2. • Describe the clinical features of GU TB. List possible
investigations. Briefly mention the advantages of each
investigations???
• 4+3+3 ( Jun 2014)
• Describe PCR. Which test based on PCR is being used in
clinical practice. What is micro-array technology??
• 3+3+4 (Dec 2013)
• Descibe the pathological findings in renal tuberculosis??
Describe the mechanism of action of five important drugs.
• 5+5 ( Dec 2011)
• Pathogenesis of GU TB.
• 10 ( Dec 2010)
• Consideration in the management of GUTB in renal allograft
recipient
• 10
4. WHO estimation
8 million new cases/Yr & 3 million deaths/Yr
GUTB 3rd commonest non-pulmonary disease
M : F = 2 : 1
Steady decline in pulmonary TB but not non-pulmonary TB
? Downward trend counteracted by increasing HIV cases
Estimated 5% develop TB
Developed country Developing country
•13/100,000 •Up to 400/100,000
•8 - 10% •Up to 20%
•Older population •Children, young adults
5. • Aerobic, non spore forming, nonmotile bacilli with a waxy
coat that retains the red dye when treated with acid ( acid
fast )
• Causative organism –
Mycobacterium tuberculosis complex (MTC)
• M.tuberculosis
• M.africanum
• M.bovis
6. • The development of disease depends on the
interaction between the pathogen and the host
immune response.
7. • Inhaled Mycobacteria are phagocytosed by alveolar
macrophages
• Hilar lymph nodes ---> blood stream ---> dissemination to
rest of the body
• T cell mediated immunity develops ( 2-3 weeks time)
CD4 +ve Helper T cells CD8 +ve suppressor T cellsCD4 and CD8 –ve T ce
8. • Age group – 20-40 years
• Kidney is usually primary organ to get infected.
• Primary infection - Epidydymis in men and fallopian tubes
in women
9. 1. Hematogenous spread - the bacilli can spread to the renal tract,
fallopian tubes, prostate and epididymis.
2. Lymphatic spread
3. Miliary TB- Multiorgan infection
4. Primary GU - BCG treatment for Ca bladder
5. Transplant recipient
11. • 20%- Fever, Night sweat, Malaise and Weight Loss
• 50%- Dysuria
• 50%- Storage symptoms
• 33%- Hematuria and flank pain
• < 10%- Renal colic- Passage of necrotic papilla, clots,
stones, caseous material
12.
13. Merchant S, et al. Indian Journal of Radiology and Imaging. 2013; 23 (1): 46-63.
Diagrammatic representation: Varied effects of tuberculosis of urinary tract
14. • Level 1: Nondestructive form, TB of parenchyma
• Level 2: Small destructive form, TB papillitis
• Level 3: Destructive form with 1 or 2 caverns (cavernous kidney TB)
• Level 4: Widespread destructive form with > 2 caverns
(polycavernous kidney TB)
• Complications of KTB:
• TB of urinary tract (TB of ureter, bladder grades 1–4, urethra), strictures,
fistula & renal failure
Kulchavenya E. Ther Adv Urol. 2013; 5(3): 143-151.
15. • Radiologic abnormalities
usually affect both kidneys
in approximately 20–30 %.
• Calcification is seen over
renal areas and in lower
GU tract in 50 % cases .
• Calcification is intraluminal
as opposed to intramural
as in schistosomiasis
Putty Kidney: Diffuse, uniform,
extensive parenchymal
calcifications
17. Merchant S, et al. Indian Journal of Radiology and Imaging. 2013; 23 (1): 46-63.
Diagrammatic representation: Varied effects of tuberculosis of urinary tract
18. Merchant S, et al. Indian Journal of Radiology and Imaging. 2013; 23 (1): 46-63.
Diagrammatic representation: Varied effects of tuberculosis of urinary tract
19. Merchant S, et al. Indian Journal of Radiology and Imaging. 2013; 23 (1): 46-63.
Diagrammatic representation: Varied effects of tuberculosis of urinary tract
20. Earliest abnormality –
an indistinct feathery outline
Irregularity of surface of one
or more papillae or calyces
with normal renal size and
contour.
Fuzzy & irregular calices due
to papillary necrosis.
21. On IVP :
Collecting system shows contrast material
in a large papillary cavity, the “golf ball” (∗).
Blunted calyx, the “tee,” is adjacent
(arrow).
23. • Cortical scarring with dilatation
& distortion of adjoining
calyces coupled with strictures
of the pelvicaliceal system.
• Cause luminal narrowing either
directly or by causing kinking
of the renal pelvis at the UPJ.
26. • CECT scan
• At level of right renal hilum shows wedge-shaped hypoperfused
areas with localized caliectasis
• MRI
• Gadolinium-enhanced T1-weighted images obtained with fat suppression
show hypoperfused areas
27. • Tuberculosis involving entire segment
of left urinary tract. Sonogram shows
severe nonuniform caliectasis
• Contrast-enhanced CT scan shows wall
thickening and enhancement of left
ureter
28. • Tuberculosis involving
entire segment of left
urinary tract.
• CT urogram using curved
multiplanar reformation
shows severe nonuniform
caliectasis and multifocal
strictures involving renal
pelvis and ureter.
• Calcification is noted in
left distal ureter
31. • Fusion of multiple strictures
may create a long, irregular
narrowing. Several
nonconfluent strictures can
produce a “beaded” or
“corkscrew” ureter
Mucosal thickening of ureter
32. • Rigid ureter: irregular and
lacks normal peristaltic
movement, fibrotic strictures
noted.
Old pipe stem
33. • Is divided into four stages [Kulchavenya, 2014]:
• stage 1, tubercle infiltrative;
• stage 2, erosive ulcerous;
• stage 3, spastic cystitis (bladder contraction, false
microcystitis), in fact overactive bladder;
• stage 4, real microcystitis up to full obliteration.
34. Always secondary to renal TB
Starts around ureteric orifice -->
inflamed, red & edematous -->
ulcer
Fundus & base lesions, velvety
lesions in whole bladder =>
penetration into muscle --> fibrosis
& contracted bladder- thimble
bladder
Urinary frequency, urgency, pain,
and dysuria- Capacity < 100 ml
36. • Orchiepididymitis (unilateral and bilateral)
• Prostate TB (infiltrative or cavernous forms)
• TB of seminal vesicles
• TB of penis
• Complications of MGTB:
• Strictures, fistula, infertility, sexual dysfunction
Kulchavenya E. Ther Adv Urol. 2013; 5(3): 143-151.
37. Second most common. (10-
55%)
Haematogenous spread,
70% have old PTB
Bilateral in 34%
Starts in Globus minor -->
‘Beaded’ vas may be the
only presenting symptom
Early Morning Urine
negative
Discharging sinus may
develop (50%) => obtain
culture
Epididymectomy if no
38. • Gray-scale sonogram shows
swelling and heterogeneous
hypoechogenicity of left
epididymal tail
• Power Doppler sonogram
shows increased vascularity
in swollen epididymis
• Gray-scale sonogram
shows swelling and
hypoechogenicity of left
spermatic cord
39. • Tuberculosis involving left epididymis and spermatic cord.
• T1 – Weighted images
• Left epididymis and spermatic cord are swollen
40. • Tuberculosis involving left epididymis and spermatic cord.
• T2 – Weighted images
• Internal low signal intensity on T2-weighted images means chronic
inflammation or fibrosis.
41. • Tuberculosis involving left epididymis and spermatic cord.
• Gadolinium-enhanced T1 – Weighted
• Enhancement of gadolinium-enhanced T1-weighted images.
42. • Uncommon
• Usually detected
incidentally on TUR
specimen
• Rarely in acute
fulminant cases –
abscess and rupture –
perineal sinus
formation
43. • Tuberculosis involving seminal vesicle and vas
deferens. Gray-scale sonogram shows dilatation
and wall thickening of seminal vesicle
44. • Tuberculous prostatitis. Gray-
scale sonogram shows
hypoechoic nodule in
peripheral zone
• Tuberculous prostatitis. Color
Doppler sonogram shows
hypervascularity in same
nodule
45. Gray-scale sonogram shows low-echoic
mass replacing prostate . Posterior
enhancement of mass
T1-weighted MR image shows swelling of
prostate and internal low signal intensity
T2-weighted MR image shows low
signal intensity surrounding high
signal intensity
On gadolinium-enhanced T1-weighted image,
area of low signal intensity on T2-weighted
image shows enhancement, implying
a wall of abscess
46. • Superficial ulcer, solid
nodule on glans penis
or TB cavernositis .
• Urethral involvement
is uncommon
47. • Fallopian tube – tube
diameter normal in early
phases.
• Advanced disease –
nodular transformation
• Adhesions bet ovaries
and pelvic organs with
loss of fimbria
• Patent ostia along with
grossly diseased
fallopian tubes –
Classical feature
• Ovary – 10% , fimbrial
adhesions, adnexal
mass
• Cervix – ulcer, mass
mimicking malignancy
• External genitalis –
nonhealing ulcers on
the vulva.
50. LAB INVESTIGATIONS
Urine for AFB microscopy:
Ideally 5 or atleast 3 consecutive morning
samples are to be examined.
51. • Make a thin smear of the material for study and heat fix by passing the
slide 3-4 times through the flame of a Bunsen burner or use a slide
warmer at 65-75 C. Do not overheat.
• Place the slide on staining rack and pour carbol fuschin over smear
and heat gently underside of the slide by passing a flame under the
rack until fumes appear (without boiling!). Do not overheat and allow it
to stand for 5 minutes.
• Rinse smears with water until no color appears in the effluent.
• Pour 20% sulphuric acid, wait for one minute and keep on repeating
this step until the slide appears light pink in color (15-20 sec).
• Wash well with clean water.
• Cover the smear with methylene blue or malachite green stain for 1–2
minutes.
• Wash off the stain with clean water.
• Wipe the back of the slide clean, and place it in a draining rack for the
smear to air-dry (do not blot dry).
• Examine the smear microscopically, using the 100x oil immersion
52.
53. • Classically ‘ Sterile pyuria in acidic urine ‘
• 20 % have no leucocytes in urine
• 20 % have E. Coli
• 50 % have microscopic hematuria
• Sensitivity is approximately 52 %
• Specificity is 89-96 %.
54. Tuberculin Test
Interferon-Gamma Release
Assays
• IGRAs are blood tests that
measure the level of IFN-γ
(a surrogate of cellular
immune reactivity)
produced in response to
MTBC-specific antigens
• Two IGRA available
• QuantiFERON-TB Gold In-
Tube test (QFT-GIT)- TB
Platinex.
• T-SPOT. TB test.
55. QFT-GIT
• Whole blood is collected in
three specialized test tubes,
one containing the MTBC
antigens ESAT-6, CFP-10,
and TB7.7, and two controls
(negative and positive).
• The blood is incubated
directly in the collection
tubes for 16 to 24 hours.
• Plasma is then separated
and IFN-γ is measured using
enzyme-linked
immunosorbent assay
(ELISA).
T-SPOT.TB assay
• In the, peripheral blood
mononuclear cells are
separated from whole blood
and then incubated with
ESAT-6 and CFP-10 in wells
coated with antibodies that
capture IFN-γ.
• Enzyme-linked immunospot
(ELISPOT) assay is used to
detect an increase in the
number of cells (appearing as
spots in each test well) that
secrete IFN-γ in relation to a
negative control.
• Spots are manually counted
56. • A person’s ability to respond to local concentration of
injection may be decreased by malignancy, nutritional
deficiencies, steroid therapy, irradiation & AIDS
• A positive skin test supports diagnosis of TB, but a
negative skin test does not necessarily exclude extra-
pulmonary manifestation. This is especially true in cases
of GUTB
Cek M, et al. EAU Guidelines for the Management of Genitourinary Tuberculosis. Eur Urol. 2005;
57. Cek M, et al. EAU Guidelines for the Management of Genitourinary Tuberculosis. Eur Urol. 2005;
48: 353-362.
CDC has
recommended 3 cut
points for defining
positive tuberculin
reaction: induration
of 5 mm or greater,
10 mm or greater,
and 15 mm or
greater
58. • The different mediums used are
1) Lowenstein Jensen's medium
2) Middle brook & H – 10 agar
• The specimens are incubated at 37degrees under 5%
CO2
• All mycobacteria grow slowly- 4 to 8 weeks
59. • The ways of identifying the bacteria are
1)Colony Morphology
2)Growth time
3)Colony Pigmentation
4)Biochemical test
60. • Although not widely used, the following tests are also available : -
• Luciferase and fluorescent techniques:
• Staining with auramine or rhodamine and examining by
fluorescence microscopy can detect low numbers of
mycobacteria.
• High-performance liquid chromatography (HPLC) test:
• HPLC quickly reveals qualitative and quantitative differences
in mycolic acid in cell walls.
• DNA probe:
• This probe provides species specification in a few hours
61. • Invented by Kary
Mullis in 1987.
• It detects
mycobacterial DNA in
clinical specimens as
a replacement for
culture and shortens
diagnostic time to 24
hours.
62. The Polymerase chain reaction (PCR) test is
highly sensitive, specific, and rapid.
Sensitivity : 87-100% (usually >90%) and
Specificity : 92-99.8% (usually >95%).
This compares to Cultures (52 %),
Bladder biopsies (45 %), and
IVP (88%).
Along with clinical assessment, PCR is the best available
tool to avoid delay in starting treatment because it
takes only about 6 hours.
Polymerase chain reaction (PCR)
63. • LACK OF SPECIFICITY was more of a problem than lack
of sensitivity.
• Dead and living organisms cannot be differentiated
therefore, a positive result does not indicate active
disease.
• False positive results are also a major concern due to
contaminated DNA in the specimen which can also be
amplified.
• Its greatest value is in low prevalence populations to
detect latent infections.
64. • Hybridisation of
amplified nucleic acids
with fluorescent-labelled
probes spanning DNA
regions of interest and
monitored inside
thermal cyclers .
• The fluorescent signal
increases in direct
proportion to the
amount of amplified
product in the reaction
tube.
65. • The sensitivity in these studies has ranged from
71–98%, with specificity close to 100%
• The main advantage of real-time PCR is its
speed in giving results, 1.5–2 h after DNA
extraction, and the decrease in the risk of
contamination since both reaction and detection
occurs in a single tube
J Clin Microbiol 2003; 41: 4565–4572.
Broccolo F, Scarpellini P, Locatelli G, et al.
67. The following PCR tests are available with more or less
similar quality:
• Genus-specific 16S rRNA PCR test
• Species-specific IS6110 PCR test
• Roche Amplicor MTB PCR test
• Amplified Mycobacterium tuberculosis Direct
Detection Test (AMDT
Polymerase chain reaction (PCR)
68. ELISA TEST :
Ig G antibodies if raised indicate past infection
Ig M antibodies indicate acute / recent infection
69. • To assess extent of disease
• Response to therapy
• Bladder Biopsy : This is contraindicated in presence
of acute tuberculous cystitis .
Tubercles are rare in the bladder; if present, they usually appear at
the ureteral orifice.
Malignancy should be considered with any isolated tubercles away
from the ureteral orifices
The yield of biopsy for TB is about 45 %.
77. • Rates of acquired drug resistance were higher among
patients receiving three times weekly dosing throughout
therapy than among patients who received daily drug
administration throughout treatment.
• Moreover, in patients with pretreatment isoniazid
resistance, three times weekly dosing during the
intensive phase was associated with significantly higher
risks of failure and acquired drug resistance than daily
dosing during the intensive phase.
78. • Daily dosage may be standardized for 3 or 4 wt bands
(e.g-30-39,40-54,55-70 and above 70 kg
• Or single dose for most pt with additional rifampicin for pt
over 60 Kg and individual calculation for children as in
India
79. • Although 6 months is the duration of standard short-
course therapy, clinical scenarios regularly arise that
require prolongation of treatment. Both the type of clinical
disease present and the antituberculous drugs used
affect duration of treatment (CDC, 2003).
80. • Treatment for at least 9 months is recommended for
1. Extensive pockets of infection
2. Concurrent smear-positive cavitary pulmonary disease
3. Central nervous system involvement
4. Delay in positive cultures converting to negative.
5. If the patient is unable to take pyrazinamide for at least 2
months, because of either side effects or drug resistance.
• Some clinicians recommend 12 months of
therapy for GU TB because of high relapse
rates of up to 22% when therapy is given for
only 6 months (Gokalp et al, 1990).
91. • Hydrazide of Iso Nicotinic acid
• Highly bactericidal
• Rapidly absorbed
• Diffuses rapidly to all fluids and tissues
• Metabolism- Deacylation- Fast and slow acetylators
94. • Isoniazid may increase the toxicity of carbamazepine,
benzodiazepines metabolized by oxidation (such as
triazolam), acetaminophen, valproate, serotonergic
antidepressants, disulfiram, warfarin and theophylline.
95. • Macrocyclic antibiotic
• Inhibit RNA synthesis
• Bactericidal, sterilizing – cellular , extra cellular location
• Lipid soluble
• Deactylation in liver
• T1/2 – 2-3 hrs
• 30 min before meal
96. • Serious immunological reactions resulting in renal
impairment, haemolysis or thrombocytopenia are on
record in patients who resume taking rifampicin after a
prolonged lapse of treatment. In this rare situation,
rifampicin should be immediately and permanently
withdrawn.
• Clinical monitoring (and liver function tests, if possible)
should be performed during treatment of all patients with
pre-existing liver disease, who are at increased risk of
further liver damage.
97. • Patients should be warned that treatment may cause
reddish coloration of all body secretions (urine, tears,
saliva, sweat, semen and sputum), and that contact lenses
and clothing may be irreversibly stained.
98. • GI Upset
• Fever, Flu like symptoms,Thrombocytopenia
• Exfoliative dermatitis
• Temporary oliguria,dyspnoea,hemolytic anemia – 3/7
• Rise in liver enzymes, bilirubin
100. • Weak bactericidal activity
• Potent sterilizing activity in acidic environment
• Metabolized in liver
• Excreted in urine
101. • Contraindications •
• Known hypersensitivity. •
• Active, unstable hepatic disease (with jaundice)
• • Porphyria.
• Precautions
• Patients with diabetes should be carefully monitored since blood
glucose concentrations may become labile.
• Gout may be exacerbated.
• LFT monitoring in patients with pre-existing liver disease.
• In patients with renal failure dose is three times per week, rather
than daily.
102. • GI Upsets
• Hypersensitivity reaction
• Raise in liver enzyme level
• Hyperuricemia
103. • Aminoglycoside
• Contraindications
• Known hypersensitivity
• Auditory nerve impairment
• Myasthenia gravis
• Pregnancy.
• The dose should be maintained at 12‒15 mg/kg but at a
reduced frequency of 2–3 times per week.
• Where possible, serum levels should be monitored
periodically and dosage adjusted appropriately to ensure
that plasma concentrations, as measured when the next
dose is due, do not exceed 4 μg/ml.
106. • Contraindications
• Known hypersensitivity
• Pre-existing optic neuritis from any cause.
• Precautions
• Patients should be advised to discontinue treatment immediately
and to report to a clinician if their sight or perception of colour
deteriorates.
• Ocular examination is recommended before and during treatment
117. • 55% of patients require surgical treatment for GU TB.
• The optimal timing of surgery is 4 to 6 weeks after the
initiation of medical therapy. This delay allows active
inflammation to subside, the bacillary load to decrease,
and lesions to stabilize.
118. 1. Drainage for hydronephrosis (ureteric stenting or
percutaneous nephrostomy)
2. Drainage of abscesses or localized collections
3. Definitive local treatment of the affected part of the
kidney (cavernotomy/partial nephrectomy)
4. Nephrectomy of the non-functioning tuberculous kidney
(open/laparoscopic/retro-peritoneoscopic techniques)
5. Reconstruction of the upper urinary tract (uretero-
calycostomy, ureteric reimplantation, ileal ureteric
replacement).
119. • PUJ or ureteric stricture with hydronephrosis
• Drainage, prevents further deterioration
• The strictures should be monitored with CT or IVU.
• If there is deterioration or no improvement after a six-
week period, then surgical reimplantation or other
minimally invasive procedures including balloon dilatation
may be necessary.
120. • Multiple infundibular stenoses with individual calyces
being dilated and non-communicating
• DJ stenting may not be effective in such circumstances,
as the individual calyces do not communicate with each
other.
• PCN- Single/Multiple
• Once the disease process has stabilized, one should
plan a definitive procedure after two months of intensive
phase of chemotherapy.
123. • Most common site is UVJ.
• Next most common is UPJ
• Most uncommon is mid ureter
• Rarely whole ureter is stenosed,fibrous and calcified
124. • Uncommon as by this time the kidney is usually
destroyed
• Initial management should be DJ stenting for 6
months or PCN if DJ stenting fails.
• If after stent removal dilatations reappears or
deteriorates or function decreases surgery is
indicated
• Surgery – Anderson Hynes or Culp Deward
pyeloplasty with DJ stent
• Endopyelotomy – not assessed
125. • Rare
• Treatment-DJ stenting for atleast 6 weeks.If fails or is not
possible –Davis intubated ureterostomy
126. • Occur in 9% cases
• Either DJ stenting or initially prescribe chemotherapy and
wait.
• If no improvent after 3 weeks add corticosteroids.
• If no improvement after 6 weeks –ureteric dilatation if
fails then reimplantation
127. • Ureteral dilatation
Has high failure rates and requires repeated
procedures
• Surgical management
• Most strictures are less than 5cm and confined to
intramural part
• RGP should be done to estimate length of stricture
• Cystoscopy done to localise normal appearing
mucosa for reimplant site
128. • Simple mobilization of the lateral attachments of the
bladder on the contralateral side, accompanied by
division of the superior vesical artery, may provide 2 to 3
cm of length.
• In patients with good bladder capacity, a psoas hitch may
also be performed. Care must be taken to avoid the
genitofemoral and femoral nerves when placing these
sutures. A well-performed psoas hitch can bridge a gap of
up to 5 cm.
• A Boari flap is another method of bridging a longer gap of
10 to 15 cm and may be performed in combination with a
psoas hitch. Poorly executed Boari flap - Compromise
bladder capacity.
129. • Ureteroureterostomy
• Extensive stricture involving one or both the ureters
• Longer of the 2 ureters reimplanted into bladder or Boari flap
• Ileal ureter
• replacing excessive length of ureter
130. • Augmentation cystoplasty
• Indication
• Intolerable frequency of micturation with pain , urgency ,
hematuria
• Capacity less than 100ml
• Deterioration of renal function due to reflux or obstruction
• 4 weeks of chemotherapy required before surgery
• Severely contracted- Ileo-caecum and sigmoid
• Only half of bladder is diseased- Ileum
• Rarely- Stomach and caecum
131.
132. • Urinary diversion:
• Indications
• Psychiatric illness or subnormal intelligence
• Enuresis not related to small bladder capacity
• Intolerable diurnal symptoms that with incontinence that
has not responded to chemotherapy or bladder dilatation
• Ileal or colonic conduits used
135. • Indications
1. Nonfunctioning kidney with or without calcification
2. Extensive disease involving the whole kidney together with
hypertension and UPJ obstruction ( HTn improves in 65%
patients)
3. Coexistent renal cell carcinoma
• 90% of all nonfunctioning kidneys are destroyed
• More chances of flank sinuses,abscesses and
hypertension if such kidneys are preserved
• Inspite of sterile cultures with chemotherapy 50% of
kidneys show active tuberculosis.
136. • Indications
1. Localised polar lesion containing calcification that
has failed to respond after 6 weeks of intensive
chemotherapy
2. An area of calcification that is slowly increasing in
size and is threatining to gradually destroy the whole
kidney
• With modern chemotherapy, response of a local lesion is
rapid and effective, making partial nephrectomy less
common.
137. • Indications of epididymectomy
1. A caseating abscess that is not responding to chemotherapy
2. A firm swelling that has remained unchanged or has slowly
increased in size despite the use of anibiotics and
antituberculous therapy
• Epididymis is infected with sparing of the testis-
epididymectomy with preservation of blood supply to
testis
138. • Involovement of testis is uncommon , orchidectomy being
required in only 5% cases
• Testicular atrophy is seen in 6% cases
• If the testes are infected, a scrotal orchiectomy can be
done.
• Involvement of the vas deferens by TB is usually distal to
the external ring, and ligation at the level of the ring is
possible and sufficient.