TUBERCULOSIS (Extrapulmonary)

Dr. Shahab RiazLecturer of Pathology

PMC

Bacteriology Slender bacillus, 3 ųm long, non-

motile, non-sporing Acid fast, ZN staining or Auramine

Rhodamine staining Löwenstein Jensen medium (37ºC,

aerobic atmosphere, several weeks, 6 weeks before discarding)

Faster growth in fluid media 14C-tagged substrate into medium

(detection of free 14CO2 above liquid culture indicates growth of bacilli, growth + susceptibility to drugs)

Resistant to drying in dust for several months, susceptible to UV light, rapidly killed in sunlight

Common Agent

Mycobacterium tuberculosis (Mostly pulmonary focus, spreads by ingestion of infected sputum or

blood-borne)

Mycobacterium bovis (Tonsillar / intestinal TB in children, eradicated from developed

countries, pasteurization of milk and removal of infected herds)

Gross Specimen

• Patient Name: Talha• Age: 25 years• SP No: 899/2008• Specimen: Ileal Resection

Pathogenesis

Transient acute inflammatory response neutrophils rapidly killed Monocytes (blood) macrophage infiltration destruction of organisms AFB phagocytosed by macrophages pale cytoplasm, eosinophilic

nuclei, elongated and vesicular “Epitheloid Cells” Some macrophages instead of Epitheloid cells fuse to form Langhans Giant

cells Surrounding altered macrophages, wide zone of small round cells, mostly

lymphocytes and fibroblasts 10-14 days necrosis in centre (altered macrophages and cells of tissue) firm

Coagulative necrosis “Caseation” High content of lipid (structureless and eosinophilic) T-cell mediated

reaction released cytokines TNF Hypersensitivity to tuberculoprotein, Ischemia?? “Tubercle Follicle” central caseation, surrounded by epitheloid and Giant

Cells, in turn closed in wide zone of small round cells DDx deep-seated mycoses, for TB Dx, organism must be seen in ZN stain

or LJ medium

Microscopy

Types of Microscopic LesionsPreviously mentioned lesion “ Productive” or

“Proliferative” (cells primarily)

Variant “Exudative form of TB”, (inflammatory exudate rich in fibrin, considerable infiltration of

lymphocytes and often polymorphs but epitheloid and Giant cells scanty, e.g., serous cavities like pericardium/peritoneum, epithelial surfaces also exhibit this character e.g., sterile pyuria in open renal TB)

Compact organs like liver, kidney productive lesion Lungs both types and latter is serious (extensive

caseation and rapid spread of infection)

Types of TB

1. Acute Caseous TB

2. Chronic TB

a. Caseous

b. Fibro-caseous

c. Fibroid

( immunity, bacilli destroyed, healing/fibrosis side by side with caseous destruction)

3. Non-Reactive TB ( most serious, extensive caseation, teeming with bacilli, no cellular reaction,

leukemia complication and elderly people, tuberculin test – ve /over whelming infection)

Fate of Tuberculous Lesion

Hallmark of Healing ≈ Fibrous tissue

a. Solid Fibrous nodule

b. Calcareous nodule (rim of fibrous tissue, caseation slow dystrophic calcification, organisms survive,

years later become active again)

Hallmark of Activity ≈ Caseation and softening

(macrophages bacilli lymphatics/tissue spaces satellite follicles) (caseous material phosphatides inhibit autolytic enzymes) (liquefaction serious, pyogenic secondary infection?? Delayed hypersensitivity

reaction?) (Cold Abscess pus like material, tracks down to spread)

• Bones, joints, lymph nodes, epididymis no immediately available passages

• Large cold abscesses accumulate e.g., collar stud abscess of neck cervical LN TB

• In other cases pus tracks through tissues advancing tuberculous lesion destroys tissue (sinuses formed lined by tuberculous granulation tissue formed of systems of tubercle follicles irregularly disposed in a mass of newly formed fibrous tissue heavily infiltrated with lymphocytes and macrophages)

• Sometimes pus tracks for long distances e.g., infected vertebrae psoas sheath psoas abscess and finally points below inguinal ligament

• Open TB abscesses serious bcz open and infectious character & aerobic organism exposed to atmosphere

Spread of Tuberculosis in Body• 1. Local Spread (macrophages or pus tracking)

• 2. Lymphatic Spread (tuberculous lymphadenitis, primary focus + attending lymphangitis + lymphadenitis = Primary Complex)

• 3. Blood Spread (as an extension of lymphatic involvement)

Miliary TB (lungs, spleen, liver, kidneys) Caseous LN adjacent pulmonary vein (fever, wasting, hepato-

splenomegaly, leucopenia, thrombocytopenia) Tuberculous meningitis miliary TB direct involvement of choroid

plexus or small sub-cortical lesion (Rich’s Focus) rupturing into subarachnoid space

Miliary TB large number of organisms via blood stream or pulmonary vein Sometimes in older children and adults small pulmonary vein branch

few bacilli destroyed by mononuclear phagocyte system or lodged as metastatic disease (a) progresses immediately to produce clinical effects or (b) remain dormant, reactivation years later (local metastatic TB) e.g., kidney, adrenals, uterine tubes, epididymis, bones, joints, tendon sheaths

(thyroid, pancreas, heart and voluntary msls?? Spleen…

Spread (cont…..)

• 4. Spread in Serous Cavities (pleurisy of lung lesions, localized peritonitis found around tuberculous salpingitis, TB meningitis)

• 5. Spread along epithelial lined surface e.g., intra bronchial spread of TB when sputum inhaled into adjacent lung

segments when coughed up can produce tuberculous laryngitis when swallowed, ileo-cecal region of bowel (tuberculous enteritis) Rectal involvement ischio-rectal abscess TB kidney ureter trigone of bladder TB salpingitis endometrial disease

Why ileo-cecal area is common site of infection?• Gastrointestinal tract tuberculosis usually

involves the ileo-cecal region , because of abundant lymphoid tissue and relative stasis.

Tissue Response Factors• 1. Dose and Virulence of Organism• 2. Innate and Acquired resistance of body

a. Innate Immunity:

Black Africans, American Indians, Australian Aborigines are susceptible b. Age and Sex: 1st 5 years ---- resistance poor, high mortality 5-15 years ----- resistance at peak 15-30 years ---- resistance breaks down esp. in women After 30 years --- resistance quite high Old age ---- again breaks down esp. in men c. General Health of Individual: Malnutrition & over crowding prison camps/ slums TB predisposed Psychological stress, chronic debilitating diseases lower resistance DM esp. notorious rapidly spreading type of infection Like wise glucocorticoid therapy can reactivate previously quiescent TB

foci (use with caution in TB)

d. Occupational Factors:

Silicosis risk works tunnellers, miners and quarrymen

asbestosis strangely doesn’t increase the risk

e. Effects of previous infection: (Koch’s Phenomenon):

• 2nd infection different from primary one Robert Koch in Guinea pigs

• TB bacilli skin 10-14 days, nodule, ulcerates and persists until death

• Organisms RLN blood MTB death

• TB bacilli injected into 4-6 weeks previously infected different response bcz of T cell mediated response

• Site of injection indurated 1-2 days ulcerates/heals no RLN

• This 2nd response is called Koch’s Phenomenon, due to immunity and hypersensitivity (tuberculin)

• Tuberculin hypersensitivity develops month to 6 weeks T cell mediated

• Partial degree acquired immunity no effect on primary infection

Morphology of Tuberculous Infection

Extra-pulmonary:In Children: Developed countries rare, Pakistan common Alimentary tract mostly children (bovine bacilli in milk) Abdominal disease primary focus in bowel so small rarely identifiable First manifestation usually mesenteric lymphadenopathy, Tabes

mesenterica Ruptured MLN may cause Acute TB peritonitis Usually calcification and recovery, sometimes progressive lymphatic spread

to thoracic duct Miliary TB Rarely primary focus is tonsillar unnoticed until CLN softening and

discharge through skin (scrofula) In children mostly primary focus small extensive LN involvement

• In Adults: Enteric TB: Same features of pathogenesis as lungs, Depends on resistance of pt. fibrosis or extensive cavitation Severe cases tissue destruction Blood spread and LN involvement lesser than in children Swallowing infected sputum of pulm. TB Ileal wall ulceration, localized peritonitis, strictures/fistulae Renal TB: Cortical focus spreads to destroy surrounding renal parenchyma Other lesions in medulla bacilli passage renal tubules pelvis cavitation Destructive lesion of tuberculous pyelonephritis kidney converted to ragged

cavity lined by tuberculous granulation tissue down the ureter If ureter occluded large tuberculous pyonephrosis Skeletal TB: Metaphysial area of bone great local destruction Unlike pyogenic osteomyelitis, it destroys epiphyseal cartilage easily Soon the neighboring joint is affected

“Hence feature common in adult lesions is tendency to extensive local destruction with little lymphatic involvement”

Koch’s Phenomenon Application• Adult lesion almost always secondary to primary lesion of childhood

(difference in response of the 2 infections)• As in Koch’s Phenomenon 2nd infection localized so in adults no LNs Exception: Previously Mantoux – ve young adult TB even then adult type lesion rather than juvenile

type LN –ve tissue maturation?? Or may be avirulent atypical in childhood as primary possibility?? But even then all the adult lesions should not be called as Secondary

• So older the patient, lesser the LN involvement• Hence Childhood and Adult TB is more accurate terminology than Primary

and Secondary TB.• In lungs of adults either Reactivation of quiescent primary lesion (Post-

primary TB) OR development of new lesion produced by re-infection from some external

sourceOther organs like kidneys and bones TB mostly of reactivation of small

lesions produced during bacteremia phase of earlier primary infection