8. Heme
• Iron porphyrin complex
• Tetrapyrrole rings with
central iron atom (Fe²⁺ form)
• Iron attached to nitrogen
atom of each pyrrole ring
• Oxygen binds to iron to form
oxyhemoglobin
10. Attachment of heme to globin
• Four units of heme in each Hb
• Each unit of heme attached to one of the
four polypeptide chain of globin
• Four iron atoms in each Hb
• Four molecules or 8 atoms of oxygen in
one Hb
13. Factors affecting synthesis
• Proteins: Necessary for globin synthesis
• Iron: Needed for heme synthesis
• Other metals:
- Copper: Helps in utilization of iron
- Cobalt: Increase erythropoietin
• Vitamin C: Helps in iron absorption
14. Normal content
– Men: 14 - 18 gm/dL
– Females: 12 - 16 gm/dL
– Newborns: 18 - 23 gm/dL
– After birth levels start to decrease &
stabilize at 3 months - 10.5 g/dL
– Gradually reaches to 12 g/dL at the
end of 1 year
15. Oxygen carrying capacity
• Amount of oxygen carried by fully saturated
hemoglobin
• 1.34 ml of oxygen is carried by 1 g of fully
saturated Hb
• So oxygen carrying capacity is: 1.34 x 15 = 20.1
ml/dL of blood
18. Transport of oxygen from lungs to tissues
• Initially in lungs 1 molecule of O₂ attach loosely &
reversible to Fe atom of Hb to form
oxyhemoglobin (Hb + O₂→ HbO₂)
• Attachment of one oxygen molecule increases the
affinity for next subsequent oxygen molecule
• Affinity is influenced by pH, temperature, 2,3-BPG
19.
20. Transport of carbondioxide from tissues to lungs
• CO₂ from the tissues is transported by
combining with amino acids of the globin
• Deoxygenated Hb forms carbaminohemoglobin
more readily than oxygenated Hb (So, venous
blood is more suitable for the transport of CO2
from tissues to lungs)
21. Control pH of blood
• Most important acid base buffer system in the
body
• Six times the buffering capacity as that of
plasma proteins
22. If haemoglobin would have been freely
present in the plasma instead of in
RBCs…..
it may lead to
• 1.Increased viscosity of blood →
increased blood pressure.
• 2.Increased osmotic pressure
• 3.Removal by tissue macrophages
• 4.Excreted by the kidney—
Haemoglobinuria
25. Adult hemoglobin
• HbA (α₂β₂)
- 97% of Hb of adult red cells
- After birth: HbF replaced by HbA
- Normal adult pattern by 6 months
• HbA2 (α₂δ₂)
- 3% of Hb in adult red cells
- Concentrationincreased in some
type of anemias
26. Fetal Hemoglobin (HbF)
• Seen in fetal RBC
• 2α & 2γ chains
• 70 to 90% of hemoglobin at term
• Normally replaced by HbA soon after birth
• 50% by 2 months
• Adult level (1%) by one year
• HbF concentration in adults increases in
some types of anemias,
hemoglobinopathies & leukemia
27. ADULT HEMOGLOBIN FETAL HEMOGLOBIN
Structure α2β2 α2γ2
Resistant to alkalies LESS MORE
Oxygen affinity LESS MORE
Life span 120 DAYS 80 DAYS
28. HbF is having greater affinity towards
O2 than adult Hb. Why???
• Adult Hb - 2,3 BPG binds with deoxygenated
Hb β subunits→ decrease affinity for O2
• poor binding of 2,3-BPG by the gamma
polypeptide chain in HbF
29. Embryonal Hb
–Confined to embryonic stage of
development
–3 types
–Gower 1 Hemoglobin (ζ2ε2)
–Gower 2 Hemoglobin (α2ε2)
–Hemoglobin Portland (ζ2γ2)
30. Hemoglobinopathies
• Abnormal formation of hemoglobin due to the
disorders of globin synthesis where heme
synthesis being normal
• Basic pattern is of two types:
- Formation of abnormal polypeptide chain
(Sickle cell anemia, HbC, HbD, HbE)
- Suppression of synthesis of polypeptide
chain of globin (Thalassemia)
33. Prevelance
• More in African population
• Present in Central India
• In Kerala common among tribes of Wayanad
& Attapady
• Individual with sickle cell trait has resistance
to falciparum type of malaria
35. Pathophysiology
Low oxygen tension/low pH at tissue level
↓
HbS become less soluble and precipitates as crystals
↓
Crystals elongate and RBCs become sickle shaped
↓
Sickle shaped RBC block the microcirculation (as less
flexible)
37. Consequences of sickling of RBCs
• Decreased flexibility
• Increased adhesiveness
• Microvascular (capillary-venule) occlusion
-Microinfarction
-Tissue ischemia
-End organ malfunction
• Shortened survival of RBCs → Hemolytic anemia
• Reticulocytosis
• Increase in HbF concentration
38. Sickle cell disease crisis
Low oxygen tension in the tissues causes sickling
↓
ruptured RBCs
↓
further decrease in oxygen tension
↓
still more sickling & RBC destruction
↓
serious decrease in RBCs within a few hours & in
some cases - death
39. Clinical symptoms-Sickle cell anemia
• Hemolytic anemia
• Jaundice
• Gall stones
• Leg ulcer- Ischemia & super
infection
• Increased susceptibility to
infections
• Brain - stroke
• Kidney - Necrosis
• Aseptic necrosis of bone
• Acute chest syndrome
• Hand and foot syndrome
43. Treatment
• Symptomatic treatment (Analgesics, fluid
intake, treat underlying infection…)
• Hydroxy urea to increase HbF (HbF decreases
the polymerization of deoxygenated HbS)
• Bone marrow transplantation
44. Double heterozygous states
• Combinationof HbS with other
hemoglobinopathies
• Sickle thalassemia, Sickle C disease etc
45. Hemoglobin C
• Substitutionof lysine for glutamic acid at β6
Hemoglobin D
• Substitutionof glutamine for glutamic acid
at β121
Hemoglobin E
• Substitutionof lysine for glutamic acid at
β26
47. β Thalassemia
–β chain : Decreased or absent
–Commonest type
Effects :
1. Excess of HbA2 (α2δ2)
2. Excess of HbF (α2γ2)
3. Abnormal globin chain precipitates
48. • Peripheral smear
- Microcytic hypochromic anemia
- Target cells (+)
– Serum iron & ferritin are normal
49. Two types of β Thalassemia
• β Thalassemia Major (Hb F > Hb A2)
• β Thalassemia Minor ( Hb A2 > Hb F)
50. β Thalassemia major
• Also known as Cooley’s or Mediterranean
anemia
• Most severe form
• Less common
• Homozygous transmission (from both
parents)
• Anemia develops in first few months of
life & becomes progressively severe
50
51. • Spleen & liver are enlarged (Extramedullary
hemopoiesis)
• Total absence of β chain synthesis
• HbF - Markedly increased
• Life span - Shorter
• Skeletal deformities present (Increased
erythropoiesis)
• growth retardation
• Blood transfusion for survival (Hemosiderosis)
52. β Thalassemia minor
• More common
• Heterozygous transmission (From one
parent)
• Anemia - mild
• Partial synthesis of β chain
• HbF - Normal or slightly increased
• Life span - Longer
• Transmit gene to offspring
53. α Thalassemia
• α chain : Decreased or absent
• Hydrops Foetalis
- No α chains are formed
- Made up of four γ chains (Hb
Barts)
- Cannot carry oxygen
- Life incompatible
- Still born or dies soon after
birth
55. Oxyhemoglobin
• Hemoglobin binds with oxygen
• Unstable & reversible form
• Iron in ferrous state
Reduced/Deoxygenated hemoglobin
• Hemoglobin from which oxygen is released
Carbaminohemoglobin
• Binding of hemoglobin with carbon dioxide
• Binds to globin chain of heme
56. Carboxyhemoglobin/Carbon monoxy
hemoglobin
• Hemoglobin binds with
carbon monoxide
• Hb has 200 to 250
times more affinity for
CO than for oxygen (CO
can displaces oxygen
from Hb even in low
concentration)
• Reduced oxygen
carrying capacity of
blood
57. • Reversible form
• Very low concentrationin normal situation
• In smokers high concentrationleading to
impairment of tissue oxygenation
58. Methemoglobin
• Iron in ferric state
• Cannot unite reversibly with oxygen atom
• Normally present in very low concentration
• Increased levels:
• Congenital methemoglobinemia - Defect of enzyme
system (NADH- MetHb reductase) which converts
metHb back to Hb
• Presence of some chemicals or drugs
59. Cyanmethemoglobin
• Methemoglobin + Potassium cyanide
Nitroso hemoglobin
• Nitric oxide + Hb
Sulfhemoglobin
• Sulphur (drugs or chemicals) + hemoglobin
• Iron in ferrous state
• Oxygen affinity of sulfHb is 100 times less than normal Hb
60. Glycosylated or glycated hemoglobin
• Non enzymatic attachment of glucose to
terminal valine in the beta chain of HbA
• Designated as HbA1C
• Normal value is <4%
• Glycation depends on glucose levels & free
radicals
61. • If >6.5% →chronic hyperglycemia
• Estimation of blood levels in treatment
of diabetes
• Gives an idea of glucose levels of
prolonged periods
63. • Long Essay
- 8 Year old girl from Wayanad came to OP with
complaints of sever chest pain & leg ulcers. On
examination her Hb conc is 7g/dl; serum
bilirubin- 4 mg/dl, gall stones present.
- Name the condition.
- What is the cause of this condition?
- Effects of this condition.
- Diagnostic investigation.
64. Physiological basis
• Sickle RBC in sickle cell anemia
• Life Span of RBC is increased if splenectomy is
done in sickle cell anemia
Spleen is the site of RBC destruction
Splenectomy→↑life span of RBC
It is helpful in sickle cell disease to prevent
anemia
