submucosa
Character Skip lesions Continuous disease
Goblet cells Increased Depleted
Gross feature Cobble-stone Pseudopolyps
appearance
Table 76: differences between IBD types

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Clinical features of CD and UC:
Features Crohn’s disease Ulcerative colitis
Diarrhea Usually, non-bloody Bloody
Weight loss More Less
Malabsorption Present Absent
Mouth and anus May be involved Not involved
Presentation RIF mass LIF pain
Crypt abscess Less common More common
Relapsing-remitting Present Present
Abdominal pain Present Present
Table 77: Clinical features of CD vs. UC

Extraintestinal manifestations in CD and UC:

System involved Manifestation
Eye Uveitis, Scleritis, Episcleritis
Cutaneous Erythema nodosum
Pyoderma gangrenosum
Hepatobiliary Primary sclerosing cholangitis
Liver cirrhosis
Gallstones (Bile acid malabsorption in CD)
Pancreas Pancreatitis
Genitourinary Nephrolithiasis
Pulmonary Chronic bronchitis
Bronchiectasis
Musculoskeletal Seronegative arthritis
Hematology Anemia
Increased thromboembolic events
Table 78: Extraintestinal manifestations in CD and UC

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Complications of CD and UC:
Features Crohn’s disease Ulcerative colitis
Complications Stricture Toxic megacolon
Obstruction Cholangitis
Fistula
Malabsorption
Colorectal cancer Less risk More risk
Table 79: Complications of CD vs. UC

Toxic megacolon: a severe life-threatening complication of IBD

seen more commonly in UC, characterized by dilatation of colon
with a risk of rupture

The drugs used in the treatment of CD and UC:

- 5-Aminosalicylic acid (5 ASA):
o E.g., mesalazine, olsalazine
o Mild to moderate relapses in UC
o Long-term treatment to maintain remission
o Side effects include: rash, infertility, agranulocytosis,
headache, diarrhea, and renal failure
- Steroids:
o The main treatment for active disease
o Given as a short tapering dose to induce remission
- Immunosuppressants:
o E.g., azathioprine, mercaptopurine
o Used in steroid-refractory cases, or those requiring
frequent steroid courses
o Side effects: Bone marrow suppression and
hepatotoxicity
- Methotrexate: Used in patients with CD but not effective in
UC
- Metronidazole and ciprofloxacin: Used for isolated perianal
Crohn’s disease
- Anti-tumor necrosis factor-alpha (Anti-TNF)
o Infliximab, adalimumab
o Used in active Crohn’s disease refractory to
conventional therapy
o Screen for TB and HBV for all patients before starting
Anti-TNF

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 - Nutritional support for malnourished patients
- Surgery:
o Curative for UC
o Symptomatic relief for CD
o Used for treatment of complications.

Treatment of Ulcerative colitis:

Mild UC (< 4 bowel - 5 ASA (maintenance)
movements/ day)
Moderate UC - Steroid for remission
- 5 ASA agent (maintenance)
Severe UC (> 6 bowel - I.V glucocorticoids; then
movements/ day) - Anti-TNF antibody
- Surgery for refractory cases
(curative)
Table 80: Treatment of UC

Treatment of Crohn’s disease:

Mild to moderate CD - Budesonide or mesalamine
No fever, no (remission)
- 6-MP, azathioprine, or
tenderness, < 10%
methotrexate (for maintenance)
weight loss
Moderate to severe - Prednisolone for remission
CD - 6-MP, azathioprine, or
methotrexate (for maintenance)
Fever, abdominal
- Anti-TNF for refractory cases
pain, > 10% weight
loss
Severe fulminant CD - I.V glucocorticoids (for remission)
Fever, severe - Anti-TNF antibodies
- Surgery for refractory disease (not
tenderness, and
curative)
weight loss despite
steroids.
Fistula - Azathioprine, 6-MP, Anti-TNF
Table 81: treatment of CD

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 Microscopic Colitis
- Chronic diarrhea, no abdominal pain, no weight loss
- More common in women 45 – 60 years old
- No increased risk of colon cancer
Causes: NSAIDs, PPI, and SSRIs have been implicated as causative
agents
Colonoscopy: Gross examination of the mucosa is normal, but
microscopic examination shows colitis (collagenous or
lymphocytic)
Treatment:
- Loperamide, Bismuth
- Stop NSAID, PPI, or SSRI (if possible)
- Budesonide (the best efficacy – used for severe cases)

Irritable bowel syndrome (IBS)

- It is a functional disorder of the large bowel, not explained
by investigations.
- IBS is the most common cause of GI referral
- More in young adults, more in females than males
- 10-15% of the population
- Cause is unknown
Pathogenesis: abnormal uncoordinated contractions of bowels
Types according to Symptoms:
- Pain-predominant
- Diarrhea-predominant (IBS-D)
- Constipation-predominant (IBS-C)
- Mixed types (IBS-M)
Diagnosis: Rome IV criteria for IBS diagnosis:
Abdominal pain for at least 1 day per week, for at least 3 months in
the past 6 months with 2 out of the following:
- Relieved with defecation
- Associated with a change in consistency
- Associated with a change in frequency

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Investigations:
- Usually not needed (Apply criteria)
- CBC, TSH, tissue transglutaminase, CRP, stool analysis and
Culture, and sigmoidoscopy are only indicated if there is an
alarming sign to rule out celiac disease, anemia, infection,
IBD, and thyroid disease.
Treatment:
- Diet modification
- Antispasmodics for pain in all types of IBS
- For IBS-D
o TCA for pain
o Loperamide, cholestyramine for diarrhea
o Eluxadoline (for both pain and diarrhea)
o Rifaximin (an antibiotic used for global symptoms)
- For IBS-C:
o SSRIs for pain
o Lubiprostone (for women)
o Linaclotide

Red Flag for IBS (Alarming symptoms):

- Age of onset ≥ 50 years
- A family history of IBD
- Weight loss, Anemia, Fever
- Blood or pus in the stool
- Nocturnal defecation
- Abnormal gross findings on flexible sigmoidoscopy
If red flags present, consider a diagnosis other than IBS
Table 82: Alarm symptoms for IBS

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 Hepatology
CHAPTER 6

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Introduction to hepatology
The normal Liver functions
General facts:
- The liver is the second largest organ of the human body
after the skin
- Located at the right upper quadrant (RUQ) of the abdomen
- It has two lobes (right and left lobe)
The function of the liver:
- Metabolism of nutrients (carbohydrates, proteins, lipids)
- Metabolism of drugs and hormones (e.g., estrogen)
- Storage of (Iron, copper, vitamin A, vitamin B12, and D3)
- Protein synthesis (albumin, complement, clotting factors,
ceruloplasmin, transferring and protease inhibitor- Alpha-1-
antitrypsin)
- Bile formation and excretion
- Removal of ammonia from the portal blood

Figure 39: The liver and biliary tree

(1) Right hepatic duct (2) Left hepatic duct (3) Common hepatic duct (4) Cystic
duct (5) Pancreas (6) Common bile duct (7) Pancreatic duct (8) Sphincter of Oddi
(9) Duodenum (10) Gall bladder

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 Liver function test (LFT)
PT, INR:
- It reflects the ability of the liver to synthesize proteins
- Caused by decreased vitamin K-dependent clotting factors.
- Prolonged INR and Low serum albumin imply severe
hepatocellular dysfunction.
Serum albumin level:
- Could be deficient in liver disease, Nephrotic syndrome, GI
loss
- This is a marker of liver capacity to synthesize proteins.
- If decreased, ascites and edema can present
Serum bilirubin:
- Bilirubin has two types (direct and indirect)
- Can be increased in pre-hepatic, intrahepatic, or post-
hepatic conditions
- Indirect hyperbilirubinemia indicates a pre-hepatic cause
(e.g., hemolysis) or impaired uptake (e.g., Gilbert syndrome)
- Direct hyperbilirubinemia can result from obstructive (post-
hepatic) or hepatocyte dysfunction (intrahepatic).
AST and ALT
- They are liver enzymes that, if elevated, indicate damage in
hepatocytes.
- ALT More specific than AST
- ALT > 5000 u/l indicates acetaminophen hepatotoxicity or
hepatic ischemia
- If AST > ALT and AST/ALT ratio > 2, alcoholic liver disease
- The most common cause of minimal elevation of ALT and
AST is a non-alcoholic fatty liver disease
Alkaline phosphatase (ALP)
- It is an indicator of obstructive liver disease if very high with
less prominent elevated AST and ALT (Confirm obstructive
liver disease by elevated GGT)
- If isolated high ALP, consider a bone disease
- ALP can be produced by the placenta and is elevated in
the case of pregnancy.

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 Jaundice
- Jaundice is a yellowish discoloration of the skin and mucous
membranes
- It manifests clinically when plasma bilirubin > 2.5 mg/dl
- The indirect (unconjugated) bilirubin is fat-soluble, while the
direct (conjugated) type is water-soluble

Figure 40: Bilirubin metabolism and excretion

Terms:
- Conjugated hyperbilirubinemia: total bilirubin above
normal with conjugated (direct) fraction > 20% of total
bilirubin
- Unconjugated hyperbilirubinemia: total bilirubin above
normal with conjugated (direct) fraction <15% of total
bilirubin
Table 83: Bilirubin metabolism

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Types of jaundice:
- Pre-hepatic jaundice:
o Isolated raised bilirubin with normal other LFTs
o Due to the destruction of RBC (hemolysis)
o Elevated unconjugated bilirubin
- Intra-hepatic jaundice:
o The inability of the liver to uptake, conjugate, or
secretion bilirubin by hepatocytes
o Both direct and indirect bilirubin are increased
- Post-hepatic jaundice:
o Impaired secretion due to mechanical obstruction
o Alkaline phosphatase is significantly elevated
o Increased conjugated bilirubin levels
Gilbert syndrome:
- An autosomal dominant familial condition
- The mutation results in a decreased UDP-glucuronosyl-
transferase enzyme
- The patient will exhibit mild jaundice (< 3 mg/dl
unconjugated hyperbilirubinemia)
- The jaundice is more prominent in dehydration and stress
- Normal AST and ALT and absence of hemolysis along with
indirect hyperbilirubinemia are enough for diagnosis (without
extensive testing)
- Patient otherwise asymptomatic
- No need for treatment

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 Acute liver diseases
Viral Hepatitis
- It is the viral infection and inflammation of the parenchyma
of the liver
- If hepatitis persists for more than 6 months, it is called chronic
hepatitis (acute hepatitis is less than 6 months)
- Virus A, B, C, D, and E are causes of viral hepatitis
- Other causes are called non-A-E hepatitis (hepatitis X), rare
- HDV is preventable by HBV vaccine (HDV requiring HBsAg
for entry into hepatocyte)
- Hepatitis A & B have vaccinations, but C and E do not
- HBV and HCV are associated with an increased risk of
Hepatocellular carcinoma and glomerulonephritis.

Clinical features of hepatitis:

- Most cases are asymptomatic
- Prodrome for 1-2 weeks followed by jaundice
- Jaundice
- Enlargement of (liver, spleen, and lymph nodes)
- Right upper quadrant pain and fever
- Rash and arthritis (more in HBV and HCV)
Lab results expected in hepatitis:
- Elevated AST and ALT (do not correlate with the disease
progression)
- Elevated Alkaline phosphatase (hepatitis leads to a degree
of cholestasis)
- Abnormal protein synthesis by the liver (prolonged PT, high
INR, and low serum albumin)
- Metabolic disturbances (hypoglycemia, lactic acidosis, and
hyperammonemia)

Virus Incubation period Transmission Chronicity Virus type

HAV 15 – 19 days Oral fecal Never RNA
HBV 60 – 180 days Parenteral Yes DNA
HCV 14 – 160 days Parenteral Yes RNA
HDV 21 – 42 days Parenteral Yes RNA
HEV 21 – 63 days Oral fecal Never RNA
Table 84: General information about hepatitis viruses

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 The most common infection transmitted by infected needle sticks
is hepatitis B (30%), followed by hepatitis C (3%), and HIV (0.3%)

Hepatitis A virus
- HAV is the most common hepatotropic virus
- It can only cause acute hepatitis (no chronicity)
- Usually infectious before the appearance of jaundice
- Infection with HAV provides lifelong immunity
Clinical features:
- HAV is associated with abrupt onset of fatigue, nausea,
vomiting, fever, jaundice, and abdominal pain.
- In small children, especially less than 5 years old, it may
present without jaundice (Anicteric HAV infection)
- Symptoms are more severe in adults than children.
Diagnosis:
- Clinical suspicion is important for diagnosis
- Elevated ALT and AST (usually > 1000 u/l)
- IgM Anti-HAV (the most accurate)
Prevention of HAV:
- HAV Inactivated (Killed vaccine) provides 10 – 20 years of
immunity
- HAV immunoglobulins (intramuscular injection) provide
protection for 3 months

Indications of HAV vaccine:

- It was added to the Jordanian routine vaccination
program for pediatrics on 2020
- Travelers to endemic areas
- IV drug users
- Homosexual men
- Patients with chronic liver disease and clotting factors
deficiency.

Treatment: (only supportive)

- Intravenous hydration
- Fat-soluble vitamin supplementation (for prolonged
cholestasis)
- If an acute liver failure occurs, refer for liver transplantation

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 Hepatitis B virus
- HBV is strongly associated with polyarteritis nodosa and
associated with an increased risk of hepatocellular cancer
as well as hepatoma
- HBV, HDV transmitted by blood transfusion, saliva, sex,
vertical transmission (from mother to fetus)
- HDV is preventable by HBV vaccine (HDV requiring HBsAg for
entry into hepatocyte)

HBV marker The meaning

HBsAg Infection
HBeAg Active infection
Anti-HBs Immunity
Anti-HBc IgM Acute
Anti HBc IgG Chronic

Acute active Chronic active Chronic inactive

HBV infection HBV infection HBV infection
+ HBsAg + HBsAg + HBsAg
+ HBeAg + HBeAg - HBeAg
+ Anti-HBc IgM + Anti-HBc IgG + Anti-HBc IgG
Vaccinated Recovered Recovering
+ Anti-HBs + Anti-HBs + Anti-HBs
- Anti-HBc + Anti-HBc + Anti-HBc
- Anti-Hbe + Anti-Hbe
Table 85: HBV markers interpretation
Prevention:
- HBV vaccine is a part of a routine immunization program in
Jordan
- HBV vaccine should be provided at 3 doses (0, 1, 6 months)
for all healthcare providers
- Needlestick patients and infants born to hepatitis B-positive
mothers should receive the first dose of HBV vaccine and
HBV immunoglobulin at 2 different sites within 12 hours after
exposure.

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Treatment:
- Supportive measures
- No need to treat inactive HBV infection
- Interferon-α2b (IFN-α2b):
o It has immunomodulatory and antiviral effects
o The treatment duration is 24 weeks
o Side effects are: flu-like symptoms, marrow
suppression, depression, retinal changes, autoimmune
disorders
- Other antiviral agents (Lamivudine, Tenofovir)
Complications:
- Acute liver failure (coagulopathy and encephalopathy)
- Hepatocellular carcinoma
- Membranous glomerulonephritis (due to HbeAg deposition
in the glomerulus)

Hepatitis C virus
- HCV is the most common hepatitis that transmitted by a
blood transfusion
- Acute HCV is asymptomatic, and patients usually present
with signs and symptoms of chronic liver disease
- HCV transmission is like HBV but less likely to be transmitted
by sex
Testing:
- ALT and AST are normal in 40% of HCV infection cases
- Order Anti-HCV to diagnose its presence
- Order HCV RNA (if positive, indicates active disease)
- HCV genotyping should be performed at the time of
diagnosis to help to choose the treatment regimen
Treatment:
- Peginterferon and ribavirin are approved by the FDA for use
in children older than 3 years of age with HCV hepatitis
- Sofosbuvir and simeprevir are newer treatments

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 Fulminant Hepatic Failure (FHF)
- Fulminant hepatic failure: Severe hepatic failure with
development of hepatic encephalopathy and
coagulopathy within 8 weeks after onset of acute liver
disease in the absence of evidence of pre-existing liver
disease, its major cause of death is cerebral edema
- Sub-fulminant hepatic failure: 8 weeks to 6 months
- Chronic hepatic failure: more than 6 months
Causes:
- Acute viral hepatitis (most common cause 70%). The most
common virus is HBV (50%).
- Drugs (e.g., paracetamol, amoxicillin-clavulanate,
Valproate, phenytoin)
- Malignancy (most commonly lymphoma)
- Shock, ischemia
- Herpes infection
- Mushroom poisoning
- Wilsons disease
- Acute fatty liver of pregnancy
Clinical picture:
- Jaundice
- Hepatic encephalopathy
- No hepatomegaly
Investigations:
- Deterioration in LFT
- Toxicology screen
- Hepatitis profile
- Wilsons disease workup
- Autoimmune hepatitis workup (ANA, ASMA, Anti-LKM)
Treatment:
- Supportive therapy
- Treatment of hepatic encephalopathy (lactulose)
- Treatment of the cause
o Chelation with penicillamine or trientine for Wilson's
disease
o N-acetylcysteine for paracetamol poisoning
o Penicillin G or silymarin for Mushroom poisoning
- Liver transplant for candidate patients

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Poor prognostic factors of non-paracetamol related FHF:
- Drug or Non-A-E-hepatitis
- Extreme age (< 10 or > 40 years)
- The interval from onset of jaundice to encephalopathy > 7
days
- Serum bilirubin > 18 mg/dl
- PT > 50 seconds
Table 86: Poor prognostic factors of FHF

Paracetamol poisoning
- Also called acetaminophen poisoning
- Acute overdose > 140 mg/kg or 7 grams in adults
- In alcoholic patients, a lower dose of paracetamol can
cause liver failure
- Paracetamol is metabolized by glucuronidation and
sulfation, with a small amount by the cytochrome P450
enzyme system
Clinical picture:
- Early 24 – 48 hours: Nausea, vomiting, pallor
- After 48 hours: Hepatotoxicity, RUQ tenderness,
hepatomegaly, deteriorating KFT and LFT, and Hepatic
failure
Diagnosis: Serum paracetamol level
Treatment:
- Gastric lavage (as soon as possible)
- Activated charcoal (within 4 hours)
- N-acetylcysteine administration if:
o Paracetamol concentration of ≥ 100 mg/dL at 4 hours
o Paracetamol concentration of ≥ 15 mg/dL at 15 hours
o When the ingestion time is not known, regardless of
the paracetamol concentration
- Liver transplantation:
o If arterial PH < 7.3, 24 hours after ingestion, or
o Serum creatinine > 300 umol/l, PT > 100 sec, and
Grade III-IV encephalopathy

Poor prognostic factors of paracetamol-induced liver failure:

- PH < 7.3 (regardless of the grade of encephalopathy)
- PT > 100 second, creatinin > 300umol/l, and grade III to IV
encephalopathy.
Table 87: Poor prognostic factors of paracetamol-induced liver failure

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 Chronic liver diseases
Liver Cirrhosis
- Liver cirrhosis is a fibrosis and nodule formation of liver tissue
Causes:
- Chronic hepatitis (B, C, B+D) but not hepatitis A and E
- Alcoholic and Non-alcoholic fatty liver disease
- Autoimmune hepatitis
- Alpha-1-antitrypsin deficiency (10% cause liver disease)
- Drug-induced liver cirrhosis.
- Right side Heart failure (chronic liver congestion will result in
cardiac cirrhosis)
Symptoms:
- The patient may remain asymptomatic for 20 years/stage 1
liver cirrhosis, but if stage 2 starts, symptoms will manifest.
- Loss of appetite, low energy, weakness, and weight loss
Signs:
- Ascites (the most common symptom)
- Coagulopathy
- Asterixis and encephalopathy
- Clubbing
- Feminization (scanty pubic hair, testicular atrophy,
gynecomastia)
- Hypoalbuminemia and edema
- Skin (Palmer erythema, jaundice, Itching, spider nevi)
- Portal HTN and varices
- Fetor hepaticus (breath with bad smell seen in portal HTN
with a portosystemic shunt)
- Thrombocytopenia, anemia, or pancytopenia
- Hepatorenal syndrome
- Hepatopulmonary syndrome
Diagnosis:
- CBC: the first sign is low platelets
- PT, INR (the second sign is elevated INR)
- Serum albumin: low albumin
- Serum bilirubin: high bilirubin
- Hypoglycemia (indicate terminal condition)
- Liver biopsy is the most accurate test

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Treatment:
- Treatment of the cause
- Avoid hepatotoxic agents (alcohol, drugs)
- Treatment and prevention of complications:
o Upper endoscopy for all new patients (to evaluate for
varices)
o Ultrasound to diagnose ascites
o Paracentesis for all new patients to:
▪ Determine SAAG and diagnose the cause
▪ Cytology and culture to rule out SBP
o Vaccination for HAV, HBV, and other routine
vaccinations.
- The definite treatment is a liver transplant

Child-Pugh score for liver cirrhosis:

1 point 2 points 3 points
Ascites None Slight Moderate
Encephalopathy None Grade 1 or 2 Grade 3 or 4
Bilirubin mg/dl <2 2–3 >3
Albumin g/dl > 3.5 2.8 – 3.5 < 2.8
PT (sec) <4 4–6 >6
INR < 1.7 1.7 – 2.3 > 2.3
- Class A (5 – 6 points): 1-year survival is 100%
- Class B (7 – 9 points): 1-year survival 80%
- Class C (10 – 15 points) 1-year survival 45%
Table 88: Child-Pugh score for liver cirrhosis

Complications of cirrhosis:
- Causes of death in cirrhosis: Renal failure (hepatorenal
syndrome), Sepsis. GI bleeding, and Hepatocellular
Carcinoma.
- Other complications:
o Low PLT, WBC, Hb (pancytopenia)
o Bleeding tendency
o Infections
o Peptic ulcers

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 Alcoholic liver diseases
- Requires regular drinking rather than binge drinking
- No clear relationship between the dose and liver damage
- Women are at higher risk than men
Clinical features:
- Alcoholic fatty liver: (hepatomegaly, good prognosis,
disappear 3 months of abstinence)
- Alcoholic hepatitis (jaundice, malnutrition, hepatomegaly,
portal HTN)
- Alcoholic cirrhosis (in chronic alcohol intake, same features
as mentioned in liver cirrhosis)
Lab test:
- High AST and ALT (usually < 300 and almost always < 500)
- AST: ALT ration ≥ 2
- High GGT
- High Ferritin level (acute phase reactant)

AST is higher than ALT in alcoholic hepatitis due to hepatic

deficiency of pyridoxal 5’-phosphate, an ALT enzyme co-factor.

Management:
- Stop alcohol
- Good nutrition
- Steroids for acute alcoholic hepatitis (contraindicated in
sepsis, varices, pancreatitis, and kidney disease)
- Liver transplant (End-stage liver disease)

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 Non-alcoholic fatty liver diseases (NAFLD)
- Prevalence increased with obesity, Dyslipidemia, insulin
resistance, and T2DM
- Hepatomegaly is often present
Classifications:
- Simple fatty infiltration (steatosis): No morbidity
- Fat and inflammation: non-alcoholic steatohepatitis (NASH).
It may progress to fibrosis, cirrhosis, or cancer
- Liver cirrhosis
Clinical picture:
- Most commonly asymptomatic abnormal LFT (especially
high ALT, AST, GGT)
- A clinical picture of cirrhosis
Investigations:
- ALT higher than AST (best initial test)
- Abdominal U/S (high echogenicity of the liver indicates
NASH)
- Liver biopsy (gold standard)
Treatment:
- Modify risk factors
- Treat complications
- Avoid hepatotoxic drugs

Primary biliary cholangitis (PBC)

- Autoimmune condition: the interlobular bile ducts become
damaged by a chronic inflammatory process leading to
progressive cholestasis and liver cirrhosis
- It is more common in women 40 – 60-year-old
Clinical features:
- 50% are asymptomatic
- Pruritus, fatigue, weight loss, jaundice
- The complications of portal hypertension
- Features of fat-soluble vitamin deficiency.
- Usually associated with other autoimmune diseases (E.g.,
Sjögren’s syndrome, autoimmune hepatitis)
Diagnosis:
- LFT (high direct bilirubin, Alkaline phosphatase, and GGT)
- Anti-mitochondrial antibodies (AMA) (highly specific)
- Anti-smooth muscle antibodies (ASMA) in 30% of patients
- Raised serum IgM

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Treatment:
- Cholestyramine (treatment of pruritus)
- Fat-soluble vitamin supplementation
- Ursodeoxycholic acid (UDCA):
o Used early, even in asymptomatic patients.
o A hydrophilic bile acid that decreases the bile injury
by the more hydrophobic bile acid
o It increases the biliary secretion
o It has an anti-inflammatory and immunomodulatory
effect
o UDCA delays the histologic progression of PBC
- Liver transplantation for candidate patients

Primary sclerosing cholangitis (PSC)

- IBD (especially ulcerative colitis) is present in 80% of PSC
- It is characterized by autoimmune damage for both
intralobular and extralobular biliary tree.
- Males are affected more than females
- Clinically presents with itching and features of
hyperbilirubinemia
Diagnosis:
- High direct bilirubin level
- High alkaline phosphatase level
- ERCP or MRCP (beading of the biliary system)
- ASMA, ANCA
- Liver biopsy shows onion skin fibrosis (the most accurate)
Treatment:
- Endoscopic therapy for extrahepatic strictures
- Liver transplant
Patients with PSC are at risk of developing gallbladder cancer,
cholangiocarcinoma, or colon cancer (when associated with IBD)

PBC PSC
Age group Women 40 – 60 years Men 20 – 30 years
Affected ducts Small bile ducts Medium/large ducts
Association Autoimmune diseases IBD
Diagnosis Anti-mitochondrial ab. ERCP or MRCP
Treatment UDCA Endoscopic therapy
Table 89: PBC vs. PSC

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 Autoimmune hepatitis
- Autoantibodies against liver tissue
- More common in women
Clinical picture:
- Consider autoimmune hepatitis in a young woman with
hepatitis or hepatic failure who is serology negative to
hepatitis viruses and has other associated autoimmune
conditions
- Signs of acute hepatitis (fever, jaundice, fatigue, RUQ pain)
- Signs of chronic hepatitis

Associated autoimmune diseases:

- Thyrotoxicosis
- Myxoedema
- Ulcerative colitis
- Hemolytic anemia
- Glomerulonephritis
- Nephrotic syndrome
- Vitiligo

Investigations:
- LFT (Liver function test)
- ANA (sensitive but not specific)
- ASMA (anti-smooth muscle antibody)
- ALKM (Anti-liver kidney microsomal antibody)
- ASLA (Anti-soluble liver antigen) (most specific, not sensitive)
- BIOPSY (the most accurate test)
Treatment:
- Steroids
- Azathioprine (started once LFT returns to normal)

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 Complications of liver cirrhosis
Ascites
- Ascites is an accumulation of fluids in the peritoneal cavity
- Paracentesis should be done if (new-onset ascites, fever, or
abdominal pain and tenderness)
Symptoms:
- Asymptomatic if less than 1 liter of fluid
- Abdominal distension starts if more than 1 liter
- Shifting dullness and fluid thrill on examination
- Signs and symptoms of the cause
Pathogenesis: Ascites occurs due to increase permeability in
intestinal capillaries due to splanchnic vasodilatation, which also
activates the renin-angiotensin system and causes sodium water
retention
Investigations:
- Abdominal U/S is best to detect ascites
- Paracentesis to determine the cause
SAAG < 1.1 SAAG ≥ 1.1
Ascitic protein Nephrotic syndrome Cirrhosis
< 2.5 g/dl
Ascitic protein Malignancy, TB, or CHF, or Budd-Chiari
≥ 2.5 g/dl pancreatitis syndrome
Table 90: Differential diagnosis of ascites
Treatment:
- Stop ACEI, ARB, and NSAIDs in patients with ascites
- Treatment of the cause
- Sodium restriction
- Diuretics (spironolactone is the best but furosemide may be
used)
- Paracentesis
- TIPSS (Trans-jugular intrahepatic portosystemic shunt)

- SAAG is the serum ascites albumin gradient

- TIPSS can increase the risk of hepatic encephalopathy
- Paracentesis is diagnostic and symptomatic treatment
- Treatment of ascites is symptomatic and does not prolong
the life

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 Spontaneous Bacterial Peritonitis (SBP)
- Bacterial infection in a patient with ascites but without
perforation of the bowel
- E. coli (most common)
- More common in patients with GI bleeding
Symptoms:
- Maybe asymptomatic in 30% of cases
- Abdominal pain, fever, chills, hypotension
- May worsen encephalopathy
Diagnosis
- All patients with ascites should have paracentesis to rule out
SBP (30% of patients are asymptomatic)
- High ANC (Absolute neutrophil count) in ascites (best initial
test)
- Culture 80% sensitivity (usually not needed for diagnosis)
(most accurate test)
Prophylaxis Indications:
- Cirrhosis or GI bleeding: IV ceftriaxone daily or norfloxacin
bid * 7d
- Previous episode of SBP: Long-term prophylaxis with daily
norfloxacin or TMP/SMX
Treatment:
- Antibiotics: (Cefotaxime or ceftriaxone)
- Albumin: Decreases mortality and the risk of renal failure
Complications:
- Acute kidney injury
- Encephalopathy

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 Portal HTN and esophageal varices
- The normal Portal vein pressure gradient is 5 mmHg
- Portal hypertension is defined as the portal pressure of more
than 10 mmHg
- If the portal pressure exceeds 12 mmHg, there will be a high
risk of esophageal variceal bleeding
- When portal pressure is high, collaterals will appear to shunt
blood to the systemic circulation, esophageal Variceal,
Caput medusa, rectal varices
Manifestations of portal HTN:
- Splenomegaly (high sensitivity to portal HTN)
- Caput medusa (collaterals at the abdominal wall)
- Esophageal varices
- Rectal varices
Investigations:
- Periodic upper endoscopy (for esophageal varices)
- Abdominal U/S (splenomegaly, ascites, etc.)
- CT /MRI angiography to detest portal patency
- CBC: anemia of chronic disease and low platelets (due to
hypersplenism)
- Portal pressure measurement (the most accurate)
o Transjugular approach
o Percutaneous transhepatic approach
Treatment of portal HTN without GI bleeding:
- Propranolol (80-160 mg/day), Nadolol
- Treatment of the cause and complications
Treatment of esophageal variceal bleeding:
- The priority, in this case, is to restore circulation with I.V fluids,
Blood, and plasma
- The hemoglobin transfusion goal is 7 g/dl (increasing Hb
more than 7 will lead to increased portal pressure and thus
more bleeding)
- All should receive prophylactic antibiotics "ciprofloxacin" to
prevent hepatic encephalopathy and SBP.
- Terlipressin or Octreotide:
o Vasopressin analog that reduces the portal pressure
o Terlipressin reduces mortality in Variceal bleeding
- Endoscopy:
o Diagnostic and therapeutic
o Banding can be used to stop bleeding

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 - Balloon tamponade:
o Sengstaken-Blakemore tube can be inserted and
inflated to stop bleeding. It should be deflated 10
minutes every 3 hours to avoid esophageal necrosis
- Transjugular intrahepatic portosystemic shunt (TIPSS):
o A stent inserted between the portal and hepatic vein
o It increases the risk of hepatic encephalopathy

Hepatic encephalopathy
- Hepatic encephalopathy is a neuropsychiatric manifestation
of liver disease
- Measuring the plasma ammonia level can be helpful (but
monitoring serial ammonia value is not helpful).
Pathogenesis:
- Nitrogenous substances produced by gut bacteria
(Ammonia or Gamma-aminobutyric acid) are usually
metabolized by the liver and do not cause harm
- If there is liver failure or the blood is bypassing the liver,
ammonia will accumulate in the brain and cause a
decreased level of consciousness.

EEG will show a diffuse slowing in alpha waves

Clinical grading of hepatic encephalopathy:

- Grade 1: poor concentration, slurred speech, slow
mentation, disordered sleep rhythm
- Grade 2: drowsy, aggressive behavior
- Grade 3: marked confusion, sleepy, response to pain
- Grade 4: coma, unresponsive

Precipitating factors of hepatic encephalopathy are trauma,

infection, heavy protein meals, GI bleeding, hepatoxic drugs, or
constipation

Prophylaxis:
- Give lactulose (titrated to 3 stools per day)
- Do not use protein restriction as prophylaxis for hepatic
encephalopathy

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Treatment:
- Treatment of the precipitating cause
- Lactulose (laxative): decreases colon PH and the protein
content of the GI tract; thus, ammonia absorption
- Rifaximin 400 mg TID: Non-absorbable antibiotics to reduce
the gut bacteria

Neomycin is no longer recommended for hepatic

encephalopathy due to its significant side effects.

Liver storage diseases

Hemochromatosis
- Increase total body iron and iron deposition in the liver
leading to damaged hepatocytes and other organs
- Normal body iron: 4 - 5 grams
- Hereditary Hemochromatosis is an autosomal recessive
disorder; HFE gene mutation leads to increased iron
absorption from the intestine
- Secondary hemochromatosis results from iatrogenic iron
overload from repeated blood transfusions or maybe dietary
Affected organs in hemochromatosis are the liver,
heart, skin, pancreas, testes, and endocrine glands.

Symptoms: At 40 years old, they present with:

- Fatigue and Arthropathy (early symptoms)
- DM, HF, arrhythmias, Impotence, loss of libido, testicular
atrophy
- Destructive Arthropathy of the second MCP joints with Hook-
like osteophytes
- Unusual sites Osteoarthritis (e.g., ankle, shoulder)
- Liver cirrhosis that may progress to Hepatocellular cancer
- Gray skin pigmentation (bronzed diabetes)
Investigations:
- The most appropriate screening test is fasting serum
transferrin saturation
- High serum ferritin and Plasma iron
- Liver biopsy (best to confirm the diagnosis)
- Genetic testing to identify the mutation

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Treatment:
- For hereditary hemochromatosis:
o Venesection weekly 500 ml (250 mg iron) – until serum
iron is normal, then as required (liver and heart will
improve BUT not DM)
o Screening for the first-degree relatives
- For secondary hemochromatosis:
o Hydroxyurea to reduce the need for blood transfusion
o Deferoxamine (iron-chelating agent)

Wilson's disease
- Copper is normally absorbed in the stomach and proximal
small intestine, taken to the liver for storage, and then
incorporated into ceruloplasmin
- Wilson’s disease is an autosomal recessive disorder of
copper metabolism on chromosome 13, reducing
ceruloplasmin synthesis and copper accumulation.
- The affected organs are the liver, basal ganglia of the brain,
eyes, kidneys, and skeleton.
Clinical picture: at age 5 – 45 years
- Acute hepatitis (may progress to fulminant hepatic failure)
- Chronic hepatitis and liver cirrhosis
- Neurological (extrapyramidal, parkinsonism, dementia)
- Eye (Kayser-Fleischer ring)
Investigations:
- Low serum ceruloplasmin (best lab for diagnosis)
- High free serum copper
- High urine copper
- Very high hepatic copper (biopsy) (the best)
Treatment:
- Low copper diet
- A chelating agent (penicillamine for life)
- Liver transplant, if indicated

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P a g e |230
 Hematology
CHAPTER 7

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Introduction to Hematology
The normal Hemostasis
- Hemostasis: is a process that causes bleeding to stop; it
depends upon the interaction between vessel wall,
platelets, and clotting factors.
- Hemostasis is triggered by injuries resulting in damaged
vessels and collagen exposure
Phases of hemostasis:
- Phase I (Primary hemostasis):
o Vasoconstriction (first response in hemostasis)
o Platelets aggregation and formation of the plug
o The platelet adhesion is mediated by vWF
- Phase II (Secondary hemostasis):
o The plasma proteins normally circulate in the plasma
in their inactive form.
o Activation of coagulation cascade and formation of
a cross-linked fibrin clot
- Phase III:
o Natural inhibitors of the coagulation system inhibit
excessive coagulation
o Anti-thrombin destroys the activated factors Xa, Xia,
and thrombin (IIa).

Figure 41: The coagulation cascade in secondary hemostasis

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Screening assays:
PT (Prothrombin time):
- Assess the function of factors I, II, V, VII, and X
- It measures the time for clot
- Normally 11 – 14 sec
International normalized ratio (INR):
- INR = (PT patient/ PT normal)ISI
- Normally 0.9-1.2
Partial thromboplastin time (PTT):
- Assesses the intrinsic and the common pathways
- It assesses factors I, II, V, VIII, IX, X, XI, and XII.
- Normally 60 – 70 sec
Table 91: the laboratory tests used in assessing hemostasis

Table 92: The clotting factors affecting PT and PTT

# Clotting factor name # Clotting factor name
I Fibrinogen VIII Antihemophilic factor
II Prothrombin IX Christmas factor
III Thromboplastin (tissue factor) X Stuart-Prower factor
VI Ionized calcium XI Plasma thromboplastin
antecedent
V Proaccelerin XII Hageman factor
VII Proconvertin XIII Fibrin-stabilizing factor
Table 93: Clotting factors names and numbers

- Factor VII has the shortest half-life

- Vitamin K-dependent clotting factors are (X, IX, VII, II,
proteins C and S)
- Factor 13 deficiency causes bleeding tendency without
increasing in PT or PTT
- Factor 12 deficiency causes an increase in PTT but without
a bleeding tendency.

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 The normal hematopoiesis
- Hematopoiesis is a process of blood formation
- Erythropoietin is a hormone secreted by kidneys in response
to hypoxia to activate hematopoiesis
Sites of hematopoiesis:
- Embryo: Yolk sac
- Children: spleen, Liver, and Lymph nodes
- Adults: pelvis, sternum, and vertebral bodies

Figure 42: The normal hematopoiesis

Blood products life span:

- RBC: 120 days usually removed by spleen
(reticuloendothelial system)
- Platelets: 7 to 10 days
- WBC: hours

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Lymphocytes:
- They are a type of WBC that is a part of the immune system
- B cells: produce antibodies
- T cells: destroy infected cells
- All lymphocytes are formed in the spleen and enter the
circulation via lymphatic circulation
- Differentiated in the thymus (T cells) and Lymph nodes (B
cells)
- Lymphocytes will be elevated in viral infection, some
malignancies, and low in case of immunodeficiency or viral
infections.

Hematologic investigations
Complete Blood Count (CBC)
- Also known as CP (complete picture), FBC (Full blood count)
Terms:
- RBC count: number of RBCs per mm3 of blood
- Hb: Amount of hemoglobin in each liter of blood
- HCT: Hematocrit usually equals Hb*3
- MCV: Mean corpuscular volume, RBC size
o Normally (80-100 fl): Normocytic
o If < 80 fl: Microcytosis
o If > 100 fl: Macrocytosis
- RDW: RBC distribution width (RBC size variation)
- WBC count: number of WBC per mm3 of blood
- PLT count: number of platelets in mm3 of blood
- WBC differentials: number and percentage of each type of
WBCs in blood
- Reticulocytes count: number of immature RBCs in circulation

Blood film
- Also known as peripheral smear
- Blood film is used to diagnose hematological disorders and is
routinely employed to look for blood parasites, such as
malaria and filariasis.
- RBCs do not have nucleus reticulocytes have one
Blood film will show the following:
- RBCs size: (microcytic, normocytic, or macrocytic)
- RBCs color: (hypochromic, normochromic or Polychromasia)
- RBCs Shape: Poikilocytosis: increased proportion of RBCs of
abnormal shape

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 Target cells Tear-drop Poikilocytes Spherocytes

SCA/Thalassemia
IDA Myelofibrosis Hereditary
Hyposplenism spherocytosis
Liver disease AIHA
Basophilic stippling Howell-Jolly bodies Heinz bodies

G6PD deficiency
Hyposplenism
Lead poisoning Alpha-thalassemia
Thalassemia
Sideroblastic anemia
Schistocytes (helmet Pencil Poikilocytes Burr cells
cells) (echinocyte)

Intravascular
Uremia
hemolysis Iron deficiency anemia Pyruvate kinase
MAHA
deficiency
Table 94: Blood film interpretation

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 Bone Marrow examination
- A sample of Bone marrow taken from the posterior iliac crest
or sternum
- Bone marrow aspiration: taking a fluid marrow sample
- Bone marrow Biopsy: a sample of intact bone marrow

Anticoagulants
Heparin
- There are two types of heparin, Unfractionated heparin (UH)
and low molecular weight heparin (LMWH)
- Heparin prevents the activation of factors II, IX, X, and XI

UH LMWH
Molecular weight 15 kilodalton 4.5 kilodalton
Dosing IV high dose Subcutaneous
Half-life 90 minutes 4 – 5 hours
used as outpatient inpatient In or outpatient use
Response Unpredictable Predictable
Risk of bleeding Higher Less
Risk of osteoporosis Higher Less
Risk of HIT syndrome Higher Less
Monitoring Needed (PTT) No need
In renal failure Better than Contraindicated when
patients LMWH unfractionated,
heparin can be used
safely
Response to antidote Better poor
Table 95: Unfractionated vs. LMWH

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 Warfarin
- Warfarin has been used for many years as a first-line in
treating venous thrombosis and reducing the risk of stroke in
atrial fibrillation and valvular replacement patients.
- Monitoring of the warfarin effect is best done by the INR
Mechanism of action:
- Warfarin is a vitamin K antagonist (VKA)
- It inhibits clotting factors II, VII, IX, X, and protein C
Indications of warfarin:
- It prevents thrombosis in mechanical heart valves
- As second-line treatment after direct oral anticoagulants for
DVT, PE, AF
The target INR in patients on warfarin:
- Unprovoked DVT/PE: 2 – 3 for 6 months
- Provoked DVT/PE: 2 – 3 for 3 months
- Recurrent DVT/PE: 2 – 3 for life
- Atrial fibrillation with high CHA2DS2VAS score: 2 – 3 lifelong
- Aortic valve replacement: 2 – 3 lifelong
- Mitral valve replacement: 2.5 – 3.5 lifelong
Side effects:
- Bleeding
- Teratogenic effects in pregnancy
- Skin necrosis (paradoxical thrombosis)

Warfarin-induced skin necrosis:

- It is a rare condition due to acquired protein C deficiency
following treatment with anti-vitamin K anticoagulants.
- This condition is treated by Fresh Frozen Plasma (FFP) or
pure activated protein C
- Surgical management of the necrotic area may be
needed.
Table 96: warfarin-induced skin necrosis

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 Potentiate warfarin effect Reduce warfarin effect
- Amiodaron - Rifampicin
- Erythromycin - Antithyroid drugs
- Fluconazole - Carbamazepine
- Fluoxetine - Cholestyramine
- Metronidazole - Sucralfate
- High dose salicylate - Furosemide
- Tamoxifen - Green tea
- TMP/SMX - Ginseng
- Thyroxine - Ribavirin
- High Alcohol dose
Table 97: Warfarin drug interactions

Warfarin overdose
- An INR level of more than 5 in a patient who is taking
warfarin is considered an overdose
- This condition carries a high risk of bleeding, including major
and life-threatening.
Treatment of warfarin overdose if there is no bleeding:
- INR 5 – 8:
o Hold warfarin for 2 doses
o Restart warfarin in a lower dose when INR < 5
- INR > 8:
o Hold warfarin
o Vitamin K 1 – 5 mg PO
o Repeat Vitamin K dose if INR still > 8 for > 24 hours
o Restart warfarin in a lower dose when INR < 5
Treatment of warfarin overdose with minor bleeding:
- Hold warfarin
- Vitamin K 1 – 3 mg intravenously
- Repeat Vitamin K dose if INR still > 8 for > 24 hours
- Restart warfarin in a lower dose when INR < 5
Treatment of warfarin overdose with major bleeding:
- Hold warfarin
- Vitamin K 5 mg intravenously
- Provide Prothrombin complex concentrate
- Provide FFP is Prothrombin complex concentrate is not
available

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 Vitamin K administration in valve replacement patients will leave
them un-anticoagulated for several days. Therefore, you may
need to provide heparin after vitamin K administration until the
target INR is achieved again.
Avoid vitamin K in valve replacement patients unless necessary

Heparin vs. warfarin

Warfarin Heparin
Action Antagonize vitamin K Agonize antithrombin III
Factors affected Vitamin K dependent Factors 9, 10, 11, 12
Half-life 2 – 3 days 90 minutes
Monitoring PT, INR PTT
Side effects Skin necrosis High liver enzymes
Osteoporosis Hyperkalemia
Bleeding Bleeding
Thrombocytopenia
Osteoporosis
Antidote Vitamin K, FFP, and Protamine sulfate
Prothrombin complex
concentrate
Table 98: Heparin vs. Warfarin

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 Direct oral anticoagulants (DOAC)
Indications for DOAC:
- Non-valvular AF with high CHA2DS2VAS score
- Prevention of thromboembolism in hip or knee surgeries
- Treatment of DVT and PE
Dabigatran (Pradaxa):
- It is a direct thrombin inhibitor
- Excreted mainly by kidneys; doses adjustment in chronic
kidney disease is required
- Dose and renal adjustment:
o CrCl > 30 mL/min: 150 mg PO BID
o CrCl 15 – 30 mL/min: 75 mg PO BID
o CrCl < 30 mL/min or dialysis: It should never be
prescribed
- The antidote: Idarucizumab capsules
Rivaroxaban (Xarelto):
- It is a direct factor Xa inhibitor
- Excreted mainly by the liver
- Dosage and renal adjustment:
o If CrCl > 50 mL/min, 20 mg PO daily with evening meal
o If CrCl < 50 mL/min 15 mg PO daily
- The antidote: Andexanet alpha
Apixaban (Eliquis):
- It is a direct factor Xa inhibitor
- Excreted mainly by the stool
- Dosage and renal adjustment
o Normal KFT: 5 mg PO BID
o Serum creatinine > 1.5 mg/dL: 2.5 mg PO BID
o ESRD on dialysis: 5 mg PO BID
o ESRD on dialysis plus age ≥ 80 years: 2.5 mg PO BID
o ESRD on dialysis plus weight ≤ 60 kg: 2.5 mg PO BID
- The antidote: Andexanet alpha
Edoxaban (Savaysa)
- It is a direct factor Xa inhibitor
- Excreted mainly by the stool
- No authorized antidote
- Dosage and renal adjustment
o CrCl >95 mL/min: Do not use (increase ischemic stroke
risk)
o CrCl >50 to 95 mL/min: 60 mg PO daily
o CrCl 15-50 mL/min: 30 mg PO Daily

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 Blood products and transfusion
Blood compositions
- Blood is composed of cells, Plasma, and proteins
The cells:
- The cells are RBCs, platelets, and WBCs
- The life-span for blood cells:
o RBCs: 90 – 120 days
o Platelets: 7 – 10 days
o WBCs: several hours
The plasma:
- Plasma is a yellowish fluid that holds cells and clotting factors
- Serum: is the same as plasma but without clotting factors
and fibrinogen (collected by centrifuge of blood)
Blood Proteins:
- The main blood proteins are albumin, globulin,
immunoglobulins, prothrombin, and fibrinogen.
- They are responsible for transport, immunity, coagulation,
and oncotic pressure maintenance.

Blood grouping systems

ABO blood grouping system:
- The first blood grouping system recognized in 1900 was the
ABO system
- The major blood groups in this system are A, B, AB, and O.
- Group A blood contains A antigen and anti-B antibodies,
while group B contains B antigen and anti-A antibodies.
- The possibility of RBC or plasma transfusion is linked to the
fact that antibodies should not meet the antigens.
Rh blood grouping system:
- It is the second most important grouping system after the
ABO system
- Rh antigen is a protein that, if found on the RBC membranes,
is considered Rh-positive and vice versa
- Unless sensitized, Rh-negative patients usually do not have
anti-D antibodies in their plasma.
- Ignoring the ABO blood group, Rh-negative blood can be
transfused to the Rh-positive one. However, Rh-positive
blood can cause sensitization in Rh-negative patients.
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 Blood products
PRBC (packed Red Blood Cells)
- It contains red blood cells
- Each unit contains 450 ml and increases Hb by 1 g/dl
- Stored at 1 – 6 co for 35 days maximum
- Need a crossmatch
- Not used as a volume expander
Platelets:
- Contains platelets
- Each unit (300 cc) increases PLT count by 5000-10000
- Stored at 22-24 co degree (room temperature) for 5 days
maximum
- No need for crossmatch
- It has the highest infection rate
FFP (Fresh Frozen Plasma):
- All clotting factors but low levels of factor 8 and vWF
- Each unit = 300 cc
- Stored at -25 c degree for 36 months maximum
- Use IgA deficient donor FFP for IgA deficient recipient
- Need a crossmatch
Cryoprecipitate:
- Rich in factors I, VIII, XIII, vWF
- Each unit = 50 cc
- Stored at -25 c degree for 36 months maximum
- Better to do a crossmatch

Blood Transfusion and transfusion reactions

Indications of blood products transfusion:
- Whole blood: acute active bleeding
- PRBC transfusion:
o Hb of less than 7 g/dl
o Hb of less than 8 g/dl in patients with IHD.
o Acute bleeding with significant Hb drop
- Platelet transfusion: low platelet counts with a major
bleeding
- FFP and cryoprecipitate:
o Warfarin overdose, Vitamin K deficiency
o DIC
o Hepatic failure

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Immediate hemolytic transfusion reaction:
- It occurs due to ABO incompatibility
- Intravascular, fatal hemolysis
- Clerical error is the most common cause
- Symptoms: fever, chills, chest pain, back pain, loin pain, and
dark urine (hemoglobinuria).
- Diagnosis:
o Positive Coomb's test (best)
o Increased free Hb
o Hemoglobinuria
o Decreased haptoglobin < 5 mg/dl
- Treatment: stop transfusion, send sample again to cross-
match, I.V fluids, osmotic diuresis (mannitol), alkalinization of
urine
Delayed hemolytic transfusion reaction
- Extravascular hemolysis up to 7 days post-transfusion
- Caused by Rh or minor blood group incompatibility
- Not detected by the crossmatch
- Not fatal
- Treated by steroids and supportive care
Non-hemolytic febrile reaction
- Due to the presence of WBC
- It can be decreased by giving filtered blood without WBCs
- Treatment: paracetamol
Urticaria and anaphylactic reaction
- Most common in IgA deficient patients
- Maybe mild to fatal
- To avoid this complication, use blood from IgA deficient
donor
Transfusion infection
- The most common infection is CMV
- Others: HBV, HCV, HIV, malaria
- More with platelet and plasma
Iron overload:
- Repeated transfusion after about 20 units
- Each unit PRBCs contains 250 mg of iron
Electrolyte disturbances
- Hyperkalemia (hemolyzed RBCs)
- Hypocalcemia (from citrate)

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Other blood transfusion reactions:
- Thrombophlebitis: In the used vein
- Air embolism: Usually need 50 cc of air to manifest
- Dilatational thrombocytopenia: Most common complication
after massive transfusion
- Clotting factor deficiency: Most commonly, factors V and VIII
- Volume overload (Pulmonary edema)
- Metabolic acidosis
- Hypothermia

Anemia of reduced RBC production

Introduction to anemia
- The normal Hb is 13-18 g/dl in males and 12-16 g/dl in
females.
- Anemia is defined as a hemoglobin concentration of less
than 13 g/dl for men or less than 12 g/dl for women
- Whatever the cause of anemia, the symptoms will be the
same, but symptoms vary with severity and chronicity.
General symptoms of anemia:
- Fatigue, Headache, Faintness
- Breathlessness, Palpitation, angina
- Typical exertional chest pain
- Intermittent claudication
General signs of anemia:
- Pallor
- Heart murmur (Flow murmur)
- Signs related to the causes: (splenomegaly, hepatomegaly,
CKD, hematuria, Koilonychia (IDA), Rectal piles, varices, or
anal fissure)
Classification of anemia: according to MCV:
- Microcytic anemia: MCV < 80 femtoliter/cell
- Normocytic anemia: MCV 80 - 100 fl
- Macrocytic anemia: MCV > 100 fl

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 Microcytic Normocytic Macrocytic
IDA (most common) Acute bleeding B12 deficiency
Thalassemia Acute hemolysis Folate deficiency
Lead poisoning Chronic diseases (70%) Methotrexate
Sideroblastic anemia Liver disease Alcoholism
Chronic disease (30%) Aplastic anemia Liver disease
Myelofibrosis Hypothyroidism
Leukemia MDs
Table 99: Causes of anemia according to the MCV

Iron metabolism
- Normal body total iron is 4-5 grams.
- Of this, about 2.5 g is contained in the hemoglobin needed
to carry oxygen through the blood, and most of the rest is
contained in ferritin complexes that are present in all cells
but most common in bone marrow, liver, and spleen
- Two major iron forms are ferrous (Fe+2) and ferric iron (Fe+3)
- The site for absorption is the proximal duodenum
- To be absorbed, it is reduced from ferric (Fe+3) to ferrous
form (Fe+2) by an enzyme called ferric reductase enzyme
(secreted by enterocyte of the duodenum)
Factors that increase iron absorption:
- Increased acidity
- Alcohol
- Use of vitamin C supplement
- When iron is complemented with lactose
- The iron of animal source (ferrous) is more absorbable than
plant source (ferric)
Factors that decrease iron absorption:
- Tea drinking (converts ferrous to ferric)
- Use of PPIs or any acid suppressant
- Plant-source iron (ferric type)

Normal dietary allowance of iron:

- In adults: 8-11 mg/day
- In premenopausal women: 18 mg/day
- In pregnant women: 27 mg/day
Table 100: The normal dietary allowance of iron

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 Iron Deficiency Anemia (IDA)
- IDA is the most common type of anemia
Causes:
- Poor intake
- Decrease absorption (e.g., celiac disease, gastrectomy)
- Increased Iron demands (pregnancy, adolescence)
- Chronic Blood loss (most common cause)
- GI bleeding (Most common blood loss in men and
postmenopausal women)
- Excessive menstruation (The most common cause of IDA in
young females)
Signs and Symptoms:
- Signs and symptoms of anemia (mentioned above)
- Brittle nails and nail cracking
- Koilonychia (flattening or concavity of the nails)
- Angular stomatitis
- Sore tongue
- Pica (eating unusual substances like soil and ice)
- Plummer-Vinson syndrome (esophageal web, dysphagia +
IDA)
Diagnosis:
- Clinical impression by the presence of signs, symptoms, and
maybe the source of blood loss
- Hypochromic, microcytic anemia
- Blood film:
o Poikilocytosis (Variable RBC shapes)
o Anisocytosis (Variable RBC sizes)
o Target cells
- Investigations for the cause:
o Stool for occult blood
o Urinalysis for RBC in urine
o Upper and lower endoscopy may be needed

Low values High values

Hemoglobin RDW
MCV, MCH Transferrin level
Serum ferritin and iron TIBC
Transferrin saturation
Table 101: Expected lab tests in IDA

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Treatment:
- Treatment of the cause
- Iron replacement (oral is the first line, IM, or IV)
- Blood transfusion may be needed for severe cases
o HB less than 7 g/dl
o HB less than 8 g/dl in a patient with Heart disease

Iron needed = Body weight (kg)*2.3*(15 – Hb) + 500 mg (for store)

Anemia of chronic disease

- Present in chronic infections, chronic inflammations, and
neoplasia (TB, Osteomyelitis, endocarditis, IBD, Chronic renal
failure, SLE, RA, Malignancy)
- Usually Mild and asymptomatic (chronic process)
- Mostly associated with normal MCV (60- 70%) but may
present with low MCV (30-40%) (initially normal MCV then
decreased)

Pathophysiology of anemia of chronic disease:

- Decreased release of iron from Bone marrow to developing
erythroblast
- Decreased erythropoietin production and response
- Decreased RBC survival (less than 120 days)

Diagnosis:
- Signs and symptoms of anemia
- Signs and symptoms of chronic disease
- CBC: Normocytic anemia (maybe microcytic)
- Low serum Iron, Normal Ferritin level, and low TIBC
Treatment:
- Treatment of the underlying cause
- Erythropoietin (EPO) injection
- Rarely need a Blood transfusion (usually mild anemia)

- EPO will not be effective if the serum ferritin is low and

ferrous treatment will not be effective if the serum ferritin is
high or normal.
- The target Hb should not exceed 11 g/dL.

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 Sideroblastic anemia
- In this type of anemia, Iron inside the cells is inadequately
utilized to form normal hemoglobin levels
Causes of sideroblastic anemia:
- Congenital sideroblastic anemia: X-linked or can be
autosomal recessive
- Alcohol abuse
- B6 deficiency
- Lead toxicity
- Drugs (INH, phenacetin, chloramphenicol)
- MDs (the only type associated with high MCV)
- Myeloid Leukemias
Pathogenesis:
- Normally heme is composed of Iron plus protoporphyrin
- A defect in protoporphyrin leads to Failure of iron utilization
in Bone marrow (enzyme defect)
- Iron overload and accumulation of iron in mitochondria
(Ring sideroblasts)
Clinical features:
- Only symptoms of anemia with no specific other symptoms
- Suspect diagnosis when Microcytic anemia present but
other causes of Microcytic anemia excluded
- Hepatosplenomegaly and signs of organ damage due to
iron overload.
Diagnosis:
- Microcytic anemia
- High iron and ferritin level
- Peripheral smear: basophilic stippling, target cells
- Prussian blue stain of bone marrow: iron granules around the
nucleus (ring sideroblasts) (most accurate test)
- Genetic study
Treatment:
- Anemia usually responds to pyridoxine (Vitamin B6)
- If there is severe anemia, provide a blood transfusion
- Iron chelating agent (deferoxamine)
- Folic acid can improve iron utilization
- If there is a secondary cause, stop the causative agent
- MDs usually do not respond to pyridoxine

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 Lead poisoning
- Lead poisoning is a known cause of sideroblastic anemia in
which it inhibits the heme synthesis enzymes leading to
microcytic anemia
The classic presentation:
- Microcytic anemia
- Autonomic neuropathy
- Motor neuropathy
- Abdominal pain
Diagnosis:
- History of exposure (occupational, living in old houses)
- The classic presentation (anemia, neuropathy, abdominal
pain)
- Ferritin level is normal or high
- Blood film shows basophilic stippling
Treatment:
- Treatment of anemia (may need PRBC transfusion)
- Edetate Di-sodium (Chelating agent)

Aplastic anemia
- Pancytopenia in CBC
- Bone marrow will show Hypocellularity
Causes:
- Congenital (Fanconi anemia)
- Primary aplastic anemia (autoimmune) – most common
cause
- Secondary aplastic anemia:
o Viral infection (parvovirus B19)
o Toxic (drugs, chemicals)
o Radiation
o Pregnancy, SLE, PNH
Clinical features:
- Signs and symptoms Anemia - low Hb
- Infection - low WBC
- Bleeding- Low PLT
Treatment:
- Supportive
- Bone marrow transplantation if < 50 years
- Immunosuppressant if autoimmune (cyclosporine, anti-
thymocyte globulin)
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 Macrocytic anemias
Introduction and causes
- Macrocytic anemia is anemia with high MCV > 100 fl
- It can be macrocytic megaloblastic or macrocytic non-
megaloblastic

Megaloblastic anemia Non-megaloblastic anemia

B12 deficiency Alcohol excess
Folic acid deficiency Liver disease
Methotrexate (anti-folate) Hypothyroidism
MDs

Facts about Cobalamin (vitamin B12):

- The liver stores B12 enough for 3 years (B12 deficiency takes
years to manifest)
- Vegetarian or strict vegan persons are more prone to
B12deficiency because it is present in animal sources.
- Absorption of vitamin B12 takes place by the intrinsic factor
terminal ilium pathway or by the passive diffusion at higher
doses.
- Pancreatic enzymes are needed to remove B12from R-
protein so it can bind to the intrinsic factor.

Parietal cells produce intrinsic factor (IF) that binds to the

ingested B12 in the stomach. When they reach the terminal ileum,
B12 is absorbed there.

Facts about Folic acid (Vitamin B9):

- Folate sources are leafy vegetables, liver, and kidney.
- Folate deficiency can be caused by psoriasis, skin loss, and
turnover.

Vitamin B12 Folic acid (B9)

Type Water soluble Water soluble
Source Animal source Animal and plant
Daily requirements 1 microgram 400 IU
Table 102: Vitamins B12 vs. folate

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 Megaloblastic anemia
- It is an anemia characterized by megaloblasts (distinctive
morphologic appearances of the developing RBCs) in the
bone marrow.
- It is caused mainly by either B12 or folate deficiency
- The MCV in this condition will be high (>100 fl)
Etiology:
- Vegetarians and vegans have a high risk of B12 deficiency
- Pernicious anemia is a known cause of B12 deficiency
- Folate deficiency is the most common cause of anemia with
megaloblasts in chronic alcoholics

- Pernicious anemia is an autoimmune disease that leads to

gastric mucosal atrophy, failure of the intrinsic factor
secretion, and B12 malabsorption.
- Intrinsic factor antibodies in 50% or Anti-parietal cell
antibodies can be detected
- It is associated with other autoimmune diseases like thyroid
diseases, Addison's disease, and vitiligo

Clinical features:
- Hematologic features:
o Varying degrees of anemia with high MCV
o Reduced platelet and WBC may present
o High LDH and high bilirubin (due to intramedullary
hemolysis)
o Blood film will show oval macrocytes and
hypersegmented Neutrophils (>6 lobes)
o Bone marrow examination will show hypercellularity
- Neurological manifestations:
o Gloves and stockings neuropathy
o Subacute combined degeneration of the spinal cord
and ataxia
o Dementia
o Optic atrophy
- Other blood tests:
o Low serum B12 or folate levels
o High methylmalonic acid level (the most sensitive test
for B12 deficiency)
o High homocysteine and normal methylmalonic acid
are associated with folate deficiency.

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Treatment:
- High dose oral B12 1000 – 2000 micrograms daily
- Intramuscular B12 indications:
o Severe anemia not responsive to oral treatment
o Neurological dysfunction not responsive to oral B12
o Malabsorption syndromes
- For folic acid deficiency, oral folic acid of 1 – 5 mg per day

Notes:
- Replacement of folate and B12 leads to Hypokalemia (due
to rapid cell production)
- Replacement of folate in a patient with B12 deficiency
before correcting B12 will aggravate neuropathy

Schilling test
- This test is used to differentiate the causes of B12
malabsorption
- All steps of the schilling test should be done after filling the
B12 binding sites by administration of 1000 mcg intramuscular
B12 injection.
The possible causes of B12 malabsorption:
- Pernicious anemia
- Ileal resection or ileal disease
- Bacterial overgrowth
- Chronic pancreatitis
Steps of schilling test:
- Step 1: radiolabeled B12 is administrated orally, and 24-h
urine collection is done to check for radiolabeled B12
excretion
- Step 2: same as step 1, but now it is combined with intrinsic
factor (IF)
- Step 3: same as step 1, but now it is combined with intrinsic
factor (IF), pancreatic enzymes, and a 5-day course of
antibiotics (often tetracycline)

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The Schilling test results interpretation:
Radiolabeled With With With 5-day
cobalamin intrinsic pancreatic antibiotic
factor enzymes course
Pernicious Low Normal Low Low
anemia
Chronic Low Low Normal Low
pancreatitis
Bacterial Low Low Low Normal
overgrowth
Ileal disease Low Low Low Low
Table 103: schilling test interpretation (Low: < 3%, Normal: > 7%)

Anemia of high RBC destruction

Hemolytic anemia introduction
- It is defined as increased RBCs destruction that will lead to
bone marrow hypercellularity and reticulocytosis
Causes:
- Extravascular: RBC removed by liver and spleen prematurely
- Intravascular: RBC lysis in circulation

Intravascular hemolysis Extravascular hemolysis

Immediate transfusion reaction Delayed transfusion reaction
G6PD deficiency Sickle cell anemia
MAHA Thalassemia
PNH Hereditary spherocytosis
Cold agglutinin AIHA Hemolytic disease of newborn
DIC Warm autoimmune AIHA
Table 104: Causes of Intravascular and Extravascular hemolysis

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Classifications according to the cause:
- Congenital defects in:
o RBC membrane (Spherocytosis, Elliptocytosis)
o RBC hemoglobin (thalassemia, sickle cell disease)
o Enzymes (G6PD deficiency)
- Acquired:
o Alloimmune: Hemolytic transfusion reaction
o Autoimmune: cold and warm antibodies
o Paroxysmal nocturnal hemoglobinuria (PNH)
o Microangiopathic hemolytic anemia (MAHA)
o Mechanical (prosthetic valve, burn)
o Hypersplenism
o March hemoglobinuria
o Infections (malaria, sepsis)
o Drugs and chemicals
Clinical features:
- Features of anemia (fatigue, pallor, etc.)
- Jaundice (high bilirubin from RBCs destruction)
- Red urine (from hemoglobinuria)
- Gall stones (manifest in chronic hemolysis)
Diagnosis:
- CBC, blood film, bilirubin level, LDH, and coombs test should
be done when hemolytic anemia is suspected
- Fragmented RBCs may present in blood film
- Positive Coombs test in immune cases only.

Elevated Reduced
Reticulocytes Hemoglobin
LDH Serum haptoglobin
Indirect bilirubin RBCs survival
Urinary urobilinogen and Hb
Urine hemosiderin
In hemolytic anemia, there is a slight increase in MCV since
reticulocytes are larger than normal RBCs
Table 105: Expected lab results in hemolytic anemia

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 Coombs test
- There are two types of Coombs test (Direct and indirect)
- Direct Coombs test detects antibodies bound to RBCs
- The indirect Coombs test detects the presence of Anti-RBCs
antibodies in plasma
Direct antiglobulin test (DAT):
- It will be positive in case of autoimmune Hemolytic anemia,
transfusion reaction, and hemolytic disease of the newborn
- Blood sample mixed with antibodies to human globulin:
o If agglutinated, Positive DAT (immune cause)
o If no agglutinated, negative DAT (nonimmune cause)
Indirect Antiglobulin Test (IAT):
- Stage 1: Plasma mixed with RBCs with known antigen
- Stage 2: then mixed with antibodies to human globulin:
o If agglutinated, Plasma contains RBCs antibodies
o If no agglutinated, no RBCs antibodies in the plasma

Hereditary Spherocytosis (HS)

- Autosomal dominant diseases
- The most common abnormality is a deficiency of membrane
proteins (Beta-spectrin or ankyrin), leading to loss of RBCs
elasticity and RBCs destruction when passing through the
spleen.
Clinical picture:
- Maybe asymptomatic compensated hemolytic anemia
- Recurrent episodes of hemolysis and intermittent jaundice
- A family history of anemia is usually present.
- 50% have gall-stones (which may lead to cholecystitis)
- Clinical course may be complicated by a crisis:
o Hemolytic crisis (associated with infection)
o Megaloblastic crisis (associated with folate
deficiency)
o Aplastic crisis (associated with parvovirus B19 infection)

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Diagnosis:
- Hb: 6 – 10 g/dL (depends on the degree of compensation)
- Reticulocytosis (usually 6 – 20%)
- High indirect bilirubin and LDH
- Blood film: Spherocytes (small round hyperchromic RBCs
without central pallor)
- Negative Coombs test
- The osmotic fragility test is no longer recommended
- Flow cytometric EMA (eosin-5-maleimide) binding test (the
most accurate test)

- The presence of positive family history, typical clinical

features, spherocytes, high MCHC, and high reticulocytes
do not require any additional tests.
- If the diagnosis is not certain, an EMA test should be done

Treatment:
- Folic acid supplement (5 mg/week for life)
- May need a transfusion in hemolytic crisis
- Screening for first-degree relatives
- Splenectomy in moderate to severe cases: 2 weeks before
Splenectomy, the patient should receive:
o Pneumococcal vaccine
o Meningococcal C vaccine
o H. influenza B vaccine
o Then regular H. influenza and pneumococcal

Hereditary Elliptocytosis
- It is an autosomal dominant disorder
- It is the same as spherocytosis, but blood film shows
Elliptocyte
- The disease is milder and usually requires no treatment.
- If more severe, treatment is the same as spherocytosis.

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 Hemoglobinopathies
Thalassemia Syndromes
- It is a group of genetic disorders of globin chain production
- Abnormal hemoglobin leads to cell membrane damage and
decreased RBC survival
Types of Hemoglobin:
- Adult Hb (HbA):
o Composed of 2 alpha and 2 β chains
o It has a good ability to carry oxygen and the best
stability
o By the 24th week of GA, HbA constitutes 5% of Hb
o At term, it becomes 30% of the total Hb
o At 6th – 12th months of age, it rises to 98%
- Fetal Hb (HbF):
o Composed of 2 alpha and 2 gamma chains (major
Hb in fetal life but adult comprises less than 1% of total
Hb)
o It has a better ability to carry oxygen than HbA but is
less stable.
o After the 8th week, HbF is the predominant
hemoglobin
o At birth, 70% of the hemoglobin’s are HbF
o After 6 – 12 months, only a trace is present
- HbA2: composed of 2 alpha and 2 sigma chains (normally
presents in about 1 – 2% of total Hb)
- HbS: Substitution of valine amino acid for glutamine amino
acid in the 6th position of β-chain of hemoglobin (sickle cell
anemia)
Types of thalassemia:
- β-Thalassemia: reduced β chains synthesis
- Alpha-Thalassemia: reduced Alpha chains synthesis

β-thalassemia
- It is the most common type of thalassemias due to a failure of
synthesis of β chains
- In β-Thalassemia, there is a decreased or absent HbA, and an
increase in HbF and HbA2

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Types of β-thalassemia:
- Homozygote: β-Thalassemia Major (Cooley’s anemia)
o Inability to produce Hb A
o After 6 months of life, they develop profound anemia
- Heterozygote: β-Thalassemia Minor (trait)
o Reduced alpha chain production leads to reduced
but not absent HbA.
o Usually, patients have asymptomatic mild microcytic
hypochromic anemia, with little or no symptoms and
normal ferritin level
Features of Thalassemia major:
- Severe anemia requiring transfusion in the first year of life
- Recurrent infections
- Bone marrow hyperplasia causing bossing of the head and
prominent malar eminence
- Splenomegaly (early), hepatomegaly (slow)
- Iron overload in a transfusion-dependent patient (usually
after 20 units of blood transfusion)results in features of
Hemochromatosis
Investigations:
- CBC: Microcytic hypochromic anemia
o Severe in thalassemia major
o Mild in thalassemia minor
- Peripheral blood film:
o Hypochromic Microcytic anemia
o Poikilocytosis (abnormally shaped RBCs)
o Basophilic stippling
- Hb electrophoresis: (most accurate test)
o Thalassemia minor (Hb A: 80-95%, Hb A2 4-8% and Hb
F: 1-5%)
o Thalassemia major (Hb A: 0%, Hb A2: 4-10%, and Hb F:
90-96%)
- Skull X-ray shows hair on end appearance.

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Treatment:
- Thalassemia minor usually requires no treatment.
- Blood transfusion to keep Hb > 10 g/dl (some may need
repeated transfusion while Thalassemia minor may need no
treatment)
- Chelating agent to prevent iron overload (start after blood
transfusion of > 100ml/kg)
- Folic acid supplement 5mg daily is indicated
- Hydroxyurea: increases the production and concentration of
fetal hemoglobin (Hb F), which reduces transfusion
requirements.
- A possibility of a cure in selected children using HSCT

Alpha-Thalassemia
- Occurs due to reduction or absence of alpha chain synthesis
- Normally there are 4 alpha genes
Pathology:
- 1-alpha gene deletion: no clinical effect
- 2-alpha gene deletion: alpha thalassemia minor (trait)
- 3-alpha gene mutation: Hb H disease
o Hb H is useless
o There are moderate anemia and splenomegaly
- All the 4-alpha gene deletion:
o Stillbirth at (28-40 weeks gestation, or die shortly after
birth (They are pale, oedematous, Hydrops fetalis)
Diagnosis:
- Genetic study (most accurate test)
- Alpha thalassemia minor (trait):
o Mild Microcytic hypochromic anemia
o Electrophoresis: Normal Hb A2 and Hb F and NO Hb H
o It is a diagnosis of exclusion
- Hb H disease:
o Microcytic hypochromic anemia of variable severity
o Electrophoresis shows Hb H (10-40% of total Hb)
Management:
- For alpha thalassemia trait, no treatment
- For Hb H disease:
o Folic acid
o Avoid oxidative drugs
o Supportive treatment if needed
o Blood transfusion as needed

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 Sickle cell anemia (SCA)
- SCA is usually well compensated with reticulocytes count
that is always high
- More common in African American origin
Pathogenesis:
- SCA is an autosomal recessive disorder that leads to the
substitution of valine amino acid for glutamine amino acid in
the 6th position of the β-chain of hemoglobin resulting in Hb S
formation
- Hb S can crystallize if the patient has dehydration or
infection, giving RBC a sickle shape.
- These RBCs are vulnerable to destruction → anemia → Bone
marrow hypercellularity as compensation → bone marrow
hyperplasia → Bone deformity (Skull bossing)
- The abnormal charge of these sickle cells leads to
adherence to endothelium and vasoocclusion that may lead
to splenic infarction (called autosplenectomy)
Clinical picture:
- Features of hemolytic anemia
- Gall stones due to chronically elevated bilirubin
- Recurrent infection: due to autosplenectomy (especially
encapsulated organisms)
- Bone deformities (skull bossing)
- Tissue infarction due to Vaso-occlusion:
o Chronic skin ulcers
o Avascular necrosis of the femoral head
o Renal impairment
o Blindness: due to retinal detachment or proliferative
retinopathy
o Stroke
Acute crises:
- Hemolytic crisis
- Aplastic crisis (parvovirus B19 infection can precipitate that)
- Vaso-occlusive crises:
o Bone pain, painful infarction of the spleen, stroke
o Papillary necrosis and renal impairment
o Mesenteric infarction
o Chest Pain (Bone involvement or pulmonary
infarction)
o Penile involvement (Priapism: persistent painful
erection of the penis)

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Diagnosis:
- Low hemoglobin (7-10 g/dl)
- High Reticulocytes count (usually 10-25%)
- High WBC and platelets
- High bilirubin
- Hb electrophoresis: (Hb S: 85-98%, Hb A: 0%, Hb F: variable)
(most accurate test)

Salmonella is the most common cause of osteomyelitis in SCA

patients (as twice as staph aureus)

Treatment:
- An allogenic Bone marrow transplant
- Hydroxyurea (Increase level of Hb F and Reduce frequency
of painful crisis)
- Iron chelating agent to prevent iron overload
- Supportive treatment
o Folic acid to prevent megaloblastic crisis
o Treatment of infections to avoid crises
o Avoid dehydration and hypoxia to avoid
sequestration
- Management of crises:
o Pain crisis: IV fluids, opioid analgesia, O2 therapy
o Hemolytic crisis: Blood transfusion, supportive
o Vaso-occlusive crisis: IV fluids, Analgesia, Exchange
transfusion
Sickle cell trait:
- Sickle cells < 40% in electrophoresis
- Asymptomatic, no treatment
- Genetic counseling is required

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 Autoimmune hemolytic anemia (AIHA)
- RBCs Autoantibodies
- Divided into warm and cold types (according to which
temperature the antibodies best cause hemolysis)
- Characterized by a positive DAT (Coomb’s test)
- Causes of warm AIHA include: 50% are idiopathic, SLE,
Neoplasia (lymphoma, CLL, lung cancer), Drugs (Quinidine,
NSAIDs, Methyldopa, Penicillin’s, Cephalosporins,
ciprofloxacin, Rifampicin, Phenytoin)
- Causes of cold AIHA include: Neoplasms (CLL, Myeloma,
Lymphoma, Waldenström macroglobulinemia), and
Infections (Mycoplasma pneumonia, EBV, CMV, HIV, Hepatitis
C, malaria, E. coli)

Warm AIHA Cold AIHA

Antibody type IgG IgM
Lysis temperature Room temp. 4 °C
Hemolysis site Extravascular Intravascular
Management Steroids, Avoid cold
splenectomy, IVIG exposure
Table 106: Warm vs. cold AIHA

Evan's syndrome:
It is an autoimmune thrombocytopenia present in 10% of patients
with AIHA

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 Non-immune hemolytic anemia
Paroxysmal nocturnal hemoglobinuria (PNH)
- Stem cell disorder that can progress to Aplastic anemia,
Myelodysplasia, Or AML
- In acquired hemolysis (intravascular hemolysis), RBCs
become sensitive to lysis by complement in acidosis.
- Deficiency of complement regulatory proteins CD55 and CD59
- During sleep, there is hypoventilation and mildly increased
CO2, which do not affect the normal population but cause
hemolysis in patients with PNH
Clinical picture:
- Hemolysis and hemoglobinuria (may present in first-morning
urine but can be in all urine samples in severe cases)
- Anemia (also IDA due to an iron loss in the urine)
- Patients are more prone to venous thromboembolism
(thrombosis is the most common cause of death in PNH)
Diagnosis:
- High urine hemosiderin
- IDA, pancytopenia
- Hypoplastic bone marrow
- Flow cytometry: absent CD55, CD59 (most accurate test)
Treatment:
- Supportive (Iron replacement, folic acid replacement, blood
transfusion as needed)
- Eculizumab (inhibits complement activation)
- BMT (the only way to cure)

Microangiopathic hemolytic anemia (MAHA)

- It is defined as intravascular destruction of RBCs that leads to
hemoglobinemia, hemoglobinuria, and schistocytes in blood
film (fragmented RBCs)
- It can be caused by TTP, ITP, DIC, HUS, prosthetic heart valve,
or vasculitis

March hemoglobinuria:
Damage of RBCs in feet, associated with prolonged marching or
running

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 Disorders of primary hemostasis
Idiopathic thrombocytopenic purpura (ITP)
- Autoantibodies against platelets leading to platelet
destruction, thrombocytopenia, and bleeding
- If platelets < 20,000 u/l, patients are at risk of spontaneous
bleeding
- Typically preceded by a viral infection, especially in children
Symptoms: Easy bruising, epistaxis, menorrhagia, petechial rash

Look for a healthy person with isolated thrombocytopenia

Diagnosis:
- ITP is a diagnosis of exclusion
- If the patient is elderly, think about B-cell malignancy and
perform a bone marrow biopsy
- If connective tissue diseases are suspected, perform
autoantibodies
- If Viral infection is suspected, hepatitis profile, HIV testing,
CMV testing, etc.
Treatment:
- If no bleeding and Platelet count > 30,000: No treatment
- Mild bleeding or platelet count < 30,000: Steroids
- Severe bleeding or platelet count < 10000: IVIG
- Recurrent episodes, steroid-dependent: splenectomy
- If splenectomy and steroids are not effective: rituximab,
azathioprine, cyclosporine, mycophenolate

- Platelet transfusion is only indicated if there is life-

threatening bleeding and the platelet count is less than
20*10^9/L/
- Bleeding from platelet disorders is superficial in the form of
epistaxis, gum bleeding, petechia, purpura, or vaginal
bleeding
- Bleeding from clotting factors deficiency is usually deep in
the form of hemarthrosis (bleeding in joints) or bleeding
inside muscles.
- Brain hemorrhage and GI bleeding can result from both
platelet and factor disorders
- Despite that the platelet is destructed in the spleen by the
macrophages, there is no splenomegaly in ITP patients

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 Thrombotic Thrombocytopenic Purpura (TTP)
- Both TTP and HUS are different versions of the same basic
disease (deficiency of metalloproteinase ADAMTS 13)
- Hemolytic Uremic Syndrome (HUS) is associated with E. coli
O157:H7 (more frequent in children)
Pathogenesis:
- TTP patient has an ADAMTS13 (vWF-cleaving protease)
deficiency
- TTP can occur in patients with cancer, transplant recipients,
HIV, SLE, and those who receive quinine, clopidogrel,
ticlopidine, or cyclosporine.
- Platelets and fibrin are deposited in the arteriolar walls,
leading to the destruction of RBCs when passing through
these arterioles (Microangiopathic hemolytic anemia -
MAHA).
Clinical presentation and diagnosis:
- Fever
- Neurological manifestations (headache, confusion, ataxia,
seizures, and mental status and focal abnormalities)
- Microangiopathic hemolytic anemia
- Fragmented RBCs (schistocytes)
- High reticulocytes and LDH levels
- Indirect hyperbilirubinemia
- Other features of intravascular hemolysis
- Coombs test is negative
- Thrombocytopenia
- Renal impairment
Treatment:
- Immediate discontinuation of the causative drug.
- Emergency plasma exchange

- Platelet transfusion in TTP-HUS can exacerbate the

microvascular occlusion.
- PT, aPTT, D-dimer, and fibrinogen levels are normal in TTP-
HUS and abnormal in DIC.

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 Heparin-Induced Thrombocytopenia (HIT)
- It is a drop of platelet count ≥ 50% after starting heparin
- This condition is not dose-dependent (can occur after
administration of any amount of heparin)
- Both types of heparin can cause HIT syndrome, but in LMWH,
it is less likely
Clinical features:
- The onset is 5 – 15 days after starting heparin but can occur
within hours if there was previous exposure.
- Thrombosis is the most common manifestation
- Venous thrombosis (3 times more common than arterial):
DVT, PE, Cerebral sinus thrombosis …
- Arterial thrombosis: MI, CVA, Acute limb ischemia, Organ
infarction, Skin necrosis
Diagnosis:
- Platelet factor 4 (PF4) antibodies
- Heparin-induced antiplatelet antibodies
- > 50% decrease in platelet after heparin administration
Treatment:
- Stop heparin and use a direct thrombin inhibitor (such as
argatroban or lepirudin)
- Because of 90% cross-reactivity, LMWH should not be
substituted

HIT type I HIT type II

Onset 1 – 4 days 5 – 15 days
Pathogenesis Heparin-induced Antibodies to PF4
aggregation
Thrombosis Not present Present
Treatment No need to stop Mandatory to Stop
heparin heparin
Table 107: Types of HIT syndrome

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 Von Willebrand disease (vWD)
- VWD is the most common inherited bleeding disorder
- It is an autosomal dominant disease
- Decreased level of functioning vWF
Clinical picture:
- Bleeding tendency: easy bruising, epistaxis, menorrhagia, GI
bleeding
- Family history of bleeding tendency

- vWF is a protein that has two functions:

o Carrier for factor VIII (if deficient vWF, factor VIII
will be decreased)
o Binding platelets to sub-endothelial collagen
(primary hemostasis)
- The nature of bleeding due to vWF deficiency is similar to
bleeding from platelet disorders (superficial)

Diagnosis:
- Symptoms and Family history suggestive of the disease
- High bleeding time (BT)
- Normal PT, normal platelet count
- High PTT in 50% of patients
- Low plasma factor VIII
- Low vWF
Treatment:
- Mild bleeding: Tranexamic acid
- Desmopressin (DDAVP) increases the level of vWF
- Severe bleeding: Cryoprecipitate or Factor VIII

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 Platelet dysfunction
Uremia-induced platelet dysfunction:
- Uremia prevents the normal function of platelets
- Look for a patient with uremia and platelet type bleeding
- BT is prolonged, vWF is normal
- Treatment: DDAVP, dialysis, and estrogen
- The platelet dysfunction here is reversible by dialysis
Aspirin and clopidogrel mediated platelet dysfunction:
- They permanently cause the platelet to lose their function
- The bleeding time will be elevated until the platelet is
replaced by new ones
Glanzmann’s thrombasthenia:
- It is an autosomal recessive rare disorder leading to an
absence of the platelet Gp IIb/IIIa receptor (defective
aggregation)
- The difference between ITP and Glanzmann’s is that in ITP,
there are antibodies against GP IIb/IIIa receptors

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 Disorders of secondary hemostasis
Hemophilia
- An X-linked recessive disease that has two types (almost
exclusively in males)
- Type A: Factor VIII deficiency
- Type B: Factor IX deficiency, also known as Christmas
disease
Clinical picture:
- Usually, diagnosis at the age of 6 months (patient becomes
more mobile and susceptible to injuries)
- Symptoms vary according to the severity of the disease
- Hemarthrosis, muscle hematomas, prolonged bleeding
The severity of hemophilia:
- Mild: factor level > 0.05 – 0.4 u/l
- Moderate: factor level 0.01 – 0.05 u/l
- Severe: factor level < 0.01 u/l
Diagnosis:
- Clinical picture and family History suggestive of hemophilia
- Normal Bleeding time (Normal BT)
- Normal PT and High PTT
- Low factor VIII or factor IX (most accurate test)
- Normal vWF
Treatment:
- Desmopressin (DDAVP) I.V or intranasal (For mild bleeding or
to cover minor surgeries) – (not effective in severe
hemophilia A or B)
- I.V factor VIII for severe bleeding (for hemophilia A)
- Factor IX concentrate (for hemophilia B)
Anti-factor VIII antibody can develop in 30% of cases; this will
make treatment ineffective (in this case, activated factor VII
should be provided)

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Disseminated intravascular coagulation (DIC)
- DIC is a consumptive coagulopathy that leads to
thrombocytopenia, elevated PT and PTT, and schistocytes
- DIC never occurs in healthy people without risk factors
Risk factors:
- Sepsis, malignancy, drug toxicity
- Burns, snake bites
- Cancer
- Obstetric problems (placental abruption, missed abortion,
amniotic fluid embolism)
Types:
- Chronic DIC:
o It causes venous thromboembolic manifestations
o PT, PTT may be normal or high (well-compensated)
- Acute DIC (Rapidly evolving):
o Coagulation: Tissue factor released from destructed
tissues causes widespread activation of coagulation
o Bleeding: The consumption of the coagulation factors
and platelets will lead to Thrombocytopenia,
elevated PT, PTT, and INR, and low fibrinogen
o MAHA: Delayed dissolution of fibrin polymers by
fibrinolysis may result in the mechanical disruption of
RBCs, producing schistocytes.
Investigations:
- Thrombocytopenia
- Prolonged PT, PTT, and INR
- Normal to Low fibrinogen (at least 50% reduction from the
baseline)
- Elevated D-dimer (the most sensitive)
- Blood film: Schistocytes in 50% of cases.
Treatment:
- Treatment of the underlying cause
- If there is no serious bleeding or thrombosis, no specific
treatment
- Platelet transfusion to maintain platelet count > 50,000
- FFP: to correct coagulation factors
- Cryoprecipitate: to maintain fibrinogen > 150 mg/dl (if FFP
failed to control bleeding)
- Correct dehydration, Renal failure, Acidosis, and treat shock
- For slowly evolving chronic DIC, heparin is the choice

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 PT aPTT BT Platelet
Hemophilia Normal High Normal Normal
vWD Normal High High Normal
ITP Normal Normal High Low
Warfarin High Normal Normal Normal
Aspirin Normal Normal High Normal
DIC High High High Low
Table 108: Interpretation of the blood test results

Venous thromboembolism (VTE)

Deep vein thrombosis (DVT)
- The lower limb is the most common site for DVT, but axillary
DVT presents in 2 – 3% of cases
- The major concern about DVT is the risk of PE development
- The risk factors of DVT are the same as that of PE

Virchow’s Triad (Risk factors for DVT/PE):

- Venous stasis: (major surgery, prolonged travel, pregnancy,
lower limb injury)
- Endothelial damage (i.e., trauma)
- Hypercoagulability state:
o History of DVT/PE
o Hormone replacement therapy (e.g., estrogen)
o Malignancy (of any kind)
o Nephrotic syndrome (due to antithrombin III loss)
o Coagulopathies (e.g., factor V Leiden)
Table 109: Virchow's triad (the risk factors for hypercoagulability)

Clinical features:
- Some patients may be asymptomatic
- Pain, swelling, and erythema of the affected limb
- A palpable cord and low-grade fever (less common)
- Patient may present with complications

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Complications of DVT:
- Pulmonary embolism (the most important)
- Phlegmasia alba dolens: severe arterial spasm due to
massive iliofemoral DVT (pale, swollen limb with absent
peripheral pulses)
- Phlegmasia cerula dolens: severe congestion and cyanosis
due to a massive iliofemoral DVT (swollen blue limb with a
high risk of gangrene)
- Venous gangrene
Investigations:
- D-Dimer: high sensitivity, done for low probability cases
- Doppler U/S: accuracy is 80-85%
- Duplex scan: sensitivity and specificity are 90-100%
- Enhanced Helical CT scan: shows thrombus in small veins
- Ascending venography

Normal veins DVT

Vein diameter Normal Dilated
Blood flow Spontaneous Poor
Echogenic material None Present
Distal compression Augments blood flow Poor augmentation
Blood flow Phasic flow Loss of phasic flow
Table 110: Difference between normal and thrombosed veins

Treatment:
- DOAC (Apixaban or Rivaroxban):
o It should be started once the diagnosis is suspected
o The first-line treatment for patients who do not have
contraindications
o In the active malignancy patients, DOAC became
preferred over LMWH
- Warfarin:
o The second line treatment after DOAC
o Used in severe renal impairment (GFR < 15 mL/min)
o Used as first-line if the patient has antiphospholipid
syndrome.
- LMWH:
o Used as a bridge for warfarin (to prevent skin necrosis)
o Used as monotherapy for 6 months in malignancy or
pregnant patients (second line after DOAC)

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 - Inferior vena cava filter indications:
o Contraindications to anticoagulants
o Recurrent emboli while on adequate anticoagulation
o Right ventricular heart failure
Length of anticoagulation:
- 3 months: for provoked DVT/PE (known risk factor)
- 6 months: for unprovoked cases (unknown risk factor)
- 3 – 6 months: for people with active cancer
- Lifelong: for recurrent DVT/PE

Pulmonary Embolism (PE)

- PE is an occlusion of the pulmonary artery or its branches by
an embolus
- Clot migration from DVT site to lodge in the pulmonary artery
- Less than 30% have clinical evidence of DVT
Clinical features:
- Symptoms:
o Sudden dyspnea (the most common symptom)
o Pleuritic chest pain (the 2nd most common symptom)
o Lungs should be clear, and chest x-ray should be
normal
- Signs:
o Tachypnea (most common sign)
o Pleural rub (the second most common sign)
o Accentuated S2
o Tachycardia, cough, and hemoptysis
o Signs of DVT are not always present
o Low Oxygen saturation /hypoxia
o Hypotension (a sign of massive PE)
Diagnosis:
- Apply wells criteria:
o Score > 4 (high probability): CTPA (Best investigation)
o score ≤ 4(low probability): Perform D-dimer, then do
CTPA (if positive)
o If CTPA is contraindicated, VQ scan is the next step

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 Well’s Criteria for PE:
Clinical signs and symptoms of DVT 3
No alternative diagnosis 3
Heart rate > 100 bpm 1.5
Immobilization ≥ 3 days or surgery in the past 4 weeks 1.5
Previous DVT or PE 1.5
Hemoptysis 1
Malignancy 1
Table 111: Well's Criteria, A scoring system for the diagnosis of PE

- Chest X-Ray
o The most common finding is a normal chest x-ray
o The most common abnormality is Atelectasis
o Wedge shape infarction, Pleural-based lesion
(Hampton hump)
o Oligemia (Westermark sign)
- ECG
o Sinus tachycardia (the most common)
o Nonspecific ST-T changes (2nd most common)
o S1Q3T3 (The classic ECG changes in PE)
o Other changes include (RBBB, right ventricular strain,
and Right axis deviation)
- Venous Doppler U/S for DVT detection
- ABGs: hypoxia with respiratory alkalosis.
Treatment:
- Admission to hospital
- Thrombolysis is the first-line treatment for massive PE
(hypotensive patients)
- The same treatment approach for DVT
- Treatment of complications (effusion, respiratory failure, etc.)

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 Myeloproliferative disorders
- These are chronic conditions characterized by clonal
proliferation of marrow precursor cells
- Most patients have one disorder, but these disorders can
overlap in one patient
They include:
- Polycythemia Vera (PV)
- Myelofibrosis
- Essential thrombocythemia (ET)
- Chronic myeloid leukemia (CML)

Polycythemia Rubra Vera (PV)

- Increase in bone marrow erythropoiesis despite low
erythropoietin level
- It is a genetic problem caused by JAK2 mutation
- Usually, in the age above 40 years
Clinical features:
- Maybe asymptomatic with an incidental finding of high Hb.
- Splenomegaly is common
- Symptoms of Hyperviscosity:
o Headache, blurred vision, tinnitus, HTN
o Dizziness
o Pruritus, especially after a hot bath (histamine-
mediated)
- Erythromelalgia (painful erythema on the hand relieved by
aspirin)
Diagnostic criteria: (ABC or ABD are diagnostic)
- Major criteria:
(A) Hb > 16.5 for males or > 16 form females
(B) Hypercellular bone marrow on biopsy
(C) Positive JAK2 mutation
- The minor criterion:
(D) Subnormal Erythropoietin level

Secondary polycythemia should always be excluded first

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Other laboratory findings:
- Low serum iron (iron consumption)
- High vitamin B12 level (unknown etiology)
- Platelets and WBCs may be elevated as well
Treatment:
- Aspirin; to prevent peripheral arterial or cerebrovascular
diseases
- Venesection; to maintain Hb less than 15 g/dl, decrease
symptoms of Hyperviscosity
- Hydroxyurea, interferon-alpha to suppress myeloproliferation
- Radioactive phosphate for the older patient (decrease
transformation to acute leukemias)
- Antihistamine (symptomatic treatment)
- Allopurinol (protect against high uric acid)
Complications:
- In 25% of cases, this disorder can transform into acute
leukemia or Myelofibrosis
- Peripheral arterial diseases or CVA's
- Venous thromboembolism
- Peptic ulcer disease and upper GI bleeding

Myelofibrosis
- Bone marrow fibrosis, due to increased production of
fibroblasts
- Usually, in patients > 50 years
Clinical features:
- Weight loss, night sweat
- Hepatomegaly, Massive splenomegaly
- Features of anemia

In myelofibrosis, hematopoiesis shifts to the spleen and liver that

cause hepatosplenomegaly (it is called extramedullary
erythropoiesis)

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Lab tests:
- Pancytopenia (Platelets and WBC can be high early in the
disease)
- Teardrop poikilocytosis in blood film
- Bone marrow aspiration and biopsy (replacement of normal
tissue with fibrous tissue)
- JAK-2 mutation
- Others: Folate deficiency, High uric acid level
Treatment:
- Supportive: blood transfusion, folic acid
- Hydroxyurea: reduce splenomegaly and reduce WBC
- Splenectomy may be required (reduce the risk of splenic
rupture)
- HSCT (definitive treatment)

Essential thrombocythemia (ET)

- It is a myeloproliferative disease of the megakaryocytes in
the bone marrow, leading to increased platelet production.
- It is more common in females aged 50 – 60 years
Clinical picture:
- It can be an incidental finding in CBC (asymptomatic)
- Unusual site venous thrombosis (mesenteric, hepatic, or
portal veins)
- Erythromelalgia may present
- Splenomegaly in 25% of cases
- Bleeding may present (abnormal quality of platelets)
Diagnosis:
- CBC shows thrombocytosis
- Blood smear shows large size platelets
- Bone marrow: shows a large number of megakaryocytes
Treatment:
- Hydroxyurea
- Aspirin
- Plateletpheresis in case of severe bleeding

Reactive thrombocytosis:
Platelets count is high but does not exceed 1,000,000, usually
secondary to another disorder (e.g., RA, IBD, TB, or Vasculitis)

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 Malignant white cell disorders
Acute leukemias
- It is a disorder in the hematopoietic tissue maturation
leading to the accumulation of blast cells in the bone
marrow and peripheral circulation.
- Heredity factors, radiation, chemicals, and drug exposures
may be implicated in the development of leukemia.
Classification:
- Acute leukemia is classified into myelogenous and
lymphocytic types (refers to the type of blast that build up in
bone marrow and blood)
- ALL is the most common in children, but AML is 8 times more
common than ALL in adults

Blast cells can be differentiated into:

- Lymphoblasts: are positive for TdT nuclear staining
- Myeloblasts: are positive for myeloperoxidase enzyme
and Auer rods (a crystallized version of the enzyme)

Clinical features:
- Bone pain
- Symptoms of pancytopenia (fatigue, bleeding, infection)
- Organ infiltration (hepatomegaly, splenomegaly, gum
hypertrophy, L.N enlargement, etc.)
Diagnosis:
- Cytopenia on CBC and blast cells in peripheral smear
- Bone marrow examination showing blast cells of > 20%
- DIC workup (PT, PTT, D-dimer, fibrinogen)
- Tumor lysis workup (UA, LDH, potassium, Cr, Phosphorus,
Calcium)

Leukemoid reaction:
This is not leukemia; in some infections, there will be a very high
leukocyte count of> 40,000. It can be differentiated from
leukemia by having a high LAP score (high leukocyte alkaline
phosphatase that is high in Leukemoid reaction and low in
leukemia).

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Blasts in circulation: usually give us a high leukocyte count, but not
all leukemias have high leukocytes count.
- Subleukemic leukemia
o Normal leukocyte count
o High blood blast cells
o High bone marrow blasts
- Aleukemic leukemia
o Normal leukocyte count
o No blood blast cells
o High bone morrow blast

Acute lymphoblastic leukemia (ALL)

- In 75% of cases, it is B-cell in origin
- Philadelphia chromosome t(9;22) is common and indicates
a poor prognosis in ALL patients.
Treatment:
- Intensive combination chemotherapy often followed by
allogeneic HSCT
- Intrathecal chemotherapy with or without radiation for CNS
prophylaxis
- Tyrosine kinase inhibitor dasatinib for Philadelphia-positive
patients

Acute myelogenous leukemia (AML)

- It is more common than ALL in adults
- It is further classified into (M0 to M7)
- Lymphadenopathy or hepatosplenomegaly indicates
another diagnosis as they are rarely present in AML.
Diagnosis:
- Bone marrow biopsy showing > 20% blast cells is diagnostic
- Auer rods may be seen on a peripheral blood smear
Treatment:
- Platelet transfusion whenever platelet count < 10,000
- Chemotherapy for non-promyelocytic leukemia
- Allogeneic and autologous HSCT

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 Acute Promyelocytic Leukemia (APML):
- It is the M3 subtype of AML
- It occurs due to t(15;17) mutation
- A high number of Auer rods and increased risk of
coagulation; can present with DIC
- Treatment by vitamin A derivative (ATRA)

Chronic leukemias
Chronic Myeloid Leukemia (CML)
- A myeloproliferative disorder resulting from malignant
transformation of hematopoietic stem cells
- About 90% of CML patients have gene mutation t(9;22)
called Philadelphia chromosome (it indicates a good
prognosis in CML)

Philadelphia chromosome leads to the production of BCR-ABL

gene, which encodes for BCR-ABL protein with a tyrosine kinase
activity responsible for abnormal cell differentiation.

Clinical features:
- Chronic phase:
o The patient will have non-specific symptoms like night
sweating, weight loss, abdominal fullness (due to
massive splenomegaly)
o Can present as an incidental finding of high WBC
count
o Responsive to treatment and easily controlled
- Accelerated phase:
o Fever, bone pain, splenomegaly
o More difficult to control disease
- Blast crisis phase:
o Transformation to acute leukemia
o Present as bone marrow failure
o Not responsive to treatment
Diagnosis:
- Persistently high WBC: > 150,000 all are neutrophils in CML
- Usually, no anemia or thrombocytopenia at the presentation
- Bone marrow biopsy with cytogenetics and genetic study for
Philadelphia chromosome are confirmatory tests.

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Treatment:
- Hydroxyurea (alleviates leukocytosis and splenomegaly)
- Tyrosine kinase inhibitor (imatinib, dasatinib, or nilotinib) is
used for disease control for lifelong treatment
- Allogenic HSCT for accelerated phase and blast crisis

Causes of massive splenomegaly (> 1 kg):

- CML
- Myelofibrosis
- lymphoma
- Kala-azar (visceral leishmaniasis)
- Malaria (chronic)
- Gaucher's syndrome
Table 112: Causes of massive splenomegaly

Chronic lymphoblastic leukemia (CLL)

- CLL is the most common leukemia in adults
Clinical features:
- Most patients diagnosed when having asymptomatic
lymphocytosis
- Lymphadenopathy 80%, hepatosplenomegaly 50%
- Autoimmune hemolytic anemia (warm IgG antibodies)
- Anemia, thrombocytopenia, high WBC > 20,000
Diagnosis:
- High WBC count > 20,000 in CLL (predominantly
lymphocytes)
- 50% of patients have hypogammaglobulinemia
- Smudge cells: lab artifact (the fragile nucleus is crushed by
the coverslip)
- Bone marrow biopsy
Rai staging system of CLL:
- Stage 0: lymphocytosis alone
- Stage 1: lymphocytosis and lymphadenopathy
- Stage II: lymphocytosis and hepatosplenomegaly
- Stage III: lymphocytosis and anemia
- Stage IV: lymphocytosis and thrombocytopenia

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Treatment:
- For stage 0 and stage 1, no treatment
- For stages II, III, and IV, Chemotherapy (fludarabine)
- For refractory cases, cyclophosphamide (more efficacy but
more toxic)
- For severe infections, IVIG
- For autoimmune hemolytic anemia, prednisolone
- Supportive treatment
- BMT if the disease is not controlled

Richter phenomenon:
Conversion of CLL to high-grade lymphoma occurs in 5% of
patients

Myelodysplastic syndrome (MDs)

- A pre-leukemic disorder presents in older patients (> 60
years)
- Failure of maturation of blast cells and accumulation of blast
cells in the bone marrow of less than 20%
- Can progress to AML, causing Pancytopenia (but usually
death occurs due to infection or bleeding before
transformation to leukemia)
- Caused by radiation, chemotherapy or can be a primary
process
- Consider a diagnosis of MDs in a patient with Macrocytic
anemia and pancytopenia in a patient with normal B12 and
Folate
- It is the only case in which sideroblastic anemia presents with
macrocytosis
- Prussian blue stain shows ring sideroblasts

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 Lymphomas
- It is a malignant tumor of lymphoid tissue, characterized by
abnormal T and B cells proliferation
- They are most commonly B-cell in origin
- Classified according to biopsy findings into 2 types
Types are:
- Hodgkin's lymphoma (HL)
- Non-Hodgkin's lymphoma (NHL)

Non-Hodgkin's lymphoma (NHL)

- B cell origin in 70% and T cell in 30%
- There will be a proliferation of lymphocytes in lymph nodes
and spleen
- Usually widespread at presentation and can affect any
lymphoid tissue (e.g., Tonsils, Adenoid, Gut, Nasopharyngeal
glands, Skin)
- NHL and CLL are similar, but NHL is solid mass while CLL is
circulating in the blood.
Clinical features:
- Painless L.N enlargement
- It may involve pelvic, retroperitoneal, or mesenteric
structures
- B symptoms
- Tiredness, weight loss, fever
- Lower limb weakness: metastasis to extradural space
compressing the spinal cord
- Bone pain
Types according to the rate of cell division:
- Low grade (incurable with conventional therapy)
- Intermediate grade
- High grade (curable with conventional therapy)

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 Ann-Arbor staging of lymphoma:
Four major stages:
- I: single lymph node (LN)
- II: ≥ 2 LN/regions on the same side of the diaphragm
- III: involvement is at both sides of the diaphragm
- IV: widespread disease
Each stage may be subdivided into A or B:
- A: No systemic symptoms other than pruritus
- B: A presence of B symptoms
Table 113: Ann-Arbor staging of lymphoma

Diagnosis:
- Excisional L.N biopsy (best initial test)
- CBC is normal in most cases
- LDH (if high indicates worse severity)
- Bone marrow biopsy, Abdominal, chest, and pelvic CT (for
staging)
Treatment:
- For stages Ia and IIa, local radiation with a small dose of
chemotherapy
- For stage III or IV or the presence of B symptoms: rituximab
and CHOP (Cyclophosphamide, Hydroxydaunorubicin,
Oncovin (vincristine), Prednisolone)

Hodgkin's lymphoma (HL)

- Same as NHL in presentation, diagnosis, B symptoms, and
staging
- Associated with biopsy finding of large binucleated cells of B
cell origin called Reed Sternberg cells.
- Maybe Associated with a previous infection with infectious
mononucleosis
- B cell in origin
- Occur usually at age 20 – 35, a second peak at 50 – 70 years
Subtypes:
- Nodular sclerosing (NSCHL) (Most common type)
- Lymphocyte predominant (the best prognosis)
- Mixed cellularity (good prognosis, associated with a large
number of Reed Sternberg cells)
- Lymphocyte depleted (the worst prognosis)

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Treatment:
- For stages Ia and IIa, local radiation with a small dose of
chemotherapy
- For stage III or IV or the presence of B symptoms, ABVD
(Adriamycin (doxorubicin), Bleomycin, Vinblastine,
Dacarbazine)

Relapse after radiotherapy is treated by chemotherapy, but

relapse after chemotherapy is treated with extra high dose
chemotherapy and BMT

Hodgkin Non-Hodgkin
Presenting stage Stage I or II (80%) Stage III or IV in (80%)
Usual site Cervical area Disseminated
Reed-Sternberg Present Not present
cells
Extra-nodal disease Less common More common
Best prognosis Lymphocyte Low-grade type
predominant
Worst prognosis Lymphocyte High-grade type
depleted
Table 114: Hodgkin vs. Non-Hodgkin lymphoma

The drug Common side effect

Doxorubicin Cardiomyopathy
Bleomycin Lung fibrosis
Vincristine Neuropathy
Cyclophosphamide Hemorrhagic cystitis
Table 115: Side effects of the lymphomas drugs

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 Burkitt's lymphoma
- It is a high-grade B cell lymphoma
- It is associated with the c-myc gene translocation t(8: 14).
- Microscopy finding is starry sky appearance
- The Epstein-Barr virus (EBV) is strongly implicated in the
development of the African type of Burkitt's lymphoma and,
to a lesser extent, the sporadic type
Types:
- Sporadic type: abdominal (e.g., ileocecal) tumors are the
most common (more common in HIV patients)
- Endemic (African) type: typically involves maxilla or
mandible
Treatment:
- Chemotherapy: tends to produce a rapid response which
may cause tumor lysis syndrome.

- Tumor lysis syndrome (TLS) is a side effect of chemotherapy

due to the rapid destruction of a large number of cells
- Features of TLS include: hyperkalemia,
hyperphosphatemia, hyperuricemia, hypocalcemia, and
acute renal failure
- TLS should be treated by IV fluids, Mannitol, urinary
alkalization, and correct electrolytes.

Mutation The associated disease

t(9;22) Philadelphia chromosome (CML and ALL)
t(15;17) Acute promyelocytic leukemia
t(8;14) C-myc gene in Burkitt's lymphoma
t(14;18) Follicular lymphoma
Table 116: Common gene translocations in hematology

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 Plasma cell dyscrasias
Multiple Myeloma (MM)
- The peak incidence is 60 – 70 years old
- Uncontrolled increased plasma cells production leads to
abnormal production of paraproteins
- Paraproteins are most commonly IgG
Clinical features:
- Hypercalcemia: due to osteoclastic activation
- Renal impairment: due to renal deposition of
immunoglobulins and Bence-Johns protein
- Anemia: plasma cells replace the normal HCS
- Bone disease: the most common presentation
o Due to an osteoclastic activating factor
o Cause lytic lesion on skeletal survey

Two of the following 3 are diagnostic:

- Bone marrow aspiration > 10% plasma cells
- Paraproteins in plasma and/ or urine (protein
electrophoresis)
- Lytic lesions on skeletal survey
Table 117: Diagnostic criteria for multiple myeloma

- In MM, plasma cells produce dysfunctional antibodies

leaving the patient susceptible to infections
- Renal failure and infection are the most common cause of
death in MM
- bence-Johns proteinuria is detected by
immunoelectrophoresis, not routine urinalysis
- hyperuricemia and normal alkaline phosphatase are
expected in MM
- A high level of light chains in the plasma may lead to
hyperviscosity syndrome

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Treatment:
- If asymptomatic, no Treatment
- Supportive therapy: high fluid intake, analgesia, allopurinol,
protein plasmapheresis for Hyperviscosity
- Specific treatment:
o Thalidomide + melphalan + prednisolone: for older
patients
o Chemotherapy followed by HSCT: improves the
quality of life but does not cure MM
- Bisphosphonates: decrease bone pain and prevent bone
fracture

Monoclonal gammopathy of unknown

significance (MGUS)
- IgG or IgA spikes in serum protein electrophoresis
- A small number of plasma cells are present in bone marrow
biopsy
- 1% transform to Multiple Myeloma (The more the number of
immunoglobulins in the spike, the more the risk of
transformation to Multiple Myeloma)
- No need for treatment

Waldenström macroglobulinemia
- Overproduction of IgM from malignant B-cells leading to
Hyperviscosity
- No bone lesions
- Associated with cold agglutinin hemolytic anemia and
features of hyperviscosity
Treatment:
- Plasmapheresis to remove the IgM and decrease
Hyperviscosity
- Rituximab, prednisolone, and cyclophosphamide reduce
IgM production from abnormal B cells.

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 Rheumatology
CHAPTER 8

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Introduction to Rheumatology
Analysis of arthritis
Arthritis can be analyzed as the following
- Acute vs. chronic
- Inflammatory vs. non-inflammatory
- Monoarticular, oligoarticular, or polyarticular

Inflammatory arthritis:
- Hotness, redness, tenderness, pain, and swelling
- Morning stiffness > 60 minutes
- Associated with fatigue, fever, and malaise (constitutional
symptoms)
- High synovial fluid leukocyte count (> 2000 u/l)
- Neutrophils in acute inflammation and monocytes in
chronic inflammation.
- Labs: High ESR, CRP, and anemia of chronic disease
Non-inflammatory arthritis:
- Not hot, tender, or red (bony enlargement and joint
effusion may present in OA)
- Morning stiffness < 30 minutes
- No constitutional symptoms
- Synovial fluid leukocyte count (200 – 2000 u/l)
- Monocytes are predominant
- Normal CRP and ESR
Classification according to number of joints involved:
Monoarthritis: arthritis involving one joint
Oligoarthritis: arthritis involving 2 – 4 joints
Polyarthritis: arthritis involving ≥ 5 joints
Table 118: Classifications of arthritis

Normal Non-inflammatory Inflammatory Septic

Leucocytes < 200 200 – 2000 u/l > 2000 u/l > 50000
PMN cells% < 25 < 25 > 50 > 75
Table 119: Joint aspiration rule in different types of arthritis

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C-reactive protein (CRP):
It is an acute-phase reactant synthesized by the liver in response
to inflammation; it adheres to the bacteria, activates the
complement system, and promotes phagocytosis.
CRP rapidly responds to inflammation, rises, and falls more
quickly than ESR.
- Level > 0.8 mg/dl indicates inflammatory condition
- Level < 0.8 mg/dl is indeterminate
Table 120: The acute phase reactant; CRP

Autoantibody tests
Test Associated diseases
ANA Directed against the nuclear antigen
SLE, SSc, Sjögren’s syndrome, MCTD
Titer does not correlate with the disease activity
RA Rheumatoid factor (RA), directed against the Fc
portion of IgG
Not specific, present in different rheumatologic
diseases
Anti-CCP Anti-cyclic citrullinated peptide
Rheumatoid arthritis (most specific)
Anti-Sm Most specific for SLE (does not correlate to disease
activity)
Anti-dsDNA SLE; correlate to disease activity, especially in
kidney disease
Anti-U1-RNP MCTD
ASMA Autoimmune hepatitis
Anti-La/SSB Neonatal SLE, Sjögren’s syndrome, SSc, RA
Anti-Ro/SSA Subacute cutaneous SLE, Sjögren’s, neonatal
heart block, SSC, RA
Anti-scl-70 Diffuse cutaneous systemic sclerosis
Anti-Histone Drug-induced SLE
c-ANCA Granulomatosis with polyangiitis
p-ANCA Not specific
Anti-Jo-1 Polymyositis
Table 121: autoantibodies and their associated disorders

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 Types of hypersensitivity
Type Description and examples
Type I Anaphylaxis, immediate type
An antigen reacts with IgE bound to mast cells
Anaphylaxis, Atopy, Asthma
Type II Cytotoxic type
IgG or IgM binds to an antigen on the cell surface
AIHA, ITP, Rheumatic fever
Type III Immune complex disease
Free antigen and antibody
SLE, Post-streptococcal GN, EAA
Type IV Delayed type
T-cell-mediated
Graft versus host disease (GVHD), chronic EAA, MS,
GBS
Type V New type
Antibodies that recognize and bind to the cell surface
receptors, this either stimulating or blocking them
Grave's disease, Myasthenia gravis
Table 122: Types of hypersensitivity

HLA associated diseases

HLA type Associated diseases

HLA-B27 Ankylosing spondylitis
Reactive arthritis
Enteropathic arthritis
HLA- DR4 and DRB1 RA
HLA- DR3 Sjögren's syndrome
SLE
Table 123: different HLA types and the associated disorders

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 Raynaud’s disease
- It is a condition characterized by decreased blood flow to
the fingers
- It is more common in female
- The exact cause is unknown, but several factors are
suggested
Factors leading to Raynaud’s disease:
- The sensitivity of the small arteries and arterioles to cold
(mostly hands)
- Increased sympathetic tone
- Psychological instability
- Presence of cold agglutinins in the blood which causes
agglutination of RBCs on exposure to the low temperature
Diagnosis:
- The attack consists of three consecutive phases
o Pallor (due to digital arteriolar spams)
o Cyanosis (due to dilatation of the capillaries, which
are filled with deoxygenated blood)
o Redness (present after the flow of oxygenated blood
as the attack passes off)
- The attacks are precipitated by coldness or emotional
excitements and relieved by warmth
- The disease is bilateral and symmetrical
- Radial and ulnar pulses are preserved
- No major gangrene (only minute patches of ulceration or
gangrene may present)
Grades of Raynaud’s disease:
- Grade I: presents only with Raynaud’s phenomena
- Grade II: presents with mild trophic changes in the tip of
fingers and nails
- Grade III: the presence of gangrene on the tip of fingers
Treatment:
- Conservative measures are tried early (avoid cold, wear
gloves, Vasodilators as calcium channel blockers)
- In severe cases, cervicodorsal sympathectomy

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 Raynaud’s Phenomenon:
color changes similar to those of Raynaud’s disease may
accompany a large group of organic diseases such as:
- Thoracic outlet syndrome
- Certain occupations (Typist, pianist, use of vibrating tools)
- Collagen disease (Rheumatoid arthritis, SLE, or
scleroderma)
- Vascular disorders (Atherosclerosis, Buerger’s diseases)
- Drugs (Ergot-containing drugs)
Treatment: treat the cause
Table 124: Raynaud’s Phenomenon

Erythema nodosum
- It is an inflammation of subcutaneous fat cells, resulting in
tender nodules usually seen in the body's shins and extensor
surfaces.
- Patients with erythema nodosum may have a false-positive
result for venereal disease (as in SLE)
Clinical features:
- Flu-like symptoms are the first symptoms
- Typically, tender, erythematous, nodular lesions
- Joint pain and inflammation may present for a few weeks
- Usually, it heals without scarring within 2 weeks and may
leave a residual bruised appearance
- Ulcerative forms: seen in Crohn’s disease
Causes: (NODOSUM)
- No cause (idiopathic)
- Others: Pregnancy, Infection: (Streptococci, TB, Brucellosis)
- Drugs: (penicillin, sulfonamides, NSAIDs, Sulfa drugs)
- Oral contraceptives
- Steroids
- Ulcerative colitis/ Crohn’s disease and other Systemic
diseases (sarcoidosis, Behcet's)
- Malignancy/lymphoma
Treatment:
- Treatment of the underlying cause
- Cold compressors
- Bed rest and NSAIDs

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 Stevens-Johnson syndrome (SJS)
- It is a mucocutaneous disease that is often caused by a
drug-induced immunologic reaction
- Mucosal involvement is present in > 90% of SJS
- It generally affects adults
Causes: it is Associated with First time exposure to Drugs
(Sulfonamides, penicillin, steroids, NSAIDs, cephalosporines,
quinolones)
Clinical features:
- Mucosal erosions with erythematous macules
- Nikolsky sign: separation of the superficial skin layer with
slight Rubbing and epidermal detachment
- Erosions and hemorrhagic lesions in the mucous membranes
(eyes, mouth, and genitalia)
Diagnosis:
- Mainly clinical diagnosis with the history of the cause
- Biopsy is the most accurate test
Complications: (same as Burn complications)
- Electrolyte disturbance
- Secondary infection
Treatment:
- Stop the offending agent
- Cover the skin and manage fluid and electrolytes
- Steroids, Cyclosporine, and IVIG, may have a rule in
treatment

Stevens-Johnson Toxic Epidermis

syndrome (SJS) Necrolysis (TEN)
TBSA% involved < 10% > 30%
Mucosal involvement > 90% of cases > 90% of cases
Nikolsky sign Present Present
Table 125: Stevens-Johnson vs. Toxic Epidermis Necrolysis

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 Rheumatoid arthritis (RA)
- RA is a chronic symmetrical polyarthritis of unknown cause,
also characterized by extra-articular features.
- Female: male ratio is 3: 1
Risk factors:
- Genetic factors account for the majority of disease
susceptibility within the population, and it is associated with
HLA- DRB1
- Environmental factors may play a role:
o Smoking: conveys up to a fivefold increase in RA risk
o Occupational exposure to silica, asbestos
Autoantibodies:
- Anti-CCP (most specific 95% and 70% sensitivity)
- RF (70% sensitive), (can be positive in the normal population
10%)
- Autoantibodies are neither necessary nor sufficient for the
diagnosis of RA

Diagnostic criteria:
Feature Points
One large joint 0
Two to ten large joints 1
One – three small joints 2
Four – ten small joints 3
More than ten small joints 5
Negative RF and Anti-CCP (below UNL) 0
Low positive RF and Anti-CCP (< 3 times UNL) 2
High positive RF and Anti-CCP (> 3-time UNL) 3
Normal ESR and CRP 0
Abnormal ESR and CRP 1
Duration of symptoms < 6 weeks 0
Duration of symptoms ≥ 6 weeks 1
A score of ≥ 6/10 is needed for the diagnosis
Table 126: The diagnostic criteria for RA

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Typical features:
RA can present as acute onset with marked systemic features or as
chronic relapsing-remitting
- General symptoms (fever, fatigue, malaise)
- Arthritis:
o Deforming, bilateral, and symmetrical
o Inflammatory (Swollen, painful, hot joints in hands and
feet)
o Gradually gets worse with larger joints becoming
involved
o Distal interphalangeal joints are rarely affected
- Morning stiffness > 60 minutes
- Rheumatoid nodules (most often over bony prominences)
- Late features (joint deformities):
o Swan neck deformity
o Boutonnière deformities
o Z deformity of the thumb

Figure 43: Hand Joints deformities in Rheumatoid Arthritis

(1) Normal (2) Swan-neck (3) Boutonniere (4) Mallet deformity

- Synovitis of the upper cervical spine leading to atlantoaxial

subluxation
- Baker's cyst: extension of inflamed synovium into popliteal
space
- Rupture of flexor or extensor tendons may occur as a
complication

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Extra-articular manifestations:
- Systemic: (Fever, fatigue, weight loss)
- Musculoskeletal system: (Muscle wasting, Tenosynovitis,
Bursitis, Osteoporosis)
- Skin:
o Rheumatoid nodules: usually on extensor surfaces
o Pyoderma gangreonosum: painful lesion on lower
limbs
o Rheumatoid vasculitis: purpura, petechiae, splinter
hemorrhage, livedo reticularis, and digital infarction
may occur
- Ocular:
o Keratoconjunctivitis sicca (the most common eye
manifestation in RA, SLE, and Sjogren’s syndrome)
o Episcleritis, Scleritis, Uveitis, Keratitis (in more severe
RA)
- Pulmonary:
o Pleuritis (the most common pulmonary manifestation)
o Exudative pleural effusion
o Rheumatoid nodules (peripheral, < 1 cm in diameter)
o Pulmonary fibrosis (usually lower lobe fibrosis)
- Cardiac:
o RA is an independent risk factor for CAD and heart
failure
o Pericarditis (common but often asymptomatic)
o Myocarditis, Endocarditis, and rheumatoid nodules in
the heart may occur
- Hematological: (Anemia, Eosinophilia, Thrombocytosis)
- Lymphatic: (Splenomegaly, Felty's syndrome)
- Vasculitis: (Mononeuritis multiplex, Visceral Vasculitis)
- Neurological: (Cervical cord compression, Peripheral
neuropathy, Mononeuritis multiplex)
- Renal: mesangioproliferative Glomerulonephritis,
Amyloidosis)

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 - The most common cause of death in RA is CAD
Felty's syndrome:
- RA + splenomegaly + neutropenia + leg ulcers
- Absolute neutrophil count < 2.0 *109/L
- Fever, anemia, thrombocytopenia, and vasculitis may
present
- It predisposes to recurrent bacterial infection
- May require the use of granulocyte colony-stimulating
factors
Caplan's syndrome: RA + pneumoconiosis + lung nodules
Poor prognostic factors for RA:
- Functional limitations
- Extraarticular disease
- Positive RF and Anti-CCP
- Radiographic bony erosions
Treatment:
- Physiotherapy and appropriate exercise (protect joints from
damage)
- Stop smoking (smoking is a risk factor for RA, it decreases the
response to DMARDs it exacerbates the Rheumatic lung
disease)
- Analgesia (NSAIDs):
o NSAIDs are the first-line treatment
o Not used as monotherapy
o Do not change the destructive course of RA
- Glucocorticoids:
o Can be used orally or intra-articular
o Used until the slower acting DMARDs achieve the full
effect
o The lowest dose and the shortest period are indicated
due to side effects
- Disease-modifying Anti-Rheumatic drugs (DMARDs)
o non-biologic DMARDs:
▪ Methotrexate is the most widely used one
▪ Leflunomide: the first choice if methotrexate
side effects or intolerance present
▪ Others (sulfasalazine, hydroxychloroquine)
o Biologic DMARDs:
▪ TNF- alpha inhibitors (e.g., etanercept)
▪ Tocilizumab
▪ Rituximab (anti-CD20 monoclonal antibody)
- Surgery
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DMARD’s Side effects
Methotrexate Liver toxicity
Bone marrow suppression, Pulmonary
toxicity
TNF-inhibitors Reactivation of TB, Infection
Hydroxychloroquine Retinal toxicity
Sulfasalazine Bone marrow toxicity, Hemolysis in G6PD
deficiency, Rash
Rituximab Infection
Prednisone Bipolar disorder
Table 127: DMARDs and their side effects

Systemic lupus erythematosus (SLE)

- SLE is an autoimmune disorder with several autoantibodies
- Associated with HLA B8, DR2, DR3
- The females are more affected than males (F: M ratio is 9:1)
- Several Autoantibodies associated with this condition
Clinical features:
- General symptoms (fever, fatigue, malaise)
- Arthritis with early morning stiffness and tenosynovitis
- Serositis
- Raynaud's phenomenon
- Skin manifestations:
o Malar butterfly rash
o Discoid lupus rash
o Photosensitive rash
o Painless oral ulcers
o Lupus panniculitis (painful induration with overlying
erythema)
- Renal: (Typically proliferative glomerulonephritis- nephritic)
- Cardio:
o Pericarditis (most common cardiologic manifestations
in SLE)
o Libman-sacks Endocarditis (sterile vegetation)
- Respiratory: (Pleuritis, Pleural effusion, Pulmonary fibrosis,
Alveolitis)
- Neurologic: (Carpel tunnel syndrome, Chorea, Lymphocytic
meningitis)

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 - Hematological: (Neutropenia, Lymphopenia,
Thrombocytopenia, Anemia)
- GI: oral ulcer, mesenteric vasculitis (risk of bowel infarction)

The Most common presentation is: arthralgia

with arthritis and Raynaud's phenomena

Diagnosis:
Antibodies Characteristics
ANA Most sensitive (99%)
RA 20% sensitive, not specific
Anti-sm Most specific (>99%), sensitivity 30%
Anti-DsDNA Specificity (99%), sensitivity 70%, indicates activity
Anti-histone Specific for drug-induced SLE (80 – 90%)
anti-U1 RNP Associated with MCTD
Anti-Ro (SSA) Associated with neonatal SLE
Anti-La (SSB) Usually associated with anti-Ro
APS antibodies They may present in SLE patients
Table 128: antibodies associated with SLE

Signs of active SLE:

- High ESR and Anti-dsDNA
- Low CRP, C3, and C4

CRP is not elevated in SLE unless there is serositis or synovitis

present.

Treatment:
For mild disease (skin and joint involvement):
- Analgesia (NSAIDs)
- Hydroxychloroquine
- Prednisolone (short course)
For severe disease (heart, renal, or cerebral involvement):
- I.V methylprednisolone combined with I.V
cyclophosphamide
Maintenance therapy: Azathioprine, Methotrexate

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Drug-induced SLE:
- The symptoms are limited to arthritis, fever, and serositis
- Anti-Histon antibody is the most appropriate test, but do
not order it in a patient with renal involvement of SLE.
The most common drugs that can cause drug-induced lupus:
- Procainamide (the most common offender)
- Hydralazine (the second most common offender)
- Other agents: Isoniazid, Tumor necrosis factor (TNF) alpha
inhibitors, Minocycline, and Quinidine)

Discoid lupus erythematosus (DLE):

- DLE is a benign, autoimmune disorder generally seen in
younger females. It can transmit into SLE in < 5% of cases.
- It is characterized by erythematous, raised rash, sometimes
scaly, and photosensitive, which is more common on the
face, neck, ears, and scalp.
- The main treatment is achieved by avoiding sun exposure,
topical steroid cream, and hydroxychloroquine (second
line)

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 Antiphospholipid syndrome (APS)
- Antiphospholipid antibodies (including lupus anticoagulant
and Anticardiolipin antibodies) interact with the coagulation
cascade
- Elevated PTT, normal PT, and increased risk of
thromboembolism (venous or arterial) and abortions
Classical features:
- Venous thrombosis (DVT, PE, Livedo reticularis, etc.)
- Arterial thrombosis (MI, stroke, gangrenes, etc.)
- Neurological involvement (epilepsy, migraine, chorea)
- Osteoarticular involvement (arthralgia, arthritis)
- Obstetric conditions (eclampsia, abortion, premature birth)
- Hematologic involvement (thrombocytopenia, AIHA)
Diagnosis:
- Mixing study (patient plasma mixed with normal plasma; if
PTT is still elevated, APS is likely. Nevertheless, if PTT is
corrected, clotting factor deficiency is likely)
- Best: (Russell viper venom test): testing for Antiphospholipid
antibodies
- ANA usually negative
Note: Anticardiolipin antibodies are also present in syphilis, so they
will give a false-positive result for APS

Treatment:
- For primary thromboprophylaxis:
o Low dose aspirin
- Arterial or initial venous thrombosis:
o Lifelong warfarin with an INR target of 2 – 3
- For recurrent venous thrombosis while on warfarin:
o Add aspirin and increase the INR target to 3 – 4
- Steroids and immune suppressive drugs can be used

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 Systemic sclerosis (SS)
- It is a generalized disorder of connective tissue of unknown
cause
- Systemic sclerosis is also known as scleroderma
- Fibrosis of skin, blood vessels, and viscera
- More common in female 4:1
Clinical features:
- Skin changes:
o Non-pitting edema
o Shiny skin with atrophy and ulceration of finger-tip
o Limbs, face, and trunk may be affected
- Visceral involvement:
o GERD (esophageal involvement)
o Malabsorption (small bowel involvement)
o Lower lobe lung fibrosis
o Cardiomyopathy
o Real failure and malignant HTN
- Musculoskeletal involvement:
o Raynaud's phenomena
o Arthralgia and arthritis
o Muscle weakness
Classifications:
- Diffuse cutaneous scleroderma 20%:
o Rapid development of symmetrical skin thickening of
proximal and distal extremities, face, and trunk
o The patient has a greater risk of kidney and visceral
involvement earlier.
- Limited cutaneous scleroderma (CREST syndrome) 80%:
o Symmetric skin thickening is limited to the face and
distal extremities.
o Less frequent involvement of internal organs
o After a long time, the patient may have pulmonary
HTN and biliary cirrhosis
o It was called CREST syndrome: (Calcinosis, Raynaud's
phenomena, Esophageal dysmotility, Sclerodactyly,
Telangiectasia)
- Localized scleroderma:
o Limited to skin, subcutaneous tissue, and muscles
o Morphea: single or multiple plaques of skin induration
o Linear type: sclerotic lesion appears as streaks or
band

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Diagnosis:
- ANA 90% positive
- ESR is usually normal
- RF Positive in 30%
- Anti-centromere antibody (ACA) – associated with limited
type
- Anti-topoisomerase (Anti-Scl-70) – associated with the diffuse
type (most specific)
Treatment:
- No definite cure for this condition
- Treatment of complications
- Steroids may relieve symptoms
- Nifedipine: for Raynaud's phenomena
- ACE inhibitors: for HTN crisis in renal involvement even if
creatinine is elevated.
- PPI: for GERD and esophageal dysmotility
- Treatment of pulmonary HTN
- Cyclophosphamide: for pulmonary fibrosis (improves
dyspnea and PFTs)

Sjögren's syndrome
- An autoimmune disorder of unknown cause
- Antibodies against lacrimal and salivary glands
- 90% affect women
- Pathogenesis: Impairment of exocrine glands
- The most dangerous complication of Sjögren's syndrome is
lymphoma
Symptoms:
- Dry mouth, Dysphagia, Parotid enlargement 30%
- Dry eyes (keratoconjunctivitis sicca)
- Less common: (vasculitis, Renal tubular acidosis, chronic
interstitial nephritis, Pancreatitis)
Diagnosis:
- Autoantibodies (RF, ANA, Anti-Ro, Anti-La)
- Schirmer's test: filter paper to measure tear formation
- Lip or parotid gland biopsy (the most accurate test)
Treatment:
- Artificial Tears
- Artificial saliva
- Pilocarpine may stimulate saliva production
- Pancreatic enzyme replacement
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 Sjögren's syndrome is associated with:
- RA
- SLE
- Primary biliary cirrhosis
- Polymyositis
- Hashimoto thyroiditis

Mixed connective tissue disease

(MCTD)
- It is a condition of overlapping clinical features
- Presence of at least two of the following (SLE, Scleroderma,
fibromyositis, and rheumatoid arthritis)
Diagnosis: Anti-U1-RNP (anti-U1-Riboneucleoprotein) (highly
sensitive)
Treatment: According to predominant symptoms

Spondyloarthropathies
- They are also called seronegative arthritis (negative RA)
- The gene most strongly associated with seronegative
spondyloarthropathies is HLA B27
- Usually involves men under the age of 40 years
This group includes:
- Ankylosing spondylitis
- Reactive arthritis (Reiter's syndrome)
- Psoriatic arthritis
- Enteropathic arthritis (associated with IBD)
General manifestations:
- Inflammation of the axial skeleton, tendons, and enthesis
- They generally involve the spine and large joints
- Usually asymmetrical oligoarthritis
- Lower limbs are affected more than upper limbs
- Negative rheumatoid factor (RF)
- Steroids are not a good treatment for seronegative
Spondyloarthropathies
- Reactive arthritis and psoriatic arthritis may be more severe
in patients with HIV infection

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 Ankylosing spondylitis
- Chronic inflammation affects the sacroiliac joint and spine
- It affects the SI joint and progress cranially without skipping
any region
- Associated with progressive stiffening and fusion of axial
skeleton
- Male to female ratio is 3: 1
- Associated with HLA B27 (70%)

Figure 44: Anatomy of the sacroiliac joint

(1) lumbosacral joint, (2) sacroiliac joint, (3) Symphysis pubis

Symptoms:
- Low Back pain is worse at rest (early morning and inactivity)
- Decreased chest expansion
- Restriction of lumbar spine movement in all directions
- Reduced lateral flexion
- Reduced forward flexion – Schöber's test - a line is drawn 10
cm above and 5 cm below the dimples of Venus. The
distance between the two lines should increase by more
than 5 cm when the patient bends as far forward as possible
Extraarticular manifestations:
- Skin: psoriasis may coexist
- Ocular: Anterior Uveitis (usually unilateral and recurrent)
- GI: asymptomatic intestinal ulcerations
- GU: Urethritis (rare)
- Cardiovascular: Aortic insufficiency, Aortitis, CAD, AV block
- Respiratory: restrictive lung disease (typically upper lobe)
- Heel pain (due to plantar fasciitis)
- Enthesis (Achilles tendonitis)

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Diagnosis:
- ESR – high, RF - absent
- Lumber X-Ray:
o Maybe normal early in the disease
o Sacroiliitis: subchondral erosions and sclerosis.
o Square vertebrae with tramline appearance
o Bamboo spine: a late finding with a fusion of
vertebrae
- Lumbar MRI (most accurate)
Treatment:
- NSAIDs
- Regular exercise
- Anti-TNF drugs (etanercept, adalimumab, or infliximab)

Reactive arthritis (Reiter's syndrome)

- Reactive arthritis is caused when a joint reacts to an
infection elsewhere in the body.
- May develop days or weeks after GI or GU infection with
Salmonella, Shigella, Campylobacter, Chlamydia, or
Ureaplasma urealyticum
- Male to female ratio is 20:1
- Associated with HLD B27 (70%)
Symptoms:
- Conjunctivitis 50%
- Urethritis
- Arthritis (Knee and ankle is the commonest sites)
- Keratoderma blennorrhagica 10% (psoriasiform rash on sole
and feet)
- Circinate balanitis (psoriasiform rash on the penis)
- Systemic features: Fever, weight loss, Carditis, Aortic
regurgitation
Diagnosis: Only clinical diagnosis
Treatment:
- NSAIDs
- Tetracycline for 3 months (if urethritis present)
- Sulfasalazine, if no response to NSAID and tetracycline

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 Psoriatic arthritis
- Patients with psoriasis or a family history of psoriasis
- Sometimes there will be no history of psoriasis or a small spot
of psoriasis present on the scalp, gluteal cleft, or umbilicus
Symptoms:
- Arthritis
- Usually, in distal interphalangeal joints
- May precede rash by 10 years
- Extra-articular symptoms:
o Psoriasis of the skin (not always present, or maybe
small and un-noticeable during examination)
o Nail pitting
o Sausage digits
o Eyes: Iritis
Diagnosis:
- RA negative
- ESR: mild elevation
- X-ray of DIP joints involved shows pencil in a cup deformity
Treatment:
- NSAIDs
- Methotrexate (if severe disease not responsive to NSAIDs)
- Anti-TNF drugs (etanercept, adalimumab, or infliximab)

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 Osteoarthritis (OA)
- Chronic slowly progressive erosive damage of the joint
surfaces, leading to loss of articular cartilage and pain
minimal or absence of inflammation
- OA is the most common form of arthritis
- OA is the most common cause of disability in patients over
age 65 years
- The most common affected joints are (the first MCP joint,
interphalangeal joints, knee joint, and hip joint)
- In hands, distal interphalangeal joints (DIP) are more
affected than proximal (PIP)
Risk factors:
- Advanced age
- Female sex
- Obesity
- Joint injury and joint overuse
- Family history
Patterns:
- Nodal OA:
o DIP joints (Heberden's nodes)
o PIP joints (Bouchard's nodes)
- Non-Nodal OA: Less prominent in DIP joints
- Erosive OA:
o Destructive Subchondral erosion of PIP and DIP joints
o Radiographic erosions are seen
- OA of the knee: Associated with obesity and more common
in women

OA may follow infectious arthritis, avascular necrosis, or

inflammatory arthritis (such as gout, RA, or Pseudogout)

Pathogenesis:
- Cartilage loss
- Synovial membrane infiltrated with mononuclear cells
- Osteophytes formation
- Subchondral bone thickening and cyst formation

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Clinical features:
- Joint pain:
o Worse in the evening, relieved by rest
o Progressive with time
o Associated with morning stiffness (less than ½ hour)
- Disability:
o Muscle wasting
o Limited range of motion
- Joint swelling (effusion), crepitus, and deformity
- The chronic effusion may lead to the formation of a Baker
cyst
Diagnosis:
- X-Ray (narrow joint space, osteophytes formation, cyst
formation, and dense subchondral bone)
- CBC, ANA, RF, and ESR are normal
Treatment:
- Weight loss, moderate exercise, walking stick
- Analgesia:
o Paracetamol is the first line (≤ 3 g/day)
o NSAIDs second line (unless contraindicated)
o NSAIDs and paracetamol combination may be used
o Tramadol: used if paracetamol and NSAIDs are
ineffective or contraindicated
- Intraarticular steroid injection:
o Methylprednisolone or Triamcinolone
o Will be effective within days to weeks
o Can increase the risk of joint infection, subcutaneous
atrophy, and local skin pigmentation
o The use is limited to 3 monthly
- Intraarticular Hyaluronic acid injection:
o Analgesic effect for knee OA
- Joint replacement surgery (Total arthroplasty)

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 Neuropathic joint (Charcot joint)
- It is progressive destructive arthritis associated with loss of
pain sensation, proprioception, or both.
Associated disorders:
- Diabetes mellitus (the most common)
- Amyloidosis
- Tabes dorsalis (neurosyphilis affecting the spinal cord and
the peripheral nerves)
- Meningomyelocele
- Syringomyelia (a cyst or cavity in the spinal cord)
Pathogenesis:
- The joint is subjected to repeated traumas due to the loss of
protective mechanisms
- This will lead to progressive cartilage and bone damage
- The pathologic changes are similar to those found in severe
osteoarthritis
Clinical features:
- Usually starts at a single joint and then becomes apparent at
other joints
- Boney overgrowth and progressive enlargement of the
affected joints
- Joint instability, subluxation, and crepitus
Diagnosis:
- Clinical features of the disease and the associated disorders
- Typical radiologic findings:
o Changes of OA with joint space narrowing (initial)
o Arthrocentesis: Xanthochromic or bloody non-
inflammatory findings
Treatment:
- Cast for 2 – 3 months
- Treat the associated disorders (e.g., DM)
- Surgical management (for selected cases)

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 Infective arthritis
- Any kind of joint infection, also known as septic arthritis
- Most common site: knee and wrist joint
- In I.V drug users: spine and sacroiliac joint is more common
Cause:
- The most common organism is Staphylococcus aureus (40%)
- Others: (streptococci, E. coli, Pseudomonas)
- The most common cause of septic arthritis in a recently
placed artificial joint is Staphylococcus epidermidis.

- The risk of infection is directly proportional to the degree of

joint damage.
- Osteoarthritis has a slightly increased risk of septic arthritis
due to slight damage
- Rheumatoid arthritis has the highest risk of septic arthritis due
to severe joint damage

Source of infection:
- Hematologic spread (septic skin, endocarditis, UTI)
- Direct entry to joint (after trauma – penetrating wound)
Clinical features:
- Sudden onset
- Joint pain aggravated by movement
- Hotness, redness, and tenderness of affected joint
- Fever, fatigue, malaise
Diagnosis:
- CBC: leukocytosis
- Blood culture positive in 50%
- Joint aspiration with cytology and culture (best)
Treatment:
- Analgesia, Antibiotics, and joint drainage may be needed
- If prosthetic joint arthritis, remove the joint, treat with
antibiotics, and replace the joint after 6 – 8 weeks.
- Antibiotics treatment in septic arthritis:
o Flucloxacillin for 4 to 6 weeks
o If penicillin-allergic patients: use clindamycin
o If gonococcal arthritis: use cefotaxime or ceftriaxone
o If the infection is not responding to antibiotics:
perform repeated percutaneous aspiration

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 Intravenous antibiotics are used for 1-week until the swelling
subsides, and blood cultures become negative. This is followed
by a 1-month course of oral antibiotics.

Gonococcal arthritis:
- It is one of the common causes of septic arthritis in a
previously sexually active patient
- Blood cultures are 40% positive; culture may be positive
from genitalia, throat, and rectum
- The difference in presentation from septic arthritis;
Gonococcal arthritis will have polyarticular involvement,
tenosynovitis, and petechial rash.
- Treatment is achieved by ceftriaxone 1g IV for 2 days,
then ciprofloxacin 500mg PO BID for 7 days

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 Crystal-induced arthropathies
Gout (podagra)
- Gout is a disease of uric acid metabolism which leads to the
accumulation of sodium Urate crystals in (joints, soft tissues,
and urinary tract stones)
Causes:
- Overproduction of uric acid:
o Idiopathic
o Increased cell turnover (cancer, chemotherapy)
o Enzyme deficiency (Lesch-Nyhan syndrome,
glucagon storage disease)
- Under-secretion of uric acid:
o Renal insufficiency
o Ketoacidosis or lactic acidosis
o Drugs: (thiazide, aspirin)
Clinical features:
- Joint involvement (most common site: 1st Metatarso-
phalangeal joint)
- Hotness, redness, and tenderness associated with severe
pain
- Tophi: characteristic skin lesion in gout
- Urate stones and renal colic

Precipitants of Gout include:

- Diuretics (e.g., thiazide)
- Alcohol
- Diet rich in meat and seafood
- Recent surgery or trauma

Diagnosis:
- Synovial fluid aspiration:
o Negative birefringent needle shape Urate crystals
o High leukocyte count (predominantly neutrophils)
- Serum uric acid:
o Elevated in 95% of cases
o The normal uric acid level does not exclude Gout
- Joint X-Ray: Shows punched-out erosions

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Treatment:
- Lifestyle modifications:
o Adequate hydration
o Limit alcohol intake (especially in the acute attack)
o Weight loss (for obese patients)
o Proper diet (decrease high purine diets such as meat
and seafood)
o High vitamin C intake can reduce the serum uric acid
- Between attacks:
o Allopurinol (the first line)
o Febuxostat (the second line)
- Additional measures:
o Losartan is the drug of choice for HTN in the presence
of gout
o Always stop thiazide diuretic
- In acute presentation:
o NSAIDs (better than colchicine) – the first line
o Colchicine (if NSAIDs or steroids cannot be used)
o Corticosteroids (if no NSAIDs are ineffective or
contraindicated)
o If the patient is taking allopurinol, do not stop it.

The indications for uric acid lowering agents:

- 2 or more attacks in the past year
- The presence of tophi
- Renal disease
- Uric acid renal stones
- Patients on diuretics

Instructions about Allopurinol according to recent guidelines:

- In the case of acute gouty arthritis, if the patient is
already on allopurinol, do not stop it. However, if the
patient is not on allopurinol, start it 2 weeks after the
acute attack.
- Colchicine cover should be considered when starting
allopurinol (may be continued for 6 months)

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 Pseudogout
- Also known as calcium pyruvate deposition disease
- Unknown cause but may be associated with
hemochromatosis, hyperparathyroidism, hypothyroidism,
and true gout.
Clinical features:
- Acute synovitis (hotness, redness, tenderness, pain, swelling)
- Chronic arthritis (pain + morning stiffness + functional
impairment)
- The knee joint is the most common site
- DIP and PIP are not affected
Diagnosis:
- Serum calcium and uric acid is normal
- Synovial fluid aspiration:
o Positive birefringent cuboidal calcium pyrophosphate
crystals
o Bloodstained or turbid aspirated fluid
- Joint X-Ray shows Chondrocalcinosis
Treatment:
- NSAIDs (best initial treatment)
- Intraarticular steroid (if NSAIDs resistant)
- Joint aspiration to relieve swelling and pain
- Colchicine for prophylaxis

Figure 45: Joint X-Ray shows Chondrocalcinosis

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 Vasculitis
- It is an inflammation of the vessel wall
- All types of vasculitides can cause: (fever, fatigue, weight
loss, arthralgia, and myalgia)
Classification:
- Large vessel:
o Giant cell arteritis (Temporal arteritis)
o Takayasu's arteritis
- Medium vessels:
o Polyarteritis nodosa (PAN)
o Kawasaki's arteritis
- Small vessels:
o Microscopic polyangiitis
o Granulomatosis with polyangiitis (Wegener's)
o Churg-Strauss syndrome
o Henoch Schönlein purpura
o Essential cryoglobulinemia
o Polyarteritis nodosa (PAN)

Polyarteritis nodosa (PAN)

- Vasculitis affecting small and medium-sized arteries
- More in males than females
- Chronic hepatitis B and C are associated with PAN
- The most common cause of death is Myocardial infarction.
Clinical features:
- Fever, malaise, arthralgia, weight loss, hypertension
- Hematuria, renal failure (need biopsy for diagnosis)
- Neurological:
o The peroneal nerve is the most commonly involved
leading to a drop foot
o Mononeuritis multiplex
o Sensorimotor polyneuropathy
- GI: Postprandial angina, GI bleeding
- Skin:
o Lower extremity ulcers (most common skin symptoms)
o Livedo reticularis, purpura, nodules.

- No lung involvement in PAN

- Test all patients with PAN for hepatitis B and C

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Diagnosis:
- pANCA (less than 20%)
- Hepatitis B serology positive in 30% of patients
- Biopsy of the affected organ shows fibrinoid necrosis of the
vessel wall (the most accurate)
- Angiography: multiple aneurysms, bleeding
Treatment:
- Antiviral in Hepatitis B related type
- Steroids with azathioprine or cyclophosphamide

Polymyalgia Rheumatica (PMR)

- Usually, occur in those over 50 years of age
- Strongly associated with giant cell arteritis
Clinical features:
- Systemic features: fever, malaise, weight loss
- Sudden onset of severe pain and stiffness in shoulder, neck,
and pelvic girdle muscles
Diagnosis:
- ESR: markedly elevated
- Normocytic anemia
- CPK is not elevated (no muscle destruction)
- Temporal artery biopsy: Giant cell arteritis
Treatment: Steroid (rapid response, even at a low dose)

Giant cell arteritis (temporal arteritis)

- This disease seems to be on a spectrum of PMR.
Clinical features:
- Severe headache and scalp tenderness
- Jaw claudication may be present: progressive jaw pain on
mastication
- May present with sudden painless vision loss (maybe
permanent or temporary)
- Symptoms in other arteries: (decreased arm pulse, aortic
regurgitation)

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Diagnosis:
- ESR very high
- CRP: high
- Temporal artery biopsy (most accurate test): it will be false
negative after 36 hours of steroid therapy
Treatment: High dose steroid (do not wait for biopsy)

Normal ESR is less than (Age in years/2) (+ 5 for females)

Causes of markedly elevated ESR (> 100 mm/hour)

- Subacute bacterial endocarditis
- Tuberculosis
- Giant cell arteritis, PMR
- SLE, RA
- Leukemia and Lymphoma
- Multiple Myeloma
Causes of markedly low ESR (0 mm/hour)
- Afibrinogenemia
- Agammaglobulinemia
- Extreme polycythemia (HCT > 65%)
- Increased plasma viscosity
Table 129: causes of markedly elevated or markedly low ESR

Behcet's syndrome
Vasculitis of unknown cause that involves venules, associated with
HLA B5
Clinical features:
- Oral ulcers, Genital ulcers, inflammatory arthritis
- Skin: Erythema nodosum, acne
- Eye: Anterior uveitis, retinal Vasculitis, iritis
- Neurological: aseptic meningitis
- Superior vena cava obstruction may occur (venous
involvement)
Diagnosis: Positive pathergy test is suggestive (puncture site
following needle prick becomes inflamed with small pustule
forming)
Treatment:
- Oral ulcer: topical steroid
- Erythema nodosum: colchicine
- Systemic symptoms: steroid or immunosuppressive therapy

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 Takayasu's arteritis
- Usually, effect large elastic arteries like the aorta and its
branches
- Usually present with general features of vasculitis followed by
asymmetrical limb pulse
- Diagnosis: ESR: high, Leukocytosis, Aortography, MRA
Treatment:
- Steroid
- Surgical (bypassing stenosis or aneurismal site)

Dermatomyositis
- An inflammatory disorder causing symmetrical, proximal
muscle weakness and characteristic skin lesions
- Associated with cancers in 20% of cases (ovarian, lung, GI,
or lymphoma)
- No facial or ocular muscle involvement
Clinical features:
- Symmetrical proximal muscle weakness
- Photosensitivity (Malar involvement)
- Photo distributed poikiloderma:
o Shawl sign: erythema of the back and shoulders
o V sign: neck and back or the neck and upper chest
o Holser sign: along the lateral thigh
- Heliotrope rash: edematous and purplish eyelids
- Mechanic’s hand: palmer fishering and hyperkeratosis
- Gottron's papules: scaly patches at PIP and MCP joints
Diagnosis:
- High CPK
- Antibodies: ANA positive (60%), Anti-Mi-2 (25%)
- EMG
- Muscle biopsy (best)
Treatment: Prednisolone, IVIG, Mycophenolate

Polymyositis:
- A variant of Dermatomyositis where skin manifestations are
NOT prominent
- Anti-Jo-1 antibodies are more common in Polymyositis
than in dermatomyositis

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 Fibromyalgia
- The cause of fibromyalgia is unknown
- The female to male ratio is 9:1
- It may be associated with RA, SLE, or Sjögren’s syndrome
- Fibromyalgia has an unexplained decrease in opioid
receptors, so it has a poor response to opioid analgesia
Clinical features:
- Chronic pain: generalized pain or pain at multiple sites
(neck, shoulders, back, hip, etc.)
- Stiffness, numbness, fatigue, and sleep disorders
- It is often associated with somatic conditions such as
headaches, TMJ, or pelvic pain.
Treatment:
- Aerobic exercise (the best for functional improvement)
- Cognitive therapy
- Medications:
o Anticonvulsant (Pregabalin)
o Dual serotonin-norepinephrine reuptake inhibitor
(Duloxetine, Milnacipran)
o SSRI and TCA may be used

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 Neurology
CHAPTER 9

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Introduction to neurology
The central nervous system (CNS) is formed of two main parts:
- Intracranial part (cerebrum, brain stem, cerebellum)
- Spinal part (spinal cord, cauda equina)
Cerebrum:
- Formed of two hemispheres connected via corpus
callosum and the upper part of the brain stem
- It is divided into 4 lobes (frontal, parietal, temporal, and
occipital lobes)
- Formed of outer gray matter and inner white matter
- At the base of each cerebral hemisphere, there are
several groups of nuclei at different levels within the
white matter; they form the basal ganglia (thalamus,
subthalamus, and hypothalamus)
Brain stem:
- Formed of midbrain, pons, and medulla
- Connected to the cerebrum and cerebellum by
peduncles
- The motor nuclei of the cranial nerves in the brain stem
are arranged as the following:
o Cranial nerves III, IV: midbrain
o Cranial nerves V, VI, VII: pons
o Cranial nerve IX, X, XI, XII: medulla
o Cranial nerves I, II, VIII: sensory nerves perceived in
special areas in the cerebral cortex
Cerebellum:
- Occupies the most posterior cranial fossa
- Concerned with coordination, voluntary motor activity,
and equilibrium
Spinal cord:
- Lies in the spinal canal
- The lowermost 3 segments spinal cord in S3, 4, 5 are called
conus medullaris
- The above 4 segments, L5,4 and S1,2, are called Epiconus
- Formed of outer white matter and inner gray matter
- The Gray matter has an H shape (2 anterior and 2
posterior horns)
Cauda equina:
- A collection of lumbosacral roots
- Filling the spinal canal below the level of L1

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 Cranial nerves
- The cranial nerves are a set of 12 paired nerves that arise
directly from the brain

They are as following:

Nerve General information
CN I - Name: Olfactory nerve (Sensory)
- Function: smelling, if impaired, no smell and taste
CN II - Name: Optic nerve (Sensory)
- Function: The nerve of vision
- If impaired, visual field defect will present
CN III - Name: Oculomotor nerve (Motor)
- Function: The nerve of eye movement
- 3rd nerve palsy will result in outward downward
deviation of the eye associated with ptosis
CN IV - Name: Trochlear nerve (motor)
- Function: Innervates single muscle (superior
oblique muscle of the eye)
- Comes from the posterior side of the midbrain
- The greatest intracranial length
- It is the smallest nerve, least number of axons
CN V - Name: Trigeminal nerve (Mixed)
- Function: face sensation, biting, and mastication
- It has 3 divisions (Ophthalmic, Maxillary, and
Mandibular)
CN VI - Name: Abducent nerve (Motor)
- Function: Abduction movement of the eyes
- If impaired, horizontal diplopia, inward deviation
(esotropia)
CN VII - Name: Facial nerve (Mixed motor and sensory)
- Function: Controls the muscles of facial expression
and functions in the conveyance of taste
sensations from the anterior two-thirds of the
tongue
- If impaired, Bell's palsy will develop (weakness of
facial muscles)
CN VIII - Name: Vestibulocochlear nerve
- Function: Transmits sound and equilibrium
(balance) information from the inner ear to the
brain

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CN IX - Name: Glossopharyngeal nerve (mixed)
- Function: Provides motor, parasympathetic and
sensory information to your mouth and throat.
CN X - Name: Vagus nerve (autonomic)
- Function: Parasympathetic control of the heart,
lungs, and digestive tract.
- The longest nerve of the autonomic nervous
system in the human body
CN XI - Name: Accessory nerve (Motor)
- Function: Supplies the sternocleidomastoid and
trapezius muscles.
CN XII - Name: Hypoglossal nerve (motor)
- Function: Innervates all the extrinsic and intrinsic
muscles of the tongue
Table 130: the cranial nerves

7th nerve palsy (Bell's palsy)

- Most are idiopathic, but Lyme disease, viral infection,
sarcoidosis, and tumors may be a cause
Clinical features:
- Paralysis of the entire side of the face (upper and lower
parts)
- Difficulty closing eyes, absent wrinkles on the same side of
the forehead
- Hyperacusis: loud sound (7th nerve supplies stapedius muscle
which acts like shock disturber)
- Taste disturbances (7th nerve supply sensation of taste)
Diagnosis:
- No need for special testing (only clinical diagnosis) but EMG
and NCS are the most accurate
Treatment:
- 60% recover fully without treatment
- The best initial therapy is prednisolone
- Artificial tears to protect the affected eye
- Physiotherapy

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 Aphasia
Speech centers are located on the left side of the brain (90%); they
include:
- Wernicke's area (sensory): left temporal area is responsible
for understanding; this area forms the speech before
sending it to Broca's area
- Broca's area (motor): left frontal lobe is responsible for the
expression
- Arcuate fasciculus: the connection between Wernicke's and
Broca's area

Note: The speech center is located on the left side of

the brain in right-handed persons and on the right
side of the brain in left-handed persons.

Types of aphasia:
- Wernicke's (receptive) aphasia: Lesions result in sentences
that make no sense and word substitution, but speech
remains fluent
- Broca's (expressive) aphasia: Speech is non-fluent and
labored
- Conduction aphasia: Speech is fluent, but repetition is poor.
Aware of the errors they are making
- Global aphasia: Large lesion affecting all 3 of the above
areas resulting in severe expressive and receptive aphasia

Horner's syndrome
- Classically, presented with Ptosis, Miosis, anhidrosis, and
Enophthalmos
- Cased by interruption of sympathetic nerve supply to the
eye
- Maybe due to an apical (Pancoast) tumor of the lung

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 Neurological terms to know
- Upper motor neuron lesion: is an injury to motor tract above
the anterior horn (or above the nucleus for cranial nerves)
- A lower motor neuron lesion: is an injury to motor tract below
the anterior horn (or below the nucleus for cranial nerves)
- Muscle tone: a spontaneous local tendon stretch reflex
o Hypotonia (also known as flaccidity): decreased
muscle tone (LMNL)
o Hypertonia (also known as spasticity): increased
muscle tone (UMNL)
- Tendon jerk (deep reflex): induced local axon stretch reflex
by tapping the tendon.
o Hyporeflexia: weak or decreased deep tendon reflex
(LMNL)
o Hyperreflexia: exaggerated deep tendon reflex
(UMNL)
- Clonus: rhythmic contractions induced by a sudden
sustained stretch of muscle-tendon
- Babinski reflex: upward deviation of toes when scratching
the dole of foot called positive Babinski, it is a feature of
UMNL

UMNL LMNL
Hypertonia without Hypotonia with muscle wasting
wasting
Hyperreflexia Hyporeflexia
Clonus may present No clonus
Planter reflex (Babinski) Planter flexion or no response
Table 131: UMNL vs. LMNL

Deep tendon reflex Nerve root

Ankle jerk S1,2
Knee jerk L3,4
Biceps and supinator jerk C5,6
Triceps jerk C7
Finger jerk C8
Table 132: types of deep tendon reflexes and their nerve roots

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 - Dysarthria: the difficulty of speech articulation, though the
formation of speech is intact
- Hemiplegia: paralysis of one side of the body
- Paraplegia: paralysis of both lower limbs,
- Quadriplegia: paralysis of all 4 limbs
- Ataxia: incoordination of voluntary motor movement in the
absence of motor weakness
- Chorea: involuntary static, irregular, dysrhythmic, sudden
jerky movement of any part of the body, including face,
trunk, or limbs

Thunderclap headache
- A thunderclap headache is a severe headache that
reaches its maximum intensity within 1 minute
Diagnosis Features
SAH Thunderclap headache, neck rigidity,
photophobia, vomiting, suspected berry
aneurysm.
Carotid artery Frontal thunderclap headache, with visual
dissection symptoms (amaurosis fugax, diplopia, Horner's
syndrome)
Vertebral artery Occipital thunderclap headache, nausea,
dissection vomiting, and brain stem findings (vertigo,
ataxia, diplopia, tinnitus, dysarthria)
Cerebral venous Sudden onset headache in a
thrombosis hypercoagulable patient
Table 133: Differential diagnosis of Thunderclap headache

Red flags for headache:

- First or worst headache
- Abrupt onset headache
- Progression or change in the pattern of headache
- Neurologic symptoms more than 1 hour
- Age < 5 or > 50 years
- New-onset in a patient with malignancy or coagulopathy
- Change in the level of consciousness
- Headache increased by exertion, sexual activity, or
Valsalva maneuver
Table 134: The red flags (alarm symptoms) of headache

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 Subarachnoid hemorrhage (SAH)
- The most common cause of thunderclap headache
- 85% are caused by ruptured saccular 'berry' aneurysm
- More common in women than men ≥ 40-year-old
[

Berry aneurysm is more frequent with:

- Polycystic kidney disease
- Tobacco smoking
- High alcohol consumption
- HTN
- Hyperlipidemia

Clinical features:
- Sudden severe "thunderclap" headache, usually occipital
- May present as a new headache during exertion
- Vomiting is a frequent symptom
- Irritability, with photophobia
- Neck rigidity
- Loss of consciousness
Diagnosis:
- CT scan (maybe negative)
- CSF examination 'LP':
o High opening pressure
o High protein
o High RBCs count > 10,000 *106 /L
o Xanthochromia: yellow discoloration of CSF due to
the presence of bilirubin (≥ 4 hours after onset of
headache)
- Cerebral angiography (Best)
Treatment:
- Control vital signs
- Nimodipine 30 – 60mg iv (to prevent vasospasm in the acute
phase)
- Endovascular insertion of coils or surgical clipping of the
aneurysm (to reduce recurrence)

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 Cerebral venous thrombosis
Cavernous sinus thrombosis:
- Presents after dental or sinus bacterial infection
- Sudden headache, proptosis, periorbital edema, and
ophthalmoplegia
- Treated with early antibiotics and surgical drainage
Other forms of cerebral venous thrombosis:
- Thunderclap headache in a patient who is hypercoagulable
- Signs of increased intracranial pressure
- The pain increases with Valsalva
- Focal findings like 6th cranial nerve palsy.
- Treated with LMWH and warfarin even in those with
hemorrhagic parenchymal lesions

Headache Syndromes
- Headache is one of the most common neurological
symptoms
Type of Characteristics
headache
Migraines Throbbing in character, Aura, photophobia, and
headache visual disturbances related to menses, associated
with nausea and vomiting, may be associated with
chocolate, wine, and cheese.
Cluster Frequent, short-duration, high-intensity headache,
headache associated with a red, tearing eye with rhinorrhea
Giant cell Jaw claudication, visual symptoms associated with
arteritis visual loss, tenderness at the temporal area with
very high ESR
Pseudotumor Associated with obesity, venous sinus thrombosis,
cerebri oral contraceptives, and vitamin A toxicity, mimic
(benign brain tumor with nausea and vomiting and visual
intracranial disturbances
HTN) Papilledema with diplopia from 6th CN palsy.
Tension-type It is the most common type
headache It is a diagnosis of exclusion
Table 135: Differential diagnosis of Headache syndromes

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 Migraines headache
- More common in females than males
- In women may be associated with menstruation
- Migraine can be precipitated by emotional stress, noises,
alcohol, caffeine, and oral contraceptive pills
Clinical features:
Recurrent, severe headache which is usually: (POUND)
- Pulsatile
- One day duration
- Unilateral
- Nausea and vomiting
- Disability

- Patients with more than 3 of the POUND criteria can be

diagnosed with migraine without additional testing
- Migraine with aura is a strong contributor to stroke
when combined with DM, HTN, and obesity

Acephalic migraine: the presence of migraine aura without

headache
Basilar migraine: with brainstem aura (vertigo, ataxia,
diplopia, tinnitus, dysarthria)
Hemiplegic migraine: migraine associated with a degree of
motor weakness
Status migrainous: migraine attack > 72 hours duration

Treatment:
- Simple analgesia (aspirin, paracetamol)
- Antiemetic (symptomatic treatment)
- Triptans (e.g., sumatriptan) 5-HT agonists
o Side effect: increased risk of ischemic events
o Contraindicated in both basilar and hemiplegic
migraine
- Prophylaxis:
o Beta-Blockers (e.g., Propranolol, Metoprolol, Timolol)
o Valproic acid
o Topiramate

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 Cluster headache
- More common in males than females
- One of the most painful types of headaches
Clinical features:
- Sudden unilateral severe pain around the eye that may
awake the patient from sleep
- It may be associated with conjunctival injection and tearing
- It may be associated with miosis and ptosis
- Timing of headache:
o Occur in cyclical patterns or clusters,
o Once or twice a day, each episode lasting 15
minutes to 2 hours
o Clusters last 4-12 weeks
Treatment:
- At the time of pain:
o 100% O2: the patient will respond within 15 minutes in
80% of cases
o Subcutaneous Triptans
- Prophylaxis: Verapamil

Tension-type headache
- The most common type of headache
Clinical features:
- Mild to moderate bilateral squeezing, dull, like pressure in
nature and non-throbbing
- Radiate forward from the occipital region
- Precipitated by a stressful event
Treatment:
- Rest, Pain killers (paracetamol, NSAIDs…)
- Antidepressants

Trigeminal neuralgia
- Unknown cause, but maybe due to compression at the fifth
cranial nerve root
- Unilateral lancinating facial pain in the 2nd and 3rd division of
trigeminal nerve territories, which may remit and relapse
over a year
- The pain may be precipitated by touching the face,
mastication, or even pronouncing certain words.

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Treatment:
- Carbamazepine (First line)
- Pregabalin, Gabapentin, Steroids (If the patient can't
tolerate Carbamazepine)
- Surgical (last resort): Decompression of the trigeminal nerve
root

Benign intracranial HTN (BIH)

- Also known as Pseudotumor cerebri, or idiopathic
intracranial HTN (IIH)
- There is an increase in intracranial pressure without
identifiable structural pathology
- 90% of affected patients are female
- Associated with obesity, venous sinus thrombosis, OCP use,
and vitamin A toxicity
Diagnosis:
- Throbbing headache worse in the morning, and with
Valsalva maneuver
- Papilledema (almost always present on examination)
- CSF opening pressure ≥ 250 mm H2O
- Brain MRI: shows small ventricles
Treatment:
- Weight loss
- Carbonic anhydrase inhibitors: Acetazolamide (first line),
Topiramate (add the benefit of weight loss)
- Repeated lumbar punctures
- Lumboperitoneal shunt (if failed medical treatment)

Post-herpetic neuralgia
- Shingles is associated with pain syndrome after resolution in
about 15% of the cases
- Since shingles can affect the head, this must be discussed in
the headache section, but it can occur at any dermatome
in the body.
- Acyclovir and famciclovir seem to reduce the incidence of
post-herpetic neuralgia
- Treatment: (Tricyclic antidepressants, Pregabalin,
Gabapentin, Carbamazepine, Phenytoin)

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 Acute stroke
- Acute stroke is a rapid appearance of a neurological deficit
of brain function due to the death of brain tissue
- The strongest risk factor is HTN
- Other Risk factors are the same as IHD (DM, obesity,
dyslipidemia, male sex, etc.)
Causes:
- Ischemic 85%
o Thrombosis (most common)
o Embolism: lodge in small perforating vessels "lacunar
infarction"
- Bleeding 15%

The source of embolism in CVA:

- Heart (e.g., AF)
- DVT (paradoxical embolus through PFO)
- Carotid stenosis

Presentation:
- Middle cerebral artery stroke:
o Weakness and sensory loss on the opposite side
o Loss of visual field on the opposite side of the stroke
(homonymous hemianopsia)
o Aphasia: speech center present on the left side in 90%
of cases
- Anterior cerebral artery stroke:
o Cognitive defect
o Urine incontinence
o Weakness in Leg more than arm
- Posterior cerebral artery stroke:
o Ipsilateral sensory loss of face
o Contralateral sensory loss of limbs
o Limb ataxia

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 If blockage of the blood vessel is reversed while neurons are still
viable (< 24 hours), this condition is called TIA, but if the blockage
is prolonged (> 24 hours), infarction and permanent damage with
resulting permanent symptoms can occur

Diagnosis:
- Clinically, neurological deficit, with signs of upper motor
neuron lesion
- Neuroimaging (CT, MRI): CT can exclude non-stroke lesions;
infarction takes up to 48 hours to show in the CT scan
- Evaluation for the cause: ECG, Holter monitor,
Echocardiogram, carotid doppler
Treatment:
- Ischemic stroke less than 3 – 4.5 hours since onset:
Thrombolysis (can increase the risk of hemorrhagic
transformation)
- Ischemic stroke more than 3 – 4.5 hours since onset: Aspirin
- If recurrent TIA's: Carotid endarterectomy and angioplasty
- Ischemic stroke in a patient already on aspirin: add
dipyridamole or switch to Clopidogrel
- Hemorrhagic stroke: control vital signs only (surgical drainage
will not help outside posterior fossa)
- Hospital admission for TIA is recommended for all patients
with an ABCD2 score of ≥3.

ABCD2 scoring system for TIA

Age ≥ 60 years 1 point
Blood pressure ≥ 140/90 1 point
Clinical features:
Focal weakness with TIA 2 points
Speech impairment without weakness 1 point
Duration:
≥ 60 minutes 2 point
10 – 59 minutes 1 point
DM present 1 point
Table 136: ABCD2 score for TIA patients

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 Epilepsy
- Seizure is a clinical syndrome caused by an abnormal
electrical discharge in the brain
- Epilepsy is a tendency to have a seizure; a single seizure is
not epilepsy, But an indication for investigations
- The recurrence rate after the first seizure is 70%
Types of seizures:
Focal seizures: (no loss of consciousness)
- Simple sensory: e.g., déjà vu
- Simple motor: e.g., Jacksonian march
- Complex: e.g., Automatism
Generalized seizure: (associated with loss of consciousness)
- Tonic-clonic (grand mal)
- Absence (petit mal)
- Tonic, Clonic, Myoclonic, and Atonic types.
Focal to generalized seizure: (starts as focal then becomes
generalized)
Secondary causes of seizures:
- Metabolic (Hypoglycemia, hypernatremia, hyponatremia,
hypocalcemia, hypomagnesemia, Uremia)
- CNS infection (Meningitis, encephalitis, abscess)
- Brain tumors, trauma, hypoxia, CVA, hemorrhage
- Toxic substances (alcohol, cocaine)
Clinical features:
Can varies according to the function of the affected area of the
brain
- Occipital onset: cause visual symptoms (lights, blobs of color)
- Temporal area onset: cause Déjà vu,
- Sensory strip involvement: tingling sensation, burning
sensation
- Motor strip involvement: jerking

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Diagnosis:
- Rule out secondary causes first
- Cerebral imaging (CT, MRI)
- Lab tests to rule out secondary causes (CBC, FBS, KFT, LFT,
electrolytes, CXR)
- EEG (if secondary cause excluded)
Treatment:
- Education of family and patient
- During convulsion:
o Place the patient in the left lateral position
o Do not insert anything in the mouth (tongue bite
unpreventable)
o Medications Lorazepam, Diazepam
o If prolonged, treat as status epilepticus
- For epilepsy control, Start treatment under the following
conditions:
o After 2 unprovoked attacks
o Single attack with focal finding in imaging or EEG
o Single attack after severe head trauma

AED Uses
Sodium valproate First-line in generalized epilepsy
Lamotrigine First-line in focal seizure
Carbamazepine A cost-effective option for focal seizure
Effective against tonic-clonic seizure
Not effective in absent and myoclonic
seizure
Levetiracetam Wells tolerated
Few side-effects
Safe in pregnancy
Ethosuximide First-line in absent seizure
Lamotrigine, They may be used in generalized and focal
levetiracetam, seizures
topiramate,
valproate,
zonisamide
Table 137: Antiepileptic drugs (AEDs) and their indications

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 Status Epilepticus
- Status epilepticus is a seizure not resolving spontaneously or
recurrent seizure without recovery of consciousness for > 5
minutes
- It can be due to a sub-therapeutic level of anti-epileptic
drugs in a patient known to have epilepsy or may be
precipitated by secondary causes like metabolic infection,
tumor, etc.
Treatment:
- ABC management (airway, breathing, circulation, blood
glucose check)
- Correct underlying cause if present
- Send lab tests (KFT, LFT, electrolytes)
Approach to treat status epilepticus:
- 1st line: Lorazepam/ Diazepam
- 2nd line: Phenytoin/ Fosphenytoin
- 3rd line: Phenobarbital
- 4th line: ICU transfer, intubation, ventilation with general
anesthesia

Essential tremor
- Essential tremor occurs in both rest and intention
- More common in hands, but the head may be affected
- It may affect some skills like handwriting
- Caffeine makes it worse, and alcohol makes it better
- The treatment of choice is propranolol

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 Dementia
Dementia: is a decline in memory or other thinking skills severe
enough to reduce a person's ability to perform everyday activities

Alzheimer's disease (AD)

- The most common cause of dementia
- Slowly progressive loss of memory in older patients > 65 years
old
Clinical features:
- Gradual memory impairment to new information
- Both short and long-term memories may be affected
- Depression and aphasia are common
Diagnosis:
- Diagnosis of exclusion
- All patients with memory disturbances should be tested for
(B12 level, Brain CT scan, and Thyroid function test)
Treatment: Donepezil, Rivastigmine, Galantamine

Normal-pressure hydrocephalus
- Also known as Hakim's syndrome
- Symptoms can be remembered as WWW "Wet, Weird,
Wobbly"
o Wet: urinary incontinence
o Weird: dementia
o Wobbly: wide-based gait/ ataxia
- Caused by an abnormal accumulation of CSF in the
ventricles of the brain
Diagnosis:
- CT and MRI to rule out mass lesions in the brain
- LP – shows normal pressure
Treatment: Ventriculoperitoneal shunt

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 Other diseases of dementia
Picks disease (frontotemporal dementia)
- Abnormal behavior and personality changes precede other
symptoms
- Memory loss
- No movement disorders
- Frontal and temporal lobe atrophy in brain imaging
- Treatment is the same as Alzheimer's disease

Creutzfeldt-Jakob disease (CJD)

- Rapidly progressive dementia and presence of myoclonus
- The patient is younger than Alzheimer's disease
- The most accurate test is a brain biopsy
- EEG and CSF analysis used in the diagnosis

Lewy body dementia

- Presence of parkinsonism plus dementia
- Presence of vividly detailed hallucinations

Huntington's disease/chorea
- Age affected: 30 – 50 years
- Family history is common
- CAG trinucleotide repeats on chromosome 4
- Presence of dementia + chorea + psychiatric disturbance
and personality changes
- Diagnosis: by genetic testing
- Treatment: tetrabenazine (for chorea) and antipsychotics

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 Parkinson's disease (PD)
- Loss of cells in the substantia nigra resulting in decreased
dopamine secretion
- A clinical syndrome of Bradykinesia + rigidity + tremor + loss
of postural reflexes
Causes:
- Idiopathic
- Repeated head trauma
- Drugs (e.g., Haloperidol, Lithium, TCA, Metoclopramide)
- Degenerative diseases (e.g., Alzheimer's disease)
- Encephalitis
- Wilson's disease, Huntington's disease
- Genetic condition
Symptoms:
- Resting tremor improved on catching any subject
- Bradykinesia (slow movement)
- Shuffling gait
- Depression, anxiety
- Cognitive impairment
- Rigidity (increased muscle tone)
- Hypomimia (limited facial expression)
- Micrographia (small handwriting)
Diagnosis:
- Clinical diagnosis
- CT Brain to rule out secondary causes
- If < 50 years, test for Wilson's and Huntington's disease
Treatment:
- Anticholinergics (benztropine) and amantadine for mild
cases
- Dopamine agonist (best initial therapy for severe
parkinsonism)
- Levodopa/Carbidopa (most effective)
- COMT inhibitor (tolcapone, entacapone) (used as add on
to levodopa/carbidopa, it blocks the metabolism of
dopamine)
- MAO-B inhibitors (selegiline, rasagiline) (single or as add on, it
blocks the metabolism of dopamine)
- Deep brain stimulation (electrical stimulation)

Lowy body dementia: parkinsonism + dementia

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 Alcoholic encephalopathies
Wernicke's encephalopathy
- Seen in alcoholism due to Thiamine (Vitamin B1) deficiency
- Symptoms precipitated by glucose infusion in a patient with
alcoholism (B1 is responsible for glucose metabolism)
Symptoms:
- Confusion
- Ataxia
- Ophthalmoplegia
- Memory impairment
Treatment:
- Thiamine injection
- Avoid glucose infusion before thiamine

Wernicke-Korsakoff disease
- History of chronic heavy alcohol use
- Caused by longstanding heavy drinking with an inadequate
diet
Clinical features:
- If Wernicke's encephalopathy is not treated, it could
progress to an irreversible deficit (Korsakoff syndrome).
- Severe short-term memory deficit
- Confabulation
Prevention is by proper treatment of Wernicke's encephalopathy
No treatment if Wernicke's Korsakoff develop

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Neurological autoimmune disorders
Multiple sclerosis (MS)
-It defined as an autoimmune demyelinating disease of the
CNS
- Cell-mediated autoimmune attack of myelin-producing
Oligodendrocyte of the CNS
- More common in white women living in cold climates
Common presentations:
- Visual symptoms (e.g., Optic neuritis, optic atrophy,
internuclear Ophthalmoplegia*)
- Sensory symptoms (numbness, trigeminal neuralgia,
Lhermitte's sign*)
- Motor symptoms (weakness – Most commonly in legs)
- Cerebral symptoms (ataxia, tremor)
- Urinary and sexual symptoms (incontinence, impotence)

- Lhermitte’s sign: an electrical sensation at the spine on

limbs on head flexion
- Internuclear ophthalmoplegia (INO): inability to
adduct one eye with nystagmus in the other eye.
- Corpus callosum lesion on MRI is pathognomonic for
MS because it is highly vascular, so strokes are unlikely.

Clinical courses (types):

- Relapsing-remitting course (80%) – Most common type
- Primary progressive course (10%)
- Secondary progressive disease
- Fulminant disease (leads to an early death)
Diagnosis:
- MRI – (periventricular demyelination)
- CSF – increased IgG
Treatment:
- Acute relapse: I.V Methylprednisolone for 3 – 5 days
- Disease-modifying drugs (e.g., Beta-interferon, Fingolimod)

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 Myasthenia gravis (MG)
- An Autoantibodies to Acetylcholine receptors in the
neuromuscular junction
- Usually, at 15-50 years, women are affected more than men
- 15% of patients have thymoma, and the majority of others
have thymus hyperplasia
- Penicillamine can trigger the antibody-mediated
myasthenic syndrome
Clinical features:
- Fatigue and weakness:
o Ocular: double vision
o Facial: difficulty chewing
o Limb muscles: weakness
- Symptoms worsen at the end of the day
- Respiratory muscle involvement (aspiration, pneumonia,
respiratory failure)
Diagnosis:
- Tensilon test: I.V anti-cholinesterase (Edrophonium) causes
improvement within 30 seconds up to 3 minutes
- EMG
- Autoantibodies: (anti-acetylcholine receptor antibodies >
80% of cases)
- Chest CT scan (to rule out thymoma, thymus hyperplasia)
Treatment:
- Long-acting anticholinesterase, e.g., pyridostigmine
- Immunosuppression: prednisolone initially
- Thymectomy
- Management of myasthenic crisis: (Plasmapheresis, IVIG)

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 Lambert-Eaton myasthenic syndrome
- Autoimmune response against voltage-gated calcium
channel in the peripheral nervous system affecting the
somatic and autonomic nervous system
- It is a type II hypersensitivity reaction
- Associated with small cell lung cancer (as a paraneoplastic
syndrome) or may present independently
Clinical features:
- Limb-girdle weakness (lower limbs first)
- Hyporeflexia (improved after sustained muscle contraction)
- Autonomic symptoms: (dry mouth, impotence)
Diagnosis: EMG
Treatment:
- Treatment of underlying cancer
- Immunosuppression (prednisolone and/or azathioprine)
- 3,4-diamino pyridine (increases the presynaptic Ca
concentration)
- IVIG and plasma exchange

Guillain-Barre Syndrome (GBS)

- Immune-mediated demyelination of the peripheral nervous
system
- Often triggered by an infection (classically Campylobacter
jejuni)
- Most common variation: Acute inflammatory demyelinating
polyneuropathy (AIDP)
- Rare variation: Miller Fisher syndrome (Ophthalmoplegia,
ataxia, and areflexia)
Clinical features:
- Paresthesia with pain precedes weakness in ascending
pattern
- The most common cause of death is respiratory failure
Diagnosis:
- Clinical feature of ascending paralysis preceded by
infection
- High CSF protein with normal cell count in CSF
- Nerve conduction study: delayed conduction

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Treatment:
- Monitoring of Respiratory function (patient may need
intubation)
- IVIG
- Plasma exchange
- Steroids have no benefits in GBS treatment.

Amyotrophic lateral sclerosis (ALS)

- It is a progressive degenerative disease that affects both
upper and lower motor neurons
- An autosomal dominant mutation in the copper-zinc
superoxide dismutase on chromosome 21
Clinical features:
- Progressive generalized weakness
- Dysphagia and nasal speech
- Neck weakness and head drop
- Frontotemporal dementia is a common late manifestation
- Signs of UMNL: hyperreflexia, spasticity, Babinski sign
- Signs of LMNL: muscle atrophy and fasciculations.

Eye muscles, bowel, and bladder functions are preserved in ALS

Diagnosis:
- EMG and NCS: both widespread UMN and LMN injuries that
do not fall in a nerve root distribution
- CSF analysis will be normal
- Cervical spine MRI to rule out nerve compression
Treatment:
- Riluzole: improves survival by 6 months
- Noninvasive positive pressure ventilation whenever FEV1 <
50% of predicted
- Percutaneous endoscopic gastrostomy (PEG) tube
placement for nutritional support

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 CNS infections
Meningitis
- It is the inflammation of meninges that presents with
headache, fever, and meningism
Causes:
Patient group Most common organism
The most common cause in general Viral meningitis
Age 0 -1 months Group B streptococci
Age 1 month – 6 years Neisseria meningitidis
Streptococcus pneumonia
Age 6 years to 60 years Neisseria meningitidis
Streptococcus pneumonia
Above the age of 60 years Streptococcus pneumonia
Neisseria meningitidis
Immunosuppressed patients Listeria monocytogenes
Post-traumatic meningitis Streptococcus pneumonia
Table 138: The most common causes of meningitis

Hydrocephalus is most commonly occurring as a complication

after H. influenza meningitis

Neisseria meningitidis (meningococcal meningitis):

- Look for a young patient with asplenia who present with
sudden high fever and signs of meningitis plus
characteristic rash (reddish or purplish rash)
- It is a rare but serious infection.
- It needs isolation, and prophylaxis for close contacts
(rifampicin, ciprofloxacin, or ceftriaxone)
- No need to give prophylaxis to nurses who take care of a
meningococcal patient, only persons with kissing or
another type of saliva-type contact need a prophylaxis
(e.g., who share cups, kissing)

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Clinical features:
- Headache and fever
- Neck stiffness
- Meningococcal meningitis cause rash, usually fatal
Signs of meningitis:
- Kernig’s sign: Severe stiffness of the hamstrings causes an
inability to straighten the leg when the hip is flexed to 90
degrees
- Brudzinski’s sign: hip and knee flexion if the neck is flexed
Diagnosis:
- Antibiotics should be started immediately, do not wait for
Culture results
- CSF analysis, CSF Culture (drain LP and then directly start
antibiotics)
- CBC, CRP, blood culture

Bacterial Viral TB
Appearance Cloudy Clear Slightly cloudy
Glucose Low (< 40 Normal (> 45 Low
mg/dl) mg/dl)
Protein High Normal/high High
WBC 10-5000/mm3 15-1000/mm3 10-1000/mm3
Polymorphs Lymphocytes lymphocytes
Table 139: CSF interpretation for meningitis patients

Treatment:
- Switch antibiotics according to culture results but do not
wait for culture without giving empiric therapy.

Age group Empirical therapy to start

0 – 3 months of age I.V cefotaxime and Amoxicillin
3 months – 50 years I.V cefotaxime
Above 50 years I.V cefotaxime and Amoxicillin
Pneumococcal or HiB I.V cefotaxime
Meningococcal meningitis I.V cefotaxime or Benzylpenicillin
For viral Meningitis Acyclovir
Table 140: Empirical antibiotic treatment in meningitis

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 Encephalitis
- Encephalitis is an acute inflammation of the brain due to
either a viral infection or an autoimmune process
- The most common cause is a herpes infection
Clinical features:
- The patient presents with headache and fever of acute
onset associated with confusion
- Photophobia and stiff neck may present
Diagnosis:
- Brain CT scan
- PCR of CSF (most accurate)
Treatment: Antiviral agent (acyclovir)

Organophosphate poisoning
- Organophosphate is a substance that is used widely in
insecticides; most of the war gases are organophosphates
as well
- The time from exposure to the onset of symptoms is 30 – 120
minutes
The mode of action:
Inhibits the enzyme acetylcholinesterase, leading to increased
acetylcholine activity at nicotinic and muscarinic receptors in the
CNS and skeletal muscles
The mode of intoxication:
- Ingestion: for suicide or accidentally
- Inhalation (when spraying crops)
- Dermal absorption

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 GI effects Respiratory Heart
Nausea, Dyspnea, cough Bradycardia
vomiting Bronchial Hypotension
Diarrhea secretion Heart block
Abdominal pain Wheezing
Hypersalivation Pulmonary edema
Respiratory arrest
Eyes CNS Nicotinic effect
Myosis Anxiety Muscle twitching
Blurry vision Restlessness Weakness
Tremor Fasciculations
Convulsions Respiratory Muscle
Confusion paralysis
Coma Ocular, limbs paralysis
Table 141: Systemic effects of Organophosphate poisoning

Diagnosis:
- Clinical history and physical examination
- Acetylcholinesterase activity is less than 50% of the normal
Treatment:
- Oxygen
- Gastric lavage (but never induce vomiting – risk of
aspiration)
- Wash the patient’s skin and remove all clothes (to avoid
dermal absorption)
- Atropine 2 mg iv q 15 min until symptoms controlled, then
0.02 – 0.08 mg/kg/hour infusion.
- Use diltiazem to protect the heart if the heart rate exceeds
130 bpm
- Pralidoxime 1 – 2 g infusion over 20 minutes (the antidote)
- Mechanical ventilation, if indicated

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 Common ENT conditions
Meniere disease
- It is an episodic attack of tinnitus, hearing loss, and vertigo
lasting for minutes to hours
- Due to endolymphatic overaccumulation (Endolymphatic
hydrops)
Treatment:
- Bed rest
- Antiemetics
- Antivertiginous drugs (betahistine, meclizine,
diphenhydramine) and anticholinergics (e.g., scopolamine)
- Surgery: Selective vestibular neurectomy or labyrinthectomy

Benign Paroxysmal Positional Vertigo (BPPV)

- It is a spinning sensation upon changes in the position of the
head.
- Each episode lasts less than 1 minute
Clinical features:
- Nausea and vomiting
- Vertigo—Spinning dizziness
o Paroxysmal (Sudden with a short duration)
o Positional: (Induced by a change in head position)
- Rotatory nystagmus
- Visual disturbance (difficulty reading or seeing during an
attack due to nystagmus)
Diagnosis:
- Clinical diagnosis (Dix–Hallpike test or the roll test, or both)
o Dix–Hallpike test:
▪ To assess the posterior semicircular canal.
▪ Lower your patient quickly to a supine position,
with the neck extended
▪ Nystagmus will start if the test is positive

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 o Roll test:
▪ To assess the horizontal semicircular canal
▪ Done while the patient is supine with their head
at 30° of cervical flexion.
▪ The examiner quickly rotates the head 90° to
the left side
▪ Vertigo and nystagmus will present if the roll
test is positive
Treatment:
- Repositioning maneuvers
o Epley maneuver
o Semont maneuver
o Roll maneuver
o Brandt–Daroff exercises
- Medications: Rarely needed
o Antihistamines (meclizine)
o Anticholinergics (butylbromide 'scopolamine')
o Betahistine

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 Infectious diseases
CHAPTER 10

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Principles of microbiology
- Bacteria are classified as aerobic and anaerobic types
- They are further classified according to their staining and
shape
Examples of anaerobic bacteria:
- Clostridia (C. difficile, C. tetani, C. botulinum)
- Spirochetes (Treponema, Pallidum)
- Bacteroides
Gram positive cocci:
- In chains: streptcocci
- In clusters: staphylococci
- In pairs: Enterococci
Gram positive bacilli:
- Large with spores: bacillus, clostridia
- Small pleomorphic: Corynebacterium, Propionibacterium
- Filamentous, beaded: Aocardia Actinomyces.
- Other: Listeria, Lactobacillus
Gram-negative cocci:
- Diplocicci: Neisseria gonorrhea, N. meningitides, Moraxella
catarrhalis
- Other: Acinetobacter
Gram negative bacilli:
- Enterobacteriaceae: E. coli, Klebsiella, Enterobacter,
- Others: Haemophilus, Proteus, Salmonella, Shigella, Yersinia,
Pseudomonas.
Acid-fast bacteria: (Ziehl-neelson stain)
- Mycobacteria
- Nocardia (weakly acid-fast)

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 Pyrexia of unknown origin (PUO)
PUO is defined as a fever of 38oC degree or above for 3 weeks, but
no explanation is found despite investigations by a physician.
Causes:
- Infection (bacterial, viral, fungal, parasitic)
- Malignancy (leukemia, lymphoma, MM, solid tumors)
- Connective tissue disease (SLE, Vasculitis, RA...)
- Others (IBD, pancreatitis, hemolytic anemia, sarcoidosis,
FMF)
Diagnosis:
- Full history and physical examination
- Lab tests:
o CBC, Blood Culture, Urine Culture, CSF, CSF Culture
o Serology (Autoantibodies, complement,
Immunoglobulins)
o Echocardiogram, Abdominal U/S
o CT/MRI of the chest, abdomen, pelvis, and brain
o Biopsy Lymph node, liver, Bone marrow, temporal
artery
Treatment:
- If the cause is obvious after investigations, treat the cause
- If the cause is still undetectable, use broad-spectrum
antibiotics and supportive treatment.

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 Bacterial infections
Brucellosis
- Brucella is a bacterial zoonosis transmitted directly or
indirectly from animals to humans.
- It may be transmitted by ingestion of raw milk from infected
animals
- It is also known as undulant fever or Malta fever
- It is caused by the Brucella organism (G-negative
coccobacilli)
- The incubation period varies from 1 week to several months
Species and sources:
Brucella type The main sources Notes
B. melitensis Sheep, goats, and Most common
camels Most aggressive
B. abortus Cattle or buffalo It tends to be chronic
B. suis Swine It causes abscess
B. canis Dogs Causes Acute GI symptoms
B. ceti Marine mammals (seals New species
B. pinnipedialis and dolphins)
Table 142: Species of brucella and their most common sources

Clinical Features:
- Fever of undulant pattern, night sweat, malaise
- Hepatosplenomegaly
- Sacroiliitis: spinal tenderness may be seen
Diagnosis:
- Isolation of brucellae from blood, CSF, bone marrow, joint
fluid, or a tissue aspirate or biopsy sample is definitive in
diagnosing brucellosis.
- Brucella antibody titer
- AST, ALT, bilirubin bay be elevated
- Peripheral leukocytes may be normal or low
- Mild anemia, thrombocytopenia, and DIC may manifest
- ESR and CRP are usually normal but may be elevated

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Treatment:
- Streptomycin 1g for 21 days + doxycycline 100 bid for 6
weeks
- An alternative regimen is doxycycline 100 mg bid +
Rifampicin 600 – 900 mg/d for 6-8 weeks.
Complications:
- Infective endocarditis (the most common cause of death)
- Osteomyelitis (usually vertebral)
- Others: Meningoencephalitis, orchitis, neuropathy.

Toxic shock syndrome (TSS)

- This condition results from staph aureus or group A
streptococcal infection associated with exotoxins released
- TSS is caused by bacterial exotoxins that act as
superantigens.
- In streptococcal toxic shock syndrome, the streptococcal
strains produce pyrogenic exotoxins A, B, or C
- In staphylococcal TSS, the staphylococcal strains may
produce TSST1 or staphylococcal enterotoxins B and C
Clinical features:
- Vomiting, diarrhea.
- Fever >38.9 °C (102.0 °F) and hypotension (SBP <90 mm Hg)
- Rash that later peels several days after the onset.
Diagnosis:
- Look for menstrual history and the tampon use
- Look for any abscess, nasal packing, or any gauze packed
in the wound
Treatment:
- Identify and remove the source of infection
- Intravenous fluid
- Broad-spectrum antibiotics
- IVIG may be helpful

- Staphylococci are a normal commensal in human skin

and anterior nares
- A generation of bacteria resistant to methicillin is called
Methicillin-Resistant Staph. aureus (MRSA); the drug of
choice is vancomycin
- For Vancomycin-Resistant staph aureus (VRSA), the drug
of choice is Daptomycin

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 Sepsis
- Sepsis is a systemic inflammatory response to microbial
invasion
Causes:
- Gram-negative bacilli (Most common cause)
- Others: Gram-positive cocci, Viruses, Fungi, Parasites
Clinical features:
- Fever, chills, hypothermia, hypotension, oliguria,
hyperventilation, Skin rash
- Mental status changes
- Focal signs that localize the site of infection
- Features of complications:
o ARDS
o Renal failure
o DIC
o Hyperglycemia (common in DM patients)
o Hypoglycemia (common in non-DM patients)
Diagnosis:
- CBC, KFT, LFT, Electrolytes
- Chest X-Ray, ABGs
- Blood Culture, Urine analysis, and Culture, CSF analysis, and
Culture
- Abdominal U/S
Treatment:
- Empirical broad-spectrum antibiotics then switch according
to culture results
- Treatment the cause
- Supportive treatment (Fluid, Inotropes, electrolyte
maintenance, Blood sugar control, etc.)
- Treatment of complications

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 Lyme disease
- Caused by bacteria Borrelia burgdorferi
- Transmitted to humans via infected tick bite of (Ixodes)
Clinical features: There are three stages:
- Stage 1 (early localized disease): a skin reaction around the
site of the tick bite "Erythema migrans", associated with
fever, headache, and regional lymphadenopathy.
- Stage 2 (early disseminated disease): hematologic and
lymphatic dissemination, fever, malaise, arthralgia, and
metastatic areas of erythema migrans, Other complications
(meningitis, cranial nerve palsy, Peripheral neuropathy,
carditis, heart block)
- Stage 3 (late disease): arthritis (large joints), polyneuritis, and
encephalopathy

Figure 46: Erythema migrans in Lyme disease

Diagnosis:
- Clinical diagnosis is important with a history of travel to
specific areas
- Anti-Borrelia antibodies (more sensitive in late-stage)
Treatment: Doxycycline or Amoxicillin for 14 days

15% will develop Jarisch–Herxheimer reaction: a reaction

to the endotoxin-like products due to bacterial death by
antibiotics, symptoms resemble bacterial sepsis.

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 Tetanus
- Clostridium tetani is a gram-positive spore-forming
anaerobic bacteria
- It is excreted by animal feces to contaminate soil, dust,
water, and wounds, including the umbilical stump.
Vaccination site... etc.
- After contamination, the spores germinate and proliferate
locally and produce 2 toxins (tetanospasmin and
tetanolysin) which travel along the nerve trunks and
bloodstream to CNS and redistribute to the spinal cord,
brain, and motor system
- The Incubation period is 1-14 days, and maybe longer
Clinical features:
- Mild Tetanus: pain and stiffness at the site of injury for a few
weeks (mortality < 1%)
- Generalized tetanus: spasm occurs in descending form with
intact consciousness
o Trismus: difficult mouth opening (masseter muscle
spasm)
o Risus sardonicus: (facial spasm and grimacing face)
o Laryngeal spasm: (stridor, suffocation)
o Opisthotonus: (arched back)
o Tonic seizure
- Cephalic tetanus:
o Follow head injury or otitis media
o Short incubation period with high mortality
o Cranial nerve palsy
- Tetanus neonatorum:
o Infantile form, generalized tetanus
o 3-12 weeks after birth
o Umbilicus stump may appear dirty and contaminated
o Paralysis
o Spasms and stiffness precipitated by touch

The most common cause of death is respiratory failure

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Treatment and prevention:
- DTaP immunization at 2,4,6,18 months, and then at 4 years of
age
- At the time of injury:
o Surgical management of wound (better to be left
open)
o Tetanus immunoglobulin or tetanus antitoxin (toxoid)
for contaminated wounds

Type of Completed vaccination Incomplete vaccination

wound (3 or more doses) (< 3 doses)
< 5 yr 5 – 10 yr > 10 yr
Clean None None 1-dose TV Complete TV vaccination
Non-clean None 1-dose TV 1-dose TV Complete TV vaccination
Tetanus immunoglobulin
Table 143: WHO recommendations for tetanus vaccine (TV) and tetanus
immunoglobulin administration

Typhoid fever (Enteric fever)

Organism: salmonella typhi and paratyphi (A, B, C), gram-negative
bacilli
- Humans are only reservoirs
- Route: oral-fecal transmission
- Bacteria proliferate in Peyer's patches in the small intestine,
then cause primary bacteremia and redistribute to the
reticuloendothelial system.
Clinical features:
- Prodromal '1st week':
o Headache, anorexia, fever, coated tongue, sore
throat, relative bradycardia, abdominal pain, and
constipation.
- 2nd week:
o Higher fever
o Tachycardia (due to Myocarditis)
o Diffuse abdominal pain with splenomegaly and
maybe hepatomegaly
o Rose spots (erythematous Maculopapular rash on
lower chest and abdomen) last 7-12 days

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 - 3rd week – stage of complications:
o Intestinal hemorrhage
o Encephalitis
- 4th week: Gradual improvement and decline of fever
Diagnosis:
- CBC: anemia and leucopenia (due to toxic depression on
bone marrow)
- Positive blood culture (40 – 60 % in the 1st week)
- In the 2nd week:
o Positive stool culture
o Positive Widal test (not specific)
- In the 3rd week: Urine culture
- PCR
- Bone marrow cells culture (if affected)
Treatment:
- Bed-rest, light diet
- Symptomatic treatment
- Antibiotics: ceftriaxone or Ciprofloxacin with Azithromycin 5 –
7 days

- Every 1 °C rise in temperature is expected to increase the

heart rate by 15 – 20 beats per minute.
- Faget’s sign (relative bradycardia) is a condition in which
the patients have a lower heart rate than might be
expected for a given body temperature
- The causes of Foget’s sign are:
o Salmonella typhi
o Brucella
o Legionella pneumophila
o Mycoplasma pneumoniae
o Corynebacterium diphtheriae
o Plasmodium species
o Drug fever
o CNS lesions
o Malignant lymphoma

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 Viral infections
Herpes simplex virus (HSV)
Organism: Herpesvirus type 1 and type 2
Clinical features:
- Can be a primary or recurrent infection
- Primary: ulcerative stomatitis, Keratitis, Finger infection,
Vulvovaginitis, Balanitis, encephalitis
- Recurrent infection: commonest at Lips (herpes labialis) or
genital lesions
Treatment:
- No need for treatment in mild infection
- If severe: Acyclovir oral, IV, eye drops
Herpes labialis can be activated in case of
pneumococcal infection

Shingles
- Organism: Varicella-zoster virus
- Primary infection: chickenpox (will be discussed in
pediatrics)
o Fever, pruritus, rash of different stages, history of
contact
o Treatment: symptomatic only
- Secondary infection: shingles
o This virus may become latent after primary infection,
then later in adulthood, will reactivate and present
with (Shingles)
o Present with severe burning pain at a specific
dermatome site with a vesicular rash that does not
cross the Medline of the body
o Shingles is not contagious
o It may be followed by neuropathic pain after
resolution (Gabapentin or Pregabalin is the drug of
choice for neuropathic pain)
o Treatment: Analgesia and antiviral (acyclovir,
valacyclovir, Famciclovir)

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 Infectious mononucleosis (Glandular fever)
- Organism: EBV (DNA virus)
- The virus spreads via infected droplets but is rarely blood-
borne (It is also known as Kissing disease)
- Incubation period: 30-50 days
Clinical features:
- Sore throat, Fever, Fatigue, Vomiting
- Lymphadenopathy (most commonly cervical)
- Splenomegaly (rapidly occurring, tender, risk of splenic
rupture)
- Hepatitis
- Myocarditis may occur

If ampicillin or amoxicillin is given, a diffuse rash will develop.

EBV is an oncogenic virus incriminated in:
- Nasopharyngeal carcinoma
- Burkitt's lymphoma

Diagnosis:
- Blood smear (lymphocytosis with atypical lymphocytes)
- Heterophil antibody (Monospot test)
- Detection of EBV IgM (specific)
- 80-100% of patients have elevated liver enzymes
Treatment:
- Supportive only
- Avoid antibiotics
- Avoid contact sport for 2-3 weeks; risk of splenic rupture
- Steroids in selected cases (AIHA, low platelets, meningitis...)

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 Rabies
- It is a viral infection that can cause brain infection
- Rabies is a DNA rhabdovirus
- Most commonly transmitted by a dog bite then, the virus
travels up at nerve axons to CNS
- The incubation period is 1-2 months
Clinical features:
- Headache, fever
- Hydrophobia
- Hypersalivation
- Negri bodies (found in the cytoplasm of infected axons)
Treatment:
- Clean wound with soap and water
- Do NOT stitch the wound (it increases the risk of transmission
of the virus to the CNS)

- Anti-rabies serum:
o If the dog is dead, brain biopsy and give anti-rabies
serum if positive for the virus
o If the dog is live, put in quarantine; give anti-rabies
serum if the dog dies within 10 days for any reason
o If the dog is not reachable, give the anti-rabies serum

Anti-rabies serum is given in 6 doses at: (0, 3, 7, 14, 30 and 90 days)

Infiltrate human rabies immunoglobulin around the site of the bite

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 COVID-19
- Coronavirus disease 19 is a disease caused by the beta
Coronavirus (SARS-CoV-2 virus)
- It is a single-strand RNA virus
- The source of the virus in the first place was transmitted from
Bats to humans; then, the virus can be transmitted from
human to human
- Human-to-human transmission is by droplets
- Incubation period up to 2 – 14 days
Poor prognostic factors:
- Increasing age (> 40 – 50-year-old)
- Pre-existing comorbidities
- Males are more affected than females
Clinical features: (Mainly respiratory or GI infection)
- Some patients do not have symptoms (asymptomatic)
- Fever (the most common symptom)
- Cough (with or without sputum) (the 2nd most common)
- Shortness of breath
- Upper respiratory symptoms (sore through, runny nose)
- Gastrointestinal symptoms (Nausea, vomiting, diarrhea)
- Non-specific symptoms like fatigue, myalgia, malaise,
headache, confusion
Complications:
- Adult respiratory distress syndrome
- Respiratory failure
- Viremia and septic shock
- DIC
- Multiple organ failure
- Renal failure
Diagnosis:
- CBC (neutropenia, lymphopenia, thrombocytopenia)
- High AST and ALT level
- High LDH
- CXR: bilateral pulmonary infiltration
- Chest CT scan: bilateral ground-glass opacities, pulmonary
infiltrates, multilobar consolidation (the most sensitive)
- Real-time Polymerase chain reaction (RT-PCR) – detects the
viral RNA (the most accurate test)
Prevention:
- Routine vaccination according to the protocol
- All cases of COVID-19 need complete Isolation

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 - Avoid travel to a disease outbreak area
- Avoid crowded areas
- Careful handwashing with soap and water
- Wearing a surgical mask is not recommended for
nonhealthcare workers
Treatment:
- Oxygen therapy:
o SpO2 needs to be 90-96%.
o If SpO2 < 94%, nasal cannula with titration of O2 flow
o If still < 90 on nasal cannula at a flow rate of 15L/min,
switch to face mask
o A non-rebreathing mask is used if the patient is still
hypoxic despite the use of a face mask at a flow rate
of 15L/min
o Consider C-PAP or BiPAP for COPD patients
- Mild cases:
o Paracetamol for fever > 38 c
o Encouraging patients to drink fluids
- Moderate cases:
o Paracetamol
o Prophylactic dose LMWH
o Oral vitamin D (2000 IU daily)
- Severe cases:
o Dexamethasone 6mg daily IV for 10 days
o LMWH
o Favipiravir:
▪ 1600 mg twice for the first day
▪ Then 600 mg Twice daily for 14 – 10 day
o Tocilizumab if the following points are present:
▪ Evidence of hyperinflammatory state
▪ Pulmonary infiltrates on chest imaging

Signs of hyperinflammatory status: (at least 3 of the following)

- Fever > 38 c
- CRP > 100 mg/L
- IL6 > 60 pg/ml
- High Serum ferritin > 5X UNL
- High LDH

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 Sexually transmitted diseases
Syphilis
- Mainly sexually transmitted disease
- Transmitted by: sex, blood transfusion, vertical
(transplacental)
- Organism: the spirochete Treponema Pallidum, incubation
period: between 9-90 days
Clinical features: There are 3 stages of the disease
- Primary stage:
o Chancre - painless genital ulcer with indurated edges
o Local painless lymphadenopathy
- Secondary stage: (6-10 weeks)
o Systemic symptoms: fevers, lymphadenopathy
o Rash
o Alopecia areata
- Tertiary stage:
o Neurosyphilis:
▪ Vasculitis, stroke
▪ Memory and personality changes
▪ Tabes dorsalis (spinal cord degeneration)
o Aortitis:
▪ Ascending aortic aneurysms
▪ Aortic dissection
▪ Aortic regurgitation
o Gummas (skin & bone granulomatous lesions)
Diagnosis: serology test for syphilis
Treatment:
- For primary and secondary syphilis, a single penicillin
injection or oral doxycycline
- For tertiary syphilis, I.V penicillin

Jarisch- Herxheimer reaction:

The occurrence of fever and worsening of symptoms after
treatment of syphilis. It is managed by aspirin and antipyretics
only

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 Gonorrhea
- Sexually transmitted disease, by vaginal, anal, or oral sex
- Organism: Neisseria gonorrhea (gram-negative diplococci)
- Incubation period: 2-10 days
Clinical features:
- It may be asymptomatic (10% in men, 80% in women)
- In men: Mostly symptomatic
o Urethritis with urethral discharge
o Epididymo-orchitis may present
- In women: Mostly asymptomatic
o Urethral involvement
o Bartholin's gland/duct involvement
o Endocervical canal involvement
o Rectal involvement
o Acute pelvic inflammatory disease
Diagnosis:
- Mainly clinical
- Direct smear (Gram-negative diplococci)
Treatment: Ceftriaxone 500mg IM single dose

Chlamydia infection
- A bacterial infection that is transmitted similarly to gonorrhea
- Clinically also similar to gonorrhea
- In men: urethral symptoms are mild, and < 50% of cases
- In women:
o The most common sites are the cervix and urethra
o It may cause vaginal discharge and dysuria
o It may cause intermenstrual or postcoital bleeding
Treatment:
- Azithromycin 1g PO single dose (first-line)
- Doxycycline 100mg bd for 7 days

Note: When gonorrhea or Chlamydia is not responsive to

treatment, consider that both bacteria may be present at the
same time

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 HIV infection
- HIV is an RNA retrovirus that affects CD4 (T helper cells)
- Depletion of CD4 count takes a long period, so it has a long
incubation period (from one year to ten years)
- The main cause of death is decreased CD4 count and
opportunistic infections
Route of transmission:
- Sexual contact
- Exposure to blood or blood products (I.V drug users,
occupational)
- Organ transplantation.
- Vertical transmission (transplacental, during birth, or
breastfed)
- Kissing is not proven to transmit HIV
Clinical features:
- Primary infection: (2-4 weeks)
o Occur in 70% of HIV infections
o 50% asymptomatic
o High viral load
o Fever, pharyngitis, lymphadenopathy, myalgia,
arthralgia, headache, diarrhea (same symptoms of
mononucleosis)
o Maculopapular rash (usually at the trunk), oral and
genital ulcer
o Symptomatic recovery takes 1-10 weeks
- AIDS phase:
o It is the development of opportunistic infections,
tumors, and other clinical features.

CD4 count The most common diseases

(cells/mm³)
< 50 CMV retinitis, Mycobacterium avium/intercellulare
50 – 100 Aspergillosis, Candidiasis, Meningitis, CNS lymphoma
100 – 200 Cerebral toxoplasmosis, PCP, HIV dementia
200 – 500 Oral thrush, Shingles, Kaposi sarcoma
Table 144: Diseases affecting HIV patients

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Diagnosis:
- In primary infection: PCR (antibody may be negative)
- Then HIV antibody test
Treatment:
- Prevention (avoid contaminated water, avoid animal-borne
infection, control malaria) vector in an endemic area,
cotrimoxazole prophylaxis, pneumococcal, influenza, and
HBV vaccines)
- HAART (human antiretroviral therapy)
o Reduce viral load
o Improve CD4 > 200 cells/mm3
o Prolongs life expectancy
o Reduce transmission

Common parasites
Malaria
- A parasitic infection transmitted by Mosquito (Anopheles)
affects blood and liver cells
- Patients with sickle cell anemia are protected against
malaria
- The mosquito has the plasmodium in their saliva → and
injects it into the human bloodstream → Sporozoites reach
the liver and engage in Asexual reproduction (this is called
extra-erythrocytic phase) → erythrocytic phase: parasite
enters the RBCs → asexual replication and hemolytic
anemia
Diagnosis:
- History of travel to an endemic area
- General features: fever, headache, splenomegaly
- Fever is cyclic
- Signs and symptoms of hemolytic anemia with coombs
negative
Labs:
- Blood film (Thick-film: more sensitive, Thin-film: determine
species)
- Thrombocythemia is characteristic

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 - Normochromic normocytic anemia
- Normal white cell count
- Reticulocytosis
Caused by Plasmodium species:
Plasmodium Characteristics
species
Plasmodium Complications include:
falciparum - Cerebral malaria
- Acute renal failure: Blackwater fever
- ARDS
- Hypoglycemia
- DIC
Plasmodium vivax - The most common cause of non-
falciparum malaria
- Found in Central America and India
- Can have hypnozoite stage
- Cyclical fever every 48 hours
Plasmodium ovale - More common in Africa
- Can have hypnozoite stage
- Cyclical fever every 48 hours
Plasmodium - Associated with nephrotic syndrome
malariae - Cyclical fever every 72 hours
Plasmodium - Found in south-East Asia
knowlesi
Table 145: Species of Plasmodium and their characteristics

Treatment
- Chloroquine-sensitive areas: ACT or chloroquine
- Chloroquine-resistant areas: ACT
- Primaquine: after treatment of ovale or vivax malaria (to
destroy liver hypnozoite and prevent relapse)

- ACT: Artemisinin-based combination therapy

- ACTs should be avoided in pregnant women
- Plasmodium falciparum is chloroquine-sensitive

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 Chagas disease
- Also known as American trypanosomiasis
- Found in Mexico, south and central America
- Transmitted by Reduviid insect vector Triatominae (Kissing
bug)
- The infected triatomine feeds on the human blood, and it
defecates at the same time to make room for the new meal
- Triatominae in the stool are rubbed into the bite site by the
host

Other modes of transmission (Through the placenta, Organ

donation, Blood transfusion, Ingestion of contaminated food)

Clinical presentation:
- Acute phase:
o Usually asymptomatic
o Local swelling at the site of inoculation (Romana’s
sign: usually around one eye when the conjunctiva is
the portal of entry)
o Fever, lymphadenopathy, cardiomegaly, and
hepatosplenomegaly
- Chronic indeterminate phase:
o Asymptomatic increasing levels of antibody
o Most infected persons (60-70%) remain in this phase
and do not go on to manifest a determinate phase
- Chronic determinate:
o Chronic dilated cardiomyopathy
o Esophagomegaly
o Megacolon 10 – 25 years after acute infection (30-
40%)
Investigations:
- Thin and thick blood smears stained with Giemsa stain
- Serology test
- PCR
Treatment:
- Acute and Indeterminate phase: Nifurtimox or Benznidazole
- Chronic determinate:
o Symptomatic treatment
o Surgery: Heart transplant, Esophagectomy,
Colectomy

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 Clinical pharmacology
CHAPTER 11

Phone number: +962798843824

E-mail: Afeeef.2005@gmail.com

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 Drugs and their antidotes
- Antidotes: are substances that contract a form of poisoning.
- They may be manufactured by injecting the toxin into an
animal in small doses and extracting the resulting antibody

Drug Antidote
Adenosine Theophylline
Atropine Physostigmine
Benzodiazepines Flumazenil
Beta-Blockers Glucagon
Calcium channel blockers Calcium
Digoxin Digibind
Heparin Protamine sulfate
Iron Deferoxamine
Lead Editate di-sodium
Methanol Ethanol
Morphine Naloxone
Paracetamol N-Acetylcysteine
Warfarin Vitamin K
Table 146: Common drugs and their antidotes

Antibiotics
- Bacteriostatic antibiotics: Antibiotics that slow the growth of
bacteria
- Bactericidal antibiotics: Antibiotics that kill the bacteria
- Beta-lactam antibiotics: a class of broad-spectrum
antibiotics consists of a beta-lactam ring in their molecular
structure (e.g., penicillin, cephalosporins, Carbapenems,
Aztreonam).

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Classification according to the site of action on bacterial cells:
Action site Examples
Inhibits cell wall formation Penicillin
Cephalosporins
Glycopeptides
Carbapenems
Inhibits protein synthesis Aminoglycosides
(by acting on the ribosome) Chloramphenicol
Clindamycin
Macrolides
Streptogramin
Tetracyclines
Inhibits DNA synthesis Quinolones
Damages DNA Metronidazole
Inhibits folic acid formation Sulfonamides
Trimethoprim
Inhibits RNA synthesis Rifampicin
Table 147: antibiotics classification and their site of action

Bactericidal antibiotics Bacteriostatic antibiotics

1. Penicillin 1. Chloramphenicol
2. Cephalosporins 2. Macrolides
3. Quinolones 3. Sulfonamides
4. Aminoglycosides 4. Tetracyclines
5. Isoniazid 5. Trimethoprim
6. Metronidazole
7. Nitrofurantoin
8. Rifampicin
Table 148: antibiotic classification and their type of action

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 Penicillins
- It is of the most widely effective and least toxic antibiotic
- The mechanism of action: inhibits bacterial cell wall synthesis
- Examples are: Amoxicillin, Ampicillin, Dicloxacillin, Nafcillin,
penicillin G, penicillin V
- Penicillin is the initial therapy for otitis media, dental
infections, endocarditis prophylaxis, Lyme disease, UTI during
pregnancy

Bacteria covered by amoxicillin: (HELPS)

- H. influenza
- E. coli
- Listeria
- Proteus
- Salmonella

Penicillinase-resistant penicillin:
- Penicillinase enzyme is secreted by some bacteria leading
to the destruction of Beta-lactam antibiotics resulting in
insensitivity to this drug.
- Their use is restricted to treating infections caused by
penicillinase-producing staphylococci, including methicillin-
sensitive S. aureus (MSSA).
- Penicillinase-resistant drugs include methicillin, nafcillin,
oxacillin, dicloxacillin, cloxacillin, amoxicillin with clavulanic
acid, and ticarcillin with clavulanic acid.
- Penicillinase-resistant antibiotics have no activity against
gram-negative bacteria.

Beta-lactam antibiotics are the most common antibiotics to

cause anaphylaxis

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 Cephalosporins
- Beta-lactam antibiotics that cover a wide range of bacteria
- Cross-sensitivity between cephalosporins and penicillin is 8%:
o If penicillin causes skin rash, switch to cephalosporins
o If penicillin causes anaphylaxis, switch to non-beta-
lactam antibiotics

First Second Third Fourth Fifth

Cephalexin Cefaclor Ceftriaxone Cefepime ceftaroline
Cefazolin Cefuroxime Cefotaxime Cefpirome
Cefoxitin Ceftazidime
Table 149: cephalosporine generations

First Second Third Fourth Fifth

G-positive +++ ++ + ++ ++
G negative + ++ +++ +++ +++
Anaerobes +/- ++ + + ?
Pseudomonas No No Ceftazidime Yes No
MRSA No No No No Yes
Table 150: the bacterial coverage in cephalosporines

Indications:
- First-generation: Osteomyelitis, arthritis, endocarditis, cellulitis
- Second generation:
o Cefuroxime: is a drug of choice for respiratory
infections such as otitis, bronchitis, and sinusitis)
o Cefoxitin: is a drug of choice in PID (with doxycycline)
- Third generation:
o Pneumococcal pneumonia
o Meningitis
o Community-acquired pneumonia (with macrolides)
o Gonorrhea
o Lyme disease involving the heart or brain
o Cefotaxime used in the treatment of SBP
- Fourth generation:
o Ventilator-associated pneumonia
o Pseudomonal infections

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 Carbapenems
- E.g., Imipenem, Meropenem, Ertapenem, Doripenem
- Covers gram-negative bacilli
- The difference between all carbapenems and Ertapenem is
that all cover pseudomonas while Ertapenem Does not.

Fluoroquinolones
- E.g., Ciprofloxacin, Levofloxacin, Moxifloxacin
- The best therapy for community-acquired pneumonia
- Covers gram-negative bacilli, including pseudomonas
- Ciprofloxacin is used for the treatment of cystitis and
pyelonephritis
- Precautions:
o Contraindicated in children (<18 years) and pregnant
women (cause bone growth abnormalities)
o Can cause tendonitis and Achilles tendon rupture

Aminoglycosides
- E.g., Gentamycin, Tobramycin, Amikacin
- They are synergistic with beta-lactam antibiotics for
enterococci and staphylococci
- They are nephrotoxic and ototoxic

Trimethoprim/sulfamethoxazole (TMP/SMX)
- Used to treat cystitis, PCP, minor MRSA infections
- Side effects: hemolysis in G6PD deficiency patients, bone
marrow suppression, rash

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 Doxycycline
- Used for treatment of Chlamydia, Lyme disease, Cellulitis,
Syphilis, Mycoplasma
- Adverse effects: Tooth discoloration of children, type II RTA,
esophagitis, photosensitivity

Some antibiotics that are active against Pseudomonas:

- Carbapenems (except Ertapenem) (the first line)
- Tigecycline
- Cefepime (4th generation cephalosporin)
- Aminoglycosides (gentamycin, Amikacin)
- Fluoroquinolones (Except Moxifloxacin)
Table 151: Antipseudomonal agents

MRSA: methicillin-resistant Staph. aureus:

Minor infection with MRSA treated with: TMP/SMX, doxycycline,
clindamycin, or Linezolid
Major infection treated with Vancomycin
Red-man syndrome: a side effect of vancomycin will occur if
vancomycin is given as a rapid infusion. Vancomycin must be
given over 90 minutes to avoid this syndrome.

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 Drugs used in DM
Oral hypoglycemic agents
Biguanides (Metformin):
- First-line in the treatment of T2DM
- Work by blocking gluconeogenesis and increasing insulin
sensitivity
- Do not cause hypoglycemia
- Contraindicated if > 80 years old or GFR less than 30 ml/min
(Risk of lactic acidosis)
- Best for treatment of DM in obese patients (Metformin helps
reduce weight)
- The most common side effect is Gastrointestinal Upset
(diarrhea, vomiting, nausea) and rarely Lactic acidosis
Sulfonylureas:
- It can be used as add-on therapy in Metformin fails to
achieve the A1c target
- Stimulate the release of insulin from the pancreas
- Can cause weight gain; best for non-obese Diabetics
- Can cause hypoglycemia
- Sulphonylurea should not be used in renal impairment as
there is a risk of hypoglycemia
- Examples:
o Gliclazide, Glipizide, Chlorpropamide
o Glibenclamide (More risk of hypoglycemia, avoid in
elderly)
Alpha-glucosidase inhibitor:
- Decrease intestinal absorption of glucose
- Side effects (flatulence, abdominal pain, diarrhea)
- Examples:
o Acarbose
o Miglitol
Thiazolidinediones (glitazones):
- Enhance action “but not amount” of endogenous insulin
- Hypoglycemia not happens
- Examples:
o Rosiglitazone (increased risk of MI, so withdrawn in
2010)
o Pioglitazone (exacerbate heart failure, avoid in HF
patients)

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Dipeptidyl peptidase-4 (DPP-4) inhibitors:
- Well tolerated with no increased incidence of hypoglycemia
- Do not cause weight gain
- Examples: (Vildagliptin, Sitagliptin)
Glucagon-like peptide (GLP) mimetics:
- Increase insulin secretion and inhibit glucagon secretion
- Can be used with Metformin and Sulfonylurea as a third
agent
- Cause weight loss, used if BMI ≥ 35 kg/m2
- Examples:
o Exenatide injection BID
o Liraglutide injection once daily

Insulin
- Used in T1DM and patients with T2DM who are not controlled
or oral agents
- Can be rapid-acting, short-acting, intermediate-acting, or
long-acting
- Premixed insulin composed of rapid or short-acting
combined with intermediated acting insulin
- The type of insulin that can be given IV is called regular
insulin

Insulin type Examples Onset Peak Duration

Ultra-rapid Faster Aspart 6-12 m 1-3 h 3-5 h
Rapid-acting Lispro, Aspart, 5-20 m 0.5-3 3-8 h
Glulisine h
Short-acting Regular insulin 30 m 2-4 h 5-8 h
Intermediate NPH 2-4 h 6-10 h 18-28 h
acting
Long-acting Detemir, Glargine 2h None 20-24 h
Table 152: The different types of insulin

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 Common cardiac medications
HTN and heart failure medications
ACE inhibitors
- Block the conversion of angiotensin 1 to angiotensin 2 and
prevent sodium water retention
- Examples: Enalapril, Perindopril, Ramipril, Lisinopril
- Indications: HTN, Nephroprotective in DM, CHF, CAD, post-MI
- Side effects: Dry cough, Hyperkalemia, Hypotension,
Angioedema
- Contraindications: Renal artery stenosis, Low GFR (caution)
Additional notes:
- It is the drug of choice in a patient with DM and HTN
- Monitor creatinine 1 week after starting ACEI; stop it if
elevated > 30%.

ARB (angiotensin receptor blockers)

- Block the angiotensin receptor and prevent sodium water
retention.
- Examples: Valsartan, Candesartan, Irbesartan
- Side effect: same as ACEI, but does not cause a dry cough
- Indications and contraindications are the same as ACEI
Additional notes:
- Same indications and contraindications as ACEI
- If ACEI causes cough so, switch to ARB
- Losartan is the drug of choice in a patient with HTN and gout

Direct renin inhibitors (DRI)

- The block renin directly
- Example: Aliskiren
- Indications: HTN
- Side effects: Same as ACEI, Rhabdomyolysis, Seizures

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 Beta-blockers
- Classified as β1 selective or non-selective
- Block β receptors to decrease heart rate, contractility, and
oxygen demands in the heart muscle
- Examples:
o Selective β1: Bisoprolol, Atenolol, Metoprolol
o Non-selective: Propranolol, Labetalol, Carvedilol
- Side effects: Hypotension, fatigue, light-headedness,
depression, bradycardia, hyperkalemia, bronchospasm,
cold extremities, impotence, exacerbation of Raynaud’s
phenomenon, and claudication
- Indications: HTN, CAD, acute MI, post-MI, CHF (start low and
go slow), A. Fib, SVT, and hyperthyroidism
- Contraindications: Sinus bradycardia, 2nd or 3rd-degree
heart block, hypotension, WPW.
- Caution in asthma, claudication, Raynaud’s phenomenon,
and decompensated CHF

Calcium channel blockers

Action:
- Non-dihydropyridines: block calcium channels in smooth
and myocardial muscles, cause decreased Heart rate,
contractility, and oxygen demands in the heart, also act as
a vasodilator
- Dihydropyridines: Block smooth muscle calcium channels
causing peripheral vasodilation
Examples:
- Dihydropyridines: (peripherally acting): amlodipine,
nifedipine, felodipine
- Non-dihydropyridines: (centrally acting): diltiazem,
verapamil
Indications:
- Dihydropyridines: HTN, Raynaud's phenomena
- Non-dihydropyridines: HTN, CAD, SVT, diastolic dysfunction
Side effects:
- Dihydropyridines: Hypotension, edema, flushing, headache,
light-headedness
- Non-dihydropyridines: Hypotension, bradycardia, lower limb
edema

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Contraindications:
- Dihydropyridines: Severe aortic stenosis and liver failure
- Non-dihydropyridines: Sinus bradycardia, 2nd or 3rd-degree
heart block, hypotension, WPW, CHF also, it is
contraindicated to use with Beta-blockers

Thiazide diuretics
- Action: Reduce Sodium reabsorption in the distal
convoluted tubule
- Examples: hydrochlorothiazide, chlorthalidone, metolazone
- Indications: HTN
- Side effects: Hypotension, Hypokalemia, Polyuria, Hyper-
GLUC (hyperglycemia, hyperlipidemia, hyperuricemia, and
hypercalcemia)
- Contraindications: Sulfa allergy, pregnancy

Loop diuretics
- Action: Blocks Sodium/Potassium pump in the loop of Henle
- Examples: furosemide, Bumetanide, Torsemide
- Indications: Edema, congestive heart failure
- Side effects: Hypokalemia, Hypovolemia, alkalosis,
hyperuricemia, gout, dehydration, ototoxicity, and
hypocalcemia
- Contraindications: Hypokalemia, Hypovolemia

Potassium-sparing diuretics
- Action: Antagonize aldosterone receptors
- Examples: spironolactone, eplerenone, Amiloride,
Triamterene
- Indications: HTN, HF, Hypokalemia
- Side effects: Hyperkalemia, Gynecomastia
- Eplerenone does not cause gynecomastia
- Contraindications: pregnancy, renal failure, hyperkalemia

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 Digitalis (Digoxin)
- Action: Inhibit the sodium/potassium pump, increase
intracellular Sodium and calcium concentration, and
increase myocardial contractility.
- It also slows AV node conduction
- Indications: Congestive heart failure, atrial fibrillation
- Side effects: Hyperkalemia, Arrhythmias, yellow vision,
Nausea, and Vomiting
- Contraindications: 2nd or 3rd degree AV block,
Hypokalemia, WPW

Antiplatelet medications
Salicylates
- Action: Antiplatelet (irreversible), preventing Thromboxane
A2-mediated platelet aggregation
- Examples: Aspirin
- Indications: CAD, PAD, CVA, MI,
- Side effects: bleeding, GI ulcers, GI upset
- Contraindications: active bleeding or peptic ulcer disease

Clopidogrel
- Action: Antiplatelet affect the ADP-dependent activation of
glycoprotein IIb/IIIa complex
- Indications: CAD, PAD, CVA, MI,
- Side effects: bleeding, GI upset

Nitrates
- Action: relax vascular smooth muscles
- Examples: nitroglycerine
- Indications: CAD, MI, HF
- Side effects: headache, hypotension
- Contraindications: Concurrent use of Viagra, angle-closure
glaucoma, increased
- Intracranial pressure

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 Statins
- Action: HMG-CoA reductase inhibitors – reduce cholesterol
synthesis
- Examples: Atorvastatin, Simvastatin, rosuvastatin
- Indications: Dyslipidemia, decreased mortality in CAD, MI
- Side effects: abdominal pain, myalgia, rhabdomyolysis
- Contraindications: liver failure, Muscle disease

Amiodarone
- Action: class III antiarrhythmic drug, block potassium
channel to prolong cardiac repolarization
- Indications: AF, ventricular arrhythmias
- Side effects: hypothyroidism, hyperthyroidism, bradycardia,
GI upset, hepatitis, pulmonary infiltrate, salt-gray skin,

Adrenaline
- Action: sympathomimetic amine with both alpha and beta-
adrenergic stimulating properties
- Indications: anaphylaxis cardiac arrest
- Dose: anaphylaxis (0.5 ml 1: 1000 IM), arrest (10 ml. 1: 10,000)
- Side effects: tachycardia, palpitations, headache

GI medications
Antacids
- Action: neutralize gastric acid
- Examples: aluminum hydroxide, magnesium carbonate
- Indications: GERD, dyspepsia
- Side effects: decreased absorption of digitalis, ferrous
preparations, diarrhea or constipation
H2 blockers
- Action: block histamine 2 receptors in the stomach and
decrease acid secretion
- Examples: famotidine, ranitidine, cimetidine
- Indications: GERD, dyspepsia, peptic ulcer
- Side effects: headache, dizziness, decreased absorption of
digitalis, ferrous preparations, diarrhea or constipation

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 Proton pump inhibitors (PPI's)
- Action: bind irreversibly to the proton/hydrogen pump in the
stomach, reduce hydrogen secretion, and decrease acidity
- Examples: omeprazole, lansoprazole, pantoprazole
- Indications: GERD, peptic ulcer
- Side effects: decreased absorption of digitalis, ferrous
preparations, diarrhea or constipation, inhibit cytochrome
P450 enzyme except for pantoprazole, nausea, vomiting,
diarrhea, headache dizziness
Laxatives
Bulk-forming laxatives:
- Action: increase fecal mass
- Examples: wheat bran
- Indications: constipation secondary to inadequate dietary
intake, patient with colostomy, ileostomy, hemorrhoids, anal
fissure
- Side effects: flatulence and abdominal distension

Stimulant laxatives:
- Action: stimulate intestinal motility
- Indications: constipation
- Side effects: abdominal cramps, diarrhea, Hypokalemia

Fecal softeners:
- Action: soften and lubricate feces
- Examples: Arachis oil, liquid paraffin
- Indications: constipation with fecal impaction
- Side effects: local irritation of the anus

Osmotic laxatives:
- Action: Increase the amount of fluid in the large bowel
- Examples: lactulose, phosphate magnesium salt
- Indications: constipation, bowel preparation for radiologic
investigations
- Side effects: abdominal distension, flatulence, diarrhea,
Hypokalemia

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Aminosalicylate:
- Action: unknown, but it seems to be a local anti-
inflammatory
- Examples: sulfasalazine, mesalazine, balsalazide olsalazine
- Indications: inflammatory bowel disease, rheumatoid arthritis
(sulfasalazine)
- Side effects: GI upset, hypersensitivity, anemia, renal
dysfunction
Cholestyramine:
- Action: form an insoluble complex with bile acid and
prevent its absorption, and promotes the reduction in serum
cholesterol
- Indications: relieve diarrhea in a patient with ileal resection
or ileal disease
- Side effects: can interfere with some drug absorption

Analgesics
Paracetamol
- Action: inhibit CNS production of prostaglandins
- Indications: mild to moderate pain
- Side effects: few side effects, hepatotoxic in large doses
- Contraindications: caution with hepatic disease

Opioids
- Action: agonize G-protein-coupled receptor in the neuronal
cell membrane
- Examples: codeine, dihydrocodeine, morphine, oxycodone,
fentanyl, pethidine, tramadol
- Indications: moderate to severe pain
- Side effects: nausea, vomiting, constipation, respiratory
depression

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 Non-Steroidal anti-inflammatory drugs (NSAIDs)
- Action: inhibit Cyclooxygenase receptor (COX), selectively
on COX2 or nonselectively, anti-inflammatory and pain-
relieving effect
- Examples: diclofenac sodium, Indomethacin, ibuprofen,
celecoxib, etoricoxib,
- Indications: arthritis, moderate pain relief
- Side effects: renal impairment, non-selective can cause
peptic ulcer disease, Stevens-Johnson syndrome
- Contraindications: peptic ulcer disease, asthma patient
(caution)

Corticosteroids
- They augment and, in some cases, replace the natural
glucocorticoid and mineralocorticoid activity of
endogenous steroids.
Glucocorticoid side-effects
- Endocrine: impaired glucose regulation, increased
appetite/weight gain, hirsutism, hyperlipidemia
- Cushing's syndrome: moon face, buffalo hump, striae
- Musculoskeletal: osteoporosis, proximal myopathy, avascular
necrosis of the femoral head
- Immunosuppression: increased susceptibility to severe
infection, reactivation of tuberculosis
- Psychiatric: insomnia, mania, depression, psychosis
- Gastrointestinal: peptic ulceration, acute pancreatitis
- Hematological: increased total WBC count, but monocytes
and eosinophils decreased, increased Platelet count.
- Ophthalmic: glaucoma, cataracts
- Suppression of growth in children
- Intracranial hypertension
Mineralocorticoid side-effects
- fluid retention
- hypertension

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 Cyclosporine
- It is an immunosuppressant medication from a natural
source
Medical uses:
- to prevent Graft-versus-host disease in BM transplantation
- Prevent rejection of kidney, heart, and liver transplants
- Severe Rheumatoid Arthritis and Psoriasis,
- Severe Atopic dermatitis, alopecia
- Acute severe ulcerative colitis not responding to treatment
with steroids.
- Treatment of eye conditions:
o Dry eyes caused by Sjögren's syndrome
o Uveitis with noninfective cause
Side effects:
- Nervous symptoms: Tremor, Headache, Numbness, and
tingling
- GI symptoms: Nausea, Vomiting, Diarrhea, Abdominal
discomfort, Indigestion, and GI upset
- Renal damage, Hyperkalemia, Hypertension
- Infection
- Hirsutism
- Gum hyperplasia
- Hypertriglyceridemia
- Leg cramps
- Dizziness, Flushing

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