Erythropoiesis and Hemoglobin PDF

Blood physiology Dr. Amira Gobran Lecturer of Medical Physiology Red blood cells/ Erythrocytes (RBCs)  Formation of RBCs (Erythropoiesis) Sites of formation 1- In the foetus: Yolk sac: in the first few weeks of pregnancy. Liver & spleen: from 6 wks. to 6 months....

Blood physiology Dr. Amira Gobran Lecturer of Medical Physiology Red blood cells/ Erythrocytes (RBCs)  Formation of RBCs (Erythropoiesis) Sites of formation 1- In the foetus: Yolk sac: in the first few weeks of pregnancy. Liver & spleen: from 6 wks. to 6 months. Bone marrow: from the 6th month. 2- In infancy & childhood: From red bone marrow of all bones. 3- In adult life:  The red bone marrow restricted to the central skeleton (flat bones as skull, vertebrae, ribs, sternum, pelvic bones), also proximal ends of long bones as humerus, femur & tibia.  The yellow bone marrow can change to active red marrow to produce RBCs as in case of severe anemia (extramedullary hemopoiesis)  1- Hypoxia Bone marrow Factors affecting erythropoiesis erythropoietin Erythropoiesis 4- 2- Dietary factors Fe, Vitamins, protien 3-  [I]- Oxygen supply to tissue: (hypoxia): (85%) hypoxia is the main stimulus for RBCs. Hypoxia (as in anemia, high altitude, heart or lung diseases)  the main stimulus for RBCs formation.  stimulates the secretion of erythropoitin hormone secretion from the kidney (85%) and the remaining from the liver.  Erythropoitin hormone (glycoprotein) stimulates the red bone marrow to form new RBCs.  Erythropoitin formation is stimulated by catecholamines, and androgens.  If hypoxia is corrected there is negative feedback inhibition of erythropoitin secretion.  In severe haemorrhage, the level of erythropoitin increases to activate the yellow bone marrow and liver and spleen (extramedullary sites) to form RBCs. [II] - Dietary factors: a-Proteins b- Metal ions C-Vitamins  a- Proteins: of high biological value as animal proteins (contain essential amino acid) to form globin part of Hb  b- Metal ions: 1- Iron:  Importance:  - for synthesis of haem part of Hb.  - for synthesis of myoglobin and enzymes as cytochrome oxidase, peroxidase & catalase.  Sources: meat, liver, green vegetables & moulases (it must be added to infant diet as the mother milk is not sufficient in iron).   Requirement: - adult male require 10 mg/day. - adult females require 15 mg/d. - pregnant requires 20 mg/d. - infants require 10 mg/d  Loss: - In faeces, sweat, exfoliated skin (about 1mg/day) and very little amount in urine and in lactating milk. - Women loss in menstruation: 0.5 mg/d (3.5 mg/period). Factors affecting iron absorption: 1-Body need of iron: 2-pH of stomach 3-Contents of food 4-Hypoxia and anemia Factors affecting iron absorption: 1- Body need of iron:  increased need as in pregnancy lead to increase absorption directly from intestinal lumen to plasma. 2- pH of stomach:  acidic pH → change of ferric to ferrous with increase absorption.  (so, patient with gastrectomy demonstrate impaired iron absorption with iron deficiency anemia). 3- Contents of food:  Oxalates, phytate & phosphate →decrease absorption.  Ascorbate, lactate & succinate →increase absorption. 4- Hypoxia and anemia→ increase iron absorption 2-Copper  Carried by plasma protein (ceruloplasmin)  Catalyze the oxidation of ferrous into ferric state to be carried as transferrin. 3-Cobalt  Stimulates erythropoietin release from the kidney,  so, increase cobalt may lead to polycythemia.  C- Vitamins: (Erythrocytic Maturation factors) 1- Vitamin B12: (Extrinsic factor) (Anti- pernicious anemia) Importance: It is very important for maturation of RBCs, biosynthesis of purine, pyrimidines, nucleic acids and DNA synthesis and cell division. Absorption:  Vit B12 present in diet as protein bound complex.  It is fred by HCl & proteolytic enzymes.  Then it combines with glycoprotein secreted from parietal cells of gastric glands called the intrinsic factor to prevent its digestion by enzymes till it reaches the terminal ileum.  In the terminal ileum, absorption of B12 occurs by pinocytosis into intestinal cells then to blood.  In the blood vit. B12 is carried by transcobalamin to bone marrow.  Requirement:  1-2 µg/day  storage in liver is very high = 1-5 mg.  So intake or absorption of vit.B12 is not manifested till 5 years.  Deficiency: Due to malabsorption → megaloblastic pernicious anemia.  2- Folic acid: - It is water soluble vitamin. - It is present in green vegetables, some fruits, liver and meat. - It is absorbed easily from all small intestine and changed into active folinic acid:  essential for DNA formation and cell maturation. - Its deficiency leads to megaloblastic anemia. 3- Vit. C:  Required for reduction of ferric to ferrous and help maturation of red blood cells. 4- Vit B complex:  Needed for normal erythropoiesis. [III]- Hormonal factors: 1. Androgens  stimulate erythropoietin production from the kidney and its effect on bone marrow causing increase RBCs. 2. Thyroid hormone  Stimulates the bone marrow cells and general metabolism & increase O2 consumption and decrease O2 supply → hypoxia which stimulates erythropoiesis. 3. Pituitary hormones: [Growth h., Gonadal h., Thyroid- stimulating h. & Adrenocorticotrophic hormones] → stimulate bone marrow. 4. Glucocorticoids:  stimulate the general metabolism and also stimulate bone marrow to produce more RBCs. 5. Haemopoietic growth factors:  Glycoproteins secreted by lymphocytes, monocytes, endothelial cells and fibroblasts to stimulate stem cells in bone marrow to produce mature RBCs.  [IV]- State of liver, bone marrow and kidney: 1- Liver: 1. It is a site for storage of iron, vit B12, folic acid & copper. 2. It shares in the formation of erythropoietin hormone. 3. It is responsible for the formation of the globin part of hemoglobin. 4. It is responsible for synthesis of RBCs in fetal life. 5. It is responsible for the destruction of old RBCs. 2- Bone marrow:  site of erythropoiesis  any disease (atomic irradiation, deep x-ray, drugs) → aplastic anemia. 3- Kidney:  The site of formation of erythropoietin.  So, its failure leads to decrease erythropoietin and retention of toxic substances as urea lead to depression of bone marrow.  Definition: It is the principal constitute (33%) of RBCs. It is a red pigment which gives the blood its red color. Normal levels:  Infant at birth: 20 gm/dl  Infant after one week: 15.5gm/dl  Children (3-12 years) =11- 14 gm/dl  Adult male: 13-18 gm/dl - Adult female: 12-16 gm/dl.  Structure: -It is formed of : (1) Globin: 2 pairs of polypeptide chains (2  and 2 ) (2) 4 Haem: each is an iron-protoporphyrin So, it is made of 4 subunits each of them is formed from one Haem and one polypeptide chain  Functions: 1. Carriage of O2& CO2. 2. Strong buffer system. Reactions of Hb: 1- Oxyhemoglobin 2-Carbamino Hb 3-Met Hb 4-Carboxy Hb Reactions of Hb: 1. Oxyhemoglobin: O2 binds iron in ferrous state so it is called oxygenation not oxidation. 2. Met Hb: strong oxidation by certain drugs or oxidizing agents → ferric state which does not carry O2→ dusky coloration of skin like cyanosis (normally, MetHb doesn’t exceed 0.5% due to the activity of NADH-MetHb-reductase enzyme in the RBCs which converts it back to normal Hb). 3. Carboxy Hb:  Carbon monoxide is a toxic gas  attached to Fe++ in high affinity (210 times as O2).  The part attached to CO doesn’t carry O2  and the remaining part of Hb, which carries O2 doesn’t give its O2 to the tissue. 4. Carbamino Hb: normally Co2 attached to the globin part of Hb.  Types of Hb  2  chain (each is consisted of 141 1-Adult (HbA): amino acids) and 2 chain (146 amino acids). (97.5% of adult Hb.) 2-HbA2 2 chains and 2 delta (146 amino acids) chains which differ from -chains in the terminal 10 A.A -3Fetal Hb (HbF:) -It contain 2 and 2 gamma (146 amino acids) chains which differ from -chains in 37 A.A -It is the type of Hb in the human fetus then it is usually replaced by adult Hb after birth 4 - Glycosylated Hb (HbA1c): (3-7% of Hb)  Glucose is attached to terminal valine amino acid in - chain.  Increases in cases of uncontrolled diabetes mellitus. 5 - HbS It is abnormal type of Hb due to congenital abnormality of -globin in which valine amino acid present instead of normal glutamic acid at position 6 of -chain. hemoglobin-S  Life span of RBCs:  The life span of RBCs is 120 days,  old RBCs destroyed in narrow capillaries and spleen → Hb released and splits by the cells of the reticuloendothelial system into globin & haem Thank you