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General Pathology

Basic Principles of Cellular and Organ

Pathology

Inflammation - III

Jaroslava Dušková

Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

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Granulomatous inflammation – table of contents

Granuloma – definition, pathogenesis, composition,

development

Granulomatous inflammatory diseases –

representatives

– Tuberculosis – definition, types, macroscopy forms,

histopathology, development

– Sarcoidosis – diff. dg. to tuberculosis

– Syphilis – definition, types, macroscopy forms,

histopathology, development

– Leprosy - definition, types, macroscopy forms,

histopathology, development

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InflammationDefinition:

complex reaction of organism to damage

(aim: homeostasis maintenance)Jarosla

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InflammationSense

defensive – agent elimination

reparative – damage reparation

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Inflammation - Classification:

Time view

acute

subacute

chronic

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Inflammation - Classification:

According to the dominant phase:

alterative

EXSUDATIVE

proliferativeJaroslava Duško

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Inflammation - Classification:

According to the dominant phase:

alterative

exsudative

PROLIFERATIVEJaroslava Duško

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Inflammation - Classification:

Types of granulation tissue:

nonspecific

„specific“

GRANULOMATOUSJarosla

va Dušková

Granuloma

Def.:

Accumulation of macrophages

transformed into epithelioid and

multinucleated giant cells

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infected

macrophage

activated

macrophage

intracellular

parasites

mature Th clone

creation

cytokins & bactericid subst.

secretion

interferon γ

interferon

receptor

interferon

receptor

Macrophage

activation

Trehalose 6,6´-Dimycolate

TDM

• one of the many lipids in the

Mycobacterial wall.

• most toxic

• most granulomagenic

• most abundant extractable lipid

from the MTB surface.

• It inhibits fagosome-lysosome

fusion and thus protects the MTB

from kiling within macrophages.

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Granuloma - composition

MACROPHAGES

lymphocytes

fibrous deposits

of collagen

central necrosisJarosla

va Dušková

Epithelioid

decreased phagocytotic activity

reduced Fc & C5 receptors

secretion function

protein kinases (signals transmission)

cholecalciferol activation-hypercalcemia

fused macrophages

tens of nuclei

function similar to

epithelioid cells

Langhans Cells

&

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Granuloma - development

fibrosis

hyalinosis

dystrophic

calcification

progressive

necrosis

cavity formation

spread with

generalisation

or metastatic

foci

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Granulomatous

Inflammatory Diseases 1.

TUBERCULOSIS sarcoidosis

syphilis

leprosy

Lyme borreliosis

inf. scleroma (rhinoscleroma)

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Granulomatous

Inflammatory Diseases 2.

lymphogranuloma venereum (inguinale)

anthropozoonoses : brucelosis, listeriosis,

tularemia,…..

cat scratch disease (Afipia felis, Barthonella)

mycoses: histoplasmosis, coccidiodomycosis…

parasites: leishmaniasis, schistosomiasis,

toxoplasmosis…

large antigen antibody complexes: rheumatoid

arthritis

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TUBERCULOSIS

Mycobacterium tuberculosis (Koch 1882)

Mycobacterium bovis

acidoresistance

M. avium,intracellulare, Kansasii

atypical mycobacterioses

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http://www.who.int/tb/publications/global_report/en/

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TUBERCULOSIS

Tuberculosis (TB) is one of the top 10 causes of death worldwide.

In 2017, 10 million people fell ill with TB, and 1.6 million died from the disease

(including 0.3 million among people with HIV).

In 2017, an estimated 1 million children became ill with TB and 230 000

children died of TB (including children with HIV associated TB).

TB is a leading killer of HIV-positive people.

Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health

security threat. WHO estimates that there were 558 000 new cases with

resistance to rifampicin – the most effective first-line drug, of which - 82% had

MDR-TB.

Globally, TB incidence is falling at about 2% per year.

An estimated 54 million lives were saved through TB diagnosis and treatment

between 2000 and 2017.

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In 2017, the largest number of new TB cases occurred in the South-East

Asia and Western Pacific regions, with 62% of new cases, followed by the

African region, with 25% of new cases.

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TUBERCULOSIS portae invasionis

– respiratory tract

– gastrointestinal tract

– skin

types of disease (clinicoepidemiol. view)

open tbc

closed

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TUBERCULOSIS

Type of infection

childhood (primary, preimmune)

adult (postprimary, immune)Jaroslava Duško

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TUBERCULOSISMorphological features

primary infect (Ghon focus) & primary complex

caseification

isolated organ metastasis

tubercle, exsudate, cavity

early and late generalisation

– milliary spread

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Disseminatio tuberculosis haematogenes

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Peritonitis tuberculosa

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TUBERCULOSIS

Type of infection

childhood (primary, preimmune)

adult (postprimary, immune)Jaroslava Duško

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TBC

postprimaria

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TUBERCULOSIS

Terms –Forms– Locations:

phtisis gallopans

scrofulosis

meningitis basillaris

tuberculoma

lupus vulgaris

mallum Potti, cold absces

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Pachymeningitis

tuberculosa

Tubercula cerebri et

cerebelli

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Scrofulosis

Laryngitis

tuberculosa

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Tuberculosis

cavernosa

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SARCOIDOSIS

etiology ?????

Pathogenesis:

changed Th and Ts ratio

modified immune reactionJarosla

va Dušková

SARCOIDOSISm. Besnier–Boeck–Schaumann

morphology similar to tbc(and important dif. dg.)

forms : localised

generalised

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Sarcoidosis

Schaumann´s

inclusions

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Syphilis

Treponema pallidum(F.Schaudin 1905)

argyrophilia

Syphilis acquisita

Syphilis congenita

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Treponema pallidum

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Syphilis acquisita

Stages (1) :

I. ulcus durum + bubo indolens

II. exanthema syphiliticum, angina syphilitica, condylomata lata

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Ulcus durum

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Syphilis II

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Exanthema syphyliticum

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Paul Ehrlich in his laboratory

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Mucose plaques

Condylomata

lata

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Syphilis acquisitaStages (2):

III. gumma - granulomatous

Late syphilis (quarterly, meta–)

neurosyphilis

paralysis progressiva

tabes dorsalis

panaortitis syphilitica

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Gumma

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Hepar lobatum

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Mastitis gummosa

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Myocarditis

gummosa

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Panaortitis

luetica

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Endarteriitis

syphilitica productiva

(Heubneri)

brain arteries

Aneurysma aortae syphiliticum

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Syphilis cerebri

•Paralysis progressiva – atrophia corticis rubra

•Tabes dorsalis

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Syphilis congenita

Forms:

fetus maceratus (hepatosplenomegalia)

hepatitis pericellularis pericholangitis syphilitica,

pancreatitis

pneumonia alba

pseudogummata

osteochondritis et periostitis syphilitica

coryza et exanthema syphiliticum

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Pneumonia alba

Pancreatitis

Hepatitis

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Syphilis congenita tarda

Trias Hutchinsoni:

keratitis parenchymatosa

labyrinthitis

Hutchinson´s teath

gummata

periostitis syphilitica tibiae

paralysis progressiva infantilis, iuvenilis

panaortitis syphilitica

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Periostitis syphilitica

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LEPROSY

700 000 new cases/year

more than 10 mil. cases in the world

mostly warm climates

related to living conditions

zoonosis - armadillo (Dasypus novemcinctus)

primates, cultivation on a nude mice

CURABLE !!!! (combination of antibiotics)

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LEPROSY

Mycobacterium leprae (Hanseni) 1873

Port of entry respiratory tract

Intracellular parasitism

macrophages, later Schwann cells

Reduced genom

(comparing to Mycobacterium tbc)

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LEPROSY

Classification (more detailed are available):

lepromatous

(in nonimmune. Virchow lepra cell)

tuberculoid (granulomatous, immune

patients)

indeterminate (early stage)

borderline (combined)

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Virchow´s cells

Lepra

maculoanesthetica

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Lepra lepromatosa

– facies leontina

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Lepra

Atrophia muscularis e

denervatione.

Ulcera trophica.

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Rhinoscleroma –infectious scleroma

endemic to Africa and Central America

Klebsiella rhinoscleromatis

chronic granulomatose inflammation – stages:

– catarrhal – granulomatous - sclerotic

Mikulicz cells – macrophages

scaring

curable - antibiotics

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Rhinoscleroma

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