: ‘of Pattne 4 x . Chronic Specific Inflammation Dr. Laila Elbarghati Pathology Department 2022 1024Chronic specific inflammation Granuloma qn Chronic specific inflammatory diseases characterized by accumulation of macrophages, lymphocytes & giant cells. Freki Vd Calls Ate “VERS x Vagmn calls Types of granuloma: 1. Infective granuloma 2. Foreign body granuloma 3. Idiopathic granuloma 1. Infective granuloma ae ™ Bacteria: as tuberculosis, syphilis, leprosy, actinomycosis, rhinoscleroma & Madura foot —> yey * Parasite: as schistomiasis = B\Wav2sasis - = Fungi: as histoplasmosis 2. Foreign body granuloma: suture, wood & glass. ,Ya\<_ powder, -- ees a ie 3. Idiopathic granuloma: as sarcoidosis & crohn disease. ~» © Www s ———— SOG ese. # AD YeS A aravntonnn . \ weaves Bremrmmmro nn E TB gornlema 2- Wor ~ n~ > : ; z oes -\ dkee AAC a NS noe “5 . mah oFTuberculosis Common disease. = 2 billion people are infected worldwide. = 140 million new cases & 1.6 million death /year (2019). = Caused by mycobacterium tuberculosis. —=, rxWoew Aw Nene. Eyidimiclegy . 6 1. Human type —? aera ackenum Ardbexedssrs ¢ ‘coms. 2. Bovine type —> 2 B- oN evs - Kaek cages = tis non motile aerobic bacillius, 3 ym, with waxy cell wall <7, ASO Pipe a iy arrow ddigths MERA 6 (Risk factors en e fa Connon : yo 1. Malnourished (mansternery SS eee care SMT? \s ) 2 et DE vemceaege . Smoker \ 4. Alcoholics ¢ : EEG. Swe be Yaad 5. Diabetes ‘\ 6. *AIDS ens 5 ree: oy ? 7. Silicosis a- oes Es & oa ; ~) a eh a EERE eng emi 1. Inhalation —> Ans 2. Ingestion Coevine SAYS) —PESAIR OF ~rewsi\s- 3. Skin contact ——y S\KIw - ' ig Pa enesi; . i : The tuberculobacilli neither produce an exotoxin, nor endotoxin. ¥ =the pathological changes in T.B pecepend upon the chemical structure of the SS] OES © pacteria. : nes ) ve 8The bacilli are made of 3 chemical components: 1. A lipid fraction: the cell wall. ot gue ree ee ZA 2. A protein fraction: the body of the organism called tuberculoprotein. The @ patfiogenicity ty of the organism depends mainly upon the antigenic nature re of the a aor ——— eC tuberculoprotein. 3. A small polysaccaride fraction. ells of T.B: Ee ANS = Neutrophils: attracted by the polysaccharide fraction of tuberculoba > their lysozmal enzymes has no effect on 1 bacteria. a aa = Macrophages: attracted by the lipid fraction of the cell wall after the first aes : day. Engulf the bacteria that are partially digested with the release of ‘tuberculoprotein. ME GW’ = In the first 3 weeks bacteria inhibit phagolysozomal formation within the the MQ, allow ‘allow unchecked bacterial proliferation. fi = The| tuberculoprotein stimulate a cell mediated immune response after 3 ‘Weeks, Type 2 IV delayed)hypersens vity reaction. = \ pcr events e3)secret IFY that activate MQ. ct _Z (1g release?) (1g release?) 1, IL-12 to generate CD+4 T cells of the TH1 subsets. 2. TNF attract monocytes that differentiate to Epithelioid cells. =—— = SS id 3. Re 1S with antibacterial activity. 4. S that generate Teactive nitrogen intermediate that destruct bacteria nl BAe exe mez pe eal 4@ wv ple, "Sensitized lymphocytes release various lymphokines which have the following OO ———— x actions, Ay 7 1, Chemotactic factors: iy attract more macrophages the area of inflammation. Chemotactic aC = SSsSsSSSSSSsSmh 2. Migration inhibition factor (MIF); inhibit migration of MQ from the _ inflammed area. marnssiis - 3, Mitogenic factor: stimulate | proliferation of lymphocytes. 4, Transfer factor: transfer sensitization to the new lymphocytes. 5. Cytotoxic factor: caused tissue necrosis (caseation). 6. Skin reactive factor: responsible for the +ve skin test (tuberculin test). Types of tuberculosis: . Primary T.B — KK. Secondary T.B ¢ Primary T.B: Occur in children (arai\) Sites: 2. Tonsils 3. Lung ——> (1) 4, Intestine @ 10*R a nronreess we a NARS SE KASH . Fy Brosh unexposed Immune competer wnhividngls Ey aac Tr arapennsis. by) abvediay Macro Qnaes : Sone MAs Can Yates rsacobacrersalh Pes & yreseny dnese Ay ow Way sua Cor pwction € Class IT mac ATO ak Ready LW Ss TW Naalyer Wyaghoetes (CDBYy ex Ts) Medwrion AY Te ite ooh NY (order Renee 4 TL-12 secreted from MGs) - Seasitinad Tat. A-2 TWA, seereke TENA etfs gaaman ACE MQ cremstackc Sach Aer substances « Arde rrinns 8 Raracrine adavation of CDY. mike od aRentnt AANA oR Ctteboic as . UEDE COA badern Sidr aloo Seong Reeve does ew. ARCA medk® Caunratas) of MERE cee aS a TERN acnenke MQs o cohense eens a* WKN Amberche: al « es z Lym congnction VINE a ackivele suythneats WAG puake s5elen e7epadetie Aedienuion ofrsevadenn ( AAson damage mde exereror Ki a Ae Seat) comse Nestows > Boe, "voy 7 , TARE SE Coded) ASRS we recht:~OccuF in childrehh———» NAM WAIT ow) - = Caused by myobacterium TB (human type) through inhalation. rey e\\ow conver <—_ } Ghon focus: Gray white inflammatory consolidation with caseous necrosis. Ip * Ghon complex: is a combination of parenchymal lesion with nodal invoverient = G\row’s Pocus Ww WAndeni'is - = Rank complex: when Ghon complex undergo fibrosis & calcification.» = Miliary T.B: few mm yellow white consolidation scattered throughout the lung. ee ee ‘i is: . \ (agin menial Goce feo 1. Ghon’s focus: at the periphery, mid zone, 1-2 cm & yellow — cep Were wf Subplearad = Array Relunn SpSmra\) a ye sew Caster. 2. Tuberculous lymphangitis (+ \ans PA AVS) —_—S=—— AOS 3. Tuberculous lymphadenitis: LN are enlarged, Soft & matted C/S is soft & yellow due to caseation. aS ee ee x8 od a >» Microsopic picture of t le: os ca) ‘© = Central caseous necrosis. —> Kooy’ ONO ‘SI AY) |@s Necrosis can lead to calcification or liquefaction & formation of a cavity if drained. inn errr @* Transformed monocytes called Epithelioid cells can form multinucleated giant (@®) calls by fusion F Mary” WAS os ie ah Os. = EBitheticid cal pithelioid cells are surrounded by a collar of lymphocytes & plasma cells ac = Fibrous connective tissue surrounds granulomas. OS eS ee CG Sloss oy YeF Ale SA NeeeeS Bett Ewald ells ae MQ; (romrotaies) & ogy 2 BAAR Cae sdk cede an Armed by fasio a~ {cee x le : cal\\s). Sx wood sexPost primary in immunized Tndividuals (adults). Post primar ee = Reactivation or reinfection» ExKenenens COXNe = Apical lobes. =——~—— J hones ot - Worrall . No = Caseation, cavity. EN Y. Local or systemic/miliary. KARAS INE marked fea bec ful C DARKEN OY 0A) tse SS mrccs 07 Aremsiony Cavitary Tuberculosis: = When soft, necrotic center drain out leave behind a cavity. When sot noe eee = Cavitation is typical for large granulomas. Lo Cavitation is common in the secondary tuberculosis. + —=—=—_———O Fate of tuberculosis: Depend on: i : ; 1. Virulence & 3-WDese Ssachewal Cafacing dos). ao 7 Dn oteyngm @ low 2. Sea 2_ Immunity = Roor YmAONS & Nace NESS \M matt SI of > Direct > Lymphatic — > Blood C Daemnnrtrogemrons ses): mplication of pulmonary T.B: 70 pBicect sprout: - TB bronchopneumonia - TB pleuri ——> v\ New afGasion - TB percarditis 2Blood spread: _——__—» asolwred ony as Endorgan 7.8: Small no. of bacteria — w ? - Miliary T.B: large no. of bacteria — al Cl Vows SS sm\\ Sw om a\\ow ei Extensive infection way be G aes Beate = ‘Hematogenous spread acd = Low immunity By ne oraars Lowy, es Sn aye > enone: Fate ri ma: 1. Liquefaction Cold Abscess ae 2. Sinus tracts es fue | Aoseso ee abe) 3. Adjacent granuloma coalesce » Large lesion —e — ibrosis & dystrophic calcification Eee Secondary amyloidosis 7 Clinical course: POPARAC = In many instances the individual is asymptomatic. == Any © the individual is ao a) Some have fever, night sweats, ‘anorexia, weight loss, cough (B symptoms). b) Some have increased sputum production & pallor. ©) A few have frank hemoptysis. Some of these will have fatal hemorrhage, but this =_ © Consolidation or cavitation in lung apices on X-ray. Consolidate? eee ® Acid fast smear to show tubercle bacilli (2 x) = Drug resistance is common but good prognosis if the disease is localized. EES 23# ils: \ reulo : Tlsiaton or gestion > BNNs LAPS = Chidren > Rrra ANRE : C Primary cervical complex consist of: ; 1. Small deep lesion in the tonsil, ia 2. TB lymphangitis. 3. TB lymphadenitis (scorfula): inflammation of the cervical L.N that are enlarged, soft, matted. Game eared Ss Sth ranted Conte) ntest uberculosis: ) += = Ingestion of bovine bovine or ham bacilli = Through ingestion jestion of contaminated milk} contaminated sputum. — ——— wane 2, i re Primary intestinal complex consist of: Rr: ao bee - Ne 1. Tubercles in payer's patches in the ileoces al ré ion followed followed by undermined M ulcer. ~~» Sr vic: = Smal cers = ed remalignant les TD, == =Premalignant lesion. ~. # * 4, ee (LY Sq nonnms cal\ Cav mone BBD CRD a Hematogenous infection affect: er a Conmmrenesix STS: ® = T.B vertebra (pott’s disease) cause: Tk BR a. 1. Deformity: kyphosis (Nerd >) 2. Cold abscess: collection of caseous material 3. Paraplegia ‘ : BE S28 fallewiy wre N\ass “\, Caseous Drvakerih NNN Aa ete sagen) > arms Dey aw A ares ne Eg didymis- ows 29 Fe Vopian Ayes Naberew\ ous salgmais:@ C=} S38 ne Spirochete: Treponema Pallidum (gram ve). => 4h eli ee ena Ay = Could be congenital (transplacental) or or acquired (sexual or bod oe i — x= — > Cause abortior abortion, still birth birth or early or late congenital syphilis. . ~) hilis (0-2 years of age): low birth weight, fever, skin sores( s\n ~c05\n) / — hepatosplenomegaly & pneumonia. —————_——S s > Inlate syphilis (2-5 years of age): > 24tnrs- Se Hutchinson teeth, _/® Deafness Deafness, 3. Blindness (12, 3 called | 2, 3 called Hutchinson triad) — — fant Sod oes nose with no bridge Types: Aesteyes: © © Primary Syphilis (2-4 weeks) —_—— — Jl. Secondary Syphilis (2-4 months) ——_ a Ayes ll-Tettiary Syphilis (years) Hee pons aw on AO ener : \ on ee Seger? Primary Syphilis:_ <= . 2 ulcer RR ¢ Chancre (1-2 cm nodule); firm, painless on external genitalia, finger, lips. & Shancre (1-2 cm nodul 7 vymphadenopathy: LN enlarged discrete not fused, rubbery & painless. =—=—= _—_—— AiSiuned® oyenencdated y zo NAer Wee - Condyloma Lata: large papules 2-3 cm in moist reas of, of body, axilla axilla, vulva, 5 —_—_$<——_ — Qed. 2 - Mucocutaneous lesions: macules, papules, pustules in ‘mouth & genitalia. Generalized Lymphadenopathy. ye ners > UE [Tertiary Svohiliss) 5 o\cin WA eos) pres oxen ® - Gumma‘a nodule single or multiple mass (tumor-like) affect liver, bone, tongue & skin (microscopic to several centimeters). .) Rares) we the en Stems oS wk 2 - Aortitis: Thoracic aorta can cause, stenosis, regurgitation & aneurysm. — ON ee @ - Neurosyphilis: General paralysis of insane dementia, depression & Paralysis. Affect spinal canal & dorsal nerve root called tabes dorsalis cause loss of sensation & muscle tone in lower limbs. ——————— ‘A gumma is a granutoma, histologically characterized by a central area of necrosis ‘Surrounded by mononuclear, epithelioid, and giant cells. CANS - - Diagnosis by smear taken from the lesion & seen with dark field microscopy@r) immunization techniques or serological tests to detect antibody. ——<—_ Dx ro eke OS 7 Senn ( demonrsrared / \dewatisd): SEK Sess 8 We 4 Blok \esion S15 wa diameter Ch vicene Sond): iw, eevee bee Cama Negron) - say comtnten Yeas Cabevateh om Sin omnes) wages o& EAS sAnce e age —> Ese eet Rt RA Sm) a \ Leprosy | AWSEW S COmsodarre (Cisreer) Wess NSCS. SORA AAS = Mycobacterium leprae (Hansen disease) Ve bawdy —See eos ebVigate Wawacewlar, may oy es \ey. \* Lepromatous leprosy DRACORANES istionsies). 1+ Tuberculoid leprosy %+ Borderline leprosy tle Ee [a ome ccs a \ More severe Less severe ) i yr: {fe ) High no. of bacilli Low no. of bacilli —_————— —<$<_ Low immunity —_— High immunity — Low T lymphocytes Normal T lymphocytes ete ae Affect skin, peripheral nerves Affect skin & peripheral & internal organs nerves ew Symmetrical Lesions Asymmetrical lesions rove Lace© oie > « Au Sane Ds Dae * = Normal commensal of mouth & GIT become pathogenic after injury or trauma. —_———_ SS OD = Common in children & young adults. Male are more affected. oOo” nl ede a CAs odir MNS = Actinomyces tre iT —. 1. Cevicofascial actinomycosis 60% —~—r maps McK, Sineses: S— = RAM ONATA © wr : 2. Thoracic actinomycosis 20% = oe NERO 3. Ileocecal actinomycosis 15% Ty enered « 4. Endometria! acti is 5% (in ute follow IUCD).. ndometriat actinomycosis 5% (in uterus Ww oe ot ™ CQ Girma porte HES © Bacillus Rhinoscleromatis —=> CAMERA OFHAKASAR > = *Rhinoscleroma (affect nose) Kilo sialla Wamosclen— —— nee 7 Laryngoscleroma —> Nov = Pharyngoscleroma —> Wasodur “ss Myestoma' (madura foot) Supparats oma (madura foot * Madurella Mycetomatis. _ Bt avnloma, $1 Cams organic (Kad). ™ Affect subcutaneous tissue & bone of feet. ee = Multiple nodules that suppurate & drain exudate contain granules through Tmufliple sinus tracts. oi EE SSS 6Histoplasmosis > A disease caused by a fungus called Histoplasma capsulatum. —— — —————_— > Common in the eastern and central United States (farmers & landscapers). _ I M25 Soy —— > It grows in‘soil and material contaminated with bat or bird droppings. You get =e Bee: ne een eee infected by breathing the fungal spores. errr pis Lad aah eh lh > Mostly asymptomatic but infants and those with compromised immune systems, histoplasmosis can be serious. bs Gere FEA sooo ane a FS Tipped _ 7 comalications dis due —<—=_ 1. Acute respiratory distress syndrome (alveoli filed with fluid). ARDS.«. Pao = 2. Pericarditis (sac filled with fluid) & heart problems. —— 3. Meningitis. 4, Adrenal insufficiency.® ald war Mav ta of schist: aT Monsont wth * oO Mansoni with lateral spine affect intestine & liver. WW SSE == "¥ -Biloatiesis \V2 GL) S$. Haematobium with terminal spine affect urinary tract $ Sw Sites: = Oe Mintestine ian + Uver * Spleen = Urinary system Lung = Male genital organs Female genital organ ross picture: >a. _» ecanmonns = Affect rectosigmoid area “TAQ. +-/~ Early: peticheal hemorrhage, edema, congestion yeliye hay ba olyps, ulcers, fibrosis & narrowing of intestinal wall » Polyp formation: 7 maces ah presi (ddeveteor) f * Bilharzial granulation tissue elevate the covering muscularis mucosa & mucosa forming a sessile polyp. ap rvihe & Wo peduds Cro Sra) = Then increase in size & its covering mucosa undergo marked hyperplasia to acquire a pedicle forming a pedunculated polyp.\_,"@ Sra . Microscopic picture: LamdQvro ade + (BD -Microsconic picture: NY ca = Diffuse or multiple granulomas (bilharziomas) with‘macrophages, neutrophils & esinophils more in submucosa. ars . = to oval egg, eosinophilic with lateral spine. = Dystrophic calcification. eee * Healing occur by fibros —e2 Complications: 1. Dysentery Bee um © SAPO ° 2. Bleeding /rectum 3. Iron SE anemia —> cornbed, » 4. Intestinal obstruction ——» Co 5. Schistosomiasis to liver —_ ~~ Liver schistosomiasis = Ova pass through Portal vein to portal tracts. * Granuloma formatio formation within portal tracts. * Fibrosis of portal tra portal tract tracts. Gn 1-Fine: small no. of ova deposited in fine portal tract. Wy Sacesrigeel as a Reyer 2- Coarse: large no. of ova & dead worms in coarse portal tract eae = Syeen ery = In early stages liver enlarg ed in size (fine type) then decrease i in size (coarse Ve. type). ee SP ee —=-—— + C/S: firm, thickened portal tract (pipe stem fibrosis). ve _\ ver fi}yosis ee i SSS” mune ‘Sranulomas surrounded by fibrosis ems 4 , Portal hypertension: = ya yi. Ascitis =? UNE. yr yi} a Congestive spl leenomegaly 5 Se ai Opening of porto-systemic anastomosis causing esophageal varices, ee aemorroides & caput medusae. — ® « tiver failure Liver failure 2S Bei, =Bilharzi: leen * Spl lenomegaly in blharzial hepatic fibrosis from mild enlargement to huge enlargement. = Retain its shape, thick capsule, dark colour & firm in consistency. x gear Hypersplenism: anemia, leucopenia & thrombocytopenia. =k rn) € X= }» Compression of surrounding structures RENIN : ary bladder, ureter alg Early: petechial hemorrhage, acute inflammation ©, eLate: ace ) yey Late: sandy patches, polyps, ulcers » § prs @ ro: multiple granulomas, eosinophils, fibrosis - r ew ey a x Epithelial changes: 174.124) Welle 7 Hyperplasia. mM c Qs pe Brunn’s nests: hyperplastic epithelium dip into submucosa forming round nests of transitional epithelium. wt 3. Cystitis cystica: hydropic degeneration in central cells of Brunn’s nests. ye Cystitis glandularis: similar to C. Cystica with metapl, 5 om es Squamous metaplasia with extensive keratinization appear as white patches 6 (leukoplakia) (precancerous lesion). = a ee SS ©. icati r ~* Bleeding: hematuria —> classical Sayan ~* Iron deficiency anemia +, Bacterial infection of bladder with stone formation 4" Hydronephrosis, hydroureter —S ae X= Oe Sone tons, Xo WK s* Squamous metaplasia, squamous cell carcinoma oro + Se 7 Vie hale Lan MC be Eapy erve\i te way = Cor Armond ic transitional epithelium. ee Oa wate ** Sister esClinical features. * Urine examination for ova, S. Haematobium (terminal spine). * Stool examination for ova, S. Mansoni (marginal spine). = Biopsy (granuloma). Examples of Granulomatous Inflammation Condition Etiological agents Special characteristics ‘| Tuberculosis M.tuberculosis Granulomas with central Caseaus necrosis; Acid-fast bacilli (AFB) Syphilis Treponema pallidum | Composed of lymphocytes, — freee MQ, plasm: = a ‘infiltration, central necrosis & thick blood vessels Leprosy M.Lepra — —_— Non casgating granulomas | aibetutod bre), SE ae Foreign body granuloma Suture, wood, glass Non-caseating granulomas “etc... “Tole - with foreign body giantcs\) uss <4, cells; demonstration of “dt foreign body. ew " foreign body. we VEN “la eae lle | Sarcoidosis Unknown Non- ting granulomas ——. (hard tubercles); asteroid & schaumann bodies in in giant cells. GReRTraw’s aoa calls - We of No tattel Necwsns oY Vb Vire SSye F/- WHY meonss EqQnniiosd callsymg Peay \yrmdro ares: EN se cellsay Tuberculosis - Pathogenesis AA PRIMARY PULMONARY TUBERCULOSIS (0-3 wees) a oP me Mannosecapped QCD pay ‘Macrophage mannose receptor polymorphism Unchecked baciiary proliferation — > | Endosomal manipulation’ “Maturation arrest + Lack of acd pH * infective phaglysosome fomaton Bacteremia with seeding Mycobacteia ‘Aveolar macrophage of mutiple sites B. PRIMARY PULMONARY TUBERCULOSIS (»3 weeks) ‘Aveolar Wa? macrophage Class il | T-cell | Nit oxide and NHC | receptor — {re adcals anuloma NTB antigen we f } + $ Chypesensivy’) Tuborculin positivity Bactoricidal activity (Chypersensitvty’) ———(immunity")ee Differences between TB & foreign body granuloma 1. The presence of foreign particle. 2. Foreign body giant cells with scattered nuclei. 3. No epithelioid cells just macrophages. 4. No central caseation. The Langhan’s giant cell — seen in ‘The foreign body giant cell — seen chronic granulomata, e.g. tuberculosis in association with particulate and sarcoidosis. insoluble material. i : Nuclei scattered Eee _-- Nuclei in horse-shoe throughout ~~~ arrangement cytoplasm Caseation if Giant cell Epithelioid cells Lymphocytes Fibrous tissueZo Edge XU Stoving Venous ulcer Punched out Neuropathic Pee Undetermined — Decubitus Rolling Basal cell ca. CoN C_ bverted Squamous ca. a ant24