Hemoglobin (Hb) - PDF

# Hemoglobin (Hb) - Is the red oxygen-carrying pigment of RBCs = 34% of RBC's weight - Hemoglobin content: amount of Hemoglobin in grams / 100 ml blood. | | | | :---- | :---- | | Adult male | 15-16 g/dl | | Female | 13-14 g/dl | | Newborn | 19 g/dl due to relative intrauterine hypoxia...

# Hemoglobin (Hb) - Is the red oxygen-carrying pigment of RBCs = 34% of RBC's weight - Hemoglobin content: amount of Hemoglobin in grams / 100 ml blood. | | | | :---- | :---- | | Adult male | 15-16 g/dl | | Female | 13-14 g/dl | | Newborn | 19 g/dl due to relative intrauterine hypoxia | ## Structure & types of Hb Hb (4 subunits), each is formed of - **Polypeptide chain** - 4 Polypeptide = globin | | | | :---------- | :----- | | Adult Hb (HbA) | α2β2 | | | (α2β2) | | | 96-98% in adult | | HBA2 | 2-4% in adults | | Fetal Hb (HbF) | α2γ2 Hb | - O2 affinity > HbA - Allow extraction of O2 from maternal blood After birth HbF is changed to HbA (completed at 4 months) - **Heme:** - (Fe2+) protoporphyrin - Iron in ferrous state ## Chemical Reactions of Hemoglobin | Hb reacts with | Form | | :--------------- | :---- | | O2 (react loosely with ferrous iron) | Oxyhemoglobin | | remains Fe2+ (oxygenation not oxidation) | | CO2 (amino groups of polypeptide chains) | Carbamino hemoglobin | | CO | Carboxy hemoglobin | | Oxidizing agent (ferrous iron oxidized to ferric) | Dark Methemoglobin cannot carry O2 | | - Small amount of methemoglobin is normally formed | | - but reduced by NADH-methemoglobin reductase →Hb | | - Congenital deficiency of enzyme | | - ↑ methemoglobin in RBC's (hereditary met-hemoglobinemia) | # Functions of RBCs: ## A. Functions of hemoglobin 1. **Gases Transport** - O2 from lung to tissue - CO2 from tissue to lung 2. **Buffering action:** Being a protein, acts as acid-base buffer. - 6 times buffering > plasma proteins - due to highest concentration = 16g/dl while plasma protein= 7 g/dl ## B. Functions of Membrane → Keeps Hb inside. - If Hemoglobin become free in the plasma → it will - Filter through renal glomeruli → block renal tubule → causes renal failure - ↑blood viscosity →↑ cardiac work - ↑ colloidal osmotic pressure from 25 (28) to 70 mmHg→ ↑blood volume & cardiac work - Life Span 120 days. # Fate of RBCs - Old RBCs (fragile), Rupture when pass via narrow vessel in especially in spleen - Release Hb→ picked up by macrophage & broken | | | | :---- | :---- | | Heme | Globin (Protein metabolism) | | Protoporphyrin | Iron is reused for formation of new RBCs | | Yellow bile pigment | | (bilirubin) | | Secreted by liver in bile | # Role of spleen: - is important organ in hematopoietic system 1. Erythropoiesis during fetal life 2. Blood filter (remove aged, abnormal RBC's) 3. Blood storage (add volume to circulation in case of acute hemorrhage) + store 30% of platelets 4. Immunity: contains immune cells as lymphocytes and macrophages - Hypersplenism→ cause excessive destruction of blood cells - Splenectomy: result in abnormal RBC's + ↑platelet count+ ↑risk of infection # ERYTHROPOIESIS Formation of new RBCs | Sites | | | :---- | :---- | | In fetus | Liver & spleen | | After birth | Red active bone marrow of all bones. | | By age 20 ys | Red marrow in long bones-> inactive (infiltrated by fat) | | | except upper humerus & femur | | | Only membranous bones produce RBC's as | | | ✓ Skull | | | ✓ Ribs | | | ✓ Vertebrae | | | ✓ Pelvis | - Bone marrow: is one of the largest and most active organs in the body (approach size and weight of the liver)  # Factors Affecting Erythropoiesis ## I.O2 supply - Role of Erythropoietin - RBCs production ↑ in hypoxia - Hypoxia (O2) as in - Hemorrhage (loss of RBCs) - High altitude - Heart failure - Lung diseases - Athletes (↑demand of O2) - Hypoxia → stimulate Erythropoietin release - Glycoprotein, molecular weight=35000 - Normally present in plasma at low concentration - Source: - In Fetus, from liver - In Adult, from - kidneys: 85% - Liver: 15% - Anemia develops in renal failure, malignancies, liver cannot compensate - ❖ Therapy: Erythropoietin injection synthesized by DNA techniques - Mechanism of action of erythropoietin: - ✓ Erythropoietin binds specific receptors on erythropoietin sensitive stem cells - stimulate mitosis and inhibit apoptosis - →stimulate all steps of erythropoiesis - Stimulation of secretion of erythropoietin: 1. Alkalosis (at high altitude), 2. Androgens 3. Adenosine 4. Adenosine antagonist (theophylline) inhibit erythropoietin secretion 5. ẞ adrenergic stimulant 6. Cobalt salts 7. Hypoxia (main stimulus) ## II. Hormones - ✓ Thyroid - ✓ Glucocorticoids - ✓ Androgens - Erythropoietin ## III. Healthy Bone Marrow - = site of erythropoiesis - Bone marrow is destroyed by: - ✓ X-ray - ✓ Radiation - ✓ Drug as chloramphenicol - ✓ Malignant tumor - Result: all blood cells → cause aplastic anemia ## IV. Healthy kidney - form - 85% of erythropoietin ## V. Healthy Liver: - form - 15% of erythropoietin. - Globin (part of hemoglobin) - Stores vitamin B12 and iron ## VI. Diet: protein, vitamins, iron, trace elements - 1. Proteins of High biological value for formation of globin - 2. Vitamins: as vitamin B12 and folic acid, vitamin C ### 1. Vitamin B12 = Cyanocobalamin = Extrinsic Factor - Source: animal origin in liver, meat, chicken - Daily requirements=5µg, liver store 5 mg - Functions (importance) of vitamin B12: essential for - DNA synthesis, division, final maturation of RBC's - Myelination of nerves - Absorption of vitamin B12: - Parietal cells of gastric glands → secrete intrinsic factor (glycoprotein) - combine with vitamin B12 - Protect vitamin B12 From being digested & - Helps binding of vitamin B12 to its receptor at in brush membrane of mucosal cell in lower ileum - Pancreatic Trypsin is also required - pancreatic disease → cause defect in vit. vit. B12 B12 absorptio absorption - Vitamin B12 + intrinsic factor via pinocytosis, enter intestinal cell - Inside cell, vitamin become free, - absorbed to blood - carried by transcobalamin II - distributed - Excess is stored in the liver - Causes of deficiency: due to failure of absorption, not due to deficiency in diet except in vegetarians. - Absence of intrinsic factor (Pernicious anemia) - familial disease of elderly women - = autoimmune disease against parietal cells intrinsic factor & HCL - Gastrectomy - ↓Absorption: diseases of lower ileum (distal small intestine) - ↓storage: Liver diseases - Effect of deficiency: - Macrocytic anemia (bigger, irregular fragile cells) - Neurological symptoms as....... - Treatment: Vitamin B12 injection. ### Folic Acid: - Source: green vegetables, some fruits, liver, meat - easily destroyed by cooking - Functions: Essential for - DNA synthesis, division, final maturation of RBC's - Effect of deficiency: - Macrocytic anemia - Causes of deficiency: - Dietary deficiency (↓intake) / need (pregnancy) - ↓Absorption→ Diseases of small intestine. - Treatment of cancers with antifolate cytotoxic drugs (methotrexate) ### 3.Trace Elements - Cobalt & Copper: co-factor for HB synthesis - Cobalt: stimulates erythropoietin secretion & part of vitamin B12. ### 4.Iron: - Total body iron (3-5g) and functions | | | | :---- | :---- | | 70% | For formation of → hemoglobin | | 3% | For formation of myoglobin | | 2% | Part of many oxidative enzymes, e.g., catalase, peroxidase & cytochrome | | 25% | Stored in | | | ✓ liver | | | ✓ Spleen | | | ✓ Enterocytes | | | ✓ Bone marrow | | | Mainly in the form of ferritin | | | Ferritin coalesce together forming hemosiderin (another storage form) | | Very small | In Plasma bound to transferrin | - Importance of binding of iron to protein - Free iron is extremely toxic as it can generate reactive oxygen species (ROS) harmful to the cells - Iron requirements and iron balance: - Iron needed: 30 mg daily for heme synthesis - Most obtained from recycled iron: released from breakdown of hemoglobin of old RBC's inside macrophages in liver, spleen - Iron loss: in sloughed epithelial cells, hair, sweat, any blood loss - Adult male 0.5-1.0 mg iron loss/ daily - Adult female higher loss (2.0 mg/day) due to menstrual blood loss - To maintain iron balance, amount of absorbed iron = daily iron loss - Iron absorption, transport and storage, Mechanism - Diet contains iron in 2 forms: - Heme (in meat, meat products) - 10% of dietary iron, - More readily absorbable - Non-heme iron (in cereals, vegetables, beans, fruits and other plant origin) - 90% of dietary iron - Less absorbable - Most Dietary iron { ferric (Fe3+) non absorbable - Phytic acid (in cereals), oxalate & phosphates form insoluble iron salts absorption - Duodenum: main site of absorption (at apical membrane) - Reductase enzyme for Iron not reduced in stomach - DMT1 (divalent metal transporter 1) transport Fe2+ into enterocytes - Heme carrier protein (HCP 1) transport Heme into enterocytes - Inside enterocyte: depends on body requirments - If No demand - Iron stored as ferritin & hemosiderin - ↑demand - Iron is transported to blood via ferroportin (iron export protein) at basolateral border & - Oxidized by ferrioxidase enzyme to Fe3+ - In the blood: Fe3+ Carried by Transferrin (has 2 binding sites) (Normally, 35% saturated with iron) - to Bone marrow, Muscle, liver (that have receptors to transferrin) - Causes of iron deficiency: - 1- intake in diet than amount needed as in growing children & pregnant females - 2-absorption: - ✓ Partial gastrectomy - ✓ Vitamin C deficiency - ✓ HCI) (achlorhydria) - ✓ ↑Phytic acid, oxalates, and phosphates in diet - ✓ Diseases of duodenum - 3- Chronic blood loss: - ✓ Ancylostomiases infestations - ✓ Bleeding peptic ulcer - ✓ Piles - ✓ Excessive menstruation