Hemoglobin & Anemias - the basics by Dr.M.Anthony David MD

ERYTHROCYTES, HEMOGLOBIN & ANEMIAS By Dr.M.Anthony David MD Professor of Physiology NOMAD:2006: BP: HBANEM

25 Trillion in an average 70 kg adult man. Men have about 4.5 to 5.5 Millions/cu.mm Women have about 4 to 5 Millions/cu.mm Decrease in the Erythrocyte Count is called Anemia Increase is called Polycythemia

POLYCYTHEMIA Increase in the number of Erythrocytes Is of two types Primary Polycythemia Secondary Polycythemia NOMAD:2006: BP: HBANEM

ERYTHROCYTE MORPHOLOGY They are biconcave discs in shape about 7.5 Microns in diameter They are about 2 – 3 Microns thick They have no nuclei. Why? They make place for Hemoglobin Hemoglobin takes up a third of the volume of each erythrocyte NOMAD:2006: BP: HBANEM

HEMOGLOBIN A CHROMO PROTEIN MOLECULE. IS PRESENT EXCLUSIVELY WITHIN THE ERYTHROCYTE. ROUGHLY ONE THIRD OF THE VOLUME OF THE ERYTHROCYTE IS OCCUPIED BY HEMOGLOBIN. IS A COMPLEX PROTEIN WITH TWO MOIETIES: HEME + GLOBIN. NOMAD:2006: BP: HBANEM

HEMOGLOBIN MOLECULE NOMAD:2006: BP: HBANEM

SYNTHESIS OF HEMOGLOBIN REQUIRES: Nutrients such as Proteins, Vitamins & Minerals. TAKES PLACE ONLY WITHIN THE NORMOBLASTCELLS.(INTRACELLULAR) HEMOGLOBIN = HEME + GLOBIN HEME = PIGMENT GLOBIN = PROTEIN NOMAD:2006: BP: HBANEM

HEME Iron containing Porphyrin. Iron-Protoporphyrin IX Porphyrin is formed from 4 Pyrrole rings joined by four methane bridges. The side chains 1,3 5, & 8 are Methyl. The side chains 2 & 4 are Vinyl. The side chains 6 & 7 are Propionic Acid. NOMAD:2006: BP: HBANEM

HEMOGLOBIN CATABOLISM Macrophages, mainly the Kupffer cells in the liver phagocytose Hemoglobin. HEMOGLOBIN = HEME + GLOBIN HEME  Fe ++ + PORPHYRIN PORPHYRIN  BILVERDIN + CO. CO  TO THE LUNGS AND OUT. BILVERDIN REDUCED TO BILIRUBIN AND SENT TO BLOOD & LIVER FOR EXCRETION. NOMAD:2006: BP: HBANEM

Fe ++ + TRANSFERRIN TO BONE MARROW FOR REUSE. Fe ++ + PORPHYRIN  HEME (In the presence of the enzyme, Heme Oxidase .) HEME + GLOBIN  HEMOGLOBIN HEMOGLOBIN CATABOLISM NOMAD:2006: BP: HBANEM

HEMOGLOBIN:NORMAL LEVELS MALES: 14 – 18 Gm% FEMALES: 12 – 15 Gm% AT BIRTH: 23 Gm% FALLS TO 10.5Gm% BY THIRD MONTH RISES GRADUALLY TO 12.5 Gm% AT 1 YEAR OF AGE. NOMAD:2006: BP: HBANEM

1 Gm OF HEMOGLOBIN, WHEN FULLY SATURATED, COMBINES WITH 1.34 ml OF OXYGEN. HEMOGLOBIN CONCENTRATION IS THEREFORE AN INDEX OF THE OXYGEN CARRYING CAPACITY OF THE BLOOD. HEMOGLOBIN LEVELS : SIGNIFICANCE NOMAD:2006: BP: HBANEM

HEMOGLOBIN FORMATION: FACTORS 1. PROTEINS: HIGH POTENCY: ANIMAL PROTEINS LIKE LIVER, SPLEEN KIDNEY & HEART MOST POTENT MUSCLE PROTEINS MEDIUM POTENT LEAST POTENCY: CEREALS, DAIRY PRODUCTS, VEGETABLES & FRUITS NOMAD:2006: BP: HBANEM

2. IRON: HEMOGLOBIN HAS 2.5 Gms OF THE TOTAL BODY IRON OF 4 - 5 Gms IN AN AVERAGE HEALTHY ADULT. HEMOGLOBIN FORMATION: FACTORS NOMAD:2006: BP: HBANEM

HEMOGLOBIN: STRUCTURE HAS FOUR POLYPEPTIDE CHAINS OF TWO TYPES: EACH IN DUPLICATE. HbA: ADULT HEMOGLOBIN HAS: 2 α CHAINS AND 2 β CHAINS. EACH CHAIN IS ASSOCIATED WITH ONE HEME GROUP. THUS THERE ARE FOUR HEMES TO THE MOLECULE, A TETRAMER OF MW 68,000 NOMAD:2006: BP: HBANEM

STRUCTURE & FUNCTION Hb A = α 2 β 2 HEMOGLOBIN COMBINES LOOSELY & REVERSIBLY WITH OXYGEN. IT’S AFFINITY TO OXYGEN IS DECREASED IN THE PRESENCE OF 2,3, DIPHOSPHO GLYCERATE (2,3 DPG) 2,3 DPG IS A PRODUCT OF GLUCOSE METABOLISM. NOMAD:2006: BP: HBANEM

 2,3 DPG   AFFINITY OF Hb TO O 2 THIS CAUSES THE OXYGEN TO BE FREELY DISSOCIATED. THIS HAPPENS AT THE TISSUE LEVEL. ENSURES FREE AVAILABLITY OF O 2 TO THE TISSUES. THUS OXYGEN DELIVERY IS A BASIC FUNCTION OF HEMOGLOBIN STRUCTURE & FUNCTION NOMAD:2006: BP: HBANEM

HEMOGLOBIN: VARIETIES HEME IS THE SAME VARIETIES ARE DUE TO CHANGES IN THE PEPTIDES OF THE GLOBIN MOIETY. PHYSIOLOGICAL VARIETIES: 1. ADULT Hb: Hb A: Hb A: α 2 β 2 : PREPONDERANT FORM: 68,000 Hb A2: α 2 δ 2 : A MINOR COMPONENT NOMAD:2006: BP: HBANEM

Hb:PHYSIOLOGICAL VARIETIES 2. FETAL HEMOGLOBIN: Hb F : α 2 γ 2 γ : GAMMA CHAINS HAVE MORE AFFINITY TO OXYGEN. THIS HELPS THE FETUS TO ACQUIRE OXYGEN FROM THE MOTHER. NOMAD:2006: BP: HBANEM

Hb: PATHOLOGICAL : SICKLE CELL DISEASE CAUSE: ABNORMAL POLYPEPTIDES DUE TO SUBSTITUTION OF AMINO ACIDS SUPRESSION OF SYNTHESIS OF POLYPEPTIDE CHAINS. Hb S: OCCURS IN 0.3 to 1 % OF WEST AFRICAN & AMERICAN BLACK PEOPLE VALINE IS SUBSTITUTED FOR GLUTAMIC ACID AT 6 POSITION OF BETA CHAIN. NOMAD:2006: BP: HBANEM

SICKLE CELL DISEASE WHEN Hb S IS REDUCED, IT BECOMES LESS SOLUBLE & ‘GELS’ THIS CHANGES THE SHAPE OF THE ERYTHROCYTES. THEY BECOME ‘SICKLE’ SHAPED THEY INCREASE THE BLOOD VISCOSITY AND UNDERGO HEMOLYSIS. THIS IS A SERIOUS CONDITION, CAN BE FATAL BY MIDDLE AGE. NOMAD:2006: BP: HBANEM

A SICKLED ERYTHROCYTE NOMAD:2006: BP: HBANEM

Hb: PATHOLOGICAL : THALASSEMIAS DEFECT IN THE SYNTHESIS OF EITHER ALPHA & BETA CHAINS OF GLOBIN. OCCURS IN HOMOZYGOUS OFFSPRING OF HETEROZYGOUS PARENTS. BETA THALASSEMIA IS MORE COMMON. BETA CHAIN NOT FORMED. NOMAD:2006: BP: HBANEM

BETA THALASSEMIA ERYTHROCYTES ARE ABNORMAL: HAVE LESS Hb A AND MORE OF Hb A 2 & Hb F. RAPID HEMOLYSIS OCCURS IN VIVO. CAUSES HYPOCHROMIC ANEMIA. CHILDREN FAIL TO THRIVE. THEY DIE YOUNG. NOMAD:2006: BP: HBANEM

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IRON METABOLISM & ANEMIAS By Dr.M.ANTHONY DAVID, MD Professor of Physiology NOMAD:2006: BP: HBANEM

IRON IN THE BODY NOMAD:2006: BP: HBANEM BIOCHEMICAL FORM SITE CONC. % OF TOTAL HEMOGLOBIN Erythrocytes 2.5 Gms 60-65 STORAGE Fe (ferritin & hemosiderin) Phagocytes & Hepatic Parenchymal cells 1 – 1.5 Gms 25 -30 MYOGLOBIN Myohemoglobin Red Muscle Fibres 0.2 Gms 150-200mg 4 Trace Heme Tissue enzymes Tissue Cells < 0.1 Gms 1

IRON BALANCE ADULT MEN: DIET :  5 – 10 mg/day LOSS: 0.4 mg : Urine 0.8 mg : Bile Traces : Mucosa of GI tract. NOMAD:2006: BP: HBANEM

HAVE MORE IRON LOSS: Monthly Menstrual Periods: 50 – 80 ml Child Bearing & Rearing : 15 Months: 900 mg (2mg/day) How? Fetal Iron Content : 400mg. Iron in Placenta/Uterus : 150mg. Blood loss in Parturition:170mg. Iron in Breast milk : 180mg. TOTAL : 900mg. IRON BALANCE: women NOMAD:2006: BP: HBANEM

IRON ABSORPTION SITE: Duodenum/Upper Jejunum via brush border. Ferrous form better absorbed than Ferric form Ascorbic Acid (Vit C) helps absorption. Phosphates/Phytates reduce ionic Iron absorption by forming insoluble salts. Heme in diet is directly absorbed Iron deficiency states enhance Iron absorption. NOMAD:2006: BP: HBANEM

ANEMIAS Deficiency of Hb in the blood caused by either:  RBC Count or  Hb in the RBCs NOMAD:2006: BP: HBANEM

ANEMIAS: CLASSIFICATION HEMORRHAGIC ANEMIA APLASTIC ANEMIA MEGALOBLASTIC ANEMIA PERNICIOUS ANEMIA HEMOLYTIC ANEMIA SICKLE CELL ANEMIA IRON DEFICIENCY ANEMIA SECONDARY ANEMIA (RENAL) NOMAD:2006: BP: HBANEM

1. HEMORRHAGIC ANEMIA (BLOOD LOSS) ACUTE : Sudden loss of blood RBC Count decreased for 1 – 3 days RBCs are restored in 3 – 6 weeks CHRONIC BLOOD LOSS : They cannot absorb Fe enough to form Hb Have Hypochromic, Microcytic Anemia. NOMAD:2006: BP: HBANEM

2. APLASTIC ANEMIA: Lack of functioning Red Bone Marrow, the hemopoietic tissue. Caused by exposure to gamma ray radiation (Nuclear Bomb Blast) Excessive exposure to X rays Exposure to certain industrial chemicals. NOMAD:2006: BP: HBANEM

3. MEGALOBLASTIC ANEMIA: Deficiency of Vit B 12 and or Folic Acid. Intrinsic Factor can also be deficient. Production of Erythrocytes becomes slow. They remain large, have odd shapes and are called ‘Megaloblasts’ Atropy of Stomach mucosa can cause loss of Intrinsic factor & this anemia is called Pernicious Anemia. NOMAD:2006: BP: HBANEM

MEGALOBLASTIC ANEMIA: Intestinal Sprue or Malabsorption Syndrome can also cause this. Megaloblasts are over sized, anisocytic. They have fragile membranes and rupture easily. TREATMENT: Vitamin B12 Folic Acid if it is nutritional. NOMAD:2006: BP: HBANEM

NOMAD:2006: BP: HBANEM MEGALOBLASTS

4. HEMOLYTIC ANEMIAS Mostly heriditary. Cells are fragile, rupture easily as they move through the capillaries. The life span of erythrocytes is reduced. HERIDITARY SPHEROCYTOSIS: Small spherical erythrocytes. Cannot be compressed even slightly Rupture and are lysed very easily. NOMAD:2006: BP: HBANEM

5. SICKLE CELL ANEMIA Affects 0.3 to 1% of West African & African blacks. The Beta chains of Hemoglobin are defective. They have Hb S Sickling occurs when Hb loses Oxygen. A vicious circle of events occurs:  Oxygen tension  Sickling  Rupture of Erythrocytes  Further  Oxygen tension This is called a crisis in sickle cell disease. NOMAD:2006: BP: HBANEM

ERYTHROBLASTOSIS FETALIS Rh Isoimmunisation causes this disease Antigen antibody reaction causes lysis of erythrocytes. Seen in Neonates and is also called Icterus Gravis Neonatorum. Excess Bilirubin enters the brain, causing ‘kernicterus’ Can become fatal. NOMAD:2006: BP: HBANEM

IRON DEFICIENCY ANEMIA The most common type of anemia . Caused by nutritional deficiency of Iron. Erythrocytes are smaller and have less Hb. So they are called Microcytic & Hypochromic. Treated by taking Iron rich diets. Dark green leafy vegetables: esp Drumstick leaves. Meats like Liver & spleen. NOMAD:2006: BP: HBANEM

IRON RICH DIETS NOMAD:2006: BP: HBANEM

SECONDARY ANEMIA(RENAL) Renal Diseases can cause decreased Erythropoietin . Erythropoietin is essential for proper production of erythrocytes (Erythropoiesis) Renal disease thus causes Anemia. NOMAD:2006: BP: HBANEM

REVIEW Erythrocytes: 4.5 – 5.5 Million/cc of blood in Males 4 – 5 Million/cc of blood in females Biconcave discs 7.5 Microns X 2.5 Microns No nucleus Hemoglobin takes up a third volume NOMAD:2006: BP: HBANEM

REVIEW Hemoglobin is a chromoprotein present exclusively within the erythrocytes. Hb synthesis takes place within the normoblasts. Hemoglobin = Heme + Globin. Heme is an Iron containing Porphyrin. Iron is present in the Ferrous form. Oxygen can be loosely attached to Hb. NOMAD:2006: BP: HBANEM

Normal blood levels of Hemoglobin: Males : 14 – 18 Gm% Females : 12 – 15 Gm% 1 Gram of Hemoglobin combines with 1.34 ml of Oxygen. Varieties of Hemoglobin include: Hb A, Hb F Hb S, Hb A 2 REVIEW NOMAD:2006: BP: HBANEM

Anemia is a decrease in either Hb or RBCs. Types of Anemia: Hemorrhagic Aplastic Megaloblastic Pernicious Hemolytic Sickle Cell Iron deficiency Secondary (Renal) REVIEW NOMAD:2006: BP: HBANEM

NOMAD:2006: BP: HBANEM THANKS FOR LISTENING!

Hemoglobin & Anemias - the basics by Dr.M.Anthony David MD

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Hemoglobin & Anemias - the basics by Dr.M.Anthony David MD