Hepatitis

Hepatitis viruses—this group of viruses causes hepatitis, a disease affecting the liver.
1. General characteristics of hepatitis.
a. The general presentation of hepatitis is the same regardless of the infecting virus; however, the time and severity of symptoms may differ.
b. Symptoms of hepatitis include fever, anorexia, malaise, nausea, jaundice, and brown-colored urine.
c. Complications of a hepatitis infection include cirrhosis, liver failure, and hepatorenal failure.

Huntington’s disease
a. Causes dementia.
b. Genetic transmission: autosomal dominant.
c. Characterized by the degeneration of striatal neurons, affecting cortical and basal ganglia function.
d. Clinically, the disease affects both movement and cognition and is ultimately fatal.

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
 

Autoimmune Diseases
These are a group of disease where antibodies  (or CMI) are produced against self antigens, causing disease process.

Normally one's immune competent cells do not react against one's own tissues.
This is due to self tolerance acquired during embryogenesis. Any antigen encountered at
that stage is recognized as self and the clone of cells capable of forming the corresponding antibody is suppressed.

Mechanism of autoimmunity

(1) Alteration of antigen

 -Physicochemical denaturation by UV light, drugs etc. e.g. SLE.
- Native protein may turn antigenic  when a foreign hapten combines with it, e.g. Haemolytic anemia with Alpha methyl dopa.

(2) Cross reaction: Antibody produced against foreign antigen may cross react with native protein because of partial similarity e.g. Rheumatic fever.

(3) Exposure of sequestered antigens: Antigens not normally exposed to immune competent cells are not accepted as self as tolerance has not been developed to them. e.g. thyroglobulin, lens protein, sperms.

(4) Breakdown of tolerance : 
- Emergence of forbidden clones (due to neoplasia of immune system as in lymphomas and lymphocytic leukaemia)
- Loss of suppressor T cells as in old age and CMI defects

Autoimmunity may be
- Organ specific.
-  Non organ specific (multisystemic)

I. Organ specific.
(I) Hemolytic anaemia:
- Warm or cold antibodies (active at 37° C or at colder temperature)
- They may lyse the RBC by complement activation or coat them and make them vulnerable to phagocytosis

(ii) Hashimoto's thyroiditis:
 
- Antibodies to thyroglobulin and microsomal antigens.
- Cell mediated immunity.
- Leads to chronic. destructive thyroiditis.

(3) Pernicious anemia

Antibodies to gastric parietal cells and to intrinsic factor.

2. Non organ specific.

Lesions are seen in more than one system but principally affect blood vessels and connective tissue (collagen diseases).

(I) Systemic lupus erythematosus  (SLE). Antibodies to varied antigens are seen. Hence it is possible that there is abnormal reactivity of the immune system in self recognition.

Antibodies have been demonstrated against:

- Nuclear material (antinuclear I antibodies) including DNA. nucleoprotein etc. Anti nuclear antibodies are demonstrated by LE cell test.
- Cytoplasmic organelles- mitochondria, rib osomes, Iysosomes.
- Blood constituents like RBC, WBC. platelets, coagulation factors.

Mechanism. Immune complexes of body proteins and auto antibodies deposit in various organs and cause damage as in type III hypersensitivity

Organs involved
- Skin- basal dissolution and collagen degeneration with fibrinoid vasculitis.
- Heart- pancarditis.
- Kidneys- glomerulonephritis of focal, diffuse or membranous type 
- Joints- arthritis. 
- Spleen- perisplenitis and vascular thickening (onion skin).
- Lymph nodes- focal necrosis and follicular hyperplasia.
- Vasculitis in other organs like liver, central or peripheral nervous system etc,

2. Polyarteritis nodosa. Remittant .disseminated necrotising vasculitis of small and medium sized arteries

Mechanism :- Not definitely known. Proposed immune reaction to exogenous or auto antigens 

Lesion : Focal panarteritis- a segment of vessel is involved. There is fibrinoid necrosis with initially acute and later chronic inflammatory cells. This may result in haemorrhage and aneurysm.

Organs involved. No organ or tissue is exempt but commonly involved organs are :
- Kidneys.
- Heart.
- Spleen.
- GIT.

3. Rheumatoid arthritis. A disease primarily of females in young adult life. 

Antibodies

- Rheumatoid factor (An IgM antibody to self IgG)
- Antinuclear antibodies in 20% patients.

Lesions

- Arthritis which may progress on to a crippling deformity.
- Arteritis in various organs- heart, GIT, muscles.
- Pleuritis and fibrosing alveolitis.
- Amyloidosis is an important complication.

4. Sjogren's  Syndrome. This is constituted by 
- Kerato conjunctivitis sicca
- Xerostomia
- Rheumatoid arthritis. 

Antibodies

- Rheumatoid factor

- Antinuclear factors (70%).
- Other antibodies like antithyroid, complement fixing Ab etc
- Functional defects in lymphocytes. There is a higher incidence of lymphoma

5. Scleroderma (Progressive systemic sclerosis)
Inflammation and progressive sclerosis of connective tissue of skin and viscera.

Antibodies
- Antinuclear antibodies.
- Rheumatoid factor. .
- Defect is cell mediated.

lesions

- Skin- depigmentation, sclerotic atrophy followed by cakinosis-claw fingers and mask face.
- Joints-synovitis with fibrosis
- Muscles- myositis.
- GIT- diffuse fibrous replacement of muscularis resulting in hypomotility and malabsorption
- Kidneys changes as in SLE and necrotising vasculitis.
- Lungs – fibrosing alveolitis.
- Vasculitis in any organ or tissue.

6.Wegener’s granulomatosis. A complex of:

- Necrotising lesions in upper respiratory tract.
- Disseminated necrotising vasculitis.
- Focal or diffuse glomerulitis.

Mechanism. Not known. It is classed with  autoimmune diseases because of the vasculitis  resembling other immune based disorders.
 

Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a phenotypic marker for an insulin-receptor abnormality as well as a marker for adenocarcinoma, most commonly of gastric origin.

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.