1

GRANULOMATOUS INFLAMMATION
- is a distinctive pattern of chronic inflammation
characterized by aggregates of activated
macrophages with epithelioid appearance
- Examples of diseases with granulomatous
inflammation:
- Tuberculosis
- Leprosy
- Syphilis
- Cat-scratch disease
- Sarcoidosis
Tuberculosis
- chronic granulomatous
disease
Mycobacterium tuberculosis
- usually involves the lungs but
may affect any organ or tissue
in the body
- Hist:
- Epithelioid granulomas with
caseous necrosis
Mycobacterium tuberculosis
1.7 billion NTB (+)
1 3 mlnJyear
A I D S
Tuberculosis {TB)
198S
Peak <: 1800
PRUWDOLW\
1992
Robert Koch
Why does TB still exist?
A I D S
Drug - resistant strains
Poverty
TB
Diabetes mellitus
Alcoholism
Chronic lung
diseases {silicosis)
Chronic renal failure
Malnutrition
Immunosuppression
AIDS
Mycobacterium
tuberculosis

inhalation

lung
bovis

milk

GIT, tonsils
Control:
Healthy cows
Pasteurized
milk
M. avium - intracellulare - TB in immunosuppressed persons
(~up 30 A!DS patients)
M.t. grow very slowly in conventional media (+-6 weeks)
O
2
2
Ziehl - Neelsen staining
Acridine
orange
staining
Tuberculosis
primary
secondary
Primary tuberculosis
Develops in a previously
unexposed
{=unsensitized) person
M.t. = exogenous
Primary tuberculosis {0 - 3 weeks)
ineffective
phagolysosome
formation
Primary tuberculosis {>3 weeks)
iNOS = inducible nitric oxide synthase
Tuberculin {Mantoux) test
- PPD test (Purified Protein Derivative):
- detects cell-mediated hypersensitivity to MBT
antigens
- does not differentiate between infection and
disease
- intracutaneous injection of PPD visible and
palpable induration {at least 5 mm in
diameter) that peaks in 2-4 d.
- False-negative reactions:
- certain viral infections, sarcoidosis, malnutrition,
Hodgkin's lymphoma, immunosuppression,
overwhelming active tuberculous disease
- False-positive reactions:
- infection by atypical mycobacteria
3
Tuberculosis
Epithelioid cells
Lymphocytes
Caseous necrosis
Multinucleated
giant Langhans
cell
Primary tuberculosis
GHON complex
{primary complex)
Ghon focus
(caseating or noncaseating
granulomas)
enlarged LN
(caseating or noncaseating granulomas)
lymphatics
(the lower part of the
upper lobe, the upper
part of the lower lobe,
close to the pleura)
1-1.5 cm
Gohn complex
Fibrosis
calcification
M.t. (+) M.t. (-)
Caseous
necrosis
TB pneumonia cavitation
blood
miliary TB
{lungs, liver, spleen,
meninges, etc.)
blood Latent lesions
- pulmonary
- extrapulmonary
M.t. (+) dormant
PRIMARY TUBERCULOSIS
ASYMPTOMATIC
ASYMPTOMATIC
SYMPTOMATIC
very rare
AIDS, MALNUTRISHED
CHILDREN, ELDERLY
Gohn complex
Fibrosis
calcification
M.t. (+) M.t. (-)
Caseous
necrosis
TB pneumonia cavitation
blood
miliary TB
{lungs, liver, spleen,
meninges, etc.)
blood Latent lesions
- pulmonary
- extrapulmonary
M.t. (+) dormant
PRIMARY TUBERCULOSIS
ASYMPTOMATIC
ASYMPTOMATIC
SYMPTOMATIC
very rare
AIDS, MALNUTRISHED
CHILDREN, ELDERLY
P
R
I
M
A
R
Y

P
R
O
G
R
E
S
S
I
V
E

T
B
4
Miliary TB
- TB ruptures into LYMPHATICS
LYMPHATIC DUCT R.V.
PULMONARY ARTERY MILIARY
PULMONARY TB
- TB ruptures into PULMONARY VEIN
L.V. SYSTEMIC MILIARY TB
millet seeds
Miliary TB ( 2 mm)
Secondary tuberculosis
Reinfection
Reactivation
Develops in a previously sensitized
person
M.t. = exogenous or endogenous
Gohn complex
Fibrosis
calcification
M.t. (+) M.t. (-)
Caseous
necrosis
TB pneumonia cavitation
blood
miliary TB
{lungs, liver, spleen,
meninges, etc.)
ASYMPTOMATIC
ASYMPTOMATIC
SYMPTOMATIC
very rare
AIDS, MALNUTRISHED
CHILDREN, ELDERLY
lungs other organs
apex other regions
blood latent lesions
M.t. (+) dormant
PRIMARY TUBERCULOSIS
Gohn complex
blood latent lesions
lungs other organs
apex other regions
Sputum
with M.t.
Assman focus caseous necrosis & fibrosis cavitation
REACTIVATION OR REINFECTION
TB pneumonia blood
Miliary TB {lungs, liver, etc.)
TB of the other
lung regions
S
E
C
O
N
D
A
R
Y

P
R
O
G
R
E
S
S
I
V
E

T
B
SECONDARY TUBERCULOSIS
Progressive pulomonary TB
symptoms
- insidious onset
- malaise, anorexia,
weight loss
- fever {low grade,
intermittent)
- night sweats
- amount of sputum,
hemoptysis
- pleuritic pain
5
Progressive pulmonary TB
changes
- lung parenchyma:
-Assman focus
-caseous necrosis
-fibrosis
-cavitation
- pleura:
-pleural effusion
-tuberculous empyema
-obliterative fibrous pleuritis
- bronchi
- trachea
Secondary tuberculosis - forms
1. Progressive pulmonary TB
2. Laryngeal TB
3. Systemic miliary TB
4. Isolated - organ TB
5. Lymphadenitis
6. Intestinal TB
Systemic miliary TB
- Liver
- BM
- Spleen
- Adrenals
- Meninges
- Kidney
- Fallopian tubes
Secondary tuberculosis - forms
1. Progressive pulmonary TB
2. Laryngeal TB
3. Systemic miliary TB
4. Isolated - organ TB
5. Lymphadenitis
6. Intestinal TB
Gohn complex
blood latent lesions
lungs other organs
apex other regions
caseous necrosis & fibrosis cavitation
S
E
C
O
N
D
A
R
Y

P
R
O
G
R
E
S
S
I
V
E

T
B
SECONDARY TUBERCULOSIS
REACTIVATION OR REINFECTION
Isolated - organ TB
- Meninges
- Kidney
- Adrenals
- Bones - vertebre {Pott
disease)
- Fallopian tubes
- Epidydymis
6
TB - rare
- Heart
- Skeletal muscles
- Thyroid
- Pancreas
Secondary tuberculosis - forms
1. Progressive pulmonary TB
2. Laryngeal TB
3. Systemic miliary TB
4. Isolated - organ TB
5. Lymphadenitis {cervical LN -
scrofula")
6. Intestinal TB
Secondary tuberculosis - forms
1. Progressive pulmonary TB
2. Laryngeal TB
3. Systemic miliary TB
4. Isolated - organ TB
5. Lymphadenitis {cervical LN -
scrofula")
6. Intestinal TB {ileum)
contaminated milk
swallowing of coughed
up infective material