Sickle Cell Disease

Sickle Cell Disease - Its Pathophysiology and Clinical Signs

Sickle cell disease is inheritable through the genes of parents who are either sicklers or carriers of the sickle cell trait genes

The normal RBC has HbA, is biconcave, non-nucleated and has a life span of 120 days. The RBC with haemoglobin S is less soluble and has a life span of about 26-35 days. Reduced oxygen tension coupled with low PH brings about distortion within the cell making them crescent shaped.

There is rapid destruction of the sickle cells leading to a thicker, heavier and sticky blood. The thickened blood is stagnated within the vessels leading to tissue hypoxia. The excess fragments resulting from excessive haemolysis become difficult for the liver and the spleen to cope with thereby resulting in overwork, hepatomegaly and splenomegaly.

The sluggish, crescent-shaped red blood cells occlude the blood vessels causing thrombosis/infarcts in organs e.g. in the lower limbs, joints, lungs, brain, kidneys and mesentery. The infarction/hypoxia cause bones/joints pain. There is chest pain due to lung infarction; dehydration due to renal concentration defects as a result of kidney infarction.

There is fatigue as a result of reduced blood and energy supply leading to decreased metabolism and further worsening in energy supply. Pyrexia is usually due to tissue hypoxia and necrosis leading to inflammatory reaction. There are signs and symptoms of nervous disturbance due to infarction and in severe cases stroke may arise.

The rapid haemolysis of the RBC and haemoglobin results in anaemia. Anaemia is then accompanied by angina pectoris, cardiomegaly, tachycardia and heart failure.

The Haem portion of the haemolysed Haemoglobin is broken down to amino acid, and Iron or ferritin (stored in the liver). The portion which contains bilirubin and biliverdin remains in circulation resulting in jaundice.

In childhood, the bone marrow attempts to compensate for the excessive RBC destruction, leading to the enlargement of the bones of the face and skull. This brings about the development of a high cheek bone and prominent forehead.

Over activity of the bone marrow brings about rapid proliferation of the white blood cells (WBC) which subsequently leads to increased susceptibility to infection. Patient may develop gallstones as a result of infection. Sometimes leg ulcers are present.

Clinical signs and symptoms

1. Joint pains
2. Fever
3. NDehydration
4. Chronic anaemia leading to tachycardia, cardiomegaly and heart failure.
5. Splenomegaly
6. Hepatomegaly
7. Reduced haemoglobin level
8. Kidney failure
9. Chronic ulcer above the ankle
10. Haematuria (blood in urine)
11. Susceptibility to infection
12. Priapism (persistent erection of the penis)
13. Paralysis due to cerebral hypoxia which may lead to hemiplegia or paraplegia
14. Mental retardation as a result of cerebral hypoxia and brain damage
15. Fatigue
16. High cheek bones
17. Prominent forehead

Diagnosis

1. Sickle Turbidity test: The blood specimen for test is mixed with anticoagulated blood and a special solution. A cloudy result at the end of the test is positive for sickle cell HbS.
2. Stained Blood Smear: This shows a few number of sickle erythrocytes.
3. ‘Fingerprint’ Electrophoresis: Reveals the status of the haemoglobin.
4. Sickle Cell Slide Preparation or Sickling Test: Reveals sickling erythrocytes.