MODULE 7: DISEASE Flashcards
When tubercle bacilli are inhaled, they reach the alveoli where they are
phagocytized by alveolar macrophages and multiply. Whether or not a
person develops TB is determined by:
- immune status of the host
- amount of exposure
- strain of MTB
- number of tubercle bacilli inhaled
- virulence
- anti-mycobacterial cellular immune response
- amount of exposure
- strain of MTB
- immune status of the host
This is also referred to as “active tuberculosis”. It is a chronic (long-term) inflammatory disease, which presents as pulmonary TB (PTB) that may progress into extrapulmonary TB (EPTB), leading into death of patients who do not receive treatment.
TB disease
The term “tuberculosis” most often refers to the
disease state with signs and symptoms
refers to a case of TB involving the lung parenchyma
pulmonary TB (PTB)
A person with PTB disease shows the following four cardinal signs and symptoms:
i. at least two weeks duration of cough
ii. unexplained fever
iii. unexplained weight loss
iv. night sweats.
Other symptoms include chest pains, sputum production (with or without hemoptysis, i.e., coughing out of blood), and fatigue.
TB
refers to a case of TB involving organs other than the lungs (e.g. larynx, pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges). Signs and symptoms may vary depending on the organ involved. it may coexist with PTB.
extrapulmonary TB
EPTB
This is also referred to as “latent tuberculosis infection” (LTBI). This occurs when a person has the tubercle bacilli within the
body, but the bacteria are present in very small numbers.
and they are kept under control by the body’s immune
system.
TB infection
A person with [?] has no symptoms, and is not infectious. i.e., he cannot spread the tubercle bacilli on to other people. In addition, unlike TB disease, he will usually have a normal chest x-ray and a negative sputum test, but a positive skin (tuberculin) test.
“latent tuberculosis infection” (LTBI)
Majority (about 90%) of those infected with MTB have LTBI, but some are at risk to develop active disease — including
young children and immunocompromised patients such as (PLHIV)
which stage of TB disease develops when a host has first contact with tubercle bacilli, usually during childhood. It may be in any part of the lung but is most often in the mid-lung fields which is well aerated, or the base.
Primary Tuberculosis
Primary Tuberculosis
the tubercle bacilli multiply virtually unrestricted within the phagosome of the nonactivated alveolar macrophages, until the
macrophages burst. Other macrophages begin to extravasate from peripheral blood. These macrophages also phagocytize MTB, but they are also nonactivated and hence, cannot destroy MTB. Tubercle bacilli spread from the initial site via the lymphatics to the regional
lymph nodes.
1 to 3 weeks after initial infection
Primary Tuberculosis
Mycobacterial proteins trigger Type IV hypersensitivity, which is often called delayed type hypersensitivity
(DTH) as the reaction takes several days to develop. At
this stage, lymphocytes begin to infiltrate. The infected macrophages present processed TB antigens on their
surface in association with MHC Class II to the
lymphocytes, specifically T-cells. This results in T-cell
activation and the liberation of cytokines including
gamma interferon (IFN), which causes the recruitment
and activation of macrophages.
3 to 4 weeks after, the host’s immune system mounts a complex, cell-mediated immune (CMI ) response
Primary Tuberculosis
Initial exposure most often results in [?]— an
exudative lesion which consists of inflammatory reaction with edema fluid, polymorphonuclear leukocytes and
later mononuclear cells around the tubercle bacilli; this may be self-limiting (heal) or may develop into
granulomatous type.
pneumonitis
Primary Tuberculosis
The activated macrophages form a cluster around the
infected macrophages resulting in productive or
proliferative lesions characterized by ganulomas, known as
tubercles
These are grayish white tissue
nodules, measuring 1-2 cm in diameter, and when fully
developed, consist of three (3) zones:
i. Central area of giant cells
ii. Mid zone of pale epithelioid cells
iii. Peripheral zone of fibroblasts, lymphocytes,
and monocytes
is large and multinucleated
resulting from the fusion of the cytoplasm of
macrophages
Giant cell
The tubercle is characterized by [?] where the center of the tubercle breaks down into necrotic lesion with semi-solid or “cheesy” consistency (L. caseus - cheese). It may heal by fibrosis followed by
calcification, where normal lung tissue is replaced by
calcium deposits.
“caseation necrosis”
This healed lesion (Ghon focus), along with hilar lymphadenopathy, is referred to as the [?]. Depending on the size and severity, the it may never subside. Typically it is readily visible as radio-opaque patches upon chest X-ray.
Ghon complex or primary complex
MTB cannot multiply within tubercles because of the
low pH and anoxic environment
MTB persist within the tubercles for extended periods
dormant
it is necessary to control an MTB infection and also responsible for much of the pathology associated with tuberculosis. Tubercles cause blockade of blood flow which will contribute to further necrosis of the tissue
cell-mediated immune (CMI) response
is evident through the tuberculin reaction in skin tests
host’s CMI against the tubercle bacilli
will not aid in the control of a MTB infection because MTB is intracellular and if extracellular, it is resistant to complement killing due to the high lipid concentration in its cell wall
antibody-mediated immune (AMI) rsponse
stage of TB that occurs in adults due to the reactivation and replication of dormant tubercle bacilli from the primary lesion. The progression to disease occurs, weeks, months or years after the primary episode of infection.
Secondary (Reactivation) Tuberculosis
Secondary (Reactivation) Tuberculosis
these liquefy, rupture, discharge their contents and form air-filled tuberculous
cavities; this liquid is very conducive to MTB growth and hence the organism begins to rapidly multiply extracellularly. This also allows MTB to spill into other airways and rapidly spread to other parts of the lung. The lesions are usually
localized in the apices of the lungs,
where the oxygen tension (PO2) is
highest.
caseous centers of the tubercles
Secondary (Reactivation) Tuberculosis
is characterized by chronic tissue
lesions, the formation of tubercles,
caseation, and fibrosis. Regional lymph nodes are only slightly involved, and they do not caseate
Reactivation tuberculosis
This refers to the seeding of many organs outside the pulmonary tree with tubercle bacilli through the blood
stream. The most common sites of spread of MTB are the spleen, highly oxygenated parts of the host’s body such
as the liver, bone marrow (especially of long bones), kidney, as well as the adrenal gland and in some cases the genital tract, usually in that order of occurrence.
Extrapulmonary Tuberculosis (EPTB) or Dissemination Tuberculosis
Extrapulmonary Tuberculosis (EPTB) or Dissemination Tuberculosis
The bloodstream can also be invaded by erosion of a vein by a [?] or lymph node. If a caseating lesion discharges its contents into a bronchus, they are aspirated and distributed to other parts of the lungs or are swallowed and passed into the stomach and intestines
caseating tubercle
Extrapulmonary Tuberculosis (EPTB) or Dissemination Tuberculosis
is derived from the fact that metastasizing tubercles are about the same size as a millet seed, a grain commonly grown in Africa
miliary tuberculosis
results in necrosis and scarring of the
renal medulla and the pelvis, ureters, and bladder. This damage is accompanied by painful urination, fever, and the presence of blood and the TB bacillus in urine
Renal tuberculosis
in males damages the prostate
gland, epididymis, seminal vesicles, and testes; in females, the fallopian tubes, ovaries, and uterus. It often affects the reproductive function in both sexes
Genital tuberculosis
is a combo complication. The spine is a frequent site of infection, though the hip, knee, wrist, and elbow can also be involved.
Tuberculosis of the bone and joint
Advanced infiltration of the vertebral column produces degenerative changes that collapse the vertebrae , resulting in abnormal curvature of the thoracic region (humpback or kyphosis) or the lumbar region (swayback or lordosis). Neurological damages stemming form compression on nerves can cause extensive paralysis and sensory loss.
Pott’s disease
is the result of an active brain lesion seeding bacilli into the meninges. Over a period of several weeks, the infection of the cranial compartments can create mental deterioration,
permanent retardation, blindness, and deafness. Untreated tubercular meningitis is invariably fatal.
Tuberculous meningitis
is known as “the great imitator” because the varied and complex clinical manifestations of this illness can mimic many other diseases.
Syphilis
Once inoculated, the treponeme penetrates an intact mucous membrane or gains access to tissue through [?]. It multiplies at the inoculation site, and then enters the lymphatic and circulatory system and spreads throughout the body.
abraded skin
The slow generation time of this bacterium as well as the delayed immune response of the host accounts for the slow, but progressive nature of the disease.
30 hours
usual incubation period varies from [?] averaging to 3 months.
2 to 10 months
This period of syphilis usually occurs at an average of 3 weeks after exposure to the organism and is marked by the appearance of the primary syphilitic lesion referred to as chancre.
Primary stage
contains live treponemes; is a painless, non-suppurative lesion that is ulcerated with raised, firm edges and a smooth, hard base. It develops at site of inoculation — commonly, the internal and external genitalia, the lips, oral cavity, nipples, fingers and the perianal region. It typically occurs singly but multiple chancres have been seen in some patients. Lymph nodes near the affected area are usually enlarged. Since it is painless, it usually go unnoticed in some cases
hard chancre - painless
soft chancre - painful
The chancre spontaneously heal without scarring in approximately [?] weeks. However, healing is deceptive since the bacteria have already started disseminating to other organs by way of local lymph nodes and the bloodstream.
2 to 8 weeks
which stage of syphilis begins about 3 weeks to 6 months (average
of 6 weeks) after the chancre heals
Secondary stage
The secondary stage is characterized by widespread dissemination of spirochetes in the host’s body, mucocutaneous as well as organ involvement, and specific symptoms that include fever, sore throat, generalized lymphadenopathy, headache, lesions of the mucous membranes, and development of a red or brown rash that breaks out on all skin surfaces including the trunk, arms, and even palms and soles. The lesions may enlarge and coalesce to produce pale plaques referred to as
condyloma lata
Just like the chancre, all secondary lesions of the skin and mucous membranes contain [?], hence are highly infectious.
viable treponemes
The spread of spirochetes into the [?] result to major complications that develop in the bones, hair follicles, joints, liver, eyes, brain, and kidneys.
organs
The secondary stage of syphilis stage usually last for [?] weeks and in some, can relapse.
2 to 8 weeks
After secondary stage of syphilis:
- 1/3 of untreated patients exhibit biological cure, with [1]
- 1/3 remain latent for life but have [2]
- 1/3 ultimately develop [3] or late syphilis
- negative serological tests
- reactive sera
- tertiary
After resolution of secondary syphilis, 30% of infected persons enter a period of latency which highly
varies and can last for
20 years of longer
During this period, the bacteria are no longer present, and clinical manifestations of the disease are
absent but anti-treponeme antibodies can be readily detected.
Latent Syphilis
The period of latency is divided into:
(1) - occurs within 1 year of infection and characterized by occasional relapses
(2) - occurs greater than 1 year of infection, relapses are uncommon
(1) Early Latent Syphilis
(2) Late Latent Syphilis
Only a fraction of patients progress into this period several years up to decades following initial infection; During this period, the combined action of the infection and the body’s response to it produce severe pathologic complications.
Tertiary stage (also, Late Syphilis)
