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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
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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
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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
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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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