Physiology of Blood

Blood in the system of body fluids

Blood content

liquid portion or plasma (52-64%) cells or formed elements (36-48%):

erythrocytes (red blood cells), leucocytes (white blood corpuscles), and thrombocytes (blood platelets).

Definite volumetric correlation between the plasma and formed elements is haematocrit (36-48%)

Blood plasma composition 90 to 92 % water 8 to 10 % dry matter, mainly proteins and salts. The total protein content is 7 to 8 %; albumins

(about 4.5 per cent), globulins (2 to 3 %), and fibrinogen (0.2-0.4 %).

non-protein nitrogenous compounds (amino acids and polypeptides), and products of protein decomposition (urea, uric acid, creatine, creatinine).

nitrogen-free organic substances are glucose 4.4-6.6 mmol/1,neutral fats and lipoids.

Mineral substances - 0.9 %. (Na+, K+, Ca2+ cations and Cl-, HPO42-, and HCO3- anions).

Functions of plasma proteins

Create oncotic pressure Buffer system Create blood viscosity Partake in blood coagulation Partake in humoral immunity Transport function Nutritive function

Parameters of blood homeostasis

Viscosity (5,0) pH (7,4 for arterial, 7,35 for venous) Osmotic pressure (7,6 atm) Glucose content (3,3-5,5 mmol/l) Protein content (65-85 gr/l) Ionic content

Erythrocytes in blood capillaries

Erythrocytes in blood tube

Sickle cell disease

Mature neutrophil

eosinophil

basophil

Phases of haemostasis

Vascular platelet haemostasis

Coagulation haemostasis

Fibrinolysis

Stages of vascular platelet haemostasis

1. Reflex spasm of the damaged vessels (serotonin, adrenaline, noradrenalin).

2. Platelet adhesion to the site of trauma due the fact that a negative electric charge of the vessel at the site of damage is altered to a positive one. Usually takes 3-10 sec.

3. The reversed platelet aggregation begins nearly simultaneously with adhesion. The 'extrinsic' ADP released from the damaged vessel and the 'intrinsic' ADP released from the platelets and erythrocytes are the main stimulators of this process. A loose platelet plug is formed through which blood plasma leaks.

4. In the irreversible platelet aggregation a platelet clot becomes impermeable to blood.

This is due to the action of thrombin that causes destruction of the platelet membrane('viscous metamorphosis' of platelets).

All the platelet factors and the new amounts of ADP are released to increase the size of a platelet thrombus.

The release of the platelet factor 3 gives rise to the production of platelet prothrombinase switching on the mechanism of coagulation haemostasis.

A small number of fibrin filaments is formed on platelet aggregations whose mesh work retains erythrocytes and leucocytes.

5. Retraction of a platelet thrombus implies its thickening and fixation at the site of damage at the expense of thrombosthenin contraction.

Coagulation haemostasisPhase I. Formation of prothrombinase.

The extrinsic (tissue) and intrinsic (blood) mechanisms are distinguished in this process.

The extrinsic mechanism is triggered by tissue thromboplastin which is released from the damaged vessel and surrounding tissues. Tissue prothrombinase takes 5-10 sec for its formation.

In the intrinsic mechanism thromboplastin and other factors are transported by blood proper. Blood prothrombinase is formed in 5-10 min.

Phase II. Thrombin formation

this process takes 2-5 sec. This rate can be explained by the

fact that prothrombinase adsorbs prothrombin and converts it into thrombin on its surface.

This process proceeds in the presence of factors V, X and Ca2+.

Phase III. Fibrinogen is converted into fibrin.

This process has three stages. In the first stage soluble fibrin monomer is

formed from fibrinogen under the action of thrombin.

In the second stage fibrin monomers are polymerized under the action of Ca2+ ions with the formation of fibrin polymer (soluble fibrin S).

The third stage involves formation of the final or insoluble fibrin

FIBRINOLYSIS

Fibrin breakdown is effected by the proteolytic enzyme plasmin

it is present in the plasma as proenzyme plasminogen.

Blood and tissue activators are required for the conversion of plasminogen into plasmin.

The fluidity of blood is preserved due to (1) smooth surface of vascular endothelium

hinders blood clotting; this prevents activation of Hageman factor and platelet aggregation;

(2) the vessel walls and formed elements have negative charges due to which blood cells are pushed away from the vascular walls;

(3) vessel walls are covered with a thin layer of soluble fibrin that adsorbs active coagulation factors, especially thrombin;

(4) blood coagulation is prevented due to a high rate of blood flow so that the coagulation factors cannot be accumulated in one place;

(5) natural anticoagulants maintain blood fluidity.

BLOOD GROUPS

In 1901 K. Landsteiner and in 1903 J. Jansky found that erythrocytes glue together when the blood of different persons is mixed up.

In 1930 K. Landsteiner was awarded a Nobel Prize for discovery of the blood groups.

More than 200 various agglutinogens have been discovered in human erythrocytes

140 of which are united into 20 systems (groups), while the rest are either common or individual.

This determines the remarkable unique nature of antigens, so every man has his own blood group.

These agglutinogen systems are distinguished from the ABO system in that they have no natural agglutinins in plasma similar to α and β -agglutinins.

Antigens on erythrocyte membrane

ANTIGENES STRUCTURE

B antigen A antigenH antigen (O blood group)

Ig G STRUCTURE

Ig M STRUCTURE

Anti А(α) & anti В(β) antibodies are Ig M, which have 10 cites to bind antigenes

Only in АВО system they are ready antibodies Anti А(α) & anti В(β)

There are no antigens on erythrocytes to the antibodies present in blood!

ANTIBODIES FORMATION

No antibodies in newborns. They are formed during the first 3-

4 months. Their max concentration is reached to 13-14 years.

Why are they formed?

Hypothesis on the mechanisms of antibodies formation

Antibodies are formed to the antigens of food or bacteria present in the intestines.

There are bacteria in the intestines with the same antigens (А or В) as erythrocytes

If there is just B antigen in the tested blood, this must be В(III) group

A or B or both antigens present B antigen

presentno A antigen

If there is just A antigen in the tested blood, this must be A(II) group

A or B or both antigens present

A antigen present

no B antigen

If there are both A & B antigens in the tested blood, this must be АВ (IV) group

A or B or both antigens present

A antigen present

B antigen present

If there are no antigens in the tested blood, this must be O (I) group

antigens A & B are both absent no B antigen no A antigen

A or B or both antigens present

no B antigen no A antigen

Which blood group is this?

In blood transfusion АВО & Rh systems are taken into account because:

These antigens are most widely spread;

They have the greatest agglutinating capacity;

There are ready antibodies in АВО system & first transfusion of incompatible blood would cause haemotransfusion.

Consequences of blood clotting in the vessels:

Capillaries are blocked with erythrocyte clots;

Kidney filter is damaged; Haemoglobin in blood plasma

increases blood viscosity, BP increases, heart rate increases

Toxins released cause fever, sweating

Rh system

Blood which erythrocytes have D antigen is called rhesus-positive Rh+ (85% of all the population).

The rest 15% don’t have this antigen and their blood is called rhesus negative Rh-.

Rh system

Antibodies to Rh-factor arte not inborn, they can be formed after Rh(+) blood is transfused to Rh(-) recepient.

These antibodies are IgG, incomplete antibodies, so they can penetrate blood-tissue barriers.

Ig G STRUCTURE

Rhesus conflicts.

In blood transfusion: first blood transfusion of Rh(+) blood to Rh(-) recipient would cause only antibodies formation. There is no agglutination until antibodies are formed.

Second transfusion of the Rh(+) blood would cause agglutination because antibodies (аnti D aglutinins) were already formed.

Rhesus conflicts.

In pregnancy : if mother is Rh(+) & fetus is Rh(-) .

Develops during second pregnancy. Mother’s antibodies can pass haemato-placentar barrier & cause erythrocytes agglutination in fetus.