L1 RBC Physiology and Plasma Proteins.pdf

Blood and Lymphatic Physiology  Plasma Proteins Prof Dr. Abdelaziz M. Hussein Prof Dr. Shereen Samir Prof and Chairman of Medical Physiology Department Prof. of Medical Physiology Contacts : Email: [email protected] Email: dr.shery98@ya...

Blood and Lymphatic Physiology  Plasma Proteins Prof Dr. Abdelaziz M. Hussein Prof Dr. Shereen Samir Prof and Chairman of Medical Physiology Department Prof. of Medical Physiology Contacts : Email: [email protected] Email: [email protected] Office hours : 10.0 AM- 11.0 AM Tuesday, Wednesday  Lecture Objectives At the end of this lecture you will be able to: 1) List the general functions of the blood 2) Recognize the different components of the blood 3) Recognize the composition of the plasma 4) List the types and sources of plasma proteins 5) Identify the different specific and non-specific functions of plasma proteins Contents 01 General functions of the blood 02 Cellular and fluids elements of the blood 03 Types, sources and dynamic state of plasma proteins 04 Functions of plasma proteins  Blood Def., Blood is a complex reddish fluid which circulates continuously inside CVS http://www.passmyexams.co.uk/GCSE/biology/images/blood_comp_01.jpg Volume: 5.6 L in 70kg man i.e. 8% of body weight 6  Blood General Functions of Blood Major Transport medium (O2, CO2, Nutrients etc..) Hemostatic Defense function functions Blood (stops bleeding (WBC, Functions from injured antibodies) blood vessel) Homeostatic functions (keep ECF constant e.g. pH ABP, Temp) 7 Blood components 8  Blood Composition http://www.americasblood.org/_img/plasma.jpg 1) Plasma (55%) 2) Blood Cells (45%) 9  Blood Composition Blood Cells Plasma (Fluid part) Represent 45 % Represent 55 % RBCs WBCs Platelets Blood Composition 11 Blood Cells 12 PLASMA 13  Plasma Def., It is a clear fluid in which blood cells are suspended Plasma Water Solids 90 % 10 % Organic (9.1%) Inorganic (0.9 %) - Plasma proteins (7%) - Cations: Na, K. - Other organic ( urea, - Anions: Cl, HCO3 creatinine, glucose, vitamins Plasma proteins 15  Plasma Proteins A) Concentration: ❑ 6- 8 gm % (or 100 ml plasma) B) Types: 4 main types (albumin, globulins, fibrinogen and prothrombin) Concentration Molecular weight (gm/dl) (Dalton) Albumin 3.5 - 5.0 69,000 Globulins 2.4 - 2.7 90.000-156.000 Fibrinogen 0.4 340.000 Prothrombin 0.01- 0.16 68.700 In addition to small amounts of other proteins e.g. most of clotting factors. 16  Plasma Proteins C) Sites of synthesis: i) Liver: Synthesizes albumin, fibrinogen, prothrombin and 50- 80% of globulins (α and β not gamma globulins). ii) Lymphoid tissues (liver, spleen, bone marrow, and lymph nodes): Plasma cells synthesize γ globulin (20-50% of globulins) 17  Plasma Proteins D) Dynamic state PP are dynamic structures which undergo continuous breakdown and resynthesis (rate of formation equals destruction rate) Albumin is transported to the interstitial fluid and 6-10 % of it degraded by tissues macrophages Degraded albumin is replaced by hepatic synthesis of 200-400 mg/kg/day→ is a slow process. 18  Plasma Proteins D) Sources of PP Amino acids needed for synthesis of PP are derived from; a) Food proteins: Proteins of high biological value (found in meat, milk and eggs and contain excess essential a a). Plant proteins favor globulin formation. b) Tissue proteins: Act as a source for plasma proteins mainly during starvation. Are mobilized to the liver and used for plasma protein synthesis. 19  Plasma Proteins D) Sources of PP Labile reserve proteins which are structurally similar to plasma proteins and stored in liver, can be mobilized within few hours from the tissues to the plasma in cases of acute protein losses as during haemorrhage 20  Albumin/globulin (A/G) ratio 1) Def., It is the ratio ( ) albumin and globulin concentrations in plasma. 2) Value: about l.2-1.6. 3) Importance: Its is of clinical importance as it is altered in many diseases such as; i) It is decreased in: a) ↓ed albumin: i. Advanced liver disease→ ↓ed formation of albumin. ii. Renal diseases→ loss of albumin in urine. iii. Burns → loss of albumin from skin. iv. Starvation → ↓ed protein intake. b) ↑ed globulins: Severe infections → ↑ed γ globulins formation. ii) It is increased in: Congenital agamma globulinaemia → ↓ed the globulin fraction. 21  Plasma Proteins Specific Non-specific 1.Osmotic pressure of 5. Buffering functions plasma by albumin 2.Defensive functions 6. Carrier functions by gamma globulins 3. Viscosity of plasma 7. Regulation of by fibrinogen capillary permeability 4. Blood clotting by prothrombin and 8. Carriage of CO2 fibrinogen 9. Use of tissue proteins 22  1) Regulation of blood volume and tissue fluid formation PP exert an osmotic pressure called colloidal osmotic or oncotic pressure across the capillary wall, because the capillary wall is relatively impermeable to them Produced mainly by albumin because it has the greatest concentration and the smallest MW of all of plasma proteins. It is about 28 mmHg (19 mmHg is caused by albumin and 9 mmHg by Na ions held in plasma by the Donnan's effect). This pressure tends to pull water into the blood→ so it is important for the regulation of the blood volume and tissue fluid formation. http://www.eplantscience.com/index/general_zoology/images/images36/fig017.jpg 23  2) Blood coagulation It is done clotting factors which are plasma proteins e.g. prothrombin and fibrinogen Done by 3) Defense function a) γ globulins (or antibodies) → defend against micro-organisms. b) Complement system 4) Blood viscosity Blood viscosity is about 3 times that of H2O and the plasma is about 1.5 times that of H2O It is due to plasma proteins (mainly fibrinogen due to its elongated shape) The viscosity is important in the production of the peripheral resistance and helps to maintain arterial blood pressure.  5) Buffering action PP are responsible for about 15% of the buffering power of the blood. Its buffering action is due to; a) The presence of free acidic (R-COOH) and basic (R-NH) groups in plasma proteins which are easily dissociated→ allow them to act as weak acids or bases depending on the pH of the plasma. At normal pH of plasma (7.4) the plasma proteins are -ve charged and act as anions (weak acids), thus combined with bases mainly (Na) forming the buffer system, (proteinic acid- Na proteinate) b) The presence of imidazole group of histidine residues in plasma proteins which is easily dissociated.  5) Buffering action Plasma proteins buffer any acid or alkali added to the blood as follow; Example : Lactic acid + Na proteinate Na lactate + proteinic acid. (Strong acid) (Weak acids) Na OH + proteinic acid Na proteinate + H2O This keep blood pH constant  6) CO2 Carriage CO2 combines with the amino groups of the plasma proteins→ carried as carbamino compounds (RNHCOOH). 7) Control of capillary Permeability The pores in the capillary walls are closed by plasma proteins → limits the capillary permeability 8) Use of plasma proteins by tissues Tissues constantly use plasma proteins for their protein metabolism. There is a state of reversible equilibrium ( ) plasma proteins and the tissue proteins under normal or diseased conditions, so that the ratio of total tissue proteins to total plasma proteins remains constant =33:1.  9) Carrier Functions Def, Plasma proteins transport many important substances as hormones, vitamins, minerals, from the sites of absorption or sites of synthesis to the sites of action or storage. Examples: i) Albumin: transports hormones (thyroxin & steroids), amino acids, vitamins and fatty acids. ii) Transferrin (β1-globulin): transports iron in the blood. iii) Ceruloplasmin (α2-globulin): transports copper in the plasma iv) Transcobalamine: transports vit. B12.  9) Carrier Functions Examples: v) Steroid hormone-binding globulin: transport steroid hormones vi)Apolipoprotein B: transport lipoproteins. vii)Transthyretin (thyroid binding prealbumin): transport thyroid hormones Importance: a) Prevents the rapid loss of substances in urine because the plasma proteins are of large MW (not filtered in glomeruli). b) Provides a reservoir of the substance when needed. c) Makes the lipids and free fatty acids miscible with water and easily transported through plasma (watery medium).  Quiz Q1: The normal osmotic Q2: The viscosity of the pressure of the plasma plasma is mainly due to : proteins is about: a)Albumin a)15 mmHg b)Alpha globulin b)20 mmHg c)Beta globulin c)28 mmHg d)Prothrombin d)50 mmHg e)Fibrinogen e)70 mmHg 30  RBCs Prof Dr. Abdelaziz M. Hussein Prof and Chairman of Medical Physiology Department  Lecture Objectives At the end of this lecture you will be able to: 1) Recognize the RBCs count and functional structure of it 2) List the RBCs functions 3) Identify the fate and life span of RBCs 4) Recognize the sites of RBCs formation 5) Identify the factors affecting erythropoiesis Contents 01 RBCs count and structure 02 Functions of RBCs 03 Life span and fate of RBCs 04 Erythropoiesis and factors affecting Red Blood Corpuscles (RBCs) 34  Red Blood Corpuscles (RBCs) Erythrocyte count: ▪ Males: 5.0-5.5 million/mm3 ▪ Females:4.5-5.0 million/mm3 ▪ Variable in: a. Low in child and old age: 3.5- 4.5 million/mm3 b. High count in newborn (6-8 million/mm3) and persons living at high altitude  Red Blood Corpuscles (RBCs) Shape : Circular, Non-nucleated, Biconcave discs Size: Its diameter → 7.8 um. Its thickness → at the thickest point is about 2.5 um. Its average volume → 90 to 95 u3.  Red Blood Corpuscles (RBCs) ❑Structure of RBCs: ❖ RBCs are not true cells, because they have no nuclei, so called corpuscles. a) The cell membrane: ❖ Is plastic semipermeable membrane ❖ Has large surface area  Red Blood Corpuscles (RBCs) ❑Structure of RBCs: b) Contents: ❖Hb (34% of RBC) is the main constituent. ❖K+ is the chief intracellular cation. ❖ Carbonic anhydrase enzyme helps CO2 transport, ❖ No mitochondria, so they obtain energy from anaerobic glycolysis http://leavingbio.net/Blood_files/image008.jpg  Functions of RBCs 1)Functions of cell membrane: a) It has a large surface area than the actual cell volume; ▪ Gives RBCs its biconcave shape. ▪ Allows easy diffusion of gases through cell membrane. b) Plastic → enhances cell flexibility → allow RBCs to be squeezed in small capillaries without rupture of it c) It keeps Hb inside RBCs So, prevent its loss in urine When Hb is filtrated into glomeruli causes its precipitation in renal tubules and acute renal failure 39  Functions of RBCs 2) Functions of Hb: a. Transport of O2 from lung to tissues by hemoglobin. b. Transport of CO2 from tissue to lung by help of carbonic anhydrase c. Hb is an excellent acid - base buffer 3) Functions of carbonic anhydrase enzyme: ❑It helps in transport of CO2. 4) Blood viscosity: ❑RBCs share in production of blood viscosity, which maintains arterial blood pressure.  Factors Affecting Erythropoiesis Tissue Oxygenation Diet Healthy (proteins, Organs (liver, Erythropoiesis and bone vitamins and Minerals) marrow) Hormones (thyroid, androgens and cortisone) 41 1) Tissue oxygenation 42  Tissue Oxygenation Hypoxia (e.g. high altitude, athletes and hemorrhage) Increase RBCS formation via erythropoietin (EPO) secretion (90% from kidneys and 10% from liver) a) EPO ++ transfer of stem cells in bone marrow to proerythroblasts b) EPO accelerates all the stages of development of mature RBCs from proerythroblasts 43  Erythropoietin ❑ A glycoprotein hormone ❑ Source: In adults: 90% from the kidney and 10% form the liver In fetus: mainly from liver ❑ Function: Stimulates the production of RBCs Accelerates all stages of its development into mature RBCs ❑ Regulation (control of secretion): 1. Hypoxia the main stimulus 2. Androgens, cobalt salts and adenosine 3. Adrenaline and noradrenaline and Prostaglandins ❑ Destruction of both kidneys (chronic renal failure) : Leads to lack of erythropoietin and decreased RBCs formation (anemia) 2) Healthy BM AND LIVER 45  Healthy Bone Marrow Healthy bone marrow RBCs formation Destruction of bone Deficiency of all marrow by blood cells (Aplastic irradiation, or drugs Anemia) 46  Healthy Liver Healthy Liver RBCs formation 1. Store Fe and Vit B12 2. Globin part of Hb 3. 10% of erythropoietin 47 3) Hormones 48  Hormones Thyroid hormones Hormones Androgens Glucocorticoids All of them stimulate erythropoiesis by promoting tissue metabolism and androgens stimulate erythropoietin hormone 49 4) Nutritional factors 50 Nutritional Factors Proteins Diets Minerals Vitamins e.g. Fe, e.g. B12, Cobalt and folic acid Copper and Vit C 51  Proteins ❑Proteins of high http://phunuhoanhao.net/wp-content/uploads/2013/07/lam-sao-de-mang-thai-1.jpg biological value (contain more essential amino acids) that present in liver, kidney and muscle are essential for erythropoiesis  Minerals 1.Iron: Important for the formation of Hb 2. Copper:Cofactor in Hb synthesis. 3. Cobalt; Cofactor in Hb synthesis.  Iron (Fe ) +2 ◊ Physiological role of iron: Is important for the formation of Hb, myoglobin, and other substances as cytochromes, cytochrome oxidase, peroxidase and catalase enzymes. ◊ Body content of iron: The total quantity of body iron is 4-5 gm as follow; o 65% → in the form of hemoglobin. o 15-30% → stored mainly in the liver and R.E.S as ferritin. o 4% → in the form of myoglobin. o 1% → in the cytochrome enzymes. o 0.1%→ combined with transferrin in plasma. ◊ Daily intake and loss: 0.6 mg in male and 1.3 mg in females Iron Absorption Feedback mechanisms regulating Iron Absorption When the body has become saturated with iron →↓ the rate of iron absorption. When the iron stores have been depleted of iron→ the rate of absorption ↑es to 5 times or more. Mechanisms: a) When all apoferritin become saturated with iron, the transferrin becomes fully saturated with iron due to its inability to release iron to the tissues→ so transferrin becomes unable to accept more iron from the intestinal mucosal cells. b) When the body already has excess stores of iron, the liver ↓es its rate of formation of apotransferrin, so less iron is absorbed.  Vitamins All vitamins are needed for erythropoiesis Vit B12 and folic acid are essential for the synthesis of DNA as they are required for the formation of TTP, one of the essential building blocks of DNA, so they are important for final maturation of the RBCs Vitamins B12 and Folic Acid Deficiency of Vit Megaloblastic B12 or Folic acid anemia  Quiz Q1: The main source of Q2: Maturation of RBCs erythropoietin in adults requires : is: a)Vit C a)Liver b)Vit B12 b)Kidney c) Cupper c)Heart d)Cobalt salts d)Spleen e)Vit D e)Pancreases 58 Thanks 59