1
Q
- recognized subset of T helper cells
- importante modulator of inflammation and CD4+ T cell recall or memory response.
- secretes IL17
- can recruit neutrophils, monocytes and CD4+ T cells producing IFN y and stimulate chemokine expression
A
Th17 cells
2
Q
- indicated by the negatives tuberculin test —
A
ANERGY
3
Q
Causes of anergy or negatives tuberculin test:
A
- malnutrition
- HIV infection
- steroid therapy
- severe TB (due to productions of inhibitory cytokines like TGF-B)
4
Q
- kill cells garbo rin intracellular pathogens,
- either exhibit granzyme/perforin-mediated killing of target T cells (first step: cell membrane destroyed) or induce apoptosis (destruction of target T-cell DNA —> LYSIS)
A
CYTOLYTIC or CYTOTOXIC T-LYPMPHOCYTES
- like CD8 T cell
5
Q
- assoc. with inc. Replication of mycobacterial rather that susceptibility to TB
- Foundation in chromosomes 2
- linked with BCG resistance gene
A
Nramp (natural resistance assoc. Macrophage protektahan)
6
Q
TB responsed and course
A
TB bacilli -> alveoli -> alveolar macrophages
Can evade intracellular killing mechanism -> Get carried to lymph Nodes and other organs.
In lungs macrophages introduce antigens to T cells -> resulting in its expansion, Development of memory Tcell of which DTH cells may be a subset -> may result tuberculin positive persistence and/or long term Protection.
Inflammatory Th1 responses -> local pulmonary infiltrates and hilar Adenopathy (PRIMARY COMPLEX).
If unable to contain: cause progressive dse -> imbalance between proinflammatory and immunosuppressive effects -> military TB
7
Q
Development of progression TB occurs in ___ % of affected individuals?
A
10%
8
Q
- After adequate treatment, some bacilli persist in a dormant state.
- clinically asymptomatic
- reactivation of dormant bacilli lead to active disease
A
Patent TB infection
9
Q
LTBD
Factors that prompte Development and Ma Inten ace of latency?
A
- Low concert ratio of O2
- Nutrients in chronic granulomas
- Local production of TNF - alpha and Nitric oxide
10
Q
Maintaned in Latent phase:
A
- TNF - alpha
- IFN - Gamma
- NO
11
Q
Reactivation of TB occurs at extrapulmonary site without apparently lung lessons in ___ % of affected individuals?
A
15%
12
Q
Leads to reactivation due to depression of cell mediated immunity:
A
- HIV infection
- malnutrition
- disease
- Druidrider
13
Q
What age is particularly susceptible to Develop TB and are at increased risk of developing disseminated dse, particularly TBM.
A
Under 2yrs of age
Reason: weaker innate and adaptive responses / immaturity of immune system
14
Q
Congenital infection identified possible reasons for the Development of dse:
A
- Impaired antigen-specific CD4p T-lymphocyte responses
- Decreased capacity of Neonatal T-lymphocytes to Secrets IFN-Y, and TNF-alpha
- cytokine production leans towards a Th2 response
- Suboptimal response of CD8p T-lymphocyte.
15
Q
TB source:
A
- exposure
- environmental factors: overcrowding, poot Ventilation
16
Q
Risk factors for TB:
AEI
A
- Household contact with a newly diagnosed Smear + case
- depends on the infectivity, proximity and duration of contact
- Age less than 5years
- most important factor
- determined the risk of progression to disease following primary infxn
Among immunocompetent children. - infants are at greatest risk
- risk remains significant in the 2nd yr if life
- lowest in children 5-10yo.
- Immunocompromised state (severe mal., HIV)
- host immunity, major determinant of dse develop´n
- high risk
17
Q
Infectivity of smear positive vs smear negative household exposure?
A
60 to 80%
30 to 40%
18
Q
TB morbidity with Family history exposure
A
2.5 Times than without knowing exposure
19
Q
Additional groups at high risk of exposure and infection?
A
- residents and employees of closed settings
- medically underserved, low income populations
- high-risk racia and ethinic minority populations
- infection drug users
- children exposed to adults with certain medical conditions.
20
Q
TB transmission and portal of entry:
A
- airborne
- inhalation of dropped nuclei
- 5micra
- 5 to 200 inhaled bacilli
21
Q
Perinatal transmission of TB occur:
A
- transplacentally through umbilical vein from mother with primary hematogenous TB daring pregnancy
- aspiration/ingestion of infected AF in utero/daring delivery
- inhalation of TB bacilli at or soon after delivery (most common)
22
Q
TB incubation period:
A
3 to 12 weeks
Shorter when the inoculum is large
23
Q
Primary infection
A
- Occurs in person without previous exposure to tubercle bacilli.
- controlled with a reactive tuberculin skin test as the only evidence of infection.
24
Q
Pathogenesis
A
Inhalation —> scavenging noon-activated, alveolar macrophages ingest the tubercle bacilli —> if not inhibited (virulance, microbicidal ability of macrophages) —> unrestrained replication —> some macrophages carry bacilli from lung to regional (hilar and mediastinal) lymph nodes —> disseminated via lymphatics or bloodstream (kidney, meninges, epiphyseal plates of long bones, vertebrae, apical segments of the upper lobes lungs) —> infected macrophages present tuberculous antigens to T lymph —> T-lym sensitized —> produce progeny —> secrete lymphokines (IFN-y, TNF) and activates macrophages —> inc lyrics enzyme (epitheloid macrophages, langhans giant cells)
CMI and DTH both inhibit the inc in Number of bacilli
25
The response of activated T-lymph in response to M. Tuberculosis antigen
Delayed-type hypersensitivity (DHT)
26
Comprises the increased capacity to ingest and destroy the bacilli of activated macrophages
Cell-mediated immunity
27
- Classic lesson in the lung of primary tuberculosis
- a caseous granuloma
- located peripherally in any part of lungs, close to pleura
GHON FOCUS
28
Soft, semi solid core surrounded by epithelioid macrophages, langhans giant T-cells and lymphocytes
Granuloma
29
Dissemination of bacilli from the primary granuloma in the lungs to the hilar nodes causes?
Granulomatous lymphadenitis
30
Combination of granulomatous hilar lymphadenitis and ghons focus
GHON COMPLEX
31
If immune mechanisms wane or fail
Lesions of the ghon complex (both lungs and lymph nodes) —>
Heal by FIBROSIS —> CALCIFICATION —>
Some die, few remain viable —>
REACTIVATE LATER (if immune mechanisms wane or fail)
32
- freq. result in disseminated dse.
- occurs when immune system is weakened and fails
- may be brought about by state of immunosuppression
- observed more commonly under 2yo.
Progressive primary tuberculosis
33
Pathogenesis of progressive primary TB —> Middle lobe syndrome
Primary Focus enlarges —> large caseous Center —>
Liquefies to form a primary cavity —> allowing TB bacilli to multiply extensively —> erosion of infected debris into bronchus —>
Causing futher intrapulmonary spread
Enlarging hilar and mediastinal nodes —> compress the bronchi —>
Cause collapse of distal lung (MIDDLE LOBE SYNDROME)
If obstruction is partial —> cause air-trapping and overdistension of a lobe or segment.
34
Pathogenesis of progressive primary TB —> Disseminated TB (miliary dse)
Occult lymphohematogenous spread —> Development of hypersensitivity to tuberculous antigens
35
- analogous to bacterial sepsis
- progressive caseous necrosis (usually hilar lymph nose) —> erodes into a blood vessel (pulmonary vein) —> bacilli spread (lungs, liver, spleen, bone marrow, meninges)
- consist of numerous small, yellow-white nodules, <2mm (millet seed-like) in all affected organs.
- denote all forms of progressive, widely disseminated hematogenous TB, even if the classical pathologic or radiologic findings are absent.
Disseminated TB (miliary TB)
36
- Occurs following re-infection with M.TB or reactivation of dormant bacilli in the ghon focus or complex.
- tissue destruction is brought about by progressive, freq. extensive caseous necrosis due to inability to contain bacteria.
- the course is variable
- localized inflammation —> may undergo organization and healing into a fibrocalcified nodule —> progress into caseating granulomas with cavitation or disseminate to other organs via rupture into a bronchus, pulmonary artery, pulmonary vein or lymphatics.
Secondary (adult-type) TB
37
Pathogenesis of secondary (adult-type) TB
- localized inflammation —> may undergo organization and healing into a fibrocalcified nodule —> progress into caseating granulomas with cavitation or disseminate to other organs via rupture into a bronchus, pulmonary artery, pulmonary vein or lymphatics.
38
Described the early course and progression over time of TB
Wallgren’s timetable of TB
39
3 to 13 wks - (after primary infxn)
1 to 3mon - (after primary infxn)
3 to 7 mons - (after primary infection)
1 to 3yrs - (after primary infection)
> 3yrs - (after primary infxn)
1st 5yrs - (after initial infxn)
5 to 25yrs - (after initial infxn)
3 to 13 wks - (after primary infxn) end of initial asymtomatic
incubation period.
- characterized by hypersensitivity rxns (fever, erythema
nodosum, +TST response, primary complex on CXR)
- hypersensitivity to tuberculoprotein antigens once
developed after infxn is expected to remain reactive for life.
1 to 3mon - (after primary infxn) following occult hematogenous spread
during incubation, highest risk for TB MENINGITIS &
DISSEMINATED & MILIARY TB.
- TB meningitis & miliary TB may also occur after anytime
interval.
3 to 7 mons - (after primary infection)
<5yo: period of secondary airway involvement due to infected
lymph nodes.
>5yo: large reactive pleural effusions can also occur.
1 to 3yrs - (after primary infection)
<5yo: period of osteoarticular TB
Adolescent: adult-type dse. May have delayed clinical onset after
calcification, ranging from as early 3mon to as late as 20yrs.
- risk for TB progression following primary infection is much less by
the time calcification appears.
> 3yrs - (after primary infxn) when calcification is completed.
- highest risk period have passed.
- very late manifestations of TB my occur (primary pulmonary
reactivation)
1st 5yrs - (after initial infxn) complications of TB occur.
- Arrested or silent lesion may reactivate, heralding complications.
5 to 25yrs - (after initial infxn) renal involvement appears.
40
Risk to develop TB of Immunocompetent adult w/o tx?
5-10% risk to develop TB during the lifetime
41
Risk in immunicompetent infants with untreated TB infxn?
Serious life threatening forms of the disease will develop within 1 to 2 years in a many as 40%
42
3 to 13 wks - (after primary infxn) end of ?
- characterized by?
- hypersensitivity to tuberculoprotein antigens once
developed after infxn is expected to?
3 to 13 wks - (after primary infxn) end of initial asymtomatic
incubation period.
- characterized by hypersensitivity rxns (fever, erythema
nodosum, +TST response, primary complex on CXR)
- hypersensitivity to tuberculoprotein antigens once
developed after infxn is expected to remain reactive for life.
43
1 to 3mon - (after primary infxn) following occult hematogenous
spread during incubation, highest risk for?
- may also occur after anytime interval.
1 to 3mon - (after primary infxn) following occult hematogenous
spread during incubation, highest risk for TB MENINGITIS &
DISSEMINATED & MILIARY TB.
- TB meningitis & miliary TB may also occur after anytime
interval.
44
3 to 7 mons - (after primary infection)
<5yo: period of?
>5yo: what occurs?
3 to 7 mons - (after primary infection)
<5yo: period of 2dary airway involvement due to infected
lymph nodes.
>5yo: large reactive pleural effusions can also occur.
45
1 to 3yrs - (after primary infection)
<5yo: period of?
Adolescent: adult-type dse. May have delayed clinical onset after?
ranging from?
- risk for TB progression following primary infection by the time
calcification appears?
1 to 3yrs - (after primary infection)
<5yo: period of osteoarticular TB
Adolescent: adult-type dse. May have delayed clinical onset after
calcification, ranging from as early 3mon to as late as 20yrs.
- risk for TB progression following primary infection is much less by
the time calcification appears.
46
> 3yrs - (after primary infxn) when calcification is completed.
- highest risk period have?
- very late manifestations of TB?
> 3yrs - (after primary infxn) when calcification is completed.
- highest risk period have passed.
- very late manifestations of TB may occur (primary pulmonary
reactivation)
47
1st 5yrs - (after initial infxn) what occurs?
| - what may reactivate, heralding complications?
1st 5yrs - (after initial infxn) complications of TB occur.
- Arrested or silent lesion may reactivate, heralding.
complications.
48
5 to 25yrs - (after initial infxn) involvement appears on?
5 to 25yrs - (after initial infxn) renal involvement appears.
49
TB-related mortality:
- infants
- under 3mon age
- highest risk following primary infection at 5-10%
- more likely to develop more severe forms of TB
- 13% of children under 3mon with TB died.
50
TB-related mortality:
| - between 1 to 4yo?
- risk decreases to 1%
51
TB-related mortality:
- 5 to 14yo?
- below 10yrs old
- lowest risk at <0.5%
| - majority of deaths occurred within the 1st yr following the primary infection
52
TB-related mortality:
- after 15 yo
- older children who developed adults-type cavitary dse,
- risk inc. to >2%
| - older children who developed adults-type cavitary dse, mortality declined more slowly
53
TB-related mortality:
- from sputum smear + household source case
- among TST + reactors
- mortality is almost twice as high compared to a infxn from an unknown source case.
- mortality rate is 3x inc among TST + reactors than those who are TST - reactors
54
How mycobacterium tuberculosis produce infection and dse in almost every tissue and organ in the body?
- result of dissemination from an initial primary focus.
- infxn usually takes place by way of the respiratory tract, the lung is the first organ involved and it is here that the initial major manifestations of dse occur,
55
Distinction between TB infxn and dse?
- Primary infxn: patients are asymptomatic
- Disease is present: early manifestations are mild with nonspecific systemic symptoms of:
low-grade fever,
lassitude,
easy fatigability,
anorexia,
weight loss or faltering,
malaise,
night sweats
- progression and chronicity, symptoms maybe respiratory or other manifestations, depending on the main site.
56
A condition in which a child is in:
- close contact with contagious adult or adolescent TB cases,
- no signs and symptoms of TB
- negative TST reaction
- no radiologic
- no laboratory findings suggestive of TB
TB exposure
| Negative for everything
57
A condition in which a child has:
- no signs and symptoms presumptive of TB
- no radiologic
- no laboratory evidence
- positive TST reaction
TB infection or Latent TB infection (LTBI)
58
A presumptive TB who after clinical and diagnostic evaluation (TST and/or radiology) is confirmed to have TB.
TB disease
59
TB disease Classification:
```
- Bacteriological status
~ Bacteriological - confirmed
~ Clinically - diagnosed
- Anatomical site
~ Pulmonary TB (PTB)
~ Extrapulmonary TB (EPTB)
```
60
Bacteriological status where biological specimen is positive by:
- smear microscopy,
- culture or rapid diagnostic tests (such as Xpert MTB/RIF)
Bacteriologically -confirmed TB Disease
61
Bacteriological status
- that does not fulfil the criteria for bacteriological confirmation but has been diagnosed with active TB by a clinical or other medical practitioner who had decided to give the patient top full course of TB treatment.
- cases diagnosed on the bases of x-ray abnormalities or suggestive histology and extrapulmonary cases w/o laboratory confirmation are also included.
Clinically - diagnosed TB disease
62
- TB disease based on anatomical site
- Refers to a case of TB involving the lung parenchyma and tracheobronchial tree.
- a patient with both pulmonary and extrapulmonary TB
Pulmonary TB (PTB)
63
- TB disease based on anatomical site
- refers to a case of TB involving organs other than the lungs and tracheobronchial tree (eg. Larynx, pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges).
Extrapulmonary TB (EPTB)
64
A patient with both pulmonary and extrapulmonary TB should be classified as a case of?
Pulmonary TB
65
Histologically Diagnosed EPTB through biopsy of appropriate sites will be considered?
Clinically diagnosed TB
66
Laryngeal TB, likely through sputum smear positive result, is considered an?
Extrapulmonary TB in the absence of lung infiltrates on CXR.
| Pulmonary TB in presence of lung infiltrates on CXR.
67
The initial stage in children who inhale the mycobacterium tuberculosis bacilli?
Primary Disease
68
- 3 elements of primary disease
| - in 95% of cases, it heals by fibrosis and/or calcification
1. Ghon focus
2. Lymphadenitis
3. Lymphangitis
69
- asymptomatic in up to 65%
- no striking clinical manifestations
- signs and symptoms can vary substantially in the population although infants and young children are likely to have more signs and symptoms than school-aged children.
Primary TB in children
70
Primary TB in children is occasionally, the initiation of the infxn is marked by:
- several days of low grade fever
- mild cough
- fever alone or sometimes, pleuritic or retrosternal pain of gradual onset can be seen
- fever, low-grade in character, can last for an average of 14-21days.
71
A condition which develops when initial infxn fails to heal and continues to progress over a period of months or years, causing further pulmonary and even distant organ involvement.
Progressive Primary Tuberculosis
72
- a condition which represents reactivation of an old, possibly subclinical infxn.
- occurs in <10% of the cases of primary infxn.
- tends to produce more damage to the lungs than does primary tuberculosis.
- more common in adolescent than in younger children.
Secondary (reactivation) Tuberculosis
73
Clinical manifestations of secondary (reactivation) tuberculosis?
Most features improve within several weeks after starting effective treatment, but the cough may persist for several months.
- chronic or persistent cough
- prolonged fever
- chest pain
- hemoptysis
- supraclavicular amenities
74
- refers to clinical disease resulting from the hematogenous dissemination of mycobacterium tuberculosis?
- arise as a result of progressive primary infxn or via reactivation of latent form with subsequent spread.
- most common clinically significant form of disseminated tuberculosis which occurs when massive numbers of tubercle bacilli are released into the bloodstream causing disease in 2 or > organs.
- originally a pathological and then a radiographic description,
- used to denote all forms of progressive, widely disseminated hematogenous tuberculosis.
Miliary Tuberculosis
75
Clinical presentation of miliary TB?
- protean and nonspecific, depending on the load of organisms and site where they lodge.
- can be acute and explosive and the patient may become gravely ill in several days, but are more likely to be sub-acute or chronic.
- can also present with relatively acute onset and rapid clinical course such as multiorgan failure, septic shock and acute respiratory distress syndrome (ARDS)
- subacute or chronic presentation:
Failure to thrive
Fever of Unknown origin
Dysfunction of 1 or > organ systems including the brain.
- clinical presentation in children is the same with adult.
- signs or symptoms or peritonitis are found in 20 to 40% of patients with advanced dse.
76
Most common extrapulmonary site if miliary TB?
- lymphatic system
- bones and joints
- liver
77
Miliary TB clinical presentation in children and adult:
```
common in pediatric population:
~ chills
~ night sweats
~ hemoptysis
~ productive cough
- More common in children compared with adults:
~ Peripheral lymphadenopathy
~Hepatomegaly
```
78
- complication of primary TB w/c results in enlargement of:
peribronchial lymph nodes with subsequent compression or
intrabronchial, the node extension into the bronchus.
Endobronchial TB
79
Endobronchial TB cause obstruction:
- sudden death due to asphyxia
- obstructive emphysema (partial obstruction with hyperaeration
of a loner segment)
- atelectasis of a distal segment due to complete obstruction of the
lumen
- right middle lobe is more vulnerable by its anatomical feature and drainage.
80
Endobronchial TB signs and symptoms of progression:
- moderately high fever
- anorexia
- night sweats
- loss of weight
- paroxysmal cough ending in cyanosis
- crepitant rales
- expiratory wheeze (often mistaken for pertussis or bronchial asthma)
81
- most common form of extrapulmonary TB and probably the most common cause of chronic lymphadenitis in children?
- prevalence children up to 14yo: 4.4/1000 cases (india)
- 6.1% of the extrapulmonary TB, mean age 5.8yo (Phil.)
- present in all ages but more frequent in 10-18yo (39.1%)
Tuberculous lymphadenitis
82
TB lymphadenitis in the cervical region?
Scrofula
83
The most common location of TB lymphadenitis?
1. anterior cervical space (children, 49.4%)
2. Axilliary
3. Supraclavicular areas
84
TB lymphadenitis may occur during?
1. Primary tuberculous infection or
2. Result of reactivation of dormant foci or
3. Direct extension from a contiguous focus
85
How TB lymphadenitis spread?
- may spread from primary focus to regional lymph nodes and continue to spread via lymphatic system to other nodes or may pass through the nodes to reach blood stream from where it can be spread virtually all organs of the body..
86
TB lymphangitis most common presentation:
```
- unilateral
single or multiple
slowly growing
non-tender lymphadenopathy
can be present for up to 12mon before diagnosis
- may have low grade fever
Acute respiratory infections maybe precipitated or aggravated by inflamed nodes
- other clinical signs:
Weight loss
Fatigue
```
87
TB lymphadenitis nodal enlargement (early in the course)?
- firm,
- painless
- rubbery
- discrete or matted
- fixed to surrounding structures
- overlying skin may be indurated,
88
Tuberculous cervical lymphadenitis complications?
Fistula formation - 10%
Lymph node abscess -> may burst infrequently leading to a chronic non-healing sinus and ulcer formation
Scrofuloderma
89
Direct extension of tuberculosis into the skin from the underlying structures or by contact exposure to tuberculosis into the underlying structure or by contact exposure tuberculosis
Scrofuloderma
90
Cervical lymph nodes may be palpable in normal young children. Enlargement can be caused by infection other than TB (carious teeth, infected tonsils, ARTICLE, hodgkin’s disease). How to know if TB?
Diagnosis of TB as a cause of lymphadenitis should include a
- careful history of exposure to infectious tuberculosis,
- tuberculin skin test and
- chest radiography.
91
can improve the diagnosis of tuberculous lymphadenopathy, and provide valuable information for appropriate treatment?
Fine-needle aspiration, combined with new, rapid molecular diagnostic tests.
92
Various forms of CNS tuberculosis:
1. Tuberculous meningitis
2. Serous meningitis
3. Other forms:
- Tuberculoma
- TB brain abscess
- spinal tuberculous leptomeningitis
93
- most severe form of extrapulmonary tuberculosis with substantial morbidity and mortality in children and adults
- most common organ involved in extraPMT with mean age 6.2y.
- develop in one of every 300 untreated primary infections
- most freq. in children _____ but uncommon in _____.
- appears within ______ after initial infection.
- accompanies _____ in ~50%.
Tuberculous meningitis (TBM)
- most severe form of extrapulmonary tuberculosis with substantial morbidity and mortality in children and adults
- most common organ involved in extraPMT with mean age 6.2y.
- develop in one of every 300 untreated primary infections
- most freq. in children <6yo but uncommon in infants <4mon.
- appears within 2 to 6 mon after initial infection.
- accompanies miliary TB in ~50%.
94
Pathophysiology TB meningitis:
Tubercle bacilli are distributed during the ______________________ into all parts of the body including the CNS.
However, they do not multiply as well in nervous system,as in other areas as the lungs.
Thus, CNS tuberculosis, although an early manifestation of infection, usually does not appear simultaneously with miliary spread.
Caseous foci in the brain and meninges may remain dormant for many years and may discharge tubercle bacilli into the subarachnoid space.
A thick gelatinous exudate develops around the basal cisterns, Sylvian fissure and the brainstem causing obstruction leading to hydrocephalus and papilledema.
Vascular is can lead to thrombosis and subsequent infarction.
Pathophysiology TB meningitis:
- Tubercle bacilli are distributed during the
lyphohematogenous spread
into all parts of the body including the CNS.
However, they do not multiply as well in nervous system,as in other areas as the lungs.
Thus, CNS tuberculosis, although an early manifestation of infection, usually does not appear simultaneously with miliary spread.
Caseous foci in the brain and meninges may remain dormant for many years and may discharge tubercle bacilli into the subarachnoid space.
A thick gelatinous exudate develops around the basal cisterns, Sylvian fissure and the brainstem causing obstruction leading to hydrocephalus and papilledema.
Vascular is can lead to thrombosis and subsequent infarction.
95
TB meningitis clinical manifestations and diagnosis:
- subacute, broad features, nonspecific clinical course
Key factor in the diagnosis of TBM?
PDE
- persistence of symptoms
- detection of pulmonary or other forms of TB
- identification of a recent close contact with infectious tuberculosis w/in the past 12mon or so.
96
Onset of TBM is usually gradual occurring over a period of _____.
Onset of TBM is usually gradual occurring over a period of ~3wks
97
Stages of TBM, clinical course?
```
- First stage:
Personality changes
Irritability
Anorexia
Listlessness
Some fever
- second stage: after 1 or 2 wks
Inc. ICP
cerebral damage appearing
Drowsiness
Stiff neck
Cranial nerve palsies
Inequality of the pupils
Vomiting
Tache cerebrale
Absence of abdominal reflexes
Convulsions (tonic or clonic, focal or generalized)
- third stage:
Coma
Irregular pulse and respiration’s
Rising fever
```
98
Diagnosis of TBM?
- TST - if positive useful
if neg does not rule out TB or TBM
- may be based only on clinical and preliminary CSF findings
LP an increased opening pressure and characteristic CSF findings.
- CSF
99
Findings on CSF of TBM
- may be clear, usually opalescent, WBC 50-500cells.mm3, polymorphonuclear leukocytes (predominant very early in the disease), lymphocytes (predominating later)
CSF glucose lower limit of normal in 2nd stage, very low in 3rd stage
Protein: normal initially but rises to a very high concentration at which pellicle forms on standing.
- CSF should be sent for acid fast smear ; single sample has low sensitivity, 20-40%
- CSF culture low sensitivity (~40-80%)
- CT scan or MRI hydrocephalus 80%, basal meningeal enhancement in 75%, hypodensities due to cerebral infarcts, cerebral edema, nodular enhancing lesions
- PCR polymerase chain reaction, ELISA latex agglutination
100
Can empiric antiTB therapy be started?
Yes, promptly in app patients suspected with TBM because treatment delay is strongly associated with death.
101
Can adjunctive treatment with corticosteroids improve survival?
Yes, but does not prevent severe disability.
102
What is the most important determinant of outcome in TBM?
Stage of the illness
At which the diagnosis is made and appropriate treatment is given.
Very poor outcome in childhood stage 3 TBM.
103
Enlarged granulomatous Foci within the brain parenchyma?
Manifest clinically as space occupying lesion
Occur most often in children younger than 10yo
Often located infratentorial or at the base of the brain around the cerebellum. In adults supratentorial,
CM: headache, seizures, papilledema, focal deficits
Tuberculomas
104
Lacks the giant cel and granulomatous reaction associated with tubercoluma,
Manifest clinically as space occupying lesion
TB brain abscess
105
The presentation of brain abscess is more subacute _______ after infection but much slower than pyogenic brain abscess.
Tuberculoma may present ______ after infection,
Brain abscess 1wk to 3months after infection
| Tuberculoma: months to years after infection
106
- may manifest as an acute, subacute, pr chronic form
- characterized by myelopathy, with progressive ascending paralysis
- may develop acute paraplegia with sensory deficits or urinary retention which often mimics transverse myelitis or Guillain-Barré syndrome.
- subacute form form is often dominated by myeloradiculopathy, with radicular pain and progressive paraplegia or tetraplegia.
- less virulent chronic form might mimic a very slowly progressive spinal cord compression or non-specific arachnoiditis.
Tuberculous spinal meningitis
107
What is most affected in tuberculous spinal meningitis?
1. dorsal cord (affected most commonly)
2. lumbar
3. cervical regions
108
- accounts to ~10-15% of extrapulmonary TB
- only 2% of all cases of TB
- mean age 6.2yrs
- seen in 1 to 5% of children with untreated primary infection and become symptomatic 1 to 3yrs after initial pulmonary infection.
Bone and joint Tuberculosis
109
How is bone and joint Tubercle bacilli are disseminated?
- disseminated to skeletal structures during lympohematogenous spread during the initial infection or may be develop as a direct extension from a caseous regional lymph node or by extension from a neighbouring infected bone.
- very young children are more vulnerable to suffer from this form than older children because of increased blood flow through the growing bones.
- the lesions usually starts as an area of endarteritis in the metaphysis of the long bone where the blood supply is more abundant.
110
why very young children are more vulnerable to suffer from skeletal TB (bones and joints) than older children?
- there is increased blood flow through the growing bones.
111
In very young children the skeletal TB usually starts as an area of endarteritis in the ?
Metaphysis of the long bone, where the blood supply is more abundant.
112
Skeletal TB should be considered immediately in any child who is?
- known to have been infected with tubercle bacilli and
- in whom a bone or joint lesion develops and
- in any children with a persistent pms not otherwise explained bone or joint lesion.
113
Most common skeletal site affected by TB, followed by hip and knee?
- spine (pott’s disease)
| - vertebral TB or TB spondylitis constitutes about 50% of all cases.
114
Potts disease often have history of?
History of trauma and contributes earthier in activation of an underlying lesion or simply to draw attention to the process.
115
In spinal TB, there is?
- destruction of the intervertebral disk space and adjacent vertebral bodies,
- collapse of the spinal elements and
- anterior wedging leading to the characteristic angulation and gibbus formation.
Distortion of spinal column leads to severe kyphosis (Pott’s disease)
116
What is gibbus?
Palpable deformity because of involvement of multiple vertebrae
117
The most frequently involved sites in spinal TB?
Upper lumbar
Lower thoracic
Lumbosacral spine
- multiple vertebrae are typically affected more frequently the vertebral body.
118
Spinal TB CM sx?
```
- back pain
Most freq symptom of sx
Slow progression and insidious
Duration: 4 to 11 months
- usually seek advice when: severe pain, marked deformity or neurological symptoms.
- night cries
- restless sleep
- daily low-grade fever
- peculiar position (torticolis with cervical lesions) or
- gait
- sensory disturbance
- bowel and bladder dysfunction
```
119
Spinal TB PE?
- marked guarding because of dorsal muscle spasm, local pain, and tenderness
- gibbus deformity or
- reflex changes including clonus
120
Serious Complications of spinal TB?
10-30% of spinal TB
- paravertebral abscess (Potts abscess)
- retropharyngeal abscess
- psoas abscess
- neurological lesions
17-44%
- neurological involvement: paraplegia and paresis result from inflammation of the spinal cord sec to adjacent cold abscess, granuloma in the extradural space or spinal vessel thrombosis.
121
Second to spine as the common site of skeletal TB?
TB of the hip
Other weight bearing joints (knee, shoulders, elbows) also freq. involved.
122
TB of joints CM?
- insidious onset of pain
| - stiffness and limp on walking (refusal to walk in children)
123
TB of femoral head and neck may lead to?
Various deformities.
124
- a TB rare in children,
- monarticular in 90% of cases
- weight bearing joint
- only exceptionally the joints of the upper extremities are primarily involved.
TB of the joints
125
Results from direct invasion of tubercle bacilli into a joint space or as a consequence of an aseptic reactive poly arthritis (poncet’s dse)
- TB arthritis
126
- Infection of the peritoneum, hollow or solid abdominal organs (intestinal tract, liver, spleen, pancreas, messengers) and abdominal lymph nodes.
- uncommon in children
- second in frequency after pulmonary dse
- significant rise observed to occur associated with HIV infxn.
GI TB
- prev of PTB with GI TB 20-60%
127
Most common forms of abdominal TB
- Nodal involvement, peritonitis and intestinal disease
- liver 6.1%
- ileum 1.5%
- perineum 1.5%
- spleen 1.5%
128
GI TB, CM?
Varied and non-specific
- abdominal enlargement
- abdominal pain (cramping, diffused or localized RUQ or LQ)
- distended abdomen
- ascites
- abdominal mass (usually RLQ)
- hepatomegaly
- extraabdominal lymphnode enlargement
- weight loss, growth failure
- malnoursish
- loss of appetite
- most appear systemically ill
- anemic with
- low grade fever
-onset is insidious
129
GI TB DX?
Dx is often delayed made through a combination of:
- radiologic
- endoscopic
- microbiologic
- histologic
- molecular techniques
130
True or false:
| The absence of radiologic or clinical signs of pulmonary disease does not exclude the diagnosis of GI TB
True
131
True or false:
Abdominal TB should be considered in the differential dx of children presenting with acute abdomen, particularly in areas with high TB incidence.
True
132
Prognosis for abdominal TB?
Poor
| In the presence of severe malnutrition, disseminated TB disease and presence of co-morbidities.
133
Cause of TB enteritis (intestinal TB)?
1. Ingestion of sputum infected with tubercle bacilli (most impt. Suggested cause)
2. Lymphoihematogenous spread
3. Direct spread from an adjacent organ (rare)
134
True or false:
Primary TB of the intestinal tract is uncommon in the Philippines because Filipinos are not fresh milk drinkers and because of pasteurisation of milk.
True
135
True or false:
| Occasionally, Tuberculous enteritis accompanies extensive pulmonary cavitation especially in older children.
True
136
Involvement of what intestinal tract in TB enteritis that results from ingestion of bronchial secretions contacting tubercle bacilli form a caseous pulmonary focus?
- ileocecal area (common)
| - extension to the mesenteric lymph nodes and peritoneum.
137
Pathophysio of TB enteritis?
Ingestion of bronchial secretions with tubercle bacilli -> form caseous pulmonary focus -> bacilli taken up by the lymphoid tissue -> giving rise to local ulcers -> followed by mesenteric amenities and peritonitis
138
TB enteritis CM?
- vague abdominal pain.
- intussusceptions
- blood in the stool
- sinus formation after an uncomplicated appendectomy
139
True or false:
Although rectal bleeding and hematemesis are rare in children, intestinal TB should be considered in the differential diagnosis of children which an intestinal bleeding, particularly in high TB incidence countries.
True
140
Often accidentally discovered on X-ray of abdomen in TB enteritis?
Enlarged caseous and falsified mesenteric lymph glands (tabes mesenterica)
On X-ray: shadow of increased density which incites local inflammatory reaction.
These mesenteric nodes become matted and result in adhesions interfering with intestinal motility, thus, producing intestinal obstruction or compression of the portal vein, giving rise to ascites and dilatation of superficial abdominal veins.
141
- commonly due to rupture of a caseous abdominal lymph node and less freq. from a focus in the intestine or Fallopian tube.
TB peritonitis
142
TB peritonitis is classiffied into?
- plastic type
| - serous type
143
- less common type of TB peritonitis
| - characterized by tender abdominal masses, doughy abdomen,
Plastic type TB peritonitis
- common to all types of TB peritonitis: fever, abdominal pain, weight loss, anorexia, and clinical evidence of ascites.
144
- more common type of TB peritonitis
| - characterized by ascites and signs of peritonitis
Serous type TB peritonitis
- common to all types of TB peritonitis: fever, abdominal pain, weight loss, anorexia, and clinical evidence of ascites.
145
True or false:
| The presence of ascites is a constant indicator of peritoneal disease
True
146
True or false:
| A dry or a sclerotic peritoneal TB are very seldom seen in children
True
147
Lab results of ascites in TB peritonitis?
- Aspiration and analysis of ascetic fluid in
shows exudative features with lymphocytic predominance
- serum ascetic fluid albumin gradient: < 1.1 g/DL
- protein: elevated >25 g/L
- ascitic fluid-blood glucose ratio: helpful in differentiating TB peritonitis from other causes of ascites.
148
- lab that is helpful in differentiating TB peritonitis from other causes of ascites.
- ascitic fluid-blood glucose ratio
TB peritonitis <0.96
Non-TB peritonitis >0.96
149
- a subset of patient with extrapulmonary TB have the infection confined solely and predominantly in the liver or biliary tract.
Hepatobiliary TB
150
Hepatobiliary TB CM?
```
-Non-specific symtoms:
Fever
Malaise
Fatigue
Night sweats
Anorexia
Weight loss
- prominent hepatic complaints:
Jaundice, abdominal pain, hepatosplenomegaly, ascites
```
151
Hepatobiliary TB is also known as?
Primary miliary TB of the liver
152
3 forms of hepatic TB?
1. Diffuse hepatic involvement with pulmonary or miliary TB
- most common
- 50-80% cause of death
2. Diffuse hepatic infiltration without recognizable pulmonary involvement
3. Focal or local tuberculoma or abscess
- very rare form
153
- The rarest form of local hepatic TB
| - overall incidence 0.3%
Isolated liver TB (ILT)
154
- hepatic TB lesions that appear as masses larger that >2mm in dm
- these lesions are indistinguishable from the other focal lesions in the liver such as hepatocellular carcinoma and Hodgkin’s disease by imaging technique (most of the time, histopathologic diagnosis is necessary)
- macronodular and pseudorumoral TB
155
- rare condition
- occurs secondarily to a generalized TB
- occasionally in far advanced cases
TB of the pancreas
156
- a chronic grnaulomatous disease caused by mycobacterium tuberculosis and rarely by mycobacterium bovis.
Cutaneous TB or skin TB
157
Cause of skin TB or cutaneous TB?
caused by mycobacterium tuberculosis and
| rarely by mycobacterium bovis.
158
Classification of cutaneous or skin TB in children?
```
Primary
Tuberculous chancre
Miliary TB
Secondary
Lupus vulgaris
Scrofuloderma
Tuberculous verrucosa cutis
Tuberculous gummy (metastatic abscess)
Orificial TB
Tuberculids
Micropapular lichen
Scrofuloderma
Popular-papulonectoric tuberculid
Nodular-nodular tuberculid (erythema induratum)
```
159
What are the clinical forms manifested by cutaneous tuberculosis?
1. Lesions by inoculation from an exogenous source or after inoculation with BCG vaccine
2. Lesions resulting from hematogenous dissemination
3. Lesions arising from an exogenous source and
4. Erythema nodosum
160
- the most common form of childhood cutaneous TB
- classified as a secondary and/or tuberculid skin TB
- indicates TB of the skin overlying a caseous lymph node that has ruptured to the outside, leaving an ulcer or a sinus
- freq. lesions are in cervical area but may involve the
inguinal, submandibular and auxiliary groups
Scrofuloderma
161
Ocular Tuberculosis frequently involves the?
- conjunctiva and cornea in the form of conjunctivitis and phlyctenular keratoconjunctivitis
162
- TB that involves the conjunctiva and cornea
- occur at any age during the primary infection or reactivation of latent disease and may be seen in 14-60% of patients with systemic TB.
- px may be immunocompetent or may have varying degrees of immunosuppression.
Ocular TB
163
Pathophysio of Ocular TB
CONJUNCTIVA serves as portal of ENTRY of bacilli (esp.after trauma) —> a local reaction is induced in the form of UNILATERAL LACRIMATION and REDDENING, with subsequent FORMATION OF YELLOWISH-GRAY NODULES on PALPEBRAL CONJUCTIVAE.
164
Ocular TB CM
- enlargement of the periauricular, submandibular and cervical lymph nodes
- choroiditis, most common ocular manifestation in px with pulmonary and systemic TB
- conjunctivitis
- phlyctenular keratoconjunctivitis
- likely to be a malnourished child with single to multiply 1-3mm, grey to yellow coloured, jelly-like nodules usually clustered on the limbus and surrounded by dilated conjunctival vessels.
- pain, redness, lacrimation and photophobia are observed and the lesions may recur for weeks, affecting one or both eyes.
- tuberculous involvement of the ciliary body, iris, uvea, and TB presenting as orbital mass are rare clinical entities.
- tubercles of the choroid, frequently multiple, often have been found in 70% of px with miliary TB and in children with uncomplicated TB. These heal slowly with deposition of retinal segment.
165
- considered a hypersensitivity reaction to tuberculin
Phlyctenular keratoconjunctivitis
166
Ocular TB that is usually unilateral
POTB presumed ocular TB
167
Confirms diagnosis for ocular TB?
- TST (tuberculin skin test)
Specificity for mycobacterium tuberculosis increases with large
skin reactions and with hx of exposure to active TB.
- Biopsy with culture
168
- uncommon complication of primary TB
- occurring very late, up to 15-20yrs after primary infection
- most commonly seen in children >7yo
- TB bacilli can be recovered from the urine of px with miliary TB and in some PTB
Genitourinary tract TB
169
Pathophysio of genitourinary tract TB?
- hematogenous spread can give rise to tubercles in the glomeruli, with resultant caseating sloughing lesions which dis-charge TB bacilli into the tubules.
- infection can be unilateral or bilateral and can spread caudal to involve the bladder.
170
Genitourinary tract TB CM?
- insidious in onset and has strikingly few specific symptoms
- 75% present with symptoms related to urinary tract inflammation: dysuria, hematuria, sterile pyuria, and flank pain
171
True or false:
Renal TB should be suspected in the presence of destructive PTB with persistent, painless, sterile pyuria associated with albuminuria and hematuria
True
172
Work up for genitourinary TB?
-urine culture
Repeated urine culture are advisable in suspected renal TB
- urine with tubercle bacilli are considered to be highly infectious and should be isolated until their urine is sterile
- complete urologic investigation is mandatory
For those with persistent pyuria
173
True or false:
| urine with tubercle bacilli are considered to be highly infectious and should be isolated until their urine is sterile
True
Pps Diplo
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