Modul Penyakit TropisModul Penyakit Tropis

dr.Susilorinidr.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

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

Learning objective

ScenarioScenarioA 68-year-old black man presented with weight loss A 68-year-old black man presented with weight loss

over a four-month period and the recent onset of over a four-month period and the recent onset of fever and chillsfever and chills at night. Admission chest x-ray at night. Admission chest x-ray

revealed an irregular opacity of the right lung with revealed an irregular opacity of the right lung with pleural effusion. Thoracocentesis was performed, pleural effusion. Thoracocentesis was performed,

and cytologic examination of the pleural fluid and cytologic examination of the pleural fluid revealed revealed cancer cellscancer cells (poorly differentiated (poorly differentiated

adenocarcinoma). Abdominal CT revealed adenocarcinoma). Abdominal CT revealed hepatomegaly and diffuse lymphadenopathy. hepatomegaly and diffuse lymphadenopathy.

The patient was treated with multiple broad-spectrum The patient was treated with multiple broad-spectrum antibiotics, but his fever did not respond. His antibiotics, but his fever did not respond. His

hospital course was also notable for electrolyte hospital course was also notable for electrolyte imbalances, including hyperkalemia and imbalances, including hyperkalemia and

hyponatremia. Despite supportive care, the patient hyponatremia. Despite supportive care, the patient expired on the fourth hospital day, and an autopsy expired on the fourth hospital day, and an autopsy

was performed. was performed.

Lung, right, carcinoma -

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

Gross, cut surfaceLow power

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

Adrenal gland, granulomatous inflammation

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: (1)Bacterial (eg, Mycobacterium

tuberculosis, M. leprae, Treponema pallidum);

(2)Parasitic (eg, schistosomiasis); (3) Fungal (eg, histoplasmosis;

blastomycosis); (4)Inorganic dusts (eg, silicosis, berylliosis); (5) Foreign body; (6)Unknown (eg, sarcoidosis)

Testis, granulomatous inflammation -

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

Low power High power

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

In CGD patients, the response to even conventional bacteria is dominated by mononuclear phagocytes. The clusters of red blood cells staining

Abcess cavity/ mononuclear phagocytes

Infiltrate of Mononuclear phagocytes

Lung, Ghon complex

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

Calcified lymphonodes

Subpleural nodul

Radiograph and gross, cut surface

Lung, tuberculosis, secondary (reactivation) -

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

Gross, cut surface, and radiograph

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