NEET MDS Lessons
General Pathology
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.
Strep viridans
Mixed species, all causing α-hemolysis. All are protective normal flora which block adherence of other pathogens. Low virulence, but can cause some diseases:
Sub-acute endocarditis can damage heart valves.
Abscesses can form which are necrotizing. This is the primary cause of liver abscesses.
Dental caries are caused by Str. mutans. High virulence due to lactic acid production from glucose fermentation. This is why eating sugar rots teeth. Also have surface enzymes which deposit plaque.
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.
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.
Monocytosis:
Causes
-Infections causing lymphocytosis, especialy tuberculosis and typhoid.
-Monocytic leukaemia.
-Some auto immune diseases.
Hepatitis C virus.
It is most often mild and anicteric but occasionally severe with fulminant hepatic failure. It is caused an RNA virus, which may be transmitted parenterally (a cause of post-transfusion hepatitis); the route of transmission undetermined in 40%-50% of cases
a. 90% of blood transfusion-related hepatitis is caused by hepatitis C.
b. 50% progress to chronic disease.
c. Increased risk for hepatocellular carcinoma.
d. Incubation period: ranges from 2 to 26 weeks, but averages 8 weeks.
- Antibody is detected by enzyme-linked immunosorbent,assay (ELISA). The incubation period is between 2 and weeks with peak onset of illness 6-8 weeks after infection
- Most patients progress to chronic liver disease, specifically chronic persistent hepatitis or chronic active hepatitis
- Cirrhosis is common in patients with chronic active hepatitis and occurs in 20%-25% of infected patients. HCV is also associated with hepatocellular carcinoma.
e. Treatment and prevention: α-interferon is used to treat chronic hepatitis C. There is currently no vaccine available.
Nonspecific or Innate Immunity
1. Genetic factors
- Species: Guinea pig is very susceptible to tuberculosis.
- Race: Negroes are more susceptible to tuberculosis than whites
- Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.
2. Age Extremes of age are more susceptible.
3. Hormonal status. Low resistance in:
- Diabetes Mellitus.
- Increased corticosteroid levels.
- Hypothyroidism
4. Phagocytosis. Infections can Occur in :
- Qualitative or quantitative defects in neutrophils and monocytes.
- Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
- Overload blockade of RES.
5. Humoral factors
- Lysozyme.
- Opsonins.
- Complement
- Interferon (antiviral agent secreted by cells infected by virus)