Blood composition

formation and fate of blood cells

blood clotting mechanism intrinsic
and extrinsic pathways, clotting factors
anticoagulants
blood transfusion (safety and security
problems)
mention haemostasis, haemolysis,
jaundice, thrombosis, ESR.
Cerebral circulation, blood brain barrier
and cerebrospinal fluid
Haemodynamic principles,

Blood

6liters , 8% of body wt.

Blood = Plasma + formed elements
Plasma = water 92% + 8% dissolved/suspended solid
materials, organic/ inorganic constituents)
Organic constituents
plasma proteins(Albumins, globulins-3 types ),
fibrinogen. All r formed in d liver, a small fraction of
globulins in lymphoid tissues)
Hormones, vt, aa, glu, lipids, urea, uric acid,
xanthine, hypoxanthine, creatine, creatinine,
ammonia.
Inorganic constituents-controls PH & O.P of blood
Na, K, Ca, Mg, P, Fe, Cu, NaCl, NaHCO3, Na2PO4

Functions of plasma
Plasma exerts OP, influence exchange of fluid btwn
blood & tissues.
Plasma prtscause OP at d capillary membrane colloid osmotic
pressure- prevents plasma from leaking out of d
capillaries into the interstitial spaces.
maintain viscosity & blood pressure mainly globulins
bcz of their assymetric strucure.
are buffers, maintain acid-base balance
Protein reserve
Mainly globulins Help trasport hormones, enzymes, Fe,
Cu,
Fibrinogen blood clotting.fibrin.
, globulins immunity

 RBC
Circular, non nucleated, biconcave, 8 microns D, Thickness- 1 at
centre, 2.2 microns at periphery), cell mem semi permeable,
Contains Hb-80-90%, Average no- 5 4.5 million.life span 90120 days. antigens present on d surface
RBC no- polycythemia
RBC/HB - Anaemia
Functions -Carries O2 & CO2, Buffering action of Hb, RBC
maintains viscosity of blood
WBC/ Leucocytes morphological difference
Agranulocytes clear non-granular cytoplasm, single large
nucleus
1. Lymphocytes round, non-granular, large round nuclei, size
8-10 D. 20-30%
2. Monocytes
Size 10- 18 D,kidney shaped nucleus, 5-8%,highly motile &
phagocytic

 Granolocytes/ploymorpho nuclear cells - Nucleus is

lobulated, granules in cytoplasm
3 types staining properties
1. Neutrophil
50-70%, nucleus multilobed, granules stained pink with neutral
dyes, size 10-12, highly motile & phagocytic.
2. Eosinophil
2-4%, 10-12 D, bilobed /spects shaped nucleus, absorb acidic
dyes(eosin), coarse granules- often stained bright red in
color, motile & non phagocytic.
3. Basophil
8-10, 1% , round granules, slightly lobulated kidney shaped
nucleus, contains-heparin, histamine, 5 hydroxytryptamine
Functions
4. Phagocytosis
5. Formation of antibody lymphocytes
6. Secrete heparin prevents intravascular clotting
7. Eosinophils detoxify toxic products

Platelets / Thrombocytes
Spherical, oval or rod shaped.2.5 D, average no.
-250,000-500,000 cells/ cubic mm of blood.
Function coagulation of blood. Serotonin
vasoconstriction

Production of RBC - Erythropoiesis

Embryonic stage liver, spleen, thymus
After birth BM
Haemocytoblast parent cell of erythrocyte

Proerythroblast nucleated,20 micron, small basophilic

cytoplasm.

Normoblast - acidophilic cell

Reticulocytes nucleus disappears

Erythrocytes
During maturation process several changes occurs,
decrease in d size of d cell, Accumulation of Hb,
cytoplasm becomes acidophilic.
Induce by hypoxia, erythropoietin

Synthesis of blood cells

Functions of blood

Transport O2, CO2, glucose, aa, fatty acids, vt, electrolytes,

trace metals from alimentary canal. wastes like urea, uric
acid, creatinine to kidney
Regulation water, PH (buffering capacity of carbonic
acid,bicarbonate & Hb), O.P, electrolyte balance, body Temp.
Protection our body has d ability to eliminate pathogens &
toxins-antigens, this is due to d antibodies produced by d
immune system.
Acquired immunity on exposure to Ag
Innate exists prior to exposure to Ag.
Humoral Antibodies capable of attacking Ag r involved, B cells
on exposure to Ag plasma & memory cells
Cellular specialized cells T, CTLs, Macrophages r involved.T
cells on exposure to Ag produces 4 types of cells,effector
cells (CTLs kills target cells),helper/ inducer ( regulate Ab
production of plasma cells), suppressor (suppress d immune
system), memory (remain in d body for a longer time,
eliminate when d pathogen enter d body for d second time)

Active immunity acquired by an earlier infection /

immunity that is induced by natural exposure to a
pathogen.
Passive person is immunized. Acquired immunity
produced by d transfer of immune products from an
immunized individual to a non-immune man.
HIV can avoid TH cells by changing its structure
(tropism) destroys TH cells.

Blood clotting

Converted to a semisolid jelly form.

Haemostasis complex sequence of biochemical
reactions that transform liquid blood into a gel.
Steps involved..
Vascular constriction occur when d vessel is cutcontraction of smooth muscles.
Formation of platelet plug when d vessel got damaged
its endothelium is lost..so platelets stick on d exposed
collagen fibers. & get activated, swell, protrude
pseudopodia & aggregate themselves to form platelet
plug.
Blood coagulation
Prothrombin + Ca2+ +Thromboplastin
Thrombin
Fibrinogen Fibrin
Fibrin + blood cells Blood clot

Disorders of blood
clotting

Haemophilia

Bleeding disorder, blood doesnt clot normally

excessive bleeding from d wounds.
Bleeding also occur inside d body.

?????? ??
A protein helps in blood clotting called clotting factor is
absent( genes r present on X chromosome)
Haemophilia A Clotting factor VIII is absent
Haemophilia B Clotting factor IX is absent

 Cerebral haemorrhage
Blood vessels in d brain breaks.. Blood flow to
brain. Affects mobility excessive bleeding from d
wounds.

 Thrombosis
Formation of blood clot ( thrombus) in d blood vessel.
Superficial .. In small veins
arterial thro
Venous th
Cerebral.. In cerebral circulation
Pulmonary .. In venous capillaries

ECG

 Electric potentials( cardiac action pot. ) --- spread

into tissues surrounding heart ---- place
electrodes on skin, opposite sides of d heart.----electrical pot. Can b tetected & recorded ( electro
cardiogram).
Equipment electro cardiograph machine
P wave depolarisation of atria
QRS complex depolarisation of ventricle prior to
contraction
T wave repolarisation of ventricles
Atrial repolarisation is not recorded on d ECG.

1. Formation of prothrombin activatorBy 2 path ways

Extrinsic injured tissue releases tissue factor,
thromboplastin.ac 7th factor
Intrinsic operates in d plasma , when blood comes in contact
with viruses / rough surface activates 12.. ? intrinsic
x activator complex. complex of 9a+8a+Pl+Ca2+

2. Prothrombin Thrombin. By 10a. In d presence

of Ca2+, 5a,PL
3. Fibrinogen Fibrin .. ( proteolysis)
Fibrin is stabilized by 13a.

Anticoagulants

Substances that inhibits blood clotting.

Heparin prevents activation of prothrombin
thrombin
Antithrombin
3 ways of action
1. Endothelial cells secrete tissue factor pathway
inhibitor inhibits 7a
2. Thrombin firstly binds to thrombomodulin & then with
Protein C..activated protein C( vt k & prtn S is
needed) inhibits 7a & 5a.
3. Antithrombin 3 inhibits thrombin, 9a,10a,11a & 12a.
AT 3 works in d presence of heparin.

Disorders of clotting

Haemophilia excessive bleeding from d wounds.

H..A classic X linked disorder, deficiency of factor 8.
HB (9 th factor deficiency
Cerebral haemorrhage
Blood vessels in d brain breaks.. Blood flow to
brain. Affects mobility
Thrombosis
Formation of blood clot ( thrombus) in d blood vessel.
Superficial .. In small veins
arterial thro
Venous th
Cerebral.. In cerebral circulation
Pulmonary .. In venous capillaries
Embolism - if d clot travels in d blood

Haemodynamic Principle

Haemodynamics is d study of interrelationships between

pressure , flow & resistance &other basic physical
principles of blood circulation.
Relationship btwn P, blood flow & R
Blood flow Amount of blood that passes a given point in d
circulation in a given period of time. 2 types of blood flow
Laminar blood flows in stream lines & in concentric layers.
Turbulent blood flows in all direction & continuously mixed.
Blood flow Q= P/R
P = pressure difference btwn d 2 ends of blood vessel.
R = resistance, delays blood flow

Re/Reynolds no. measure of the tendency for turbulent flow.

Re = V.d / N/p
V = velocity of blood flow in cm/sec
D = diameter of vessel in cm
n = viscosity
P = density
Blood pressure exerted by the blood on d wall of d vessels.
exprssed in mm of Hg.
Resistance, cannot b measured directly. if d pressure diff
btwn d 2 points in d vessels is 1mmHg & d flow is 1ml/sec,
then the resistance is 1 peripheral resistance unit ( PRU).
Conductance measure of amount of blood flow that passes
through a vessel in a given time for a given pressure
difference. Expressed as ml/sec./mmHg.
Affected by diameter of d vessel. Conductance of the vessel
will increase in proportion to the 4th power of d diameter of d
blood vessel.

 Critical closing pressure.

If d blood pressure in a blood vessel resistance to
blood flowif d pressure still falls, at a particular
Pressure the blood flow stops completely ,especially
in arterioles. This pressure ..
Vascular distensibility
When BP- Distension of blood vessels occurs & D.
Walls of arteries are stronger than those of veins.ten
times more distensible as arteries.
VD = increase in vol/increase in P original vol.

 Vascular compliance/ capacitance.

Quantity of blood that can be stored in a given portion
of d circulation for each mm Hg pressure rise.
Compliance of vein is 24 times that of its corresponding
artery.

 Circulatory filling pressure

If all blood flow in d circulatory system is stopped
simultaneously and all pressures in d circulation r
brought to equilibrium, that particular pressure is
called cir. It determines the rate of blood flow
into d R atrium of heart. which in turn determins
cardiac output.
Delayed compliance
Its d increased pressure in d vessel due to increased
volume. Gradually d vessel loses much of this pressure
due to d stretch of d vessel.
Vessel having constantly increased pressure
progressively enlarges.
Delayed compliance occurs slightly in arteries, but to a
greater extent in d veins.

Starlings Law of heat

When d rate at which blood flows into d heart from d
veins (venous return) changes, the heart
automatically adjusts its output to match inflow.
The more blood the heart receives the more it pumps.
Cardiac output is controlled by the properties of
cardiac muscle cells.
According to E.M Starling d energy of contraction of
ventricular muscles depends on d length of muscle
fibers during contraction. The force of contraction
can b increased by stretching d muscles.
If d ventricles r filled to a greater extend, then d
subsequent systolic contraction is greater and a
greater stroke volume is resulted

Cerebral circulation
Blood flow within d brain cerebral circulation.
Brain( 2% of body wt) . Receieves 15% of d cardiac
output
Brain - white matter ( 60%), grey matter ( 40%)
Cerebral flow 750ml/min/100gm.
Critical flow level 18ml/min/100gm
Cerebral vessels r not end arteries They anastomose ( branched & connected to other
arteries).

 The arterial supply

Blood enters cranium through 4
vessels.
2 internal carotid each divides
into 2 middle & anterior
cerebral arteries
2 vertebral arteries combines
basilar arterydivides2
posterior cerebral arteries
The inter communicating
branches unite d 6 arteries
on 2 sides forming Circle of
Willis.
Basilar artery supplies
occipital lobes, cerebellum,
pons, medulla
Internal carotid artery
supplies upper brain stem &
remaining parts of cerebral
hemispheres.

The venous drainage

Superficial veins , deep
veins are
interaconnected & open
into large cerebral
venous sinuses.
These sinuses are superior sagittal,
inferior sagittal,
cavernous, straight..
unite to form 2
transverse sinuses &
continuous with 2
internal jugular veins.

Regulation of cerebral circulation

? The way to increase blood flow to the brain.
As cranium is a rigid box amount of blood flows into d
brain cannot be increased furtherthe only way to
increase .is by raising the velocity of blood flow
through it
Cerebral vessels havent any well organized vasomotor
control
Cerebral flow is regulated by cerebral autoregulation Adjusting the general blood pressure through the sinoaortic mechanism
Regulating the lumen of the cerebral vessels.
1. Myogenic response of smooth muscle
2. Metabolic factors CO2 , H+ , O2 , substances
released from astrocytes. If CO2 . Cerebral
blood flow

Cerebrospinal Fluid

Capacity of cerebral cavity( enclosing brain & spinal

cord) is 1600 1700ml. Out of which 150 ml is
occupied by CSF.
Produced by
Choroid plexus ( seen on d wall of ventricles of brain)
Ependymal cells (lining d ventricles)
Brain tissue

 CSF is present in
Ventricles of brain
In d cisters around d outside of d brain
Central canal of spinal cord
Subaracnoid space around brain & spinal cord
All these chambers are interconnected with one another
& thus maintains d pressure of d fluid at a constant
level.
Normal pressure in d CSF system is 130 mm of water,
may ranges from 65 195 mm of water.

 Functions of CSF
Protection - Acts as a cushion for d brain, brain floats
in d CSF( sp. Gravity is same) (protect from contre
coup injury)
Acts as a fluid buffer provides optimum conditions to
neurons.O2, Glucose, PH, Temperature
It regulates d total volume of cranium.
If blood volume of brain - CSF drains away
- more CSF is retained
there.
Helps in d removal of wastes from d brain.. Lactate,
H+, CO2
Its the medium of transport of nutrients to d nervous
system.

Blood Brain Barrier

A semipermeable membrane separating the blood

from the cerebrospinal fluid, and constituting a barrier
to the passage of cells, particles, and large molecules.
Its formed of 2 layers
Endothelial cells of brain tissue, capillaries joined by
tight junctions.
Above this layer a complete sheath is formed by foot
processes of astrocytes.

 Its present,,,,
At d choroid plexus
At d tissue capillary membranes ( except at posterior pituitary, some
areas of hypothalamus, pineal gland, area of postrema in medulla.
Permeability of BBB
Water, urea & gases diffuses through BBB
Protein by pinocytosis
Sugars(hexoses) & anino acids carrier mediated transport
Its permeable to H2O, CO2, O2, alcohol, anesthetics
Highly permeable to Na, Cl, K
Impermeable to plasma proteins & non lipid soluble organic molecules.
Functions
Excludes particles larger than 0.5 0.7 micron D
Protects brain from harmful substances in blood as well as
endogenous & exogenous toxins
It prevents escape of neurotransmitters into circulation.
It maintains d constant level of Na+, K+, H+, Ca2+ thus Protects
cortical neurons that r sensitive to ionic changes.

Clinical importance
Selection of drugs during the treatment of
meningitis.
( sulpha & erythromycin can cross BBB )
Localization of pathological area BBB breaks down
in d area of irradiation, infection or tumor.
BBB also breaks down by sudden increase in BP or
by IV administration of hypertonic fluids.

Blood types
ABO System by Carl Landsteiner

? Is Agglutination/ clumping process in transfusion

reactions.

Rh Blood group System

It is the second most importantblood groupsystem,

after ABO.
TheRh blood groupsystem consists of 50
definedblood-groupantigens, among which the five
antigens C,D E, c, d and e are the most important.
Type D antigen is prevalent in d population & more
antigenic so a person who has this Ag isRhpositive ,
where as a person who doesnt have D is
Rhnegative.
Erythroblastosis foetalis

Blood Transfusion
Transfer of blood from one person to another / from
one animal to another of the same species is called
as blood transfusion.

Blood Disorders
Jaundice
Impart yellowish tint to skin , deep tissues.
Conjugated & non conjugated bilirubin in extra cellular fluid.
Conj. Bilirubin N level 0.5 mg/dl may upto 40mg/dl.
Causes
destruction of RBC (hemolytic)
Block in d bile duct ( Obstructive)
Hemolytic
Liver functions not impaired, but liver cells do not excrete
bilirubin as quickly as it is formed.. So conc. of plasma
bilirubin
Obstructive
Gall stones, Cancer, hepatitis
Rate of formation of bilirubin is normal.But conc. of
conjugated bilirubin( non conju conju) is excess in d
blood...when Bile canaliculi breaks / bile reaches d lymph

 Physiologic Jaundice normal jaundice noticed in

babies just after delivery large amt of RBCs r
destroyed & d liver couldnt handle this much
load.
Pathological Jaundice blood incompatability/
hepatitis/bile duct block/ infections / cirrhosis

ESR Erythrocyte Sedimentation Rate

Blood + anticoagulant narrow
graduated tube
RBC settles down at d bottom
.denser
Rate of sedimentation hw
quickly it settles down in d tube/
hr
N range , Adult 15 20 mm/ hr
Children 10 13
Other factors which rate of
sedimentation
Inflammation/ infection /
autoimmune diseases../ cancer
Proteins ( liver & immune
system) .. Stick together RBCs
.
Help monitor tuberculosis, tissue
death, arthritis
Generally it is high in d second
trimester of pregnancy

ECG