BODY FLUIDS

Blood and Lymph Physiology

HERBERT

1
Which of the following is the mechanism of action behind
heart arrhythmias caused by hyperkalemia?

• A. Increased potassium hyperpolarizes the cell

• B. Increased potassium prolongs action potential duration
• C. Increased potassium increases heart rate via funny current
channels
• D. Increased potassium depolarizes the cell bringing excitable
nerves closer to action potential
• E. Increased potassium increases intracellular calcium
concentration

2
 The amount of tension that a whole muscle can produce is
greatest in which of the following situations;

• A. in the single twitch response

• B. during maximal incomplete tetanus
• C. during submaximal complete tetanus
• D during maximal complete tetanus
•
•

3
The rate of diffusion of a particle across a membrane will
increase if ;

• A. the thickness of the membrane increases

• B. the area of the membrane increases
• C. the size of the particle increases
• D. the lipid solubility of the particle increases

4
BODY WATER:
•When water gain equals water loss i.e. water balance, the body
water remains constant.
•Body water is about 40 litres in a 70kg adult which is about 60% of
total body weight
•It consists of Intracellular Fluid and Extracellular Fluid
•Body water is made up of 2/3 intracellular fluid which is 25 litres of
about 40% of body weight
• And 1/3 Extracellular Fluid: Include Intravascular/ plasma (3 litres
& about 5% of body weight) and interstitial fluid (12 litres & about
15 % of body weight).
WATER BALANCE
•The body water remains within normal range through a balance between water
gain and water loss inside the body.
Water Gain
•It is about 2.5 litres/day (2/3 amount is taken as drinks):
•Exogenous : 2.25 litres /day as drinks or food
•Endogenous (metabolic water): 0.25 litres/day resulting from oxidation of H+ ions
during metabolic reactions especially fat metabolism inside the body.
Water Loss
i.Urine: It is about1.50 litres/day. It increases when water intake is increased or in
winter.
ii.Skin: Water loss through the skin includes – Insenisible perspiration: loss of
water by diffusion through the skin. It is about 400 cc/day. It is not a sweat
secretion. It is independent of weather – Sweating: It is about 100 cc with normal
temperature. It may reach 2 litres/hour in very hot weather.
iii.Expired air: About 400 cc/day are lost through evaporation from the
respiratory tract.
iv.Faeces : contain about 100 cc water/day.
THIRST SENSATION
•It is an organic sensation indicating that the body needs water and derives
the person to drink.
•It occurs when the osmolarity of ECF is increased.
•It is felt as dryness in the mouth and pharynx.
Mechanism of Thirst
1. Peripheral mechanism:
•Thirst sensation is felt as dryness in the mouth and throat.
•It is mediated by afferent in the glossopharyngeal and vagus cranial nerves.
•This mechanism is the stimulus for drinking i.e. indicates when to drink.
2. Central mechanism:
•Dehydration of the thirst centre located in the anterior part of the
hypothalamus sends impulses to the limbic lobe of the cerebral cortex
where the thirst sensation is perceived.
•The central mechanism determines the amount of water needed i.e. how
much to drink.
OVERHYDRATION AND DEHYDRATION
OVER-HYDRATION
•This means retention of excess water in the body i.e. positive
water balance or water intoxication.
•This occurs when the water intake exceeds the water loss.
Causes
1.Drinking excess water without Nacl in a dehydrated person e.g.
in persons working in hot humid weather as in miners.
2.Intravenous infusion of large amounts of fluids after
hemorrhage or in patients with renal diseases.
3.Excessive secretion of anti-diuretic hormone.
Symptoms of Overhydration
•As a result of decreased osmolarity of ECF water diffuses from ECF
into cells, leading to their swelling.
•Symptoms of overhydration results to :
1.Brain edema: there is excitation of the nerve cells leading to
headache, convulsions, coma and finally death.
2.Pulmonary edema: prevents normal gas exchange. It may be a fatal
condition.
3.Hypothermia: Increased blood volume leads to increased blood
flow through the skin, hence increased heat loss and consequent
decreased body temperature (hypothermia).
DEHYDRATION
•This means loss of fluid from the body (usually water and NaCl).
•Water loss exceeds the water intake (i.e. Negative water balance).
Causes
1.Excessive loss of fluids : due to severe vomiting, severe diarrhea
or excessive sweating.
2.Nephrotic kidney
3.Adrenal insufficiency: results in failure of kidneys to reabsorb
NaCl and water due to absence of aldosterone hormone.
Symptoms
1.Loss of body weight: due to loss of water and utilization of adipose
fat as source of intrinsic water.
2.Eyes: Sunken due to decreased intra-ocular pressure
3.Fontanelles: These gaps of the skull in infants are depressed.
4.Skin: Is cold due to decreased blood flow, pale, dry and wrinkled.
5.Hyperthermia: Increased body temperature due to diminished heat
los caused by decreased blood flow through the skin.
6.Hypotension and circulatory failure may develop.
7.Cerebral disturbances: coma, failure of respiratory centres and final
exhaustion and death when 20% of body water is lost.
 Introduction BLOOD

Section 1 Composition and Properties of the Blood

Blood is a fluid
tissue, a suspension
solution of blood
cells in plasma that
is circulating
through the
cardiovascular
system.

12
13
 Haematocrit (Hct)
• a cellular portion,
called formed
elements, and
• a fluid portion, called
plasma.

14
 Blood cells

• Red cells (erythrocytes )

• White cells (leucocytes)
• Platelets (thrombocytes )

15
 Plasma ‫ا‬
Straw-colored liquid consisting of water
and dissolved solutes.
Sodium ion is the major solute of the
plasma in terms of its concentration.

In addition to Na+, plasma contains many other salts

and ions, as well as organic molecules such as
metabolites, hormones, enzymes, antibodies, and other
proteins. 16
Plasma Proteins
– constitute 7-9% of the plasma
(1) Albumins (60% - 80%)
Produced by the liver
Provide the osmotic pressure and necessary to maintain
blood volume and pressure.
Effective Filtration Pressure = (capillary pressure + interstitial
osmotic pressure) – (plasma colloid osmotic pressure +
interstitial hydrostatic pressure)
(2) Globulins, divided into three types:
1) Alpha and beta globulin, produced by the liver and
function to transport lipids and fat soluble vitamins in
the blood.
2) Gamma globulins are antibodies produced by
lymphocytes and function in immunity.
17
 Gamma Globulin
• IgM
• IgG
• IgE
• IgD
• IgA

18
 Plasma pH
The plasma pH is maintained in a very narrow range (7.35 –
7.45) through numerous mechanisms.
Acids in the blood are buffered by bicarbonate in the plasma,
and blood pH is maintained by the actions of the lungs and
kidneys.
The lungs aid acid –base balance through elimination of
carbon dioxide, which regulates the amount of carbonic
acid in the blood.
(Respiratory movement – Inspiration and Expiration)
The kidneys participate in acid – base balance by excreting H
and retaining plasma bicarbonate. 19
• At the venous end of the
capillary, the capillary
blood pressure is 10-15
mmHg which is less than
the OP of plasma proteins
(25-30 mmHg).
• Therefore, fluids are
absorbed from the tissue
spaces to the blood
(reabsorption of
900cc/hour, containing
carbondioxide and waste
products).
• 100 cc water/ hour are
removed by lymph vessels
and transported to thoracic Formation of tissue fluid.
Plasma proteins remain inside the blood
duct and the big veins at capillary as the capillary membrane is
the root of the neck. not permeable to plasma proteins.
Note:
1. The Oncotic Pressure (OP)
•It is the effective colloid osmotic pressure (25mmHg).
•It equals the OP of plasma proteins (Plasma colloid OP = 28mmHg) –
OP of proteins in the interstitial fluid (interstitial fluid colloid OP) =
3mmHg).
•Colloid osmotic pressure = Plasma colloid - Interstitial fluid colloid
25mmHg = 28mmHg – 3mmHg

2. Dynamic state of plasma proteins

•Plasma proteins are continuously used by tissues then regenerate again
from the amino acids derived from diet and tissues.
•They are re-synthesized every 10-20 days (life span) so they are
dynamic and not static.
Hypoproteinaemia
•Decreased plasma proteins levels occurs in:
1.Prolong starvation: Plasma protein levels are maintained during
starvation until body protein stores are markedly depleted.
2.Mal-absorption syndrome due to intestinal diseases
3.Liver diseases: Because protein synthesis in the liver is depressed
4.Renal diseases e.g. nephrosis: Due to loss of large amount albumin
in urine. Because of the decrease in the plasma oncotic pressure,
edema tends to develop
5.Congenital protein deficiency: Rarely, there is a deficiency in one of
the plasma proteins e.g.
i.Congenital afibrinogenemia: characterized be defective blood
clotting
ii.Congenital agammablobulinaemia: characterized by lowered
resistance to infections.
The Blood Cells
The blood cells include red blood cells
(erythrocytes), white blood cells (leucocytes) and
platelets (thrombocytes).

23
24
25
 Definitions
• Haemopoiesis
• Erythropoiesis
• Leucopoiesis
• Throbopoiesis

26
The Red Blood Cells

27
Red cells (Erythrocytes)
Number: 4.8 to 5.8 million in males and 4.2 to 5.2
million in females per milliliter blood.

Shape: flat, biconcave discs,

about 7 um in diameter and 2
um thick.
Importance of the unique
shape: relates to the
transportation of oxygen and
provides an increased surface
area through which gas can
diffuse. 28
29
EM of normal red blood cells

30
 Life Span of RBCs

Erythrocytes lack a nucleus and mitochondria (they

get energy from anaerobic (but not aerobic)
respiration).
Because of these deficiencies, erythrocytes have a
circulating life span of only about 120 days before
they are destroyed by phagocytic cells in the liver,
spleen and bone marrow.
31
 Hematocrit
• The percentage of blood volume occupied by
the packed red blood cell volume is termed
hematocrit value or hematocrit.
• Normal range:
– man, 40% - 50%
– women 38% - 48%

32
 MEASUREMENT OF HAEMATOCRIT
The haematocrit ratio (Ht) is the proportion of blood made up of cells -
mainly red blood cells.
After centrifugation the
heavier red cells settle to
1.0 the bottom of the tube.
plasma The straw-coloured plasma
centri- remains at the top.
fuge The two layers are
0.5 separated by a ‘buffy coat’
buffy coat of white cells and platelets.
red cells
Normal values for Ht
0 range between 0.42 - 0.47,
generally larger in men
blood
than women.
sample 33
 Function of RBCs
1. To transport oxygen from the lungs to the tissue (function
of hemoglobin)
2. To transport carbon dioxide in blood.
3. Transport of other gases (Co 250 times O2)
4. Buffer (regulation of pH ,70% by Haemoglobin)

The arterial and venous red cell

34
 Haemoglobin
• Normal level:
– 14 – 18 g/dl Males,
– 12-16 g/dl Females
• Increases blood carrying capacity for
O2 60 times
• Consist of : Haem + Globin
• Types of Haemoglobin
– Hb A1 (2 alpha + 2 beta) 98 % of adult
Hb
– HB A2 (2 alpha + 2 delta) 2 % of adult
Haemoglobin
– HB F (2 alpha + 2 gama)

35
 Breakdown of Hb

• RBCs life span 120 days

• Where (reticulo -endothelial system)
• Hb = Haem + Globin
Haem
Biliverdin
Unconjugtaed
Conjugated
urobilinogen
• Jaundice (bilirubin more than 2 mg / 100 ml )
– Haemolytic, Hepatic & Obstructive

36
 Materials for Erythropoiesis

• Iron ( 10 mg / day Male,20 mg / day Female)

• Amino acids
• Vit B12 (liver and meet)
• Folic acid in vegetables (5 mg / day )
• Vit C (for absorption of iron)
• Pyridoxine (iron resistant anemia in infants)
• Vit E
• Trace elements (Cu,Nickel,Zinc,cobalt & manganese)
37
 Iron Metabolism
• Distribution (total 4 g)
– Hb (3 g,70%)
– Storage (1 g)
– Tissue (150 mg)
– Transport (3-4 mg)
• Iron in food
– Organic & non organic
• Absorption
• Transport and storage
• Excretion and daily requirements
– Faeces ,skin, urine and menses
38
– 10 mg in males & 20 mg in females
 Erythropoiesis
production of new red blood cells to replace the old and died
ones
In the adult, all the red cells are produced in bone marrow

39
Pluripotent stem cells in the bone marrow can produce any
type of blood cells. The pluripotent stem cell is capable of
both self-replication and differentiation to committed
precursors-cells that can produce only a specific cell line.

CPU ： colony-
forming unit

40
Committed red cell precursor undergoes several divisions.
The daughter cells becomes progressively smaller, the
cytoplasm changes color from blue to pink as hemoglobin is
synthesized, and the nucleus becomes small and dense and
then extrude. The resulting non-nucleated cells is termed a
reticulocyte since it still contains RNA.Within a few days of
entering the circulation, the reticulocytes lose their RNA and
becomes mature red cells
Early Intermediate Late

Proerythroblast Polychromatophilic Reticulocyte

(Pronormoblast) Normoblast
Basophilic Orthochromatophilic Erythrocyte
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Normoblast Normoblast
 Importance of the erythropoiesis

In health, the number of the red cells was remained

remarkable constant by erythropoiesis
Decrease rate of erythropoiesis or increased rate of red
cells destruction -- Anemia – decreased number of red
cells and weight of hemoglobin

42
 Red blood cell indices 2

• Haemoglobin - 15±2.5, 14 ±2.5 - g/dl

• PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)
– Haematocrit, effective RBC volume - better
• RBC count - 5.5 ±1, 4.8 ± 1 x1012/l
• MCHC - Hb/PCV - 30-36 - g/dl
– Hb synthesis within RBC
• MCH - Hb/RBC - 29.5 ± 2.5 pg/l
– Average Hb in RBC
• MCV - PCV/RBC 85 ± 8 - fl
43
 Regulation of erythropoiesis
A. Erythropoietin, a glycoprotein released predominantly from
the kidneys in response to tissue hypoxia. It is also produced
by reticuloendothelial system of the liver and spleen.
Effect: a, Stimulates the proliferation and differentiation of the
committed red cell precursor
b, Accelerates hemoglobin synthesis
c, Shortens the period of red cell development in the
bone marrow.
B. Adrenal cortical steroids, pituitary growth hormone,
parathyroid hormone and androgen -- stimulate
erythropoiesis
C. Estrogen – inhibit erythropoiesis 44
 Red blood cell indices 1

• Haematocrit (Hct)
– RBC volume / Blood volume (L/L)
• Mean corpuscular volume (MCV)
– Hct / RBCs
• Mean corpuscular Haemoglobin (MCH)
– Hb / RBCs
• Mean corpuscular Haemoglobin concentration (MCHC)
– MCH / MCHV

45
 RBC disorders (Anemias) :
“Anemia is decreased red cell mass
affecting tissue oxygenation”
* Low Hb <13.5 (males), <11.5 (females)
• Acquired disorders:
– Decreased production
– Increased loss
• Congenital disorders:
– Membrane, Hb & enzyme disorders.
46
CLASSIFICATION OF ANAEMIA
1. According To The Cause/Etiology of Anaemia
i. Hemolytic anaemia: Caused by increased loss of RBCs due to:
•Chemicals : such as lead or arsenic poisoning
•Diseases : e.g. malaria
•Bacteria Toxins: Certain drugs and snake venoms
•Hereditary defects of RBCs: Hereditary spherocytosis (RBCs are small spherical and
hemolyse easily), Sickle cell anaemia (RBCS contain abnormal HbS which is easily
precipitated at a low oxygen tension. RBCs appear as sickles and hemolyse easily).
• Enzyme deficiency: Glucose -6- phosphate dehydrogenase deficiency.
ii. Blood loss anaemia/Post haemorrhage Anaemias: Is type of anaemia due to
excessive loss of RBCs as a result of the following:
•Acute or chronic bleeding piles
•Uterine bleeding
•Chronic peptic ulcer
•Hook worm infestations
•Chronic menstrual bleeding.
•Here enough iron cannot be absorbed to make up the loss of blood
iii. Deficiency Anemias: Is the type of anemia due to deficiency of nutrients
leading to defective formation of RBCs. Examples: Copper, Protein,
Iron deficiency: It is microcytic hypochromic anemia due to iron deficiency.
Causes:
•Inadequate iron in diet: Normal diet contains 10-20 mg iron while the body
needs only 1-2 mg/day.
•Failure of iron absorption.
•Chronic blood loss
Prevalence:
•Infants: Iron deficiency anemia is common in infants due to deficiency of iron in
mother’s milk together with consumption of the stored iron in the infants body.
Iron is stored during intrauterine life and derived from hemolysis of excess red
cells after birth is consumed within 4-6 months after birth.
•In females: In reproductive period due to iron loss, monthly in blood of
menstruation, during pregnancy, child birth and lactation.
Folic Acid deficiency: Folic acid deficiency like vitamin B12 deficiency affects
rapidly dividing cells (DNA syntheisis). Folic acid deficiency is due to its:
•Deficiency in diet especially during pregnancy.
•Failure of absorption due to diseases of small intestine.
Treatment
•Macrocytic anaemia due to folic acid deficiency is treated by
administration of folic acid. If pernicious anemia is treated wrongly by
giving folic acid, there will be increase in the damage of nervous
tissues because folic acid stimulates the metabolism in the myelin
sheaths and increases the need for vitamin B12 which is already
deficient.
 Vitamin B12 deficiency (Pernicious anemia): Occurs as a result
of:
•Lack of intrinsic factor due to atrophy of gastric mucosa caused by
autoimmune disease or after gastrectomy.
•Diseases affecting the terminal part of ileum acusing failure of
vitamin B12 absorption.
•Liver disease causing failure of storage of viatminn B12.
•Deficiency of vitamin B12 in diet which is rare.
Features of Pernicious Anemia
•Macrocytic anaemia: Where red cell formation in bone marrow is depressed
resulting in the failure of their maturation. RBCs are larger in size than normal
(macrocytic); However, the Hb concentration relative to the size of the RBCs is
normal (normochromic).
•Atrophy of gastric mucosa: With decreased HCl and pepsin secretion
(achylia gastrica).
•Subacute combined degeneration: There is degenerative lesions in posterior
and lateral columns of the spinal cord. Degenerative lesions als occur in the
peripheral nerves.
Treatment:
•Injection of vitamin B12 for life
 Aplastic Anemia:
•Bone marrow destruction e.g. X-ray or atomic radiations, exposure to
chemical toxins and prolonged drug use (antibiotic) or malignant diseases
destroying bone marrow (leukaemia).
•It is normocytic normochromic anaemia with severe reduction of all blood
cells (RBCc, WBCs and platelets).
iv. Anaemia Due To Chronic Diseases:
•Tuberculosis, chronic infections, cancers, lung diseases etc.
•The tissue macrophages are believed to become activated so that RBCs are
removed from blood faster than they can be formed in bone marrow.
2. According to the size and saturation of RBCs with Hb
•Microcytic: Smaller than normal size of red blood cell.
•Normocytic: Normal red blood size.
•Macrocytic: Larger than normal red blood cell size.
•Normochromic: Normal Hb concentration.
•Hypochromic: Reduced or little Hb concentration than normal.
Examples:
•In iron deficiency: We have microcytic hypochromic anaemia, because of
lack of iron required for Hb formation.
•In Vitamin B12 and Folic acid deficiencies: We have macrocytic
normochromic anaemia.
•In hemolytic, blood loss, aplastic and hypersplenism: We have
normocytic normochromic anemias.
EFFECTS OF ANEMIA
•Blood viscosity is decreased leading to decreased in peripheral
resistance hence more venous return to the heart.
•Hypoxia: This leads to vasodilation and increased venous return
and increased cardiac output and work load of the heart.
•Increased heart rate (tachycardia) due to increased venous
return and hypoxia.
•Pallor and easy fatigability.
 Acquired RBC disorders :
• Decreased Production:
– Aplastic, Hypoplastic anemias
– Deficiency anemia's Iron, B12, Folate etc.
– Lack of erythropoiesis - Kidney disease
– Marrow disease, malignancy, radiation
• Increased loss/destruction:
– Blood loss anemias - parasites, bleeding
– Hemolytic anemias - Autoimmune (cold & warm
antibody) mechanical, drugs & toxins.

53
 Congenital RBC Disorders:

• Membrane Disorders:
– Spherocytosis, Elliptocytosis
• Hemoglobin Disorders:
– Hemoglobinopathies - Sickle cell, HbC etc.
– Thalassemia Syndromes - , , 
• Enzyme disorders:
– G6PD, PK deficiency
54
 Causes of High Hematocrit (Polycythemia)
• Relative or spurious erythrocytosis
– Hemoconcentration secondary to dehydration
– (diarrhea, diaphoresis, diuretics, deprivation of
water, emesis, ethanol, etc.)
• Absolute erythrocytosis (True ):
– Tissue hypoxia - High altitude, Pulmonary disease,
respiratory def. Right to left cardiac shunts, Carbon
monoxide intoxication, High oxygen-affinity Hb.
– High EPO - Renal disease, Tumors eg. HCC.
– Androgen therapy
– Primary - Polycythemia vera
– EVALUTION OF RBC STATUS- -- next lecture
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Blood and Lymph Physiology

56
The White Blood Cells

57
 Classification
• Leukocytes
• contain nuclei and mitochondria
• can move in an amoeboid fashion, so they can
squeeze through pores in capillary and get to a site
of infection.
• Number, 4000 to 10000/mm3
• Classification:
– Granular leukocytes, having granules in the cytoplasm;
– Agranular (or nongranular) leukocytes: without granules
in the cytoplasm

58
 Leucopoiesis
• Formation of white blood cells
• Site of formation
– Granulocytes :bone marrow
– Lymphocytes: bone marrow ,thymus, lymph nodes
and other lymphoid tissue collections e.g. wall of
intestine
– Monocytes:bone marrow

59
60
 Haemopoietic growth factors

• Sustain blood production through out life

• Group of glycoprotein growth factors
• First one is Erythropoietin
• Control white cells;
– CSF GM
– CSF G
• Recently used clinically to induce bone marrow
– Marrow failure
– Hematological malignancies
– infections 61
1- Granular Leukocytes

A.Eosinophils
B. Basophils
C. Neutrophils

62
 A. Basophils
o Only 0-2 %,
o release heparin and
histamine that are
responsible for the
allergic reaction
o Also contains 5HT and
RNA
o IgE
63
 B.Eosinophils
• 2-4%
• Function: Limit the action of
basophils in the rapid allergic
reactions by releasing:
– prostaglandin E
– histamine oxidase
• Phagocytosis:capable of ingesting
variety of particles,
bacteria ,destroyed cells and antigen
anti body complex
• Eosinophilia in
– parasitic infections
– Allergic conditions
– Tropical eosinophilia (reaction to filarial)
– Dermatological diseases
64
 C. Neutrophils

o 60%-70% (most abundant)

o nonspecific cellular immunity
o After attraction by chemical
substances (chemotaxis) released
by bacteria, they engulf and digest
the bacteria or other foreign
substances by means of
phagocytes

65
 Microbial killing
• Following phagocytosis the following
• events take place
– Fusion of neutrophilic granules with phagocytic
granules
– Release of antimicrobial agents from granules
(lysizymes,myeloperoxidase & lactoferrin
– Killing and digestion of the ingested organism
• Complement MAC

66
 Chemotaxis

• Attraction of white cells to site of inflammation

• Neutrophils attracted to areas of acute inflammation
– Bacterial products,
– damaged leucocytes or
– other tissue components
• Eosinophils attracted by
– Histamine,
– 5HT and antigen –
– antibody complex ,
– bradykinin and
– specific esininophil chemotactic factor
• In allergic skin and lung diseases due to histamine 67
 Phagocytosis
• Cell eating
• Neutrophils,Esinophils and Macrophage
• Action
• Killing
• Antigen presentation to T-cell

68
 2-Agranular Leukocytes

A, Monocytes.
B, Lymphocytes
o T (thymus dependent) lymphocytes,
responsible for the cellular immunity
o B lymphocytes, responsible for the humoral
immunity.

69
 A.Monocytes
• 2% - 8%. Wander into the
tissue and become fixed in
the tissue and swell to
become fixed tissue
macrophages.
• During the inflammation,
they can divide in situ and
form more macrophages -
“wall process” for preventing
spread
70
 B.Lymphocytes
• 20% - 30%
• T (thymus dependent)
lymphocytes,
responsible for the
cellular immunity
• B lymphocytes,
responsible for the
humoral immunity.

71
 T - lymphocytes

• there are millions of different T cells – the difference is in

their receptors (surface markers)

• each T cell has a unique receptor that will recognize a

different foreign substance

• mature in the thymus, where they learn to tell the

difference between self and “non-self”
- critical, because if they did attack “self”,
autoimmune disease could result

72
 T cell training
• T cell precursors arrive in the thymus
• there, they express specific T cell receptors and meet
cells that “wear” bits of self proteins, called MHC
(major histocompatibility complex), that are markers
for the body’s own cells
• there are two steps
- first, T cells must recognize self-MHC, or they are destroyed
- in a second step, T cells that bind too tightly to self-MHC are
also destroyed
• remaining T cells go to the spleen and lymph nodes,
and wait for antigens. If they recognize an antigen,
some will “go into battle” and others become memory
cells

73
 Types of T cells
Based on function, there are different types
including:
• Helper T cells (Attacked by HIV)
– start the immune response
• Cytotoxic T cells
– kill the body’s abnormal cells, like virus-infected cells
and cancer cells
• Suppressor T cells
– suppress the activities of other T cells, helping to end
the immune response

74
A Cytotoxic T Cell Attacking and Killing a Virus-
Infected Target Cell

CELLS alive!

Here, the smaller cytotoxic T cell or Tc (arrow) is attacking and killing

a much larger virus-infected cell. The T cell will survive while the
infected cell is destroyed.
75
 B - lymphocytes
• Site produced and mature in bone marrow
• Antibody each B cell produces and wears a unique
antibody on its surface
• Clonal Selection - when a B cell encounters a matching
antigen, it begins to divide rapidly.
– Some then become plasma cells that all produce the same
antibody, and then die.
– Others become memory cells.
• Plasma cells the specific antibody produced by a plasma
cell is also secreted in soluble form and circulates in the
blood
76
 Antibody structure
Each is made of two identical heavy and two
identical light amino acid chains, held together
by disulfide bonds
- parts of the antibody (Ab) are
constant, i.e., the same for
every antibody
- parts are variable - the arms of
the “Y” have different amino
acid sequences that cause
specific binding to antigen

77
 Classes of antibodies
• IgM – a pentamer – five Y-shaped immunoglobulins joined
together – the “early” Ab, it is produced before any of the other
types – it activates complement
• IgG – the most common form, and the major one for secondary
responses (small and can cross the placenta)

• IgA – mostly a dimer – two Y-shaped immunoglobulins secreted

in saliva, colostrum, milk, semen, mucus
• IgE – binds to receptors found on mast cells & basophils –
involved in allergy and parasitic infections
• IgD (receptor)

78
 Total leucocyte count
• 400-10000 cells/m (in Europeans)
• 200-40000 cells may be normal in some
tropical areas due to low Neutrophils count
(Neutropenia)

79
 Differential white cell count
• Neutrophils 60 -70 %

• Lymphocytes 20-30 %

• Monocytes 2-8%

• Eosinophils 2-4%

• Basophils 0-2% 80
 Leucocytosis

• Physiological
– Diurnal variation (low in morning ,high in
afternoon
– Following a protein meal
– Physical exercise
– Stimulation by stress or injection of adrenaline
• Disease states
– Bacterial infections (tonsillitis ,wound infection
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 Leucopenia
• A decrease in the total leucocyte count
• Malnutrition
• Typhoid fever
• Some drugs (agranulocytosis)
• Deficiency of vitamin B12 and folic acid

82
 Leukaemia

• Neoplastic growth of stem cells

– In bone marrow Myeloid leukemia
– In lymph tissue Lymphocytic leukemia
• Total count usually above 50 000/mm3
• Acute or chronic
• Causes anemia and thrombocytopenia
• Causes
– Not fully understood
– But ,chromosomal,radiation,toxins,drugs and viruses

83
Blood and Lymph Physiology

Herbert
Department of Physiology

84
Haemostasis & Platelets

85
 Objectives

• Platelets
• Vascular Spasm
• Platelet Plug
• Coagulation
• The Fate of Blood Clots
• Prevention of Inappropriate Coagulation
• Coagulation Disorders

86
 Haemostasis
• Prevent blood loss from intact vessels & stops
excessive bleeding from injured vessels

• Components
A. Local vascular factor
B. Platelets
C. Coagulation
D. Fibrinolysis

87
 A-Vascular factors
• Localized vasoconstriction
• Transient (less than 1min)
• Humeral factors
– 5HT (from platelets)
– Thromboxane A2
– Endothelin
– Adrenaline (from adrenal
medulla)
• Influenced by
– Hypoxia and
– metabolic acidosis

88
HAEMOSTASIS
•Hemostatsis means stoppage of bleeding from an injured blood vessels by the following
mechanisms:
1. Local Vasoconstriction by:
•Sympathetic stimulation due to pain
•Serotonin/5-hydroxytryptamine (vasoconstrictor) released from platelets
•Myogenic contraction of the vascular wall
2. Platelet Plug Formation
•Exposed collagen layer of the injured blood vessel attracts platelets which stick to it and
release serotonin and ADP.
•ADP attracts other platelets (platelet aggregation).
•So a loose plug of aggregated platelets is formed and may close a small vessel.
•Platelet aggregation is helped by ADP, thromboxane A2 and thrombin.
3. Blood coagulation:
•The loose platelets plug becomes firm by the fibrin threads that attach to the platelets.
•The mechanism of blood coagulation (intrinsic and extrinsic system) discussed before.
•Clot retraction
•Shrinkage of blood clot to become firmer.
•This is produced by retractozyme released by the blood platelets.
 A-Vascular factors
• Nervous reflex
• Local myogenic reflex

90
Vascular Constriction

Tissue Factor

91
 Platelets
• Throbopoiesis
– Stem cells
– Megakaryoblast
– Promegakaryocyte
– Megakaryocytic

– Platelets
• The last cell has a
diameter of 24-30
um
92
 Platelets
• Control of Throbopoiesis
– Under the effect of thrombopoietin
– Thrombopoietin increases markedly in conditions
of low platelet count (thrombocytopenia)

93
 Platelets
• From bone marrow platelets pass to through
the spleen before reaching the blood
• They survive 3-5 days

94
 Platelets

o 150- 450 x 103 / mm3.

o Non-nucleated,
o irregularly shaped, minute round cells,
o 2-3 µm in diameter.

95
 Number of platelets
• Normal platelet count
– 150- 450 x 103 / m
• Thrombocytopenia
• Thrombocytosis

96
97
 Functions of platelets
• Aggregation
• Primary haemostatic plug
• Release of substances
– 5-HT
– Platelet factor 3 (PF3)
– β thromboglobulin βTG
– PF4
– Thromboxane A2
• Secondary

98
 General Steps
• Formation of platelets
plug and blood
coagulation

99
 Formation of the Platelet Plug
Platelet adhesion: Adhere to the damaged vascular wall, such
as the collagen fibers in the vascular wall or even damaged
endothelial wall.

Due to the effect of ADP released

from the damaged tissue, the
platelet adhere together loosely.

100
First phase of platelet aggregation (reversible):

Due to the effect of ADP

released from the
damaged tissue, the
platelet adhere
together loosely.

101
Platelet Release. After the first phase (reversible) of
aggregation, the contractile proteins in the platelet contract
forcefully and cause the release of granules that contain
multiple active factors including the ADP and thromboxane A 2

102
Platelet contractile proteins

• actin
• myosin
• tropomyosin
• troposin

103
Outcome of platelet contraction

• Extrusion of platelet products

• Contraction of the aggregates
• Retraction of blood clot
• Sealing of the porous haemostatic plug

104
Second phase of aggregation (irreversible).

The ADP and thromboxane

A2 in turn act on nearby
platelets to activate as well
and cause the platelets to
adhere to the originally
activated platelets.

105
106
 DIFFERENCES BETWEEN COAGULATION AND BLEEDING TIMES

Coagulation time Bleeding time

• It tests the efficiency of • It tests the efficiency of
coagulation mechanism vasoconstriction and platelet
plug formation
• Prolonged in deficiency of • Prolonged in
coagulation factors e.g. in thrombocytopenic purpura
vitamin k defiecncy and
hemophilia
• Normal in • Normal (not affected) in
thrombocytopenia hemophilia
(decreased platelet count)
• It is 4-8minutes • It is 2 – 4 minutes
 Disorders of platelets
• Decreased Number: Thrombocytopenia
– Decreased Production
– Decreased Survival – Immune (ITP)
– Increased utilization - DIC
• Defective Platelet function (thrombothenia):
– Acquired – Drugs – Aspirin
– Congenital – Eg. Thrombasthenia.

108
 Platelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

109
• Injury to a blood vessel
exposes collagen and
thromboplastin, recruiting
platelets to the site of injury to
form a temporary plug.
• Platelets release 5-
hydroxytryptamine, among
other factors, resulting in
smooth muscle contraction
and vasoconstriction.
• Activation of the clotting
cascade in response to
collagen and thromboplastin
activates thrombin, which
converts circulating fibrinogen
to fibrin monomers.
• Fibrin monomers polymerize
and are cross-linked and
accumulate with platelets at
the site of injury to form the Summary of reactions involved in
definitive clot hemostasis
Blood and Lymph Physiology

HERBERT

111
Haemostasis & Coagulation

112
3. Blood Coagulation in the Ruptured Vessel
The third mechanism for hemostasis is formation of the blood
clot. The clot begins to develop in 15 to 20 seconds if the
trauma of the vascular wall is severed and in 1 to 2 minutes if
the trauma is minor. With 3 to 6 minutes after rupture, if the
vessel opening is not too large, the entire opening or broken
end of the vessel is filled with clot.
Bleeding time, 1-3min

113
114
4. Anticoagulation and Fibrinolysis.

115
II. Blood Coagulation

1. General Mechanism:
(1) In response to rupture
of the vessel , a complex
cascade of chemical
reactions is initiated. The
net result is formation of a
complex of activated
substance collectively
called prothrombin
activator (3) The thrombin acts as an
enzyme to convert fibrinogen
(2) The prothrombin into fibrin fibers that enmesh
activator catalyzes the platelets, blood cells, and plasma
conversion of prothrombin to form the clot 116
into thrombin
117
Prothrombin activator is generally considered to be formed in two ways: (1)
by the intrinsic pathway that begin in the blood itself and (2) by the extrinsic
pathway that begins with trauma of the vascular wall and surrounding tissues
118
In both the extrinsic
and intrinsic pathways,
a series of plasma
proteins called blood-
clotting factors play
major roles.
Most of these are
inactive forms of
proteolytic enzymes.
When converted to the
active forms, their
enzymatic actions
cause the successive,
cascading reactions of
the clotting process.

119
Activation of Factor XI, Smaller letter “a”
indicate the activated form

XIIa

Inactive XI Active XIa

+
120
2. Intrinsic Pathway Blood trauma or contact
with collagen
(1) Blood trauma causes 1) activation
of XII and 2) release of platelet XII XIIa PL
phospholipids (platelet factor)
HMW kininogen
(2) Activation of factor XI. Besides the
prekallikrein
activated XII (XIIa), this process requires
high-molecular-weight (HMW) XI XIa
kininogen and is accelerated by
Ca2+
prekallikrein (co-factor).
(3) Activation of factor IX IX IXa
VIIIa, Ca2+,
(4) Activation of factor X. This reaction needs VIIIa,
III
Ca2+ (factor IV) and platelets phospholipids. X Xa

Factor VIII is the factor that is missing in a person who has classic
hemophilia, for which reason it is called antihemophilic factor 121
122
(5) Action of activated factor X to form prothrombin
activator. Together with Factor V, Ca2+ and platelets
phospholipids.

Xa, V, Ca2+, III

Prothrombin Thrombin
II IIa

123
 3. Extrinsic Pathway
（ 1 ） Release of tissue factor. Traumatized tissue release a
complex of several factors called tissue factor or
thromboplastin.

(2) Activation of
factor X. Tissue factor
complexes with blood
coagulation factor VII
and , in the presence
of calcium ions, acts
enzymatically on
Factor X to form Xa.
124
4. Interaction between the extrinsic and intrinsic pathways
(1). After blood vessels rupture, clotting is initiated by both
pathways simultaneously. Tissue factor initiates the extrinsic
pathway, whereas contact of Factor XII and the platelets with
collagen in the vascular wall initiate the intrinsic pathway.

125
126
(2)Extrinsic pathway can be explosive in nature. With serve
tissue trauma, clotting can occur in as little as 15 seconds.
The intrinsic pathway is much slower to proceed, usually
requiring 1 to 6 minutes to cause clotting. But it can activate
much more factors, which is important for an efficient blood
clotting.

127
5. Conversion of Prothrombin (Factor II) to Thrombin (Factor
IIa) :After prothrombin activator has been formed, it then, in
the presence of sufficient amounts of Ca2+ ions, causes
conversion of prothrombin (Factor II) to thrombin (Factor IIa).

128
6. Conversion of Fibrinogen to Fibrin
The thrombin (IIa) acts on fibrinogen (Factor I) to form a
molecule of fibrin monomer (Factor Ia) that has the
automatic capability to polymerize with other fibrin monomer
molecules into long fibrin fibers that form the reticulum of
the clot.

129
The clot is composed of a meshwork of fibrin fibers running in
all directions and entrapping blood cells, platelets and plasma.
It becomes adherent to any vascular opening and thereby
prevents blood loss.

130
7. Clot Contraction
Within a few minutes after a clot is
formed, it begins to contract
(contractile fibers in platelets) and
usually expresses most of the fluid
form the clot within 20 to 60 minutes.
The fluid expelled is called serum, in
which all fibrinogen and most of the
other clotted factors have been
removed. In this way, serum differs
form plasma.
Serum can not clot because of lack of
these factors.
131
8. Role of Calcium Ions
Except for the first two steps in the intrinsic pathway, calcium
ions are required for promotion or acceleration of all the
blood-clotting reactions. Therefore, in the absence of
calcium ions, blood clotting by either pathway does not
occur.

132
In the living body, the calcium ion concentration seldom falls
low enough to affect significantly the kinetics of blood
clotting.
When blood is removed from a person, it can be prevented
form clotting by reducing the calcium ion concentration below
the threshold level for clotting, either by
deionizing the calcium by causing it to react with substances
such as citrate ion or by
precipitating the calcium with substances such as oxalate ion.

133
Review points of this chapter
Concept:
1. Blood
2. Hematocript
3. Erythropoiesis
4. Erythrocyte sedimentation rate
5. Osmosis
6. Osmotic pressure
7. Hemostasis
8. Serum
Review Questions:
1. Describe the factors that determine the erythropoiesis
2. Describe the basic process of hemostasis
3. Compare the two processes of intrinsic and extrinsic
pathway of the blood coagulation.
134
III. Intravascular Anticoagulants
1. Antithrombin
Present in a concentration of 30mg/dl in the plasma. It is a
serine protease inhibitor and can combine with active
centers of the clotting factors IIa, VII, IXa, Xa and XIIa,
blocks the effect of these factors and then inactivates them
within a few minutes.

135
2. Heparin
Produced by mast cells and located in connective tissue and
basophil cells of the blood. A large quantities of the heparin is
present in the areas of the liver and lungs.
By itself, it has little or no anticoagulant property, but when it
combines with antithrombin III, it increases a hundred-fold the
effectiveness of antithrombin III and thus acts as an
anticoagulant. Heparin is widely used in medical practice to
prevent intravascular clotting.

136
 Heparin mechanism of action

Heparin

Antithrombin III Thrombin

137
3. Protein C
It is activated by thrombin. The activated protein C plays a
powerful role to prevent clotting by
1) inactivating the factors V and VII,
2) blocking the combination of the factor Xa with platelet,
3) increasing the process of fibrinolysis due to stimulating the
release of plasminogen activators.

138
IV. Fibrinolysis
The fibrin formed within blood vessels is gradually dissolved
to restore the fluidity of the blood. The process of liquefaction
or lysis of the fibrin is called fibrinolysis.
Plasminogen Activator

Plasminogen Plasmin
Inhibitor

Fibrin and Fibrinogen Fibrin Degradation

Products (FDP)

139
 Plasminogen
t-PA
PG

Plasmin
t-PA
FDPs
PG PL

Fibrin

140
1. Activation of Plasminogen to Form Plasmin – Plasminogen
Activator
There are two types of plasminogen activator
1) Vessel activator. Some clotting factors in the intrinsic
pathway, such as XIIa, XIa, prekallikrein , HMW
kininogen, IIa (thrombin) et al.
2) Tissue activator. Released by the injured tissue and
endothelium, such as the tissue-type plasminogen activator
(t-PA) and urokinase synthesized by the kidney

141
142
2. Degradation of the fibrin
Plasmin is a most powerful proteolytic enzyme. It not only
digest the fibrin but also digest a number of other substances
in the surrounding blood, such as fibrinogen, Factor V, VIII,
prothrombin and Factor XII. Therefore, whenever plasma is
formed in a blood clot, it can cause lysis of the clot and
destruction of many of the clotting factors, thereby sometimes
even causing hypocoaguliability of the blood.

143
 Plasminogen
t-PA
PG

Plasmin
t-PA
FDPs
PG PL

Fibrin

144
Human t-PA is now produced by recombinant DNA
technique and is available for clinical use. It lyses clots in the
coronary arteries if given to patients soon after the onset of
myocardial infarction. Streptokinase, an enzyme, and
urokinase, an enzyme produced by kidney cells, are also
fibrinolytic and are used in the treatment of early myocardial
infarction.

145
3. Significance of the Fibrinolysis
The lysis of blood clots allows slow clearing (over a period of
several days) of extraneous clotted blood in the tissue and
sometimes allows reopening of clotted vessels. An especially
important function of the plasma system in to remove minute
clots from the millions of tiny peripheral vessels that
eventually would become occluded were there no way to clean
them.
The fibrinolytic system plays an important role in
maintaining the fluidity of the blood or normal capillary
flow, which benefits the repairing and healing of the damaged
tissues.

146
V. The Role of Platelets in Hemostasis
1. Formation of the Platelet Plug
2. Participation in the Blood Coagulation

147
(1) Combination with several clotting factors, such as factors
I, V, Xa, XI. This can produce a local high concentration of
the clotting factors to accelerate the formation of thrombin
and other substances in the tissue where the clotting is
needed.

148
(2) Release of several important clotting factors from its
granules
PF3, a phospholid surface, accelerates 20 thousand fold the
activation of prothrombin.
PF4, neutralize the role of heparin;
PF6 has an inhibitory effect on fibrinolysis.
Factor XIII, a fibrin-stabilizing factor, causes more and
more cross-linking bons between the adjacent fibrin fibers.
5-HT, enhances the contraction of injured vascular
muscle.

149
(3) Clot retraction
Platelets pull on fibrin
threads causing clot
retraction

150
RELATION OF VITAMIN K TO BLOOD CLOTTING
•Vitamin K is essential for formation of pro-thrombin (Factor II) and Factors VII,
IX and X in the liver.
•It acts as co-factor for the enzymatic formation of these substances.
•It catalyzes ϒ carboxylation of glutamic acid residues on various proteins
concerned with blood coagulation.
•In Vitamin K deficiency, coagulation time is prolonged and hemorrhage may
occur.
RELATION OF CALCIUM TO BLOOD CLOTTING
•Calcium is necessary for :
1.Formation of active thromboplastins (Prothrombin activator): All steps need
calcium except the first two steps of intrinsic pathway.
2.Conversion of prothrombin to thrombin
3.Stabilization of soft fibrin clot: Blood does not clot in absence of calcium
•In vivo decreased blood Ca2+ ions does not lead to bleeding because before this
happens, tetany (increased neuromuscular excitability and muscle spasm) occurs.
•This leads to spasmodic contraction of laryngeal and respiratory muscles which
may result in death from asphyxia (at plasma calcium level about 4m g%).
• ABNORMALITIES OR DISORDERS OF COAGULATION AND
HEMOSTASIS
1. Vitamin K Deficiency:
• For example: In obstructive jaundice bile salts needed for absorption of
Vitamin. K cannot pass into the intestine due to obstruction of common bile
duct leading to vitamin K deficiency hence lack of formation of prothrombin
and factor VII, IX and X leading to bleeding tendency.
• Therefore, patients with obstructive jaundice should be given Vit. K before
surgery.
2. Hemophilia
• It is an inherited, sex linked disease transmitted by females (who are usually
carriers and are rarely affected) to males who are usually affected.
• Coagulation time is prolonged (1-12hrs).
• Bleeding time is normal.
• Hemophilia is of three (3) types:
i. Hemophilia A: Due to absence of Factor VIII (AHG)
ii. Hemophilia B: Due to lack of Factor IX (Christmas factor)
iii. Hemophlia C: Due to absence of Factor XI (PTA)
Treatment of Hemophilia
Fresh blood transfusion or giving the deficient factor if available.
3.Parahemophilia: It is due to lack of Factor V. The coagulation time and
prothrombin time are prolonged.
4.Purpura
i. Thrombocytopenic purpura:
•Is a disease characterized by small subcutaneous and mucous membranes
hemorrhages.
•The platelet count is low (thrombocytopenia) to below 40,000/mm 3.
•Bleeding time is prolonged (15-20 minutes) due to deficient hemostatic
mechansms i.e. poor constriction of injured vessels (lack of serotonin) and
soft clot that poorly retracts (lack of retractozyme).
•Coagulation time is normal because coagulation factors are normal.
ii. Thromboasthenic purpura
•Due to abnormal platelets function while the platelets count is normal.
•Purpura may be due to increased fragility of capillary walls e.g. in scurvy
(lack of vitamin C).
5. Intravascular clotting (Thrombosis)
•It is the formation of blood clot inside blood vessel (thrombus).
•The condition is caused by:
i.Slow blood flow: As in prolonged recumbent position in bed e.g. thrombosis
of leg veins after labour and surgical operation.
ii.Exposure of collage fibres: When the intima (inner lining of blood vessels)
is destroyed e.g. in atherosclerosis.
iii.Increased number and sticking of platelets
iv.Increased fibrinogen and content and viscosity of blood
 Effect of intravascular clotting
• A. In veins:
• Thrombosis leads to venous obstruction, hence increased venous pressure
resulting to an increased capillary pressure and consequently increased
filtration from capillaries therefore edema occurs.
• Detached venous thrombus may cause fatal pulmonary embolism.
• B. In arteries:
• Thrombosis leads to decreased blood supply (Ischaemia) of tissues supplied
by the occluded artery.
• Occlusion of cerebral vessels leads to paralysis, coronary obstruction causes
myocardial infarction, while in the eye blindness may occur.
• Treatment
• Avoid prolonged recumbency, aspirin and anticoagulants (heparin and
dicoumarol) are used.
• Aspirin causes a moderate inhibition of thromboxane A 2 formation.
• Therefore, aspirin is given in small doses to prevent clot formation e.g. in
cerebral and coronary vessels
155
3. Maintenance of the Integrity and Repair of the Vascular
Endothelium

156
Blood and Lymph Physiology

Herbert

157
Blood Group and Transfusion

158
 Introduction
• Special antigens on the surface of the red blood cells.
• More than 100 known
• Only 15 well understood
• Two particular groups of antigens are more likely
than the others to cause blood transfusion reactions.
They are the ABO system of antigens and the Rh
system, which are of importance for blood
transfusion clinically.

159
 The ABO system
 The classifications of the ABO blood groups
depend on the presence or absence of the
agglutinogens (antigens) on the surface of the
red cell means
 Genetically determined

160
 Agglutinogens
 Two antigens- occur on the surface of the red blood cells
 type A and
 type B.
 These antigens are called agglutinogens because they often
cause blood cell agglutination, causing blood transfusion
reactions.

Group A Group B Group AB Group O

161
 Inheritance of blood groups I
• A & B antigens by A & B genes
• O gene does not produce RBC antigens
• Genotypes
–A AA or AO
–B BB or BO
–O only OO
– AB has both genes

162
 Inheritance of blood groups II
• Why know genotypes?
– Workout offspring blood groups by knowing the
genotype of parents
– Sorting out disputed parentage of the child

163
 Agglutinins
• The agglutinins are gamma globulin in the plasma.
• When type A agglutinogen is not present in a
person’s red blood cells, antibodies known as anti-A
agglutinins develop in the plasma. Also
• when type B agglutinogen is not present in the
blood cells, antibodies known as anti-B agglutinins
develop in the plasma.

164
 Major types of ABO blood group
The blood is are normally classified into four major types,
depending on the presence of absence of the two
agglutinogens, A and B.

165
 BLOOD GROUPS
Red blood cells (rbc’s) can contain surface A & B antigens.
There are four principal blood groups in humans: O, A, B and AB

anti-A
Group O Group B anti-A
anti-B

Group O rbc’s have no surface A

& B antigens: antibodies anti-A Group B rbc’s have surface
& anti-B are present in the plasma antigen B and antibody A.

Group A anti-B Group AB

Group A rbc’s have surface Group AB rbc’s have surface

antigen A and antibody B. antigens A & B and no antibodies.
166
 Agglutination and hemolysis in
transfusion reaction
When bloods are mismatched so anti-A or anti-B plasma
agglutinins are mixed with red blood cells that contain A or B
agglutinogens respectively, agglutinins will make the red cells
adhere to each other – agglutination.
The clumps of red cells will plug small blood vessels
throughout the circulatory.
During the ensuring few hours to a few days, either physical
distortion of the cells or attack by phagocytic white cells
destroys the agglutinated cells, releasing hemoglobin into the
plasma, which is called “hemolysis” of the red blood cells.
167
168
During severe hemolytic
reaction, fever, chills and Group B anti-B Group B
shock may occur. One of
the most lethal effects of

anti-B
anti-B
transfusion reactions is
kidney shutdown, which
can begin within 1 few
Group B anti-B Group B
minutes to a few hours. If
the shutdown is complete
and fails to open up, the
patient die of renal failure.

169
(5) Blood typing

170
 The rhesus blood group system
• Presence or absence of Rh antigen
• Dd,Cc & Ee
• Most important is D
– If present person is Rh +ve
– If absent person is Rh –ve
• Frequency of distribution
– 85% of Europeans are Rh +ve
– 90 – 95 % of Arab and Africans are Rh +ve
– 98% of Asians are Rh +ve

171
 Rhesus antigens
• There are at least 3 (Dd,Cc & Ee)
• D is the strongest and clinically important
• In blood banks Rh grouping is performed by
anti-D serum

172
 Rhesus antibodies
• Are not naturally occurring
• Immunoglobulin produced in response to D
antigen
• Ani-D antibody may be acquired as a result of
immunization
• Transfusion of Rh +ve blood to Rh –ve
individual
• Presence of Rh+ve fetus in a Rh –ve mother

173
 Importance of blood groups in clinical
medicine
• Blood transfusion
• ABO grouping
• Cross matching
• Possible combinations
_______Donor red cells_________

Recipient AB A B O
AB - - - -
A + - + -
B + + - -
O + + + -

174
 Complications of blood transfusion I
• A common practice in hospitals
• Blood and blood products
– Fresh frozen plasma
– Platelet concentrate
– Cryoprecipitate
• strict precautions to avoid complications
– Grouping and cross matching
– Testing for organisms

175
 Transfusion reactions
• Time
– During time of blood transfusion
– Delayed (Days or weeks)
• Outcome of reaction
– Haemolytic
– Allergic or
– Febrile reactions

176
 Complications of blood transfusion II
Complications
• Patient and donor blood
– Antigen-antibody reaction
– Incompatible blood
• Transmission of diseases (donor to patient)
– Malaria
– Viral hepatitis
– Syphilis
– AIDS virus
• Rhesus incompatibility

177
 Haemolytic disease of the newborn
• Between mother and fetus
• Mother Rh –ve X fetus Rh +ve (father)
• IgG (small and crosses the placenta)
• Mother develops anti D during first delivery
• First child escapes
• Blood transfusion (Rh +ve blood)
• Anemia may need exchange transfusion
• Use of anti D decreases the incidence of HDN (1 in
200)

178