DEGENERATION

Definition:   Reversible cell injury.

(1) Water accumulation in the form   of 

(i)          Cloudy   swelling.

(ii)         Vacuolar   degeneration.

.(ill)        Hydropic   degeneration.

This change  is commonly   seen  in parenchymal   cells  e.g.  kidneys.

Gross appearance: The organ is swollen, soft and pale.

Microscopic appearance: Cells show varying degrees of swelling. Cytoplasm may be granular, vacuolated, homogenously pale and ballooned out.     

(2)  Fatty   change An excessive,   demonstrable accumulation of fat  is common   in  parenchymal cells of liver  and heart

In the liver, it can be due to:   .

(i) Excess  fat  entry  into  the  liver  as occurs  in  starvation  and  in  steroid excess due to mobilization from stores.

(ii) Excess triglyceride formation

(iii) Reduced phosphorlyation  of fat.  

(iv) Decreased release as lipoprotein due to protein deficiency.

Causes

(i) Hypoxia  as  in severe  anaemia  and  venous  stasis

(ii) Protein  malnutrition.

(iii) Hepatotoxins like CCl₄.

(iv) Alcoholism

(v) Metabolic defects like Diabetes mellitus

(vi) Infections.

Gross appearance: The organ is enlarged, soft and greasy, with a pale yellowish colour. It may involve the organ uniformly or patchily ( thrush breast or tabby cat heart)

Microscopic appearance: The cells contain clear vacuoles (stainable by fat-sudan  stains on frozen sections). These may be small and dispersed or large, displacing the nucleus peripherally. Several such cells may fuse to form fat cysts.

(3) Hyaline degeneration

In alcoholic liver damage, the cytoplasmic organelles are damaged and give the cytoplasm a deep eosinophilic staining-Mallory hyaline.

Wuchereria bancrofti, Brugia malayi (Filariasis)
 - the microfilaria of Wuchereria bancrofti or Brugia malayi (nematodes) are transmitted to man by the bite of infected mosquitoes (Anophele, Aedes, Culex).
 - microfilaria characteristically circulate in the bloodstream at night and enter into the lymphatics, where they mature and produce an inflammatory reaction resulting in lymphedema (elephantiasis) of the legs, scrotum, etc. 

Valvular disease
A. Generally, there are three types:
1. Stenosis—fibrotic, stiff, and thickened valves, resulting in reduced blood flow through the valve.

2. Regurgitation or valvular insufficiency— valves are unable to close completely, allowing blood to regurgitate.

3. Prolapse—“floppy” valves; may occur with or without regurgitation. The most common valvular defect.

FUNGAL INFECTION

Histoplasmosis

A disease caused by Histoplasma capsulatum, causing primary pulmonary lesions and hematogenous dissemination.

Symptoms and Signs

The disease has three main forms. Acute primary histoplasmosis is usually asymptomatic

Progressive disseminated histoplasmosis follows hematogenous spread from the lungs that is not controlled by normal cell-mediated host defense mechanisms. Characteristically, generalized involvement of the reticuloendothelial system, with hepatosplenomegaly, lymphadenopathy, bone marrow involvement, and sometimes oral or GI ulcerations occurs, particularly in chronic cases

Progressive disseminated histoplasmosis is one of the defining opportunistic infections for AIDS.

Chronic cavitary histoplasmosis is characterized by pulmonary lesions that are often apical and resemble cavitary TB. The manifestations are worsening cough and dyspnea, progressing eventually to disabling respiratory dysfunction. Dissemination does not occur

Diagnosis

Culture of H. capsulatum from sputum, lymph nodes, bone marrow, liver biopsy, blood, urine, or oral ulcerations confirms the diagnosis

HERPES ZOSTER (Shingles)

An infection with varicella-zoster virus primarily involving the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the dermatome of the affected root ganglia.

caused by varicella-zoster virus

Symptoms and Signs

Pain along the site of the future eruption usually precedes the rash by 2 to 3 days. Characteristic crops of vesicles on an erythematous base then appear, following the cutaneous distribution of one or more adjacent dermatomes

Eruptions occur most often in the thoracic or lumbar region and are unilateral. Lesions usually continue to form for about 3 to 5 days

Geniculate zoster (Ramsay Hunt's syndrome) results from involvement of the geniculate ganglion. Pain in the ear and facial paralysis occur on the involved side. A vesicular eruption occurs in the external auditory canal, and taste may be lost in the anterior two thirds of the tongue

Rickets and Osteomalacia 

Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion 
4. Malabsorption disorders.

Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.

Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.

The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.

The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones 

Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.

Microscopic features

• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.