Haemoglobin

Dr. Niranjan Murthy H.L Assistant Professor Dept of Physiology SSMC

HAEMOGLOBIN • • • • • • •

INTRODUCTION STRUCTURE TYPES SYNTHESIS FATE DERIVATIVES CLINICAL- ANAEMIAS - HAEMOGLOBINOPATHIES - PORPHYRIAS

• Pigment present inside RBCs • Carries O2 and CO2 • Responsible for red color of blood • Deficiency is called anaemia

STRUCTURE OF HEMOGLOBIN • Iron-protoporhyrin-globin forms a subunit • 4 subunits join to form a molecule of Hb • Iron is in ferrous ( Fe2+) form • Fe2+ binds 4 pyrrole rings, polypeptide chain and a molecule of O2

• 4 pyrroles join to form a ring called porphyrins • 4 polypeptide chains constitute globin • α,β,γ and δ are four important polypeptide chains • α chain has 141 a.a • β and γ chain have 146 a.a

TYPES OF HEMOGLOBIN • HbA- Adult Type- α2β2 • HbA2- 2% of adult Hb- α2δ2 • HbF- Fetal Type- α2γ2

• Hb gower1- ε2ζ2 • Hb gower2- ζ2β2

SYNTHESIS SUCCINYL Co-A + GLYCINE ALA synthase

δ-AMINOLEVUNIC ACID PORPHOBILINOGEN PROTOPORPHYRIN IX

Fe2+

GLOBIN

haem synthase

HAEM

HAEMOGLOBIN

FATE OF HAEMOGLOBIN • RBCs are destroyed in RES ( mainly spleen and bone marrow) after 120 days of life. • Macrophages phagocytose – hemolyse degrade haemoglobin – form Bilirubin – transport to liver with albumin – conjugated and detoxified – secreted in bile.

H a e m o g lo b in H aem P r o t o p o r p h y r in

Iro n

B iliv e r d in

ir o n p o o l

B ilir u b in

G lo b in CO

A m in o a c id p o o l

DERIVATIVES OF Hb 1) Oxyhaemoglobin (HbO2) – oxygenation reaction – combination with Fe 2+ 2) Carbaminohaemoglobin ( CO2Hb)  carbon dioxide combines with globin part 3) Carboxyhaemoglobin (COHb)  carbon monoxide binds with Fe 2+ { 250 times more affinity than oxygen}

4) Methhaemoglobin ( HHb)  oxidized haemoglobin 5) Sulfhaemoglobin 6) Glycated haemoglobin (HbA1c)  Glucose attached to terminal Valine in β chain. – integrated index of Diabetic control over 4 to 6 weeks

FUNCTIONS OF HEMOGLOBIN • 1. Transports O2 from lungs to tissues in the form of oxy-hemoglobin • 2. Transports CO2 from tissues to lungs in the form of carbamino-hemoglobin:- 30% of total CO2 transport • 3. Acts as a buffer- important in acid-base balance- 6 times more than plasma proteins

APPLIED ASPECTS • Normal Hb value : Males  14 – 18 gm/dL Females  12 – 16 gm/dL # ANAEMIAS # HAEMOGLOBINOPATHIES # PORPHYRIAS

ANAEMIAS Classification: I . Based on severity. v) Mild – 8-12gm/dL vi) Moderate – 5-8gm/dL vii) Severe - < 5gm/dL

II) Based on morphology of RBCs • • •

Normocytic normochromic – eg. Acute blood loss Macrocytic – eg Vit B12 & Folic acid deficiency Microcytic hypochromic – iron deficiency anaemia

III) Based on aetiology : • Blood loss – RTA, Surgeries • Haemolytic anaemias – congenital, malaria • Bone marrow depression- Aplastic anaemia • Nutritional anaemias- iron deficiency, megaloblastic, • Genetic causes- thalassaemia

HAEMOGLOBINOPATHIES Sickle cell anaemia: Valine replaces glutamate in the 6th position of β chain. Is common in African blacks Confers resistance against malaria Hb crystallizes & takes sickle shape under hypoxic conditions. Increased RBC sequestration

THALASSAEMIA • Reduced or absent synthesis of globin chains. Types:- alpha & Beta - Major & Minor β-thalassemia major cooley’s anaemia Treatment  # Transfusion – packed red cell is preferred. # Splenectomy # Bone Marrow Transplant

PORPHYRIAS • DEF: Inherited disorders involving specific enzymes in heme biosynthetic pathway • TYPES: • a) Hepatic porphyrias i) ALA dehydratase deficient porphyrias ii) Acute intermittent porphyrias iii) Porphyria cutanea tarda b) Erythropoetic porphyrias i) X-linked sideroblastic anemias ii) Congenital erythropoetic porphyrias

Other molecules containing Haem:i) Myoglobin – present in muscles - combination with single polypeptide chain. ii) Neuroglobin – present in CNS iii) Cytochrome enzymes – present in mitochondria iv) Peroxidases