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)
Infected persons rarely progress to Tertiary stage because of widespread use of
antibiotics
marked by development of granulomatous lesions (called gummas) in the skin, bones, and the liver which can occasionally lead to death.
Benign tertiary syphilis
may involve any part of the nervous system but typically affects the blood vessels in the brain, cranial nerves, and dorsal roots of the spinal cord. The reactions can be diverse and include severe headaches, convulsions, behavioral changes, atrophy of the optic nerve which leads to blindness. Atrophy of the spinal cord leads to muscle wasting and loss of coordination.
Neurosyphilis
results from damage to small arteries in the aortic wall, cardiovascular lesions, aneurysms, and aortic valve insufficiency.
Cardiovascular syphilis
This results when treponemes from a pregnant woman’s circulation
passes through the placenta and are carried through the tissues of the
growing fetus.
Congenital syphilis
Although it is more common in the 2nd and 3rd trimester, an infection
that leads to congenital syphilis may occur in any of the
three trimester
The treponeme inhibits fetal growth and disrupts development that leads to consequences ranging from mild to extremes such as
spontaneous miscarriage or stillbirth
results when mothers are in the stage of early syphilis during pregnancy. It encompasses the period from birth to 2 years of age and is usually first detected 3 to 8 weeks after birth. It resembles secondary syphilis in adults and is characterized by mucocutaneous lesions, osteochondritis, anemia, hepatosplenomegaly, and CNS involvement.
Early-onset congenital syphilis
results following pregnancies when mothers have chronic, untreated infections. It occurs after age 2 years but generally are not apparent until the second decade of life. Symptoms corresponds to tertiary syphilis in adults, and include interstitial keratitis, bone and tooth deformities, deafness, neurosyphilis, and other tertiary manifestations.
Late-onset congenital syphilis
a profuse, nasal discharge
that obstructs the breathing
snuffles
A common characteristic of late congenital syphilis is notched, barrel-shaped, incisors
Hutchinson’s teeth
After exposure in susceptible hosts, the organism attaches to epithelial cells in the respiratory tract and multiplies.
Respiratory tract diseases/Primary atypical pneumonia
Most infections caused by M. pneumoniae are relatively mild; up to one-fifth of infections are actually
asymptomatic
tend to develop in children younger than 3 years of age
Upper respiratory tract infections
more often develops in adolescents and young adults (<30 years old)
tracheobronchitis or pneumonia
M. pneumoniae disease starts as [?] and spreads, causing otitis, tracheobronchitis, and primary atypical pneumonia characterized by a gradual onset of fever, headache, malaise, and cough.
pharyngitis
initially, the cough is nonproductive, but it is occasionally [?]. Later, there may be blood-streaked sputum and chest pain.
paroxysmal
was coined in the early 1940s to describe pneumonias different
from the typical lobar pneumonia caused by pneumococci. Cases of atypical pneumonia do not usually require hospitalization, and a person with it is unlikely to be significantly ill. This is why it is often called “walking pneumonia”.
atypical pneumonia
Three specific infectious bacteria cause the majority of atypical pneumonia cases
Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella pneumophila (Legionnaire's disease).
Several common respiratory viruses, including [2], were also shown to be responsible for a significant number of these pneumonias.
influenza virus and adenovirus
have autoimmune etiology
Extapulmonary sequelae
presents with multiple types of lesions- macules, papules, vesicles, target lesions (look like targets with multiple rings and dusky center showing epithelial disruption)
Erythema multiforme
characterized by fever, bullae formation and necrosis, sloughing of skin at dermal-epidermal syndrome junction, and high mortality rate. Targetoid skin lesions may appear, as seen in erythema multiforme.
Stevens-Johnson Syndrome
Dermatologic:
[1]
[2]
[1] Erythema multiforme
[2] Stevens-Johnson Syndrome
Cardiac:
[1]
[2]
- Myocarditis
- Pericarditis
Neurologic
[1]
[2]
[3]
- Meningitis
- Meningoencephalitis
- Mono- and polyneuritis
Hematologic
[1] - characterized by painful, blue fingers and toes with cold exposure.
- Hemolytic anemia
Others:
[1]
[2]
[3]
- neuritis
- hepatitis
- pancreatitis
It is a chronic, progressive disease of the skin and the nerves with a usual incubation period varying from 2 to 5 years, with extremes of 23 months to 40 years.
Leprosy or Hansen’s disease
Leprosy. From Greek lepros, meaning
[?]. Translated from a Hebrew word that refers to “uncleanliness”
“scaly” or “rough”
Leprosy
Macrophages successfully destroy the bacilli, and there are no manifestations of disease in healthy persons. However, in small percentage of cases, a weakened or slow macrophage and T-cell
response leads to [?] of the pathogen.
intracellular survival
In untreated cases of Leprosy, the bacilli grow slowly in the skin macrophages and
Schwann cells of peripheral nerves, and the disease progresses to one of several
outcomes. The neurological involvement in leprosy results in [?] leading to deformities and disability.
sensory-motor deficits
Its most severe effect is early damage to the nerves that control the muscles of the hands and feet which result to [ ? or ?]. Sensory nerve damage can also lead to trauma and loss of fingers and toes.
drop foot and claw hands
Deformation of the hands in leprosy.
The clawing and muscle wasting are
chiefly due to nerve damage hat interfere
with the [?] activity. Individuals in a later phase of the disease
can loose their fingers or their hands.
musculoskeletal
- The WHO expert committee on leprosy has defined a case of leprosy as
an individual who has one of the following cardinal signs:
= a definite loss of sensation in
a pale (hypopigmented) or reddish skin patch - a thickened or enlarged
peripheral nerve with a loss of sensation and/or weakness in the
muscles supplied by the nerve - the presence of acid-fast bacilli in an
i. Cutaneous lesion and anesthesia:
ii. Peripheral nerve involvement:
iii. Slit Skin Smear (SSS)
eprosy is defined by the [?] manifestations of the disease, which are due to the variability in the type and strength of the
body’s immune response thus making diagnosis difficult
‘spectral’
This classifies leprosy as
an immune-mediated spectral disease. The five-group system reflects
the host response or level of cellular immunity which results in the wide
variation in disease manifestation and prognosis.
Ridley-Jopling Classification for Leprosy (1966)
There are two (2) polar types of leprosy:; one at the end of the spectrum and one at the other; CLINICALLY STABLE
Tuberculoid leprosy (TT) Lepromatous leprosy (LL)
Immunologically, strong CMI correlates with the [?]
Weak CMI correlates with the [?]
- TT type
- LL type
Leprosy is a continuum of disease, which usually starts out with an indeterminate stage called
“borderline”
moving up the spectrum - towards [?]
- upgrading, and the prognosis is good
- TT lesion can even self-heal
- nerve damage-related disability can occur
TT
moving down the spectrum - towards [?]
- downgrading
- prognosis is poor
- LL can be fatal
LL
Infection of the skin and mucus membranes of the nose, lips, chin, and brows produces a moderate facial deformation, typical of lepromas.
lepromatous leprosy
lesions appear as shallow lesions
(a)Infection in dark-skinned persons manifests as hypopigmented patches or macules. (b)In light-skinned individuals, it appears as reddish patches or papules.
Tuberculous leprosy
CUTANEOUS LESIONS
- Erythematous or hypopigmented plaques with flat centers and raised demarcated borders
- <5 lesions, usually solitary, <10 cm diameter
- Dry, scaly and infiltrated
- Hairless
- Completely anesthetic (no sensation)
TUBERCULOID LEPROSY
CUTANEOUS LESIONS
- Macules, plaques, and nodular lesions (called lepromas). Diffuse dermal infiltration causes earlobe enlargement, nasal root widening (“saddle nose”), skin thrown into folds (“leonine facies”), fusiform swelling of fingers
- Numerous lesions showing tendency to symmetry in distribution.
- Shiny
- Almost normal initially Madarosis (loss of eyebrow)
- Patchy sensory loss
LEPROMATOUS LEPROSY
NERVE INVOLVEMENT
- Asymmetrical, single nerve enlargement
- Nerve to patch may be palpable
TUBERCULOID LEPROSY
NERVE INVOLVEMENT
- Symmetrical involvement of nerve trunks with glove and stocking anesthesia
- Nerves may feel normal on palpation or may be thickened
LEPROMATOUS LEPROSY
CELL-MEDIATED IMMUNITY
-Strong
TUBERCULOID LEPROSY
CELL-MEDIATED IMMUNITY
-Week
LEPROMATOUS LEPROSY
NUMBER OF ORGANISMS IN TISSUES
-Low
TUBERCULOID LEPROSY
NUMBER OF ORGANISMS IN TISSUES
-High
LEPROMATOUS LEPROSY
INFECTIVITY
-Low
TUBERCULOID LEPROSY
INFECTIVITY
-High
LEPROMATOUS LEPROSY
in most cases is an opportunistic infection associated with risk factors, most of which impair the cell-mediated immune responses, including corticosteroid treatment, immunosuppression, AIDS, and alcoholism
Nocardiosis
The most common form of infection with Nocardia species
Pulmonary nocardiosis
Pulmonary nocardiosis
The initial lesion in the lung is often a [?] that advances to necrosis. The abscesses that form can extend into the tissue and coalesce with each other. Sputum is thick and purulent. Dissemination to other organs, especially the brain, may occur, and may involve virtually every organ
pneumonitis
[?] is the most frequent cause of Cutaneous nocardiosis, which is
usually seen in the hands and feet as a result of minor trauma, such as from a thorn or wood sliver
N. brasiliensis
Cutaneous nocardiosis begins as a localized subcutaneous abscess that is invasive and may cause destruction of the tissues and underlying bone. These lesions are termed
actinomycotic mycetomas
Later features of the disease include nausea, vomitting, muscle aches,
and abdominal pain. In many cases, extensive damage to the liver,
spleen, heart, kidneys, and cranial nerves occur. Half of the patients hemorrhage profusely into organs, and some develop a rash on the
shoulders, trunk and legs
Epidemic Relapsing Fever (Louse-borne Relapsing Fever)
Epidemic relapsing fever occur whenever conditions favorable for survival and spread of the louse vector, [?], are present such as when famine, war, or natural disasters are coupled with poor hygiene,
crowding, and inadequate medical attention
P. humanus
After an incubation period of 2 to 15 days following the inoculation of the borrelae, presence of high numbers of spirochetes ([?]) in the blood (spirochetemia), triggers sudden high temperature, chills, severe headache, muscle pains, and weakness. This febrile period lasts about 3 to 7 days and ends abruptly only to recur several days to weeks later, following a less severe but similar course.
> 500,000 spirochetes/mL
The term “relapsing fever” indicates fever follows a fluctuating course that is explained by changes in the spirochete and attempts of the host immune system to control it. Hence, in the course of the disease, the
febrile periods worsen during the [?] and wane as the immune response clears the bacteria from the circulation
spirochetemia
The occurrence, clinical manifestations, and
pathologic mechanisms are similar with Borrelia
recurrentis
Endemic relapsing fever (Tick-borne Relapsing
Fever)
It is complex, and nonfatal and it often evolves into a slowly progressive syndrome; It can generally be divided into three stages
Lyme disease
Lyme disease is named after the town of [?], in 1975, where clusters of cases in children were identified
Old Lyme, Connecticut
Early infection of Lyme disease includes two stages, the first of which is localized. In most cases, patients exhibit [?], a classic
rash that is normally found at the site of larval tick bite as. It begins as a red macule and expands and resembles that of a target or bullseye, with raised erythematous ring that gradually spreads outward and a pale central region. This rash is commonly accompanied by a flulike illness with fever, headache, chills, stiff neck, and dizziness
erythema migrans (EM)
Characteristic [?] lesion, erythema migrans, observed at the site of
spirochete inoculation.
“bull’s-eye”
In unaddressed cases, the disease advances to the [?], which is disseminated and produces widely variable
symptoms that include secondary skin lesions, migratory joint and bone
pain, neurologic and cardiac disease, splenomegaly, and severe malaise and fatigue.
second stage
Stage 3 consists of late manifestations, or late persistent infections which
begins months to years later and occur mainly in the cardiac, musculoskeletal, and neurologic systems. [?] is the most common
symptom, occurring weeks to years later
Arthritis
It is essentially a zoonosis and human infection is only accidental
Leptospirosis or Weil Disease
After entry into the circulation, the organisms disseminate
widely, including into the CNS and eye
First (bacteremic or leptospiremic) phase
The incubation period ranges from 3 to 30 days but usually
averages to 10 to 12 days
First (bacteremic or leptospiremic) phase
Appearance of nonspecific, infuenza-like symptoms is
sudden and include high fever, chills, headache,
conjunctivitis, severe myalgia, malaise, and vomiting.
First (bacteremic or leptospiremic) phase
The spirochetes are found in the blood and CSF at this
period
First (bacteremic or leptospiremic) phase
The spirochetes disappear in the blood largely due to the action of phagocytes, complement and IgM
antibodies, hence the term
immune phase
Second (immune) phase
This period is marked by milder fever, headache due to meningitis, and Weil syndrome, a cluster of symptoms characterized by kidney invasion, hepatic disease, jaundice, anemia and neurological disturbances
Second (immune) phase
This period is marked by milder fever, headache due to meningitis, and Weil syndrome, a cluster of symptoms characterized by kidney invasion, hepatic disease, jaundice, anemia and neurological disturbances
Second (immune) phase
Meningitis occurring during the immune phase of leptospirosis has been termed as [?] owing to negative culture results of CSF samples from patients. This is largely due to the inability to isolate the
causative agent using routine bacteriological culture media and not because it is not present in
the sample.
“septic meningitis”
At this phase of the disease, diagnosis is mainly aided by
serological tests
Second (immune) phase
