NEET MDS Lessons
General Pathology
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.
Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.
Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.
b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.
3. Virion characteristics
a. The HIV genome includes:
(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.
b. HIV enzymes
(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins.
4. Pathogenicity
a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into the host DNA. New virions are synthesized and released by lysis of the host cell.
b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.
5. HIV infection versus acquired immunodeficiency syndrome (AIDS).
a. AIDS describes an HIV-infected person who has one of the following conditions:
(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.
6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii).
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.
7. Laboratory diagnosis of HIV
a. ELISA test—detects HIV antibodies.
False negatives do occur.
b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.
8. Treatment
a. Inhibitors of reverse transcriptase.
(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.
(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.
Eosinopenia:
Causes
-Corticoid effect (Cushing's syndrome or therapy).
-Stress.
PARASITIC DISEASES
AMEBIASIS (Entamebiasis)
Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.
Etiology and Pathogenesis
Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.
Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.
Symptoms and Signs
Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.
Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.
Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.
Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common
Haemolytic anaemia
Anemia due to increased red cell destruction (shortened life span)
Causes:
A. Corpuscular defects:
1.Membrane defects:
- Spherocytosis.
- Elliptocytosis.
2. Haemoglobinopathies:
- Sickle cell anaemia.
- Thalassaemia
- Hb-C, HBD, HbE.
3. Enzyme defects .deficiency of:
- GIucose -6 phosphate dehydrogenase (G6-PD)
- Pyruvate kinase
4. Paroxysmal nocturnal haemoglobinuria.
B. Extracorpusular mechanisms
1. Immune based:
- Autoimmune haemolytic anaemia.
- Haemolytic disease of new born.
- Incompatible transfusion.
- Drug induced haemolysis
2. Mechanical haemolytic anaemia.
3. Miscellaneous due to :
- Drugs and chemicals.
- Infections.
- Burns.
features of haemolytic anaemia
- Evidence of increased Hb breakdown:
-> Unconjugated hyperbilirubinaemia.
-> Decreased plasma haptoglobin.
-> Increased urobilinogen and stercobilinogen.
-> Haemoglobinaemia, haemoglobinuria and haemosiderinuria if Intravascular haemolysis occurs.
- Evidence or compensatory erythroid hyperplasia:
-> Reticulocytosis and nucleated RBC in peripheral smear.
-> Polychromasia and macrocytes
-> Marrow erythroid hyperplasia
-> Skull and other bone changes.
- Evidences of damage to RBC:
-> Spherocytes and increased osmotic fragility
-> Shortened life span.
-> Fragmented RBC.
-> Heinz bodies.
Mycobacterium leprae
- tuberculoid type has intact cellular immunity
- forms granulomas and kill the organisms (very few present).
- evokes a positive lepromin skin test
- localized skin lesions that lack symmetry
- nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
- lepromatous leprosy patients lack cellular immunity
- no granulomas
- organisms readily identified
- negative lepromin skin test
- Bacteremia disseminates to cooler areas like the digits.
- symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
- neural involvement is a late feature of the disease.
- lepromin skin test is to determine host immunity; not a diagnostic test.
- treatment: dapsone + rifampin