The Physiology Of Blood

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NOMAD:2006: BP: HBANEM

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

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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

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HEMOGLOBIN MOLECULE

NOMAD:2006: BP: HBANEM

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SYNTHESIS OF HEMOGLOBIN 

REQUIRES: 



  

Nutrients such as Proteins, Vitamins & Minerals.

TAKES PLACE ONLY WITHIN THE NORMOBLASTCELLS.(INTRACELLUL AR) HEMOGLOBIN = HEME + GLOBIN HEME = PIGMENT GLOBIN = PROTEIN NOMAD:2006: BP: HBANEM

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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 & 7 are NOMAD:2006: 6 BP: HBANEM

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NOMAD:2006: BP: HBANEM

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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 8 

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

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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

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HEMOGLOBIN LEVELS : SIGNIFICANCE 

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. NOMAD:2006: BP: HBANEM

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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 &HBANEM FRUITS NOMAD:2006: BP:

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

NOMAD:2006: BP: HBANEM

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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 14

STRUCTURE & FUNCTION 







Hb A = α2 β2 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 NOMAD:2006: BP: HBANEM 15 METABOLISM.

STRUCTURE & FUNCTION 









 2,3 DPG AFFINITY OF Hb TO O2 THIS CAUSES THE OXYGEN TO BE FREELY DISSOCIATED. THIS HAPPENS AT THE TISSUE LEVEL. ENSURES FREE AVAILABLITY OF O2 TO THE TISSUES. THUS OXYGEN DELIVERY IS A NOMAD:2006: BP: OF HBANEM 16 BASIC FUNCTION

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: α2 β2: PREPONDERANT FORM: 68,000 Hb A2: α2 δ2 : A MINOR COMPONENT NOMAD:2006: BP: HBANEM

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Hb:PHYSIOLOGICAL VARIETIES 2. FETAL HEMOGLOBIN:  Hb F : α γ 2 2 



γ : GAMMA CHAINS HAVE MORE AFFINITY TO OXYGEN. THIS HELPS THE FETUS TO ACQUIRE OXYGEN FROM THE MOTHER. NOMAD:2006: BP: HBANEM

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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

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NOMAD:2006: BP: HBANEM

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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 BYNOMAD:2006: MIDDLE AGE. BP: HBANEM

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A SICKLED ERYTHROCYTE

NOMAD:2006: BP: HBANEM

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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

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BETA THALASSEMIA 

ERYTHROCYTES ARE ABNORMAL: HAVE LESS Hb A AND MORE OF Hb A2 & 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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NOMAD:2006: BP: HBANEM

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NOMAD:2006: BP: HBANEM

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

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IRON IN THE BODY BIOCHEMICAL FORM HEMOGLOBIN STORAGE Fe (ferritin & hemosiderin) MYOGLOBIN Myohemoglo bin Trace Heme Tissue enzymes

SITE Erythrocytes Phagocytes & Hepatic Parenchymal Redcells Muscle Fibres Tissue Cells NOMAD:2006: BP: HBANEM

CONC.

% OF TOTAL 2.5 Gms 60-65 1 – 1.5 Gms

25 -30

0.2 Gms 150200mg < 0.1 Gms

4 1 28

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

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IRON BALANCE: women  



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. NOMAD:2006: BP: HBANEM

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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

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

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NOMAD:2006: BP: HBANEM

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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

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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 NOMAD:2006: BP: HBANEM 35  Have Hypochromic, Microcytic 

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

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3. MEGALOBLASTIC ANEMIA: 









Deficiency of Vit B12 and or Folic Acid. Intrinsic Factor can also be deficient. Production of Erythrocytes becomes slow. They remain large, hve odd shapes and are called ‘Megaloblasts’ NOMAD:2006: BP: HBANEM Atropy of Stomach mucosa can

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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

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NOMAD:2006: BP: HBANEM

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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 NOMAD:2006: BP: HBANEM 40 Rupture and are lysed very easily.

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 NOMAD:2006: BP: HBANEM disease.

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NOMAD:2006: BP: HBANEM

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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 43

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. NOMAD:2006: BP: HBANEM Meats like Liver & spleen.

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IRON RICH DIETS

NOMAD:2006: BP: HBANEM

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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

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ANEMIA: EFFECTS ON CVS  

 

Decreased Blood Viscosity Decreased Peripheral Resistance. Increased blood flow to tissues Increased Venous Return.

NOMAD:2006: BP: HBANEM

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ANEMIA: EFFECTS ON CVS  

 

So increased Cardiac Output. Hypoxia causes peripheral vasodilatation which further increases blood flow Higher work load on the heart Cardiac Reserve decreases.

NOMAD:2006: BP: HBANEM

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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 49 NOMAD:2006: BP: HBANEM

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REVIEW 

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 A2NOMAD:2006: BP: HBANEM 50

REVIEW 



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

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NOMAD:2006: BP: HBANEM

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