Blood Physiology Professor A. M. A Abdel Gader MD, PhD, FRCP (Lond Blood Physiology Professor A.M.A Abdel Gader MD, PhD, FRCP (Lond., Edin), FRSH (London) DEpartment of Physiology College of Medicine & King Khalid University Hospital King Saud University Riyadh

BLOOD

Lecture # 1 & 2 Topic: Red Blood Cells (RBCs) Composition & functions of the Blood Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

Blood Film

Blood Composition

Blood Composition 2. Plasma Red Blood Cells White Blood Cells 1. Cellular components Red Blood Cells White Blood Cells Platelets 2. Plasma Consist of: Water: 98% Ions: Na, K, HCO3, PO4 ..etc Plasma proteins (Albumin, globulin, Fibrinogen) PlasmaSame ionic composition as interstitial fluid

Functions Of the blood Transport O2 from lungs to tissues CO2 from tissues to lungs Nutrients Waste products to kidneys Hormones from endocrine glands to tissues

Functions Of Blood Cont. 2. Homoeostasis Regulation of body temperature Regulation of ECF pH

Functions Of Blood Cont. 3. Protecting the body against infections White Blood Cells Antibodies 4. Blood clotting prevent blood loss

Formation of Blood Cells -Definitions Formation of erythrocytes (RBC) >Erythropoiesis Formation of leucocytes (WBC) >Leucopoiesis Formation of thrombocytes (platelets)> Thrombopiesis Formation of blood >Haemopoiesis.

The Red Blood cell

The Red Blood cell

Red Blood Cells Structure Cell membrane: phospholipid; semi-permeable Flat Biconcave Disc Non-nucleated framework of protein (stromatin) + haemaglobin Cell membrane: phospholipid; semi-permeable Composition of RBCs 60% water 40% solids 90% of solids content is Hb 10% stromatin

Red Blood cells cont. Functions Metabolism Carry Haemoglobin Transport of Oxygen Transport of Carbon Dioxide Buffer ( pH regulation) Metabolism Metabolically active cells uses glucose for energy

Red Blood Cells cont. Life span ………. 120 days RBC Count (Practical Class): In males 4.8-5.8 million cells/mm3 In females 4.2-5.2 million cells/mm3

Sites of blood formation Adults………….. Bone Marrow (Flat bones) Children …………. Bone Marrow (Flat & long bones) Before Birth: …. Bone Marrow Liver & spleen Fetus 1st 4 months …Yalk Sac

Production of RBC-cont.

Blood Formation in the bone marrow

Monophyletic theory of cell formation Red blood cells

Hematopoiesis (17.9)

Formation of RBC – cont.

Production of Erythrocytes: Erythropoiesis Figure 17.5

Maturation Times

Erythropoiesis, (Formation/genesis of RBC) Stages of RBC development Pluripotential haemopoietic STEM CELL Committed Stem cell Proerthroblast early, intermediate and late normoblast Reticulocytes Erythrocytes

Maturation Sequence

Features of the maturation process of RBC Reduction in size Disappearance of the nucleus Acquisition of haemoglobin

Regulation of Erythropoiesis

Control of Erythropoiesis Erythropoiesis is stimulated by erythropoietin (EPO) hormone Secretion of EPO is stimulated by: Hypoxia (low oxygen) Anaemia Hemorrhage High altitude Lung disease Heart failure

Role of the kidneys in RBC formation

Tissue oxygenation and RBC formation

Control of erythropoiesis Cont. Erythropoietin glycoprotein 90% from renal cortex 10% liver Stimulates the growth of: early RBC-committed stem cells Does not affect maturation process Can be measured in plasma & urine High level of erythropoietin anemia High altitude Heart failure

Control of erythropoiesis cont. Other hormones Androgens, Thyroid, cortisol & growth hormones are essential for red cell formation Deficiencies of any one of these hormones results in anaemia

Control of erythropoiesis

Erythropoitein- Mechanism of production of Hypoxia, (blood loss)  Blood O2 levels Tissue (kidney) hypoxia  Production of erythropoietin  plasma erythropoietin Stimulation of erythrocytes production  Erythrocyte production

Nutritional requirements for RBC formation Amino acid HemoGlobin Iron Deficiency  small cells (microcytic anaemia )

Nutritional requirements for RBC formation cont. 3. Vitamins Vit B12 and Folic acid Synthesis of nucleoprotein DNA Deficiency  macrocytes megaloblastic (large) anemia Vit C Iron absorption

Nutritional requirements for RBC formation-cont. Vit B6 Riboflavin, nicotinic acid, pantothenic acid, biotin & thiamine (VB) Deficiency  normochromic normocytic anaemia Vit E RBC membrane integrity Deficiency  hemolytic anaemia

Nutritional requirements for RBC formation cont. Essential elements Copper, Cobalt, zinc, manganese, nickel Cobalt  Erythropoietin

Vitamin B12 & Folic acid Important for cell division and maturation Deficiency of Vit. B12 > Red cells are abnormally large (macrocytes) Deficiency leads: Macrocytic (megaloblastic) anaemia Dietary source: meat, milk, liver, fat, green vegetables

Vitamin B12 Pernicious anaemia Absorption of VB12 needs intrinsic factor secreted by parietal cells of stomach VB12 + intrinsic factor is absorbed in the terminal ileum Deficiency arise from Inadequate intake Deficient intrinsic factors Pernicious anaemia

Hemoglobin Globin protein consisting of 4 polypeptide chains 2 1 3 4 Globin protein consisting of 4 polypeptide chains One heme pigment attached to each polypeptide chain Each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule

HAEMOGLOBIN 14g/dl---18g/dl Protein (Globin) + Heme Each heme consist of: porpharin ring + iron The protein (Globin) consist of: 4 polypeptide chains: 2  and 2  chains

HB Structure

HAEMOGLOBIN

Types of normal hemaglobin HAEMOGLOBIN Types of normal hemaglobin HbA: 98% of adult Hb its polypeptide chains (2 & 2) HbA2: 2.5% of adult Hb (2 & 2) HbF: 80-90% of fetal Hb at birth (2 & 2) Abnormality in the polypeptide chain > abnormal Hb (hemoglobinopathies) e.g thalassemias, sickle cell

HAEMOGLOBIN cont. Functions of Hb Carriage of O2 and CO2 Buffer (Bind CO Smokers)

BLOOD PHYSIOLOGY Iron metabolism

Total Iron in the body = 3-5g Iron metabolism Total Iron in the body = 3-5g Haemoglobin: ………. 65-75% (3g) Stored iron…………. 15-30% Muscle Hb (myoglobin) ….. 4% Enzymes (cytochrome) …….. 1% Plasma iron: (transferrin) …. 0.1% (Serum ferritin  indication of the amount of iron stores)

Iron intake: Iron metabolism cont. Diet provides 10-20 mg iron Liver, beef, mutton, fish Cereals, beans, lentils and Green leafy vegetable

Iron in food mostly in the form of Ferric (F+++, oxidized) Iron metabolism, cont. Iron absorption Iron in food mostly in the form of Ferric (F+++, oxidized) Better absorbed in reduced form Ferrous (F++) Iron in stomach is reduced by gastric acid, Vit. C. Maximum iron absorption occurs in the duodenum

Intestinal mucosal cell Iron absorption Tissues Plasma Intestinal mucosal cell intestinal lumen Storage Pool & Erythropoietic Apo- Transferrin Fe3+ + Apoferritin Ferritin Ascorbic Acid Fe2+

Iron absorption cont. Rate of iron absorption depend on: Amount of iron stored Rate of erythropoiesis When all the apoferritin is saturated the rate of absorption of iron from intestine is markedly reduced

Iron absorption cont. Iron in plasma: Transporting protein: TRANSFERRIN Normally 30-40 saturated with Fe (plasma iron 100-130ug/100ml) When transferrin 100% saturated >> plasma iron: 300ug/100ml (Total Iron Binding Capacity)

Iron stores Site: liver, spleen & bone marrow Storage forms: Ferritin and haemosiderin Apoferretin + iron = Ferritin Ferritin + Ferritin = Haemosiderin

Iron excretion and daily requirement Iron losses feces: unabsorbed, dead epithelial cells bile and saliva. Skin: cell, hair, nail, in sweat. Urine Menstruation, pregnancy and child birth

Destruction of Erythrocytes At the end of RBC life span is 120 days: Cell membrane ruptures during passage in capillaries of the spleen, bone marrow & liver. Haemoglobin Polypeptide  amino acids  amino acid pool Heme: Iron  recycled  iron storage porphryn  biliverdin  bilirubin (bile)

Jaundice Yellow coloration of skin, sclera Deposition of bilrubin in tissues If Bilrubin level in blood > 2 mg/ ml > jaundice Causes of Jaundice Excess breakdown of RBC (hemolysis) Liver damage Bile obstruction: stone, tumor

ANAEMIAS Definiation Decrease number of RBC Decrease Hb Symptoms: Tired, Fatigue, short of breath, (pallor, tachycardia)

Causes of anaemia 1. Blood Loss 2. Decrease RBC production acute accident Chronic  ulcer, worm 2. Decrease RBC production Nutritional causes Iron  microcytic anaemia VB12 & Folic acid  megaloblastic anaemia Bone marrow destruction by cancer, radiation, drugs  Aplastic anaemia. 3. Haemolytic  excessive destruction Abnormal Hb (sickle cells) Incompatible blood transfusion

Microytic hypochromic anaemia (Iron deficiency anaemia) The most common cause of microcytic hypochromic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common in children and in women in reproductive years (from menstrual blood loss and from pregnancy)

Microytic hypochromic anaemia (Iron deficiency anaemia) The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

Macrocytic anemia RBCs are almost as large as the lymphocyte. Note fewer RBCs (and the hypersegmented neurotrophil)

Polycythemia Increased number of RBC Types: Relative True or absolute Primary (polycythemia rubra vera): uncontrolled RBC production Secondary to hypoxia: high altitude, chronic respiratory or cardiac disease Relative Haemoconcentration: loss of body fluid in vomiting, diarrhea, sweating