Immunohistochemistry

 This is a method is used to detect a specific antigen in the tissue in order to identify the type of disease.

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.
 

PARASITIC DISEASES

AMEBIASIS (Entamebiasis)

Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.

Etiology and Pathogenesis 

Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.

Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.

Symptoms and Signs 

Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.

Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.

Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.

Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common
 

Causes of disease

The causes of disease Diseases can be caused by either environmental factors, genetic factors or a combination of the two.

A. Environmental factors

Environmental causes of disease are many and are classified into:

 1. Physical agents

 2. Chemicals

 3. Nutritional deficiencies & excesses

 4. Infections & infestations

 5. Immunological factors

 6. Psychogenic factors

 1. Physical agents

These include trauma, radiation, extremes of temperature, and electric power. These agents

apply excess physical energy, in any form, to the body.

2. Chemicals

With the use of an ever-increasing number of chemical agents such as drugs,

3. Nutritional deficiencies and excesses

Nutritional deficiencies may arise as a result of poor supply, interference with absorption, inefficient transport within the body, or defective utilization. It may take the form of deficiency.

4. Infections and infestations

Viruses, bacteria, fungi, protozoa, and metazoa all cause diseases. They may do so by causing cell destruction directly as in virus infections (for example poliomyelitis) or protozoal infections (for example malaria).

5. Immunological factors

A. Hypersensitivity reaction

This is exaggerated immune response to an antigen. For example, bronchial asthma can occur due to exaggerated immune response to the harmless pollen.

B. Immunodeficiency

This is due to deficiency of a component of the immune system which leads to increased susceptibility to different diseases. An example is AIDS.

C. Autoimmunity

This is an abnormal (exaggerated) immune reaction against the self antigens of the host. Therefore, autoimmunity is a hypersensitivity reaction against the self antigens. 4

6. Psychogenic factors

The mental stresses imposed by conditions of life, particularly in technologically advanced

communities, are probably contributory factors in some groups of diseases.

B. Genetic Factors

These are hereditary factors that are inherited genetically from parents.

ANAEMIA
Definition. Reduction of the hemoglobin level below the normal for the age and sex of the patient

Classification
1. Blood loss anaemia:
- Acute.
- Chronic (results in iron deficiency).

2. Deficiency anaemia:

- Iron deficiency.
- Megaloblastic anaemia-BI2 and Folic acid deficiency.
- Protein deficiency.
- Scurvy-Vitamin C deficiency.

3. Marrow dysfunction:
- Aplastic anaemia.
- Marrow infiltration.
- Liver failure.
- Renal failure.
- Collagen diseases.

4 Increased destruction (Heamolysis)
- Due to corpuscular defects.
- Due to extra corpuscular defects
 

Haemolysis due to drugs and chemicals

This can be caused by :

1. Direct toxic action.
    -> Naphthalene.
    -> Nitrobenzene.
    -> Phenacetin.
    -> Lead.

Heinz bodies are seen in abundance.

2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be : 
    -> Drug induced  autoantibody haemolysis, Antibodies are directed against RBC.
    -> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.