Physiology of Blood. Dr. Hiwa S. Namiq

Transcription

1 Physiology of Blood Dr. Hiwa S. Namiq January 2019

2 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 acidbase buffering power of whole blood 11 January 2019

3 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. 11 January 2019

4 Areas of the body that produce RBC Period of Gestation/ or at birth Early weeks Middle trimester Last month of gestation and after birth Age 5 Age 20 Area that produce RBC Yolk sac Liver, spleen and lymph nodes Exclusively in the bone marrow BM of all bones BM of long bones (except tibiae and humeri) Beyond 20 Membranous bones 11 January 2019

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6 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. 11 January 2019

7 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 11 January 2019

8 Regulation of Red Blood Cell Production Role of Erythropoietin 10% 90% 11 January 2019

9 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 B 12 absorption. 11 January 2019

10 Total iron quantity Iron Metabolism 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% 11 January 2019

11 The Pathway of Iron Absorption, Transport, and Storage ferrous ferric 11 January 2019

12 The Life and Death of Erythrocytes 11 January 2019

13 Anemias 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. 11 January 2019

14 Types of Anemia Inadequate nutrition (Iron-deficiency anemia) Blood loss anemia (acute or chronic blood loss). Aplastic anemia (excessive X ray radiation, chemicals and drugs). 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). 11 January 2019

15 Effects of anemia Decrease blood viscosity Increase blood flow to the tissues Peripheral blood vessel dilatation Increase cardiac out put Increase pumping workload on the heart During exercise, cardiac failure may occur. 11 January 2019

16 Polycythemia It means increase in the total number of RBCs. Types of polycythemia: 1. Secondary polycythemia (High altitudes, cardiac failure) red cell count rises to 6 7 million cells/mm 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. 11 January 2019

17 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. 11 January 2019

18 Leukocytes And Resistance of the body to infection

19 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.

20 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).

21 Neutrophil Basophil Eosinophil Monocyte Lymphocyte

22 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)

23 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.

24 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.

25 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.

26 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).

27 Formation of antibodies and sensitized T-lymphocytes by a lymph node in response to antigen.

28 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.

29 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.

30 Specific for Ab. Binds to a particular type of Ag Structure of immunoglobulin. Determines: 1.Diffusivity 2.Adherance within tissues 3.Attachment to complement sys

31 IgG IgE IgM IgA IgD General classes of antibodies A bivalent antibody. 75 per cent of all antibodies. important when the body is subsequently (secondary response) exposed to the same antigen. Small percentage of the antibodies, especially involved in allergy. Large share of the antibodies during the primary response, have 10 binding sites (exceedingly effective in protection), there are not many IgM antibodies. Found in secretions of digestive, respiratory, genitourinary systems as well as in milk and tear. 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)

32 Mechanisms of action of antibodies Direct action and indirect (activation of complement system) Direct 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.

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34 T-Lymphocytes and Hemostasis

35 T-lymphocytes Three major groups of T-lymphocytes: Helper T cells Cytotoxic T cells Suppressor T cells.

36 Helper T-cells Produce lymphokines AIDS

37 Cytotoxic T cells Directattack cells Killer cells Hole-forming protein perforins Fluid flow Swollen, dissolve Suppressor T cells Suppresses Cytotoxic cells from causing excessive immune reactions that might be damaging to the body s own tissues

38 Injecting toxins Toxic nature has been destroyed with chemicals Tetanus and botulism Immunization (Active) Injecting dead organisms No longer capable of causing disease Typhoid fever, whooping cough and diphtheria. Achieving acquired immunity against specific diseases Infecting with liveattenuated organisms Poliomyelitis, yellow fever, measles and smallpox.

39 Hemostasis and Blood coagulation

40 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.

41 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.

42 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.

43 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

44 Clotting in a traumatized blood vessel

45 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.

46 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.

47 Conversion of prothrombin to thrombin and polymerization of fibrinogen to form fibrin fibers

48 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).

49 Lysis of Clots (Fibrinolysis) Activation of plasminogen to form plasmin - When a clot is formed, a large amount of plasminogen is trapped in the clot along with other plasma proteins. In addition to promoting 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.

50 Mechanism for dissolving blood clots (clot lysis)