VIRAL DISEASES

RABIES (Hydrophobia)

An acute infectious disease of mammals, especially carnivores, characterized by CNS pathology leading to paralysis and death.

Etiology and Epidemiology

Rabies is caused by a neurotropic virus often present in the saliva of rabid animals

Pathology

The virus travels from the site of entry via peripheral nerves to the spinal cord and the brain, where it multiplies; it continues through efferent nerves to the salivary glands and into the saliva.

microscopic examination shows perivascular collections of lymphocytes but little destruction of nerve cells. Intracytoplasmic inclusion bodies (Negri bodies), usually in the cornu Ammonis, are pathognomonic of rabies, but these bodies are not always found.

Sign/Symptoms

In humans, the incubation period varies from 10 days to > 1 yr and averages 30 to 50 days.

Rabies commonly begins with a short period of depression, restlessness, malaise, and fever. Restlessness increases to uncontrollable excitement, with excessive salivation and excruciatingly painful spasms of the laryngeal and pharyngeal muscles. The spasms, which result from reflex irritability of the deglutition and respiration centers, are easily precipitated Hysteria due to fright

Prognosis and Treatment

Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms

Bacillus anthrax
 - large Gram (+) rods that produce heat resistant spores; Clostridia and Bacillus species are the two bacterial spore formers; they do not form spores in tissue; produces a powerful exotoxin.
 - contracted by direct contact with animal skins or products  
 
 - four forms of anthrax are recognized → cutaneous (MC), pulmonary, oraloropharyngeal, and gastrointestinal.
 - cutaneous anthrax (90 to 95% of cases) occurs through direct contact with infected or contaminated animal products.
 - lesions resemble insect bites but eventually swell to form a black scab, or eschar, with a central area of necrosis ("malignant pustule").

 IMMUNO PATHOLOGY
Abnormalities of immune reactions are of 3 main groups
- Hypersensitivity,
- Immuno deficiency,
- Auto immunity.
Hypersensitivity (ALLERGY)
This is an exaggerated or altered immune response resulting in adverse effects

They are classified into 4 main types.

I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.

Clinical  situations

I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.
2. Local (atopic) allergy.
- Allergic rhinitis (hay fever)
- Asthma
- Urticaria.
- Food allergies.

2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.

The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell. 

Clinical situations

- Haemolytic anemia.
- Transfusion reaction
- Auto immune haemolytic anemia.
- Haemolysis due to some drugs like Alpha methyl dopa

2. Drug induced thrombocytopenia (especially sedormid).
3 Agranulocytosis due to sensitivity to some drugs.
4 Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.

3. Type III. (Immune complex disease). Circulating immune complexes especially small soluble complexes tend to deposit in tissues especially kidney, joints, heart and arteries.

These then cause clumping of platelets with subsequent release of histamine. and serotonin resulting in increased permeability. Also, complement activation occurs which being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to release of lysosmal enzymes

Clinical situations

- Serum sickness.
- Immune complex glomerulonephritis.
- Systemic lupus erythematosus.
- Allergic alveolitis.
- Immune based vasculitis like
    o    Drug induced vasculitis.
    o    Henoch – Schonlein purpura

4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.

Clinical situations

I. Caseation necrosis in tuberculosis.
2. Contact dermatitis to
    - Metals.
    - Rubber.
    - Drugs (topical).
    - Dinitrochlorbenzene (DNCB).
    
5. Type V. (stimulatory) This is classed by some workers separately and by other with cytotoxic type (Type II) with a stimulatory instead of toxic effect

Clinical Situations :
LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)
 

INFARCTION

 An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue 

 Nearly 99% of all infarcts result from thrombotic or embolic events 
 
other mechanisms include: local vasospasm, expansion of an atheroma, extrinsic compression of a vessel (e.g., by tumor); vessel twisting (e.g., in testicular torsion or bowel volvulus; and traumatic vessel rupture

MORPHOLOGY OF INFARCTS 

 infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or aseptic 

 All infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base 
 
 The margins of both types of infarcts tend to become better defined with time 
 
 The dominant histological characteristic of infarction is ischemic coagulative necrosis 
 
 most infarcts are ultimately replaced by scar. The brain is an exception, it results in liquefactive necrosis 
 
 RED INFARCTS:
occur in 
(1) venous occlusions (such as in ovarian torsion) 
(2) loose tissues (like lung) that allow blood to collect in the infarcted zone 
(3) tissues with dual circulations (lung and small intestine) 
(4) previously congested tissues because of sluggish venous outflow 
(5) when flow is re-established to a site of previous arterial occlusion and necrosis 

WHITE INFARCTS 

occur with: 
1) arterial occlusions 
2) solid organs (such as heart, spleen, and kidney).

Septic infarctions - occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. - the infarct is converted into an abscess, with a correspondingly greater inflammatory response

FACTORS THAT INFLUENCE DEVELOPMENT OF AN INFARCT
- nature of the vascular supply 
- rate of development of the occlusion (collateral circulation ) 
- vulnerability to hypoxia - Neurons undergo irreversible damage 
- 3 to 4 minutes of ischemia. - Myocardial cells die after only 20 to 30 minutes of ischemia 
- the oxygen content of blood
 

Hypopituitarism

Hypopituitarism is caused by

1. Loss of the anterior pituitary parenchyma
    a. congenital 
    b. acquired  
    
2. Disorders of the hypothalamus e.g. tumors; these interfere with the delivery of pituitary hormone-releasing factors from the hypothalamus.  

Most cases of anterior pituitary hypofunction are caused by the following:
1. Nonfunctioning pituitary adenomas 
2. Ischemic necrosis of the anterior pituitary is an important cause of pituitary insufficiency. This requires destruction of 75% of the anterior pituitary. 

Causes include  

a. Sheehan syndrome, refers to postpartum necrosis of the anterior pituitary, and is the most cause. During pregnancy the anterior pituitary enlarges considerably because of an increase in the size and number of prolactin-secreting cells. However, this physiologic enlargement of the gland is not accompanied by an increase in blood supply. The enlarged gland is therefore vulnerable to ischemic injury, especially in women who develop significant hemorrhage and hypotension during the peripartum period. The posterior pituitary is usually not affected. 

b. Disseminated intravascular coagulation 
c. Sickle cell anemia 
d. Elevated intracranial pressure 
e. Traumatic injury
f. Shock states

3. Iatrogenic i.e.  surgical removal or radiation-induced destruction
4. Inflammatory lesions such as sarcoidosis or tuberculosis
5. Metastatic neoplasms involving the pituitary. 
6. Mutations affecting the pituitary transcription factor Pit-1 

Children can develop growth failure (pituitary dwarfism) as a result of growth hormone deficiency.

Gonadotropin or gonadotropin-releasing hormone (GnRH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men. TSH and ACTH deficiencies result in symptoms of hypothyroidism and hypoadrenalism. Prolactin deficiency results in failure of postpartum lactation. 

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,