Professional Documents
Culture Documents
TUKUR
Highly specialized tissue usually red in colour, the degree depends on the vessels from which it
is taken. The specific gravity ranges between 1.055 - 1.065 and PH 6.8 - 7.2. Blood constitutes
7.7% of the total body wt. The total blood volume ranges from 5.0 - 6.0 liters.
FUNCTIONS OF BLOOD
1. Respiratory - Blood carries oxygen from the lungs to the tissues and carbon dioxide from
the tissues to the lungs.
2. Nutritive - Blood conveys nutrient materials (end products of digestion) like glucose,
amino acids, fatty acids and vitamins from the alimentary canal to the various tissues.
3. Excretory - The waste products of cellular metabolism such as urea, uric acid and
creatinine are removed via the blood to their area of excretion e.g. Kidneys.
4. Regulation of body temperature: - Blood has a high specific heat capacity and thus can
absorb a large amount of heat, this helps to prevent a sudden change in body temperature. It has a
high thermal conductivity, this helps the rapid distribution of heat it produces, the blood vessel
near the surface dilate and heat is lost by radiation, conduction and evaporation of sweat. If the
temperature of the outside is low, the superficial blood vessels constrict and heat lost is
prevented.
6. Transportation of hormones- Blood carries hormones from the endocrine glands to the
various parts of the body. Some of the hormones are transported in combination with plasma
proteins.
7. Buffering action - Hb & plasma proteins act as very good buffers. This buffers help to
maintain the acid base balance of the body.
↙ ↘
(c) Non protein nitrogenous substances e.g. urea, uric acid, and creatinine.
(d) End products of digestion e.g. glucose, amino acids, fatty acids, lipids, cholesterol,
glycerol, and phospholipids
(e) Hormones
(f) Enzymes.
HAEMOPOIESIS
This is the formation of blood cells. Haemopoiesis takes place in 3 stages starting from
intrauterine life.
a. Mesoblastic phase- up to the 3rd month of intra-uterine life, blood cells are formed from
mesoderm (yolk sac).
b. Hepatic phase- from the 3rd - 5th month of intrauterine life, blood cells are formed in the
liver and spleen.
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c. Myeloid phase- from the 5th month of intrauterine life onward, the bone marrow of all
bones of the body manufacture blood cells.
After the age of 20 years blood cells are formed exclusively by flat bones of the skull, sternum,
ribs, upper end of humerus, vertebra, crest of ileum and upper end of femur. Except in the areas
mentioned above, all the other parts of bone marrow are filled up with fatty substance and are
referred to as yellow bone marrow and cannot produce blood cells.
HAEMOPOIESIS
Pluripotent stem cells residing in the bone marrow, gives rise to large numbers of red cells,
neutrophils, basophils, eosinophils, monocytes, platelets and lymphocytes circulating in the
blood. Many of these blood elements are short lived and must be continuously replaced.
Cell division and differentiation is dependent on the continuous supply of highly specific protein
factors which act as regulators of haemopoiesis. These protein regulators are called the
haemopoietic colony stimulating factors (CSFs).
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All of the above CSFs except erythropoietin are Lymphokines. Lymphokines are a group of
polypeptides produced by activated leucocytes and acting on other cells in a hormonal, paracrine
or autocrine fashion. Lymphokines may also be referred to as cytokines.
Erythropoietin is a glycoprotein hormone produced by the kidneys and liver, and it acts as the
hormonal regulator of erythropoiesis, affects all committed erythroid cells and enhancing their
activity. Normal erythropoiesis also required the presence of Vitamin B12, folic acid, iron etc.
ERYTHROPOIESIS
Size is about 7.2 µ non-nucleated, biconcave disc. The thickness of both ends is 2µ and at the
middle 1 µ approximately. Average volume of RBC is 90mm3
Shape-The RBCs are non-nucleated biconcave disc. This particular shape is advantageous to
them as
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b. The biconcave shape minimizes diffusion distance between cell surface and individual
hemoglobin molecule.
c. It acts as an osmometer and helps to respond to osmotic pressure change in the peripheral
capillaries.
STRUCTURE- The red cell membrane has a semi permeable membrane. The cell membrane
has got three layers. The outer and inner layer is made up of proteins and composed principally
of glycoproteins which carry several major blood group antigens which are A, B, M, N etc. The
middle layer is made up of phospholipids.
The cell membrane is permeable to water, H+, urea, glucose uric acid etc. It is relatively
impermeable to sodium. The membrane is impermeable to proteins, K and Hb.
RBC STRUCTURE
NOTE: Average RBC diameter 7.2µ, thickness at both ends is averagely 2µ and at the middle 1
µ.
The stroma contains Hb, proteins, lipids and others e.g. enzyme and salts. The enzyme include
carbonic anhydrase which catalysis the reaction between CO2 and H2O to form carbonic acid.
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50% of the lipid present in the stroma are found in combination with proteins and are known as
lipoproteins complex.
FUNCTIONS OF RBC
1. Transportation of O2 from the lungs to other tissues and CO2 from tissues to the lungs.
3. Pigment formation various pigments are derived from Hb after destruction of the RBC
e.g. bilirubin and biliverdin.
1. Dietary factors-Foods rich in first class proteins is very important as it supplies essential
amino acids necessary for synthesis of globin portion of haemoglobin. It is also necessary for the
formation of nucleoprotein and stroma protein of RBC.
4. Maturation factors-These are factors that are responsible for the maturation of nucleated
cells up to late normoblast. They include vitamin B12, and folic acid. Vitamin B12 is an extrinsic
factor, it needs intrinsic factor before absorption. Intrinsic factor is produced by the lining of the
stomach. Disease of the stomach results to megaloblstic anaemia.
5. Factors controlling Hb formation (haematinics), Iron, copper, amino acids vitamin B6 etc
are required for synthesis of Hb.
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Female is 4.0 - 5.5million cells /mm3.
1) At high altitude -the fall in oxygen tension results in hypoxia which stimulates
erythropoiesis
3) Diurnal variation-variations during the 24 hrs of the day. The count is lowest during
sleep, then gradually rises and becomes maximal in the evening.
a) Normocytes (7.2µ)
SHAPE
1) In certain diseases, RBCS are not biconcave, but spherical. These cells are called
Spherocytes.
HAEMOGLOBIN
Haem-Blood
Globin-Protein
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Haemoglobin is a conjugated protein. It consist of a simple protein-globin, to which are attached
four molecules of an iron containing pigment called Haem. By virtue of its iron, Hb can combine
with oxygen to form oxvhaemoglobin.
H← α β→H
H← α β→H
Hb contains 4 haem groups and a globin moiety. The globin moiety consists of a pair of α-
polypeptide chain and another pair of β-polypeptide chain.
The haem portion is a combination of an iron atom with a molecule of porphyrin. Porphyrin
itself consists of four pyrolle rings joined together by methane bridges. The carbon atom of the
methane bridges are labelled as α, β, γ, and δ (for details see Biochemistry). For the biosynthesis
of Hb (Details see Biochemistry).
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FACTORS NEEDED FOR SYNTHESIS OF HAEMOGLOBIN
1. Iron, copper, vitamin B12, B6, Nicotinic acid and pantothenic acid are required for haem
synthesis.
2. For the synthesis of globin, Amino acids (Proteins) are required. In protein deficiency, globin
is not synthesized.
FUNCTIONS OF HAEMOGLOBIN
2. To carry carbon dioxide from the tissues to the lungs for excretion
3. Act as a buffer
FOETAL HAEMOGLOBIN
H← α γ→H
H← α γ→H
In foetal Hb, there is one pair of α--polypeptide chain. The β -polypeptide chain is replaced by γ
-polypeptide chain. The foetal Hb has greater affinity for the carriage of carbon dioxide.
In normal physiological conditions like pregnancy, the haemoglobin concentration may drop to
about 10-12g/dl of blood. This is because, during pregnancy, the body gains fluid and the RBC
become less concentrated, also, due to the increase in demand. In polycythemia e.g. in high
altitude Hb concentration goes up.
1. If Hb comes out into the plasma, it will be filtered by the glomerular capillaries in the kidneys
and will be lost in the urine as Haemoglobinuria. Also in the kidneys, it will be converted to
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acid-haematin which could lead to destruction of renal tubules or tissues and consequent kidney
breakdown (failure).
2. Presence of Hb in plasma will elevate the colloid osmotic pressure. The colloid osmotic
pressure may rise up to 100 mmHg. This will disturb the trans-capillary fluid exchange.
3. It will be destroyed by the reticulo-endothelial cells (REC) in the liver, bone marrow and
spleen to form bile pigments.
SICKLE HAEMOGLOBIN
The sickle Hb has two α and two β -polypeptide chains as in normal adult Hb, but there is
substitution of amino acid sequence at position 6 of the β chain amino acid is VALINE instead of
GLUTAMIC ACID. Other abnormal haemoglobin’s are HbC (Hb-C), HbSC (Hb-SC) and HbS
(Hb-S).
CATABOLISM OF RBC
After a lifespan of about 120 days RBCS are destroyed by the reticulo-endothelial cells found in
the liver, spleen as well as bone marrow. The haem part of the haemoglobin is altered by the
oxidation of one of its methane bridges. The tetra-pyrolle ring structure is thus broken and the
four pyrolle groups become arranged as straight chain to form a compound called verdo-
haemoglobin (so called because it is green in colour). Next, both iron and globin are split off and
biliverdin is formed.
The biliverdin is later reduced to bilirubin. The iron is stored in the liver and could be re-utilized
for the synthesis of haemoglobin. The globin moiety enters the general pool of proteins in the
body. Bilirubin is released into plasma bound to plasma proteins particularly albumin. In this
form bilirubin is transported to the liver. On reaching the liver, bilirubin enters the hepatic cells
and therein undergoes conjugation with glucoronic acid to form bilirubin mono-glucuronide and
bilirubin di-glucuronide. These compounds pass by way of the bile duct to the intestine where
they are converted to bilinogen by bacterial action in the large intestine. About 45% of the
bilinogen is further converted to stercobilinogen which is then eliminated through the faecal
matter. On exposure to air, stercobilinogen is oxidized to stercobilin which impacts the
characteristic yellow or brownish colour to stool. Some of the bilinogen (50%) is reabsorbed in
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the terminal ileum and goes via the portal system to the liver where it is reconverted into
bilirubin glucuronide and re- excreted into the intestine via the bile duct. This process is known
as enterohepatic circulation of bile pigments. About 5% of the bilinogen reaches the kidney
through the systemic circulation where it is converted to urobilinogen. Urobilinogen is voided
through the urine. On reaching the outside world, urobilinogen is oxidized to urobilin. Urobilin
gives the characteristic yellow colour to urine. Normal serum bilirubin content is 0.2 to 1.1 mg%.
2. Hepatic or infective jaundice (due to toxic damage to the liver cells), e.g. hepatitis.
3. Post hepatic or obstructive jaundice (due to the obstruction to flow of bile) as occurs in
gallstone.
PHYSIOLOGICAL JAUNDICE
In newborn babies between 2-7days of their life, the liver sometimes is not capable of
conjugating bilirubin with glucoronic acid. Therefore unconjugated bilirubin circulates in the
blood and causes mild jaundice. After 10 days, the liver can now adequately conjugate bilirubin
with glucoronic acid and this mild jaundice disappears.
ANAEMIA
It is the quantitative or qualitative reduction in circulating RBCs. The number of RBCs, may be
less or the amount of haemoglobin may be low or both may occur simultaneously in anaemia.
CLASSIFICATION OF ANAEMIA
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a. Intra- capsular causes (within) e.g. abnormal structure as in Cooley’s disease -Abnormal
shape e.g. sickle cell anaemia, and spherocytosis
a. X-ray radiation
b. Drug toxicity
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WHITE BLOOD CELLS (Leucocytes)
5 Several varieties are present e.g. neutrophils, Only one variety is present.
eosinophils, basophils, monocyte and
lymphocytes.
6 Some of them show active amoeboid RBCs do not show amoeboid movement.
movement.
7 They have shorter lifespans as follows. They have longer lifespan of about 120
Neutrophils (2-4 days) days.
Eosinophils (8-12days), Basophils(about two
weeks) Lymphocytes (2-3 days)
8 Their function differs from those of RBCs e.g. Their functions differs from those of
phagocytosis WBCs e.g. carriage of oxygen.
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CLASSIFICATION OF WBCs
GRANULOCYTES
Neutrophils
These cells are the most numerous in circulation. They are 12-14µ in diameter the average half-
life of neutrophil is 6 hours. The mature cells have large amounts of nuclear material which may
be composed of 2-5 inter-connected lobes (see diagram).
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The cytoplasm contains fine granules which stain pink with Leishman’s stain. The immature
forms are called band” or stab neutrophils.
Neutrophils leave the circulation and enter tissues via the process of diapedesis which involves
insinuation of the cells through capillaries between endothelial cells.
Functions of neutrophil are to seek out, ingest and kill bacteria. They therefore act as the body's
first line of defense in combating infection.
Neutrophils are attracted to the site of bacterial invasion by a substance known as chemotaxins.
Chemotaxins are chemical mediators which are attractants and cause cells to move towards them.
Upon arrival at an invasion site, neutrophils are able to actively ingest bacteria through the
process of phagocytosis.
Phagocytosis may be enhanced by bacterial opsonization. Opsonins are substances able to coat
the surface of bacteria and in so doing make the bacteria more tasty and aid phagocytosis e.g. of
Opsonins include some immunoglobulin classes and certain complement components.
The phagocytic vesicles (phagosomes) formed as a result of bacterial ingestion then fuse with the
lysosomes of the neutrophils. This process is referred to as degranulation and is associated with a
sharp increase in oxygen consumption as well as an increase in the cells rate of metabolism i.e.
the respiratory burst.
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Eosinophils
These cells are about 10-12µ in diameter. The nucleus is usually bilobed or spectacle shaped.
The cytoplasm contains coarse reddish granules, oval in shape and highly refractive. Large
parasites such as helminths, cannot be physically phagocytosed, and extra cellular killing by
eosinophils must take place. Eosinophils have granules that contain;
Eosinophils are cells which are involved in the body’s response to foreign proteins e.g. allergic
reactions, asthma, and parasites. Upon activation, eosinophils are capable of launching their extra
cellular attack mechanisms which lead to damage of the foreign cell membrane.
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Basophils
These leucocytes contain granules which stain well with basic dyes, and are the smallest type of
leucocytes present in circulation. They have a diameter of about 8- l0 µ. The nucleus is usually
C-shaped. The cytoplasm contains large granules (blue). The granules of basophils contain
histamine, heparin, slow reacting substance of anaphylaxis.
Basophil resembles mast cell (are fixed cells in tissues). The mediators released cause adverse
symptoms of allergy, but on the positive side, they may also play a role in immunity against
parasites.
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AGRANULOCYTES
Monocytes-
Are actively phagocytic cells derived also from a common progenitor haemopoietic stem cell.
They are about 12-18µ in diameter. Monocytes have an abundant a-granular cytoplasm and
kidney shaped nuclei. These cells are regarded as the body’s second line of defense, being
mobilized along with neutrophils in the inflammatory response.
Monocytes leave the circulation after 24hrs to become fixed phagocytic cells in tissues. These
cells are referred to as macrophages.
The mononuclear- phagocytic system is a group of cells composed of the macrophages present in
tissues. These cells are particularly concentrated in the lungs (alveolar macrophages), the liver
(kupffer cells) and lining the spleen sinusoid and lymph node medullary sinuses where they filter
off foreign materials. The microglia cells of the nervous system, mesangeal cells of the kidney,
and osteoclasts in the bone are examples of tissue macrophages.
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Lymphocytes
Lymphocytes are produced in the primary lymphoid organs (Thymus and bone marrow). In the
foetus, the liver and spleen may also form primary lymphoid organs.
All cells which migrate to specific areas in the bone marrow will result in the production of B-
lymphocytes, while lymphocytes produced in the thymus are called T-lymphocytes.
Lymphoid cells represent 20% of the total white blood cells present in circulation. Matured
lymphoid cells are long lived and may persist as memory cells for several years.
B cells and T cells are not only produced in different sites, but they also have important
functional and morphological differences.
T- Cells
Human T-cells are distinguishable from B-cells by the ability of T-cells to bind to sheep
erythrocytes.
1. T-helper cells-These cells which positively influence the immune response of T- cells and B-
cells.
B-Cells
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B-lymphocytes are the cells which when activated by an antigen, differentiate into plasma cells
and synthesize immunoglobulins.
Leucocytosis- A rise in leucocytes count above the physiological range (i.e. WBC count above
11,000 cells/mm3. It may also affect any of the various types of leucocytes.
Leucopenia—A fall in leucocytes count below the physiological range (i.e. while cell below
4,000cells/ mm3.
Platelets
Platelets are small cells lying outside the sinusoids of the bone marrow. They are produced by
budding off from the cytoplasm of megakaryocytes in the bone marrow.
Platelets are 2-4µ in diameter. Normal range in circulation is 150- 350,000cells/ml blood.
Platelets are rich in enzymes and contain large amounts of ATP, ADP, calcium, serotonin,
inorganic phosphates, they also contain clotting factors like factor v and vii.
Haemostasis
Is the process by which blood loss is minimized following injury to blood vessel. Although
rupture of larger vessels usually requires medical intervention, hemostasis is quite effective in
dealing with small, simple wounds. There are three steps to the process: vascular spasm, the
formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will
result in hemorrhage—excessive bleeding.
Vascular Spasm/vasoconstriction
When a vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm
occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically.
This smooth muscle has both circular layers; larger vessels also have longitudinal layers. The
circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present,
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draw the vessel back into the surrounding tissue, often making it more difficult for a surgeon to
locate, clamp, and tie off a severed vessel. The vascular spasm response is believed to be
triggered by several chemicals called endothelins that are released by vessel-lining cells and by
pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes,
although it can last for hours.
In the second step, platelets, which normally float free in the plasma, encounter the area of vessel
rupture with the exposed underlying connective tissue and collagenous fibers. The platelets begin
to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial
lining. This process is assisted by a glycoprotein in the blood plasma called von Willebrand
factor, which helps stabilize the growing platelet plug. As platelets collect, they simultaneously
release chemicals from their granules into the plasma that further contribute to hemostasis.
Among the substances released by the platelets are:
adenosine diphosphate (ADP), which helps additional platelets to adhere to the injury
site, reinforcing and expanding the platelet plug
serotonin, which maintains vasoconstriction
prostaglandins and phospholipids, which also maintain vasoconstriction and help to
activate further clotting chemicals, as discussed next
A platelet plug can temporarily seal a small opening in a blood vessel. Plug formation, in
essence, buys the body time while more sophisticated and durable repairs are being made. In a
similar manner, even modern naval warships still carry an assortment of wooden plugs to
temporarily repair small breaches in their hulls until permanent repairs can be made.
Coagulation
Those more sophisticated and more durable repairs are collectively called coagulation, the
formation of a blood clot. The process is sometimes characterized as a cascade, because one
event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous
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but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from
fibrinogen, the plasma protein introduced earlier—in which platelets and blood cells are trapped.
In the coagulation cascade, chemicals called clotting factors (or coagulation factors) prompt
reactions that activate still more coagulation factors. The process is complex, but is initiated
along two basic pathways:
Both of these merge into a third pathway, referred to as the common pathway. All three
pathways are dependent upon the 12 known clotting factors, including Ca2+ and vitamin K.
Clotting factors are secreted primarily by the liver and the platelets. The liver requires the fat-
soluble vitamin K to produce many of them. Vitamin K (along with biotin and folate) is
somewhat unusual among vitamins in that it is not only consumed in the diet but is also
synthesized by bacteria residing in the large intestine. The calcium ion, considered factor IV, is
derived from the diet and from the breakdown of bone. Some recent evidence indicates that
activation of various clotting factors occurs on specific receptor sites on the surfaces of platelets.
The 12 clotting factors are numbered I through XIII according to the order of their discovery.
Factor VI was once believed to be a distinct clotting factor, but is now thought to be identical to
factor V. Rather than renumber the other factors, factor VI was allowed to remain as a
placeholder and also a reminder that knowledge changes over time.
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*Vitamin K required.
Clotting Factors (Table 1)
Factor Type of
Name Source Pathway(s)
number molecule
Common; converted
I Fibrinogen Plasma protein Liver
into fibrin
Common; converted
II Prothrombin Plasma protein Liver*
into thrombin
Tissue thromboplastin or Lipoprotein Damaged cells
III Extrinsic
tissue factor mixture and platelets
Inorganic ions Diet, platelets,
IV Calcium ions Entire process
in plasma bone matrix
V Proaccelerin Plasma protein Liver, platelets Extrinsic and intrinsic
VI Not used Not used Not used Not used
VII Proconvertin Plasma protein Liver * Extrinsic
Platelets and
Plasma protein Intrinsic; deficiency
VIII Antihemolytic factor A endothelial
factor results in hemophilia A
cells
Antihemolytic factor B
Intrinsic; deficiency
IX (plasma thromboplastin Plasma protein Liver*
results in hemophilia B
component)
Stuart–Prower factor
X Protein Liver* Extrinsic and intrinsic
(thrombokinase)
Antihemolytic factor C
Intrinsic; deficiency
XI (plasma thromboplastin Plasma protein Liver
results in hemophilia C
antecedent)
Intrinsic; initiates
XII Hageman factor Plasma protein Liver clotting in vitro also
activates plasmin
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*Vitamin K required.
Clotting Factors (Table 1)
Factor Type of
Name Source Pathway(s)
number molecule
Stabilizes fibrin; slows
XIII Fibrin-stabilizing factor Plasma protein Liver, platelets
fibrinolysis
Extrinsic Pathway
The quicker responding and more direct extrinsic pathway (also known as the tissue factor
pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury.
Upon contact with blood plasma, the damaged extravascular cells, which are extrinsic to the
bloodstream, release factor III (thromboplastin). Sequentially, Ca2+ then factor VII
(proconvertin), which is activated by factor III, are added, forming an enzyme complex. This
enzyme complex leads to activation of factor X (Stuart–Prower factor), which activates the
common pathway discussed below. The events in the extrinsic pathway are completed in a
matter of seconds.
Intrinsic Pathway
The intrinsic pathway (also known as the contact activation pathway) is longer and more
complex. In this case, the factors involved are intrinsic to (present within) the bloodstream. The
pathway can be prompted by damage to the tissues, resulting from internal factors such as
arterial disease; however, it is most often initiated when factor XII (Hageman factor) comes into
contact with foreign materials, such as when a blood sample is put into a glass test tube. Within
the body, factor XII is typically activated when it encounters negatively charged molecules, such
as inorganic polymers and phosphate produced earlier in the series of intrinsic pathway reactions.
Factor XII sets off a series of reactions that in turn activates factor XI (antihemolytic factor C or
plasma thromboplastin antecedent) then factor IX (antihemolytic factor B or plasma
thromboplasmin). In the meantime, chemicals released by the platelets increase the rate of these
activation reactions. Finally, factor VIII (antihemolytic factor A) from the platelets and
endothelial cells combines with factor IX (antihemolytic factor B or plasma thromboplasmin) to
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form an enzyme complex that activates factor X (Stuart–Prower factor or thrombokinase),
leading to the common pathway. The events in the intrinsic pathway are completed in a few
minutes.
Common Pathway
Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is
produced to seal off the vessel. Once factor X has been activated by either the intrinsic or
extrinsic pathway, the enzyme prothrombinase converts factor II, the inactive enzyme
prothrombin, into the active enzyme thrombin. (Note that if the enzyme thrombin were not
normally in an inactive form, clots would form spontaneously, a condition not consistent with
life.) Then, thrombin converts factor I, the insoluble fibrinogen, into the soluble fibrin protein
strands. Factor XIII then stabilizes the fibrin clot.
Fibrinolysis
The stabilized clot is acted upon by contractile proteins within the platelets. As these proteins
contract, they pull on the fibrin threads, bringing the edges of the clot more tightly together,
somewhat as we do when tightening loose shoelaces. This process also wrings out of the clot a
small amount of fluid called serum, which is blood plasma without its clotting factors.
To restore normal blood flow as the vessel heals, the clot must eventually be removed.
Fibrinolysis is the gradual degradation of the clot. Again, there is a fairly complicated series of
reactions that involves factor XII and protein-catabolizing enzymes. During this process, the
inactive protein plasminogen is converted into the active plasmin, which gradually breaks down
the fibrin of the clot. Additionally, bradykinin, a vasodilator, is released, reversing the effects of
the serotonin and prostaglandins from the platelets. This allows the smooth muscle in the walls
of the vessels to relax and helps to restore the circulation.
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Anticoagulants:
1. In vivo anticoagulants like heparin produced by basophilic mast cells. Its action is the
prevention of factor IX activation.
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2. In vitro anticoagulants- These include Na citrate, oxalates. Ca precipitate is very
important in the storage of blood in the blood bank.
ANTI-CLOTTING MECHANISM
Blood does not normally clot in undamaged blood vessels of the body. This is due to;
1. Smooth endothothelial lining of the blood vessel minimizes abrasive surface contact with
platelets.
2. The negative charge of the protein layer of the endothelial cell surface repels the
negatively charged clotting factors and the platelets. However, damaged to the blood vessel lead
to the loss of both the smooth lining and the negative charge. This is when the reactions of
intrinsic pathway of clotting are initiated.
4. Mechanism which break up any clot that do form. This is known as fibrinolytic system. It
involves degradation of fibrin and fibrinogen to products which themselves inhibits the
formation of thrombin. This occurs through the catalytic action of the enzyme fibrinolysin.
Disorders of Clotting
Either an insufficient or an excessive production of platelets can lead to severe disease or death.
As discussed earlier, an insufficient number of platelets, called thrombocytopenia, typically
results in the inability of blood to form clots. This can lead to excessive bleeding, even from
minor wounds.
Another reason for failure of the blood to clot is the inadequate production of functional amounts
of one or more clotting factors. This is the case in the genetic disorder hemophilia, which is
actually a group of related disorders, the most common of which is hemophilia A, accounting for
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approximately 80 percent of cases. This disorder results in the inability to synthesize sufficient
quantities of factor VIII. Hemophilia B is the second most common form, accounting for
approximately 20 percent of cases. In this case, there is a deficiency of factor IX. Both of these
defects are linked to the X chromosome and are typically passed from a healthy (carrier) mother
to her male offspring, since males are XY. Females would need to inherit a defective gene from
each parent to manifest the disease, since they are XX. Patients with hemophilia bleed from even
minor internal and external wounds, and leak blood into joint spaces after exercise and into urine
and stool. Hemophilia C is a rare condition that is triggered by an autosomal (not sex)
chromosome that renders factor XI nonfunctional. It is not a true recessive condition, since even
individuals with a single copy of the mutant gene show a tendency to bleed. Regular infusions of
clotting factors isolated from healthy donors can help prevent bleeding in hemophiliac patients.
At some point, genetic therapy will become a viable option.
BLOOD GROUPS
Although, the RBC of all races has identical appearance, their membrane contains a variety of
antigens (agglutinogens) which vary in type in different individuals. When these antigens
combine with appropriate antibodies (agglutinins), the cells become sticky and clump together,
the process is called agglutination. The most common antigens are the A and B antigens. In this
classification individuals are grouped into four major classes. A, B, AB, and O.
The group A has antigen A on its surface, group B the antigen is B, group AB has both, while
group O has neither present.
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Red blood cell Plasma
Group A Anti B
Group B Anti A
Group AB
Group O Anti A and B
Normally the absence of A or B antigen in a person’s RBC is always associated with the
presence of appropriate antibody in their serum e.g. the absence of A antigen in the RBC means
that anti A antibody is present in the plasma. The practical importance of the blood groups is that
cells from one person transfused into another must be matched so that, they are not agglutinated
by the antibody present in the recipient plasma. It should be noted that the donors serum has little
effect on the recipient cell because of the large dilution which take place, thus the effect of
transfusion are tested for directly by testing the donors cell with recipients serum before
transfusion. This is called cross matching. The severity of a mismatch blood varies from mild to
severe reactions like fever, chills and rigors to severe hyper sensitivity reaction.
Secretors- The A & B antigens may be secreted in a soluble form found in 80% of the
population and such persons are referred to as secretors. The others are non-secretors.
In addition to the ABO blood group system there are other agglutinogens system containing
many antigenic material in the RBC. The most important of this is the Rh system which is really
a group of many antigens; the most important quantitatively is the D- antigen. Blood groups are
inherited in the Mandelian way in a given person. Blood is a complex of the mother and the
father’s blood grouping gene and individual of blood group B may be BB or BO, being
homozygous or heterozygous.
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RHESUS FACTOR AND TRANSFUSION
In addition to the four main groups there are many other agglutinogens systems. Rh negative
individuals have no D antigen on their erythrocyte surfaces while Rh positive have. 85% of
Caucasians and Nigerians are Rh positive while the proportion is more than 99% in Orientals, in
some Negroes about 95%. Transfusion of an Rh positive blood to an Rh negative individual
causes no immediate transfusion reaction. However, the anti Rh antibodies develop in the
recipient over a period of two to four months, the rate of the immune response differing from one
individual to another.
If some of the transfused red cells are still in the recipient’s blood at this time, they are
haemolysed by the tissue macrophage system i.e. a delayed transfusion reaction occurs. This is
however a mild response. If the same individual is subsequently transfused with an Rh positive
blood, serious transfusion reaction occurs since he is now immunized against the Rh factor. Such
reactions may be as severe as that which occurs in the ABO system.
In an attempt by the foetal haemopoietic system to replace the lost cells (RBCs), the liver and
spleen become greatly enlarged because of hyperactivity to produce red cells. This becomes so
rapid that many incompletely formed, erythroblast become noticeable in the foetal blood hence
the disease erythroblastosis foetalis. If the anaemia becomes so severe, there may be death in
utero or the foetus may develop severe oedema. This condition is known as hydrops foetalis.
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Bilirubin may also find its way into the brain tissues causing their destruction and permanent
mental impairment (because the blood brain barrier does not develop in foetus). This condition is
known as kernicterus.
Treatment
Replacement of newborn baby’s blood with Rh-negative blood, while the baby’s own blood is
being removed. This is called exchange blood transfusion.
1. Sensitization of the recipients to agglutinogens not cross matched for: this may cause a
transfusion reaction during subsequent transfusions.
2. Incompatibility which will result in a transfusion reaction that may be mild, moderate or
severe
IMMUNITY
Immunology is the study of the physiological responses by which the body recognizes foreign or
its own abnormal cell material and destroys or neutralizes them.
Types of immunity
Three types of immunity are recognized. We have the natural, passive, and an active immunity.
2. Active immunity-this refers to immunity that has developed as a result of the activity of
the body’s own cell such as when a person has recovered from an attack of an infectious disease
e.g. small pox cannot contract the disease again except on rare instances.
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DEFINITIONS
Antigen- a foreign molecular component which can be cellular or non-cellular that elicits an
immune response.
Complement- a group of plasma proteins which upon activation, kill microbes directly, also
facilitate every step of the inflammatory process by acting as Opsonins.
IMMUNE MECHANISMS
Are divided into two major categories, it is produced by both immediate measures. The
immediate measure or respond is phagocytosis or cellular immune system while the longer time
response which occurs between two to three weeks is the production of antibodies against the
infecting agents and is also known as humoral immune system.
Both cellular and the humoral immune system are involved in the protective reaction to a
specific protein called antigens.
The humoral response is very specific in that it can only respond to a particular antigen e.g., the
antibody that is responsible for immunity against small pox is inactive against measles or any
other infectious disease. On the other hand, cellular immune response is nonspecific and can be
evoked by many antigens. The development of the immune response is brought about by two
populations of lymphocytes. The first of these called the T- lymphocytes or cells are responsible
for cellular immunity and they populate the thymus. They do not secret antibodies but act as
killer cells which attack foreign grafts. The second populations of Cells are called the B-cells
which are responsible for humoral immunity and they populate the liver and spleen. The B-
lymphocytes often requires the presence of T-lymphocytes in order to be ligand by antigens. B-
lymphocytes are known to mature into two types. These are;
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B-lymphocytes are characterized by a large nucleus and bright blue cytoplasm when wrights
stain is used.
Plasma cells are usually loaded with secretory vacuoles or granules for they are highly
specialized to synthesize a variety of antibodies.
Immunoglobulins (antibodies)
Antibodies are heterogeneous group of proteins molecules all being capable of reacting with the
specific antigen and are separated into classes and subclasses on the basis of their chemical
properties.
1. Immunoglobulin G IgG
2. Immunoglobulin A IgA
3. Immunoglobulin M IgM
4. Immunoglobulin E IgE
5. Immunoglobulin D IgD
2. IgA also occurs in body secretions like colostrum. Saliva, tears etc.
Cellular immunity is mediated by killer T-cells. When antigens are present in the body they are
ingested by the macrophages which expose a small part of the antigen. This exposure stimulates
the inducer \helper T-cells which mediate immunity. The killer cells immediately differentiate
into memory T-cells, and suppressor T-cells, each of which swing into their respective actions.
The cytotoxic or T killer- cells have toxic molecules which destroy membranes of the target
cells. After the immune response is achieved, the actions of the cytotoxic or killer cells are put to
an end by the suppressor T- cells which develop much later. They do this by inhibiting the helper
T-cells. Furthermore, memory T-cells usually stay longer in the system in order to detect a
subsequent exposure to the same antigen and make adequate and fast response.
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HUMORAL IMMUNE RESPONSE
Like in cellular immunity, the presence of any foreign proteins like bacteria or virus results in
activation of macrophages which ingest and expose a small part of the antigen. The exposure of
the antigen by macrophages activate the inducer (helper) T-cells. The T-helper cells in turn
contact the B- cells which quickly proliferate and transform into B- memory and plasma cells.
The antibodies which are subsequently produced by the plasma cells are then put to use by
reacting with the specific antigen.
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Bloody Fluid Compartments
A 70 kg 'standard male’ contains 42 liters of water - 60% of his body weight. The hypothetical
adult female contains 55% of her body weight as water; this lower percent being due to a higher
fat content.
Neonates contain more water than adults: 75-80% water with proportionately more extracellular
fluid (ECF) than adults. At birth, the amount of interstitial fluid is proportionally three times
larger than in an adult. By the age of 12 months, this will decrease to 60% which is the adult
value.
Total body water as a percentage of total body weight decreases progressively with increasing
age. By the age of 60 years, total body water (TBW) has decreased to only 50% of total body
weight in males mostly due to an increase in adipose tissue.
Most tissues are water-rich and contain 70-80% water. The three major exceptions to this are:
The variation between individuals in the ratio of TBW to total body weight is quite large but the
majority of the variation is due to different amounts of adipose tissue. Obese adults have a lower
ratio. For any particular tissue of the body the variation is much less but any variation that occurs
is still mostly due to differences in amount of adipose tissue.
The water in the body is contained within the numerous organs and tissues of the body. These
innumerable fluids can be lumped together into larger collections which can be discussed in a
physiologically meaningful way. These collections are referred to as compartments. The major
division is into Intracellular Fluid (ICF: about 23 liters) and Extracellular Fluid (ECF: about 19
liters) based on which side of the cell membrane the fluid lies. Typical values for the size of the
fluid compartments are listed in the table.
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Body Fluid Compartments (70 kg male)
Volume
% Of Body
% of Total Body (Liters)
Weight
Water
ECF 27 45 19
Plasma 4.5 7.5 3.2
ISF 12.0 20.0 8.4
The Intracellular Fluid is composed of tiny cellular packages. The concept of a single united
"compartment" called intracellular fluid is dearly artificial. The ICF compartment is really a
"virtual compartment" considered as the sum of this huge number of discontinuous small
collections. How can the term 'intracellular fluid' be used as though it was a single body of fluid?
The reason is that though not united physically, the collections have extremely important
unifying similarities which make the ICF concept of practical usefulness in physiology. In
particular, similarities of location, composition and behavior:
• Location: The distinction between ICF and ECF is clear and is easy to understand: they
are separated by the cell membranes
• Composition: Intracellular fluids are high in potassium and magnesium and low in
sodium and chloride ions
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Because of this physiological usefulness, it is convenient to talk of an idealized ICF as though it
were a single real entity. The use of this convention allows predictions to be made about what
will happen with various interventions and within limits these are physiologically meaningful.
The Extracellular Fluid. The ECF is divided into several smaller compartments (e.g. plasma,
interstitial fluid in bone and dense connective tissue and trans-cellular fluid). These
compartments are distinguished by different locations and different kinetic characteristics.
Interstitial fluid (ISF) consists of all the bits of fluid which lie in the interstices of all tissues.
This is also a 'virtual' fluid (i.e. it exists in man. separate small bits but is spoken about as though
it was a pool of fluid of uniform composition in one location. The ISF bathes all the cells in the
body and is the link between the ICF and the intravascular compartment. Oxygen, nutrients,
wastes and chemical messengers all pass through the ISF. ISF has the compositional
characteristics of ECF (as mentioned above) but in addition it is distinguishes itself with usually
low protein concentration (in comparison to plasma). Lymph is considered as a part of the ISF,
The lymphatic system returns protein and excess ISF to the circulation. Lymph is more easily
obtained for analysis than other parts of the ISF. Plasma is the only major fluid compartment that
exists as a real fluid collection all in one location. It differs from ISF in its much higher protein
content and its high bulk flow (transport function). Blood contains suspended red and white cells
so plasma has been called the 'interstitial fluid of the blood'. The fluid compartment called the
blood volume is interesting in that it is a composite compartment containing ECF (plasma and
ICF (red cell water).
The fluid of bone & dense connective tissue is significant because it contains about 15% of the
total body water. This fluid is mobilized only very slowly and this lessens its importance when
considering the effects of acute fluid interventions.
Trans-cellular fluid is a small compartment that represents all those body fluids which are
formed from the transport activities of cells. It is contained within epithelial lined spaces. It
includes CSF, GIT fluids, bladder urine, aqueous humor and joint fluid. It is important because
of the specialized functions involved. The fluid involved with GIT fluids can be quite significant.
The electrolyte composition of the various trans-cellular fluids are quite dissimilar and typical.
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Plasma physiology
The fluid portion of whole blood, in which the blood cells are suspended. It transports nutrients,
metabolic waste products, and chemicals involved in the clotting process, as well as hormones
and drugs, to their target cells. It clots readily, and can be obtained by centrifuging or
sedimentation. The term is also used for the fluid portion of semen, in which spermatozoa are
suspended.
If 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 are removed and has higher serotonin content because of breakdown of platelet during
clotting.
(k) Non protein nitrogenous substances e.g. urea, uric acid, and creatinine.
(l) End products of digestion e.g. glucose, amino acids, fatty acids, lipids, cholesterol,
glycerol, and phospholipids.
(m) Hormones
(n) Enzymes.
Plasma proteins
Plasma proteins
Albumin
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Globulin
Fibrinogen
(6) γ-globulins (immunoglobulin). There are 5 classes: IgG, IgA, IgM, IgE and IgD
immuglobins — GAMED.
Synthesis
1. Plasma proteins particularly albumin component exert pressure of about 25mmHg across
the capillary wall. This is essential for the maintenance of adequate fluid interchange
between the blood and the interstitial space.
2. Fibrinogen is a coagulation factor.
3. Regulation of acid-base balance by absorbing FT ion.
4. Plasma proteins are essential for transport of some ions and hormones in the blood and
other substances in the blood e.g. Fe and Cu are transported by transferrin and
ceruloplasmin respectively. Also, albumin is essential for transport of thyroxin and
bilirubin in the blood
5. Gamma-globulins (immunoglobulin) fight against infections e.g. measles.
Lymph
Is the tissue fluid that enters the lymphatic vessels. It drains into the venous blood via the
thoracic and right lymphatic ducts. It contains clotting factors and clots on standing in-vitro.
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