5-Physiology for HLS system in MEd school.pptx

HLS physology

1. Physiology of the Blood Dr. Mohamamd Alqudah, BDS, Ph.D Department of physiology and biochemistry Office location M2, fifth floor Office hours 11-12 Monday- Thursday

2. Outline General overview of the blood Hematopoiesis Guyton 23 Physiology of Red Blood Cells (RBCs) Guyton 32 Physiology of White Blood Cells (WBCs) Guyton 33&34 Blood coagulation and homeostasis Guyton 35 Blood groups and transfusion Guyton 36

3. Lecture # 1 General overview of blood Blood characteristics Components of blood General functions of blood

4. Characteristics of Blood Blood is the only fluid tissue in the body Blood is a complex connective tissue in which living cells, the formed elements, are suspended in the nonliving fluid called plasma. Cells of the body served by two fluids The blood transports nutrients and wastes The interstitial flood bathes the cells of the body http://facweb.northseattle.edu/ Blood is that part of extracellular fluid within the cardiovascular system

5. Characteristics of Blood Volume : A person has 4 to 6 liters of blood , depending on his or her size. Of the total blood volume in the human body, 38% to 48% is composed of the various blood cells , also called formed elements. The remaining 52% to 62% of the blood volume is plasma , the liquid portion of blood. Color : Arterial blood is bright red because it contains high levels of oxygen. Venous blood has given up much of its oxygen in tissues, and has a darker, dull red color. pH : The normal pH range of blood is 7.35 to 7.45 , which is slightly alkaline. Venous blood normally has a lower pH than does arterial blood because of the presence of more carbon dioxide . Viscosity : Blood is about three to five times thicker than water so flows more slowly than water

6. Volume of the blood The average blood volume of an adult is about 7% of body weight, or about 5 litters     Adult male - 5-6 liters Adult female - 4-5 liters 55% of blood is plasma and 45% is red blood cells, these percentage vary with many factors such as gender, weight and other factors. Determination of blood volume Direct method: removal of all blood in experimental conditions with animals. Indirect method: ( dye dilution) injection of known amount of radio-labeled albumin or Evans blue dye to measure plasma volume and you know the Hematocrit, the blood volume will be: Total blood volume = Blood volume Plasma volume 1- Hematocrit

7. Blood viscosity (thickness and stickiness) It is the  inherent resistance of blood to flow due to internal friction of adjacent blood layers sliding past each other. Factors that contribute to blood viscosity Plasma proteins and electrolytes (specifically; albumin and fibrinogen), Plasma is about 1.8 more viscous than water. Blood cells( especially red blood cells) Temperature, cold blood is thicker and flows slowly. Blood velocity Fahraeus-Lindqvist effect ( microcirculatory of 200 microns)

8. Blood viscosity **Plasma is about 1.8 more viscous than water this is due mainly to presence of plasma protein. Whole blood viscosity is 3-4 times of that of water. This is due to presence of RBCs. Viscosity is increased when hematocrit value or no. of RBCs rise. **Increased viscosity will decrease blood flow through blood vessels.

9. Plasma osmotic pressure is 300 mmol /L or 770kPa (1) Crystal osmotic pressure results from NaCl and modulates water distribution between inside and outside of cells . (2) Colloid osmotic pressure results from albumin and regulates water distribution between inside and outside of capillary.

10. Components of the blood

11. Components of Blood (Hematocrit)

12. Components of Blood Formed elements 45% of whole blood Known as percent packed cell volume Red blood cells ( erythrocytes ) Hematocrit 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) In the buffy coat Blood smear

13. Formed elements of the blood

14. Components of Blood 2. Plasma ( blood without cells) 55% about 3 litters water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, wastes ***Plasma is obtained when unclotted blood is centrifuged. The fluid above cellular elements is PLASMA . Characteristics of Plasma Straw-colored liquid Mainly water 90% 3. Includes many dissolved substances Nutrients, Salts (metal ions) Respiratory gases Hormones Proteins, Waste products Source: DiverDave , CC-BY-SA, via Wikimedia Commons

15. Plasma proteins More than 300 different proteins are present in plasma. Can be measured Quantitative and semi quantitative measurements Serum proteins are separated into 6 groups: Albumin α 1 - globulins α 2 - globulins β 1 - globulins β 2 - globulins γ - globulins

16. Example on serum protein electrophoresis

17. Plasma proteins : you can separate plasma protein by electrophoresis 1) Albumin: 60% synthesized in the liver, main function is to provide colloid osmotic pressure in the plasma 2) Globulin: 36% of plasma proteins, made in the liver except gamma globulins  1 -globulins e.g. antitrypsin and  lipoproteins  2 -globulins e.g. caeruloplasmin,haptoglobins,alpha2 macroglobulin  -globulins e.g. beta lipoprotein, transferrin  -globulins immunoglobulins IgA, IgD , IgE , and IgM: made in plasma cells 3) Fibrinogen: fibrin, fibers (4% of plasma proteins), produced from the liver Blood Coagulation

18. Other plasma proteins (1% of plasma) Peptide hormone Like: Insulin Prolactin Glycoproteins like: TSH (thyroid- simulating hormone) FSH ( follice stimulating hormone) LH (luteinizing hormone) Plasm protein are synthesized in: Liver Synthesizes 90% of the proteins Makes the plasma cells  antibodies Endocrine or Peptide hormones

19. Note : hypoproteinemia is seen in a. liver diseases….less formation b. kidneys disease….loss of protein Most plasma proteins are produced by the liver, except for hormones and gamma globulins. Gamma globulins are formed by plasma cells . 8% by weight of plasma volume Plasma proteins serve a variety of functions, but they are not taken up by cells to be used as fuels or metabolic nutrients as are most other plasma solutes, such as glucose, fatty acids, and amino acids. Plasma proteins

20. PLASMA ELECTROLYTES 1. Electrolyte releases ions when dissolved in water 2. include: sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate and sulfate ions 3. Function: maintain osmotic pressure and the pH of the plasma. NUTRIENTS AND GASES 1. Nutrients : simple sugars, amino acids,, nucleotides and lipids 2. Blood gases: oxygen and carbon dioxide NONPROTEIN NITROGEN SUBSTANCES 1. contain nitrogen but are not proteins 2. include: urea, uric acid, creatine & creatinine 3. digestion  amino acids 4. nucleic acid catabolism  uric acid & urea 5. creatine metabolism  creatinine

21. General functions of the blood Transportation Gases : O2 & CO2 Nutrients : Amino acids, lipids, glucose, etc. Hormones : pituitary, thyroid, pancreas, ovary, and testes, synthesize hormones brought by blood to tissues requiring them. waste products : urea, lactic acid , creatinine Electrolytes : Na + K + Cl - Ca ++

22. Serum is plasma from which fibrinogen and other coagulation proteins have been removed as a result of clotting. It contains high level of serotonin (released from platelets during clotting ). ***It is obtained when clotted blood is centrifuged. The fluid above clotted blood is SERUM Plasma VS Serum

23. 2. Regulation Blood pH : H 2 CO 3 , lactic acid, citric acid, NH 3 , HCO 3 - tend to lower or raise blood pH. Buffer systems help maintain pH within limits. Fluid balance: plasma colloid osmotic pressure Body temperature: coolant properties of water and vasodilatation of surface vessels dump heat 3. Protection Infection WBC , antibodies Blood loss platelets, clotting factors  

24. Hematopoiesis Hematopoietic process Regulation of Hematopoiesis Chronological Sites for Hematopoiesis Nutritional requirement for hematopoiesis

25. Hematopoiesis Hematopoiesis is the process of blood cells ( erythrocyte (red blood cell, RBC), leukocyte (white blood cell, WBC) and thrombocyte (platelet, P ) ) formation in the bone marrow from hematopoietic stem cells. All blood cells are derived from a common stem cell called Pluripotent hematopoietic stem cell (PHSC)

26. Hemopoietic process 1: Hemopoietic stem cells- Pluripotent hematopoietic stem cell (PHSC) Unlimited self renewal, steady numbers, active differentiation. 2: committed progenitors directional differentiation (CFU-GEMM, CFU-E, CFU- GM, CFU-MK, CFU-TB). [CFU: colony- forming unit 3: precursors morphologic occurrence of various original blood cells .

27. PHSC differentiates to become: either a) Myeloid progenitor cell or b) Lymphoid progenitor cell Myeloid RBC’s and WBC’s and platelets Lymphoid B and T cells and Myeloid Lymphoid

28. Hematopoiesis Proliferative potential differentiation www.freelivedoctor.com

29. Pluripotent hematopoietic stem cell (PHSC) features Self renewal in high degree , a small portion of them remains exactly like the original pluripotential cells and is retained in the bone marrow to maintain a supply of these, although their numbers diminish with age . Multi- directional differentiation High proliferative capacity , Hematopoietic stem cells produce about 1×10 11 blood cells releasing to blood for use. Surface sign According to CFU (colony forming unit), using fluorescence-activated cell sorting (FACS), its main surface sign is CD34 + CD38 - Lin - and CD34 - CD38 - Lin - . Note CD: cluster of differentiation of antigen on the white blood cells; Lin: systemic specific antigen on the hematopoietic cells.

30. Hematopoietic Microenvironment stem cell(s ) stromal cells growth factors

31. Hematopoietic Microenvironment Stromal cells : fibroblasts endothelial cells adipocytes Growth Factors www.freelivedoctor.com

32. Regulation of hematopoiesis The process of hematopoiesis is under tight control by multiple proteins called growth factors Growth factors control the growth and reproduction of different stem cells Another group of growth factors ( differentiation inducers ) control the differentiation process. Each of the differentiation inducers cause the one type of committed stem cells to differentiate one or more step towards the final cell type responsible for basal hematopoiesis and maintaining blood counts in normal ranges

33. Hematopoiesis GROWTH FACTORS ERYTHROPOIESIS GRANULOPOIESIS MEGAKARYOPOIESIS LYMPHOPOIESIS generation of each specific lineage of mature blood cells is regulated by a specific set of hematopoietic growth factors.

34. Growth Factors Function: stimulate progenitor of the followings: GM-CSF (granulocyte-macrophage CSF) Granulocyte-monocyte G-CSF (granulocyte CSF) Granulocyte M-CSF (macrophage CSF) Monocyte EPO (Erythropoietin) Erythrocyte IL-1,3,6 (Interleukin-3, 1, 6) Myeloid lineage TPO (Thrombopoietin) Platelet Hematopoietic growth factors

35. Sites of Hemopoietic Activity Yolk sac Liver Spleen Bone marrow Tibia Vertebra Sternum Rib Femur FETAL MONTHS ADULT 1 3 20

36. Nutritional requirement of hematopoiesis Blood cell production (hematopoiesis) is a dynamic process that requires the replenishment of more than 7 × 10 9  blood cells (leukocytes, erythrocytes and platelets) per kg body weight per day Therefore, as would be expected, their maturation and rate of production are affected greatly by a person’s nutritional status. Especially important to our discussion are : Vitamin B12 Folic acid Iron

37. Role of vitamin B12 and folic acid in synthesis of cellular DNA** **Bone marrow cellular elements are among the most rapidly dividing cells in the body (because of continuous need for RBCs and WBCs). Dividing cells needs continuous formation of DNA. Both vit B12 and folic acid are needed for formation of thymidine triphosphate (one of four nitrogen bases that form the DNA). thymine

38. Role of vitamin B12 and folic acid in synthesis of cellular DNA (cont.)** **Because both Vitamin B12 and folic acid are needed for normal formation of DNA, therefore nuclear maturation and cell division of bone morrow cells (hematopoiesis) is not rapid and this leads to larger cells (macrocytes). The macrocytes have irregular ,oversized (large than normal) and oval shape with fragile cell membrane. Abnormal cell membrane of RBCs leads to short life of RBCs. Macrocytes   are red cells with an increased size, 9-12µm in diameter

39. Facts regarding Vitamin B12 (Cyanocobalamin )** Water soluble vitamin Vit B12 in diet can be destroyed by digestive enzymes. It is protected by intrinsic factor Prolonged deficiency leads to irreversible neurological damage Its absorption from gatrointestinal tract (terminal ileum) needs presence of intrinsic factor It is absorbed from terminal ileum with intrinsic factor by pinocytosis.

40. Sources of Vitamin B 12 Fish Eggs Meat and liver Dairy Products ** Dietary deficiency is rare except in vegetarians

41. Absorption of vitamin B 12 ( Cbl ) Dietary Cbl in the presence of acid and pepsin in the stomach is liberated from binding to protein and then quickly binds to R factors ( Cbl -binding proteins) in saliva and gastric juice R factor- Cbl complex is freed in the alkaline milieu of the duodenum by the action of pancreatic proteases and then binds specifically and rapidly to gastric-derived intrinsic factor (IF). IF is a 45 kDa glycoprotein with very high affinity for Cbl . The IF- Cbl complex binds to a specific ileal receptor, cubilin , from which it will be absorbed into ileal enterocytes. Then it will exit into blood and bind to transcobalamins II This complex enters cells by receptor-mediated endocytosis. Reference Stanley L Schrier , MD

42. Total body stores of Cbl are 2 to 5 milligrams, approximately one-half of which is in the liver The minimum amount of vitamin Cbl required each day to maintain normal red cell maturation is only 1 to 3 micrograms Therefore, 3 to 4 years of defective B 12  absorption are usually required to cause maturation failure anemia.

43. Folic acid The daily folate requirement for unstressed adults is estimated to be approximately 50mg/day Folate occurs in animal products and in leafy vegetables in the polyglutamate form Dietary folate in the form of the polyglutamates is cleaved to the monoglutamate in the jejunum where it is absorbed Body stores are 5-10 mg (liver) Reference Stanley L Schrier , MD

44. Megaloblastic anemia** Both vitamin B12 and folate deficiency cause an identical megaloblastic anemia Pernicious anemia is due to primary deficiency of vitamin B12 secondary to failure of vitamin B12 absorption from gastrointestinal tract. This absorption failure is due to absence of intrinsic factor (atrophic gastric mucosa).

45. Megaloblastic anemia due to Deficiency of vitamin B 12 Causes of vitamin B12 deficiency: 1. Impaired absorption Gastric atrophy: Auto immune disease can destroy the parietal cells that secrete the I.F. required for absorption of vit . B12. b. Gastrectomy c. Intestinal disease like ileal resection d. Infestation with Fish tapeworm ( Diphyllobothrium latum ) 2. Decreased vitamin B12 intake- seen in vegetarian i n these cases treatment is life long injections of vitamin B12 (oral administration wouldn't be effecient!)

46. Iron metabolism Iron is very important to our body : Hemoglobin synthesis It is an essential element of myoglobin, cytochromes , cytochrome oxidase, peroxidase, catalase Iron distribution in our body, total body Iron is 4-5 g: 65% of which is in the form of hemoglobin 4% myoglobin 1% various heme compounds .1% plasma transferrin 15-30% is stored in reticuloendothelial cells and liver parenchymal cells mainly in the form of ferritin Daily iron loss average 1-2 mg Man .6mg female about 1.3 Copyright © Cornell University

47. Iron absorption, transport and storage Copyright © Cornell University

48. Iron uptake by erythroid progenitors Copyright © Cornell University

49. Regulation of total body iron Copyright © Cornell University