Nutrition

1. HEAMOLYTIC ANAEMIAS
• Anaemias occur when the rate of blood loss of whatever form exceeds
bone regenerations and this occurs when the loss is 8 times higher than
regenerations.( Definitions of anaemia and classifications)
• The optimal haemoglobin concentration needed to meet physiologic needs
varies by: age, sex, elevation of residence, smoking habits and pregnancy
status.
• The following are common feature of haemolytic anaemia,:
• Life span of RBC is reduce below 120days by premature destruction.
• There is erythropoietin serum elevation and compensatory erythropoiesis.
• There is body accumulation of RBC haemoglobin degradation products.

2. Classifications
• Inherited haemolytic anaemia: parents pass the gene for the
condition on to their children.
• Acquired haemolytic anaemia: not in born .
• Based on site of rbc destruction :( Extravascular and Intravascular).
• ACQUIRED GENETICAL DEFECTS HAEMOLYTIC
ANAEMIA
Mechanism: 1.Deficiency of phosphatidylinositol –linked glycoproteins
antibody mediated destructions

3. • paroxysmal nocturnal haemoglobinuria, haemolytic disease of the
newborn(Rh disease) transfusion reactions and drug induced
autoimmune disorders.
• 2, Mechanical trauma:
• i,Microangiopathic haemolytic anaemia: haemolytic uraemic
syndrome, DIC and thrombocytopaenia purpura.
• ii,Cardiac traumatic haemolysis: defective cardiac valves.
• iii, Repetitive physical trauma: marathon running ,drumming karate
chopping.

4. • iv,Infections of rbc :Malaria, babesiosis
• v,Toxic or chemical injury: sepsis, snake venoms lead poisoning
• vi, Membrane lipid abnormalities: A betalipoproteinaemias severe
liver diseases
• INHERITED GENETIC DEFECT HAEMOLYTIC ANAEMIA.
• i,Red cell membrane disorders: Hereditary spherocytosis and
elliptocytosis.
• ii,Enzyme deficiencies:
• a, Hexose monophosphate shunt enzyme deficiencies:G6PD
deficiency,

5. • and glutathione synthetase deficiency.
• b,Glycolytic enzyme deficiencies: Pyruvate kinase deficiency and
hexokinase deficiency.
• iii,Haemoglobin abnormalities:
• a,Deficiency globin synthesis: Thalassemia syndromes.
• b,structurally abnormal globins (haemoglobinopathies): Sickle cell
disease, unstable haemoglobins.

6. • Characteristics of Extravascular haemolysis:
Clinical features regardless of cause-:Anaemia, splenomegaly and jaundice.
• There is reduced plasma haptoglobin.
• Intravascular haemolysis: (more commoner than extravascular.)
• Clinical features regardless of cause-: Anaemia,
haemoglobinaemia,haemoglobinuria heamosiderinuria and jaundice.
• Serum haptoglobin is depleted free haemoglobin oxidises to
methemoglobin.
• In all type of uncomplicated haemolytic anaemia the excess serum birubin
is unconjugated.

7. • Morphological changes: Regardless of cause and type of haemolytic
anaemia: Bone marrow: Increased erythroid
series,(Normoblast),haemosiderosis in bone marrow, spleen and liver.
• Extramedullary haemopoiesis can occur in liver, spleen and lymph
nodes in severe anaemia.
• Chronic haemolysis leads to elevated biliary bilirubin secretion
leading to formation of pigment gall stone (cholelithiasis.)

8. HEREDITARY SPHEROCYTOSIS
• It’s an autosomal dominant disorder in 75% case and other forms 25
% have severe forms known as compound heterozygosity.
• Its highest in Europe with a rate of 1:5000.
• This is an intrinsic defect RBC membrane skeletal defect.
• This render the rbc spheroid less deformable and vulnerable to
splenic sequestration and destructions.
• HS is caused by a mutation that lead to an insufficiency membrane
skeletal components.
• The life span of affected rbcs is reduced to average of 10to20 days.

9. • young HS rbcs are normal in shape, the deficiency of the membrane
skeleton reduces the stability of lipid bilayer.
• This leads to loss of membrane fragments as the rbc age in
circulation.
• The loss of membrane relative to cytoplasm ‘’forces’’ the cell to
assume the smallest possible diameter.
• Clinical features: (Jaundice, splenomegaly ,anaemia)
• Peripheral slide :Abnormal dark-staining small cells lacking a central
zone of pallor. Spherocytosis is distinct but not pathognomonic.

10. HAEMOLYTIC DISEASE DUE TO RED CELL ENZYME
DEFECTS:GLUCOSE-6-PHOSPHATE
DEHYDROGENASE DEFICIENCY
• Abnormality in the hexose monophosphate shunt /glutathione
metabolism due to :(deficiency or impaired enzyme function).
• This reduces the capacity to protect themselves against oxidative
stress.(injuries).
• This leads to haemolysis of the affected rbcs.
• Causes: most important G6PD deficiency, a recessive X-linked trait
making male at a higher risk for symptomatic disease.
• There are several hundred of G6PD are known but only(G6PD-,
G6PD) two variant cause most clinical significancy.

11. • G6PD- is present in about 10% of American blacks.
• G6PD (Mediterranean type) is prevalence in Middle East.
• The variants are protective against PF malaria infections.
• Older cell are more prone than young cell.
• Exposures that generate oxidant stress cause a characteristic episodic
G6PD deficiency haemolysis which can intravascular or extravascular.
• Clinical features:
• RBCS have Heinz bodies seen as black inclusion bodies on the cell
membranes.

12. • Heinz bodies may be plucked off by macrophages causing the rbc to
have a bite taken out of them the other form may present as
spherocytes.
• The condition is usually self limiting since only old G6PD are
susceptible.

13. SICKLE CELL ANAEMIA
• Sickle cell anaemia, or sickle cell disease (SCD), is a autosomal genetic
disease of the red blood cells (RBCs), the RBCs have an abnormal crescent
shape resembling a sickle.
• The four main types of sickle cell anemia are caused by different
mutations in these genes.
• Hemoglobin SS disease. ...
• Hemoglobin SC disease. ...
• Hemoglobin SB+ (beta) thalassemia. ...
• Hemoglobin SB 0 (Beta-zero) thalassemia. ...
• Hemoglobin SD, hemoglobin SE, and hemoglobin SO.
• Sickle cell trait.

14. Hemoglobin SS disease
• It’s a point mutation in the 6th codon of the ₿ globin and glutamate is
replaced with valine.
• Hbs molecule under go polymerization in low oxygen tension.
• Four major types of crises are recognised in sickle cell anaemia:
Aplastic,
• Acute sequestration,
• Hyper-haemolytic,
• Vaso-occlusive crises

15. • Interactions of HbS with other types of HB in the cells.
• Sickle cell trait in this about 40% is HbS the rest is HBA this interferes with
polymerisation. Heterozygous individual do not sickle except in very
extreme conditions of hypoxia.
• HbF inhibits the polymerisation of HbS even more than HbA thus infants
do not become symptomatic until 5-6months of age when HbF levels fall.
• In individuals with Hereditary persistentHbF have much less severe
anaemia.
• HbC variant in which lysine substitute glutamate at position 6th the ₿
globin .

16. • IN HbSC the % of HbS is 50% compared with 40% in HbAS cell.
• HbSC cell loose salt and water becoming dehydrated. This increase
the intracellular concentration of HbS these two factor cause
polymerisation. This condition is called HbSC disease but is milder
than HbS.
• MCHC: higher HbS concentrations increase the chance of
polymerisation in any low oxygen tension.
• Intracellular dehydration which increase MCHC facilitate sickling and
the converse is also true.
• PH: increased Ph reduces sickling the converse is true.

17. • Transit time of rbc through microvascular beds:Sickling is commoner
in slower microvascular beds than the fast ones. This occurs in Spleen
inflamed tissues and bone marrow with the slowest microvascular
transit time.
Morphology: Peripheral blood: sickled cells, reticulocytes, target cells
and Howell-Jolly bordies( small ) nuclear remnants. The bone marrow is
hyperplastic due to compensatory erythroid hyperplasia.
Marrow expansion lead to bone resorption and secondary new bone
formation.

18. • This leads to:
• Prominent cheek bone,
• Crew-cut skull X-ray changes
• Early splenomegaly with adult hood auto -splenectomy.
• Extramedullary haematopoiesis.
• Pigment gall stones.
• Infactions can occur in :bone,brain, kidneys liver ,retina and
pulmonary vessels among others.
• In adults vascular stagnations leads to uclers.

19. • Clinical features. Moderate to severe haemolytic anaemias associated
with reticulocytosis, hyperbilirubinemia and sickled cells.
• Crisis 4types. The vaso-occlusive in children there is the foot and hand
syndrome or dactylitis of bones.
• Acute chest syndrome very dangerous vaso- occlusive syrome.This
involves the lungs, presents with fever, cough ,chest pain and
pulmonary infitrates,it’s usually initiated by any acute inflammatory
condition in the lung and the becomes congested like a spleen.
• Sequestration and vaso-occlusive syndromes are treated with
transfusion.

20. • Chronic hypoxia toll:
• Impaired growth and development( secondary sex characteristics.
• Organ damage to the heart, kidneys ,lungs and spleen.
• Increase susceptibility to infections with encapsulated organism in
children due to altered splenic function (congestion and poor blood
flow.) In adult due to auto splenectomy.
• The alternative path way of complement activation is impaired
leading to poor psonisation. Pneumococcus Pneumoniae and
haemophilus ifluenzae meningitis and septicaemia are common.

21. • Diagnosis:
• Sickling test
• HB electrophoresis.
• Treatment: Folic acid, hydroxyurea and rehydration.
• THALASSEMIA
• These are heterogeneous groups of disorders inherited as mutations
with decreased synthesis of adult haemoglobin.
• Adult hemoglobin is composed of two alpha (α) and two beta (β)
polypeptide chains.

22. • There are two copies of the hemoglobin alpha gene
(HBA1 and HBA2), which each encode an α-chain, and both genes are
located on chromosome 16.
• The hemoglobin beta gene (HBB) encodes the β-chain and is located
on chromosome 11.
• β- thalassemia is caused by deficient synthesis of β-chain.
• α-thalassemia is caused by deficient synthesis of α-chain.
• Thalasemias are the most common blood disorder on aggregate. It’s
endemic in Mediterranean, middle East North Africa India and Asia.
• It’s also emerged as a protectiveadaptation against malaria

23. Β- THALASSEMIA
• β- thalassemia mutation and heterogeneous with more than a hundred
causative different genes. There are broadly two forms:
• Βo mutations associated with absence of β-globin chains.
• Β+ mutations characterised by reduced(but detectable) β-globin chains
synthesis.
• Types: B- thalassemia major homozygous :(Bo/ Bo,B+/B+ andBo/B+) this
form is severe require blood transfusions
• B- thalassemia intermedia variable(Bo/B+,B+/B+,Bo/B andB+/B),
severe but does not require regular blood transfusions
• B-thalassemia minor heterozygous(Bo/B and B+/B) Asymptomatic
with mild or absent anaemia,red cell abnormalities seen.

24. Α-THALASSEMIAS
• α-thalassemia
• Silent carrier -/a a/a this is asymptomatic no rbc abnormality.
• α-thalassemia trait -/- a/a asymptomatic like b- thalassemia minor.
• HbH disease -/a -/a (black Africans and Asians) -/- -/a severe,
resembles b-thalassemia intermediate.
• Hydrops fetalis -/- -/- lethal in utero without transfusion.
• Morphology: severe marked variation in size(anisocytosis) and shape
poikilocytosis,michrocytosis hypochromia and target
cells.Reticulocyte count is elevated, normoblast are seen in the
peripheral. Bone marrow and spleen are also severely affected.

25. • There is expansion of haemopoiesis in un transfused patients in the
face and skull the marrow can erode the exiting cortical bone and
induce new bone formation giving rise to a crew cut appearance on x-
ray.
• Both phagocyte hyperplasia and medullary haemopoiesis contribute
to splenic enlargement. Can be up to 1.5kg. The liver and lymph node
are also enlarged by extra medullary haemopoiesis.
• Hemosiderosis and secondary haemochromatosis occur in almost all
patients. The deposited iron most often damages the liver ,heart and
panceas.