Lecture on pathomorphology for

the 3-rd year students

By T.G. Filonenko

Tuberculosis
Tuberculosis is a chronic
communicable disease with
specific
granulomatous
inflammation caused by a
variety of tubercle bacilli,
especially
Micobacterium
tuberculosis hominis and M.
t. bovis.

Mode of transmission
By inhalation into the respiratory tract.
Ingestion. Through ingestion into GI
tract leads to development to tonsillar
or intestinal tuberculosis.
Inoculation.
Through
mucous
membranes of mouth and throat, skin.
Transplacental
route
results
in
development of congenital tuberculosis
in fetus from infected mother.
3

Classification of
tuberculosis
1. Primary tuberculosis
2. Post primary tuberculosis:
a) Hematogenous tuberculosis
b) Secondary tuberculosis

Postprimary

Pathogenesis of
Tuberculosis

As the most common portal of entry is the

respiratory tract by inhalation.
The inhaled organism enters into alveoli and is
ingested by the alveolar macrophage.
The MT can either be killed by the macrophage;
its growth inhibited or multiplies inside the
macrophage.
MT lives in symbiosis with the cell.
During the course of the next 4 to 6 weeks both
cell-mediated immunity and the delayed type of
hvpersensitivity develop in the host and these
after the host response to the infection and
result in the formation of the classic tubercle.
7

Hypersensitivity and
immunity in
tuberculosis

Hypersensitivity or allergy, and immunity or

resistance, plays a major role in the development
of lesions in tuberculosis.
Tissue changes seen in tuberculosis are not the
result of any exotoxin or endotoxin but are
instead the result of host response to the
organism, which is in the form of development
of cell-mediated hypersensitivity (or type IV
hypersensitivity) and immunity.
8

Features of Primary
Tuberculosis

Development of disease at the first getting of the

activator into the organism.
Sensibilization and allergy of HIT (Hypersensitivity of
Immediate Type) .
Prevalence of the exudative - necrotic changes.
Tendency to hematogenous and lymphogenous
generalization and also to chronic duration.
Paraspecific reactions such as: vasculitis, nodous
erythema, arthritis.
Primary Tuberculosis used to be found most often in
young children, but in industrialized countries it has
become more common in the elderly and debilitated,
in alcoholics, and in high-risk racial groups.
9

"Ghon complex" is the

characteristic gross appearance
with primary tuberculosis
The primary complex is
located in
- the lower part of the right
upper lobes or
- the upper part of the lower
lobes in 3, 8, 9, 10
segments usually.
10

PRIMARY COMPLEX OF TUBERCULOSIS

"Ghon complex
consists of
I. Pulmonary
component so
called Primary
affect or primary
focus or Ghons
focus.

III

II. Lymphatic vessel

component occurs
by Tuberculous
lymphangitis.

II
I

III. Lymph node

11
component occurs

PRIMARY COMPLEX OF TUBERCULOSIS

There is small
tan-yellow
subpleural
granuloma
in
the
mid-lung
field on the right
(1). In the hilum
is a small yellow
tan granuloma
in a hilar lymph
node next to a
bronchus (2).

12

Microscopical picture of
Primary affect
It is 1-2 cm
solitary area of
caseous
pneumonia
surrounding by
perifocal serous
inflammation. A
central area of
necrosis appears
irregular,
amorphous, and
pink. Grossly,
areas of
13

Tuberculous

lymphadenitis
Seen here in a
hilar lymph
node is a
"caseating"
granuloma.
Granulomas have
prominent
caseous necrosis.
Grossly, areas of
caseation appear
cheese-like.
14

CASEATING LYMPH
NODE TUBERCULOSIS

PRODUCTIVE
TUBERCULOSIS
OF THE LYMPH NODES

15

Primary tuberculosis of alimentary tra

In the case of
primary
tuberculosis
of
alimentary tract
due to ingestion
of
tubercle
bacilli, a small
primary focus is
seen
in
the
intestine. It is
tuberculous

16

Tuberculous mesenterial lymphadenit

The lymph nodes in this
mesentery are enlarged
and have cut surfaces
that appear yellow-tan.
These nodes are filled
with
sheets
of
Mycobacterium aviumcomplex
(MAC)
organisms,
and
the
immune response is so
poor in this AIDS patient.
The
enlarged
and
caseous
mesenteric
Lymph
nodes
may
rupture into peritoneal

17

Duration of Primary
tuberculosis
In course of time, the primary lesion can
heal, expand locally or lead to disseminated
disease.
This can occur at both the
sites: the lung and the lymph nodes.
3 variants of the duration of Primary
tuberculosis are probable:
healing of primary complex;
generalization of process (lymphogenous
and hematogenous);
chronic duration.
18

Healing of the Primary comp

com

Healing of primary
complex begins at
initial affect:
1.
Perifocal
inflammation resolute
and
exudative
inflammation
replaces by fibrous
capsule (1);
2. Caseous masses
are being dehydrated
and petrificated, and
then ossificated (2).
Such healed initial
focus
is
called 19

Calcified pulmonary lymph

nodes in tuberculosis
Healing
in
lymphatic nodes is
similar
to
pulmonary center.
Calcification

20

Hematogenous generalization
of primary tuberculosis

The most serious immediate complication is miliary

tuberculosis, in which there is invasion of the
bloodstream by MT and dissemination throughout the
body.
This occurs when the parenchymal part of the Ghon
complex involves a pulmonary artery or vein and
discharges its infected contents into the blood.
Multiple miliary granulomas develop in many organs of
the body.
Larger nodules may have central necrosis known as
caseation--a process of necrosis that includes elements of
both liquefactive and coagulative necrosis.
Few organs are spared; those most often involved are the
lung (mainly by recirculation of the organisms), spleen,
liver, kidney, meninges, and bone marrow.
The most serious complication and cause of death can be
tuberculous leptomeningitis.
21

Hematogenous generalization of
Primary Tuberculosis
The
lesions
are
classically 0.5 mm
to
2
mm
in
diameter, firm and
tan,
and
evenly
distributed through
the affected organ.
The name "miliary"
derives from their
supposed
resemblance
to
millet
seeds.
A
punctate area of
necrosis may be 22
seen in the center.

Microscopical features
of Miliary Tuberculosis
Here
are
two
pulmonary
granulomas.
Granulomatous
inflammation
typically consists
of
epithelioid
cells,macrophage
s,
giant
cells,
lymphocytes,
plasma cells, and
fibroblasts. There
may
be
some
neutrophils.
23

Giant cells are a

"committee"
of
epithelioid
macrophages. Seen
here
are
two
Langhans type giant
cells in which the
nuclei are lined up
around the periphery
of the cell. Additional
pink
epithelioid
macrophages
compose most of the
rest of the granuloma.
24

These are epithelioid cells around

the center of a granuloma. They get
their name from the fact that they
have lots of pink cytoplasm similar
to squamous epithelial cells. Their
nuclei tend to be long and stringy.
25

Lymphogenous
generalization

It is characterized by involvement the new groups of

lymph nodes, such as: paratracheal, supraclavicular ,
subclavian, cervical and development of tuberculous
mezadenitis.
The enlargement of the bronchial lymph nodes may cause
extrinsic compression on the bronchus or erode into the
adjacent structures.
The effect of external compression of the Lymph nodes
on the bronchus is similar to what happens in the
retrograde involvement from the parenchyma of the lung,
complete or partial obstruction. The enlargement of the
lymph nodes may produce a wheeze by compressing the
bronchus.

26

Growth of primary parenhymal

injurymost commonly occurs
Progressive primary tuberculosis

in

patients with suppressed or defective immunity.

The primary Ghon focus in the lung enlarges rapidly, erodes
the bronchial tree, and spreads, a sequence that results in
adjacent satellite lesions.
The lesion may enlarge in size and liquefy with a cavity
formation as in an adult or produce an area of consolidation.
The caseous material can enter into a bronchus and then
spread to other parts of the lung or the opposite lung,
resulting in a tuberculous bronchopneumonia.
When this happens the caseous material is discharged
leaving an acute cavity.
A subpleural focus can involve the pleura and cause pleurisy
followed by pleural effusion.
The infected material can by a retrograde spread, cause
bronchial lesion and result in endobronchial ulceration and
stenosis, which can produce either a complete or partial
obstruction.
This may lead to a segmental collapse, with compensatory
emphysema or an obstructive emphysema. If the collapse
persists for a long time, the affected lung may become
bronchiectatic.
27

When there is
extensive
caseation and the
granulomas
involve a larger
bronchus, it is
possible for much
of the soft,
necrotic center to
drain out and
leave behind a
cavity. Cavitation
is typical for large
tuberculous
granulomas.
Cavitation is more
common in the

28

Hematogenous
Tuberculosis

Conditions of the development :

the presence of sensibilization to tuberculin;
strongly pronounced immunity;
the presence of foci are healed
after
hematogenous
generalization
of
primary
tuberculosis (sifting);
absence of tuberculous lymphadenitis.
Hematogenous tuberculosis is characterized
by proliferative reaction or formation of the
granulomas and hematogenous spreading.

29

With a poor immune

response to the
agents producing
granulomatous
inflammation, there
is extensive spread
of infection with the
production of a
"miliary" pattern of
granulomas as seen
here in the lung of a
patient with miliary
tuberculosis. The 1
to 2 mm
granulomas are
scattered around
like millet seeds.
30

Miliary pulmonary tuberculosis

The focal
nature of
granulomato
us
inflammation
is
demonstrate
d in this
microscopic
section of
lung in which
there are
scattered

31

Classifications
of hematogenous tuberculosis

Generalized hematogenous tuberculosis:

) The most acute tubercular sepsis.
b) Acute general miliary tuberculosis.
c) Acute general large-focal tuberculosis.
d) Chronic miliary tuberculosis.

Hematogenous pulmonary tuberculosis:

) Acute miliary tuberculosis.
) Chronic miliary tuberculosis.
) Chronic
large-focal tuberculosis or hematogenousdisseminative.

Hematogenous
unpulmonary
tuberculosis:

tuberculosis
lesions
or

with
organic

Tuberculosis of the kidneys, of urinary- genital tract, of

skin, of bone- articular, of endocrine organs and others . 32

Features
of hematogenousdisseminative tuberculosis:

may by in adults only;

prevalence apex- plural localization;
proliferative tissue reaction ;
development of the pneumosclerosis
and emphysema of lungs;
cor pulmonale (hypertrophy of right
ventricle of heart);
simmetrical small cavernes;
presence of unpulmonary tubercular
foci.
33

On closer inspection,
the granulomas have
areas of caseous
necrosis with
formation of the
small cavernes. This
is very extensive
granulomatous
disease. This pattern
of multiple caseating
granulomas primarily
in the upper lobes is
most characteristic of
postprimary
hematogenous
(reactivation)
34
tuberculosis.

TUBERCULOUS OSTEOARTHRITIS
35

Tuberculous endometritis

Epithelioid cells

Langhans cell
36

Tuberculosis
of the testis (1)
and
epididymus (2)

37

Tuberculous meningitis

38

RENAL TUBERCULOSIS

Large foci of
caseous necrosis

39

MILIARY TUBERCULOSIS IN LIVER

40

Miliary tuberculosis of the spleen

41

Characteristics
of the Secondary
Tuberculosis
May
be
in
adults
only
with
postprimary disease (or reinfection);
Only Pulmonary localization (often 1st and 2-nd segments so called
Simons foci);
Contact and intracanalicular
spreading;
Shifts of the clinical-morphological
forms.
42

Forms or stages
of the secondary
tuberculosis:

1.Acute local tuberculosis.

2.Fibrous-local tuberculosis.
3.Infiltrative tuberculosis.
4.Tuberculoma.
5.Caseous pneumonia.
6.Acute cavernous tuberculosis.
7.Fibrous cavernous tuberculosis.
8.Cirrhotic tuberculosis.
43

Apical pulmonary tuberculosis

There are
several 1 cm
diameter,
partially
calcified foci
(dry,
crumbly,
and white)
that are
surrounded
by slaty,
indurated
scar tissue.

44

Lung, tuberculosis, secondary

(reactivation) - Gross, cut surface, and
radiograph

44a

Caseous, partly gelatinous pneumonia

45

Fresh tuberculous cavity

Greyish-white
wall of the
cavity 2 to 3
mm thick

46

Fibrotic scar in the wall of

tuberculous cavity consists of
fibroblast, collagen, and
scattered Langerhans giant cells

The wall of tuberculous cavity

contains foci of calcification
replacing the caseating
granulomas

47

Complications and causes of

death

Scarring and calcification.

Pneumothorax.
Empyema.
Pleural fibrosis and adhesions, with associated
pleurisy, sharp pleuritic pain, and shortness of breath.
Chronic respiratory-cardiac insufficiency due to
development cor pulmonale.
Acute hemorrhage due to erosion of vessels.
Chronic renal insufficiency due to development of
amiloidosis of kidneys.
Intoxication.
48