1. Lec NOV 2016

2. Hemoglobin (Hb) 1.Objectives Structure
Variations in the structure of Hb
Normal level
Synthesis
02 capacity
Iron metabolism
2.Functions of RBC
3.Catabolism of RBC
4.Disorder of bilirubin :jaundice

3. a protein with a molecular weight of 64,450.made up of 4 subunits.
Structure of Hb
a protein with a molecular weight of 64,450.made up of 4 subunits.
heme conjugated to a polypeptide (globin)
a.Heme
porphyrin ring pyrrole units
iron (Fe2+ (ferrous iron) in the heme.
atom inserted in the center of porhyrin ring . synthesis -----mitochondria
b. globulin-----polypeptides chain----amino acids two Paris of polypeptides in each Hb molecule
Synthesis ----ribosomes.

6. 4 pyrrole units

8. Variation in the structure of Hb
1-Normal variations.
2- Abnormal variations.
Normal variations:
designated alpha chains (a-chains) ,beta ( β) chains, gamma ( ) chains, and delta ( ) chains.

9. NORMAL Hb
1.Embryonic Hb: early in gestation:
Gower 1.
Gower 2
Portland.
2.Fetal Hb (HbF): two alpha– chains and two gamma – chains.
Before birth, fetal Hb is gradually replaced .
3.Adult Hb (HbA): there are two types:
HbA1: two: alpha – chain – two beta – chains.
about 97.5% of the total HbA.
HbA2: which consists of two alpha – chains & two – delta – chains. About 2.5% of adult Hb is HbA2.

10. 4.Glycosylated Hb (HbA1c): its normal consists of a minor variation of HbA1. has a molecule of glucose attached to the N- terminal valine of the - chains. The normal level of HbA1c in adults is 5% of Hb (HbA1).In diabetics this level is elevated.

12. So normal hemoglobin are:
Embryonic Hb (Gower 1, Gower 2, Portland).
HbF.
HbA (HbA1, HbA2).
HbA1c.

13. Level of Hb in the blood blood is 16g/dL in men and 14g/dL in women.
Synthesis of Hb
Heme ---mitochondria and globin ribosomes.
O2 carrying power of the blood i.e. O2 capacity of blood:
One gm Hb ----with 1.34 mL of O2.
Whole blood in health adults contains 15g Hb/dl blood
So O2 capacity of blood = 1.34 mL O2 x gHb/vol. of blood.
= 1.34 mL O2/gHb x 15gHb/dL
= 20.1 mL O2 combine with Hb /dL blood

14. Hb4 + O2 Hb4O2 Hb4O2 + O2 Hb4O4 Hb4O4 + O2 Hb4O6 Hb4O6 + O2 Hb4O8
Reactions of Hb
1- Reaction of Hb with O2:
Hb4 + O2 Hb4O2
Hb4O2 + O2 Hb4O4
Hb4O4 + O2 Hb4O6
Hb4O6 + O2 Hb4O8
oxyhemoglobin
deoxyhemoglobin
O2 attaching to Fe2+ (ferrous iron) in the heme.
2.Reaction of Hb with CO2: CO globin
carbamino hemoglobin (carbaminoHb).

15. 3- CO reaches with Hb --carboxyhemoglobin
(carbon monoxyhemoglobin). Carbon monoxide is a poisonous substance.
Gasoline.
Cigarette smoke also produces CO and the
blood of smokers can contain
5% - 15% carboxyHb.
4- Hb---drug and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe2+) ---- ferric iron( Fe +3)
Hb -----methemoglobin (metHb).

16. Factors that inhibit iron absorption include
Iron Metabolism:
Dietary allowances: Recommended daily intake of iron is mg for females
Average adult male needs mg of dietary iron each day.
Sources:
Absorption:
Factors that enhance iron absorption such as:
Vitamin C.
Ascorbic acid.
HCl in gastric juice.
Fish.
Red – meat.
Factors that inhibit iron absorption include
Calcium can individual consuming a high calcium diet could develop iron deficiency anemia.
Milk.
Drugs such as tetracycline , antacids.
Tannins in tea and polyphenol in coffee..
Phytic acid in cereals.
Pancreatic secretion.

19. Clinical Note
Gastric secretion dissolve the iron and permit it to form soluble complexes with ascorbic acid and other substances that aid its reduction to the Fe2+ (ferrous) form. The importance of this function in humans is indicated by the fact that iron deficiency anemia is troublesome and frequent complication of partial gastroectomy.

20. 4.-Transport:
blood plasma with B – globulin transferrin.
5-Storage
Iron in excess of need is stored intra cellularly as ferritin & hemosiderin.
6-Daily loss of iron i.e. excretion of iron:
o.2 – 0.3 mg / day. About 5 – 25 mg or more be excreted in feces / day. Iron also loss through the skin.

23. Function of red blood cells

24. 1.carry blood gases.
A- Approximately 98.5% of the O2 from the lungs ---the tissue is transported in combination with Hb in the erythrocytes.
B- About 23% of CO2 is transported in combination with blood protein (mostly Hb).
.2. the erythrocytes contains a large quantity of carbonic anhydrase.

26. CA
CO2 + H2O H2CO H+ + HCO3
Carbonic Acid
3- Hb in the erythrocytes is an excellent acid-base buffer so that the RBC’s are responsible for most of the buffering power of whole blood.
Hb- + H+ HHb

27. Catabolism of Hemoglobin
Erythrocytes normal stay in the circulation for about 120 days in males and 110 days in females. As their proteins, enzymes,
.Old damaged RBC are removed from the blood by macrophages.
Globin -----amino acids.

28. The heme ------- into iron and bile pigments (biliverdin and bilirubin).
biliverdin converted -----to bilirubin and excreted in the bile.
The iron from the heme is reused for the hemoglobin synthesis.

29. .

30. Jaundice (Icterus):
Jaundice means a yellowish staining of the skin & sclera by bile pigments,
normal total plasma bilirubin concentration is 0.5 mg/dL
total plasma bilirubin is greater than 2mg/dL (hyperbilirubin).Types :
1.Hemolytic jaundice: for example sickle cell anemia; hereditary spherocytosis; erythroblastosis fetalis.
2.Obstructive jaundice: e.g. hepatitis (damage to hepatic cells).

31. Phototherapy (exposure to light)
Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half-life than bilirubin