Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body...

56
Physiology of Blood Dr. Hiwa S. Namiq 6-11-2019 23 November 2019

Transcript of Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body...

Page 1: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Physiology of Blood

Dr. Hiwa S. Namiq 6-11-2019

23 November 2019

Page 2: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Introduction

Red blood cells (erythrocytes)

• The major function of RBC is to transport Hb which in turn carries oxygen from lungs to the tissues.

• On the other hand, water of blood is able to transport enormous amount of CO2 (in the form of bicarbonate-HCO3_) from tissues to the lungs with the aid of carbonic anhydrase (an enzyme found on RBC) that catalyzes the reversible reaction between CO2 and H2O to form carbonic acid (H2CO3).

• The hemoglobin in the RBCs is an excellent acid-base buffer, so the RBCs are responsible for most of the acid-base buffering power of whole blood

23 November 2019

Page 3: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Shape and size • RBCs are biconcave discs having a mean diameter

of about 7.8 micrometers and a thickness of 2.5 micrometers at the thickest point.

• The shape changes remarkably and can be deformed into any shape.

• In normal men, the average number of red blood cells per cubic millimeter is 5,200,000 (±300,000); in normal women, it is 4,700,000 (±300,000).

• The whole blood contains an average of 15 gm Hb for men and 14 gm for women per each dl of blood .

23 November 2019

Page 4: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Areas of the body that produce RBC

Period of Gestation/ or at birth Area that produce RBC

Early weeks Yolk sac

Middle trimester Liver, spleen and lymph nodes

Last month of gestation and after birth

Exclusively in the bone marrow

Age 5 BM of all bones

Age 20 BM of long bones (except tibiae and humeri)

Beyond 20 Membranous bones

23 November 2019

Page 5: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

23 November 2019

Page 6: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

23 November 2019 Function of the erythropoietin mechanism to increase production of

red blood cells when tissue oxygenation decreases

Tissue Oxygenation Is the Most Essential

Regulator of Red Blood Cell Production.

Conditions that decrease the quantity of oxygen

transported to the tissues ordinarily increase the

rate of RBC production:

Anemia

High altitude

Low blood volume

Chronic cardiac failure and lung disease

Erythropoietin Regulates Red Blood Cell Production

Page 7: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Regulation of Red Blood Cell Production

• The blood cells are formed in the bone marrow from a single type of cell called the pluripotential hematopoietic stem cell ( from which all the cells of the circulating blood are derived).

• The principal stimulus for red blood cell production in low oxygen states is a circulating hormone called erythropoietin.

• In the absence of erythropoietin, hypoxia has little or no effect in stimulating red blood cell production. 23 November 2019

Page 8: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• About 90 per cent of all erythropoietin is formed in the kidneys (especially renal tubular epithelial cells); the remainder is formed mainly in the liver.

• Erythropoietin stimulate proerythroblast production by the bone marrow and within about 5 days new red cells appear in the circulation.

• Patients with renal diseases that destroy the kidneys easily develop anemia.

• Vitamin B12 and folic acid (maturation factors) are especially important for final maturation of the red blood cells which are essential for the synthesis of DNA

23 November 2019

Page 9: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

23 November 2019

Regulation of Red

Blood Cell

Production—Role

of Erythropoietin 90%

10%

Page 10: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• Maturation failure occurs when there is

deficiency of either vitamin B12 or folic acid (Megaloblastic anemia) .

• In pernicious anemia (atrophic gastric mucosa), the parietal cells of gastric mucosa fail to produce intrinsic factor (a glycoprotein) which is essential for V B12 absorption.

23 November 2019

Page 11: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Total iron quantity 4 – 5 grams

HB 65 %

RES (mononuclear

phagocyte system-in LN

and spleen) and liver

(stored)

15-30%

Myoglobin 4%

Various heme compound 1%

Transferrin (bound) 0.1% 23 November 2019

Iron Metabolism

Page 12: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

The Pathway of Iron Absorption, Transport, and Storage

23 November 2019

ferric

ferrous

Page 13: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

23 November 2019

Iron transport and metabolism

Page 14: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

23 November 2019

The Life and Death of Erythrocytes

Page 15: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Anemias

23 November 2019

Anemia means deficiency of

hemoglobin in the blood, which

can be caused by either too few

red blood cells or too little

hemoglobin in the cells.

Page 16: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Types of Anemia

23 November 2019

• Inadequate nutrition (Iron-deficiency anemia)

• Blood loss anemia (acute or chronic blood loss). The

body replaces the fluid in 1 to 3 days, but the RBC

concentration returns to normal within 3 to 6 weeks. .

• Aplastic anemia (lack of functioning bone marrow due

to high-dose radiation (X ray) radiation, chemicals,

drugs and autoimmunity) .

• Megaloblastic anemia (pernicious anemia, total

gastrectomy and intestinal sprue).

• Hemolytic anemia (hereditary spherocytosis, sickle cell

anemia (HB S), erythroblastosis fetalis Rh –ve mother

born to Rh +ve baby).

Page 17: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Effects of anemia • Decrease blood viscosity. The resistance to blood flow in

the peripheral blood vessels decrease, so greater than normal quantities of blood flow through the tissues and return to the heart and greatly increasing cardiac output.

• Hypoxia resulting from diminished transport of oxygen by the blood causes the peripheral tissue blood vessels to dilate, followed by increased blood flow to the tissues

• Thus the main effect of anemia is greatly increased cardiac output and increased pumping workload on the heart.

• During exercise, which greatly increases tissue demand for oxygen, extreme tissue hypoxia results and acute cardiac failure may ensue 23 November 2019

Page 18: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Polycythemia • It means increase in the total number of RBCs.

• Types of polycythemia:

1. Secondary polycythemia (High altitudes (14,000 to 17,000 feet) and cardiac failure. The red cell count rises to 6 – 7 million cells/mm3.

2. Polycythemia vera (erythremia) red blood cell count may reach 7 to 8 million/mm3. It is caused by genetic abnormality. The viscosity of the blood sometimes increases from the normal of 3 times the viscosity of water to 10 times that of water.

23 November 2019

Page 19: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Effects of Polycythemia

• Increase in blood viscosity.

• Blood flow become sluggish.

• Venous return not change.

• Blood pressure is elevated in one third of patients.

• Skin color later becomes bluish (cyanotic) because the amount of deoxygenated blood is increased.

23 November 2019

Page 20: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Leukocytes And

Resistance of the body to infection

Page 21: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

The living body has three lines of defense against pathogens:

• 1.External barriers (skin and mucous membranes) which are impenetrable to most of the pathogens that daily assault us (Innate immunity).

• 2.Antimicrobial proteins (inflammation, fever)(innate immunity). These mechanisms are

Present from birth

Effective against a wide range of pathogens

Work even against pathogens to which the body has never been exposed.

• 3. The specific immune system (Acquired immunity), which not only defeats a pathogen but leaves the body with a “memory” of it.

Page 22: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Leukocytes (White Blood Cells)

• The leukocytes, also called white blood cells, are the mobile units of the body’s protective system. They are formed and matured partially in the

– Bone marrow (granulocytes and monocytes and a few lymphocytes)

– And partially in the lymph tissue (lymphocytes and plasma cells).

Page 23: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Neutrophil Basophil Eosinophil

Monocyte Lymphocyte

Page 24: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

LIFE SPAN OF WHITE BLOOD CELLS • After being released from the bone marrow, the

granulocytes normally remain 4 to 8 hours in circulation and 4 to 5 days in tissues.

• At times of tissue infection, their life span is often shortened to only a few hours because they are destroyed in the infected area.

• The monocytes remain 10 to 20 hours in blood and then pass into the tissues. Once in the tissues, they swell to much larger sizes to become tissue macrophages, and they can live for months unless destroyed while performing phagocytic functions

23 November 2019

Page 25: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• Lymphocytes enter the circulatory system continually, along with drainage of lymph from the lymph nodes and other lymphoid tissue. After a few hours, they pass out of the blood back into the tissues by diapedesis. Then they re-enter the lymph and return to the blood again and again

• The platelets in the blood are replaced about once every 10 days

23 November 2019

Page 26: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Leukopenia and leukemia

• Leukopenia is a clinical condition in which the bone marrow produces very few WBCs. This condition leaves the body unprotected against many bacteria and other invaders

• leukemia is uncontrolled production of WBCs caused by cancerous mutation of a myelogenous or lymphogenous cell. It is usually characterized by greatly increased numbers of abnormal WBCs in the circulating blood.

23 November 2019

Page 27: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Resistance of the body to infection

Immunity It is the ability of body to resist almost all types of

organisms or toxins that tend to damage the tissues

and organs.

Types of immunity:

1. Innate immunity (non-specific immunity)

2. Acquired immunity (specific immunity) • Much of immunity is acquired immunity that does not develop until after

the body is first attacked by a bacterium, virus, or toxin; often weeks or

months are required for the immunity to develop.

• While innate immunit results from general processes, rather than from

processes directed at specific disease organisms

Page 28: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Acquired immunity (specific)

• The body develops this immunity after being first attacked by a bacterium, virus, or toxin, and often requiring weeks or months to develop.

• Acquired immunity is caused by a special immune system that forms antibodies and/or activated lymphocytes that attack and destroy the specific invading organism or toxin.

Page 29: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Types of acquired immunity

• Humoral immunity or B-cell immunity. In

which the B-lymphocytes produce circulating antibodies.

• Cell-mediated immunity or T-cell immunity. In which the T-lymphocytes produce activated or sensitized T-cells.

Page 30: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Both types of acquired immunity are initiated by

antigens and they are the product of body's

lymphocytes.

Location of lymphocytes: 1. Lymph nodes (most extensively)

2. Lymphoid tissues (spleen, submucosal areas of

the gastrointestinal tract, thymus, and bone

marrow).

Both of them need to be preprocessed.

Page 31: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• The T-lymphocytes first migrate to and are

preprocessed in the thymus gland, and thus

they are called “T” lymphocytes

• While B-lymphocytes are preprocessed in the

liver during mid-fetal life and in the bone marrow in late fetal life and after birth. They are first discovered in birds (Bursa of Fabricius).

Page 32: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Formation of antibodies and sensitized T-lymphocytes by a lymph node in response

to antigen.

Page 33: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• Formation of memory cells by B and T cells • Subsequent exposure to the same antigen will cause a much

more rapid and much more potent response in the second time.

• This is due to formation of memory cells by both T and B lymphocytes.

Time course of antibody response to a

primary injection of antigen and to a

secondary injection several weeks later

Page 34: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Nature of the antibodies

• The antibodies are gamma globulins called immunoglobulins (Ig).

• All the immunoglobulins are composed of combinations of light and heavy polypeptide chains.

• Each chain has a variable and a constant portion.

Page 35: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Structure of immunoglobulin

.

Specific for Ab. Binds

to a particular type of

Ag

Determines:

1.Diffusivity

2.Adherance within tissues

3.Attachment to complement sys

Page 36: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

IgG

• A bivalent antibody. 75 per cent of all antibodies. important when the body is subsequently (secondary response) exposed to the same antigen.

IgE

• Small percentage of the antibodies, especially involved in allergy.

IgM

• Large share of the antibodies during the primary response, have 10 binding sites (exceedingly effective in protection), there are not many IgM antibodies.

IgA • Found in secretions of digestive, respiratory, genitourinary systems

as well as in milk and tear.

IgD

• Present on the surface of many B lymphocytes and the surface of basophil and mast (activates them to secrete antimicrobial proteins during respiratory immune response)

General classes of antibodies

Page 37: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Direct action

•Agglutination, in which multiple large particles with

antigens on their surfaces, such as bacteria or red cells,

are bound together into a clump.

•Precipitation, in which the antibody forms a complex

with the antigen (such as tetanus toxin) and makes it

insoluble and precipitates.

•Neutralization, in which the antibodies cover the toxic

sites of the antigenic agent.

•Lysis, in which potent antibodies are directly attacking

membranes of cellular agents causing their rupture.

Mechanisms of action of antibodies

Direct action and indirect (activation of complement

system)

Page 38: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within
Page 39: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

T-Lymphocytes and

Hemostasis

Page 40: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

T-lymphocytes

Three major groups of T-lymphocytes:

• Helper T cells

• Cytotoxic T cells

• Suppressor T cells.

Page 41: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Produce lymphokines

AIDS

Helper T-cells

Page 42: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Direct-attack cells

Killer cells

Hole-forming protein

perforins

Fluid flow

Swollen, dissolve

Cytotoxic T cells

Suppressor T cells

Suppresses Cytotoxic cells from causing excessive

immune reactions that might be damaging to the

body’s own tissues

Page 43: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Injecting toxins

• Toxic nature has been destroyed with chemicals

• Tetanus and botulism

Injecting dead

organisms

• No longer capable of causing disease

• Typhoid fever, whooping cough and diphtheria.

Infecting with live-

attenuated organisms

• Poliomyelitis, yellow fever, measles and smallpox.

Immunization

(Active)

Achieving acquired immunity

against specific diseases

Page 44: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

PASSIVE IMMUNITY • Temporary immunity can be achieved in a person

without injecting any antigen. It can be achieved by infusing antibodies, activated T cells, or both obtained from the blood of someone else or from some other animal that has been actively immunized against the antigen.

• Antibodies last in the body of the recipient for 2 to 3 weeks, and during that time, the person is protected against the invading disease. Activated T cells last for a few weeks if transfused from another person but only for a few hours to a few days if transfused from an animal.

23 November 2019

Page 45: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Hemostasis and

Blood coagulation

Page 46: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Hemostasis means prevention of blood loss. If a vessel is ruptured several mechanisms operate to achieve hemostasis:

• Vascular constriction.

• Formation of a platelet plug.

• Formation of a blood clot as a result of blood coagulation.

• Growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.

Page 47: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Platelets • Platelets (thrombocytes) are minute discs 1 to 4

micrometers in diameter, formed in the bone marrow from megakaryocytes.

• The normal concentration of platelets in the blood is between 150,000 and 300,000 per microliter. It has a half-life in the blood of 8 to 12 days

• Platelets have many functional characteristics of whole cells, even though they do not have nuclei and cannot reproduce.

Page 48: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

The cytoplasm contains:

1. Actin and myosin molecules (contractile proteins).

2. Endoplasmic reticulum and the Golgi apparatus residuals (store calcium ions).

3. Mitochondria (forming adenosine triphosphate (ATP) and adenosine diphosphate (ADP).

4. Prostaglandins (vascular and tissue reaction)

5. Fibrin-stabilizing factor

6. Growth factor (causes endothelium, vascular smooth muscle, and fibroblasts to multiply and grow.

Page 49: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Platelet plug formation

Contact of platelets with exposed collagen

Contractile proteins cause release of granules (contain active factors)

Stick to VWF, secret ADP and TX-A2, activating nearby platelets

Platelet plug formation + fibrin threads

Page 50: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Clotting in a traumatized blood vessel

Page 51: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Blood clotting Mechanism of blood coagulation

1. In response to rupture of the vessel or damage to the blood itself, a complex cascade of chemical reactions occurs in the blood involving more than a dozen blood coagulation factors. The net result is formation of a complex called prothrombin activator.

2. The prothrombin activator catalyzes conversion of prothrombin into thrombin.

3. The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that enmesh platelets, blood cells, and plasma to form the clot.

Page 52: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• Prothrombin is formed continually by the liver.

• Vitamin K is required by the liver for normal formation of prothrombin. Therefore, either lack of vitamin K or the presence of liver disease can decrease the prothrombin level so low that a bleeding tendency results.

Page 53: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Conversion of prothrombin to thrombin

and polymerization of fibrinogen to form

fibrin fibers

Page 54: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Prevention of intravascular clotting

Factors that prevent intravascular clotting

• Endothelial surface factors which are:

1. Smoothness of the endothelial cell surface.

2. Presence of a layer of glycocalyx on the endothelium which repels clotting factors and platelets.

3. Presence of thrombomodulin which binds thrombin.

• Antithrombin action of fibrin and antithrombin III

• Heparin (anticoagulant) (a polysaccharide produced by mast cells and basophils, specially found in the pericapillary tissues surrounding the lungs and the liver).

Page 55: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

• When a clot is formed, a large amount of plasminogen is trapped in the clot along with other plasma proteins.

• In addition to promote clotting, factor XII catalyzes the formation of a plasma enzyme called kallikrein.

• Kallikrein, in turn, converts the inactive protein plasminogen into plasmin, a fibrin-dissolving enzyme that breaks up the clot.

• In fact, many small blood vessels in which blood flow has been blocked by clots are reopened by this mechanism.

Lysis of Clots (Fibrinolysis)

Activation of plasminogen to form plasmin -

Page 56: Physiology of Blood - Suli Pharma • Blood loss anemia (acute or chronic blood loss). The body replaces the fluid in 1 to 3 days, but the RBC concentration returns to normal within

Mechanism for dissolving blood clots (clot lysis)