Makindo Medical Notes.com

Related Subjects: |Assessing Breathlessness |Fever - Pyrexia of unknown origin |TB Meningitis |Lady Windermere syndrome

About

• Mycobacterium tuberculosis is the typical and most common form affecting humans.
• Human disease from inhalation pulmonary disease or infected milk products
• Mycobacterium kansasii or avium intracellulare do not normally cause human disease
• Increasing due to HIV/AIDS and patients may not be open about a prior HIV diagnosis. May be seen when CD4 < 200

Epidemiology

• Worldwide 2 Billion infected 95% in developing world 3 million deaths per year
• IN UK - Sub-Saharan Africans, Bangladeshi, Indian, Pakistan
• Homeless, alcohol-dependent, immunocompromised - HIV
• Drug and Multidrug resistant (Rifampicin) TB is a problem

Types

• Mycobacterium tuberculosis (causes TB in human)
• Mycobacterium bovis (endemic in cattle, rarely infects human).
• Atypical mycobacteria.

Microbiology

• Mycobacterium tuberculosis bacilli are gram-positive (no cell membrane but have a cell wall with a high lipid content ) rods and are obligate aerobes growing most successfully in tissues with a high oxygen content, such as the lung apices.
• They are facultative intracellular pathogens usually infecting mononuclear phagocytes (e.g. macrophages) and slow-growing with a generation time of 12 to 18 hours (c.f. 20-30 minutes for Escherichia coli).
• They are impermeable to the usual stains, e.g. Gram's stain and are known as "acid-fast bacilli" because of their lipid-rich cell walls, which are relatively impermeable to various basic dyes unless the dyes are combined with phenol. Once stained, the cells resist decolourisation with acidified organic solvents and are therefore called "acid-fast".

Pathophysiology

Summary of Manifestations of Tuberculosis

Response to Disease

Clinical: Primary infection

• Primary Pulmonary infection: Bacillus must get directly to the distal acinus to avoid the mucociliary escalator. Spread is by usually by aerosol droplets 0.5-3 um. Infected humans are the only reservoir and host. Transmission can only occur from people with active "smear-positive" TB. Primary pulmonary tuberculosis (TB) begins when Mycobacterium tuberculosis bacteria are inhaled into the lungs and engulfed by alveolar macrophages. The bacteria survive and replicate within these cells, leading to the formation of a primary lesion known as the Ghon focus, which may extend to nearby lymph nodes to form a Ghon complex. The immune system responds by forming granulomas, structures that contain the bacteria but do not eliminate them entirely, leading to a state of latent TB infection. In some cases, particularly in those with weakened immune systems, the infection can progress, causing active TB disease. The outcome depends on the host's ability to contain the bacteria within granulomas, balancing between latent infection and active disease.
• Primary Gastrointestinal disease may be seen affects terminal ileum and tonsils. Mainly seen in children and adolescents. From infected swallowed sputum or unpasteurized milk or through hematogenous spread from a primary focus such as pulmonary TB. The bacteria reach the GI tract, particularly the ileocecal region, which is most commonly affected due to its abundance of lymphoid tissue. Upon reaching the GI tract, M. tuberculosis is engulfed by macrophages in the mucosa. However, the bacteria can survive and replicate within macrophages due to their ability to inhibit phagosome-lysosome fusion. This leads to local inflammation, with macrophages, lymphocytes, and other immune cells being recruited to the site of infection. The immune response leads to the formation of granulomas, which are structured collections of immune cells that attempt to contain the infection. Granulomas in the GI tract often involve the submucosa and may extend to the muscular layer. They can cause thickening of the bowel wall and narrowing of the lumen, particularly in the ileocecal region. Over time, the center of granulomas may undergo caseation necrosis, where the tissue becomes necrotic and cheese-like. This necrotic tissue can break down, leading to ulceration of the mucosal surface. Ulcers in GI TB are typically transverse and can lead to bleeding, perforation, or fistula formation. The bacteria can spread via lymphatic channels to regional lymph nodes, leading to lymphadenopathy. Mesenteric lymph nodes may become enlarged and can caseate, contributing to the mass effect and obstruction seen in some cases of GI TB. Chronic inflammation and healing in the GI tract can lead to fibrosis and stricture formation. These strictures may cause bowel obstruction, leading to symptoms such as abdominal pain, distension, and vomiting. The ileocecal region is particularly prone to this complication. Examples are obstruction: Due to strictures or masses. Perforation: Due to ulceration, leading to peritonitis. Fistula Formation: Between affected bowel segments or with other organs. Malabsorption: Due to extensive mucosal involvement. Haemorrhage: From ulcerated lesions.
• Systemic manifestations:as fever and fatigue and arthralgias, chest pain and pleuritic chest pain - enlarged nodes, erythema nodosum, phlyctenular conjunctivitis, pleural effusion, formation of a Ghon complex, dactylitis. CXR shows Hilar adenopathy and/or pleural effusion. Right middle lobe collapse may complicate the adenopathy. It takes 2-12 weeks for tuberculin testing to become positive
• Miliary disease: Miliary tuberculosis (TB) is a form of tuberculosis that occurs when Mycobacterium tuberculosis spreads throughout the body via the bloodstream, leading to the formation of tiny, millet seed-sized tubercles (hence the name "miliary") in multiple organs. It represents a severe and disseminated manifestation of TB that can affect not just the lungs but also the liver, spleen, kidneys, brain, and other organs. Occurs in the elderly or malnourished patients. Night sweats and weight loss, Hepatosplenomegaly, weakness and feeling unwell. Cough - dry or productive, depending on lung involvement. Swollen lymph nodes. Shortness of breath if the lungs are extensively involved. CNS symptoms if the brain is involved, symptoms such as headache, confusion, or seizures may occur. Pathology shows yellow Caseous tubercles found in other organs. May involve bone and kidney which may take years to become apparent. Millet seed-like opacities on chest film < 5 mm. Choroidal tubercles, Meningitis. May be False negative tuberculin testing
• Post primary TB: There is now a degree of immunity developed with the primary infection. There is reinfection or reactivation of the disease in someone with pre-existing immunity. There are fever and night sweats. Malaise, weight loss and breathlessness, cough and sputum. Reactivation is seen with - HIV, alcohol, Age, malignancy, alcohol, immunodeficiency, malnutrition, use of immunosuppression, Anti TNF alpha drugs
• Pulmonary disease: Cavitatory disease with Parenchymal lung destruction with areas of necrosis leading to cavity formation. May be haemoptysis. Predominately apical disease with significant tissue destruction and fibrotic reaction. This is clinically detected as areas of consolidation and collapse and fibrosis. Right middle lobe collapse and Bronchiectasis "Brock's syndrome" due to localised lymphadenopathy. Bronchiectasis from airway obstruction and bronchostenotic lesions. Pleural disease usually seen as part of the primary disease or post-primary with an effusion. Is less common in later disease. Pneumothorax is uncommon but can happen

Extrapulmonary disease

• Lymphadenopathy: nodes can suppurate and forms sinuses and even fistulas. Most notable cervical nodes can be involved causing scrofula. Mediastinal nodes also commonly affected.
• CNS meningitis. Can present with headache, confusion, seizures and personality changes and the CSF shows a raised lymphocyte count and protein levels but smears rarely positive. Tuberculomas cause symptoms of raised pressure and localising signs and symptoms of a space-occupying lesion. Steroid therapy may be considered for CNS disease.
• Skin: lupus vulgaris and erythema induratum may be seen
• Cardiac: tuberculous pericardial effusion and constrictive pericarditis. Steroids may be indicated.
• Gastrointestinal:terminal ileal disease and subacute obstruction. Weight loss, peritonitis, ascites
• Genitourinary: can affect the kidney and lead to renal failure. Send early morning urines. Image with CT or IVU. Epididymitis, endometrial or tubal involvement and infertility.
• Adrenal: adrenal insufficiency
• Bone/Joints: Osteomyelitis, arthritis, paravertebral abscesses, vertebral collapse. Spinal cord compression. Classically Pott's disease of the spine due to TB infection of the vertebrae can cause cord compression and paraplegia or form a cold abscess which can track down to the psoas muscle.

General Investigations

• Bloods: FBC, U&E LFT's CRP and ESR - may suggest anaemia or ongoing inflammatory process or organ damage
• CXR: upper zone shadowing and cavitation seen with active infectious disease. There may be an older disease with fibrosis and calcification. The trachea may be displaced. There may be hilar lymphadenopathy. In (non-HIV) - patients - pulmonary TB cavitation is synonymous with infectivity. Those with HIV may be infectious without cavitation.
• Consider HIV test in all patients with TB
• ECG: pericardial disease shows low voltage and ST-T changes

Specific Investigations

Management

Management

Typical Dosing for 70 Kg male

Drugs used and Dose and Side effects: Always take expert help

Multidrug resistant tuberculosis

• Should be suspected in a representation of a previously treated case of Tuberculosis
• Contact with drug resistant TB
• Birth in a foreign country with more than 40 cases per 100,000
• HIV infection
• London residence
• Male
• Failed treatment - smear positive after 3 months treatment

TB AND HIV

• In patients with HIV the CXR changes may be less specific and the clinical picture less classical
• HIV infection with CD4+ T-cell counts 200-300 cells/mm3 tend to present as a secondary tuberculosis type picture with apical disease and cavitation as they are more immunocompetent
• HIV infection with CD4+ T-cell counts < 200 cells/mm3 tend to present as a progressive primary tuberculosis type picture with lower/mid lobe consolidation and lymphadenopathy.
• Mantoux tests can easily be normal in those with impaired delay type hypersensitivity and should not be relied upon
• There is atypical granuloma formation and pathological changes
• The length of anti-tuberculous treatment is the same as that used for non-HIV patients - treatment includes starting HAART and trying to minimise interactions between therapies. Rifampicin is the main drug with significant interactions.
• Chest X-Ray changes tend to be the lower zone with some occasional cavitation however there may be additional changes with consolidation, collapse, effusions and hilar lymphadenopathy
• Be aware of immune reconstitution inflammatory syndrome which can lead to a worsening in symptoms and signs several weeks after stating HAART
• Drug interactions between Anti TB therapy and HAART are significant and dual therapy should only be led by specialists