Sickle Cell Disease

Sickle cell anemia is a autosomal recessive genetic disorder. It affects the BETA GLOBIN gene on the CHROMOSOME 16. In sickle cell anemia, the hemoglobin abnormality consists of a point mutation in the beta chain gene for hemoglobin; the resulting abnormal gene product is denoted HbS. If you are heterozygous for the HbS gene you will have what is called sickle trait, which is asymptomatic .

 If you are homozygous for the HbS gene  you will get sickle cell disease, which is symptomatic in most patients.
 The problem with HbS is that as it releases oxygen, it polymerizes and aggregates with other HbS molecules, making the red cell stiff and distorted. These distorted, sickle-shaped red cells are fragile so the patient can end up with a hemolytic anemia.
This can occur as pure disease (homozygous) or trait (heterozygous) or with other haemoglobinopathies. It is common. in Negroes. It is due to Hb-s  which is much less soluble than Hb-A  hence deoxygenation insoluble form  sickling of RBC.

This causes:
•    Removal by RE system. 
•    Blockage of microvessels causing  ischaemia.
 

Hepatitis B virus (“serum hepatitis”)
- Hepatitis B (HBV) may cause acute hepatitis, a carrier state, chronic active disease, chronic persistent disease, fulminant hepatitis, or hepatocellular carcinoma  
- It is caused by a DNA virus, the virions are called Dane particles. 

b. Incubation period: ranges from 4 to 26 weeks, but averages 6 to 8 weeks.
a. Symptoms last 2 to 4 weeks, but may be asymptomatic.
c. The hepatitis B viral structure has also been named the Dane particle.

Transmission is through contact with infected blood or other body fluids. It can be transmitted by sexual intercourse and is frequently transmitted to newborns of infected mothers by exposure to maternal blood during the birth process
- Associated antigens include core antigen (HBcAg) and surface antigen (HBsAg).
The latter is usually identified in the blood for diagnosis. HbsAg is the earliest marker of acute infection.
HBeAg is also associated with the core. Its presence indicates active acute infection; when anti-HBeAg appears, the patient is no longer infective
- HBV is associated with hepatocellular carcinoma; HBsAg patients have a 200-fold greater risk of hepatocellular carcinoma than subjects who have not been exposed. 

Antibodies  
- Antibodies to surface antigen (anti-HBs) are considered protective and usually appear after the disappearance of the virus.
-Antibodies to HBcAg are not protective. They are , detected just after the appearance of HBsAg and are used to confirm infection when both HBsAg and anti HBs are absent (window).
- Antibodies to HBeAg are associated with a low risk of infectivity.

d. Infection increases the risk for hepatocellular carcinoma.

e. Laboratory assay of hepatitis B antigens and antibodies:

(1) HBsAg—present only in acute infection or chronic carriers.
(2) HBsAb—detectable only after 6 months post-initial infection. HBsAb is present in chronic infections or vaccinated individuals. Note: HBsAb is also being produced during acute infections and in chronic carriers; however, it is not detectable via current laboratory methods.
(3) HBcAg—present in either acute or chronic infection.
(4) HBeAg—present when there is active viral replication. It signifies that the carrier is highly infectious.
(5) HBeAb—appears after HBeAg. It signifies that the individual is not as contagious.

f. Vaccine: contains HBsAg.

g. Prevention: immunoglobulins (HBsAb) are available.

NEOPLASIA

 An abnormal. growth, in excess of and uncoordinated with normal tissues Which persists in the same excessive manner after cessation of the stimuli which evoked the change.

Tumours are broadly divided by their behaviors into 2 main groups, benign and malignant.

Through most tumours can be classified in the benign or malignant category . Some exhibits an intermediate behaviours.

CLASSIFICATION

Some tumours can not be clearly categorized in the above table e.g.

• Mixed tumours like fibroadenoma of the breast which is a neoplastic proliferation of both epithelial and mesenchmal tissues.
• Teratomas which are tumours from germ cells (in the glands) and totipotent cells

(in extra gonodal sites like mediastinun, retroperitoneum and presacral region). These are composed of multiple tissues indicative of differentiation into the derivatives of the three germinal layers.

• Hamartomas which are malformations consisting of a haphazard mass of  tissue normally present at that site.

Nephrosclerosis
 Disease of the renal arteries.

 Clinical manifestations:
 (1) Benign (arterial) nephrosclerosis →  Caused by the formation of atherosclerotic plaques in the renal artery. Results in narrowing of the arterioles.

(2) Malignant nephrosclerosis → Caused by malignant hypertension. Common signs of malignant hypertension include severe hypertension, retinal hemorrhages, and hypertrophy of the left ventricle. Results in inflammatory changes in the vascular walls, which may lead to rupture of the glomerular capillaries.

INFARCTION

Definition : a localized area of ischaemic necrosis in an organ infarcts may be:
Pale :as in
    →    Arterial obstruction.
    →    solid organs.
Red as in
    →    Venous occlusion
    →    Loose tissue.

Morphology
Gross: infarcts are usually wedge shaped the apex towards the occluded vessel They are
separated from the surrounding tissue by an hyperemic inflammatory zone

Microscopic:
- An area of coagulative necrosis with a rim of congested vessels and acute inflammatory infiltration of the tissue .
- The polymorphs ale later replaced by mononuclear cells and granulation tissue.
- With time, scar tissue replaces necrosed tissue.
 

Immunoglobulins. (Ig)

 These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or  immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)

Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).

Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.

Characteristics of Immunoglobulin subclasses

I. Ig G:

(i) Predominant portion (80%) of Ig.

(ii) Molecular weight 150, 000

(iii) Sedimentation coefficient of 7S.

(iv) Crosses placental barrier and to extra cellular fluid.

• (v) Mostly neutralising effect. May be complement fixing.

(vi) Half life of 23 days.

2.IgM :

(i) Pentamer of Ig.

(ii) Molecular weight 900, 000

(iii) 19S.

(iv) More effective complement fixation and cells lysis

(v) Earliest to be produced in infections.

(vi) Does not cross placental barrier.

(vii) Halflife of 5 days.

3. Ig A :

• Secretory  antibody. Found in intestinal, respiratory secretions tears, saliva and urine also.
• Secreted  usually as a dinner with secretory piece.
• Mol. weight variable (160,000+)
• 7 S to 14 S.
• Half life of 6 days.

4.Ig D :

• Found in traces.
• 7 S.
• Does not cross placenta.

5. Ig E

• Normally not traceable
• 7-8 S (MoL weight 200,000)
• Cytophilic antibody, responsible for some hypersensitivity states,