Lecture slides by Prof. PN Singh, Professor @ Dept. of Physiology, JNMCH, AMU, INDIA.

1. LECTURES AT JNMC
ALIGARH MUSLIM UNIVERSITY,ALIGARH
BY: Prof. P N Singh Sir
Compiled and Uploaded By: Neyaz Ahmad

2. Contents…
 Introduction
 Hemopoiesis
 Erythropoiesis
 Classification of Anemia
 Haemoglobin and Related Disorders
 WBCs
 Blood coagulation and Fibrinolytic system
 Plasma Proteins
 ABO classification and Rh factor
 Diseases…

3. Blood
Composition of blood
Cells & Plasma
Cells 1. RBC : Erythroid
2. WBC : Myeloid
Neutrophils
Basophils
Eosinophils
:Lymphoid cells
Lymphocytes
: Macrophage system
Monocytes
3. Platelets

4. Hemopoiesis
Committed stem cells

5. Hemopoiesis
 Pleuripotent hemopoietic stem cell differentiate into Committed stem cells
maturing in a particular cell eg Colony forming unit (CFU)erythrocyte will mature
into an erythrocyte . GM-CFU into granulocytes & Monocyte.
 Growth promoters like Interleukin-3 induce growth of all the cells in bone
marrow.
 Differentiation factors like GM –CSF stimulates the differentiation of monocytes
and except basophil all the granulocytes.
 Lymphocytes are differentiate & mature in Thymus (T cell) / bursal
equivalent(B cell) eg liver in mid fetal life & bone marrow in late fetal life &
after birth.

6. Erythropoiesis
Areas : yolk sac: primitive embryo
 Liver :mid gestation Spleen & LN also contribute
 Bone marrow : After birth & adult
Stages of erythropoiesis Pleuripotent & Committed cells (
CFU- E)
Proerythoblast: First identifiable cell of series derived from
CFU-E & it give rise basophilic erythroblast (early
normoblast) with little Hb. Next generation cell
Polychromatophilic erythroblast ( intermidiate
normoblast)has Hb saturation of 34% & this gives
Orthochromatic erythroblast (Late Normoblast) &
subsequently Reticulocyte (Golgi body & mitochondrion
turns into reticulum) which disappears within 1-2 days.
1-2 % of circulating RBC are actually reticulocytes.
Early normoblast
Intermediate normoblast
Late Normoblast

7. Red Blood Corpuscle (RBC)
 RBC : biconcave disk ,7.5 μM diameter 2.5μM
thick at periphery , contains 29 pg Hb. 5.4
million/μL (male) 4.8 (Female)in number
 Characteristics of RBC
Variable Calculat
n
Male Female
Hematocrit 47% 42%
RBC Count 5.4 m/μ
L
4.8
m/μL
Hemoglobin 16 G% 14 G%
Mean
Corpuscular
Volume (MCV)
Hct x10
RBC
count
87 fL 87 fL
Mean Hb x10 29 pG 29 pG

8. Role of erythropoietin, B12 & Folate in
Erythropoiesis
Hypoxia causes increase in erythropoietin production
from kidney, erythropoietin in turn enhances RBC
production
Formation of Erythropoietin. (EP) 90%
erythropoietin in kidney 10% in liver. In the kidneys
the erythropoietin is formed in tubular epithelial
cells.
 Ep stimulates hemopoietic stem cell to proliferate
into proerythroblast.
 Vitamin B12 and folic acid are essential for the
synthesis of thymidine triphosphate, & DNA ,hence,
deficiency cause failure of nuclear maturation &
cell division. The erythroblastic cells of bone
marrow, fail to proliferate rapidly, produce
macrocytes, with weak cell membrane & oval in
shape cells.

9. Features of Iron, B12 & folate deficiency
anemias
Pathology Hemoglobi
n
RBC
Count
MCV MCH MCHC
Iron deficiency Male< 13.6
Female <
12.0
Less
Male <4.3
Female 3.5
Less
< 75 μ
L
reduced
< 25
pG
reduce
d
< 27
reduc
ed
B12 & folic
acid deficiency
Less Less > 110 Normal/
reduced
Normal

10. Bone marrow
Normoblast Megaloblast

11. Classification of Anemia according to
Underlying Cause
 Blood Loss
 Acute: trauma
 Chronic: lesions of gastrointestinal tract, gynecologic disturbances
 Defect in RBC
Increased Destruction (Hemolytic Anemias)
 (A) Intrinsic (intracorpuscular) abnormalities
(a)Hereditary membrane abnormalities
Membrane skeleton proteins: spherocytosis, elliptocytosis
(b) Hereditory Enzyme deficiencies
Glycolytic enzymes: pyruvate kinase, hexokinase,Enzymes of hexose
monophosphate shunt: glucose-6-phosphate dehydrogenase, glutathione
synthetase.

12. Classification by underlying Mechanism
Deficiency of dietary factors/ Abnormal Hb Synthesis
 Iron : Microcytic Hypochromic
 B12 : Macrocytic or Megaloblatic anemia
 Folic acid : Macrocytic or Megaloblatic anemia

13. Hereditary Spherocytosis
 In HS primary abnormality is in supportive
skeleton on IC face of RBC wall. Spectrin,
linked to membrane at two points: through
ankyrin & band 4.2 to membrane protein
band 3; & through band 4.1 to protein
glycophorin. Horizontal spectrin - spectrin &
spectrin-intrinsic membrane protein
interactions stabilize membrane & are
responsible for shape, strength, flexibility of
RBC.

14. Hereditary Spherocytosis
 Most common pathogenic feature of HS
is mutation particularly of
band3,ankyrin &spectrin gene. In all
types of HS red cell wall stability is
reduced , consequently lose membrane
fragments while retaining most of their
volume. As a result, ratio of surface
area to volume of HS cells decreases
until the cells become spherical.

15. Disorders of Hb & RBC production
 Hemoglobin
Deficient globin synthesis :Thalassemia syndrome
Abnormal globin synthesis: Sickle cell anemia
 RBC production
Failure of erythroblast maturation :
B12 & Folate deficiency
 Defect of Heme synthesis
Iron deficiency The most common cause of anemia in India followed by B12 &
folate deficiency

16. Hemoglobin
 Hemoglobin is made up of 4 subunits,
each have a Heme moiety &
polypeptide chain.
 HBA has one pair of α & one pair of β
globin chain(2α2 β)
 HbA2 (2.5%) of Hb has 2α2δ
 HbA1c glycated by glucose in diabetics if >
6.9% indicate poor control of blood sugar
 Fetal Hb (2α2γ) has more affinity for O2
since it bind less avidly to 2,3-DPG and
carries more O2 for a given pO2.

17. Reactions of Hemoglobin
 Each of four iron atoms in hemoglobin can reversibly bind one O2 molecule. Iron is
in ferrous state, so reaction is oxygenation, not oxidation. Because it contains 4
deoxyhemoglobin (Hb) units,Hb molecule represented as Hb4,& it actually reacts
with four molecules of O2 to form Hb4O
Hb4 + O2↔ Hb4O2, Hb4O2+O2 ↔ Hb4O4
H b4O4+O2 ↔ Hb4O6 Hb4O6 +O2 ↔Hb4O8
Deoxygenated Hb, globin is tightly bound in tense state so low affinity for O2.
Binding of one O2 loosens the binding & increase affinity for O2, 500 times when
all 4 Hb are bound with O2

18. Hemoglobin reactions
 Methemoglobin: Oxidizing agent & drugs convert Hb to methHb leading to dusky
color of skin. Normally meth hemoglobin formed is converted to Hb by NADH-
meth hemoglobin reductase,. Absence of which in children cause congenital
methemoglobinemia.
 Carboxyhemoglobin: Hemoglobin has more affinity for Carbon monoxide than for
O2 which replaces O2 (CO posioning) withreduced O2 carrying capacity of Hb.

19. Sickle cell anemia
 In HbS, substitution of valine for glutamic acid at
6th position of β-chain, produces HbS.
Homozygotes all HbA replaced by HbS.
Heterozygote about half is replaced.
Deoxygenation, HbS molecules crystallize which
distort RBC as elongated crescent or sickle.
Sickling initially reversible upon reoxygenation;
Later on cell wall damage occurs with each
episode of sickling, & finally cells accumulate
calcium, lose potassium and water, and become
irreversibly sickled.

20. Thalassemia
Inherited disorder caused by mutations that decreases synthesis of α- or β-
globin chains. So deficiency of hemoglobin, red cell abnormalities due to
excess of other unaffected globin chain.
The α chains are encoded by two α-globin genes, which lie in tandem on
chromosome 11, while the β chains are encoded by a single β-globin gene
located on chromosome 16. The mutations that cause thalassemia are
particularly common among Mediterranean, African, and Asian populations.

21. Beta Thalassemia
Pathogenesis of the anemia in β-thalassemia.
Reduced synthesis of β-globin leads to inadequate HbA formation, so RBC MCHC
low, cells hypochromic microcytic.
Red cell hemolysis, as results of unbalanced rates of β-globin and α-globin chain
synthesis. Unpaired α chains form insoluble aggregates & precipitate in cell &
cause membrane damage that is severe enough to provoke extravascular
hemolysis. Erythroblasts in bone marrow also susceptible to damage through same
mechanism, which in severe β-thalassemia results in destruction of majority of
erythroid progenitors before their maturation into RBC. This destruction of
erythroid precursors (ineffective erythropoiesis) is associated with an inappropriate
increase in absorption of dietary iron, which often leads to iron overload.

22. Beta Thalassemia

23. White Blood Cell (WBC)
Human blood contains 4000 to 11,000/μ L WBC Granulocytes
(polymorphonuclear leukocytes) are most numerous. Young granulocytes have
horseshoe-shaped nuclei that become multilobed as cells grow older. Most of them
contain neutrophilic granules (neutrophils), but a few contain granules that stain
with acidic dyes (eosinophils), and some have basophilic granules (basophils).
Agranulocytes found normally in peripheral blood are lymphocytes, with large
round nuclei & scanty cytoplasm, & monocytes, with abundant agranular
cytoplasm with kidney-shaped nuclei. Together, these cells provide body powerful
defenses against tumors, viral, bacterial, infection &parasitic infestations.

24. Cell counts

26. Life span of WBCs & Platelets
Cell In blood In tissue
Neutrophil 4-8
hours
4-5 days
Monocyte 10-20
hours
Month
(Macropha
ge)
Platelets 4 day
(half life
)
Lymphocytes ( blood
↔ lymph lymphoid
tissue)
Months -
Years
Month -
Years

27. Genesis of myeloid series cells
 The promyelocyte which evolves when the classic lysosomal granules, aka primary,
or azurophil, granules, are produced. Primary granules contain hydrolases,
elastase, myeloperoxidase, cathepsin G, cationic proteins, and bactericidal/
permeability-increasing protein, which kills gram-negative bacteria. Azurophil
granules also contain defensins, a family of cysteine-rich polypeptides with
broad antimicrobial activity against bacteria, fungi,& certain enveloped viruses.
Proliferation phase through metamyelocyte takes about 1 week, & maturation
phase metamyelocyte to neutrophil 01 week.

28. Neutrophils (myeloid cell)
 Promyelocyte produce myelocyte, a cell responsible for synthesis of specific, or
secondary, granules, containing lactoferrin, vit B12–binding protein,
membrane components of NADPH oxidase, required for H2O2 production,
histaminase, receptors for certain chemoattractants & adherence-promoting
factors (CR3) & receptors for BM component, laminin. During final stages of
maturation no cell division occurs, & cell passes through metamyelocyte stage &
then to band neutrophil with a sausage-shaped nucleus. During maturation
nucleus assumes a lobulated configuration. More lobes seen in folate or vit B12
deficiency. Multiple lobes allow deformation of neutrophils during migration into
tissues (Diapedisis).

29. Bactericidal role of Neutrophils
 With phagocytosis comes a burst of oxygen consumption and activation of hexose-
mono phosphate shunt. A membrane-associated NADPH oxidase, assembled &
catalyzes reduction of O2 to superoxide anion, which is then converted to hydrogen
peroxide & other toxic oxygen products (hydroxyl radical).
NADPH + H⁺ +2O2= NADP + 2H⁺ + 2O2⁻ (free radical)
2O2 ⁻+ 2H⁺ = H2O2 (in presence of superoxide
dismutase)
 Hydrogen peroxide + chloride + neutrophil myeloperoxidase generate hypochlorous
acid (bleach), hypochlorite, and chlorine. These products oxidize &halogenate
microorganisms tumor cells. Strongly cationic proteins, defensins, and probably
nitric oxide also participate in microbial killing. Other enzymes, such as lysozyme &
acid proteases, digest microbial debris. After 1 to 4 days in tissues neutrophils die.

30. Eosinophils
 Eosinophils express a specific chemoattractant receptor & respond to a specific
chemokine, eotaxin. Eosinophils are much long lived than neutrophils, Eosinophils
can recirculate. In invasive helminthic infections, such as hookworm,
schistosomiasis, strongyloidiasis, toxocariasis, trichinosis, filariasis,
echinococcosis, and cysticercosis, the eosinophil plays a central role in host
defense. Eosinophils are associated with bronchial asthma, cutaneous allergic
reactions, & other hypersensitivity states. Circulating eosinophils are increased in
allergic diseases such as asthma & in various other respiratory&gastrointestinal
diseases.

31. Eosinophilic Granules
 Eosionphilic granules contain arginine-rich protein (major basic protein)with
histaminase activity, important in host defense against parasites. Eosinophil
granules also contain a unique eosinophil peroxidase that catalyzes the oxidation of
many substances by hydrogen peroxide and may facilitate killing of
microorganisms. Eosinophil peroxidase, in the presence of hydrogen peroxide and
halide, initiates mast cell secretion in vitro and thereby promotes inflammation.
Eosinophils contain cationic proteins, some of which bind to heparin and reduce its
anticoagulant activity.

32. Basophils
 Basophils also enter tissues and release proteins and cytokines. They
resemble but are not identical to mast cells, and like mast cells they
contain histamine and heparin. They release histamine and other
inflammatory mediators when activated by a histamine-releasing factor
secreted by T lymphocytes and are essential for immediate-type
hypersensitivity reactions. These range from mild urticaria and rhinitis to
severe anaphylactic shock.

33. Monocytes
 Monocytes enter blood from bone marrow & circulate for 72 hours. They enter
tissues & become tissue macrophages. Life span is about 3 months. Do not reenter
circulation. Some become multinucleated giant cells seen in chronic inflammations
eg tuberculosis. Tissue macrophages include Kupffer cells, pulmonary alveolar
macrophages & microglia in brain.
 Macrophage activated by lymphokines from T cells. Activated macrophage migrate
in response to chemotactic stimuli & engulf kill bacteria by processes similar to as
in neutrophils.
 They play a key role in immunity. Secrete up to 100 different substances, including
factors that affect lymphocytes & other cells, prostaglandins of E series, & clot-
promoting factors.
 Lymphocytes: To be discussed with Immunity

34. Platelets
Platelets are derived from Megakaryocytes in bone marrow Normal count is 1.5 -3.0
lac/cumm of blood, though they do not have nuclei & cannot replicate, function
as whole cell.
A. Cytoplasmic active factors
 (1) Actin and myosin thrombosthenin=contractile proteins.
 (2) Residuals of endoplasmic reticulum and the Golgi apparatus synthesize enzymes
& store large amount of Ca++.
 (3).Mitochondria & enzymes capable of forming ATP &ADP.
 (4) Enzyme systems for synthesis of PG and TxA2 perform many vascular and other
local tissue reactions
(5)Fibrin-stabilizing factor,
 (6) Growth factor for vascular endothelial cells, vascular smooth muscle cells, and
fibroblasts growth, thus causing cellular growth that helps repair damaged vascular
walls

35. B. Membrane factors
 (a) Glycoproteins repulses adherence to normal endothelium & causes adherence
to injured areas of vessel wall, especially to injured endothelial cells and exposed
collagen from deep within the vessel wall.
 (b)Phospholipids activate multiple stages in the blood-clotting process.
 Thus, the platelet is an active structure. It has a halflife in the blood of 8 to 12
days, eliminated mainly by tissue macrophage system. More than one half of the
platelets are removed by macrophages in the spleen, where the blood passes
through a latticework of tight trabeculae.

36. Platelet activation
 Binding of platelets to injured vessel wall collagen via platelet receptor
glycoproteins (GPIa-IIa, & α2β1 integrin) leads to its activation and binding with
vWf through another glycoprotein GPIb-V-IX on platelet membrane surface helps in
platelet aggregation. This reaction is important in binding of platelet with the
vascular endothelium under high shear stress and stenosed arteries. Platelet
adherence to endothelium leads to release of contents of dense and α granules.
Thrombin which is continuously generated due to continuous use of prothrombin is
a stimulus for aggregation for platelets and acts through generation of intra
cellular PLCβ that leads to synthesis of intracellular messenger DAG and IP3. DAG
stimulates protein kinase C which phosphorylate platelet aggregation protein.

37. Platelet activation

38. Platelet activation & Aggregation
 Thromboxane A2 (Tx A2) is another platelet aggregation factor, synthesis of which
is stimulated by collagen binding. TxA2 is a potent vasoconstrictor of platelet origin
like serotonin.
 ADP from granules which bind on receptor on platelet and causes activation of
platelets. Tx A2 synthesis inhibited by aspirin so it inhibits platelet aggregation.
PAF is a potent platelet activation factor produced during glucose metabolism.
 All aggregation stimulating factors modify the platelet surface so that divalent
fibrinogen link on adjacent platelets by binding with a platelet membrane (integrin
IIb-IIIa), autoantibodies against which cause removal of platelet and idiopathic
thrombocytopenia.

40. Hemostasis
After injury to vessels three events stops the bleeding
1. Constriction of vessel (Serotonin TxA2
2. Temporary hemostatic plug platelet bind to
collagen & aggregate
3. Formation of definitive clot (Coagulation of
blood) .
The injured vessel contract &may obliterate
lumen, vasoconstriction is due to serotonin and
other vasoconstrictors liberated (TxA2)from
platelets

41. Coagulation of blood
Platelets in temporary plug bound together & converted to definitive clot by fibrin.
Fibrin formation involves cascade of enzymatic reactions and a series of numbered
clotting factors wherein the soluble fibrinogen converted to insoluble fibrin. The
process involves the release of two pairs of polypeptides from each fibrinogen
molecule. The remaining portion, fibrin monomer, polymerize to form fibrin. The
fibrin is initially a loose mesh of interlacing strands. It is converted by the
formation of covalent cross-linkages to a dense, tight aggregate (stabilization).
This latter reaction is catalyzed by activated factor XIII and requires Ca2+.

42. Coagulation factors

43. Coagulation of Blood
 Coagulation of blood : Two mechanisms for generation of activated factor X.
 Intrinsic & extrinsic :
 The initial reaction in intrinsic system is conversion of inactive factor XII to active
factor XII (XIIa). This activation, catalyzed by high-molecular-weight kininogen &
kallikrein,& can be initiated in vitro by exposing blood to glass, or in vivo by
collagen. Active factor XII then activates factor XI, active factor XI activates factor
IX. Activated factor IX forms a complex with active factor VIII, which is activated
when it is separated from von Willebrand factor. The complex of IXa and VIIIa
activate factor X. Phospholipids from aggregated platelets (PL) and Ca2+ are
necessary for full activation of factor X.

44. Extrinsic mechanism of blood coagulation
 The extrinsic system is triggered by release of tissue thromboplastin,
that activates factor VII. Tissue thromboplastin & factor VII activate
factors IX and X. In presence of PL, Ca2+, and factor V, activated factor X
catalyzes the conversion of prothrombin to thrombin. The extrinsic
pathway is inhibited by a tissue factor pathway inhibitor that forms a
quaternary structure with tissue thromboplastin (TPL), factor VIIa, and
factor Xa.

45. Intrinsic & Extrinsic mechanism of Coagulation

46. Anticlotting Mechanisms
The interaction between platelet-aggregating effect of thromboxane A2 &
antiaggregating effect of prostacyclin, which causes clots to form at the site when
a blood vessel is injured but keeps the vessel lumen free of clot. Antithrombin III a
circulating protease inhibitor binds to serine proteases coagulation system,
blocking its activity as clotting factors. The binding is facilitated by heparin, an
anticoagulant which is mixture of sulfated polysaccharides. The clotting factors
that are inhibited are active forms of factors IX, X, XI, and XII

47. Fibrinolytic System

48. Fibrinolytic System
 The endothelium of blood vessels also plays an active role in preventing the
extension of clots. All endothelial cells except those in cerebral microcirculation
produce thrombomodulin, a thrombin-binding protein, on their surfaces. In
circulating blood, thrombin is a procoagulant & activates factors V and VIII, but
when it binds to thrombomodulin, it becomes an anticoagulant & thrombomodulin–
thrombin complex activates proteinC. Activated protein C (APC), along with its
cofactor protein S, inactivates factors V and VIII and inactivates an inhibitor of
tissue plasminogen activator (tPA), increasing formation of plasmin which activate
Plasminogen

49. Fibrinolytic System
 Plasmin (fibrinolysin) is the active component of the plasminogen
(fibrinolytic) system. This enzyme lyses fibrin and fibrinogen, with the
production of fibrinogen degradation products (FDP) that inhibit thrombin.
Plasmin is formed from its inactive precursor, plasminogen, by the action
of thrombin and tissue-type plasminogen activator (t-PA). It is also
activated by urokinase-type plasminogen activator (u-PA) & a bacterial
enzyme Streptokinse.

50. Fibrinolytic System
 Plasminogen receptors are located on the surfaces of many different types of
cells and are plentiful on endothelial cells. When plasminogen binds to its
receptors, it becomes activated, so intact blood vessel walls are provided with a
mechanism that discourages clot formation.
 Human t-PA is now produced by recombinant DNA techniques for clinical use in
myocardial infarction and stroke.

51. Coagulation factor deficiency Syndromes

52. Plasma
 The fluid portion of the blood, the plasma , is a remarkable solution containing
an immense number of ions, inorganic molecules, and organic molecules that are
in transit to various parts of the body or aid in the transport of other substances.
Normal plasma volume is about 5% of body weight, or roughly 3500 mL in a 70-kg
man. Plasma clots on standing, If whole blood is allowed to clot and the clot is
removed, the remaining fluid is called serum. Serum has essentially the same
composition as plasma, except that its fibrinogen and clotting factors II, V, and
VIII have been removed and it has a higher serotonin content because of the
breakdown of platelets during clotting.

53. Plasma proteins
 The plasma proteins consist of albumin , globulin , and fi brinogen fractions. Most
capillary walls are relatively impermeable to the proteins in plasma, and the
proteins therefore exert an osmotic force of about 25 mm Hg across the capillary
wall ( oncotic pressure ) that pulls water into the blood. The plasma proteins are
also responsible for 15% of the buffering capacity of the blood because of the weak
ionization of their substituent COOH and NH 2 groups. At the normal plasma pH of
7.40, the proteins are mostly in the anionic form (see Chapter 1 ). Plasma proteins
may have specific functions (eg, antibodies and the proteins concerned with blood
clotting), whereas others function as nonspecific carriers for various hormones,
other solutes, and drugs.
 ORIGIN OF PLASMA PROTEINS
 Circulating antibodies are manufactured by lymphocytes. Most of the other plasma
proteins are synthesized in the liver.

54.  Data on the turnover of albumin show that synthesis plays an important role in the
maintenance of normal levels.In normal adult humans, the plasma albumin level is
3.5–5.0 g/dL, and the total exchangeable albumin pool is 4.0–5.0 g/kg body weight;
38–45% of this albumin is intravascular, and much of the rest of it is in the skin.
Between 6 and 10% of the exchangeable pool is degraded per day, and the
degraded albumin is replaced by hepatic synthesis of 200–400 mg/kg/d. Th e
albumin is probably transported to the extravascular areas by vesicular transport
across the walls of the capillaries Albumin synthesis is carefully regulated. It is
decreased during fasting and increased in conditions such as nephrosis in which
there is excessive albumin loss.

55. Plasma Proteins: Physiological fxn & properties
Name Principle function Binding
characteristic
Serum/Plasma
conc.
Albumin Binding and
carrier protein;
osmotic regulator
Hormones, amino
acids, steroids,
vitamins, fatty
acids
4500–5000 mg/dL
α 1 –Antiprotease Trypsin and
general protease
Inhibitor
Proteases in
serum and tissue
Secretions
1.3–1.4 mg/dL
α-Fetoprotein Osmotic
regulation;
binding
and carrier
protein
Hormones, amino
acids
Found normally
in fetal blood
Antithrombin-III Protease
inhibitor of
intrinsic
1:1 binding to
proteases
17–30 mg/dL

56. Name Principle function Binding
Characteristic
Serum/Plasma
Conc.
C-reactive
protein
Uncertain; has
role in tissue
inflammation
Complement C1q < 1 mg/dL; rises
in
inflammation
Fibrinogen Precursor to fi
brin in
hemostasis
200–450 mg/dL
Haptoglobin Binding,
transport of cell-
free hemoglobin
Hemoglobin 1:1
binding
40–180 mg/dL
Hemopexin Binds to
porphyrins,
particularly
heme for heme
recycling
1:1 with heme 50–100 mg/dL
Transferrin Transport of iron Two atoms
iron/molecule
3.0–6.5 mg/dL

57. Name Principal function Binding
character
Serum/Plasm
a conc.
Coagulation
factors II, VII, IX,
X
Blood clotting 20 mg/dL
Protein C Inhibition of blood
clotting
Insulinlike
growth factor I
Mediator of anabolic
eff ects of GH
IGF-I receptor
Steroid hormone-
binding globulin
Carrier protein for
steroids in blood
Steroid hormones 3.3 mg/dL
Thyroxine-
binding globulin
Carrier protein for
thyroid hormone
Thyroid hormones 1.5 mg/dL
Transthyretin
(thyroidbinding
prealbumin)
Carrier protein for
thyroid hormone in
bloodstream
Thyroid hormones 25 mg/dL

58. Blood Groups
 ABO system and Rh system are important clinically though 30 common blood
groups MNSs, Lutheran, Kell, Kidd, and many others have been identified
besides more than 100 rare blood groups. Mismatched transfusion of ABO and
Rh sytem cause transfusion reaction hence they will be considered in detail.
 The RBC membrane contain blood group antigens, called agglutinogens. The
most important are A and B antigens, & Rh(D)antigen

59. Blood Group: ABO system
 A & B antigens inherited as mendelian dominants,& on this basis 4 major blood
types . Type A have A antigen, type B have B, type AB have both,& type O have
neither. A& B antigens are complex oligosaccharide differing in terminal sugar. An
H gene codes for a fucose transferase that adds a terminal fucose, forming H
antigen present in all persons. In type A a second transferase add terminal N-
acetylgalactosamine on the H antigen,& in type B a transferase add a galactose. In
type AB have both transferases present. Individuals who are type O have neither, so
the H antigen persists.

60. Blood Group antigens

61. Blood Typing
Blood
Type &
Antige
n
Agglutinin
in Plasma
Anti sera
agglutinates
RBCs
agglutinat
ed by
plasma of
O Anti A, anti
B
None A, B, AB
A Anti B anti A B, AB
B Anti A anti B A, AB
AB None anti A, anti
B
None

62. Universal Recipient & Donor
 Persons with type AB blood are "universal recipients" because they have no
circulating agglutinins & can be given blood of any type without transfusion
reaction due to ABO incompatibility. Type O individuals are "universal donors"
because they lack A and B antigens, & type O blood can be given to anyone without
producing a transfusion reaction due to ABO incompatibility. This does not mean,
that blood should be transfused without being cross-matched except in most
extreme emergencies, since possibility of reactions or sensitization due to
incompatibilities in systems other than ABO systems always exists. In cross-
matching, donor red cells are mixed with recipient plasma on a slide checked for
agglutination.

63. Rh system
 Rh system are also of the greatest clinical importance. The Rh factor, because it
was first studied in rhesus monkey named Rh system It is composed of primarily
C, D, and E antigens. Rh system has not been detected in tissues other than red
cells. D most antigenic component, and the term Rh-positive generally have
agglutinogen D. The Rh-negative individual has no D antigen forms anti-D
agglutinin when injected with D-positive cells. The Rh typing serum used in
routine blood typing is anti-D serum. 85% of Caucasians are D-positive and 15% are
D-negative; over 99% of Asians are D-positive.

64. Transfusion Reactions
 Hemolytic transfusion reactions occur when recipient plasma has agglutinins
against donor's red cells, cells agglutinate and hemolyze. Free hemoglobin is
liberated into plasma. Severity of resulting transfusion reaction may vary from an
asymptomatic minor rise in plasma bilirubin level to severe jaundice renal tubular
damage leading to anuria & death. However when a recipient has agglutinins
against donors RBC, the plasma in transfusion is usually so diluted in the recipient
that it rarely causes agglutination even when the titer of agglutinins against
recipient's cells is high.

65. Formation of Anti-Rh
Agglutinins.
 When red blood cells containing Rh factor are injected into a person
whose blood does not contain the Rh factor that is, into an Rh-negative
person anti-Rh agglutinins develop slowly, reaching maximum
concentration of agglutinins about 2 to 4 months later. This immune
response occurs to a much greater extent in some people than in others.
With multiple exposures to Rh factor, an Rh-negative person eventually
becomes strongly “sensitized” to Rh factor.

66. Rh Transfusion Reactions.
 If an Rh negative person has never before been exposed to Rh positive blood,
transfusion of Rh-positive blood into that person will likely cause no immediate
reaction. However, anti-Rh antibodies can develop in sufficient quantities during
the next 2 to 4 weeks to cause agglutination of those transfused cells that are still
circulating in the blood. These cells are then hemolyzed by the tissue
macrophage. Thus, a delayed transfusion reaction occurs, although it is usually
mild. On subsequent transfusion of Rh-positive blood into same person, who is now
already immunized against the Rh factor, transfusion reaction is greatly enhanced
and can be immediate and as severe as a transfusion reaction caused by
mismatched type A or B blood.

67. Erythroblastosis & hemolysis in neonate
 Another complication due to Rh incompatibility arises when an Rh-negative mother
carries an Rh-positive fetus. Small amounts of fetal blood leak into maternal
circulation at the time of delivery, & mothers develops anti-Rh antibody. During
next pregnancy, mother's agglutinins cross placenta to fetus & cause hemolysis &
various forms of hemolytic disease of newborn (erythroblastosis fetalis). If
hemolysis severe, infant may die in utero or become anemic, jaundice,& edema
(hydrops fetalis). Kernicterus, in which unconjugated bilirubin deposited in basal
ganglia if birth is complicated by hypoxia. Bilirubin rarely penetrates brain in
adults, but it does in infants ,because BBB is more permeable in infancy. However,
main reasons of high unconjugated bilirubin is its increased production &immature
bilirubin-conjugating system.

68. Prevention of Erythroblastosis fetalis
 About 50% of Rh-negative individuals are sensitized (develop an anti-Rh titer) by
transfusion of Rh-positive blood. Because sensitization of Rh-negative mothers by
carrying an Rh-positive fetus generally occurs at birth, first child is usually normal.
However, hemolytic disease occurs in about 17% of the Rh-positive fetuses born to
Rh-negative mothers who have previously been pregnant one or more times with
Rh-positive fetuses. Fortunately, it is usually possible to prevent sensitization from
occurring first time by administering a single dose of anti-Rh antibodies. Such
passive immunization does not harm mother & has been demonstrated to prevent
active antibody formation by mother. This reduces overall incidence of hemolytic
disease by more than 90%.