Sickle cell disease

Pathophysiology of Sickle Cell Disease

1. SICKLE CELL ANAEMIA. OLUSIYAN OLUWATOBI

2. OUTLINE DEFINITION EPIDEMIOLOGY MECHANISM OF SICKLING CLINICAL FINDINGS LABORATORY FINDINGS TREATMENT PROGNOSIS CONCLUSION

3. SICKLE CELL ANAEMIA. This is a blood disorder resulting from the inheritance of homozygous(two) sickle Hb globin gene ( HbSS ),one from each parent. Caused by a substitution of glutamic acid by valine in position 6 in the beta -chain. Inherited as an autosomal recessive condition. The homozygous sickle anaemia( HbSS ) is the most common form of sickle cell diseases, while the doubly heterozygote conditions of HbSC and HbSD,HbSB etc also cause the sickling disease.

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5. SICKLE CELL ANAEMIA Characterised by low number of red blood cells Life span is 10-20 days. Normal cell releases O2 And maintains its biconcave shape. Deformation of cells due to Polymerization of Hb in sickle Cells when they release O2

6. HbS is insoluble and forms crystals when exposed to low oxygen tension. Deoxygenated sickle hemoglobin polymerizes into long fibres, each consisting of seven intertwined double strands with cross linking FIBRES OF SICKLE HEMOGLOBIN

7. Sickle Cell Anaemia -blood film

8. EPIDEMIOLOGY HbS gene is found primarily in populations of native tropical African origin(most African-Americans) Incidence in some African populations is as high as 40% 8% in African-Americans Rare in Caucasians of the Mediterranean descent

9. PATHOPHYSIOLOGY OF SICKLING At low Po2,deoxy-HbS polymerizes, resulting in the formation of rigid crystal-like rods( tactoids )which distorts the cell membrane and gives rise to their abnormal shape and sickled nature.. At high Po2(e.g in the lungs), deoxy-HbS unsickles and the cell assumes normal shape. The sickled cells, being rigid will block different areas of microcirculation or large vessels thereby obstructing blood flow. Vascular obstruction results in stasis of blood and ischaemia of tissue. If the ischaemic process goes unabated, it results in infarction, fibrosis and loss of tissue structure &function.

10. CLINICAL FEATURES Crises Vaso -occlusive Haemolytic Sequestration Aplastic. megaloblastic

11. CRISES(CONTD) VASO-OCCLUSIVE CRISIS: This is the most frequent and the most common clinical painful crisis-the hallmark of SCD’s during adult life.For the first 6 months of life,infants are protected by elevated levels of HbF.But as HbS replaces HbF,problem associated with sickling begins.The V-O crises occurs when the microvasculature is obstructed by sickled RBCs,causing ischemic injury to the organ supplied and resultant pain which can affect any body part often involving the abdomen,bones,joints, and soft tissues including:-

12. Organs affected by vaso -occlusive crisis Organ Brain Eye Lung Gallbladder Heart Spleen kidney Problem Stroke,seizures , hemiparesis Hemorrhage, blindness,ptosis Chest syndrome Stones Hyperdynamic flow,pulmonary hypertension. Enlarged(child);atrophic(adult) Loss of renal conc. leading to isosthenuria …

13. Contd. Organ Intestine Placenta Penis Digits Femoral head Bone Ankle Liver Problem Acute abdominal pain Stillbirths Priapism Dactylitis (Hand-foot syn.) Avascular necrosis Infarction,infection ( osteomyelitis ) Leg ulcers Chronic damage thru microinfarcts,hepatomegaly .

14. Dactylitis

15. PRECIPITANTS/TRIGGERS OF VASO-OCCLUSIVE CRISES Hypoxemia(Subnormal oxygenation of blood). Dehydration Infection (especially malaria, URTI and UTI) Extremes of temperature Emotional disturbance Stress Pregnancy

16. VISCERAL SEQUESTRATION CRISES These are caused by sickling and pooling of blood within organs which results in hypovolemia,hypotension and ultimately reduced venous return. Complications of this crises include; Splenic sequestration(which occurs often during the first 5 yrs of life in children). The acute sickle chest syndrome etc.

17. CRISES (CONTD) Aplastic crisis :-These occur as a result of infection with parvovirus B-19 or from folate deficiency.This virus infects RBC progenitors in bone marrow,resulting in impaired cell division. They are characterized by a fall in reticulocytes as well as haemoglobin . Hemolytic crisis:- characterized by a catastrophic fall in hematocrit,rise in reticulocytes,increased intensity of jaundice, and increasing reticulocyte count.

18. LABORATORY FINDINGS Hb conc is usually low compared to symptoms of anaemia:6-9g/ dL . Sickle cells,target cells and anisopoikilocytosis is observed in blood films. Features of splenic atrophy may be present. Screening tests for sickling are positive when the blood is deoxygenated with dithionate. Hemoglobin electrophoresis: In HbSS,no Hb A is detected. Amount of Hb F is variable, usually 5-15% (Larger amount are associated with milder disorders).

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20. MANAGEMENT OF SCA PROPHYLACTIC:- Avoidance of the precipitants of crises. The use of routine medications (Folic acid, multivitamins, malarial prophylaxis). Dehydration should be prevented. Maintenance of good general hygeine and nutrition. 22

21. TREATMENT(CONTD) Vaccination : Pneumococcal, Haemophilus and meningococcal vaccinations and regular oral penicillin are effective at reducing infection rate. Hepatitis B vaccination is also given as transfusion may be needed. Crises –Identify and remove the precipitating factor if possible. Treat by rest,warmth,rehydration by oral fluid/normal saline and antibiotics if infection is present. N:B-Blood transfusions is given only if there is severe anaemia with symptoms .E.g Routine transfusions throughout pregnancy are given to those with a poor obstetric history/a history of frequent crises.

22. Vaso -occlusion Pain control ( Analgesias,morphine pentazocine df118,NSAIDS and opiates,H ) Regular blood transfusion. Haemolytic Exchange blood transfusion Sequestration Exchange blood transfusion Patient must be monitored at regular intervals as attacks tend to be recurrent. Aplastic Blood transfusion Treatment for Parvovirus B19 Folic acid 24

23. Drugs Clotrimazole and magnesium both prevent dehydration of sickle cells. Reactivation of fetal globin genes with butyrate and hydroxyurea / hydroxycarbamide which can increase HbF levels. Gene therapy Sickle and thalassaemic transgenic mice models. Pre-implantation genetics.

24. PROGNOSIS Sickle cell anemia has no widely available cure. However, treatments to improve the anemia and lower complications can help with the symptoms and complications of the disease in both children and adults. Blood and marrow stem cell transplants may offer a cure for a small number of people but should be done in very severe cases.

25. CONCLUSION Sickle cell anemia varies from person to person. Some people experience episodes of chronic pain crises. However, with proper care and treatment, many people with the disease can have improved quality of life and good health most of the time. Because of improved treatments and care, people who have sickle cell anemia are now living into their forties, fifties, or longer.

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