Tuberculosis Flashcards
What type of bacteria is Mycobacterium tuberculosis?
Mycobacterium tuberculosis is a gram positive acid fast bacteria which is aerobic and inhibits phagolysosome activity.
Mycobacterium tuberculosis is aerobic and inhibits phagolysosome activity.
What are the effects of tuberculosis?
There is typically cavitation necrosis and caseating granuloma which typically occurs in the lower lobes . It is transmitted via inhalation or ingestion of dairy products containing mycobacterium bovis (tuberculosis in cattle). It survives in immune cells after phagocytosis with slow rate of reproduction once every 24 hours.
What cytokines do macrophages produce to recruit macrophages for inflammatory activity?
- IL-1
- IL-6
- TNF-Alpha
These cytokines contribute to the formation of granulomas.
What is a Ghon focus?
A granuloma typically found in the middle and lower lobes
It releases IFN-gamma.
What is the Ghon complex?
A granuloma with hilar lymphadenopathy
What occurs during primary tuberculosis?
Associated with Ghon focus after first exposure to the pathogen and there is commonly a progression to a latent asymptomatic period with fibrocalcification lesion, unless risks cause secondary tuberculosis.
Symptoms are typically present in primary progressive tuberculosis or secondary reactivated tuberculosis.
It may progress to a latent asymptomatic period.
What occurs in latent tuberculosis?
Ghon complex undergoes fibrosis and is known as a Ranke complex. It can turn into secondary tuberculosis with HIV, immunosuppression medication, post-transplant, diabetics and CKD
What can lead to secondary tuberculosis?
- HIV
- Immunosuppression medication
- Post-transplant
- Diabetes
- Chronic kidney disease
These risks can cause reactivation of latent tuberculosis.
What characterizes secondary tuberculosis?
Progression from lower lobes to highly oxygenated upper lobes, due to its aerobic nature where it reactivate, causing caesating necrosis that forms fibrocavitary lesions. It is characterised by diurnal fevers causing caseating necrosis
It is characterized by diurnal fevers.
What are the complications with secondary tuberculosis
The caesating necrosis can extends into the pleura, increasing the risk for penumothorax and affecting bronchial vessels to cause haemoptysis. There is reduced pathogen clearance and can increase the risk for bronchopneumonia and pleural effusion.
What are common symptoms of tuberculosis?
- Productive cough
- Shortness of breath
- Fever
- Night sweats
- Hemoptysis
- Weight loss
There may be a cold abscess in the neck due to isolation of disease in pus-filled pockets
There may be cold abscesses in the neck due to pus-filled pockets.
What is included in systemic military TB?
Sterile pyuria due to infiltration of the kidney, resulting in WBC
Meningitis
Cervical lymphadenoapathy
Constrictive pericarditis
Hepatitis and hepatomegaly
Addison’s disease due to inflammation of adrenal glands
Pott’s disease, where it infiltrates the lumbar vertebrae
Osteomyelitis
Why does systemic military TB occur?
MAC complexes are responsive for the miliary TB that disseminates systemically. This should be managed with ethambutol with rifampin and macrolide antibiotic. Additionally, aminoglycosides and fluoroquinolones can be used for refractory cases.
What are the risk factors for TB?
- are younger than 5years
- have excessive alcohol intake
- are injecting drug users
- have had solid organ transplantation
- have a haematological malignancy
- are having chemotherapy
- have had a jejunoileal bypass
- have diabetes
- have chronic kidney disease or receive haemodialysis
- have had a gastrectomy
- are having treatment with anti‑tumour necrosis factor‑alpha or other biologic agents
- have silicosis
What is genitourinary tuberculosis?
Genitourinary tuberculosis affects the kidneys, bladders, ureters and genitalia, from ahematogenous spread froom primary pulmonary focus. It can cause severe complications such as:
Obstructive uropathy
Hydronephrosis
Renal failure: causes calcifications of the parenchyma and form granuloma which are at risk of rupture and worsening infection and there may be amyloidosis
Infertility due to infection of the genitalia with the ovaries and fallopian tubes/prostate or epididymis
These complications stem from hematogenous spread from primary pulmonary focus.
How is tuberculosis diagnosed?
Mantoux tuberculin test
Interferon gamma release assay
CXR
Sputum sample
NAT (nuclei acid amplification test)
What does a positive Mantoux test indicate?
Mantoux skin test involves injection of purified protein derivative of TB. It indicates prior exposure to tuberculosis via type 4 hypersensitivity reaction causing swollen area in 48-72 hours. Larger than 5mm indicates active TB assessment.
A positive test is indicated by a swollen area 48-72 hours after injection.
What causes a false positive PPD test?
False positive PPD tests can occur with use of live BCG vaccine so may require interferon gamma release assay
What causes a false negative PPD test?
False negative PPD can occur in patients with poor immune response such as HIV patinets or sarcoidosis
Which test is reccomended for patients that have received a BCG vaccine?
BCG vaccine use in the past requires an interferon gamma release assay, due to release of IFN-gamma form the caesating necrosis granuloma
What are the findings on CXR for tuberculosis?
CXR showing:
* fibrocalcification lesions
*Tree and bud sign, which represents endobronchial spread of infection in tuberculosis, pneumonia and influenza.
*Diffuse nodular opacities on bilateral lung fields -> indicates miliary TB
*No changes indicates latent TB
What do fibrocalcification lesions on the middle/lower lobes indicate?
Typically has hilar lymphadenoapthy indicates Ghon complex and primary TB
What do fibrocalcification lesions on the upper lobes indicate?
Upper lobes indicates secondary tuberculosis
How are sputum samples taken in tuberculosis?
Sputum sample-> 3 deep cough samples with acid fast smear. This can be further stimulated with bronchoalveolar lavage to insert saline or hypertonic saline nebuliser to increase mucus clearance.
What does a “tree and bud” sign on CXR indicate?
Tree and bud sign, which represents endobronchial spread of infection in tuberculosis, pneumonia and influenza.
How is extra-pulmonary TB asssessed?
Analysing cerebrospinal fluid, pleural fluid or ascitic fluid
X-ray and bronchoscopy
CT scan and MRI for meningitis, where CNS involvement is suspected
Ultrasound, aspiration of lymph node, nuclei ACS acid amplification test
Assessment of constrictive pericarditis with echocardiogram, biopsy of pericardium or pericardial fluid
What should be tested prior to latent tuberculosis treatment?
HIV, Hep B and C testing should be performed prior to treatment
What are the treatment options for latent tuberculosis?
- Isoniazid with B6 supplement for 9 months combined with Rifampicin for 4 months
HIV, Hep B, and C testing should be performed prior to treatment.
What regiment to treat latent tuberculosis is reccomended for immunosuppressed patients?
- 6 months of isoniazid with pyridoxine for patients on long-term drugs Due to rifampicin interfering with the effects of immunosuppressant drugs.
What is the treatment regimen for active tuberculosis?
Rifampin with isoniazid with pyrazinamide and ethambutol/streptomycin for 2 months
Followed by Rifampin and isoniazid with pyrodozinw for 4 months
Rifampin can cause orange urine and is a cytochrome P450 inducer.
What side effects are associated with Isoniazid?
- Peripheral neuropathy Due to B6 deficiency
- Hepatotoxicity -> monitor LFTs
- Anion gap metabolic acidosis by increasing risk for ketoacidosis and lactate levels
- Induction of lupus
Liver function tests should be monitored.
What are the side effects of pyrazinamide?
Pyrazinamide increases uric acid levels and increase risk of gout and hepatotoxicity, so LFTs should be monitored.
What are the side effects of ethambutol?
Ethambutol causes optic neuritis and colour blindness
What are the side effects of streptomycin?
Streptomycin may cause Nephrotoxicity, teratogenic, and cause ototoxicity with decreased hearing and worsens myasthenia gravis.
What additional treatment should be offered for CNS involvement in TB?
offer dexamethasone/prednisolone at high doses To reduce the risk of meningitis
What is the role of Rifampin in tuberculosis treatment?
Inhibits RNA polymerase
It increases the clearance of drugs and can cause false positive urine opiates.
What is the action of streptomycin?
Streptomycin inhibits the 30s ribosomal subunit in tuberculosis antigen.
Which drug inhibits fatty acid synthase in tuberculosis treatment?
Pyrazinamide inhibits fatty acid synthase for mycolic acid synthesis
It increases uric acid levels and the risk of gout.
What is the action of ethambutol?
Ethambutol inhibits arabinosyl transferase for formation of arabinosyl gala tan in the cell wall of the tuberculosis antigen
What is the significance of the ‘tree and bud sign’ in imaging?
Represents endobronchial spread of infection in tuberculosis, pneumonia, and influenza
What is a common imaging finding in miliary tuberculosis?
Diffuse nodular opacities on bilateral lung fields
What is the primary method for diagnosing extra pulmonary tuberculosis?
Cerebrospinal fluid, pleural fluid, or ascitic fluid analysis
Imaging such as CT scans and MRIs may also be utilized.
What is the purpose of contact tracing in tuberculosis management?
To identify and manage individuals exposed to the infected patient
What is the mechanism of action for Ethambutol?
Inhibits arabinosyl transferase for formation of arabinosyl galactan in the cell wall of the tuberculosis antigen
True or False: Mycobacterium leprae can cause nerve palsy.
True
What are the risk factors for tuberculosis?
- Positive PPD
- Younger than 5 years
- Excessive alcohol intake
- Injection drug use
- Solid organ transplantation
- Hematological malignancy
- Chemotherapy
- Jejunoileal bypass
- Diabetes
- Chronic kidney disease
- Gastrectomy
- Anti-tumor necrosis factor-alpha treatment
- Silicosis