NECROSIS

Definition: Necrosis is defined as the morphologic changes caused by the progressive degradative
action of enzymes on the lethally injured cell.

These changes are due to
I. Autolysis and
2. Heterolysis.

The cellular changes of necrosis i.e. death of circumscribed group of cells in continuity with living tissues are similar to changes in tissues following somatic death, except that in the former, there is leucocytic infiltration in reaction to the dead cells and the lytic
enzymes partly come from the inflammatory cell also. (Heterolysis). Cell death occurs in the normal situation of cell turnover also and this is called apoptosis-single cellular dropout.

Nuclear changes in necrosis

As cytoplasmic changes are a feature of degeneration ,similarly nuclear changes are the hallmark of necrosis. These changes are:
(i) Pyknosis –condensation of chromatin
(ii) Karyorrhexis - fragmentation
(iii) Karyolysis - dissolution

Types of necrosis

(1) Coagulative necrosis: Seen in infarcts. The architectural outlines are maintained though structural details are lost. E.g, myocardial infarct.
(2) Caseous necrosis: A variant of coagulative necrosis seen in tuberculosis. The architecture is destroyed, resulting in an  eosinophilic amorphous debris.
(3) Colliquative (liquifactive). Necrosis seen in Cerebral infarcts and suppurative necrosis.

Gangrenous necrosis: It is the necrosis with superadded putrefaction

May be:
a. dry - coagulative product.
b. Wet - when there is bacterial liquifaction.

Fat necrosis

May be:
a. Traumatic (as in breast and subcutaneous tissue).
b Enzymatic (as in pancreatitis). It shows inflammation of fat with formation of lipophages and giant cells.

This is often followed by deposition of calcium as calcium soaps.

Hyaline necrosis: Seen in skeletal muscles in typhoid and in liver ceIs in some forms of hepatitis.

Fibrinoid necrosis: In hypertension and in immune based diseases.
 

Connective tissue diseases
Marfan’s syndrome
a. Genetic transmission: autosomal dominant.
b. Characterized by a defective microfibril glycoprotein, fibrillin.
c. Clinical findings include tall stature, joints that can be hyperextended, and cardiovascular defects, including mitral valve prolapse and dilation of the ascending aorta.

Ehlers-Danlos syndrome
a. Genetic transmission: autosomal dominant or recessive.
b. This group of diseases is characterized by defects in collagen.
c. Clinical findings include hypermobile joints and highly stretchable skin. The skin also bruises easily. Oral findings include Gorlin’s sign and possible temporomandibular joint (TMJ) subluxation. 
The oral mucosa may also appear more fragile and vulnerable to trauma. 

Systemic Candidiasis (Candidosis; Moniliasis)

Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.

Infections due to Candida sp account for about 80% of all major systemic fungal infections.

Symptoms and Signs

Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.

Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.

ADRENOCORTICAL TUMORS

Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features. 

Patholgical features
Adrenocortical adenomas

- They are generally small, 1 to 2 cm in diameter. 
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells 
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content. 

Adrenocortical carcinomas 

These are rare and may occur at any age, including in childhood.  
- Carcinomas are generally large, invasive lesions. 
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.  

Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus 

- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.

Infections caused by gonorrhea

1.  Acute urethritis.  Mostly in males.  Generally self-limiting.  Dysuria and purulent discharge.

2.  Endocervical infection.  Purulent vaginal discharge, abnormal menses, pelvic pain.  Often co-infection with other STD’s.  Some women are asymptomatic.

3.  Pelvic Inflammatory Disease (PID).  Consequence of ascending endocervical infection.  Causes salpingitis, endometriosis, bilateral abdominal pain, discharge, fever.  May lead to sterility, chronic pain, and ectopic pregnancy because of loss of fallopian cilia.

4.  Anorectal inflammation.  Mostly in homosexual men.  Pain, itching, discharge from anus.

5.  Dermatitis/arthritis.  Occurs after bacteremia.  Skin will have papules on an erythematous base which develop into necrotic pustules.  Asymmetric joint pain.  These infections are susceptible to penicillin.

6.  Neonatal infections.  Ophthalmia neonatorum is a conjunctival infection from going through infected vagina.  After one year of age, suspect child abuse.