Goljan Path Review: High Yield

Cell Injury
Tissue Hypoxia Hypoxia: inadequate tissue oxygenation O2 Content: (Hb x 1.34) x SaO2 + PaO2 x 0.003 Pulse Ox: falsely SaO2 w/ metHb &COHb Ischemia: arterial blood inflow or venous outflow Hypoxemia: PaO2 Alveolar PCO2 = Alveolar PO2 = PaO2 = SaO2 Ventilation Defect: perfused but NOT ventilatedintrapulmonary shunt Perfusion Defect: ventilated but NOT perfuseddead space Diffusion Defect: interstitial fibrosis or pulmonary edema Anemia: normal PaO2 & SaO2 MetHb: Heme Fe3+ & SaO2 o Tx w/ IV methylene blue CO Poisoning: normal PaO2 & SaO2 o Tx w/ O2 via nonbreather mask High Altitude: 2,3-BPG synthesis & Respiratory ALKALOSIS CO & CN: inhibit Cytochrome Oxidase o Poisoninghouse fires o Tx CN poisoning w/ Amyl Nitrite & Thiosulfate Uncouplers: Theromgenin & Dinitrophenol Mitochondrial Toxins: Alcohol & Salicylates Watershed Areas: Cerebral Vessels & Mesenteric Arteries ST Segment Depression: Subendocardial Ischemia Kidney Cortex: Proximal tubule most susceptible to hypoxia Kidney Medulla: thick ascending limb most susceptible to hypoxia Neurons: most adversely affected cell in tissue hypoxia Zone III Hepatocytes: most susceptible to hypoxia Anaerobic Glycolysis: 1 source ATP in hypoxiaLactic Acidosis Ca in Cytosol: point of no returnactivates enzymes Free Radical Cell Injury Cytochrome C in Cytosol: activates APOTOSIS Hydroxyl Free Radicals: most destructive Free Radicals Oxidase Rxns: produce superoxide FR Acetaminophen: Drug FRs formed in liver Fe & Cu: generate hydroxyl FRs Free Radicals

o steal e- from molecules o damage membrane & DNA FR Neutralization: SOD, GSH & Vitamins C & E Vitamin C: best hydroxyl FR neutralizer Acetaminophen: FR injury liver & kidneys N-acetylcysteine: generates GSH Reprofusion Injury: superoxide FRs & cytosolic Ca Excess Fe & Cu: hydroxyl FR damage of tissue

Cell Organelle Injury SER Hyperplasia: drug metabolism SER Inhibition: drug metabolism 1 Lysosomes: derive from Golgi Apparatus Phagolysosomes: contain lysosomal enzymes I-Cell Disease: defect in post-translational modification of lysosomal enyzmes Lysosomal Storage Disease: lysosomal enzymes CHS: giant lysosomal Defect Tublin Synthesis G2 Phase: Etoposide & Bleomycin B Mitotic Spindle Defects: Vinca Alkaloids, Colchicine & Paclitaxel Ubiqutin: marker for intermediate filament degradation Intracellular Accumulations *Alcohol = most common cause of FATTY * Fatty Liver: TG synthesis & TG secretion G3-P: substrate for TG synthesis Fatty in Cardiac Muscle: anemia & diphtheria Serum Ferritin: in Fe deficiency anemia Hemosiderin: Ferritin degradation product Dystrophic Calcification: calcification of NECROTIC tissue Metastatic Calcification: calcification of NORMAL tissue Adaptation to Cell Injury: Growth Alterations Atrophy o size/weight of tissue or organ o Autophagic vacuoles o lipofuscin in cells Hypertrophy: cell size & workload Hyperplasia: # of cells Labile/Stable Cells: can divide

Permanent Cells: cannot divide Metaplasia: 1 cell type replaces another Barretts Esophagus: glandular metaplasia gastric reflux Metaplasia/Hyperplasia: in some cases may progress dysplasia Dysplasia: disordered cell growth & may progress to cancer

Cell Death Coagulation Necrosis: preservation of structural outlines Infarctions: pale & hemorrhage types Dry Gangrene: predominately coagulation necrosis Infarction LESS likely w/ dual or collateral blood supply Cerebral Infarction: LIQUEFACTIVE necrosisNOT coagulative Wet Gangrene: predominantly LIQUEFACTIVE necrosis Tuberculosis: most common cause of CASEOUS necrosis Enzymatic Fat Necrosis: Acute Pancreatitis Traumatic Fat Necrosis: NOT enzyme-mediated Fibrinoid Necrosis: necrosis of IMMUNE-mediated dz Apoptosis: programed cell death Extrinsic Pathway of Apoptosis: requires TNF BCL2 Gene: ANTI-apoptosis gene TP53 Suppressor Gene: guardian of cell BAX Gene: apoptosis gene Caspases: group of cysteine proteasesactivation INDUCES apoptosis Apoptotic s: deeply EOSINOPHILIC cytoplasm & PYKNOTIC nucleus

Delayed Separation Umbilical Cord: selection or CD11a:CD18 def Chemostaxis: directed migration of neutrophils Opsonins: IgG & C3b Brutons Agammaglobulinemia: opsonization defect Chediak-Higashi Syndrome: cannot form phagolysosomes O2 Dependent MPO System: most potent microbicial system End-Product O2 Dependent MPO System: bleach Chronic Granulomatous Dz: absent NADPH Oxidase & Respiratory Burst MPO Deficiency: normal respiratory burst NADPH: microbicidal defect Histamine: most important chemical mediator of acute inflammation Chemical Mediators: short lives S aureus: most common cause of SKIN ABSCESS Pseudomembranous Inflammation: Diptheria, Clostridium difficle, noninvasive bacteria FEVER IS GOOD Clearance of Neutrophils in AI: apoptosis

Inflammation & Repair

Acute Inflammation AI: chemical, vascular & cellular responsesNOT synonymous w/ infection Rubor, Calor, Tumorhistamine mediated Mast Cells: release PREFORMED histamine Neutrophils: 1 leukocytes in acute inflammation Selectins: responsible for neutrophil rolling 2 Integrins: neutrophil/endothelial adhesion moleculesfirm adherence Neutrophil Leukocytosis: Catecholamines, Corticosteroids & Lithium Neutropenia: Endotoxins

Chronic Inflammation Infection: most common cause of chronic inflammation Monocytes & Macrophages: 1 leukocytes in chronic inflammation Granulation Tissue: converted to scar tissue Fibronectin: key adhesion glycoprotein in ECM Cell Types in Tuberculous Granuloma: macrophages & CD4 T helper Epithelioid Cells: macrophages activated by -interferon from CD4 T helper cells TNF-: important in formation & maintenance of granulomas G1 Phase: most variable phase in cell cycle G1-S Phase: most critical phase in cell cycle Genes Controlling G1-S Phase: RB & TP53 suppressor genes BAX Gene: activation by TP53 initiates apoptosis Laminin: Key adhesion glycoprotein in BM Granulation Tissue: essential for normal CT repair Lysyl Oxidase: cross-links tensile strength Ascorbic Acid: hydroxylates proline & lysine Copper: cofactor in lysyl oxidase Ehlers-Danlos Sydrome: defects in Type I & III collagen Zinc: cofactor in collagenase

Infections: most common cause of impaired wound healing Vitamin C Deficiency: cross-linking of tropocollagen tensile strength Glucocorticoids: prevent scar formation Keloids: excess Type III collagen Severe Injury Liver: regenerative nodules & fibrosis Lung Injury: Type II penumocyte is repair cell Brain Injury: Proliferation of astrocytes & microglial cells Peripheral Nerve Transection: Schwann Cell key cell in reinnervation IgM: predominant immunoglobulin in acute inflammation IgG: predominant immunoglobulin in chronic inflammation Corticosteroid Effect in Blood: neutrophils, eosinophils & lymphocytes ESR: fibrinogen, anemia CRP: necrosis marker & disease activity SPE Acute Inflammation: albumin, NO alteration in -globulin peak Polyclonal Gammopathy: sign of chronic inflammation

Myasthenia Gravis & Graves Disease: antibodies against receptorstype II HSR Type III: complement activation by circulating antigen-antibody complexes Antibody Mediated HSR: Type I, II, & III Type IV: cellular immunityDelayed Rxn Hypersensititivity CD4 cells interact w/ macrophages, TB granuloma Contact Dermatitis o activated CD4 (1mediator) + CD8 cells o Poison Ivy, Nickel

Immunopathology
Immune System Cells Innate Immunity: 1st defense against pathogens Natural Killer Cells: large granular lymphocytes in peripheral blood TLRs: recognize non-self antigens on pathogen NF: master switch to nucleus IgM & IgG Synthesis: begin AFTER birth MHC

Transplantation Immunology ABO Blood Group Compatibility: most important requirement for successful transplantation Autograft: best survival rate Fetus: allograft NOT rejected by mother Hyperacute Rejection: irreversible, type II HSR Acute Rejection: most common type, type IV & II HSR Chronic Rejection: irreversible Immunosuppressive Therapy: danger of Squamous Cell Cacrinoma GVH Rxn: jaundice, diarrhea, dermatitis Corneal Transplant: best allograft survival rate Autoimmune Diseases Organ-Specific Disorders: Addisons Dz & Pernicious Anemia Serum ANA: antibodies against DNA, histones, acidic protein, nucleoli Anti-dsDNA: SLE w/ glomerulonephritis Rim Pattern: associated w/ anti-dsDNA antibodies SLE: genetic + environmental factors Most Common Cardiac Finding in SLE: fibrinous pericarditis w/ effusion Procainamide: most common drug associated w/ drug-induced lupus Drug Induced Lupus: Anithistone Antibodies Screen for SLE: serum ANA Confirm SLE: anti-dsDNA & anti-Sm antibodies LE Cell: neutrophil w/ phagocytosed, altered DNA Systemic Sclerosis o excess collagen deposition & digital vasculitis o anti-topoisomerase antibodies

APCs: B cells, macrophages, dendritic cells HLA-B27: anklyosing spondylitis

Hypersensitivity Rxns Type I: IgE activation of mast cells Mast Cell Activation: allergens cross-link allergen-specific antibodies Mast Cells: early & late phase rxns Anaphylactic Shock: potentially fatal Type I hypersensitivity rxn Type II: antibody-dependent cytotoxic rxns

Raynauds Phenomenon: most common initial sign of systemic sclerosis CREST Syndrome: Calcinosis/Centromere Antibody, Raynauds Phenomenon, Esophageal Dsyfxn, Sclerodactyly, Telangiectasia Dermatomyositis & Polymyositis o heliotrope eyes & Gottron Patches o serum creatine kinase Mixed Connective Tissue Dz: anti-ribonucleoprotein antibodies

Congenital Immunodeficiency Disorders IgA Deficiency: most common congenital immunodeficiency AIDS: most common acquired immunodeficiency dz worldwide Pediatric AIDS: most dt vertical transmission Risk per unit of blood = 1 per 2million units transfused HIV: cytoxic to CD4 T helpr cellsloss of cell mediated immunity Anti-gp120: detected in ELISA tes screen Western Blot: confirms HIV Reservoir Cell for HIV: follicular dendritic cells in lymph nodes Most Common Malignancy in AIDS: Kaposi Sarcoma CMV: most common cause of blindness in AIDS Death in AIDS: disseminated infection C3a & C5a: anaphylatoxins C3b: opsonization C5a: activate neutrophil adhesion molecules, chemotaxis C5-C9: cell lysis, MAC Hereditary Angioedema: deficiency C1 esterase inhibitor Decay Accelerating Factor: deficient in PNH Classical Pathway Activation: C4 & C3, normal factor B Alternative Pathway Activation: factor B, C3 & normal C4 Amyloidosis Amyloid: o apple green birefringence in polarized light o abnormal folding of protein -Amyloid: associated w/ Alzheimers in Down Syndrome

Water, Electrolyte, Acid-Base & Hemodynamic Disorders

Water & Electrolyte Disorders

Compartment Sizes: ICF > ECF & Interstitial > Vascular Na & K: major ECF & ICF cations respectively EOsm = 2 (serum Na) + serum glucose/18 Osmosis: H2O moves between ECF & ICFcontrolled by serum Na Serum Na TBNa/TBW TBNa: signs of vol depletion TBNa: pitting edema, body cavity effusion Starling Pressure Alterations: control water movement in ECF compartment Isotonic Loss: TBNa/TBW, loss whole blood, secretory diarrhea Isotonic Gain: TBNa/TBW, excessive infusion isotonic saline Isotonic Loss or Gain: normal serum Na Hypotonic Disorders: hypoNa always present, ICF expansion Gain in Fluid: ECF always expands Loss in Fluid: ECF always contracts Hypertonic Loss: TBNa/TBW, loop diuretics, Addisons Dz, 21hydroxylase def Central Pontine Myelinolysis: rapid correction of hypoNa w/ saline Hypotonic Gain of Water: TBNa/TBW Pitting Edema States: right-sided heart failure, cirrhosis, nephrotic syndrome, CO Hypertonic Disorder: hyperNa or hyperglycemia, ICF contraction Hypotonic Loss Na + Water: TBNa/TBW, osmotic diuresis, sweating Hypotonic Loss of Water: TBNa/TBW, diabetes insipidus, insensible water loss Hypertonic Gain: TBNa/TBW, excess NaHCO3, infusion of Na containing antibiotic Diabetic Ketoacidosis: hypertonic state w/ dilutional hypoNa, osmotic diuresis Proximal Tubule: reabsorb Na, reclaim HCO3, EABV FF Po>Ph Ph>Po Carbonic Anhydrase Inhibitor: causes proximal renal tubular acidosis Heavy Metal Poisoning: produces Fanconi Syndrome Na/K/2Cl Symporter: generates free water CL Binding Site in Na/K/2Cl Symporter: inhibited by loop diuretics Loop Diuretic: hypoNa, hypoK, metabolic alkalosis Thiazides:

o inhibit Cl site in Na/Cl symporter o HypoNa, hypoK, metabolic alkalosis, hyperCa HypoK: risk of metabolic alkalosis Amiloride & Triamterene: diuretics w/ K sparing effects Spironolactone: aldosterone inhibitor, K sparing Addisons Disease: hypoNa, hyperK, metabolic acidosis 1 Aldosteronism: o hyperNa, hypoK, metabolic alkalosis o low plasma renin type hypertension o absence of pitting edema Bartters Syndrome: normotensive, hypoK, metabolic alkalosis, aldosterone & PRA +CH2O: indicates dilution, absence of ADH SIADH: o small cell carcinoma of lung most common o serum Na <120 mEq/L, dilution disorder o Tx: restrict water Serum Na usually <120 mEq/L136-145 mEq/L -CH2O: concentration, presence of ADH oCH2O: chronic renal failure, no concentration or dilution CDI & NDI: hyperNa, polyuria, concentration disorder CDI: desmopressin UOsm (concentration) NDI: desmopressin no significant UOsm pH s: may cause shift of K into or out of ICF Insulin, 2-Agonist: may shift K into cell, hypoK Digitalis, -Blocker, Succinylcholine: may shift K out of cells HyperK, Loop & Thiazide Diuretics: most common cause of hypoK HypoK: EKG shows U wave Renal Failure: most common cause of hyperK PseudohyperK: RBC hemolysis from difficult venipuncture HyperK: EKG shows peaked T waves

Respiratory Alkalosis: PaCO2 <33mmHg Tetany: commonly occurs in acute respiratory alkalosis Metabolic Acidosis: HCO3 <22 mEq/L AG Metabolic Acidosis: anions of acid replace buffered HCO3 Lactic Acidosis: most common AG metabolic acidosis, anaerobic glycolysis in shock Normal AG Metabolic Acidosis: Cl anions replace HCO3 Loop & Thiazide Diuretics: most common causes of metabolic alkalosis Metabolic Alkalosis: HCO3 > 28 mEq/L Clues for Mixed Disorder: normal pH, extreme pH Salicylate Intoxication: often mixture of 1 Metabolic Acidosis & 1 Respiratory alkalosis, nl pH pH defines what is the 1 disorder vs what is the compensation Edema: excess fluid in interstitial space Transudate: protein-poor & cell-poor fluid Pitting Edema: o transudate, hydrostatic pressure &/or oncotic pressure o right-sided heart failure dt hydrostatic pressure, cirrhosis dt oncotic pressure Exudate: protein rich & cell rich fluid Lymphedema: lymphatic obstruction after modified radical mastectomy & radiation Myxedema: excess hyaluronic acid in interstitial tissue

Acid-Base Disorders Chronic Bronchitis dt Smoking: common cause of respiratory acidosis Respiratory Acidosis: PaCO2 >45mmHg Full Compensation: rarely occurs Formulas: help recognize single vs multiple acid-base disorders Anxiety: most common cause of respiratory alkalosis

Thrombosis Endothelial Cell Injury: arterial thrombi Stasis of Blood Flow: venous thrombi Most common site for venous thrombosis: deep vein in lower extremity BELOW knee Venous Thrombi Composition: entrapped RBCs, platelets, WBCs Heparin & Warfarin: anticoags that prevent venous thrombosis Arterial Thrombus Composition: fibrin clot composed of platelets Aspirin: prevents formation of arterial thrombi Mixed Thrombus: prevented by aspirin along w/ anticoag therapy Embolism Pulmonary Thromboemolism: majority originate in femoral veins

Pulmonary Infarction: uncommon dt dual blood supplypulmonary arteries, bronchial arteries Systemic Embolism: majority originate in Left side of heart Fat Embolism: o long bone frx o dyspnea, petechial over chest/UE Amniotic Fluid Embolism: abrupt onset dyspnea, hypotension, bleeding (DIC) Decompression Sickness: N gas bubbles occlude vessel lumens Pneumothorax, Pulmonary Embolism & Aseptic Necrosis: complications of scuba diving

o most involve enzyme deficiencies PKU: phenylalanine, tyrosine Von Gierkes Dz: G-6-Pase Deficiency (gluconeogenic enzyme), fasting hypoglycemia, hepatorenomegaly Most Common AR Disorder: hemochromatosis AD Inheritance: heterozygotes w/ dominant mutant gene express dz Reduced Penetrance: individual w/ mutant gene does NOT express dz, transmits to children Most Common AD Disorder: von Willebrand Dz

Shock Hypovolemic Shock: o most often caused by blood loss o CO2, LVEDP, PVR, MVO2 MVO2: best indicator of tissue hypoxia Cardiogenic Shock: o most often caused by acute MI o CO2, LVEDP, PVR, MVO2 Septic Shock: o most often caused by sepsis dt E. coli o initial phase: CO2, LVEDP, PVR, MVO2 Multiorgan Dysfxn: most common cause of death in shock

X-Linked Recessive Disorders XR Inheritance: asymptomatic female carrier transmits mutant gene to 50% sons Most Common X-Linked Disorder: Fragile X Syndrome XD Inheritance: female carriers are symptomatic Chromosomal Disorders Barr Body: o inactivated X chromosome o # of Barr Bodies = #X chromosomes - 1 Nondisjunctional: unequal separation of chromosomes in meiosis Mosaicism: nondisjunction in mitosis Cri du Chat Syndrome: deletion short arm chromosome 5 Down Syndrome: o most cases dt nondisjunction o most common cause of mental retardation o duodenal atresia, Hirschsprungs o Alzheimers dz at young age Advanced Maternal Age: risk for bearing offspring w/ trisomy syndromes Edward Syndrome: trisomy 18 Patau Syndrome: trisomy 13 Turners Syndrome: o 45 X o Menopause before menarche o Most common cause of 1 amenorrhea Webbed Neck: Cystic Hygroma Klinefelters Syndrome: testosterone & inhibin, LH & FSH XYY Syndrome: paternal nondysjxn, aggressive behavior

Genetic & Developmental Disorders

Mutations Missense Mutation: Sickle Cell Dz/Trait -Thalassemia Major: nonsense mutation w/ stop codon Frameshift Mutation: Tay-Sachs Dz Anticipation: additional trinucleotide repeats dz severity in future generations Mendelian Disorders Most common type of medialian disorderautosomal recessive AR Inheritance: o both parents must have mutant gene

Other Patterns of Inheritance Polygenic Disorders: more common than mendelian & chromosomal disoders Mitochondrial DNA: associated w/ maternal inheritance, ova have mutant gene Genomic Imprinting: inheritance depends on whether mutant gene is on maternal or paternal origin Prad-Willi Syndrome: microdeletion on paternal chromosome 15 Angelman Syndrome: microdeletion on maternal chromosome 15 Sex Differentiation Disorders Y Chromosome: determine genetic sex of individual Testicular Feminization: o most common cause of male pseudohermaphroditism o vagina ends as blind pouch Congenital Anomalies Malformation: o disturbance in morphogenesis in embryonic period o open neural tube defect, cleft lip/palate Deformation: o Extrinsic disturbances in fetal development o Oligohydramnios causing Potters Facies, clubfeet Congenital Abnormalities: genetic + environmental factors Maternal Diabetes: macrosomiahyperinsulinemia muscle mass & fat Alcohol: most common teratogenfetal alcohol syndrome CMV: most common pathogen causing congenital infection TORCH Syndrome: Toxoplasmosis, Other Agents, Rubella, CMV, HSV Retinoic Acid in Pregnancy: disrupts HOX gene fxn, craniofacial, CNS & cardiovascular defects Selected Perinatal & Infant Disorders Stillbirth: most often caused by abruption placentae Spontaneous Abortion: frequently caused by trisomy 16 SIDS: majority of deaths occur before age 6mo Large for Gestational Age (LGA): most often dt maternal diabetes Prematurity: most common cause of neonatal death/morbidity Intrauterine Growth Retardation (IUGR):

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Maternal factors most often responsible in SGA infants Often have oligohydramnios

Genetic & Developmental Disorder Dx Open Neural Tube Defects: Folate deficiency prior to conception, AFP Triple Marker for Down Syndrome: AFP, hCG, urine estriol Aging

Age-Dependent: inevitable w/ ageGFR & prostate hyperplasia Age-Related: common but NOT inevitable w/ ageAlzheimers Dz, systolic htn

Environmental Pathology
Chemical Injury Smoking: most important preventable cause of dz & death in US Cotinine: metabolite of nicotine, used for screening Nicotine Patch: effective in txing ulcerative colitis Alcohol Metabolism: NADH is key to lab abnormalities Women: less gastric alcohol dehydrogenase than men Alcohol Abuse: most common cause of thiamine deficiency Anion Gap Metabolic Acidosis in Alcohol Abuse: lactic acid & hydroxybutyric Acid Alcohol Liver Dz: Aspartate aminotransferase > Alanine aminotransferase, -glutamyltransferase Hepatitis B: most common systemic complication of IVDU Salicylate Poisoning: danger of hyperthermia Both acetaminophen & aspirin cause fulminant hepatitis Unopposed Estrogen: thrombogenic, carcinogenic, cholestasis Oral Contraceptives: o risk for endometrial & ovarian canceronly surface type o Most common cause of htn in young women angiotensinogen Physical Injury Bee/Wasp/Hornet Sting: most common cause of death dt venomous bite Contact Gunshot Wound: fouling Intermediate Range Wound: powder tattooing

Motor Vehicle Collisions: most common cause of accidental death in people ages 1-39 Shaken Baby Syndrome: retinal hemorrhages 1st & 2nd Degree Burns: no permanent scarring Most common cause of death in burn ptssepsis caused by pseudomonas Heat Exhaustion: <40C, no anhidrosis/no mental status s Heat Stroke: >40C, anhidrosis, impaired conscioiusness AC electricity more dangerous than DC Most Common Drowning: Wet drowning High Altitude: o O2 [ ] 21%, atmospheric pressure o Respiratory alkalosis, right shifted O2 Binding Curve Ionizing Radiation: damage to DNA Lymphoid Tissue: most sensitive to radiation Bone: least sensitive tissue to radation Total Body Radiation: lymphopenia 1st hematologic sign Ultraviolet Light B: pyrimidine dimers distorts DNA helix Basal Cell Carcinoma: most common UVB light-related skin cancer

Pancreas bile salts/acid intestinal cells

Protein-Energy Malnutrition Kwashiorkor: o inadequate protein intake o pitting edema o fatty liverapoB synthesis & VLDL synthesis Marasmus: o total calorie deprivation o extreme muscle wasting Eating Disorders Anorexia: o Distorted body image o 2 amenorrhea, osteoporosis o Most common cause of deathventricular arrhythmia Vomiting in Bulimia Nervosa: produces hypoK metabolic alkalosis BMI: weight in kg/height in m2 Obesity: o abdominal visceral fat most important o adipose causes synthesis insulin receptors Leptin: hormone, maintains energy balanceintake & output 3500 Calories = 1lb Leptin Gene: often defective in obesity Fat Soluble Vitamins -carotenemia: yellow skin, white sclera Vitamin A: vision, cell differentiation, growth/reproduction Night Blindness: 1st sign of vitamin A deficiency Vitamin A in tx: acne, acute promyelocytic leukemia Vitamin A Toxicity: consumption of bear liver Sunlight: major source of Vitamin D Vitamin D o Liver & kidney hydroxylation o Bone mineralization, maintain serum Ca & P Renal Failure: most common cause of Vitamin D deficiency Vitamin E: o Cell membrane antioxidant

Nutritional Disorders
Nutritional & Energy Requirements in Humans BMR: o most important factor in determining daily energy expenditure o hypothyroidism & hyperthyroidism Dietary Fuels Carbohydrate Digestion: begins in mouth, 4kcal/g Disaccharides: o lactase, maltase, sucrose o produce glucose, galactose, fructose Amino Acids: substrates for gluconeogenesis Protein Digestion: begins in stomach, pepsin & acid Essential Fatty Acids: linolenic, linoleic acids Fat Digestion o Begins in small intestine

o Toxicity: synthesis vitamin K-dependent coagulation factors Vitamin K o Majority synthesized by colonic bacteria o -carboxylates, II, VII, IX, X Broad Spectrum Antibiotics: most common cause of vitamin K deficiency in hospital Newborns: require vitamin K injection Rat Poison contains coumarin derivatives

Copper Excess: Wilsons Dz Iodide Deficiency: multinodular goiter Chromium: useful in diabetics Selenium: antioxidant Fluoride: o component of Ca hydroxyapatite o Deficiency: dental caries

Water-Soluble Vitamins Thiamine: o present in outer shell & seed of grains o important in ATP synthesis Chronic Alcoholism: most common cause of thiamine def in US Riboflavin: FAD & FMN in citric acid cycle Niacin: NAD & NADP cofactors Corn Based Diets: deficient in tryptophan & niacin Tryptophan: o used to synthesize niacin o deficiencyHartnup Dz& Carcinoid Syndrome 3 Ds of Pellagra: dermatitis, diarrhea, dementia Pyridoxine: heme synthesis, transamination, neurotransmitters Isoniazid Therapy: most common cause of pyridoxine def Vitamin B12: o Only in animal products o DNA synthesis, odd-chain fatty acid synthesis Pernicious Anemia: most common cause of vitamin B12 def Folic Acid: DNA synthesis Goat Milk: lacks folate & pyridoxine Alcohol Excess: most common cause of folate def Biotin Deficiency: eating raw eggs Ascorbic Acid: o collagen synthesis, antioxidant, reducing agent o cofactor conversion dopamine to norepinephrine o Scurvydef of ascorbic acid

Dietary Fiber Fiber Types: insoluble, soluble Soluble: lowers cholesterol Fiber: risk for sigmoid diverticulosis, certain cancers & heart dz Na Restriction: htn, heart failure, chronic liver/kidney dz Protein-Restricted Diet: chronic renal failure, cirrhosis

Neoplasia
Nomenclature Benign Tumors: epithelial or CT origin Epithelial Tissue Origin: ectoderm or endoderm CT Origin: mesoderm Teratoma: derives from ectoderm, endoderm, & mesoderm Carcinomas: derive from squamous, glandular (adenocarcinoma), transitional epithelium Sarcomas: derive from CT Hamartoma: non-neoplastic overgrowth of tissue Choristoma: normal tissue where it should not be

Trace Elements Zinc Deficiency: poor wound healing, dysgeusia, perioral rash

Properties of Benign & Malignant Tumors Parenchyma: neoplastic component Grade of Cancer: does the cancer resemble its parent tissue or not Malignant Tumors: o nuclear/cytoplasmic ratio, abnormal mitotic spindles o 30 doubly times before detected Benign & Malignant Tumors: monoclonal Malignant Tumors: upregulation telomerase activity Basal Cell Carcinomas of Skin: invade tissue but do NOT metastasize

Invasion: 2nd most important criterion for malignancy Resist Invasion: cartilage, elastic tissue Loss of intercellular Adherence Cell invasion

Rx GERD: risk for distal adenocarcinoma of esophagus

Metastasis Extranodal Metastasis: has greater prognostic significance than nodal metastasis Lymph Nodes: o 1st line of defense in carcinomas o Most common tissue metastized to Route of Metastasis: lymphatic, hematogenous, seeding of body cavities Seeding: common w/ surface-derived ovarian cancers Bone Metastasis: vertebra most common site, paravertebral venous plexus Osteoblastic Metastasis: serum alkaline phosphatase Osteolytic Metastasis: potential for hyperCa, pathologic frx Bone Metastasis: osteoblastic (radiodense) or ostelytic (radiolucent) Cancer Epidemiology Cancer is 2nd most common cause of death in US Lifetime risk of cancer: MEN > women Blacks: greater overall risk for cancer Most common cancer in children: Acute Lymphoblastic Leukemia Cancer in Men: prostate, lung & colorectal Cancer in Women: breast, lung & colorectal Gynecologic Cancer: endometrium, ovary, cervical Most common cause of cancer death in adults: lung cancer Malignant Melanoma: most rapidly ing cancer Actinic (solar) Keratosis: precursor of squamous cell carcinoma Cessation of is most important factor in ing risk for cancer HBV Immunization: risk for hepatocellular carcinoma HPV Immunization: risk for cervical cancer Cervical Cancer: least common gynecologic cancer in US Cervical Pap Smear: most responsible for incidence/mortality rate for cervical cancer PSA: more sensitive than specific Rx H. pylori Infection: risk for developing gastric lymphoma/adenocarcinoma

Carcinogenesis Point Mutations: most common type of mutation in cancer Proto-oncogenes: involved in normal growth & repair Suppressor Genes: protect against unregulated cell growth BCL2 Gene Family: antiapoptosis genes BAX Gene: apoptosis gene Repair Genes: correct errors in nucleotide pairing, excise pyrimidine dimers Enzymes Involved in Dimer Excision: endonuclease, exonuclease, polymerase, ligase Carcinogenic Agents Chemical Carcinogenesis: initiation promotion progression Pathogens & Cancer: viruses > bacteria > parasites Leukemia: most common cancer dt ionizing radiation Basal Cell Carcinoma: most common cancer dt excessive UV light exposure Clinical Oncology Cytotoxic CD8 T Cells: most effective host defense against cancer Prognosis: Extranodal Metastasis > Lymph Nodes > Tumor Size Anemia of Chronic Dz: most common anemia in cancer Hemostasis in Malignancy: thrombogenic Gram Sepsis: most common cause of death in cancer HyperCa: most common paraneoplastic syndrome Acanthosis Nigricans: may be associated w/ stomach cancer Signs of Ectopic Hormone Production: hyperCa, hypoNa, hypoglycemia, hypercortioslism, polycythemia Hormone Tumor Marker: calcitoninmedullary carcinoma of thyroid

Vascular Disorders
Lipoprotein Disorders

Chylomicron: o diet-derived triglycerides o absent during fasting o turbid supranate Capillary Lipoprotein LipasesCPL o Located in adipose, muscle, & myocardium o Induced by insulin o Activated by apoCII o VLDL IDL LDL VLDL: o liver-derived triglyceride o TG/5 Hypertriglyceridemia: causes turbidity in plasma LDL o Transports cholesterol o (CH HDL-TG)/5 Serum CH: fasting NOT required HDL o good CH o source of apolipoproteins CII & E o removes cholesterol from plaques for disposal in liver VLDL causes HDL Type I: CPL or apo CII Type II: o LDL dt LDL receptors o CH synthesis o CH excretion in bile Achilles Tendon Xanthoma: pathognomonic for familial hypercholesterolemia Type III: o deficiency in apoE o cylo remnants & IDL o Palmar santhomas Type IV: o VLDL o most common lipid disorder o Alcohol Excessmost common cause o Eruptive xanthomas o Rx: carb & alcohol intake

Oral Contraceptives o Estrogen TG synthesis in liver o Variable effects on LDL & HDL Type V o VLDL + Chylomicrons o Hyperchylomicronemia syndrome ApoB Deficiency: chylomicrons, VLDL & LDL

Arteriosclerosis Medial Calcification: dystrophic calcification in muscular arteries Atherosclerosis: endothelial cell injury, platelets/macrophages pivotal rules Fibrous Cap: pathognomonic lesion of atherosclerosis C-Reactive Protein: excellent marker of disrupted fibrous plaques Abdominal Aorta: most common site for atherosclerosis, no vasa vasorum Complications of Atherosclerosis: aneurysms, thrombosis, ischemia Hyaline Arteriosclerosis: diabetes mellitus & htn Vessel Aneurysms Abdominal Aortic Aneurysm: most common aneurysm in men >55yo Rupture Triad: left flank pain, hypotension, pulsatile mass Fungal Vessel Invaders: B. fragilis, P. aeruginsos, Salmonella CNS Berry Aneurysms: jxn communicating branch w/ main vessel Aortic Arch Aneurysms: tertiary symphilis, vasa vasorum vasculitis Syphilitic Aneurysms: produces aortic regurgitation, bounding pulses Aortic Dissection o cystic medial degeneration o pain radiates into back o absent pulses o most common cause of death in Marfans & EDS pts o cardiac tamponademost common cause of death Venous System Disorders Superficial Varicosities: valve incompetence Phlebothrombosis: stasis of blood flow most common cause Stasis Dermatitis: sign of DVT Thrombophlebitis: pain & tenderness overlying vein SVC Syndrome: compression of SVC by primary lung tumor

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Thoracic Outlet Syndrome: common among weight lifters, tight scalene muscles Acute Lymphagitis: S. pyogenes cellulitis Turners Webbed Neck: lympathic abnormality

Vascular Tumors & Tumor-like Conditions Bacillary Angiomatosis: Bartonella henselae, common in AIDS Vasculitic Disorders ANCA: antibodies against components of neutrophils Small Vessel Vasculitis: palpable purpura Medium-Sized Vessel Vasculitis: thrombosis, aneurysm formation Large Vessel Vasculitis: absent pulse, stroke Hypertension Systolic Blood Pressure o Correlates w/ SV, aorta compliance o SBP: preload & contractility o SBP: preload & contractility, afterload Diastolic Blood Pressure o Correlates w/ tonicity of TPR arterioles o DBP: vasoconstriction peripheral resistance arterioles o DBP: vasodilation peripheral resistance arterioles Pathogenesis HTN: renal retention of Na commonly involved Most common type of HTNessential htn Renovascular HTN o most common cause of 2 htn o atherosclerosis in men o fibromuscular hyperplasia in women Plasma Renin Activity: in involved kidney & in unaffected kidney Fibromuscular Hyperplasia: beaded appearance of renal artery Complications of HTN: acute MI, stroke & renal failure

Afterload: resistance ventricle contracts against to eject blood in systole Preload: equivalent to LVEDV &/or RVEDV Ventricular Hypertrophy o afterload causes CONCENTRIC hypertrophy o preload causes ECCENTRIC hypertrophy Consequences of Hypertrophy: Heart Failure, S4, Angina (LVH) S4: blood entering noncompliant ventricle

Heart Disorders
Ventricular Hypertrophy Wall stress gene controlled sarcomere duplication

Congestive Heart Failure Left-Sided Heart Failure = forward failure pulmonary edema Systolic Dysfxn o most common type of LHF o ventricular contraction, EF Diastolic Dysfxn o most common cause of HTN o resistance to filling ventricle, normal EF Dyspnea: cannot take full inspiration Pulmonary Edema: hydrostatic pressure > oncotic pressure Kerleys Lines: septal edema Heart Failure Cells: alveolar macrophages w/ hemosiderin S3 Heart Sound: 1st cardiac sign of LHF Paroxysmal Nocturnal Dyspnea/Orthopena: venous return to right side of heart at night Brain Natriuretic Peptide: useful in confirming/excluding LHF Right-Sided Heart Failure = backward failure in venous hydrostatic pressure LHF: most common cause of RHF RHF o venous hydrostatic pressure o Neck vein distention, hepatomegaly, dependent pitting edema, ascites ACE-I: afterload, preload -Blockers: myocardial O2 consumption, HR TPR = Viscosity/Radius of Vessel Causes of high output failure: SV, TPR, arteriovenous fistula Ischemic Heart Disease Tachycardia: diastole & filling of coronary arteries

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LAD: most common site of coronary artery thrombosis Angina Pectoris o most common manifestation of coronary artery dz o age most important risk factor o MALES > females Stable Angina o Most common type of angina o Exercise-induced substernal chest pain o Subendocardial ischemia w/ ST-segment depression Prinzmetals Angina o vasospasm w/ transmural ischemia o ST-segment elevation o Ca Channel Blockers vasodilate coronary arteries Unstable Angina: angina at rest,multivessel dz, disrupted plaques Chronic Ischemic Heart Dz: replacement of muscle by fibrous tissue Sudden Cardiac Death o unexpected death w/in 1 hr after symptoms o coronary artery thrombosis NOT usually present Mitral Valve Prolapse Sudden Death: arrhythmias from mitral regurgitation or CHF Acute Myocardial Infarction o most common cause of death in US o Q wave type transmural o Non-Q wave type subendocardial o Coagulation Necrosis w/in 24hrs o Heart softest 3-7danger of rupture o Retrosternal pain, radiation to left arm/shoulder, diaphoresis Rupture of disrupted plaque platelet thrombus AMI Cocaine: AMI w/ normal coronary arteries Reperfusion: short/long-term survival Contraction Band Necrosis: reperfusion, hypercontraction myofibrils dt Ca Q Wave AMI: early mortality rate Non-Q Wave AMI: risk for sudden cardiac death Ventricular Fibrillation: most common cause of death in acute MI Myocardial Rupture: most common at 3-7 days Posteromedial Papillary Muscle Rupture: RCA thrombosis, mitral regurgitation Mural Thrombus: danger of embolization

Fibrinous Pericarditis: earlyacute inflammation & late complications autoimmune Ventricular Aneurysms: CHF most common cause of death RV AMI: hypotension, RHF, preserved LV fxn Reinfarction: reappearance of CK-MB after 3 days cTnl, cTnT: cannot dx reinfarction EKG Findings in AMI: inverted T waves, elevated ST segment, Q waves

Congenital Heart Disease Chorionic Villus: primary site for O2 exchange Umbilical Vein: highest PO2 in fetal circulation Fetal Circulation: foramen ovale & ductus arteriosus are patent Single Umbilical Artery: risk congenital abnormalities Ductus Arteriosus: become ligamentum arteriosum Newborn: foramen ovale & ductus arteriosus are CLOSED Congenital Heart Dz: risk w/ maternal age CHD Shunts: L-R & R-Loften cyanoic L-R Shunts: danger of shunt reversal if uncorrected Ventricular Septal Defect o most common CHD in children o defect in membranous septum Atrial Septal Defect o Most common CHD in adults o Patent foramen ovale o Fixed splitting of S2 Patent Ductus Arteriosus o Closed w/ indomethacin o Machinery murmur Tetralogy of Fallot o Most common cyanotic CHD o Degree of Pulmonary Valve stenosis correlates w/ presence or absence of cyanosis Cardioprotective Shunts: ASD & PDA Tet Spells: squatting, systemic vascular resistance, PaO2 Transposition: aorta empties RV, pulmonary artery empties LV, atria normal Infantile Coarctation: associated w/ Turners Syndrome

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Adult Coarctation: disparity between upper/lower extremity blood pressure > 10mmHg Hypertension: dt activation of Renin-Angio-Aldosterone system Coarctation Collaterals: Anterior Intercostal Arteries Posterior Intercostal Arteries to aorta, Superior Epigastric Artery-Internal Thoracic Artery to external iliac artery

Acquired Valvular Heart Disease Acute Rheumatic Fever o After group A strep pharyngitis o Immune-mediated type II hypersensitivity rxn o Cell-mediated immunity Type IV o Migratory polyarthritis most common initial presentation o Myocarditis most common cause of death o Mitral Valve most often involved followed by Aortic Valve o Dx w/ Jones Criteria o Carditis, Arthritis, Chorea, Erythema Marginatum, SubQ Nodules o ASO & DNase B titers Rheumatic Fever o Mitral regurgitation in acute attack o Mitral stenosis in chronic disease Mitral Valve Stenosis o most common cause is recurrent Rheumatic Fever o pulmonary venous htn o RHF o Opening snap followed by an early to mid-diastolic rumble Atrial Fib: common cause of mitral stenosis Mitral Valve Prolapse o most common cause of mitral regurgitation o association /w Marfans & Ehlers-Danlos syndromes o myxomatous degeneration o excess dermatan sulfate o Systolic click followed by murmur o Preload alters click & murmur relationship to S1/S2 Symptomatic Mitral Valve Prolapse: -Blockers Mitral Valve Regurgitation o pansystolic murmur o S3/S4

o No intensity w/ deep held inspiration Calcific AV Stenosis: most common cause in pts >60yo AV Stenosis o Ejection murmur o S4 o intensity w/ preload o intensity w/ preload o Most common valvular lesion causing syncope & angina w/ exercise o Microangiopathic hemoly anemia w/ schistocytes o Hemoglobinuria Isolated AV Root Dilation: most common cause of aortic regurgitation AV Regurgitation o pulse pressure o Early diastolic murmur o Bounding pulses o S3 & S4 o No intensity w/ inspiration o Hyperdynamic circulation Austin Flint Murmur: sign for AV replacement Tricuspid Valve Regurgitation o functional most common cause adults o infective endocarditis o carcinoid heart disease o pansystolic murmur o S3/S4 o intensity w/ deep held inspiration Pulmonary Valve Regurgitation: pulmonary htn Carcinoid Heart Disease: PV stenosis or TV Regurgitation Strep viridans: most common cause of infective endocarditis Staph aureus: most common pathogen producing infective endocarditis in IV drug use Strep bovis: most common pathogen producing infective endocarditis in ulcerative colitis/colorectal cancer TV regurgitation in IV drug abusers is dt infective endocarditis Infective Endocarditis o fever most consistent sign o microembolization

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o immuncomplex vasculitis o + blood culture majority of cases Libman-Sacks Endocarditis: associated w/ SLE, Mitral Valve involved Marantic Endocarditis: sterile vegetations, paraneoplastic syndrome

ventricular compliance

Myocardial & Pericardial Diseases Coxsackievirus: most common cause of myocarditis & pericariditis Chagas Disease: most common cause of myocarditis leading to CHF in Central/South America Drugs: Doxorubicin & Daunorubicin Myocarditis: CK-Mb, troponins I & T Pericarditis o coxsackievirus most common cause o precordial rub o pain relieved by leaning forward Young woman w/ peridcarditis & effusionmost likely has SLE Pericardial Effusion on Inspiration: JVD, systolic blood pressure > 10mmHg Constrictive Pericarditis o incomplete filling of chambers o pericardial knock Cardiomypoathy Cardiomyopathy: dilated, hypertrophic, restrictive Dilated Cardiomyopathy o Most common cardiomyopathy o Myocarditis most common cause o Doxorubicin & daunorubicin o Global enlargement of heart Hypertrophic Cardiomyopathy o Most common cause of sudden death in young individuals o Obstructive BELOW aortic valve o Preload changes on murmur intensity opposite of those for AV stenosis o Sudden cardiac death dt V Tachy/Fib o Tx w/ -Blockers Restrictive Cardiomyopathy o Least common cardiomyopathy o Low-voltage EKG

Heart Tumors Heart Tumors: metastasis > primary tumors Cardiac Myxoma o most common in LEFT atrium o myxomas occur in adults Rhabdomyomas: occurs in children

Red Blood Cell Disorders

Erythropoiesis EPO o synthesized by interstitial cells in peritubular capillary bed o stimuli for EPOhypoxemia, left-shifted OBC, high altitude Reticulocyte Count o measure of effective erythropoiesis o Correction: Hct/45 x Reticulocyte Count o Corrected Reticulocyte Count: <3% ineffective erythropoiesis & >3% effective erythropoiesis o Polychromasia: divide original reticulocyte correction by 2 Extramedullary Hematopoiesis o most often occurs in LIVER & SPLEEN o heaptosplenomegaly Anemia Prematurity: loss of iron from mother & blood loss from venipuncture Fetal Hb: left-shifts OBC causing an in Hb Children: more right-shifted OBCs than adults Anemia in Children: <11.5 g/dL Anemia in Adults: <13.5 g/dL Anemia in Nonpregnant: <12.5 g/dL Pregnancy: 2x greater in plasma vol than RBC mass Thalassemia: Hb & Hct, RBC count, MCV/RBC <13 Anemia: o O2 sat & arterial PO2 normal o Sign of disease o Not a specific dx o O2 content MCV: classification of anemia

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MCHC: in microcytic anemia & in spherocytosis RDW: measure of size variation of RBCs Fe Deficiency: RDW Mature RBC: anaerobic glycolysis, lactic acid end-point Cori Cycle: lactic acid converted to glucose in liver glucose to RBC GSH: neutralizes peroxide & other free radicals MetHb Reductase: reduces Fe3+ to Fe2+ 2,3BPG: product of glycolytic cycle Unconjugated Bilirubin: end-porduct of heme degradation in macrophages Ferritin: synthesized in bone marrow macrophages Serum Ferritin: Fe Deficiency, Anemia of Chronic Dz, Fe Overload Dz Serum Fe: Fe Deficiency, Anemia of Chronic Dz, Fe Overload Dz Total Fe Binding Capacity (TIBC) o TIBC = Transferrin o TIBC = Transferrin Ferritin Stores: TIBC, Fe Deficiency, Ferritin Stores: TIBC, ACD, Fe Overload Fe Saturation: Fe deficiency, ACD, Fe saturation, Fe Overload Dz HbA: 2/2 or 2/2 HbF: 2/2

Microcytic Anemia Microcytic Anemia: defects in Hb synthesisHeme + Globin Chains Types of Fe: ReducedFe2+ heme Fe in meat & OxidizedFe3+ nonheme Fe in plants Oxidized Fe3+: must be reduced to Fe2+ for reabsorption in duodenum Fe: majority stored in marrow macrophages Ascorbic Acid: reduces nonheme Fe3+ into Fe2+ Fe Deficiency o most commonly caused by BLEEDING o Fe, % saturation, ferritin o TIBC & RDW o Stages: all lab studies abnormal before anemia is present Koilonychia: spoon nails, sign of Fe deficiency Thrombocytosis: common finding in chronic Fe deficiency Rx Fe Deficiency: ferrous sulfate Anemia of Chronic Dz

o most common anemia in hospitalized pts o most common anemia in malignancy o alcohol excess o Fe, TIBC, % saturation, Ferritin Hepcidin: antimicrobial peptide synthesized/released by liver Blacks: can have or -thalassemia -Thalassemia: dt gene deletions -Thalassemia Trait o 2 gene deletions o HbA, HbA2, HbFnormal electrophoresis o RBC count HbH: 4 chains Hb Bart: 4 chains -Thalassemia o mildDNA splicing defect o severestop codon -Thalassemia Minor o /+ o HbA, RBC count, HbA2, HbF -Thalassemia Major o 0/0 o no HbA, HbA, HbF Sideroblastic Anemia o defect in heme synthesis in mitochondria o ringed sideroblasts o alcohol most common cause o serum Fe, Fe saturation, Ferritin o MCV & TIBC Pyridoxine Deficiency: Isoniazid Therapy most common cause Pb Poisoning o paint, batteries o denatures ferrochelatase, ALA dehydrase, ribonuclease o coarse basophilic stippling o Pb deposits in epiphyses o Rx: chelation therapy Macrocytic Anemia Vitamin B12 o only present in animal products o reabsorbed in terminal ileum

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o odd chain fatty acid metabolism Parietal Cells: synthesize intrinsic factor (IF) & HCl Vitamin B12 Deficiency o pernicious anemia most common cause o posterior columns, lateral corticospinal tract, dorsal spinocerebellar tract o causes macrocytic anemia neurologic dz Intestinal Conjugase: inhibited by phenytoin Monoglutamate Reabsorption: inhibited by alcohol & oral contaceptives Folate Deficiency: alcohol most common cause Vit B12/Folate Deficiency o delayed nuclear maturation o megaloblasts o pancytopenia, apoptosis, macrophage phagocytosis Homocysteine: folate (most common) & vitamin B12 deficiency Thymidylate Synthase: irreversibly inhibited by 5-Fluorouracil Dihydrofolate Reductase: inhibited by methortrexate (reversible) & Trimethoprim Pernicious Anemia: o incidence gastric cancer o Type II hypersensitivity o antibiodies & gastrin levels Methlymalonic Acid: most sensitive test for Vit B12 deficiency Hypersegmented Neutrophil: marker for folate or B12 def Schilling Test: defines the cause of B12 def Maternal Folate Intake: risk for open neural tube defect RBC Folate: best indicator of folate stores Alcohol Liver Dz: round macrocytic target cells

Anemia Malignancy: ACD, blood loss, metastasis to marrow, immunologic

Normocytic AnemiaCorrected Reticulocyte Count or Index: <3% Acute Blood Loss: external or internal Signs of Vol Depletion: BP & pulse Aplastic Anemia o most cases idiopathic o drugs most common known cause o fever, bleeding, fatigue o pancytopenia Anemia Chronic Renal Failure: EP most common cause Chronic Renal Failure: platelet dysfxn

Normocytic AnemiaCorrected Reticulocyte Count or Index: <3% Types of Hemolytic Anemia: intrinsicRBC defect or Extrinsicfactors outside RBC Extravascular Hemolysis: macrophage phagocytosis, unconjugated hyperbilirubinemia Intravascular Hemolysis: serum haptoglobin, hemoglobinuria Hereditary Spherocytosis o intrinsic defect o extravascular hemolysis o black, Ca bilirubinate gallstones o RBC osmotic fragility Aplastic Crisis: parvovirus induced Hereditary Epliptocytosis: >25% elliptocytes in peripheral blood Paroxysmal Nocturnal Hemoblgobinuria o loss of anchor for decay accelerating factor (DAF) o intrinsic defect o intravascular hemolysis o pancytopenia o screensucrose hemolysis tests o confirmacidified serum test Trait x Trait: 25% normal, 50% trait, 25% disease Sickle Cell Anemia o Intrinsic defect o Extravascular hemolysis o Missense mutation o Substitution of VALINE for GLUTAMIC acid o Sickling: HbS & deoxyHb o Severe hemolytic anemia o Vasoocclusive crises Irreversible Sickle Cell: adherence to endothelial cells Dactylitis: most common presentation in infants w/ sickle cell Acute Chest Syndrome: most common cause of death in adults w/ sickle cell Howell-Jolly Bodies: sign of splenic dysfxn in sickle cell Pathogens associated w/ Sickle Cell: Streptococcus pneumonia sepsis, Salmonella paratyphi osteomyelitis

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Sequestration vs Aplastic Crisis: reticulocytosis for sequestration & reticulocytopenia for aplastic crisis Sickle Cell Trait: no anemia, microhematuria HbAS: HbA 55-60%, HbS 40-45% HbSS: HbS 90-95%, HbF 5-10% & no HbA Target Cells: excess RBC membrane, sign of hemoglobinopathy or alcohol excess G6PD Deficiency o most common enzyme deficiency causing hemolysis o intrinsic defect o primarily intravascular hemolysis o oxidant damage with Heinz Bodies & Bite Cells o O2-dependent MPO system dysfxn o Lack of NADPH cofactor o Active hemolysis screen w/ Heinz Body Prep o Enzyme analysisconfirmatory test Drugs causing G6PD Def: primaquine, dapsone, sulfonamides PK Deficiency o Intrinsic defect o Extravascular hemolysis o 2,3BPF right shifts OBC o Offsets clinical effects of anemia Immune Hemolytic Anemia: Autoimmune warm type (IgG) most common cause Drug-Induced: drug adsorptionpenicillin, immuncomplexquinidine, autoantibodymethyldopa IgG-Mediated: extravascular hemolysis, spherocytosis Complement-mediated: intravascular or extravascular hemolysis IgM-Mediated: intravascular (most common) or extravascular hemolysis Direct Antihuman Globulin (DAT): most important marker of immune hemolytic anemia Micro/Macroangiopathic Hemolytic Anemia o Aortic stenosismost common cause o Extrinsic o Intravascular hemolysis o Schistocytessign of MHA Malaria o Anopheles mosquito o Intravascular hemolysis correlates w/ fever spikes

o o o o o o o

Extrinsic, intravascular hemolysis P. vivaxmost common type w/ fever every 48hr P. falciparummost lethal type w/ fever quotidian P. malariafever every 72hr Chloroquine prevention Rx P. vivax/ovalechloroquine + primaquine Rx P. falciparum: chloroquine sensitivechloroquine alone, resistantquinine sulfate + doxycycline

White Blood Cell Disorders

Benign Qualitative WBC Disorders Qualitative WBC Defects o Defects in structure & fxn o Unusual pathogens, cold abscesses, frequent infections Jobs Syndrome: defect in chemotaxis, IgE Absolute Count = %leukocytes x total WBC count Leukemoid Reaction: benign, exaggerated leukocyte response Leukoerythroblastic Rxn in Woman >50yo: usually dt breast cancer metastatic to bone Benign Quantitative WBC Disorders Neutrophilic Leukocytosis: neutrophil count >7000 cells/mm3 Neutropenia: neutrophil count <1500 cells/mm3 Eosinophilia o eosinophil count >700 cells/mm3 o Type I hypersensitivity o Invasive helminthes o Hypocortisolism Eosinopneia: hypercortisolism Basophilia: consider myeloproliferative disease Lymphocytosis o Adult: lymphocyte count >4000 cells/mm3 o Child: lymphocyte count >8000 cells/mm3 Atypical Lymphocytes o angtigenically stimulated o EBV, CMV, Viral Hepatitis, Phenytoin B Cells have CD21 receptor sites for EBV Infectious Mono: rash develops if pt placed on ampicillin

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Heterophile Antibodies: IgM antibodies directed against horse, sheep, bovine RBCs Anti-VCA-IgG/IgM: excellent test if screening test is negativemono Lymphopenia o Adult: lymphocyte count <1500 cells/mm3 o Child: lymphocyte count <3000 cells/mm3 Lymphopenia in HIV: CD4 helper T cell lysis by virus Corticosteroids: produce neutrophilic leukocytosis, eosinopneia & lymphopenia Monocytosis: chronic infection, autoimmune dz, malignancy

Leukemias Leukemia o malignant transformation of marrow stem cells o arises in the marrow & disseminates ALL o most common leukemia & cancer in CHILDREN o CNS o Testicle involvement AML: 15-60yo CML: 40-60+yo CLL: most common overall type of leukemia Acute Leukemia o abrupt onset o key finding of blasts >20% in bone marrow Skin Involvement: T cell leukemias Bone Marrow Exam: most important test for diagnosing leukemia Chronic Leukemia o Insidious onset o Key finding of blasts <10% in bone marrow Acute vs Chronic Leukemia: bone marrow aspirate w/ blast count

Neoplastic Myeloid Disorders Myeloid Disorders: neoplastic stem cell disorders Polycythemia Vera o most common chronic myeloproliferative disorder o serum EPO best initial test

o only polycythemia w/ PV & EPO o phlebotomy viscosity-induced thrombosis RBC Count = RBC mass/PV Relative Polycythemia: RBC count, PV, normal RBC mass, Sao2, EPO Appropriate Absolute Polycythemia: RBC mass, EPO, normal PV, Sao2 Inappropriate Absolute Polycythemia o Ectopic Secretion EPO: RBC mass, EPO, normal PV, normal Sao2 o PRV: RBC mass, EPO, PV, normal Sao2 PRV o mutation of JAK2 gene o thrombotic events CML: t9:22 translocation ABL proto-oncogene Philadelphia Chromosome = chromosome 22 w/ translocation CML Blast Crisis o myeloblasts or lymphoblasts o no Auer Rods o only leukemia w/ thrombocytosis BCR-ABL Fusion Gene: most sensitive & specific test for CML Myelofibrosis & Myeloid Metaplasia (MMM) o JAK2 gene mutation o Extramedullary hematopoiesis o Marrow fibrosis o Massive splenomegaly o Tear drop RBCs o Leukoerythroblastic smear Essential Thrombocythemia (ET) o Dysplastic/nonfxnal platelets o platelets o JAK2 gene mutation Myelodysplastic Syndromes (MDS) o Cytopenias o Hypercellular marrow o >30% progress to acute leukemia Acute Promyelocytic Leukemia: t(15:17) Acute Monocyte Leukemia: gum infiltration AML: Auer rods in cytoplasm of myeloblasts Auer Rods: only in AML & NOT in CML

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 Lymphoid Leukemias ALL o Most common cancer & leukemia in children o CD10 & TdT positive, most common type o T(12:21) offerst favorable prognosis Adult T-cell Leukemia o association w/ HTLV-1 o skin lesions o lytic bone lesions w/ hyper Ca TAX gene: inhibits TP53 suppressor gene CLL o Most common leukemia o Most common cause of generalized lymphadenopathy in those >60yo o Hypogammaglobulinemia o Smudge cells Hairy Cell Leukemia (HCL) o Spleen primary site for neoplastic cells o Absence of lymphadenopathy o Positive TRAP stain o Dramatic response to purine nucleosides

Toxoplasmosis: mononucleosis-like syndrome w/ painful cervical lymphadenopathy Tularemia: rabbits, ulceroglandular type most common

Non-Hodgkins Lymphoma Sinus Histiocytosis Axillary Nodes: favorable sign in breast cancer NHL o majority B-cell origin o most common malignant lymphomas adults/kids Extranodal Sites: stomach (most common), CNS, Peyers Patches Epstein-Barr Virus: Burkitts Lymphoma, CNS lymphoma H. pylori: malignant lymphoma of stomach Lymphoma in Autoimmune Dz: Sjorgrens Syndrome, Hashimotos Thyroiditis Mycosis Fungoides: CD4 T helper cells neoplasm, skin involvement Sezary Syndrome: mycosis fungoides in leukemic phase Hodgkins Lymphoma Nodular Sclerosing HL o female dominant o most common type of HL EBV: association w/ mixed cellularity HL Reed-Sternberg Cell o neoplastic cell of HL o CD15+, CD30+ o Required to make HL dx HL o Pel-Ebstein Fever o Prognosisstage more important than type of HL Nodular Sclerosing HL: anterior mediastinal mass + single group of nodes above diaphragm Rx for HL: risk for 2nd malignancies

Lymphoid Tissue Disorders

Lymphadenopathy B Cells: germinal follicles T Cells: paracortex, thymus Histocytes: sinuses, skin, Langerhans cells Nodal Enlargement: <30 usually benign, >30 usually malignant Painful Lymphadenopathy: infection Painless Lymphadenopathy: metastasis or 1 malignant lymphoma Left Supraclavicular Node Metastasis: stomach or pancreatic carcinoma Hilar Nodes Metastasis: lung cancer Para-aortic Node Metastasis: testicular cancer Follicular Hyperplasia: prominent germinal follicles Dermatopathic Lympadenitis: melanin pigment in macrophages

Langerhans Cell Histiocytoses Histiocytes: CD1+, contain Birbeck granules Malignant Histiocytoses: skin involvement common, lytic bone lesions Hand-Schuller-Christian Dz: lytic skull lesions, diabetes insipidus, exophthalmos

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Eosinophilic Granuloma: benign histiocytosis, unifocal lytic lesions in bone

Mast Cell Disorders Mast Cell Dz: pruritus, swelling, hyperpigmentation Urticaria Pigmentosum: dermatographism, lesions remain hyperpigmented Mast Cells: metachromatic granules Plasma Cell Dyscrasias Plasma Cell Dyscrasia: monoclonal spike, usually IgG Bence Jones Protein: light chains in urine Myeloma o Rare <40yo o Normal plasma cell MGUS myeloma o Sepsis & renal failure common causes of death Bone Findings in Myeloma: lytic lesions, pathologica frx, hyperCa BJ Renal Dz in Myeloma: proteinaceous casts w/ multinucleated giant cell rxn MGUS: most common monoclonal gammopathy Spleen Disorders Red Pulp: fixed macrophages White Pulp: B & T cells Malaria: most common cause splenomegaly in developing countries Gauchers Dz: glucoerebrosidase, glucocerebroside Massive Splenomegaly: infarcts common w/ pain, friction rub, & Leftsided pleural effusion Splenomegaly in Cirrhosis: sugar coated spleen Hypersplensim: destruction of hematopoietic cells producing cytopenias Splenic Dysfxn: risk for strep pneumo sepsis Mechanisms: IgM, Tuftsin, splenic macrophages

Hemostasis Disorders
Normal Hemostasis & Hemostasis Testing Heparin-like Molecules: enhance ATIII activity

ATIII: neutralizes activated serine protease coagulation factors PGI2: vasodilator, inhibits platelet aggregation Proteins C & S: inactivate factors V & VIII, enhance fibrinolysis tPA: activates plasminogen to release plasmin TXA2: vasoconstrictor, enhances platelet aggregation vWF o platelet adhesion molecule o synthesized in Weibel-Palade bodies in endothelial cells o vWF causes VIII:c o Platelet adhesion o Prevents degradation of VIII:c in plasma Factor VIII: c synthesized in the liver + reticuloendothelial cells Tissue Thromboplastin: activates factor VII in extrinsic coagulation system Platelet Receptors: GpIb binds to vWF & GpIIb-IIIa binds to fibrinogen Ticlopidine, Clopidogrel & Abciximab: interfere w/ GpIIb-IIIa receptor fxn Important Platelet Storage Proteins: ADP, vWF, fibrinogen Platelet Fxn: stabilizes intercellular adherens jxns in venular endothelial cells Extrinsic System: factor VII, activates factors IX & X Intrinsic System: factors XII, XI, IX, VIII Factor XIIa: activates kininogen system Final Common Pathway: factors X, V, II, I Factor XIII: cross-links insoluble fibrin monomers Vitamin K Dependents Factors: procoagulants II, VII, IX, X, anticoagulants protein C&S Vitamin K: liver-activated by epoxide reductase Calcium: binds -carboxylated vitamin K-dependent factors Factors Consumed in Clot to Produce Serum: I, II, V, VIII Plasminogen Activators: tPA, streptokinase, urokinase Aminocaproic Acid: inhibits plasminogen D-Dimers: cross-linked fibrin monomers Platelet Sequence in Hemostasis: adhesion, release rxn, synthesis TXA, temporary plug TXA2: enhances fibrinogen attachment to GpIIb-IIIa receptors Temporary Platelet Plug: held together by fibrin BT: test of platelet fxn to formation of temporary plug Ristocetin Cofactor Assay: test of vWF fxn

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Coagulation Tests PT: evaluates factors VII, X, V, II & I INR: standardizes PT for warfarin therapy PTT: evaluates factors XII, XI, IX, VIII, X, V, II, I Fibrinolytic System Tests Fibrinogen Degradation Products: w/ lysis of fibrinogen & fibrin in fibrin thrombi D-Dimer Assay: specific for lysis of fibrin thrombi (clots), detects crosslinks Platelet Disorders TTP/HUS: platelet consumption + hemolytic anemia w/ schistocytes Thrombocytosis: chronic Fe deficiency, malignancy, splenectomy Aspirin: most common cause of qualitative platelet defect Petechiae: only w/ thrombocytopenia Senile Purpura: vessel instability Platelet Dysfxn: bleeding from superficial scratches, easy bruising, ie aspirin Thrombocytopenia: petechial, bleeding from superficial scratches, easy bruising Coagulation Disorders Coagulation Disorders o production, inhibition, consumption o Late rebleeding o Hemarthrosessevere deficiency Hemophilia A o X-linked recessive o % VIII:c never changes o Correlates w/ severity of dz o VIII:c o PTT Hemophilia B o X-linked recessive o Factor IX deficiency vWD

o AD inheritance o Associated w/ MVP, Marfan Syndrome, angiodysplasia o Most common hereditary coagulation disorder o Combined platelet & coagulation factor disorder o PTT, bleeding time o VIII:c, vWF o Rx: desmopressin acetate, OCP Circulating Anticoagulant: PT &/or PTT NOT corrected w/ mixing study Vitamin K Dependent Factors: II, VII, IX, X, protein C&Sactivated by carboxylation Newborns: lack bacterial colonization in bowel, no synthesis vitamin K Vitamin K Deficiency in Hospitalized Pts: dt antibiotic therapy Rat Poison: contains warfarin Warfarin: inhibits epoxide reductase, vitamin K is nonfxnal Cirrhosis o synthesis of Vit K dependent factors, activation of Vit K o Multiple hemostasis abnormalities Sepsis: most common cause of DIC DIC o Consumption of coagulation factors o Thrombohemorrhagic disorder o Lab Findings: PT, PTT, D-dimers, BT, platelets o Rx: treat underlying dz most important, component replacement D-Dimers: most sensitive screen for DIC

Fibrinolytic Disoders Primary Fibrinolysis o Open heart surgery o Prostatectomy o Diffuse liver dz o +test for FDPs, - test for D-dimers, nl platelet count, PT & PTT Secondary Fibrinolysis o D-dimer & FDPs o platelet count o PT & PTT Thrombosis Syndromes Acquired Thrombosis Syndromes: anticardiolipin, antibody, lupus anticoagulant Antiphospholipid Syndrome

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o thrombosis syndrome o spontaneous abortions, strokes, DVTs, hepatic vein thrombosis Anticardiolipin Antibody: false + syphilis serologic test Other Thrombosis Syndromes: post-op state, malignancy, OCPs, folate/B12, hyperviscosity Factor V Leiden: most common hereditary thrombosis syndrome ATIII Deficiency: normal PTT after standard dose of heparin Hemorrhagic Skin Necrosis: associated w/ warfarin therapy in protein C deficiency

Immunohematology Disorders
ABO Blood Group Antigens Blood Group O o Most common blood group o Anti-A-IgM, anti-B-IgM, anti-A & anti-B-IgG M Cells: transport A & B antigens in Peyers patches to B lymphocytes Group A: anti-B-IgM Group B: anti-A-IgM Group AB: no natural antibodies Newborns: lack natural antibodies Elderly People: frequently lose natural antibodies Blood Group AB Parents: cannot have O child Blood Group O Parents: cannot have AB, A or B child Forward Typing: identifies blood group antigen Back Typing: identifies natural antibodies Rh & Non-Rh Antigen Systems 5 Rh Antigens: D, C, c, E, e Rh Positive: D antigen positive Alloimmunization: antibodies develop against foreign antigens Atypical Antibodies: may produce Hemolytic Transfusion Rxn Individual with an atypical antibody must receive blood lacking the antigen Fy Antigen Negative RBCs: protection against P vivax malaria Blood Transfusion Therapy Autologous Transfusion: safest transfusion

CMV: most common pathogen transmitted by transfusion Newborn Transfusion: must irradiate blood to destroy lymphocytes Major Crossmatch: pt serum + donor RBCs A negative antibody screen ensures that a major crossmatch will be compatible Blood Group O: universal donors Blood Group AB: universal recipients Allergic Transfusion Rxn: IgE Mediated IgA Deficient Pts: must receive IgA deficient blood products Febrile Transfusion Rxn: anti-HLA antibodies against donor leukocytes Anti-HLA Antibodies: come from previous exposure to HLA antigens blood transfusion, transplant Acute Hemolytic Transfusion Rxn (HTR) o dt blood group incompatibility or presence of an atypical antibody o intravascular or extravascular hemolysis Suspected HTR: keep IV open w/ normal saline, d/c transfusion

Hemolytic Dz of Newborn (HDN) ABO HDN o most common HDN o mother group O, fetus blood A or B o positive direct Coombs test on fetal cord RBC Jaundice in 1st 24hrs: most common cause is ABO HDN Rh HDN o mother Rh negative, fetus Rh postive o anemia & amount of unconjugated bilirubin > ABO HDN o unconjugated bilirubin is freenot bound o positive direct Coombs test on fetal RBCs Kernicterus: free unconjugated bilirubin deposits in basal ganglia ABO Incompatibility: protects mother from Rh sensitization Prevention of Rh HDN: Rh immune globulinanti-D globulin Bilirubin Absorbance: 450nm OD 450: bilirubin wavelength in amniotic fluid, degree of correlates w/ severity of hemolysis Blue Fluorescent Light/Sunlight: converts bilirubin in skin to watersoluble dipyrrole

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Upper & Lower Respiratory Disorders

Pulmonary Fxn Tests A-a Gradient: hypoxemia of pulmonary origin Normal A-a Gradient: hypoxemia of extrapulmonary origin PAO2 = % O2 (713) arterial PCO2/0.8 Medically Significant: A-a 30 mmHg Hypoxemia + A-a: ventilation, perfusion, diffusion defects, R-L cardiac shunts Hypoxemia + normal A-a: depression of respiratory center, upper airway obstruction, chest bellows dz Volumes not directly measured by spirometry: TLC, FRC, RV Normal FEV1sec/FVC: 4/5L = 80% FRC - ERV = RV TLC & RV: TLC end of maximal inspiration, RV end of maximal expiration Obstructive Pattern: nonuniform empyting, expiratory curve shift to left of normal curve Restrictive Parenchymal: expiratory curve shifted to right of normal curve Upper Airway Disorders Choanal Atresia: newborn cannot breathe through the nose, cyanosis when breast-feeding Allergic Polyp: most common polyp, adults Triad Asthma: aspirin, nasal polyp, asthma Obstructive Sleep Apnea o excessive snoring w/ periods of apnea o apnea causes respiratory acidosis & hypoxemia o risk for developing cor pulmonale Polysomnography: confirmatory test for obstructive sleep apnea Sinus Infection: most common cause of sinusitis Srep pneumo: most common bacterial pathogen causing sinusitis Sinusitis o blockage of sinus drainage in nasal cavity o CT scan most sensitive Nasopharygneal Carcinoma: association w/ EBV Laryngeal Carcinoma o cigarette smokingmost common cause

o o

most on true vocal cords squamous cancer

Atelectasis Resorption Atelectasis o most common cause of fever 24-36hr after surgery o absent vibratory sensation, dullness to percussion, absent breath sounds Compression Atelectasis: air under pressure or fluid in pleural cavity Surfactant o Synthesized by type II pneumocytes o Cortisol s synthesis o Insulin inhibits synthesis o surface tension RDS o dt a in surfactant o prematurity, diabetes, C-section o intrapulmonary shunting o grunting, tachypnea, intercostal retractions o O2 complications, blindness, bronchopulmonary dysplasia Fetal Surfactant: w/ maternal intake of glucocorticoids Hypoglycemia in Newborn: dt excess insulin in response to fetal hyperglycemia Acute Lung Injury Left-sided Heart Failure: most common cause of pulmonary edema ARDS o noncardiogenic pulmonary edema o risk: sepsis, gastric aspiration, severe trauma o acute alveolar-capillary damage, sepsismost common cause o neutrophil damage to Type I & II pneumocytes o severe hypoxemia, PA wedge pressure <18 mmHg, A-a gradient Alveolar Macrophages: cytokines chemotactic to neutrophils

Pulmonary Infections Strep pneumo: most common cause of typical community-acquired pneumonia

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Bronchopneumonia: acute bronchitis w/ local extension into parenchyma Typical Pneumonia: signs of consolidationalveolar exudate Chest Radiograph: gold standard for diagnosing pneumonia Positive Gram Stain: more useful than culture Mycoplasma pneumonia: most common cause of atypical pneumonia Atypical Pneumonia: interstitial pneumonia, no signs of consolidation Water Loving Bacteria: Pseudomonas & Legionella pneumophila Pseudomonas: nosocomial pneumonia, contracted from respirators Pneumocystis jiroveci: most common pathogen in AIDS pneumonia TB o acid-fastness dt mycolic acid o cord factor = virulence factor o PPDdoes NOT distinguish active from inactive TB o Primary TBupper part lower lobes, lower part of upper lobes, Ghon complex o Reactivation TBupper lobe cavitary lesions o Drenching night sweats, fever, weight loss o Kidneys most common extrapulmonary site o Potts DiseaseTB in vertebra o MAC: most common TB in AIDS Lung Abscesses o Most often dt aspiration of oropharyngeal material o Mixed aerobic/anaerobic infection o Chest Xray shows cavitation & fluid level Superior Segment Right Lower Lobe: most common site for aspiration

Main Cause of 2 Pulmonary HTN: respiratory acidosis & hypoxemia Pulmonary HTN o Exertional dyspneamost common symptom o Tapering of pulmonary arteries on CXR Cor Pulmonale: PH + RVH

Vascular Lung Lesions Source of Pulmonary Thromboemoli: femoral veins Bronchial Arteries o protect lungs from infarction o arise from aorta & intercostal arteries Saddle Embolus: sudden death Pulmonary Infarctions o dyspnea & tachypnea most common S&S, respiratory alkalosis, hypoxemia o normal ventilation scan, abnormal perfusion scan o D-Dimers Dx of Pulmonary Embolism: V/Q scan, spiral CT 24

Restrictive Lung Dz Goodpasure Syndrome: hemoptysis followed by renal failure Alveolitis interstitial fibrosis Restrictive Lung Dz o compliance, elasticity o volumes/capacities, normal to FEV/FVC ratio Pneumoconiosis: inhalation of mineral dust Particle Size 1-5m: bifurcation respiratory bronchioles & alveolar ducts Particle Size <0.5m: alveoli Coal Workers Pneumoconiosis o Anthracotic pigen o Also element of obstructive lung dz o Complicated CWP: black lung dz o No risk for lung cancer or TB Dust Cells: alveolar macrophages w/ anthracotic pigment Caplan Syndrome: pneumoconiosis & cavitating rheumatoid nodules Silicosis o most common occupational dz o opacities contain collagen & quartz o egg0shell calcification in hilar nodes o risk lung cancer & TB Asbestos Fibers deposit in respiratory unit Ferruginous Bodies: Fe coated asbestos fibers Benign Pleural Plaques: most common lesions in asbestos-related dz Bronchogenic Carcinoma: most common asbestos-related cancer Malignant Mesothelioma: arises from serosa of pleura, encases lung Asbestos: not risk for TB Berylliosis: risk for lung cancer Sarcoidosis o most common noninfectious granulomatous dz of lungs o CD4 T helper cells interact w/ unknown antigen o Noncaseating granulomas o Skin nodules have granulomas on biopsy

o Most common noninfectious granulomatous dz of liver o ACE o HyperCa dt hypervitaminosis D o Dx of exclusionr/o other granulomatous dz Idiopathic Pulmonary Fibrosis: alveolitis leading to interstitial fibrosis, honeycomb lung Collagen Vascular Dz w/ Interstitial Fibrosis: systemic sclerosis, SLE, RA Pleural Effusion in Young Woman: consider SLE Farmers Lung o antigen is thermophilic actinomyces in moldy hay o type III & IV hypersensitivity Silo Fillers Dz: inhalation of gasesoxides of Nitrogen Byssinosis: contact w/ cotton, line, hemp products, Monday Morning Blues Drug associated w/ Interstitial Fibrosis: amiodarone, bleomycin, cyclophosphamide, methotrexate Radiation-induced Lung Dz: cause of interstitial lung dz

Obstructive Lung Dz Emphysema o Targets respiratory unit o Cigarette Smokingmost common cause of emphysema o compliance, elasticity o TLC, RV o FEV/FVC o Normal to arterial PCO2respiratory alkalosis Cigarette Smoke: chemotactic to neutrophils, inactivates AAT & Glutathione Destruction of Elastic Tissue: loss of radial traction Air trapping behind collapsed distal terminal bronchioles Centriacinar Emphysema: destruction of distal terminal bronchioles & RBs, upper lobe Panacinar Emphysema o targets distal terminal bronchioles & entire respiratory until, lower lobe o loss 1-globulin peak on SPE Emphysema: pink puffers, blow off CO2 Chest Xray in Emphysema: hyperlucency, AP diameter, vertically oriented heart, depressed diaphragms

Paraseptal Emphysema: risk for spontaneous pneumothorax Irregular Emphysema: scar emphysema Chronic Bronchitis o Productive cough at least 3mo for 2 consecutive yrs o Cigarette smokingmost common cause o Hypersecretion of mucous glands o Blue bloaters, retain CO2 & develop cyanosis o Stocky & obsess o Horizontally oriented heart o Chronic respiratory acidosis & hypoxemia o Hypoxemia early in CB Asthma o episodic & reversible airway dz o wheezing o AP diameter Extrinsic Asthma: type I hypersensitivity rxn IL-4: isotype switching to IgE production IL-5: production & activation of eosinophils Eosinophils: major basic protein & cationic protein damage epithelial cells LTC-D-E4: potent bronchoconstrictors Curschmann Spirals: shed epithelial cells Bronchial Asthma o Initially present w/ respiratory alkalosis o Normal pH or respiratory acidosis indicates need for intubation Intrinsic Asthma: nonimmune O3: free radical, O2 combining w/ oxides of nitrogen & sulfur Bronchiectasis: permanent dilation of bronchi & bronchioles Cystic Fibrosis o most common cause of bronchiectasis o autosomal recessive o 3 nucleotide deletion chromosome 7 coding for phenylalanine o Defective CFTR CL- is degraded in golgi apparatus o Loss of NaCl in sweat, loss of NaCl in luminal secretions (dehydrated) o Respiratory Infectionsmost common cause of death in CF o Chronic pancreatitis producing malabsoprtion & type I diabetes o Males infertile > females o Meconium ileus, rectal prolapse

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Primary Ciliary Dyskinesia: absent dynein arm in cilia Bronchiectasis o dilated bronchi extend to periphery o productive cough, hemoptysis Horner Syndrome: lid lag, miosis, anhydrosis Eaton-Lambert Syndrome: muscle weakness, antibody against Ca channel

Mediastinum Disorders Anterior Compartment: most common site for mediastinal masses Neurogenic Tumors: most common mediastinal mass, located in posterior mediastinum Symptoms in Thymomas: most often associated w/ Myasthenia Gravis Pleural Disorders Pleural Fluid Movement: parietal pleura to pleural space to lungs Congestive Heart Failure: most common overall cause of pleural effusion Pleural Fluid Exudate o acute inflammation, infarction, pneumonia, metastasis o tuberculosis & malignancy most common cause Chylous Effusion: lymphatic fluid, malignancy most common cause Pseudochylous Effusion: pleural effusion in RA Pleural Effusion: blunting costophrenic angle, obscure diaphragm Spontaneous Pneumothorax o commonly seen in tall, thin, young men o rupture of apical subpleural bleb o loss of negative intrathoracic pressure o sudden onset of dyspnea & pleuritic chest pain Tension Pneumothorax o penetrating trauma to lungs o check valve type of pleural tear o in pleural cavity pressure w/ each breath o Trachea deviates to contralateral side

Cleft Lip/Palate o most common congenital disorder of oral cavity o failure of fusion of facial processes Pre-AIDS-Defining Lesions: thrush, hairy leukoplakia, apthous ulcers Kaposi Sarcoma: hard palate, HHV-8 Dental Caries: caused by Strep mutans Fluoride: prevents dental caries Behcets Syndrome: recurrent apthous ulcers, uveitis, genital ulcers Melanin Pigmentation in Oral Mucosa: Addisons Dz, Peutz-Jeghers Syndrome Tooth Discoloration: tetracycline, fluoride erythropoietic porphyria Macroglossia: myxedema, Down Syndrome, Acromegaly, Amyloidosis, MENIIb Glossitis: deficiency of Fe, B12, Folate, Vitamin C, niacin, scarlet fever, hairy leukoplakia Leukoplakia/Erythroplakia o smoking & alcoholmajor risk factors o biopsy to r/o squamous dysplasia or cancer Wickhams Stria: association w/ squamous dysplasia or cancer Dentigerous Cyst: association w/ 3rd molar & amelobiastoma Squamous Papillomas: most common benign tumor in oral cavity Ameloblastoma: most common odontogenic tumor, soap bubble appearance in mandible Squamous Cell Carcinoma o Smoking products most common risk factor o Lower lipmost common site Basal Cell Carcinoma: upper lipmost common site Sjogrens Syndrome: dry eyes, dry mouth Parotid Gland: most common site for salivary gland tumors Pleomorpic Adenoma: most common salivary gland tumor Warthins Tumor: heterotopic salivary gland tissue in lymph node Mucoepidermoid Carcinoma: most common malignant salivary gland tumor

GI Disorders
Oral Cavity & Salivary Gland Disorders

Esophageal Disorders Dysphagia for Solids: obstructive lesion

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Dysphagia for Solids & Liquids: motor disorder TE Fistula o Proximal esophagus ends blindly, distal esophagus from trachea o Polyhydraminos VATER Syndrome: vertebral abnormalities, anal atresia TE fistula, renal dz & absent radius Plummer-Vinson Syndrome: associated w/ chronic Fe deficiency Zenkers Diverticulum: most common esophageal diverticulum Hiatal Hernia o s w/ age o Sliding type most common o Proximal stomach in thoracic cavity o Acid reflux most common symptom Paraesophageal Hernia: gastroesophageal jxn at level of diaphragm GERD o Relaxed lower esophageal sphincter o Nocturnal cough/asthma o Acid injury to enamel o Barretts esophagus o Atypical presentationesophageal pH monitoring, endoscopy, manometry Barretts Esophagus Complications: distal adenocarcinoma, stricture AIDS-related Esophagitis: HSV, CMV, Candida Corrosive Esophagitis: strictures, perforation, squamous cancer Left Gastric Vein drains from distal esophagus & proximal stomach into the portal vein Esophageal Varices: portal htn dilates left gastric vein Ruptured Esophageal Varices o most common cause of death in CIRRHOSIS o endoscopy most important diagnostic procedure Mallory-Weiss Syndrome: mucosal tear of distal esophagus Boerhavves Syndrome: rupture of distal esophagus Pneumomediastinum: air in subQ tissue, crunching sound on physical Achalasia o most common neuromuscular disorder of esophagus o autoimmune destruction ganglion cells myenteric plexus o loss of smooth muscle motility o destruction NO synthase producing neurons causes incomplete relaxation lower esophageal sphincter

nocturnal regurg Barium Swallowdilated aperistalic esophagus, beak-like tapering distal end Leiomyoma: most common BENIGN esophageal tumor Distal Adenocarcinoma: most common esophageal cancer Squamous Cell Carcinoma o cigarette smoking most common cause o dysphagia for solids + weight loos o symptoms often relate to LOCAL invasion

o o

Stomach Disorders Peptic Ulcer Dz o most common cause of hematemesis & melena o duodenal ulcers NEVER malignant o Gastric ulcerssmall % malignant Melena: hematin, sign of upper GI bleed Gastric Analysis: measures BAO & MAO (Basal Acid Output & Max Acid Output) Congenital Pyloric Stenosis: o Hypertrophy of pyloric sphincter muscles o Vomiting of non-bile stained fluid Gastroparesis o sign of autonomic neuropathyie diabetes o early satiety o vomiting undigested food Hemorrhagic Gastritis: NSAIDs most common cause, alcohol 2nd Type A Chronic Atrophic Gastritis: body & fundus, pernicious anemia Type B Chronic Atrophic Gastritis: antrum & pylorus, H. pylori H. pylori o Urease producer o Colonizes mucous layer, noninvasive o Intestinal metaplasia precursor for cancer o Stool Antigen Tests Results: + infection, - infection o Urea Breath Test/Serology: do NOT distinguish active vs old infection o Rx: risk of gastric cancer & lymphoma Menetriers Dz: giant rugal folds, mucus w/ protein loss, achlorhydria Zollinger-Ellison Syndrome o gastrin, acid

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o Malignant islet cell tumor o single or multiple ulcers o Peptic Ulcer Dz + Diarrhea o Association w/ MEN I Syndrome Gastric Polyps: complication chronic gastritis, achlorhydria Leiomyoma: most common BENIGN stomach tumor Gastric Cancer o incidence in Japan o Lesser curvature pylorus & antrum most common sites o Virchows Left supraclavicular node metastasis o Acanthosis nigricans o Leser Trelat Sign Diffuse Gastric Cancer: linitis plastic, not related to H. pylori Intestinal Metaplasia: precursor lesion for gastric adenocarcinoma Krukenberg Tumor: metastatic signet-ring cells to BOTH ovaries Gastric Lymphoma: H pylorimost common cause

Small & Large Bowel Disorders Colicky Pain: symptom of bowel obstruction Bowel Obstruction: small bowel > large bowel Dysentery: bloody diarrhea w/ mucus Melanosis Coli: black bowel from laxatives Hematochezia: sigmoid diverticulosis, angiodysplasia Types of Diarrhea: osmotic, secretory, invasive Fecal Smear for Leukocytes: screen for invasive diarrhea Secretory Diarrhea: loss of isotonic fluid Osmotic Diarrhea: loss of hypotonic fluid Stool Osmotic Gap: distinguishes secretory from osmotic diarrhea Lactase Deficiency: disaccharidase deficiency in brush border, avoid dairy products Causes of Malabsorption: pancreatic insufficiency, bile salt/acid deficiency, small bowel dz Pancreatic Insufficiency: malabsorption of fat & proteinsNOT carbs Bile Salts/Acids: required to micellarize monoglycerides & fatty acids Small Bowel Dz: loss of villous absorptive surface General Malabsorption Screening Tests: stool for fat, serum beta carotene D-Xylose: reabsorption indicates small bowel dz

Serum Immunoreactive Trypsin: in chronic pancreatitis Chronic Pancreatitis: CT scan dystrophic calcification Tests Bile Salt/Acid Def: serium bile acids, bile breath tests Clinical Malabsorption: steatorrhea, fat-/water-soluble vitamin def, anemia, ascites Celiac Dz o immune dz directed against gluten o greatest associationg w/ dermatitis herpetformis o tTG has pivotal role o anti-tTG, anti-EMA, anti-gliadin antibodies o Steatorrhea, weight loss o Flattened villi, hyperplastic glands o Gluten free diet Whipples Dz o Caused by Tropheryma whippelii o Foamy macrophages Small Bowel Obstruction o Bowel distention, air/fluid levels o Colicky Painpain w/ alternating w/ pain free intervals = sign of SM obstruction o Adhesions from Previous Surgery: most common cause Indirect Inguinal Hernia: most common hernia SMA & IMA Jxn: watershed area Occlusion of SMA: most common cause of small bowel infarct Atrial Fib: most common arrhythmia associated w/ systemic embolization Small Bowel Infarct o sudden onset diffuse abdom pain, bloody diarrhea o distention, absent bowel sounds, no rebound tenderness Ischemic Colitis: mesenteric angina after eating fear of eating & weight loss Angiodysplasia o dilation cecal submucosal venules, hematochezia o 2nd most common cause hematochezia o Association w/ vWD & calcific aortic stenosis Newborn w/ Fecal Material in Umbilical Area: persistence of vitelline duct Meckel Diverticulum o bleeding most common complication

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o mimics acute appendicitis Small Bowel Diverticula: duodenal most common site, diverticulitis, bacterial overgrowth Sigmoid Diverticular Dz o constipation most common cause o diverticulitis most common complication o left-sided appendicitis o CT scan best for dx o Most common cause hematochezia & fistulas Ulcerative Colitis: mucosal/submucosal ulcerations Crohns Dz: transmural inflammation IBS o Intrinsic colonic motility disorder o Most common fxnal bowel disorder o Alternating bouts of constipation/diarrhea o mucus in stool o Mainstay is adequate fiber intake Small Bowel: least common site for malignancy in GI tract Carcinoid Tumors o malignant neuroendocrine tumors o terminal ileummetastasis to liver causes carcinoid syndrome o bright yellow o Carcinoid Syndromeliver metastasis is necessary o Flushing, diarrhea, wheezing, urine 5-HIAA Bowel Primary Lymphoma: usually in Peyers Patches in terminal ileum Sigmoid Colon: most common site for GI polyps, diverticula, cancer Hyperplastic Polyp: most common polyp in adults Juvenile Polyp: most common polyp in children Hyperplastic & Juvenile Polyps: NO malignant potential Peutz-Jeghers Polyposis o predominance small intestine polyps o risk colorectal, breast, gynecologic cancer Vermiform Appendix: most common site for carcinoid tumor Tubular Adenoma: most common neoplastic polyp Villous Adenoma o may cause hypoproteinemia & hypoK o greatest risk for developing colon cancer

Familial Polyposis: auto dom, ALL pt develop colon cancer, complete penetrance Turcots Syndrome: auto rec, colon cancer, brain tumors Colon Cancer o 3rd most common cancer in men & women o 3rd most common cause of mortality dt cancer Rectosigmoid: most common site for colon cancer Fecal Occult Blood Test: most tests do NOT distinguish hemoglobin from myoglobin Left Sided Colon Cancer: tend to obstruct, small diameter Right Sided Colon Cancer: tend to bleed, large diameter, Fe deficiency Colon Cancer Prevention: aspirin, FOBT, dietary alterations, stop smoking Acute Appendicitis o most common abdom surgical emergency o pain precedes nausea & vomiting o periappendiceal abscess most common complication o Dx: spiral CT or plain CT w/ rectal contrast Acute Diverticulitis & Appendicitis: initially periumbilical & shifts to RLQ C Fibers: refers to midline A Fibers: localize pain Retrocecal Appendicitis: sentinel loop Pyelophlebitis: portal vein inflammation Subphrenic Abscess: persistent fever post-op Anorectal Bleeding: internal hemorrhoids most common cause Internal Hemorrhoids o straining at stool, painless bleeding o commonly prolapse out of rectum o anal pruritus, soiling of underwear External Hemorrhoids: painful thrombosis inferior hemorrhoidal veins Rectal Prolapse o In kids <2yo: whooping cough, trichuriasis, cystic fibrosis o Elderly: straining at stool Pilonidal Sinus/Abscess: painful mass in deep gluteal fold Pruritus Ani: internal hemorrhoids, diabetes, pinworm Anorectal Fistula: Crohns Dz, Cryptoglandular infection Anal Fissure: most are posteriorly located, anal tag marks location Anal Carcinoma o Basaloid carcinoma most common

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Squamous cancer has HPV 16 & 18 relationship

Hepatobiliary & Pancreatic Disorders

Lab Eval of Liver Cell Injury Unconjugated Bilirubin o End-product of heme degradation in splenic macrophages o Lipid soluble o 20% recycled to liver & kidneys Conjugated Bilirubin: glucuronic acid makes bilirubin water soluble Intestinal Bacteria: convert CB UBC Urobilin: color of stool & urine Viral Hepatitis: most common cause of jaundice Giberts Dz: 2nd most common cause of jaundice, fasting unconjugated hyperbilirubinemia Viral Hepatitis Phases Acute Hepatitis: prodrome, jaundice, recovery Transminases: peak before jaundice Hepatitis A: most common viral cause of jaundice Hepatitis A Virus: anti-HAV-IgM indicates infection, anti-HAV-IgG indicates recovery/vaccination Extravascular Hemolysis: UBG, no UB Hepatitis B o HBsAg: 1st antigen to arrive & last to leave w/ recovery from Hep B o HBeAg & HBV-DNA: infective particles o Anti-HBc-IgG: present after 6mo o Anti-HBs: protective antibody, immunization or recovery from past infection o HBsAG > 6mo defines chronic HBV o Health Carrier: HBsAG, anti-HBc-IgC o Infective Carrier: HBsAg, HBeAg, HBV-DNA, anti-HBc-IgG Hepatitis C & D o HCV Testing: screens w/ EIA, confirm w/ RIBA & HCV RNA o HCV RNA: gold standard test o HCV, HDV: no protective antibodies Viral Hepatitis: urine UBG++, urine bilirubin++ Serum ALT: last enzyme to return to normal

Other Inflammatory Disorders Autoimmune Hepatitis o type I most common in US o +serum ANA, +anti-smooth muscle antibodies Neonatal Hepatitis: multifactorial, biopsy shows multinucleated giant cells Rye Syndrome o association w/ aspiring & infectionchickenpox, flu o encephalopathy, fatty in liver, transaminases o sleepy but respond stuporous obtundation coma o transaminases, bilirubin, PT, ammonia o glucose Fatty Liver of Pregnancy: dysfxn in -oxidation fatty acids, deliver baby Preeclampsia: periportal triad liver cell necrosis, HELLP syndrome o HELLP: hemolytic anemia w/ schistocytes, elevated serum transmainases, low platelets Fulminant Hepatic Failure o viral hepatitis most common overall cause o transaminases, PT & Ammonia Fulminant Hepatitis: acetaminophen most common drug cause Circulatory Disorders Hepatic Artery Infarct o Uncommon dt dual blood supply o Liver transport rejection, Polyarteritis Nodosa Portal Vein Thrombosis: ascities, portal htn, no hepatomegaly, air in portal vein Intrahepatic Obstruction to Blood Flow: cirrhosis most common cause Centrilobar Necrosis o Combined LHF & RHF o nutmeg liver o May progress to cardiac cirrhosis Peliosis Hepatis: anabolic steroids, Bartonella henselae Polycythemia Vera: most common cause of hepatic vein thrombosis Hepatic Vein Thrombosis: hepatomegaly, portal htn, ascites Veno-Occlusive Dz: complication of bone marrow transplant Hematobilia: blood in bile from liver trauma

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Alcohol-Related & Drug/Chemical Induced Liver Disorders Alcohol Liver Disease: fatty , hepatitis cirrhosis Alcoholic Hepatitis o acetaldehyde damages hepatocytes o fatty , neutrophil infiltration, Mallory Bodies Intrahepatic Fibrosis: methotrexate, amiodarone Obstructive (Cholestatic) Liver Dz Intrahepatic Cholestasis: Oral Contraceptive Pills, anabolic steroids Extrahepatic Cholestasis: Stone in common bile ductmost common cause Cholestasis o urine UBG o, urine bilirubin++ o pregnancy: effect of estrogen on intrahepatic bile secretion Extrahepatic Biliary Atresia: jaundice in newborn Primary Sclerosing Cholangitis o Obliterative fibrosis intrahepatic & extrahepatic bile ducts o Strong association w/ ulcerative colitis > Crohns Dz o Cirrhosis, cholangiocarcinoma o ERCP diagnostic beading of bile ducts Cirrhosis Cirrhosis: irreversible fibrosis, regenerative nodules Regenerative Nodules: produce intrasinusoidal htn Alcoholic Liver Dz: most common cause of cirrhosis Hepatic Encephalopathy o reversible metabolic disorder o false neurotransmitters, serum ammonia o Alternations mental status, somnolence, asterixis Ammonia o derives from amino acid metabolism & urease-producing bacteria in bowel o Ammonia: protein intake, antibiotics, lactulose Encephalopathy Precipitating Factors: protein, alkalosis, sedatives, portasystemic shunts Portal Vein o Splenic vein superior mesenteric vein o Htn: dt intrasinusoidal htn from regenerative nodule compression

Portal HTN & Shunts: shunts that bypass the liver can precipitate encephalopathy Splenorenal Shunt: does NOT bypass lier, most physiologic shunt Transjugular Intrahepatic Portosystemic Shunt: portal vein pressure, connects portal vein w/ hepatic vein Ascites o Transudate dt alterations in Starling Pressures o Secondary aldosteronism o Liver vs peritoneal: serum albuminascitic fluid albumin, >1.1g/dL liver origin & <1.1g/dL peritoneal origin Hepatorenal Syndrome o Reversible renal failure w/out parenchymal dz o Liver transplantation only curative tx Hyperestrinism in Males: gynecomastia, spider telangiectasia Postnecrotic Cirhosis: chronic hepatitis HBV & HCV Primary Biliary Cirrhosis o Autoimmune destruction of bile ducts in triads o Damage to mitochondrial proteins in bile duct epithelium in triads, destruction by CD8 T cells o Antimitochondrial antibodies o Pruritis before jaundice o Jaundice is late finding o serum ANA, AMA, IgM Secondary Biliary Cirrhosis: cystic fibrosis Hemochromatosis o Unrestricted reabsorption of Fe o Missense mutations HFE gene on chromosome 6 o Bronze diabetes o Malabsorption, restrictive cardiomyopathy, infertility o serum Fe, % saturation ferritin, TIBC o % saturation best screen o Serum ferritinused to follow therapy Fe initiates synthesis hydroxyl free radicals Hemosiderosis: acquired Fe overload dz Wilsons Dz o incorporation Cu into ceruloplasmin, excretion Cu into bile o Ceruloplasmin: enzyme synthesized in liver that contains Cu

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Kayser-Fleischer Ring: excess Cu in Descemets membrane of cornea o Lenticular degeneration in CNS, movement disorder, dementia o Hemolytic anemia o Renal dz o total serum Cu, serum/urine free Cuf o Rx: penicillamineCu chelator 1-Antitrypsin Def o M is normal allele o Z & S are deficiency variant allels o Cirrhosishomozygous ZZ variant, ATT not secreted properly & accumulates in liver o Cirrhosisserum BUN, serum ammonia Hypoglycemia in Cirrhosis: gluconeogenesis, glycogen stores Cirrhosis: lactic acidosis, hypoNa, HypoK Severe Liver Dysfxn: serum albumin, PT HypoCa in Cirrhosis: serum albumin, 25(OH)-Vit D

Liver Tumors Focal Nodular Hyperplasia: central stellate scar w/ radiating fibrous septae Cavernous Hemangioma: most common benign tumor, potential for intraperitoneal hemorrhage Liver Cell Adenoma: Oral contraceptive pills, intraperitoneal hemorrhage Metastasis: most common liver cancer, lung most common 1 site Hepatocellular Carcinoma o Pre-existing HBV or HCV cirrhosis most common risk factors o Pre-existing cirrhosis o Bile in neoplastic cells o Pain, ascites, fever, blood in ascetic fluid o serum -fetoproteinAFP o Rapidly ing bloody ascites Ectopic Hormones: PTH-related protein, insulin-like factor, EPO Liver Angiosarcoma: exposure to vinyl chloride (plastic pipes)

Gallbladder & Biliary Tract Dz Choledochal Cyst: most common biliary tract cyst in kids, pain w/ intermittent jaundice

Cystic Diseases: risk for cholangiocarcinoma Caroli Disease: association w/ juvenile polycystic kidney dz Primary Sclerosing Cholangitis: most common cause of cholangiocarcinoma Bile: bile salts/acid, phospholipid protein, CB, free cholesterol, electrolytes, bicarb Cholesterol Gallstones o most common stone o cholesterol in bile, bile salts & lecithin o Female, fat, forty, fertile Estrogen: HDL & delivery cholesterol to liver, LDL receptors & HMGCoA reductase activity Black Pigment Gallstone: sign of extravascular hemolysis, Ca bilirubinate Brown Pigment Gallstone: sign of common bile duct infection Stone Complications: cholecystitis, common bile duct obstruction, cancer, acute pancreatitis Stage 1: stone lodges in cystic duct, midepigastric colicky pain Stage 2: stone impacts in cystic duct, pain shift to RUQ, radiation to right scapula/shoulder Stage 3: bacterial invasion gallbladder wall, +Murphy Sign, subsides if stone falls out Stage 4: perforation Stone Pain Radiation: right scapula/shoulder Ultrasound: gold standard for stone dx HIDA Scan: identifies stone in cystic duct & common bile duct Jaundice: indication for common bile duct exploration Pain in Cholecystitis: merperidine NOT morphine Chronic Cholecystitis o Most common symptomatic disorder of gallbladder o Chemical inflammation Cholesterolosis: excess cholesterol in bile, speckled yellow mucosal surface Hydrops: chronic cystic duct obstruction Gallbladder Cancer o Association w/ stones o Porcelain gallbladderrisk for gallbladder cancer, immediate surgery

Pancreatic Disorders

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Major Pancreatic Duct: empties into terminal part of common bile duct, stone blocking CBD causes acute pancreatitis Alcohol Abuse: most common cause of acute pancreatitis Seat Belt Trauma: most common cause of pancreatitis in kids Pancreatitis: pain radiates into the back, described as knife-like pain 3rd Space Fluid: fluid unavailable for maintenance of vol in vascular compartment Hypoxemia: circulating phospholipase destroys surfactant Grey-Turner Sign: flank hemorrhage Cullens Sign: periumbilical hemorrhage Persistent in Serum Amylase: consider pancreatic pseudocyst Pancreatic Abscess: higher fever from gram sepsis, amylase, CT shows bubbles Pancreatic Ascites: leaking pseudocyst Amylase: NOT specific for pancreatitis Acute Pancreatitis: clearance of amylase in urine Serum Lipase: more specific & lasts longer than amylase in acute pancreatitis, excellent screen for acute pancreatitis Serum Immunoreactive Trypsin o excellent newborn screen for cystic fibrosis o acute pancreatitis, chronic pancreatitis CT Scan: gold standard for pancreatic imaging Plain Radiograph: sentinel loop, left-sided pleural effusion Chronic Pancreatitis o Adults: alcohol abuse most common cause o Kids: cystic fibrosis most common cause o Malabsorption, type I diabetes mellitus o CT scan shows dystrophic calcification o Tests pancreatic insufficiency: secretin stimulation, bentiromide Pancreatic Carcinoma o smoking most common cause, chronic pancreatitis o CT scan best test Carcinoma in Head of Pancreas: jaundice, light-colored stool, palpable gallbladder Pancreatic Cancer o metastasis left supraclavicular node o CA19-9 gold standard tumor marker

Kidney Disorders
Important Lab Findings in Renal Dz Second Hydroxylation of Vitamin D: 1--hydroxylase in proximal tubule Renal Stone: most common upper urinary tract cause of hematuria Infection: most common cause of lower urinary tract hematuria Transitional Cell Carcinoma Bladder: most common noninfectious cause of lower urinary tract hematuria Benign Prostatic Hyperplasia: most common cause of microscopic hematuria in adult males Anticoagulants: most common drugs causing hematuria Persistent Proteinuria: usually indicates intrinsic renal dz Renal Fxn Tests Urea: some extrarenal loos (ie skin) w/ high serum [ ] Congestive Heart Failure: most common cause of serum BUN Creatinine o End-product of creatine metabolism o Filtered, not reabsorbed or secreted Azotemia: serum BUN & creatinine Urea: filtered, partly reabsorbed in proximal tubules Prerenal Azotemia: GFR, ratio >15 Renal Azotemia: intrinsic renal dz, extrarenal loss of urea, ratio 15 Postrenal Azotemia: obstruction behind kidneys, initially ratio >15, 15 if obstruction persists Nephrotoxic Drugs in Elderly: must adjust dose & interval for normal in CCr CCr: normally s with age CCr: normal pregnancy, early diabetic glomerulopathy Urinalysis: gold standard test to evaluate renal dz Clinical Anatomy of Kidney Renal Medulla: relatively ischemic Renal PGE2: vasodilation afferent arteriole ATII: vasoconstriction of efferent arterioles Glomerular Basement Membrane: size & charge determine protein filtration Albumin: negative charge, repelled by negatively charged GBM

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Fusion of Podocytes: sign of nephrotic syndrome Crescents: proliferation of parietal epithelial cells

Congenital Disorders & Cystic Dz of Kidneys Horseshoe Kidney: association w/ Turner Syndrome Renal Dysplasia: most common cystic dz in kids Glomerular Disorders Linear Immunofluorescence: anti-GBM dizie Goodpastures Granular Pattern: immunocomplex type of glomerulonephritis Electron Microscopy: immunocomplex deposits are e- dense Immunocomplex o most common mechanism causing glomerulonephritis o activate complement C5a produced attracts neutrophils damage tissue Nephritic Syndrome o Neutrophil-related injury to glomeruli o Moderate proteinuria o dysmorphic RBCs, RBC casts Pitting Edema: does NOT distinguish nephritic from nephrotic syndrome Nephrotic Syndrome o Cytokine injury to podocytes o Loss of negative charge on GBM o Proteinuria >3.5 g/24hr o Fatty casts o Less glomerular inflammation than nephritic syndrome Diabetic Glomerulopathy: type 1 > type 2 diabetes Minimal Change Dz: most common nephrotic syndrome in children Focal Segmental Glomerulosclerosis: most common nephrotic syndrome in adults Diffuse Membranous Glomerulopathy: HBsAg association Type 1 MPGN: HBV, HCV (most common) association Diabetic Glomerulopathy: poor glycemic controlmost common cause Nonenzymatic Glycosylation: vessel/tubular permeability to protein Osmotic Damage: sorbitol Hyaline Arteriolosclerosis of Efferent Arteriole: GFR producing hyperfiltration injury Microangiopathy: deposition type IV collagen Microalbuminuria: 1st lab sign of diabetic glomerulopathy

ACE-I/Receptor Blockers: slow progression of nephropathy in type 1/type 2 diabetes Alports Syndrome: hereditary nephritis, sensorineural hearing loss, ocular defects Thin Basement Membrane Dz: persistent hematuria Rapidly Progressive GN & Focal Segmental Glomerulosclerosis: most common cause of chornic glomerulonephritis

Disorders Affecting Tubules & Interstitium Acute Tubular Necrosis o most common cause of Acute Renal Failure o BUN:creatinine ratio 15 o hyperK, metabolic acidosis Ischemic ATN: most common type of ATN Prerenal Azotemia: most common cause of ischemic ATN Renal Tubular Cell Cast: key cast of ATN Aminoglycosides: most common cause of nephrotoxic ATN Acute Pyelonephritis o most common cause of Tubulointerstitial Nephritis (TIN) o women > men o E. coli most common cause Vesicoureteral Reflux: urine refluxes into ureters during micturition Ascending Infection: most common mechanism for upper/lower UTIs in females Findings in APN & NOT Lower UTIs: fever, flank pain, WBC cases in urine Causes of Chronic Pyelonphritis o vesicoureteal reflux in young girls, chronic hydronephrosis o cortical scars overlie blunt calyces o visible w/ intravenous peylogram o glomerular scarring, tubular atrophy (thyroidization) Reflux Nephropathy: htn in children Drugs Causing TIN: methicillin, NSAIDs, rifampin, sulfonamides Acute Drug Induced TIN: abrupt onset fever, oliguria, eosinophilia Analgesic Nephropathy: acetaminophen + aspiring, renal papillary necrosis Prevention of Urate Nephropathy: allopurinol BEFORE aggressive cancer therapy Chronic PB Poisoning: proximal tubule w/ nuclear acid-fast inclusions Bence Jones Proteinuria: casts incite foreign body giant cell rxn

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Chronic Renal Failure Chronic Renal Failure o normocytic anemia, qualitative platelet defect o htn, pericarditis, CHF, atherosclerosis o anion gap metabolic acidosis o serum phosphorus/K o serum Ca o Free water clearance: 0 o Waxy castssign of CRF Renal Osteodystrophy: dt 2 hyperparathyroidism, osteomalacia, osteoporosis Cystatin C: biomarker of kidney fxn Vascular Disorders Benign Nephrosclerosis: kidney of essential htn, dt hyaline arteriolosclerosis Malignant HTN o pre-existing benign nephrosclerosis most common cause o 210/120 mmHg o Encephalopathy, renal failure o IV nitroprusside Renal Infarctions o Embolization most common o Hematuria & flank pain Sickle Cell Trait/Dz: hematuria, loss concentration, renal papillary necrosis, APN Diffuse Cortical Necrosis: anuria followed by ARF in pregnant women Obstructive Disorders Hydronephrosis: most common complication of upper urinary tract obstruction Renal Stones o most common cause of upper urinary tract obstruction o Ca oxalate most common, Ca phosphate o Ipsilateral colicky pain in flank radiating to groin o Hematuria o Plain films: 80% stones radiopaque o Spiral CT: best overall sensitivity & specificity

o Preventionhydration is very important o Rx for Ca stones: hydrochlorothiazide HyperCa: most common metabolic abnormality causing Ca stones Thiazides: reabsorption of Ca out of urine Struvite Stone: Mg Ammonium phosphate, urease producers, alkaline urine pH Ultrasound: detects hydronephrosis, not stone

Kidney & Renal Pelvis Tumors Angiomyolipoma: hamartoma associated w/ tuberous sclerosis Renal Cell Carcinoma o yellow tumor w/ renal vein invastion o derives from proximal tubule cell o smoking most common cause o invades renal vein, poor prognosis o Triad: hematuria, flank pain, abdominal mass o Ectopic secretion EPO & PTH-related peptide Transitional Cell Carcinoma Renal Pelvis: smokingmost common cause Wilms Tumor o Most common primary renal tumor in kids o Kids w/ unilateral flank mass & htn o Htn dt renin secretion

Lower Urinary Tract & Male Reproductive Disorders

Common Ureteral Disorders Congenital Megaloureter: association w/ Hirschsprungs Dz Ureteritis Cystica: risk factor bladder adenocarcinoma Hydronephrosis: most common complication of retroperitoneal fibrosis Transitional Cell Carcinoma: most common cancer of ureter Urinary Bladder Disorders Exstrophy o developmental failure anterior abdominal wall & bladder o risk factor for bladder adenocarcinoma Urachal Cyst Remnants: most common cause of bladder adenocarcinoma, drainage of urine from umbilicus Indwelling Catheters: most common cause sepsis/UTIs in hospital Cyclophosphamide: hemorrhagic cystitis, prevented w/ mesna

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Schistosoma hematobium: egg w/ large TERMINAL spine E. coli: most common uropathogen, sepsis in hospital S. saprophyticus: lower urinary tract infection in young sexually active female, coagulase negative C. trachomatis: most common cause of acute urethral syndrome in women & nonspecific urethritis in men Lower Urinary Tract Signs: dysuria, frequency, urgency 105 CFUs/mL: gold standard for lower urinary tract infection Asymptomatic Bacteriuria: tx pregnant women w/ amoxicillin, no tx for healthy elderly women Sterile Pyuria: neutrophils in urine, negative standard culture Malacoplakia: Michaelis-Gutmann Bodies Acquired Bladder Diverticula: most common cause is BPH, chronic E. coli infection Cystocele: bladder wall protrudes into vagina Cystitis Cystica/Glandularis: risk of bladder adenocarcinoma Retain Urine: sympathetic activityrelax detrusor muscle, contract internal sphincter muscle Void Urine: parasympathetic activitycontract detrusor muscle, relax internal sphincter muscle Transitional Cell Carcinoma o Most common bladder cancer o Smoking cigarettesmost common cause o Multifocal tumor, recurrences are the rule o Painless hematuriamost common sign Squamous Cell Carcinoma of Bladder: S. hematobium infection Bladder Squamous Cancer: S. hematobium Killing Helminth Eggs: type II hypersensitivity rxn involving eosinophils Embyronal Rhabdomyosarcoma: most common sarcoma in kids, boys protrude from urethra Cancers Invading Bladder: cervical & prostate cancer

Penis Disorders Hypospadias o abnormal opening on ventral surface of penis o most common malformation of urethral grove o faulty closure urethral folds, androgen dysfxn Epispadias: abnormal opening on dorsal surface of penis, defect of genital tubercle Phimosis: orifice of prepuce cannot retract over head of penis Balanoposthitis: infection of glans & prepuce Peyronies Dz: fibromatosis, lateral curvature of penis, infertility Priapism: persistent painful erection Risk Factors for Invasive Squamous Cell Carcinoma: Bowens Dz, erythroplasia of Queyrat Bowenoid Papulosis: HPV 16, no invasive cancer Penis Cancer: squamous cell carcinoma Circumcision: Protects against developing cancer of penis, HPV 16, 18 relationship Testes Transabdominal Phase: mullerian inhibitory factor Testis Inguinoscrotal Phase: androgen & hCG dependent Cryptorchid Testis o most common GU disorder in male kids o risk for seminoma & infertility of cryptorchid testis + normally descended testis Orchitis: mumps, syphilis, HIV Epididymitis o <35yrs oldconsider STD, >35yoE. coli, Pseudomonas o Scrotal pain w/ radiation into spermatic cord Prehns Sign: elevation of scrotum pain Varicocele o most often left-sided, spermatic vein empties into left renal vein o smoker w/ sudden onset of left varicocele, consider renal carcinoma invading renal vein o bag of worms appearance Torsion of Testicle o violent movement or traumamost common o absent cremasteric reflex, testis high in inguinal canal Hydrocele o most common cause of scrotal enlargement

Urethral Disorders STD Urethritis: Chlamydia trachomatis & Neisseria gonorrhoeae Reiters Syndrome: Chlamydial urethritis, conjunctivitis, HLA-B27 arthritis Urethra Cancer: squamous cell carcinomamost common cause

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o persistent tunica vaginalis, inguinal hernia also present Seminoma: most common testicular cancer Testicular Cancer o seminomas & nonseminomas o cryptorchidismmost common risk factor o Unilateral, Painless Testicular Mass o Markers: AFP, hCG Testicular Cancer Metastasis: para-aortic nodes NOT inguinal nodes

Prognosis: markedly improved bc of early detection & improved tx

Prostate Disorders Dihydrotestosterone: embryologic development of prostate Prostatitis: chronic > acute Acute Prostatitis: <35yoconsider Chlamydia, Neisseria Chronic Prostatitis o majority are abacterial o can radiate to lower back, perineum, suprapubic area BPH o Most common cause of enlarged prostate in men >50yo o Periurethral/transitional zones o 30%-50% have PSA o Most common cause of bladder diverticula o NOT risk factor for prostate cancer o Rx: -adrenergic blockers of smooth muscle o Surgery: Transurethral Resection of Prostate DHT: primary mediator for developing BPH, estrogen co-mediator Obstructive Uropathy: most common complication of BPH, produces bladder diverticula Prostate Infarct: pain on DRE, PSA Prostate Cancer o Most common cancer in men o Peripheral in location o Advanced aginggreatest risk factor o DHT-dependent o Generally silent until advanced stage o Osteoblastic metastases, lumbar spine, pelvis PSA o More sensitive than specific in prostate cancer o free PSA consider BPH, bound PSA consider prostate cancer o Dx: transrectal needle core biopsies

Male Hypogonadism FSH: stimulates spermatogenesis LH: stimulates testosterone synthesis in Leydig cells Testosterone: enhance spermatogenesis, libido Sex Hormone Binding Globulin (SHBG) o Synthesized in Sertoli cells & liver o SHBG causes free testosterone o SHBG causes free testosterone Impotence: most common manifestation of male hypogonadism testosterone causes libido Hypogonadism: impotence, female 2 sex characteristics, osteoporosis 1 Hypogonadism o LH, testosterone o Leydig Cell Dysfxn: testosterone & sperm count, LH, nl FSH o Leydig Cell + Seminiferous Tubule Dysfxn: testosterone & sperm count, LH & FSH 2 Hypogonadism o LH, testosterone o Causes: constitutional, Kallmanns Syndrome, Hypopituitarism o Kallmanns Syndrome/Hypopituitarism: testosterone, sperm count, LH & FSH Male Infertility Seminiferous Tubule Dysfxn: accounts for 90% of cases of male infertility End-organ Dysfxn: obstruction of vas deferens Semen Analysis: gold standard test for infertility Erectile Dysfxn Impotence + Preserved Nocturnal Penile Tumescence: psychogenic cause of impotence Vascular Insufficiency: most common cause impotence men >50yo Parasympathetics for Erection: S2-S4 Sympathetic for Ejaculation: T12-L1 Neurologic Causes Erectile Dysfxn: multiple sclerosis, diabetes Drugs Erectile Dysfxn: leuprolide, methyldopa, psychotropics

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Endocrine Dz Erectile Dysfxn: diabetes, 1 Hypothyroidism, prolactinoma Sildenafil: cGMPcauses vasodilation in corpus cavernosum Yohimbe: vasodilation

Female Reproductive Disorders & Breast Disorders

Vulva Disorders Lichen Sclerosis: thin epidermis, parchment-like skin Lichen Simplex: leukoplakia (hyperplasia) Papillary Hidradenoma: painful apocrine gland tumor Vulvar Intraepithelial Neoplasia: HPV 16 association Extramammary Pagets Dz: intraepithelial adenocarcinoma, PAS + (Periodic Acid-Schiff) Melanoma: PAS Vagina Disorders Rokitansky-Kuster-Hauser Syndrome: absence of upper vagina/uterus Gartners Cyst: woffian duct remnant Embryonal Rhabdomyosarcoma: grape-like mass protruding from vagina Diethylstilbestrol (DES): inhibits mullerian differentiation Vaginal Adenosis: red superficial ulcerations Clear Cell Adenocarcinoma of Vaginia/Cervix: association w/ DES exposure, adenosis precursor lesion Other DES Abnormalities: incompetent cervix, abnormal uterine shape Cervix Disorders Transformation Zone: site where squamous dysplasia & cancer develop Acute Cervicitis o vaginal dischargemost common complaint o C. trachomatis & N. gonorrhoeae >50% of cases Follicular Cervicitis: caused by C. trachomatis Reticulate Bodies: produce elementary bodiesinfective particle of Chlamydia Cervical Pap Smear: screen for dysplasia/cancer, evaluates hormonal status Superficial Squamous Cells: adequate estrogen Intermediate Squamous Cells: adequate progesterone Parabasal Cells: lack of estrogen & progesterone

Cervical Polyp o non-neoplastic o postcoital bleeding, vaginal discharge Cervical Intraepithelial Neoplasia: most cases associated w/ HPV, smoking = risk factor Koilocytosis: HPV effect in squamous cells Cervical Dysplasia: precursor for squamous cancer Cervical Cancer o least common gynecologic cancer, important of Pap smear o abnormal vaginal bleeding most common sign o renal failurecommon cause of death

Reproductive Physiology & Selected Hormone Disorder Sequence to Menarche: breast budding, growth spurt, pubic hair, axillary hair, menarche Proliferative Phase: estrogen-mediated, most variable phase Ovulation: estrogen surge LH surge ovulation Subnuclear Vacuoles: sign of ovulation Secretory Phase: progesterone-mediated, least variable phase Arias-Stella Phenomenon: exaggerated secretory phaseoccurs in pregnancy Menses: drop in hormones initiates apoptosis Newborn Girls: may have vaginal bleeding FSH: prepares follicle, aromatase synthesis, LH receptor synthesis LH Proliferative Phase: testosterone synthesis for conversion by aromatase into estradiol in granulosa cells LH Secretory Phase: synthesize 17-OH-progesterone hCG o LH analogue o Maintains corpus luteum of pregnancy for 8-10wks Oral Contraceptives: prevents LH surge & ovulation, progestins cause gland atrophy Estradiol: estrogen of a nonpregnant woman Estrone o estrogen of a postmenopausal woman o androstenedione from adrenal converted by aromatase to estrone Estriol: estrogen of pregnancy DHEA-Sulfate: almost exclusively synthesized in adrenal cortex

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Testosterone: synthesized in ovary & adrenals Sex Hormone-Binding Globulin o synthesized in liver o higher binding affinity for testosterone than estrogen o SHBG, Free Testosterone o SHBG, Free Testosterone Pregnancy o RBC mass/plasma vol = Hb & RBC count (dilutional effect) o plasma vol causes GFR & CCr o Respiratory alkalosis o Estrogen/progesterone stimulation of respiratory center o serum T4/cortisoldt in binding proteins Menopause o No menses for 1 yr after age 40 o Hot flushes, night sweats, mood swings o FSH best marker, absence of menses for 12mo Hirsutism o excess hair in normal hair-bearing areas o polycystic ovary syndromemost common cause o Ovarian Cause: testosterone o Adrenal Cause: DHEA-S, testosterone Virilzation: hirsutism + male 2 sex characteristics Hirsutism & Virilzation: hyperandrogenicity of ovarian, adrenal, or drug origin Polycystic Ovary Syndrome o estrogen & androgens o Oligomenorrheamost common complaint o LH, FSH, LH:FSH ratio >2 o Rx: low-dose oral contraceptives or medroxyprogesterone Menorrhagia: loss >80mL per period 1 Dysmenorrhea: dt PGF2, uterine contractions 2 Dysmenorrhea: endometriosismost common cause Dysfxnal Uterine Bleeding o abnormal bleeding unrelated to an anatomic cause o occurs most often after menarche & in perimenopausal period o Anovulatory: most common type of DUB, excessive estrogen stimulation

Ovulatory: inadequate luteal phase, progesterone, irregular shedding of endometrium, persistent luteal phase 1 Amenorrhea o most cases dt constitutional delay o Turners Syndrome1 Amenorrhea + poor female 2 sex characteristics 2 Amenorrhea: most cases dt pregnancy Hypothalamic/Pituitary Cause Amenorrhea: FSH, LH, estrogen Ovarian Cause Amenorrhea: FSH, LH & estrogen End Organ Defect: normal FSH, LH, estrogen Asherman Syndrome: removal of stratum basalis by curettage

Uterine Disorders Acute Endometritis o Uterine infection following delivery or abortion o Group B strepcommon path Intrauterine Device: Actinomyces infection Chronic Endometritis: presence of plasma cells in biopsy Adenomyosis: glands & stroma in myometrium Endometriosis o Fxning glands & stroma outside the confines of the uterus o Reverse mensesmost common cause o Coelomic metaplasia, vascular/lymphatic spread o Ovariesmost common site of implantation o Triad: dysmenorrhea, dyspareunia, infertility Rectal Pouch of Douglas: site for collection of blood, malignant cells, pus, endometrial implants Endometrial Polyp: common cause of menorrhagia, no risk for endometrial cancer Endometrial Hyperplasia o Prolonged estrogen stimulation o Atypical hyperplasia greatest risk for endometrial cancer o Postmenopausal bleeding Endometrial Carcinoma: most common gynecologic cancer Oral Contraceptives: risk for endometrial cancer Endometrial Cancer: postmenopausal bleedingmost common finding Leiomyoma: most common benign connective tissue tumor in women Leiomyoma Clinical: menorrhagia, obstructive delivery Leiomyosarcoma: most common sarcoma of uterus

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Carcinosarcoma: association w/ previous irradiation

Fallopian Tube Disorders Hydatid Cysts: cystic mullerian remnant, may undergo torsion Pelvic Inflammatory Dz o most common cause of female infertility & ectopic pregnancy o most common cause is N. gonorrhoeae & C. trachomatisboth present in 45% of cases o cervical motion, adnexal, uterine tenderness, highly predictive of PID o Rx: ceftriaxone (N. gonorrhoeae) + doxycycline (C. trachomatis) Salpingitis Isthmica Nodosa (SIN): tubal diverticulosis Ectopic Pregnancy o most common cause is previous PID o Triad: vaginal bleeding, pelvic pain, adnexal mass o most common cause of death in early pregnancy o most common cause of hematosalpinx Ovarian Disorders Follicular Cyst: most common ovarian mass, non-neoplastic Corpus Luteum Cyst: most common ovarian mass in pregnancy, nonneoplastic Oophoritis: complication of mumps or PID Stromal Hyperthecosis: hirsutism/virilization, htn, insulin resistance (metabolic syndrome) Ovarian Cancer o risk w/ age o genetic factors, excess estrogen exposure o abdominal enlargement dt fluid most common sign o palpable ovaries in postmenopausal women is cancer until proved otherwise Oral Contraceptives/Pregnancy: risk for surface derived ovarian cancers Surface-Derived Tumors: most common group of ovarian tumors Serous Cystadenocarcinoma: most common ovarian cancer, bilaterality, psammoma bodies Malignant Surface-Derived Cancers: commonly seed abdom cavity Germ Cell Tumors: teratoma (benign) & dysgerminoma (malignant) most common

Sex Cord Stromal Tumors o hormone producing tumors, most are benign o estrogen/androgen Surface Derived Tumors: CA125

Gestational Disorders Fetal Surface: chorionic plate Maternal Surface: cotyledons Chorionic Villi: extract O2 from maternal blood Trophoblast: lines villi, syncytiotrophoblastsynthesizes hCG, HPL, & cytotrophoblast HPL: directly correlates w/ placental mass, anti-insulin activity Umbilical Cord: 2 arteries, 1 vein, umbilical vein has most O2 Placenta Infections: group B strep most common Chorioamnionitis: infection fetal membranes, danger neonatal sepsis/meningitis Placenta Previa o implantation over cervical os, previous C-section risk factor o painless vaginal bleeding o do NOT perform pelvic exam, dx by ultrasound Abruptio Placentae o retroplacental clot o most common cause of late pregnancy bleeding o HTN greatest risk factor o Triad: painful vaginal bleeding, tetanic contractions, fetal compromise Placenta Accreta: implanation into muscle, danger of hemorrhage at delivery Velamentous Insertion: cord inserts away from placental edge, danger of tearing vessels Accessory Lobe: risk for hemorrhage if detached Enlarged Placenta: Rh HDN, congenital syphilis, diabetes mellitus Monochorionic Twin Placentas: identical twins, single fertilized egg Dichorionic Twin Placentas: identical or fraternalseparate fertilized eggs Preeclampsia o usually occurs during 3rd trimester o placental hypoperfusion, vasoconstriction overrides vasodilation o premature aging of placenta, placental infarctions

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o HTN, proteinuria, pitting edema o Rx: delivery is tx of choice, Mg sulfate for seizures Complete Mole o Whole placenta is neoplastic, no embryo, 46XX *both male Xs) o Ultrasound w/ snowstorm appearance, too large for gestational age Partial Mole: part of placenta neoplastic, embryo present 69 chromosomes Choriocarcinoma o malignancy of trophoblastic tissue, no chorionic villi o complete mole50%, spontaneous abortion25%, normal pregnancy25% Amniotic Fluid: high salt content causing ferning when dried on glass slide Polyhydramnios: TE fistula, duodenal astresia, maternal diabetesfetal polyuria Oligohydramnios: juvenile polycystic kidney Dz AFP in Pregnancy: open neural tube defect, inadequate folate prior to pregnancy L:S Ratio >2: adequate surfactant Estriol: derived from fetal adrenal gland, placenta, maternal liver Estriol: fetal-maternal-placental dysfxn Down Syndrome Triad: urine estriol, serum AFP, serum hCG

Breast Disorders Outer Quadrant Cancer: axillary node involvement Inner Quadrant Cancer: internal mammary node involvement Galactorrhea o mechanical stimulation of nipple most common physiologic cause o primary hypothyroidism, TRH stimulates prolactin release o drugs very common cause Prolactinoma: most common pathologic cause of galactorrhea Bloody Discharge: intraductal papilloma, ductal cancer Purulent Discharge: acute mastitis during breast feeding Breast Pain: most common cause is fibrocystic change Fibrocystic Change: most common breast mass in women <50yo Cysts & Fibrosis: lumpy bumpy feeling on breast exam Slcerosing Adenosis: often contain microcalcification seen on mammogram

Atypical Ductal Hyperplasia: risk for breast cancer Mammary Duct Ectasia: common in menopause, greenish brown nipple discharge Traumatic Fat Necrosis: usually painless indurated mass, associated w/ trauma to breast tissue Silicone Breast Implant Rupture: foreign body giant cell rxn Fibroadenoma: o most common breast tumor women <40yo o commonly develop in women taking cyclosporine o benign tumor derived from stroma Phyllodes Tumor: benign, borderline, or malignant, depends on stromal cellularity Intraductal Papilloma: most common cause of blood nipple discharge in women < 50yo Breast Cancer o most common cancer in women o risk: prolonged estrogen stimulation, genetically susceptible background o genetic basis <10% o Risk Factors: unopposed estrogen, recent use of oral contraceptives o Factors ing Risk: breast-feeding, exercise, health body weight o Clinical: painless mass skin/nipple retraction o Most common cancer metastatic to lungs & bone o Extranodal spread has greater significance than nodal metastasis alone o Sentinel Node: initial node draining the tumor Mammography: detect nonpalpable masses Initial Management of Breast Mass: fine needle aspiration Microcalcifications: DCIS, sclerosing adenosis ERA-PRA Receptor Assays: positive assay confers better prognosis for breast cancer ERBB2 Oncogene: if positive in breast tissuepoor prognosis for breast cancer Winged Scapula: damage to long thoracic nerve Breast conservation therapy has similar survival rate as modified radical mastectomy Gynecomastia o Benign glandular proliferation of male breast tissue

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Normal in newborn, adolescence, elderly Cirrhosis (hyperestrinism)most common pathologic Genetic Causes: Klinefelters Syndrome, testicular feminization Drug Causes: spironolactone, ketoconazole, DES, Digoxin, Flutamide, Leuprolide o Cancer Causes: choriocarcinoma Estrogen Sources: peripheral aromatization of androgens, Leydig cells in testis Breast Cancer in Men: Klinefelters BRCA2 suppressor gene inactivation

o o o o

Endocrine Disorders
Overview of Endocrine Dz Negative Feedback: Ca, PTH or Ca, PTH Endocrine Gland Hypofxn o use stimulation tests o autoimmune dzmost common cause Endocrine Gland Hyperfxn o Use suppression tests o Pituitary Cushing Syndrome & prolactinoma can be suppressed o Benign adenomamost common cause Hypothalamic Dysfxn: 2 hypopituitarism, Central Diabetes Insipidus, prolactin, precocious puberty, visual field defects, mass effects hydrocephalus Precocious Puberty: true if CNS origin, pseudo if peripheral cause Pineal Gland Disorders Pineal Gland: midline above quadrigeminal plate Melatonin: chemical messenger of darkness Pineal Gland o Commonly undergoes dystrophic calcification o Majority are germ cell tumors Pineal Gland Tumors: paralysis of upward gazesetting sun sign Pituitary Gland Disorders Pituitary Infarction: invariably produces panhypopituitarism Hypopituitarism in Adults: nonfuxning adenomamost common cause MEN I: pituitary adenoma, hyperparathyroidism, pancreatic tumor Hypopituitarism in Children: craniopharyngiomamost common cause

Rathkes Pouch: develops anterior pituitary Sheehans Pospartum Necrosis: sudden cessation of lactation, pituitary infarction 2 to shock Pituitary Apoplexy: hemorrhage into preexisting adenoma Lymphocytic Hypophysitis: autoimmune destruction, occurs during or after pregnancy Empty Sella Syndrome: subarachnoid space extends into sella, CSF pressure compresses gland Posterior Pituitary: storage of ADH & release of oxytocin Prolactinoma o most common pituitary tumor o 2 amenorrhea + galactorrhea o In Men: impotence dt loss of libido, headache o Rx: dopaime analogues, surgery Growth Hormone: gluconeogenesis, amino acid uptake in muscles, stimulate IGF-1 in liver IGF-1: stimulates bone, cartilage, soft tissue Gigantism: linear/lateral bone growth in children, epiphyses NOT fused Acromegaly o lateral bone growth onlyepiphyses NOT fused o Organomegaly, hyperglycemia o Comparing old vs new photovaluable diagnostic tool o Heart failure from cardiomyopathycommon cause of death

Thyroid Gland Disorders Thyroid Hormone: iodide attached to tyrosine TSH: mediates trapping organification & proteolysis FT4: prohormone, metabolically active by outer ring deiodinase (FT3) FT4/FT3: negative feedback w/ TSH Total Serum T4: T4 bound to TBG + FT4 Estrogen: TBG which total serum T4, but NOT FT4 TBG: total serum T4, no effect on FT4 & TSH Serum TSH: best screening test for thyroid dysfxn 123I Uptake: evaluates synthetic activity of thyroid gland 123I Uptake: synthesis of thyroid hormone, Graves Dz 123I Uptake: thyroiditis, pt taking excess thyroid hormone Cold Nodule: 123I Uptake Hot Nodule: 123I Uptake

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Mass at Base of Tongue: lingual thyroid Thyroglossal Duct Cyst: cystic midline mass Branchial Cleft Cyst: located in anterolateral neck Acute Thyroiditis: thyrotoxicosis, 123I Uptake Subacute Granulomatous Thyroiditis: most common cause of painful thyroid, virus induced, no adenapthy Hashimotos Thyroiditis o autoimmune thyroiditis o type IV (mainly) & type II hypersensitivity o most common cause of hypothyroidism o muscle weaknesscommon complaint o weight gain, dry brittle hair o periorbital puffiness, hoarse voice, signs of myxedema o cold intolerance, constipation o HTN from Na retention, delayed reflexes Reidels Thyroiditis: fibrous tissue replacement of gland & surrounding tissue Subacute Painless Lymphocytic Thyroiditis: develops post partum, progression to hypothyroidism Hypothyroidism: hypometabolic Brain: requires thyroxine for maturation Cretinism o most often caused by maternal hypothyroidism before fetal thyroid is developed o severe mental retardation 1 Hypothyroidism: serum T4/FT4, serum TSH, cholesterol Myxedema Coma: stupor, hypothermia, hypoventilation, IV levothyroxine, corticosteroids Thyrotoxicosis: hormone excess from any cause Hyperthyroidism: thyrotoxicosis dt excess synthesis of thyroid hormone Graves Dz o most common cause of hyperthyroidism & thyrotoxicosis o anti-TSH receptor antibody, type II hypersensitivy o Unique to Graves: exophthalmos, pretibial myxedema, thyroid acropachy o In Elderly: cardiac & muscle findings predominate, apathetic appearing Transient Hyperthyroidism in fetus Thyroid Acropathy: digital swelling & clubbing

Toxic Multinodular Goiter: 1 or more nodules in a multinodular goiter becomes TSH-independent Thyrotoxicosis o Weight loss w/ a good appetite o Heat intolerance, diarrhea o Oligomenorrhea o Lid stare, sinus tachycardia, systolic HTN, brisk reflexes o glucose, Ca, lymphocytes o cholesterol A Fib: always order a TSH test to r/o hyperthyroidism Graves Hyperthyroidism: serum T4/FT4, 123I Uptake, serum TSH Graves Dz Tx: -blockers, thionamides Thyroid Storm: tachyarrhythmias, hyperpyrexia, coma, shock Euthyroid Sick Syndrome o serum T3 & T4 abnormalities, normal gland fxn o block in outer ring deiodinase conversion of T4 to T3, T4 converted to inactive reverse T3 o serum T3 & reverse T3 Goiter: thyroid enlargement Nontoxic Goiter o Absolute or relative deficiency of thyroid hormone o Hyperplasia/hypertrophy followed by involution initially diffuse then nodular Toxic Nodular Goiter: 1 or more nodules become TSH-independent Solitary Nodule in Women: majority are benign, 15% malignant Solitary Nodule in Men/Kids: more likely to be malignant Solitary Nodule w/ Hx of Radiation Exposure: more likely to be malignant40% Follicular Adenoma: most common benign thyroid tumor Papillary Carcinoma o most common endocrine & thyroid cancerlymphatic invasion o psammoma bodies Follicular Carcinoma o most common thyroid cancer presenting as solitary cold nodule o hematogenous rather than lymphatic spread MEN IIa: medullary carcinoma, HPTH, pheochromocytoma Medullary Carcinoma o derives from C cells o calcitonintumor marker

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o Calcitonin converted into amyloid 1 B-Cell Lymphoma: most often derives from Hashimotos thyroiditis Anaplastic Thyroid Cancer: rapidly aggressive, uniformally fatal

Parathyroid Gland Disorders Superior & Inferior Parathyroids: derive from 4th & 3rd pharyngeal pouch PTH o renal Ca reabsorption, renal phosphorus & bicarb reabsorp. o hypoCa/hyperP PTH o hyperCa/hypoP PTH Sunlight = major source of vitamin D Liver: 25-hydroxylase converts cholecalciferol to 25-(OH)2D = calcitriol Kidney: 1-hydroxylase converts 25-(OH)D to 1,25-(OH)2D = calcitriol Calcitriol: Ca/P reabsorption in bowel, osteoclast production Calcitriol Feedback: hypoCa synthesis, hyperCa synthesis Total Serum Ca: Ca bound + Ca free (ionized) Hypoalbuminemia: total serum Ca, normal ionized Ca & PTH Alkalosis: normal total serum Ca, ionized Ca, PTH, tetany Tetany o Et comes close to Em, initiates action potential o Thumb adduct into palm, facial twitching after tapping facial nerve Hypoparathyroidism o autoimmune hypoparathyroidism most common cause o serum Ca & PTH o serum phosphorus DiGeorge Syndrome: failure of descent of 3rd/4th pharyngeal pouches, absent parathyoids & thymus Hypomagnesemia o most common pathologic cause of hypoCa in hospital o diarrhea, aminoglycosides, diuretics, alcohol Chronic Renal Failure: most common cause of hypoCa, cause hypoVitaminosis D 1 HPTH o MENI, IIa association o Benign Adenoma: most common cause o Peptic Ulcer Dz, acute pancreatitis o Osteitis fibrosa cystica, subperiosteal bone resortpion, osteoporosis, pseudogout

o Diastolic HTN o stones, bones, abdom groans, & psychic moans o Intact serum PTH (iPTH)best initial screen o serum Ca/PTH o serum P/Bicarb o Cl/P ratio >33 o serum calcitriol 1 Hyperplasia: all 4 glands involved 1 HPTH vs Malignancy: PTH1 HPTH & PTHmalignancy Malignancy: most common cause of hyperCa in hospital 2 HPTH: compensation for hypoCa Insulin Therapy: danger of developing hypoP HypoPhosphatemia: alkalosismost common cause HyperPhosphatemia: renal failuremost common cause

Adrenal Gland Disorders Adrenal Cortex o glomerulosa mineralcorticoids o fasciculata glucocorticoids o reticularis sex hormones Peripheral Tissue Sites to Produce DHT: skin, testis, prostate, seminal vesicles, epididymis, liver Adrenal Medulla: produce catecholamines Metabolic End-Products of Epi/Norepi: metanephrines, VMA Abrupt Withdrawal of Corticosteroids: most common cause of acute adrenocortical insufficiency Waterhouse-Friderichsen Syndrome: N. meningitides sepsis DIC bilateral adrenal hemorrhage Autoimmune Dz: most common cause of Addisons dz in US Miliary TB: most common cause of Addisons Dz in developing countries Adrenogenital Syndrome: most common cause of Addisons Dz in kids Addisons Dz o diffuse hyperpigmentation, hypotension, weakness o serum Na, cortisol, bicarb o serum K & ACTH o Hypoglycemia, eosinophilia, lymphocytosis, neutropenia Metyrapone Test: cortisol ACTH 11-deoxycortisol 17-KS, Testosterone, DHT: ambiguous genitalia females, precocious puberty males & females

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Newborn w/ Ambiguous Genitalia: 1st step is to determine genetic sex w/ chromosome analysis 17-KS, Testosterone, DHT: delayed menarche & 2 sex characteristics, males develop pseudohermaphroditism Mineralocorticoids: Na retention w/ HTN Mineralocorticoids: Na losers w/ hypotension Classic 21-OHase Deficiency o most common cause of adrenogenital syndrome o impaired cortisol & mineralcorticoid production (salt loser), androgens Non-Classic 21-OHase Deficiency: impaired cortisol synthesis only, virilzation 11-OHase Deficiency: impaired cortisol + mineralocorticoid excess (salt retainer), androgens 17-OHase Deficiency: impaired cortisol & androgens, mineralocorticoid production 17-OH Progesterone: excellent screening test, 21-&11-OHase deficiency, 17-OHase deficiency Cushing Syndrome o Corticosteroid therapy (iatrogenic) most common cause o Pituitary Cushing most common pathologic cause o Truncal obesity, thin extremities, purple stria o Hyperglycemia, hypoK, metabolic alkalosis Pituitary Cushing o ACTH, Cortisol o Suppression of cortisol by high-dose dexamethasone Adrenal Cushing: ACTH, Cortisol Ectopic Cushing: ACTH, Cortisol Hypercortisolism: thin extremities, purple stria Hyperinsulinemia: truncal obesity Cushing: HTN, hirsutism Screening Tests for Cushing: urine free cortisol, no suppression of cortisol w/ low dose of dexamethasone Nelsons Syndrome: bilateral adrenalectomy causes enlargement of preexisting pituitary adenoma 1 Hyperalodsteronism: HTN, hyperNa, HypoK, metabolic alkalosis 2 Aldosteronism: compensation for cardiac output, activation of RAA system Pheochromocytoma

o majority benign, unilateral, arise in adrenal medulla o orthostatic hypotension, chest pain, ileus o hyperglycemia, neutrophilic leukocytosis Association: neurofibromatosis, MEN IIa/IIb, von-Hippel-Lindau dz Unique Findings: palpitations, paroxysmal HTN, anxiety, drenching sweats, headache Dx: plasma free metanephrinesbest screen Urine Tests: 24hr collection for metanephrine (best test), VMA Neuroblastoma o Malignant tumor postganglionic sympathetic neurons o Childhood tumor & cause of HTN o small cell tumor, neurosecretory granules o Child w/ abdom mass + HTN Opsoclonus-myoclonus Syndrome: paraneoplastic syndrome, myoclonic jerk, chaotic eye movements Insulinoma: serum insulin, C-peptide Pt Injection Excess Insulin: serum insulin, C-peptide

Diabetes Mellitus DM most common cause of blindness, peripheral neuropathy, chronic renal failure, below-knee amputation Maturity Onset Diabetes of the Young (MODY): Auto dom, not obese, impaired glucose-induced secretion of insulin Metabolic Syndrome: insulin resistance exacerbated by obesity Associations: acanthosis nigricans, Alzheimers Dz Hyperinsulinemia: VLDL, HTN, CAD, HDL-CH Good glycemic control prevents complications of diabetes Nonenzymatic Glycosylation (NEG): HbA1C hyaline arteriolosclerosis, glomerulopathy Aldose Reductase: converts glucose to sorbitol, osmotic damage Osmotic Damage: cataracts, peripheral neuropathy, retinopathy Microangiopathy: diabetic nephropathy, deposition type IV collagen Insulin-Induced Hypoglycemia: most common complication of diabetes DKA: complication of type I DM Gluconeogenesis: most important mechanism of hyperglycemia in DKA Ketoacids: synthesized from acetyl-CoA derived from -oxidation of fatty acids Hypertriglyceridemia: capillary lipoprotein lipase activity, hydrolysis of chylomicrons & VLDL

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DKA Electrolytes: serum Na (dilutional), Bicarb (metabolic acidosis), serum K, anion gap metabolic acidosis Hyperomolar Nonketotic Coma: complications of type 2 DM HbA1C: marker of long term glycemic control Impaired Glucose Tolerance (IGT): prediabetic state, insulin resistance Gestational Diabetes: anti-insulin effect of HPL, cortisol, progesterone Macrosomia: insulin causes in adipose & muscle Respiratory Distress Syndrome: insulin inhibits fetal surfactant production Neonatal Hypoglycemia: insulin drives glucose into hypoglycemic range, given newborn glucose at birth

Polyglandular Deficiency Syndromes Type I: Addisons Dz, 1 Hypoparathyroidism, mucocutaneous candidiasis Type II: Addisons Dz, Hashimotoss Thyroiditis, Type I DM Hypoglycemia Hypoglycemia: subdivided into fed & fasting state Reactive Hypoglycemia: excess insulinmost common cause, adrenergic symptoms Fasting Hypoglycemia o alcohol excess, insulinoma, cirrhosis o Kids: look for inborn errors of metabolism Alcohol Excess: glycogen stores, gluconeogenesis, pyruvate converted to lactate Neuroglycopenia: dizziness, mental status s, motor disturbances Dx: prolonged fast, satisfy Whipples Triad

MSK & Soft Tissue Disorders

Bone Disorders Osteogenesis Imperfecta: Auto dom, defect in synthesis type I collagen Blue Sclera: reflection of underlying choroidal veinsie in osteogenesis imperfect Achondroplasia

o Auto dom, mutation in fibroblast growth factor receptor gene o Normal head/axial skeleton, short arms/legs Osteopetrosis o Deficiency of osteoCLASTStoo much bone o Pathologic frx, visual/hearing loss Osteomyelitis o usually hematogenous spread to bone, metaphysismost common site o S. aureusmost common pathogen o Salmonellasickle cell pts o TBPotts dz = vertebral column involvement o Pseudomonaspuncture through rubber soled shoe Sequestra: devitalized bone Involucrum: reactive bone formation in periosteum Draining Sinuses: danger of squamous cancer Osteoporosis o Most common metabolic abnormality of bone o Loss of mineralized bone + organic bone matrix (osteoid) o Women > men o 2 Causes: cortisol, heparin, hypogonadism, malnutrition, space travel o Dx: dual photon absorptiometry o Prevention: weight-bearing exercises, Ca, Vit D, stop smoking o Rx: bisphosphonates 1st line drug Estrogen: inhibits production of osteoclasts, enhance osteoblast Estrogen: osteoclastic activity, osteoblastic activity Postmenopausal Osteoporosis: compression vertebral frxmost common Aseptic Necrosis o disruption of microcirculation causes bone infarctions o femoral head most common site o subcapsular frx disrupts blood supply o Scaphoid Bone: most common wrist bone frx, susceptible to aseptic necrosis o Localized pain o MRI most sensitive early tests Osteochondrosis: aseptic necrosis of ossification centers Legg-Calve-Perthes Dz: aseptic necrosis of femoral head ossification center

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Osteochondritis Dissecans o variant of osteochondrosis limited to articular epiphysis o trauma 1 insult, ischemia 2 injury o distal femurmost common site o osteoarthritis late complication Osgood-Schlatter Dz o Painful swelling tibial tuberosity in boys o Permanent knobby-appearing knees Pagets Dz o Primarily in men >50yo, ? viral etiology o Osteoclastic phase followed by an osteoblastic phase o alkaline phosphatase in osteoblastic phase o Weak, thick, vascular bone o Complications: frx, osteogenic sarcoma, high-output heart failure Fibrous Dysplasia o Defect in osteoblastic differentiation & maturation o Medullary bone replaced by fibrous tissue w/ cyst formation o Ribsmost common site o Complications: pathologic frx, osteogenic sarcoma, fibrosarcoma Albrights Syndrome: polyostotic bone involvement, caf au lait spots, precocious puberty Metastasis: most common bone malignancy Osteochondroma: most common benign tumor Giant Cell Tumor: epiphysis distal femur, proximal tibia

Joint Disorders Monosodium Urate Crystals (MSU): negative birefringenceyellow when parallel to slow ray Calcium Pyrophosphate: positive birefringenceblue when parallel to slow ray Group 1: noninflammatory osteoarthritis, neuropathic joint Group II: inflammatory, RA, gout Group III: septic, Lyme Dz, Disseminated gonococcemi Group IV: hemorrhage, trauma, hemophilia Morning Stiffness: RA, SLE, polymyalgia rheumatic Joint Effusion: blood, exudate Hot Joint: acute inflammation, septic arthritis Joint Crepitus: crackling feeling, osteoarthritis

Osteoarthritis: most common disabling joint dz Alkaptonuria: homogentisic acid deposits in intervertebral disks, black color Osteoarthritis o femoral head, knee, cervical/lumbar vertebrae, hands o wearing down of articular cartilage, bone rubs on bone o osteophytes at joint margins o clefts, subchondral cysts o no fusion of joint o painmost common complaint o joint stiffens after inactivity Ochronosis: auto rec, deficiency homogentisic acid, osteoarthritis Articular Cartilage: proteoglycans, type II collagen OA Fingers o Heberdens NodesDIP joint enlargement/pain o Bouchards NodesPIP joint enlargement/pain OA Vertebral Column: cervical/lumbar, degen disk dz, compression neuropathies Neuropathic Joint o loss of proprioception, deep sensation leading ot recurrent trauma o Causes: diabetes, syringomyelia, tabes dorsalis RA o B cells produce rheumatoid factor (RF), an IgM antibody w/ specificity against Fc portion of IgG o FR combines w/ IgG to produce immunocomplexes that activate complement o Hand: involves MCP & PIP joints, bilateral ulnar deviation o Lung: interstitial fibrosis, effusions o Blood: ACD, AIHA, Feltys Syndromeautoimmune neutropenia, splenomegaly o Cervical Spine: subluxation atlantoaxial joint, cord/vertebral artery compression o Caplan Syndrome: rheumatoid nodules in lung + pneumoconiosis o Cardiovascular: pericarditis, aortitis, vasculitis o Labs: +serum RF, ANA Pannus: granulation tissue, releases cytokines that destroy articular cartilage

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Repair by fibrosis causes fusion of jointankylosis Bakers Cyst: outpouching of posterior joint space in knee Sjorgrens Syndrome o destruction minor salivary glands & lacrimal glands o dry eyes, dry mouth o Lab: + serum ANA, RF, anti-SS-A/anti-SS-B, lip biopsy confirms Juvenile Rheumatoid Arthritis o RF is usually negative o Stills Dz: fever, rash, polyarthritis o Polyarticular: limited arthritis, uveitis & potential for blindness o Pauciarticular: limited arthritis, uveitis, & potential for blindness Gout o Male dominant dz o Most cases dt underexcretion of uric acid o Associations: urate nephropathy, renal stones, HTN, artery dz, Pb poisoning Acute Gout o 1st metatarsophalangeal jointmost often involved o Free uric acid crystals responsible for initiating the attack o Must confirm w/ joint aspiration o Non-Pharm Rx: eliminate high purine diet, moderation in alcohol intake o Pharm Rx: NSAIDs or colchicine o Pharm Prevention: uricosuric agents for underexcretros, allopurinol for overproducers Tophus: MSU deposits in soft tissue around the joint Calcium Pyrophostate Dihydrate Depositition (CPPD) o deposition of Ca pyrophosphate in tissues o w/ hemochromatosis, hemosiderosis, 1 HPTH o OA Variant: kneemost common joint, chondrocalcinosis present Chondrocalcinosis: linear deposits of Ca pyrophosphate in articular cartilage Seronegative Spondyloarthropathies o RF negative arthritis o Key Points: - RF, +HLA-B27, male, sacroiliitis, spondylitis Ankylosing Spondylitis o Over time develop fusion of vertebraebamboo spine o Aortitis, uveitis w/ potential for blindness

Reiters Syndrome o C. trachomatis urethritis, arthritis, conjunctivitis o Achilles tendon periostitis is diagnostic sign Psoriatic Arthritis: sausage-shaped DIP joints, pencil-in-cup deformity N. gonorrhoeae: most common cause of septic arthritis in urban populations Disseminated Gonococcemia: septic arthritis, tenosynovitis, dermatitis B. burgdorferi: gram spirochete, cause of Lyme Dz Lyme Dz o vector Ixodes tick, reservoir white-tailed deer o Erythema Chronicum Migrans: pathognomonic of Lyme Dz o Disabling arthritis, Bells Palsy, Myocarditis Babesiosis: tick-transmitted hemolytic anemia Pasteurella multocida: septic arthritis/tendinitis dt cat/dog bite

Muscle Disorders Type I: slow-twitch (red), rich in mitochondria, oxidative enzymes, poor in ATPase enzymes Type II: fast-twitch (white), poor in mitochondria, oxidative enzymes, rich in ATPas enzymes Muscle Weakness: motor neuron, neuromuscular synapse, muscle dysfxn Neurogenic Atrophy: motor neuron of axon degenerates Trichinosis o Trichnella spiralis (nematode), from eating encysted larvae in pig muscle o Calcified larvae visible on Xray o Muscle pain, periorbital edema, splinter hemorrhages o Pronounced eosinophilia Invasive Group A Strep o Necrotizing fasciitis, myositis, Strep Toxic Shock Syndrome o Exotoxin A (superantigen), exotoxin B (protease) Duchennes Muscular Dystrophy (DMD) o X-linked rec, absence of dystrophin o Pseudohypertrophy of calf muscles o Waddling gait dt weakness of pelvic muscles o serum CK at birth, as muscles degenerate Myotonic Dystrophy o Most common adult muscular dystrophy

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CTG trinucleotide repeat Sagging face, frontal balding, cataracts, testicular atrophy, cardiac involvement o Autoantibodies against Ach receptors, synthesized in thymus o Ptosis, diplopia common finding o Oropharyngeal dysphagia for solids/liquids Myotonia: inability to relax muscles Tensilon: inhibits AChase

o o

Soft Tissue Disorders Dupuytrens Contracture: fibromatosis palmar fascia Liposarcoma: most common adult sarcoma Unhappy Triad: damage to medial meniscus, MCL & ACL Soft Tissue Tumors o Lipoma: trunk, neck, prox extremities, most common BENIGN soft tissue tumor, from subQ tissue o Liposarcoma: thigh, retroperitoneum, most common adult sarcoma, lipoblasts IDed w/ fat stains o Fibrosarcoma: thigh, upper limb, after irradiation o Dermotafibroma: LE, benign, spindle cells prolif in dermins, umbilicated red nodule o Malignant Fibrous Histiocytoma: retroperitoneal, thigh, radiation therapy & scarring o Rhabdomyoma: heart, tongue, vagina, benign, associated w/ tuberous sclerosis o Embryonal Rhabdomyosarcoma: penis & vagina, most common sarcoma in kids, grape-like necrotic mass o Leiomyoma: uterusmost often, stomach o Leiomyosarcoma: GI tract & uterus o Neurofibrosarcoma: major nerve trunks, associated w/ neurofibromatosis o Synovial Sarcoma: around joints, does NOT arise from synovial cellsmesenchymal cells, biphasic patternsepithelial cells forming glands + intervening spindle cells Orthopedic Disorders Colles Fx: FOOSH, distal radius fx w/ or w/out ulnar styloid fx Rotator Cuff Tear: supraspinatus, infraspinatous, teres minor, subscapularis, pain/weakness w/ ABduction

Tennis Elbow: extensor tendon pain, lateral epicondyle Golfers Elbow: flexor tendon pain, medial epicondyle DeQuervains Tenosynovitis: chronic stenosing tenosynovitis of 1st dorsal wrist compartmentABductor pollicis longus & extensor pollicis brevis, excessive friction thickens tendon sheath, Finkelsteins Testulnar deviat. Ganglion (Synovial) Cyst: bulge on wrist dorsum when flexed, F>M Compartment Syndrome: pressure in fascial compart., ischemia, 5Ps pain, paresthesias, pallor, paralysis, pulselessness, Volkmanns Ischemic Contracturedisplaced supracondylar fx of distal humerous causing compression of brachial artery & median nerve Carpal Tunnel Syndrome: median nerve entrapment, causesRA, pregnancy, obesity, excessive use, acromegaly, ape hand, DxPhalens & Tinels Intervertebral Disk Dz: degen of fibrocartilage/nucleus pulposus, ruptured disk may herniated posteriorly & compress nerve root/cord o Radicular Pain: leg pain aggravated by straight leg raising o L3-L4 Hern: loss of knee jerkfemoral n. L2-L4 o L4-L5 Hern: NO loss of reflexes o L5-S1 Hern: loss of ankle reflextibial n. L4-S3 Knee Joint Injuries o Valgus: away from midline via lateral force o Varus: toward midline via medial force o McMurray Test: meniscus injuries o Anterior/Posterior Drawer Tests: ACL & PCL injuries o Unhappy Triad: medial meniscus, ACL, MCL Scoliosis: idiopathicteen girls , usually right thoracic curve

Skin Disorders
Skin Histology & Terminology Stratum Basalis: stem cells for division Stratum Corneum: site for superficial dermatophyte infections Melanocyte: neural crest origin Melanin: synthesized from tyrosine, synthesized in melanosomes Melanosomes: transferred by dendritic processes to keratinocytes

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Blacks: melanosomes in all layers, melanocytes larger/more dendritic processes

Selected Viral Disorders Common Wart: HPV Molluscum Contagiosum o poxvirus, umbilicated lesions w/ viral particles o common in AIDS Rubeola o Regular measles o Prodrome 3 Cs: cough, coryza, conjunctivitis o Rash after Koplik spots disappear o Giant cell pneumonia, acute appendicitis (kids), otitis media Rubella o Maculopapular rash w/ discrete lesion, not confluent, fades in 3 days o Painful postauricular lymphadenopathy o Teratogenic Erythema Infectiosum Parvovirus: slapped face appearance Polyarthritis in Adults: rubella & parvovirus Roseola o HHV-6 o Most common viral exanthema children <2yo o Common cause of febrile convulsions Varicella o Predominantly a childhood dz o Infectiousweek before rash, week after rash until vesicles become crusted o Macules, vesicles, pustules o Complications: KidsReye syndrome, cerebellitis & Adults penumonia, encephalitis, hepatitis Herpes Zoster o Incidence s w/ age, cancer, immunocompromised o Painful vesicles/pustules follow sensory dermatomes Selected Bacterial Disorders S. aureus o gram + coccus in clumps o abscess, postsurgical wound infections, hidradenitis impetigo

TSST: produces desquamating sunburn-like rash S. pyogenes: erythrogenic toxin, erythematous sandpapery rash that desquamates Scarlet Fever o Erythrogenic toxin, erythrematous sandpapery rash that desquamates o risk post-strep glomerulonephritis, rheumatic fever Erysipelas: cellulitis w/ raised borders Tuberculoid o Granuloma, intact cellular immunity, +lepromin skin test o Digital autoamputation, hypopigmented skin Lepromatous o organisms present, impaired cellular immunity, - lepromin skin test o leonine facies Acne Vulgaris o Chronic inflammation of pilosebaceous unit o Comedones: openblackhead, closedwhitehead o Androgen receptors located on sebaceous glands o Propionbacterium acnes produces lipase

Selected Fungal Disorders Superficial Dermatophytes: live in stratum corneum Woods Lamp: detects fluorescent fungal metabolites T. tonsurans: most common cause in blacks, Woods Lamp M. canis/audouinii: most common cause in whites, + Woods Lamp Tinea capitis: oral terbinafine, topical imidazoles do NOT work T. rubrum: most common cause of all other tineasexcept versicolor Tinea corposris: annular, outer border raised/scaly, central clearing Tinea pedis: most common tinea infection, sweating important cause Tinea cruris: sweat most important in pathogenesis Onychomycosis: raised, discolored nail, nail plate white, thick, crumbly Tinea versicolor: alteration in skin prigmentation, hypopigmentation or hyperpigmentation M. furfur: tinea versicolor, spaghetti & meatballs KOH appearance Candida skin infections: intertrigo, diaper rash, onychomycosis Seborrheic dermatitis o dandruff, M. furfur o called cradle cap in newborns

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Sporotrichosis o SubQ mycosis, Sporothrix schenckii o Traumatic implantation o Chain of suppurating lymphocutaneous nodules Cutaneous Larva Migrans o Dog/cat hookwormAncyclostoma o Larvae penetrate skin, serpiginous tunnels Chigger o Small, red mite o Intensely pruritic, red popular/urticarial/vesicular rash Human Itch Mite o Sarcoptes scabiei o Females bury between fingers o Eggs cause pruritus o Infantsno burrows, rash on palms, soles, face Head Louse o Pediculus humanis capitis o Lay eggsnitson hair shafts Body Louse o Pediculus hominis corporis o Adutls live on skin & breed in clothing o Treat clothing NOT pt Phthirus pubis: louse, pubic hairs Bedbug: Cimex lectularius, common infest dwellings, feed on blood

Malignant Melanoma: exposure to excessive sunlight at early age most significant risk factor Radial Growth Phase: initial phase of invasion spread laterally in papillary dermis, no metastatic potential Vertical Growth Phase: final phase of invasion, penetrate reticular dermis, metastatic potential ABCD Signs of Melanoma: asymmetry, borders irregular, color s, diameter Superficial Spreading Melanoma: most common type of malignant melanoma Lentigo Maligna Melanoma: elderly, occurs on face, least likely to have vertical phase Nodular Melanoma: no radial phase only vertical phase Acral Lentiginous Melanoma: not UV related, palms/soles, Asians & AA Prognosis in Malignant Melanoma: depth of invasion most important Melanoma Prevention: sunscreen >15 SPF, protect skin w/ clothing

Melanocytic Disorders Solar Lentigo: common in elderly, liver spots, melanocytes Freckles: normal # of melanocytes w/ in melanosomes Vitiligo: autoimmune destruction of melanocytes Albinism: deficiency of tyrosinase, absent melanin in melanocytes Melasma: malar hyperpigmentation pregnancy/oral contraceptives Nevus Cells: modified melanocytes Junctional Nevus: most common nevus in kids Intradermal Nevus: most common nevus in adults Dysplastic Nevus Syndrome: majority develop malignant melanoma Melanoma o Leading cause of death dt skin cancer o Most rapidly cancer worldwide

Benign Epithelial Tumors Seborrheic Keratosis: most common benign tumor in older people Leser-Trelat Sign: phenotypic marker for stomach adenocarcinoma Ancanthosis Nigricans o Velvety pigmented lesion, common in axilla o Associations: metabolic syndrome, insulin receptor deficiency, Polycystic Ovary Syndrome, Stomach cancer Keratoacanthoma o Benign tumor that histologically mimics squamous cancer o Appears w/in 4-6wks, disappears w/in 6mo Epidermal Inclusion Cyst o derives from epidermis of hair follicle o Locations: face, base of ears, trunk Pilar Cyst o Derives form hair root sheaths o Located on scalp & face Fibroepithelial Tag: flesh colored tag of skin w/ stalk, common in elderly Premalignant & Malignant Epithelial Tumors Actinic (solar) Keratosis o Squamous dysplasia, precursor for squamous cancer o Lesions recur after being scraped off

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Basal Cell Carcinoma o Most common malignant skin tumor o Invade but do NOT metastasize o Arise from basal cell layer Squamous Cell Carcinoma o Excessive exposure to UV light, actinic keratosis, scar tissue o Most common cancer complicating immunosuppressive therapy BCCfavors upper lip SCCfavors lower lip

Selected Skin Disorders Ichthyosis vulgaris: most common inherited skin disorder, stratum corneum Xerosis: most common cause of dried skin & pruritis in elderly Skin s Elderly o hair follicles, sweat glands, skin thickness o dermal collagen/elastic tissue but cross-linking Polymorphous Light Eruption o Most common photodermatitis o Common in Native Americans o Rash occurs abruptly after sun exposure Eczema o Group of inflammatory dermatoses o Acute weep, chronic dry Atopic Dermatitis: Type I IgE-mediated hypersensitivity Contact Dermatitis: type IV hypersensitivity, poison ivy, nickel in earrings Tetracycline: drug w/ photosensitizing effects Lupus Skin Involvement: immunocomplexes along basement membrane Pemphigus Vulgaris o IgG antibodies against desmosomes between keratinocytes o Intraepithelial vesicles, +Nikolsky sign, basal cells resemble tombstones Bullous pemphigoid: subepidermal vesicles, - Nikolsky sign PV & Bullous pemphigoid: type II hypersensitivity rxns Dermatitis herpetiformis (DH): associated w/ celiac dz, subepidermal vesicles w/ neutrophils Lichen planus (LP) o pruritic, violaceous, flat-topped papules o oral mucosa commonly involved, Wickhams Striae

o associated w/ hepatitis C Psoriasis o Strong HLA relationship o Unregulated proliferation of keratinocytes o Commonly preceded by strep pharyngitis o Erythematous plaques w/ silver scales o Rash in areas of trauma (ie elbows), pitting of nails o Munro microabscesses in stratum corneum, Auspitz Sign Piyriasis Rosea: herald patch (plaque) followed by rash in Christmas Tree distribution Erythema multiforms (EM) o triggered by infection (mycoplasma, HSV) or drugs o rash has targetoid appearance, palmar involvement o Stevens-Johnson Syndrome involves skin & mucous membranes o Panniculitis involving anterior portion of shins o Systemic fungal infectios, TB, leprosy, sarcoid, pregnancy, Oral Contraceptives Granuloma annulare: association w/ diabetes mellitus Porphyria cutanea tarda o deficiency uroporphyringoen decarboxylase, association w/ HCV, alcohol abuse o Precipitating Factors: HCV, alcohol abuse, Oral Contraceptives, Fe Urticaria o Mast cell release of histamine o May exhibit dermatographism Cherry Angiomas: bright red papules, invariably present in elderly Acne rosacea o causal relationship w/ miteDemodex folliculorum o pustules & flushing of cheeks, rhinophyma Pyoderma gangrenosum o Ulcerative cutaneous dz associated w/ systemic dz o Ulcerative colitis/Crohns Dz, MPD, RA o Dysregulation of immune system

Selected Skin Disorders in Newborns Erythema toxicum: 30-70% newborns, self-limited Sebaceous hyperplasia: yellow-white papules on face, self-limited Milia

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o superficial epidermal inclusion cysts, pearly white papules o called Epsteins pearls when in mouth Miliaria crystalline: pinpoint clear vesicles, sweat in occluded sweat glands Miliaria rubra: prickly heat, erythematous papulovesicles Both types of miliaria respond to cooling Mongolian Spot o Bluish black to gray spot, dark-skinned babies o Disappears in preschool years

Selected Hair & Nail Disorders Anagen Phase: new hair shaft, hair length determined Telogen Phase: resting phase, loss of hair Estrogen: causes synchronous hair growth, risk for massive hair loss Massive Hair Loss: postpartum, Oral Contraceptives, stress, radiation/chemo Alopecia areata: hairs in areas of hair loss have appearance of exclamation marks Nail Anatomy: lunula, nail plate, nail matrix Psoriasis: nail pitting Fe Deficiency: koilonychiasspoon nails Splinter Hemorrhages: subacute infective endocarditis, trichinosis Mees Lines: transverse white lines, arsenic poisoning, systemic illness Beaus Lines: transverse grooves parallel to lunula, infections Subungual Hematoma: blood clot under nail plate, confused w/ acral lentiginous melanoma

Nervous System & Special Sensory Disorders

Cerebral Edema, Pseudotumor Cerebri, Herniations, Hydrocephalus Cerebral Edema: intracellular & extracellular types Intracellular Edema: serum Na (SIADH), dysfxnal Na/K ATPase pump (global hypoxia) Extracellular Edema: vessel permeability, meningitis, metastasis Respiratory Acidosis, Hypoxemia: cerebral vessel permeability, enhance cerebral edema

Papilledema: sign of cerebral edema Intracranial HTN: papilledema, bradycardia, projectile vomiting, HTN Pseudotumor Cerebri o ICP w/out evidence of tumor or obstruction o Most common in young obese women o CSF resorption in arachnoid granulations o Headache, blurry vision, diplopia Cerebral Hernation: complication of intracranial HTN Subfalcine Herniation: compression of anterior cerebral artery Uncal Herniation o compression of CN III, Posterior Cerebral Artery, parasympathetic fibers o eye deviated down & out, mydriasis Tonsillar Herniation: coning of cerebellar tonsils, cardiorespiratory arrest Hydrocephalus: enlargement of ventricles CSF: produced by choroid plexus, reabsorbed by arachnoid granulations Communicating Hydrocephalus: production CSF, reabsorption CSF Noncommunicating Hydrocephalus: obstruction CSF outflow into ventricles Sylvius Aqueduct Blockage: most common cause of hydrocephalus in newborns Hydrocephalus o Children: ventricles dilate & enlarge head circumference o Adults: no in head size, dementia, gait disturbance, urinary incontinence Hydrocephalus ex vacuo: dilated ventricles 2 to brain atrophy Normal Pressure Hydrocephalus o dilated ventricles + triaddementia, urinary incontinence, widebased gait o potentially reversible cause of dementia w/ shunting o Wide-Based Gait/Urinary Incontinence: stretching of sacral motor fibers o Dementia: stretching of limbic fibers

Developmental Disorders Neural Tube Defects: failure of fusion of lateral folds of neural plate, AFP Maternal Folate level must be adequate BEFORE pregnancy Anencephaly: absence of brain, maternal polyhdraminos

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Spina Bifida Occulta: dimple/tuft of hair overlying L5-S1 Meningocele: cystic mass w/ meninges Meningomyelocele: cystic mass w/ meninges & spinal cord Arnold-Chiari: caudal extension medulla/cerebellar vermis through foramen, hydrocephalus, meningomyelocele, syringomyelia Dandy-Walker: partial/complete absence of cerebellar vermis, cystic dilation of 4th ventricle, hydrocephalus Syringomyelia o degenerative dz of spinal cord, usually cervical cord o cervical cord enlargement, fluid-filled cavity o pain/temp sensation in hands, loss intrinsic hand muscles o MRI shows cervical enlargement & cavity Phakomatosis: neurocutaneous syndromes Neurofibromatosis o Auto dom, incomplete penetrance o Both Type 1 & 2caf au lait macules, neurofibromas NF1 o optic gliomas, Lisch Nodules, axillary/inguinal freckling o associations: pheochromocytoma, Wilms Tumor, CML (juvenile) NF2: bilateral acoustic neuromas, juvenile cataracts, meningiomas Tuberous Sclerosis o Auto dom o Mental retardation, hamartomas in brain, kidneys o Key Findings: seizures, mental retardation, angiofibromas, ash leaf lesions o Rhabdomyoma of Heart: highly predictive of tuberous sclerosis Sturge-Weber Syndrome: vascular malformations of face, ipsilateral arteriovenous malformation in meninges in some pts

Head Trauma Coup Injuries: site of impact Contrecoup Injuries: opposite site of impact Epidural Hematoma: temporoparietal skull fx, Middle Meningeal A. tear CT Scan: imaging test of choice Subdural Hematoma o Venous bleed between dura & arachnoid membranes o Most often caused by trauma, risk w/ cerebral atrophy o Tear of bridging veins producing venous blood clot o CT Scan: imaging test of choice

CNS Vascular Disorders Global Hypoxic Injury o Hypotensive episodes, chronic CO poisoning o Complications: cerebral atrophy, watershed infarcts, stroke Red Neurons: apoptotic neuron Hypoglycemia: effect on brain as global hypoxia Strokes: incidence w/ age Atherosclerotic Stroke o Most common overall stroke, ischemic type o Pale infarction extending to periphery of cerebral cortex o Most occur in MCA distribution o Infarction w/ liquefactive (NOT coagulative) necrosis TIA: transient neurologic deficit lasting <24hr, microembolization of plaque material Amaurosis Fugax: temporary loss of vision, embolic material trapped at bifurcation of retinal vessels MCA Stroke: contralateral paresis/sensory loss in face/upper extremity, head/eyes deviate to side of lesion ACA Stroke: contralateral paresis/sensory loss in lower extremity Embolic Stroke o Ischemic type of stroke dt embolism o Hemorrhagic infarction extending to periphery of cerebral cortex Intracerebral Hemorrhage o complication of HTN, rupture of aneurysm o basal ganglia most common location Rx HTN the incidence of stroke by more than 40% Subarachnoid Hemorrhage o Rupture of congenital Berry Aneurysm o Severe occipital headache, described as worst headache ever Berry Aneurysms: jxn of communicating branch w/ main cerebral artery Lacunar Strokes o microinfarction <1cm o hyaline arteriolosclerosis dt HTN/diabetes Stroke Dx: CT w/out contrastbest test

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 CNS Infections CNS Infection: most dt sepsis Meningitis o inflammation of pia mater o CSF proteinbacterial, fungal & some viruses o CSF glucosebacterial, fungal Bacterial Meningitis: majority of organisms originate in nasopharynx Viral Meningitis: most often transmitted by fecal-oral route Encephalitis: inflammation of brain, headache, drowsiness, coma Cerebral Abscess: hematogenous, contiguous spread Demyelination Disorders Demyelination: destruction normal myelin/oligodendrocyte, abnormal myelin Multiple Sclerosis o Most common demyelinating disease o CD4 T cells react against self antigens in myeline sheath, cytokines activate macrophages that destroy myelin o Genetic factors & environmental triggers o Blurry vision dt optic neuritisMS most common cause Demyelinating Plaques: white matter looks like gray mater Sensory Dysfxn: paresthesis, loss pain/temperature/vibratory sensation Upper Motor Neuron Dysfxn: spasticity, deep tendon reflexes, muscle spasm, Babinski, weakness Autonomic Dysfxn: urge incontinence, sexual dysfxn, bowel motility dysfxn SIN: scanning, speech, intention tremor, nystagmus Bilateral Internuclear Ophthalmoplegia: pathognomonic for MS, demyelination of medial longitudinal fasciculus Lab: CSF lymphs, CSF protein, CSF MBP, normal CSF glucose Oligoclonal Bands in High-Resolution Electrophoresis: sign of demyelination Central Pontine Myelinolysis: dt rapid IV correction of hypNa00usually in an alcoholic Adrenoleukodystrophy: XR, peroxisomal enzyme deficiency in oxidation of fatty acids Metachromatic Leukodystrophy: LSD, deficiency arylsulfatase A

Krabbes Dz: LSD, deficiency -galactocerebrosidase w/ in galactocerebroside in lysosomes

Degenerative Disorders Alzheimers o Most common overall cause of dementia o Sporadic late onset typemost common type o Prevalence s w/ age o phosphorylated A neurotoxic o density of NF tangles & senile *neuritic) plaques in brain, occipital lobe usually spared o Prominent early signdecline in short-term memory o Presumptive dx w/ mental status testing, r/o all other causes of dementia Activated GSK-3: phosphorylates A A o can be converted into amyloid, deposits in cerebral vessels o metabolic product of APP, coded for on chromosome 21 Secretases: -secretases followed by -secretases cleave APP A Insulin Degrading Enzyme: involved in clearance of A Apo Gene E, Allele 4: sporadic early onset AD Activated GSK-3: hyperphosphorylates tau protein Neurofibrillary Tangle: hyperphosphorylated tau protein in neuron PIN1 Enzyme: dephosphorylates hyperphosphorylated tau protein, deficient in some cases of AD Senile (Neuritic) Plaques: core of A surrounded by neuronal cell processes w/ tau protein Amyloid Angiopathy: risk for cerebral hemorrhage Confirmation of AD: must be made at autopsy Parkinsonism o Alteration in dopaminergic pathways involved in voluntary muscle movement Dopamine: principle NT in nigrostriatal tract Idiopathic Parkinsons Dz o most common cause of Parkinsonism o depigmentation substantia nigra neurons, dopamine o Clinical: rigidity, resting tremor, bradykinesia o Expressionless face, blepharospasm, seborrheic dermatitis Huntingtons Dz

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o Auto dom, trinucleotide repeat disorder o Atrophy of caudate nucleus, putamen, globus pallidus o Chorea, oculomotor abnormalities Friedreichs Ataxia o Auto rec, trinucleotide repeat disorder, deficiency frataxin o Degeneration Sites: dorsal root ganglia, posterior/spinocerebellar/corticospinal tracts o Hypertrophic cardiomyopathy, type I diabetes mellitus Amyotrophic Lateral Sclerosis o Degeneration of Lower & Upper Motor Neuron o Atrophy of intrinsic muscles of hand1st LMN sign o No sensory s, bowel & bladder fxn intact Werdnig-Hoffmann Dz: Lower Motor Neuron dz in children

o Female predominance o Psammona bodies Ependymoma: 4th ventricle in kids & cauda equina in adults Medulloblastoma: small cell tumor in cerebellum Oligodendroglioma: frontal lobe calcifications in an adult 1 CNS Lymphoma: occurs in AIDS, EBV-mediated cancer Metastasis: most common brain malignancy

Toxic & Metabolic Disorders Wilsons Dz: cystic degeneration of basal ganglia Lenticular Nucleusputamen & globus pallidus in the basal ganglia Acute Intermittent Porphyria o Urine colorless when 1st voided, exposure ot light produces color o Deficiency uroporphyringoen synthase, bellyful of scars, peripheral neuropathy, dementia o Rx: carbohydrate loading inhibits ALA synthase Vitamin B12 Deficiency: subacute combined degeneration, dementia Wernicke-Korsakoff Syndrome o hemorrhage in mammillary bodies o confusion, ataxia, nystagmus, ophthalmoplegia Alcoholics receiving IV infusion w/ glucose: supplement IV w/ thiamine to prevent acute Wernickes Encephalopathy CNS Tumors Glioblastoma Multiforme: most common 1 CNS tumor in adults Childhood Tumors: cystic astrocytoma & medulloblastomaboth in cerebellum Clinical: headache, seizures, intracranial HTN Astrocytoma: most common neuroglial tumor Glioblastoma Multiforme: grade IV astrocytoma, often crosses corpus callosum, hemorrhagic/cystic Meningioma o Most common benign brain tumor in adults

Peripheral Nervous System Disorders Sensory s: demyelinationparethesias, glove & stocking distribution Motor s: axon degenerationmuscle fasciculations, atrophy Charcot-Marie-Tooth Dz o Most common hereditary neuropathy o Lower legs have inverted bottle appearance Guillain-Barre Syndrome o Most common acute peripheral neuropathy o Preceding Infections: M. pneumonia, C. jejuni, viruses o Causes ascending paralysis o Rx: IV immunoglobulin or plasma exchange Diabetes Mellitus: most common cause of peripheral neuropathy Idiopathic Bells Palsy o Facial muscle paralysis dt inflammation of CN VII o HSV most common association Upper Motor Neuron Bells Palsy: contralateral weakness lower face, sparing of upper face Drugs: vincristine, hydralazine, phenytoin Vitamin Deficiencies: thiamine, pyridoxine, vitamin B12 Schwannoma: benign Schwann cell tumor Acoustic Neuroma: schwannoma of CN VIII

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