PBL 2: Long history of non-productive cough.

Anatomical Pathology
1) Describe the gross & microscopic features of sarcoidosis & TB.

SARCOIDOSIS
Sarcoidosis is a multisystem disease of unknown etiology characterized by
noncaseating granulomas in many tissues and organs.
Microscopic:
The diagnostic histopathologic feature of sarcoidosis is the noncaseating
epithelioid granuloma, irrespective of the organ involved. This is a discrete,
compact collection of epithelioid cells rimmed by an outer zone of largely CD4+ T
cells. The epithelioid cells are derived from macrophages and are characterized by
abundant eosinophilic cytoplasm and vesicular nuclei. It is not uncommon to see
intermixed multinucleate giant cells formed by fusion of macrophages.
A thin layer of laminated fibroblasts is present peripheral to the granuloma; over
time, these proliferate and lay down collagen that replaces the entire granuloma
with a
hyalinized scar.
Two other microscopic features are sometimes seen in the granulomas: (1)
Schaumann bodies, laminated concretions composed of calcium and proteins;
and (2) asteroid bodies, stellate inclusions enclosed within giant cells. Their
presence is not required for diagnosis of sarcoidosisthey also may occur in
granulomas of other origins. Rarely, foci of central necrosis may be present in
sarcoid granulomas, suggesting an infectious process. Caseation necrosis typical
of tuberculosis is absent.

Gross:
The lungs are involved at some stage of the disease in 90% of patients. The
granulomas predominantly involve the interstitium rather than air spaces, with
some tendency to localize in the connective tissue around bronchioles and
pulmonary venules and in the pleura (lymphangitic distribution). The
bronchoalveolar lavage fluid contains abundant CD4+ T cells. In 5% to 15% of
patients, the granulomas eventually are replaced by diffuse interstitial fibrosis,
resulting in a so-called honeycomb lung.
Intrathoracic hilar and paratracheal lymph nodes are enlarged in 75% to 90%
of patients, while a third present with peripheral lymphadenopathy. The nodes are
characteristically painless and have a firm, rubbery texture. Unlike in tuberculosis,
lymph nodes in sarcoidosis are nonmatted (nonadherent) and do not ulcerate.
Skin lesions are encountered in approximately 25% of patients. Erythema
nodosum, the hallmark of acute sarcoidosis, consists of raised, red, tender
nodules on the anterior aspects of the legs. Sarcoidal granulomas are uncommon
in these lesions. By contrast, discrete painless subcutaneous nodules can also
occur in sarcoidosis, and these usually reveal abundant noncaseating granulomas.
 Involvement of the eye and lacrimal glands occurs in about one fifth to
one half of patients.

TUBERCULOSIS
Tuberculosis is a communicable chronic granulomatous disease caused by
Mycobacterium tuberculosis. It usually involves the lungs but may affect any organ
or tissue in the body. Typically, the centers of tubercular granulomas undergo
caseous necrosis.

Microscopic:

Gross:

2) Discuss the pathophysiology of Sarcoidosis and TB.

SARCOIDOSIS
Although the etiology of sarcoidosis remains unknown, several lines of evidence
suggest that it is a disease of disordered immune regulation in genetically
predisposed persons exposed to certain environmental agents. The role of each of
these contributory influences is summarized in the following discussion.
Several immunologic abnormalities in sarcoidosis suggest the development of
a cell-mediated response to an unidentified antigen. The process is driven by
CD4+ helper
T cells. These abnormalities include:
Intra-alveolar and interstitial accumulation of CD4+ TH1 cells
Oligoclonal expansion of T cell subsets as determined by analysis of T cell
receptor rearrangement
Increases in T cellderived TH1 cytokines such as IL-2 and IFN-, resulting in T
cell expansion and macrophage activation, respectively
Increases in several cytokines in the local environment (IL-8, TNF, macrophage
inflammatory protein-1) that favor recruitment of additional T cells and
monocytes and contribute to the formation of granulomas
Anergy to common skin test antigens such as Candida or purified protein
derivative (PPD) that may result from pulmonary recruitment of CD4+ T cells and
consequent peripheral depletion
Polyclonal hypergammaglobulinemia, another manifestation of TH cell
dysregulation
The role of genetic factors is suggested by familial and racial clustering of cases
and association with certain human leukocyte antigen (HLA) genotypes (e.g., class
I
HLA-A1 and HLA-B8)
After lung transplantation, sarcoidosis recurs in the new lungs in 75% of patients.
Finally, several putative antigens have been proposed as the inciting agent for
sarcoidosis (e.g., viruses, mycobacteria, Borrelia, pollen), but thus far there is no
unequivocal evidence to suggest that sarcoidosis is caused by an
infectious agent.
 TUBERCULOSIS

3) Describe the types of Granulomas.

Types of Granulomas
Epitheloid Granuloma
A sharply circumscribed nodule that mainly consists of epitheloid cells
(modified macrophages).
Tuberculous granuloma.
Sarcoidal granuloma.
Histiocytic Granuloma
An ill-defined nodule that consists of phagocytic histiocytes (tissue
macrophages).
Foreign-body granuloma.
Rheumatoid granuloma.
Rheumatic granuloma.

Morphology of Granulomas
Sarcoid Granuloma
Small granulomas that mostly consists of epitheloid cells. No necrotizing
center, but fibrosis may be present. The outer layer consists mostly of
collagen. Sarcoid granulomas can occure in:
Sarcoidosis.
Crohn`s disease.
Berylliosis.
Extrinsic Allergic Alveolitis.
Primary Billiary Cirrhosis.
Tuberculous Granuloma

Necrotizing granuloma scheme, 1 = zone of caseating necrosis, 2 =

epithelioid cells, 3 = Langhans (giant) cells, 4 = lymphoid cells
 Necrotizing granuloma, tuberculosis (compare with scheme).

A large circumscribed granuloma consisting of epitheloid cells around a

caseous necrotic core with interspersed Langhans cells. The outer layer
consists mostly of lymphocytes. Tuberculous granulomas can occure in:
Tuberculosis.
Leprosy.
Syphilis - A granuloma in syphilis is called gumma. They have
coagulative necrosis and central vessels in their core, and plasma cells
in their peripheral zone.

Pseudotuberculous Granuloma
As the name implies, they are quite similar to tuberculous granulomas.
They are ill-defined granulomas consisting of macrophages and epitheloid
cells. Granulocytes (mostly neutrophils) are present in the caseous core.
They may form abscesses. Pseudotuberculous granulomas can occure in:
Yersinia Pseudotuberculosis.
Brucellosis.
Listeriosis.
Histoplasmosis.
Cryptococcosis.
Typhoid fever.
Rheumatic Granuloma
A granuloma with specialized macrophages (called Anitchov cells) around a
core of fibrinoid collagen necrosis. Aschoff cells (a variant of giant cells) are
interspersed between the other cells, while lymphocytes make up the outer
layer. Rheumatic granulomas mostly occure in myocardium and only in
rheumatic fever.
Rheumatoid Granuloma
A granuloma with a core of fibrinoid collagen necrosis, surrounded by a wall
of epitheloid cells. Several centimeters in diameter. Lymphocytes are
present in the outer layer. Often occuring in multiple subcutaneous
locations and articular nocules in rheumatoid arthritis.

Foreign-Body Granuloma
A granuloma with epitheloid cells surrounding a material that cannot be
broken down, or that provides large enough difficulties in doing so. The
foreign body is surrounded by epitheloid cells and giant cells. The outer
layer consists of lymphocytes, fibroblasts and vessels.

4) Explain how TB and Sarcoidosis are diagnosed.

5) Discuss the significance of bilateral hilar lymphadenopathy.
 Bilateral hilar lymphadenopathy is a bilateral enlargement of the lymph nodes of
pulmonary hila. It is a radiographic term that describes the enlargement of
mediastinal lymph nodes and is most commonly identified by a chest x-ray.

Bilateral hilar lymph node enlargement can arise from many causes which include:
sarcoidosis
infection
o tuberculosis
o mycoplasma
o histoplasmosis
o coccidiodomycosis
malignancy
o lymphoma - more common on hodgkin lymphoma than non-hodgkin
lymphoma.
o carcinoma -
inorganic dust disease
o silicosis
o berylliosis

Although the multisystem involvement of sarcoidosis can manifest in

many clinical guises, bilateral hilar lymphadenopathy or lung involvement
(or both), visible on chest radiographs, is the major presenting
manifestation in most cases.

Pharm
6) Describe the mechanism of action of trimethoprim/Sulfamethoxazole.
(toxicity, interaction, side effects)
7) How is TB treated?

Public Health
8) List the risk factors for TB and sarcoidosis
Risk Factors

TB Sarcoidosis
Weakened immune Age and sex. Sarcoidosis often
system occurs between the ages of 20
Has health problems that and 40. Women are slightly more
make it hard for the body to likely to develop the disease.
fight bacteria:
o HIV/AIDS
o Diabetes
o End-stage kidney disease
o Certain cancers
o Cancer treatment, such as
chemotherapy
o Drugs to prevent rejection of
 transplanted organs
o Some drugs used to treat
rheumatoid arthritis, Crohn's
disease and psoriasis
o Malnutrition
o Very young or advanced age

Alcohol abuse or use of Race. African-Americans have a

illegal drugs
IV drug use or alcohol abuse
weakens your immune
system and makes you more
vulnerable to tuberculosis.
higher incidence of sarcoidosis
than do white Americans. Also,
sarcoidosis may be more severe
and may be more likely to recur
and cause lung problems in
African-Americans.

Tobacco use. Using tobacco Family history. If someone in

greatly increases the risk of your family has had sarcoidosis,
getting TB and dying of it. you are more likely to develop
the disease yourself.

Traveling or living in
certain areas. The risk of
contracting tuberculosis is
higher for people who live in
or travel to countries that
have high rates of
tuberculosis and drug-
resistant tuberculosis, such
as:
Sub-Saharan Africa, India,
China, Russia, Pakistan

Has been recently

infected with TB bacteria
(in the last 2 years); and
Was not treated correctly
for TB infection in the
past

9) Describe how TB is spread.

Mycobacteria are slender rods that are acid-fast (i.e., they have a high
content of complex lipids that readily bind the Ziehl-Neelsen [carbol fuchsin]
stain and subsequently stubbornly resist decolorization). M. tuberculosis
hominis is responsible for most cases of tuberculosis; the reservoir of infection
typically is found in persons with active pulmonary disease.
Transmission usually is direct, by inhalation of airborne organisms in aerosols
generated by expectoration or by exposure to contaminated secretions of
infected persons. Oropharyngeal and intestinal tuberculosis contracted by
drinking milk contaminated with Mycobacterium bovis infection is now rare in
developed nations, but it is still seen in countries with tuberculous dairy cows
and sales of unpasteurized milk. Other mycobacteria, particularly
Mycobacterium avium complex, are much less virulent than M. tuberculosis and
rarely cause disease in immunocompetent persons. However, they cause
disease in 10% to 30% of patients with AIDS.

10) Discuss the management of pulmonary TB.

MicroB
11) How is TB cultured? (special conditions & media)

There are four specimen collection methods for pulmonary TB disease (Table
4.2):
Coughing
Induced sputum
Bronchoscopy
Gastric aspiration

Table 4.2 Methods of Obtaining a Sputum Specimen

Method Description Advantage Disadvantage
Spontaneous Patient coughs up
sputum sample sputum into a 1 Inexpensive 1 Patient may
sterile container 2 Easy to do not be able
to cough up
sputum
without
assistance
or may spit
up saliva
instead of
sputum
2 Health-care
worker has
to coach
and
 supervise
the patient
when
collecting
sputum

Sputum Patient inhales a

induction saline mist which 1 Easy to do 1 Specimens
can cause a deep 2 Use to may be
cough obtain watery and
sputum may be
when confused
coughing with saliva
sputum is (should be
not labeled
productive induced
specimen)
2 Requires
special
equipment
3 May cause
bronchospas
m

Bronchoscopy Bronchoscope is Use to obtain

passed through sputum when 1 Most
the mouth or nose coughing or expensive
directly into the inducing sputum is and invasive
diseased portion of not productive or procedure
the lung, and other diagnoses 2 Requires
sputum or lung are being special
tissue is removed considered equipment
3 Must be
done by a
specialist in
a hospital or
clinic
4 Requires
anesthesia

Gastric washing Tube is inserted Use to obtain

through the samples in 1 Must be
patients mouth or children, who do done as
nose and passed not produce soon as
into the stomach sputum when they patient
to get a sample of cough wakes up in
gastric secretions the
that contain morning;
sputum that has patient may
been coughed into be required
 the throat and to stay in
then swallowed hospital
2 Can be
uncomforta
ble for the
patient

AFB Smear and Culture

Also known as: TB culture and sensitivity; Mycobacterial smear and culture
Formal name: Acid-fast bacillus smear and culture and sensitivity

Chem Path
12) What is the significance of the FEV1/FVC ratio? (Give the normal
values)
FVC (Forced Vital Capacity) -- This is the total volume of air expired after
a full inspiration. Patients with obstructive lung disease usually have a normal or
only slightly decreased vital capacity. Patients with restrictive lung disease have
a decreased vital capacity.
FEV1 (Forced Expiratory Volume in 1 Second) -- This is the volume of air
expired in the first second during maximal expiratory effort. The FEV1 is
reduced in both obstructive and restrictive lung disease. The FEV1 is reduced in
obstructive lung disease because of increased airway resistance. It is reduced in
restrictive lung disease because of the low vital capacity.
FEV1/FVC -- This is the percentage of the vital capacity which is expired in
the first second of maximal expiration.
In healthy patients the FEV1/FVC is usually around 80%.
In patients with obstructive lung disease FEV1/FVC decreases and can
be as low as 20-30% in severe obstructive airway disease.
Restrictive disorders have a near normal, or even increased, FEV1/FVC.

FEV1/FVC is extremely important in the diagnosis of obstructive

and restrictive lung diseases.

13) Review ABGs with specific reference to resp. acidosis, alkalosis

& metabolic acidosis and alkalosis.

Immunology
14) Describe the immune response to TB and Sarcoidosis.
 Haematology
15) Review CBS (I dont think we need to present this, it was just mentioned).
16) Review Arterial Blood Gases.