(SGD) Pathology

SGD CASE NO.
1 FOR SECTION D (TO BE DISCUSSED ON AUGUST 12, 2016)

A 65 year old female is brought to the emergency room of a government hospital in Tondo, Manila
in the wee hours of the morning due to hemoptysis after waking up due to coughing. History
revealed that in the past few months, the patient had been experiencing loss of appetite, weight
loss, night sweats with occasional low grade remittent fever and cough. She didnt put much
attention into it and attributed these to environmental condition and fatigue because she works
washing laundry of her clients in a nearby subdivision. She occasionally takes Biogesic and
Alaxan which afforded temporary relief. She lives in a 20 square meter house with her husband,
three adult children, and a 4 year old grandson. The area where they live is congested with a very
high population. Electric and water supply is good, however, environmental sanitation is poor due
to poor ventilation, improper waste disposal and toilet practices.
You examined the patient physically and requested for laboratory examinations to be done.
GUIDE QUESTIONS:
1. Based on the history, what will be your initial clinical impression? Indicate your
basis/bases.
Pulmonary (Post-primary or Adult Type) Tuberculosis
The patient exhibits signs and symptoms associated with Adult PTB which are diurnal fever, night
sweats, weight loss and anorexia. The patient is suffering of hemoptysis which develops in 2030% of cases. (Harrisons) Also, judging from the environment where the patient is residing where
the place is congested and sanitation is poor, TB is said to flourish where there is poverty and
crowding. Most infections are acquired by person-to-person transmission from an active case to a
susceptible host. It is possible that the patient acquired this around the vicinity of their residence.
*Hemoptysis, which is the exploration of blood from the respiratory tract, can arise at any location
from the alveoli to the glottis. It can range from the expectoration of blood-tinged sputum to life
threatening large volumes of bright red blood. The most common etiology of hemoptysis is
infection of the medium-sized airways. Worldwide, the most common cause of hemoptysis
infection is with Mycobacterium tuberculosis, presumably because of high prevalence of
tuberculosis and its predilection for cavity formation. (Harrisons)
2. What is/are your differential diagnosis/es?

a. Pneumonia
Pneumonia could be caused by a bacterial, viral or fungal infection; TB is

bacterial
Physical signs of pneumonia include fever, headache, sweating and myalgia; TB

have chronic cough, weakness and hemoptysis
Pneumonia have bulk sputum w/ productive cough, TB have mild or absent

sputum and produces a nonproductive cough
b. Bronchitis
c.
Bronchitis have productive cough and have sputum production with it
Patient may be cyanotic, produces a wheezing sound, shortness of breath
Lung Cancer
History of tobacco smoking is generally present in cases of lung cancer while it may
be present or absent in TB
Fever in TB is low-grade w/ evening rise, whereas in lung cancer, it is non-specific
Weight loss is sudden in Lung Ca, in TB it is gradual
There is dyspnea due to central airway narrowing or partial or complete collapse of a

distal segment of a lung
There is poorly localized chest discomfort and hoarseness of voice due to vocal cord
paralysis
3. What diagnostic/laboratory examinations would you request and what do you expect
the result/s would be if your impression is correct? (mention the common ones
requested and the highly specialized test/s that can be done)
Chest X-ray (upper-lobe infiltrates with caviation), Serological Tests, AFB Microscopy,
Mycobacterial culture, Tuberculin Skin Test
3. What is the pathogenesis of your main clinical impression?

Infection leads to the induction of a Th1-mediated delayed hypersensitivity response that
activates macrophages (via interferon-y) to the following:
Promote endocytosis and killing via Nitric Oxide (NO) and/or autophagy
Promote cytocidal activity through tumor necrosis factor and defensing production
Surround microbes with granulomatous inflammation
When Mycobacteria gain access to the lungs by inhalation, they tend to localize in the periphery
of the lung where they excite a transient neutrophil enzyme activity, probably because of their
thick and resistant glycolipid cell wall. They are then ingested by macrophages where they may
initially continue to divide within macrophage cytoplasm. The macrophages present mycobacterial
antigen to T Lymphocytes, which become activated and initiate a cell mediated (type IV
hypersensitivity) response. The sensitized lymphocytes produce various soluble factors
(cytokines), which attract and activate the macrophages, enhancing their ability to secrete
substances that kill Mycobacteria.
Entry into macrophages. M. tuberculosis enters macrophages by phagocytosis

mediated by several receptors expressed on the phagocyte, including mannose
binding lectin and CR3.
Replication in macrophages. M. tuberculosis inhibits maturation of the phagosome

and blocks formation of the phagolysosome, allowing the bacterium to replicate
unchecked within the vesicle, protected from the micro- bicidal mechanisms of
2+
lysosomes. The bacterium blocks phagolysosome formation by inhibiting Ca
signals and the recruitment and assembly of the proteins that mediate phagosomelysosome fusion. Thus, during the earliest stage of primary tuberculosis (<3 weeks) in
the nonsensitized individual, bacteria proliferate in the pulmonary alveolar
macrophages and air spaces, resulting in bacteremia and seeding of multiple sites.
Despite the bacteremia, most people at this stage are asymptomatic or have a mild
flu-like illness.
Multiple pathogen associated molecular patterns of M. tuberculosis, including
lipoproteins and glycolipids, are recognized by innate immune receptors, including
Toll-like receptors such as TLR2. This initiates and enhances the innate and adaptive
immune responses to M. tuberculosis, as described below.
The TH1 response. About 3 weeks after infection, a T-helper 1 (T H1) response is
mounted that activates macrophages, enabling them to become bactericidal. The
response is initiated by mycobacterial antigens that enter draining lymph nodes and
are displayed to T cells. Differentiation of TH1 cells depends on IL-12, which is
produced by antigen-presenting cells that have encoun- tered the mycobacteria.
Stimulation of TLR2 by mycobacterial ligands promotes production of IL-12 by
dendritic cells.
TH1-mediated macrophage activation and killing of bacteria. TH1 cells, both in lymph
nodes and in the lung, produce IFN-. IFN- is the critical mediator that enables
macrophages to contain the M. tuberculosis infection. First, IFN- stimulates
maturation of the phagolysosome in infected macrophages, exposing the bacteria to
a lethal acidic, oxidizing environment. Second, IFN- stimulates expression of
inducible nitric oxide synthase, which produces nitric oxide (NO). NO combines with
other oxidants to create reactive nitrogen intermediates, which appear to be
particularly important for killing of mycobacterium. Third, IFN- mobilizes
antimicrobial peptides (defensins) against the bacteria. Finally, IFN- stimulates
autophagy, a process that sequesters and then destroys damaged organelles and
intracellular bacteria such as M. tuberculosis.
Granulomatous in ammation and tissue damage. In addition to stimulating
macrophages to kill mycobacteria, the T H1 response orchestrates the
formation of granulomas and caseous necrosis. Macrophages activated by IFN differentiate into the epithelioid histiocytes that aggregate to form granulomas;
some epithelioid cells may fuse to form giant cells. In many people this response
halts the infection before signi cant tissue destruction or illness occur. In other people
the infection progresses due to advanced age or immunosuppression, and the
ongoing immune response results in case- ation necrosis. Activated macrophages
also secrete TNF and chemokines, which promote recruitment of more monocytes.
The importance of TNF is underscored by the fact that patients with rheumatoid
arthritis who are treated with a TNF antagonist have an increased risk of tuberculosis
reactivation.
Role of other immune cells. In addition to the TH1 response, NKT cells that recognize
mycobacterial lipid antigens bound to CD1 on antigen-presenting cells, or T cells that
express a T-cell receptor, also make IFN-. However, it is clear that T H1 cells
have a central role in this process, since defects in any of the steps in generating a
TH1 response result in absence of resistance and disease progression.
Host susceptibility to disease. People with genetic de cien- cies in the IL-12 pathway
and the IFN- pathway, including STAT1 a signal transducer for IFN-, are
vulnerable to severe mycobacterial infections. Polymorphisms in a large number of
genes, including HLA, IFN-, IFN- receptor, and TLR2 have been found to be
associated with susceptibility to tuberculosis, but the contribution of these
associations to disease development is still under investigation.

Immunological state in active tuberculosis. It is not entirely clear why some people
progress from latent to active tuberculosis. Recent studies demonstrate that neutrophils in the blood of people with active tuberculosis express a group of genes that are
upregulated by type I and type II interferons. The expression levels of these
interferon-responsive genes correspond to the extent of lung disease as assessed by
radiographic analysis. Furthermore, the expression levels of these genes fall in
response to treatment for tuberculosis. This type of analysis suggests that an early
interferon response is a harbinger of development of active disease, and has
potential utility for diagnosis of active tuberculosis or for monitoring the extent of or
response to treatment of active disease. A caveat is that while most patients with
latent tuberculosis do not have this pattern of gene expression, 10 to 20% of them
do.
In summary, immunity to M. tuberculosis is primarily mediated by TH1 cells,
which stimulate macrophages to kill the bacteria. This immune response, while
largely effective, comes at the cost of accompanying tissue destruction.
4. What are the clinical features of the main disease you are thinking? (include
complications that may arise)
Early in the course of disease, symptoms and signs are often non-specific and insidious,
consisting mainly of diurnal fever and night sweats due to defervescence, weight loss, anorexia,
general malaise and weakness. However, in up to 90% of cases, cough eventually develops
often initially nonproductive and limited to the morning and subsequently accompanied by the
production of purulent sputum, sometimes with blood streaking. Hemoptysis develops in 20-30%
of cases, and massive hemoptysis may ensue as a consequence of the erosion of a blood vessel
in the wall of a cavity. Hemoptysis, however, may also result from rupture of a dilated vessel in a
cavity (Rasmussens aneurysm) or from aspergilloma formation and in an old cavity. Pleuritic
chest pain sometimes develops in patients with subpleural parenchymal lesions or pleural
disease. Extensive disease may produce dyspnea and in rare instances, adult respiratory distress
syndrome. Occasionally, rhonci due to partial bronchial obstruction and classic amphoric breath
sounds in areas with large cavities may be heard. Systemic features include fever (often lowgrade and intermittent) in up to 80% of cases and wasting. In some cases, pallor and finger
clubbing may develop. The most common hematologic findings are mild anemia, leukocytosis
and thrombocytosis with a slightly elevated erythrocyte sedimentation rate and/or C-reactive
protein level.
5. What organ/s may be involved in the disease process?

Lungs
6. What are the gross and microscopic findings that you would expect in this disease?
Microscopic Findings:
Important too note about the histology of mycobacterial infections are:

o
Granulomatous pattern of chronic inflammation due to delayed type of

hypersensitivity reaction
Caseous necrosis
Suppurating granulomas (with neutrophils in the central necrotic area of the

granuloma) also referred to as Mycobacteria other than tuberculosis (MOTT) or
non-tuberculous Mycobacteria (NTM)
The characteristic histological lesion in tuberculosis is the granuloma, which is known as

the tubercle.
Initial tubercle (primary TB) is known as Ghon focus, usually situated in

the subpleural area in the midzone of the lung undergoes fibrosis
At the center is a caseous necrosis containing Mycobacteria, surrounded by a

zone of epitheloid macrophages with abundant eosinophilic cytoplasm
Some macrophages fuse to produce multinucleate giant cells called

Langhans giant cells
Peripheral to the macrophages is a rim of lymphocytes
Progressive central necrosis results in enlargement of the tubercle and the zone
of peripheral macrophages and lymphocytes becomes relatively thinner
With further development, spindle-shaped fibroblasts appear in the peripheral

lymphocytic zone of the tubercle where they are stimulated by factors produced
by epitheloid macrophages to lay down collagen in the extracellular tissue
Gross Findings:
Typically, the inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or
the upper part of the lower lobe, usually close to the pleura. As sensitization develops, a 1- to 1.5cm area of gray-white in ammation with consolidation emerges, known as the Ghon focus. In
most cases, the center of this focus undergoes caseous necrosis. Tubercle bacilli, either free or
within phagocytes, drain to the regional nodes, which also often caseate. This combi- nation of
parenchymal lung lesion and nodal involvement is referred to as the Ghon complex.
During the first few weeks there is also lymphatic and hematogenous dis- semination to other
parts of the body. In approximately 95% of cases, development of cell-mediated immunity
controls the infection. Hence, the Ghon complex undergoes progressive brosis, often followed by
radiologically detectable calci cation (Ranke complex), and despite seeding of other organs, no
lesions develop.
7. Epidemiologically how often is this disease entity in the world and in the
Philippines? (check on the latest data)
WORLDWIDE: According to the World Health Organization (WHO), tuberculosis is estimated to
affect more than a billion individuals worldwide, with 8.7 million new cases and 1.4 million deaths
each year. But there is signi cant progress toward WHO targets for reduction in cases of
tuberculosis. Globally, between 2010 and 2011, new cases of tuberculosis fell at a rate of 2.2%,
and mortality has decreased by 41% since 1990. Infection with HIV makes people susceptible to
rapidly progressive tuberculosis; 13% of the people who developed tuberculosis in 2011 were
HIV-positive. In 2011 there were 10,528 new cases of tuberculosis in the United States, 62% of
which occurred in foreign-born people.
Tuberculosis nourishes wherever there is poverty, crowding, and chronic debilitating illness. In the
United States, tuberculosis is mainly a disease of older adults, immigrants from high-burden
countries, racial and ethnic minorities, and people with AIDS. Certain disease states also increase
the risk: diabetes mellitus, Hodgkin lymphoma, chronic lung disease (particularly silicosis),
chronic renal failure, malnutrition, alcoholism, and immunosuppression.
PHILIPPINES: TB is the number six leading cause of death, with 73 Filipinos dying everyday of
TB. An estimated of 200,000 to 600,000 Filipinos have active TB.

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SGD CASE NO.

1 FOR SECTION D (TO BE DISCUSSED ON AUGUST 12, 2016)

2. What is/are your differential diagnosis/es?

Pneumonia could be caused by a bacterial, viral or fungal infection; TB is

Physical signs of pneumonia include fever, headache, sweating and myalgia; TB

Pneumonia have bulk sputum w/ productive cough, TB have mild or absent

Bronchitis have productive cough and have sputum production with it

Patient may be cyanotic, produces a wheezing sound, shortness of breath

Fever in TB is low-grade w/ evening rise, whereas in lung cancer, it is non-specific

Weight loss is sudden in Lung Ca, in TB it is gradual

There is dyspnea due to central airway narrowing or partial or complete collapse of a

3. What is the pathogenesis of your main clinical impression?

Surround microbes with granulomatous inflammation

Entry into macrophages. M. tuberculosis enters macro- phages by phagocytosis

Replication in macrophages. M. tuberculosis inhibits matu- ration of the phagosome

associations to disease development is still under investigation.

5. What organ/s may be involved in the disease process?

Important too note about the histology of mycobacterial infections are:

Granulomatous pattern of chronic inflammation due to delayed type of

Suppurating granulomas (with neutrophils in the central necrotic area of the

The characteristic histological lesion in tuberculosis is the granuloma, which is known as

Initial tubercle (primary TB) is known as Ghon focus, usually situated in

At the center is a caseous necrosis containing Mycobacteria, surrounded by a

Some macrophages fuse to produce multinucleate giant cells called

Peripheral to the macrophages is a rim of lymphocytes

With further development, spindle-shaped fibroblasts appear in the peripheral

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