NEET MDS Lessons
General Pathology
Tuberculosis
Causative organism
-Mycobacterium tuberculosis
-Strict aerobe
-Pathogenic strains
-hominis, bovis, avium, murine& cold blooded vertebrate strain
Koch’s bacillus
-small slender, rod like bacillus, 4umnon-motile, aerobic -high lipid content
-divides every 16 to 20 hours, an extremely slow rate
-stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolicacid content of its cell wall
-can withstand weak disinfectant and survive in a dry state for weeks.
Demonstrated by
-ZiehlNeelsenstaining
-Fluorescent dye method
-Culture in LJ media
-Guinea pig inoculation
Modes of transmission
Inhalation , Ingestion, Inoculation , Transplacental
Route Spread
Local , Lymphatic , Haematogenous , By natural passages,
Pathogenesis
- Anti‐mycobacterial CMI, confers resistance to bacteria → dev. of HS to tubercular Ag
- Bacilli enters macrophages
- Replicates in phagosomeby blocking fusion of phagosome& lysosome, continues for 3 weeks →bacteremiabut asymptomatic
- After 3 wks, T helper response is mounted by IL‐12 produced by macrophages
- T cells produce IFN, activates macrophages → bactericidal activity, structural changes
- Macrophages secrete TNF→ macrophage recruitment, granuloma& necrosis
Fate of granuloma
- Caseousmaterial undergo liquefaction---cold abscess
- Bones, joints, lymph nodes & epididymis---sinuses are formed & sinus tract lined by tuberculousgranulation tissue
- Dystrophic calcification
Types of TB
1. Primary Pulmonary TB
2. secondary TB (miliary, fibrocaseous, cavitary)
3. Extra-pulmonary TB (bone, joints, renal, adrenal, skin… )
Primary TB
Infection in an individual who has not been previously infected or immunised
Primary complex
Sites
-lungs, hilarlymph nodes
-tonsils, cervical lymph nodes
-small intestine, mesenteric lymph nodes
Primary TB
In the lung, Ghon’scomplex has 3 components:
1. Pulmonary component -Inhalation of airborne droplet ~ 3 microns.
-Bacilli locate in the subpleuralmid zone of lung
-Brief acute inflammation –neutrophils.
-5-6 days-invoke granulomaformation.
-2 to 8 weeks –healing –single round ;1-1.5 cm-Ghon focus.
2. Lymphatic vessel component
3. Lymph node component
Fate of primary tuberculosis
- Lesions heal by fibrosis, may undergo calcification, ossification
-a few viable bacilli may remain in these areas
-bacteria goes into a dormant state, as long as the person's immune system remains active
- Progressive primary tuberculosis: primary focus continues to grow & caseousmaterial disseminated to other parts of lung
- Primary miliarytuberculosis: bacilli may enter circulation through erosion of blood vessel
- Progressive secondary tuberculosis: healed lesions are reactivated, in children & in lower resistance
Secondary tuberculosis
-Post-primary/ reinfection/ chronic TB
-Occurs in immunized individuals.
-Infection acquired from
-endogenous source/ reactivation
-exogenous source/ reinfection
Reactivation
-when immune system is depressed
-Common in low prevalence areas.
-Occurs in 10-15% of patients
-Slowly progressive (several months)
Re-infection
-when large innoculum of bacteria occurs
-In areas with increased personal contact
Secondary TB
-Sites-Lungs 1-2 cm apical consolidation with caseation
-Other sites -tonsils, pharynx, larynx, small intestine & skin
Fate of secondary tuberculosis
•Heal with fibrous scarring & calcification
•Progressive secondary pulmonary tuberculosis:
-fibrocaseoustuberculosis
-tuberculouscaseouspneumonia
-miliarytuberculosis
Complications:
a) aneurysm of arteries–hemoptysis
b) bronchopleuralfistula
c) tuberculousempyema
MiliaryTB
• Millet like, yellowish, firm areas without caseation
• Extensive spread through lympho-hematogenousroute
• Low immunity
• Pulmonary involvement via pulmonary artery
• Systemic through pulmonary vein:
-LN: scrofula, most common
-kidney, spleen, adrenal, brain, bone marrow
Signs and Symptoms of Active TB
• Pulmonary-cough, hemoptysis, dyspnea
• Systemic:
• fever
• night sweats
• loss of appetite
• weight loss
• chest pain,fatigue
•If symptoms persist for at least 2 weeks, evaluate for possible TB infection
Diagnosis
•Sputum-Ziehl Neelsen stain –10,000 bacilli, 60% sensitivity
-release of acid-fast bacilli from cavities intermittent.
-3 negative smears : low infectivity
•Culture most sensitive and specific test.
-Conventional Lowenstein Jensen media-10 wks.
-Liquid culture: 2 weeks
•Automated techniques within days
should only be performed by experienced laboratories (10 bacilli)
•PPD for clinical activity / exposure sometime in life
•X-ray chest
•FNAC
PPD Tuberculin Testing
- Read after 72 hours.
- Indurationsize -5-10 mm
- Does not d/s b/w active and latent infection
- False +: atypical mycobacterium
- False -: malnutrition, HD, viral, overwhelming infection, immunosuppression
- BCG gives + result.
Tuberculosis Atypical mycobacteria
- Photochromogens---M.kansasii
- Scotochromogens---M.scrofulaceum
- Non-chromogens---M.avium-intracellulare
- Rapid growers---M.fortuitum, M.chelonei
5 patterns of disease
- Pulmonary—M.kansasii, M.avium-intracellulare
- Lymphadenitis----M.avium-intracellulare, M.scrofulaceum
- Ulcerated skin lesions----M.ulcerans, M.marinum
- Abscess----M.fortuitum, M.chelonei
- Bacteraemias----M.avium-intracellulare as in AIDS
Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.
2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.
PRIMARY LYMPHEDEMA
can occur as:
1- A congenital defect, resulting from lymphatic agenesis or hypoplasia.
2- Secondary or obstructive lymphedema
- blockage of a previously normal lymphatic; e.g. Malignant tumors
- Surgical procedures that remove lymph nodes
- Postirradiation
- Fibrosis
- Filariasis
- Postinflammatory thrombosis and scarring
G-6 PD Deficiency
Occurs in Negroes, Mediterranean races, India and far East. It confers a protection Against falciparum malaria.
It is transmitted as X-linked trait of intermediate dominance (variable effect in homozygous females).
Haemolysis may be induced by :
• Primaquin and other anti malarials.
• Other drugs like chloramphenicol , analgesics, antitubercular drugs etc.
• Infections.
• Ingestion of Vicia faba bean (favism).
• Diabetic acidosis
Paget Disease (Osteitis Deformans)
This unique bone disease is characterized by repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength. Paget disease usually does not occur until mid-adulthood but becomes progressively more common thereafter. The pathognomonic histologic feature is a mosaic pattern of lamellar bone (likened to a jigsaw puzzle) due to prominent cement lines that haphazardly fuse units of lamellar bone. (Fig. 12-5) The axial skeleton and proximal femur are involved in the majority of cases. In patients with extensive disease, hypervascularity of the marrow spaces can result in high-output congestive heart failure. Cranial nerves impingement also occurs and can lead to head ache and auditory disturbances. Rarely Paget disease is complicated by bone sarcoma (usually osteogenic).
Biliary cirrhosis(16%)
It is due diffuse chronic cholestaisis (obstruction of the biliary flow) leading to damage and scarring all over the liver. Two types are known
1. Primary biliary cirrhosis and
2. Secondary biliary cirrhosis.
Primary biliary cirrhosis
It is destructive chronic inflammation of intrahepatic bile ductules and small ducts leading to micronodular cirrhosis.
-Typically affects middle aged women.
- Patients present with fatigue, pruritis and eventually, jaundice.
Cause:- Autoimmune. Patients have autoantibodies directed against mitochondrial enzymes (AMA).
Pathology:-
Liver is enlarged, dark green in color (cholestaisis). Cirrhosis is micronodular.
M/E :-
- Early, portal tracts show lymphocytes and plasma cell infiltrate the bile ducts and destroy them.
- Granulomatous inflammation surrounding the damaged and inflamed bile ducts is the hallmark of (PBC).
- Cholestatic changes such as bile ductular proliferation, periportal Mallory’s hyaline and increased copper in periportal hepatocytes.
- In the end stage disease, micro nodular cirrhosis occurs and the inflammatory changes subside
Secondary biliary cirrhosis:-
It is extra hepatic (surgical) cholestaisis due to prolonged extra hepatic major bile duct obstruction.
Causes - Obstruction of hepatic or common bile duct by:
- Congenital biliary atresia.
- Pressure by enlarged LN or tumor * Biliary stones.
- Carcinoma of the bile duct, ampulla of Vater or pancreatic head
Effects of obstruction:-
Complete obstruction leads to back pressure all over the biliary tract
- damage by inspessated bile
- inflammation and scarring.
Incomplete obstruction leads to acute suppurative cholangitis and cholangiolitis.
Lymphocytosis:
Causes
-Infections in children and the neutropenic infections in adults.
-Lymphocytic leukaemia.
-Infectious mononucleosis.
-Toxdplasmosis.
-Myast'henia gravis.