Blood Physiology

1. Blood Physiology By Dr. Abdulhalim Serafi, MB ChB, MSc, PhD, FESC Assistant Professor & Consultant Cardiologist Faculty of Medicine Umm Al-Qura University Makkah Al-Mukarramah Drserafi.com Serafi @uqu.edu.sa

2. Major Components of the Circulatory System Heart Blood vessels Blood

3. Composition of Blood Blood is a specialized connective tissue made of cells or (corpuscles) suspended in a clear yellowish fluid called the plasma. (A) Cellular elements: (formed elements, or cells, or corpuscles): The cellular elements constitute 40 –45% of the total blood volume and are of 3 types: erythrocytes = RBCs (>95%). leukocytes = WBCs. thrombocytes = platelets (cell fragments). (B) Plasma: The plasma constitutes 55-60% of the total blood volume, and it consists of water (90%) and dissolved solutes (10%).

4. The cellular elements constitute 40 –45% of the total blood volume and are of 3 types:a. Red blood cells = red blood corpuscles (RBC) or erythrocytes: mature red blood cells lack nuclei and all sub-cellular organelles. Normally, there are about 5 million RBCs per mm3. When they are decreased the condition is called anemia and when increased, it is called polycythemia.b. White blood cells (WBC) or leucocytes or leukocytes: Normally, there are 4000 to 11000 WBCs per mm3. When they are decreased the condition is called leucopenia and when increased, it is called leucocytosis. c. Thrombocytes or blood platelets - Normally, there are 300000 platelets per mm3. When they are decreased the condition is called thrombocytopenia and when increased, it is called thrombocytosis.

5. Formed Elements of Blood Red blood cells (erythrocytes) White blood cells (leukocytes) granular leukocytes neutrophils eosinophils basophils agranular leukocytes lymphocytes = T cells, B cells, and natural killer cells monocytes Platelets (special cell fragments)

6. Plasma The plasma constitutes 55-60% of the total blood volume, and it consists of water (90%) and dissolved solutes (10%). The later include: a. Organic substances: plasma proteins (7.1%), lipids, hormones, enzymes and nutrients and waste products (2%).) b. Inorganic substances (0.9%) which include the various electrolytes e.g. Na+, Cl-, HCO3-, Ca++, PO4-, etc.

7. Components of Blood Hematocrit 55% plasma 45% cells 99% RBCs < 1% WBCs and platelets

8. Physical Properties of Blood 1. Volume = 7-9% of body weight: 5-6 L in adult males. 4-5 L in adult females. 2. Temperature ~ 100.4 oF (38 oC). 3. The color of blood is red – due to Hb. 4. Blood is opaque due to cellular elements, particularly the RBCs. So, after hemolysis blood becomes transparent. 5. The pH of arterial blood is 7.4 ( venous blood has a slightly lower pH). 6.Viscosity – blood is about 5 times as viscous as water because of cells and plasma proteins (plasma’s viscosity is 2 times that of water). Blood viscosity is important in maintaining arterial blood pressure 7. The net effective colloid pressure of the plasma is 25 mm Hg and is known as the oncotic pressure . 8. Osmolarity of the plasma – 290-300 mosmoles/L

9. Osmolarity NaCl solution of molarity equal to 150 mmol/L has an osmolarity of 300 mosmoles/L because of disassociation to Na+ and Cl. The osmolarities of glucose solutions are equal to their corresponding molarities. Osmolality of the plasma is 290 – 300 mosmoles/L. Iso-osmotic solutions are solutions with the same osmolarity as plasma (e.g. 0.9 % NaCl solution, i.e., 0.9 g of NaCl dissolved in 100 mL of water or 9 g of NaCl dissolved in 1 L of water, has an osmolarity of about 300 mosmoles/L. Hypo-osmotic solutions are solutions with a lower osmolarity than plasma.

10. Major Functions of the Blood 1. Nutrition (by transporting the absorbed food from the GIT to the tissues). 2. Respiration. 3. Excretion (by transporting the waste products from the tissues to the excretory organs e.g. urea and creatinine to the kidneys). 4. Regulation of metabolism (by transporting hormones from various endocrine glands to the tissue and also by regulating their secretion). 5. Regulation of the body temperature. 6. Marinating the acid-base balance. 7. Regulation of water balance. 8. Blood clotting.

11. Plasma Proteins The amount of the plasma proteins averages 7 gm% (6-8 gm%) which are divided as follows: Albumin – 4g/100ml. Globulins – 2.7g/100ml (1, 2, 1, 2). Fibrinogen – 0.3g/100ml. In addition to small amounts of other proteins (e.g. certain hormones, prothrombin and most of the other clotting factors). Site of Plasma Protein Synthesis: All plasma proteins are formed in the liver except the gamma globulins which are formed by plasma cells.

12. A/G Ratio Normally, this ratio is 1.2 The determination of the A/G ratio is important clinically; it can be used as a liver function test. It is increased in cases of congenital agammaglobulineima. It is decreased in cases of advanced liver diseases and severe infections.

13. Functions of Plasma Proteins 1. The effective osmotic pressure in the vascular system is produced 70-80% by albumin because of its greater amount 2. Defense (immunity). 3. Haemostatic function (blood clotting). 4. They share in the production of blood viscosity. 5. They produce up to 15% of the buffering power of the blood 6. Plasma proteins combine loosely with many substances, including hormones. This prevents rapid diffusion of these substances in the tissue spaces or their rapid loss in urine.

14. Characteristics of Erythrocytes * Small, biconcave disk discs with an average diameter of ~ 7.5 microns. * Non-nucleated. * No ribosomes. * No mitochondria. * What type of ATP synthesis can they do? * Life span ~ 120 days (or less). * Normal count averages 5 million/cubic mm.

15. Physiological Factors Affecting Red Cell Count * Age: it is high in newly born infants and low in old individuals * Sex: it s higher in males than in females for two reasons: a. androgens stimulate the production of RBC b. women lose blood via menstration * High altitude

16. Structure of RBC The red blood cells is formed of a mass of cytoplasm enclosed by plasma or a cell membrane. The cytoplasm is formed mostly of hemoglobin (Hb). Each red blood cell contains about 30 picograms of Hb. It also contains electrolytes and several enzymes. The plasma membrane contains glycoproteins and glycolipids. The biconcave shape of the red blood cells is produced by ankyrin and spectrin.

17. Normal, RBC's. They have a zone of central pallor about 1/3 the size of the RBC.). A few small fuzzy blue platelets are seen. In the center of the field are a band neutrophil on the left and a segmented neutrophil on the right.

18. Normal Blood Film:

21. Functions of the RBCs Transport of the respiratory gases Play an important role in producing blood viscosity

22. Factors affecting RBCS formation (erythropoiesis) 1. The bone marrow: A healthy bone marrow is essential for normal hemopoiesis. 2. Diet: The followings must be sufficiently supplied for adequate erythropoiesis: Proteins of high biological values, Iron, Other minerals especially copper and cobalt, All vitamins particularly vitamin B12 and folic acid

23. Factors affecting RBCS formation (erythropoiesis) 3. Blood O2 tension: Erythropoiesis is inhibited when the blood O2 tension increases and stimulated when it is decreased (e.g. at high altitude and in lung diseases). 4. The kidneys: The kidneys secret erythropoietin, which specifically simulate red blood cell formation in the bone marrow. O2 lack stimulates erythropoiesis indirectly through stimulating release of erythropoietin. 5. The liver: It stores vitamin B12 and several minerals required red cell formation specially iron.

24. Pronormoblast Normoblasts

25. Osmotic fragility of the red blood cells A 0.9% NaCl (saline) solution is isotonic with plasma. When red cells are suspended in hypotonic saline, water diffuses into the cells so they swell and may rupture ( = hemolysis). The ability of the red blood cells to resist hemolysis in hypotonic saline solutions determines their osmotic fragility.

26. Causes of hemolysis . 1. Incompatible (mismatched) blood transfusion 2. Snake venom, certain bacterial toxins and some chemicals (e.g. arsenic). 3. Fat solvents e.g. ether. 4. Blood freezing. 5. Hereditary spherocytosis. . 6. Abnormal Hb . 7. GDPD deficiency . 8. Pyruvate kinase deficiency 9. Abnormal immune rections that cause formation of red cell antibodies.

27. Blood grouping and blood transfusion The outer layers of the red blood cell membranes contain certain antigens, which are called agglutinogens. They are chemically glycoproteins and glycolipids. There are two types of such antigens called A & B agglutinogens, and according to the present type, the human blood is divided into the following 4 types or groups: 1. Group A (42%) when only type A is present 2. Group B (9%) when only type B is present 3. Group AB (3%) when both types A and B are present 4. Group O (46%) when both types A and B are absent

28. The plasma contains certain gamma globulins called agglutinins, which are antibodies to the red blood cell agglutinogens. These antibodies are of two types: anti-A and anti-B agglutinins. At birth, the quantity of agglutinins is almost zero. However, they begin to be produced within a few months after birth. Infants develop agglutinins against the agglutinigens not present in their own red blood cells. Thus, Type A subjects develop anti-B agglutinins Type B subjects develop anti-A agglutinins Type AB subjects develop neither Type O subjects develop both

29. Therefore, agglutinogens normally never exist with their corresponding agglutinins, otherwise An antigen-antibody reaction would occur that leads to the dangerous process or red cell agglutination. This occurs in cases of mismatched blood transfusion.

30. Blood Groups and Blood Types

31. The Rh antigen (factor) This is the agglutinogen normally present in the red blood cells of Rhesus monkeys (hence the name Rh). There are 6 varieties known as the C, D, E, c, d, e antigens. These antigens were also discovered in the human red blood cells, particularly the D and d antigens and D has the strongest antigenic effect. They are inherited from both the father and the mother, and D is dominant while d is recessive, so that the genotypes DD and Dd are Rh+ while genotype dd is Rh. The Rh agglutinins are not normally present but they are formed in the plasma of Rh- persons only after exposure to Rh+ blood. The Rh agglutinins have a small size, so they can cross the placenta more easier than the other agglutinins.

32. ABO Blood Typing • With ABO, person makes antibodies (agglutinens) against factors (agglutinogens) he/she does NOT have on his/her cells

33. Blood Type A B AB[1] O[2] Agglutinogens (antigen) Present A B A & B (neither) Makes Agglutinins (antibodies) Against B A (neither) A & B May Receive Blood From: A, O B, O A, B, AB, O O May Give Blood To: A, AB B, AB AB A, B, AB, O Genotype IAIA or IAi IBIB or IBi IAIB ii Rh Factor Present or Absent (A+ or A-) Present or Absent (B+ or B-) Present or Absent (AB+ or AB-) Present or Absent (O+ or O-) ABO Blood Types [1] Universal Recipient [2] Universal Donor

34. Blood Type Rh+ Rh- Agglutinogen D (antigen proteins) Present or Absent Present Absent Makes Agglutinins (antibodies) Against Agglutinogen No Yes[1] May Receive Blood From: Rh+ or Rh- Rh-[2] May Give Blood To Without Reaction[2]: Rh+ Rh+ or Rh‑ Genotype DD or Dd dd Rh Blood Types [1]Only makes antibodies (agglutinens) after exposure to Rh+ blood cells (via transfusion or during birth process) [2] Transfusion of Rh- individual with Rh+ blood results in production of anti-D agglutinens; sensitizes person to Rh factor and may result in anaphylaxis if exposed a second time. Erythroblastosis fetalis arises when Rh- mother has been exposed to Rh+ blood and is carrying Rh+ child.

35. Importance of the Rh factor Transfusion reactions.1 2. Hemolytic disease of the new-borne