Modul Penyakit Tropis

dr.Susilorini
Overview
 Agen biologis penyebab infeksi
 Barier tubuh terhadap agen infeksi
 Prinsip-prinsip terjadinya infeksi
 Cara agen biologis menyebabkan
penyakit
 Mekanisme pertahanan tubuh terhadap
agen biologis
Pelajarilah bahan praktikum dengan sebaik- baiknya
Agen biologis penyebab
infeksi
 Prion: protein penjamu yang telah mengalami modifikasi, bersifat
resisten terhadap protease.
 Virus; agen intraselular obligat yang tergantung pada sel hidup.
Berukuran 20-300nm, hanya terlihat dengan ME, sebagai badan inklusi
pada MC
 Bakteriofaga, plasmid, transposon: elemen genetik yang dapat
berpindah dan menginfeksi bakteri serta secara tidak langsung
sebabkan penyakit pada manusia (mengubah bakteri non patogen
menjadi patogen)
 Bakteri: prokariot yang tidak memiliki inti sel dan retikulum endoplasma
 Klamidia, riketsia, Mikoplasma: mirip bakteri tetapi tidak mempunyai
struktur tertentu. Clamidia:Obligat intrasel yang berkembang biak dalam
fagosom sel epitel dan sitoplasma sel endotel.riketsia ditularkan melalui
arthophoda. Mycoplasma organisme hidup- bebas terkecil yang
diketahui (125nm- 300nm)
 Fungus: memiliki dinding sl yang sangat tebal
 Parasit protozoa, cacing,, Ektoparasit
Barrier terhadap infeksi
 Kulit: kulit padat berkeratin, ph kulit
rendah sekitar 5,5
 Saluran urogenital: saluran urine dalam
keadaan Normal steril karena dibilas
beberapa kali sehari
 Saluran napas: lapisan mukosiliaris, sel
kupfer
 Saluran cerna: cairan lambung, enzim
litik pankreas dan empedu, sekresi IgA
Prinsip terjadinya infeksi
 Bagaimana agen biologis tadi bisa
menembus barier
 Port de entre
 Bagaimana agen biologis
menyebar
 Bagaimana bisa menghindari
respon imun
Cara agen infeksi
sebabkan penyakit
 Kontak langsung ke dalam sel,
sebabkan kematian sel
 Produksi endo/ eksotoksin
 Memicu respon imun yang
memperparah kerusakan jaringan
Phagocytosis schematic
Mechanisme of oxigen
depending microbial killing
 Pathologic Basis of Disease 7th Ed., p.
47-118;
Basic Pathology 7th Ed., p. 33-77

Learning objective

1. Compare and contrast acute vs chronic inflammation with respect to

causes, nature of the inflammatory response, and tissue changes.
2. Compare and contrast the clinical settings in which different types of
inflammatory cells (eg, neutrophils, eosinophils, monocyte-macrophages,
and lymphocytes) accumulate in tissues. Compare and contrast the
contents of neutrophil and eosinophil granules.
3. Define the term macrophage activation, and list the products of activated
macrophages (Figure 2-28, PBD, p. 80 or Figure 2-21, BP, p. 55).
4. Define granuloma and list the causes of granulomatous inflammation
 Scenario
A 68-year-old black man presented with weight loss
over a four-month period and the recent onset of
fever and chills at night. Admission chest x-ray
revealed an irregular opacity of the right lung
with pleural effusion. Thoracocentesis was
performed, and cytologic examination of the
pleural fluid revealed cancer cells (poorly
differentiated adenocarcinoma). Abdominal CT
revealed hepatomegaly and diffuse
lymphadenopathy.
The patient was treated with multiple broad-
spectrum antibiotics, but his fever did not
respond. His hospital course was also notable for
electrolyte imbalances, including hyperkalemia
and hyponatremia. Despite supportive care, the
patient expired on the fourth hospital day, and an
autopsy was performed.
 Lung, right, carcinoma
Low power
-
Gross, cut surface

Cancer cells surrounding blood vessels and bronchi have spread into the lung
tissue. This image is just to illustrate the lung cancer in this patient
At this stage, do not be concerned
about the gross appearance of
cancer, as this will be dealt with
later on. However, consider what
effects the presence of a
debilitating disease like cancer
may have on the body's
competence to control infectious
disease. You should be able to
establish the relationship after the
next few images
 Lung, left, caseous
necrosis

There is a large central area of caseous necrosis, which is seen as granular

pink structureless material with complete destruction of the lung parenchyma.
The caseous material is surrounded by a cellular zone that contains
epithelioid cells and giant cells. These cells are seen at a higher
magnification in the next image. At the periphery, some alveolar spaces can
be seen
 Higher magnification

 In this higher magnification of the lung lesion, caseous necrosis is

seen as pink granular structureless material that has destroyed
the lung alveoli. Epithelioid cells surrounding the caseous material
are elongated cells with indistinct cell boundaries. Individual
epithelioid cells are difficult to see in this lesion. A large
multinucleated giant cell is clearly visible. The cells with dark
round nuclei are lymphocytes
 What is the origin of epithelioid
cells?
 Is this lesion an example of
granulomatous inflammation or
granulation tissue?
A focal collection of epithelioid cells
is called a granuloma.
Giant cells formed in granulomas by
fusion of macrophages.
The other cells in a granuloma are
Lymphocytes, mainly CD4+, that
caused the granulomatous
reaction.
Healing granulomas are surrounded
by fibroblasts..
Caseous necrosis
 Caseous necrosis is caused by
tuberculosis, leprosy, and fungal
infection.
 In caseous necrosis, there is total
loss of tissue structure, whereas in
coagulative necrosis, cell outlines
are retained
How does caseous necrosis differ
from coagulative necrosis under the
microscope?

 In caseous necrosis, there is total

loss of tissue structure.
 whereas in coagulative necrosis,
cell outlines are retained
 Lung, left, acid-fast stain -
High power

Reddish rods = acid-fast bacteria (Mycobacterium tuberculosis) seen

within an area of caseous necrosis
 Why do you think this
patient developed
tuberculosis?
 Can this explain the other

clinical features in this

patient?
 Patients with cancer are often
immunosuppressed. It is most likely that
immunosuppression allowed
reactivation of some old focus of
tuberculosis in this patient after he
developed cancer. Disseminated TB
could cause the lymphadenopathy and
hepatomegaly. Destruction of the
adrenal cortex by tuberculosis is
responsible for the electrolyte
imbalance
 Granulomatous inflammation
Adrenal gland, granulomatous
inflammation

Do you know the difference between granulation tissue and granulomatous

inflammation?

What are the causes of granulomatous inflammation?

The different are
Granulation tissue contains new small
blood vessels, fibroblasts, and
mononuclear cells in an edematous
extracellular matrix; it is part of the
repair response.
A granuloma is a circumscribed
collection of epithelioid cells, usually
surrounded by lymphocytes; it is a form
of chronic inflammation
There are 6 causes:
See PBD, Table 2-7, p. 83 or BP, Table 2-5,
p. 56:
• Bacterial (eg, Mycobacterium
tuberculosis, M. leprae, Treponema
pallidum);
• Parasitic (eg, schistosomiasis);
• Fungal (eg, histoplasmosis;
blastomycosis);
• Inorganic dusts (eg, silicosis, berylliosis);
• Foreign body;
• Unknown (eg, sarcoidosis)
 Testis, granulomatous
inflammation -
Low power High power

Granulomatous inflammation with caseous necrosis is shown. The pink

granular caseous material also contains some bluish nuclear debris.
There is no identifiable testis tissue in this image

All granulomas look similar

 Lymph node, noncaseating
granulomas - Low power

This image is of a lymph node from a patient with sarcoidosis. Each of these
clusters of pink cells is a granuloma composed of interlacing epithelioid cells
and giant cells. Note the absence of caseous necrosis.
 While granulomas in sarcoidosis do not
have caseous necrosis, it should be
remembered that early lesions in tuberculosis
may also have noncaseating granulomas.
Conversely, caseous necrosis may be seen
in granulomas caused by some other microbes
(which ones?).
Hence, it is essential to look for specific
organisms to establish a cause of the
granulomatous process (for example, by
performance of specific stains that visualize
mycobacteria, fungi, or other organisms, and
by microbial
Possible questions for
discussion
 1. How does the inflammatory infiltrate in this
patient's lung, adrenal gland, and testis differ
from that in previous cases, and what clinical
significance might these differences have?
What is the likely etiology of this
inflammation?
 2. What, if any, is the relationship between the
patient's adenocarcinoma and the
inflammatory process?
 3. Assuming the same inflammatory pathology
in a patient without neoplastic disease, what
would be the likelihood of regeneration of the
affected tissues?
 Lung, abscess in chronic
granulomatous disease -
Medium power
Abcess cavity/
Infiltrate of Mononuclear
mononuclear
phagocytes
phagocytes

In CGD patients, the response to even conventional bacteria is

dominated by mononuclear phagocytes. The clusters of red blood cells
staining
 Lung, Ghon complex
Radiograph and gross, cut surface
Calcified lymphonodes

Subpleural nodul

In the radiograph and in the photograph, a calcified, well-circumscribed

nodule in the left lung represents an old healed focus of primary
tuberculosis;
these are characteristically peripheral in location. In addition, other
calcified nodules can be seen in the radiograph in the left hilar region
where the clavicle appears to touch the arch of the aorta. This is a former
focus of infection by TB in draining lymph nodes
 Lung, tuberculosis, secondary
(reactivation) -
Gross, cut surface, and radiograph

The cavities in the upper lobes are the pathologic and radiographic findings in
secondary, or reactivation, tuberculosis. The major bronchi have been opened to
reveal mucosal hyperemia, which indicates congestion or inflammation of the
bronchial mucosa. In addition, patchy consolidation is present in the upper lobe;
this may represent either superimposed bronchopneumonia or progressive spread
of tuberculosis
Spleen, miliary
tuberculosis - Gross, cut
surface

This cut surface of the spleen shows multiple light

tan areas of caseous necrosis, which look like
multiple small abscesses grossly. Miliary
tuberculosis may occur in patients after either
primary or secondary (reactivation) tuberculosis
 Miliary tuberculosis is the
consequence of blood-borne
spread of tuberculosis. It more
commonly occurs in patients who
are immunosuppressed, such as
patients undergoing cancer
chemotherapy or dialysis,
transplant recipients, or HIV-
infected persons. In developing
countries, children are also
particularly