Problem 3.07- haemoptysis

• Haemoptysis


  Expectoration [coughing] of blood or blood-stained sputum derived from below the level of the glottis

  
• Pseudohemoptysis


  Expectoration of blood that comes from the upper respiratory tract and/or the upper gastrointestinal tract, can mimic hemoptysis

  
• Massive hemoptysis


  100–600 mL of coughed up blood in 24 hours

  
• Degrees of haemoptysis


  • No consensus for quantifying the degree of hemoptysis

  
• It is not the loss of blood that is usually the danger; rather, it is the hypoxia due to blood obstructing the larger airways and gas exchange surfaces
• Appearance of sputum and possible causes

  • Bright red blood or blood clots - Carcinoma of lung, TB, pulmonary embolism
  • Blood streaked, purulent sputum - Bronchitis, bronchiectasis, pneumonia
  • Blood-tinged, white, frothy sputum - Congestive heart failure
  • Foul-smelling, bloody sputum - Anaerobic lung abscess
  • Rusty Red - Pneumococcal pneumonia

  
• Review of systems should seek symptoms suggesting possible causes, including fever and sputum production (pneumonia); night sweats, weight loss, and fatigue (cancer, TB); chest pain and dyspnea (pneumonia, pulmonary embolism); leg pain and leg swelling (pulmonary embolism); hematuria (Goodpasture syndrome); and bloody nasal discharge (granulomatosis with polyangiitis)

  
• Respiratory causes of haemoptysis

  • Primary Lung carcinoma
  • Chronic bronchitis, usually an acute exacerbation
  • Pulmonary infarction (from pulmonary embolism)
  • Bronchiectasis
  • Lung abscess
  • Pneumonia
  • Tuberculosis
  • Fungal lung disease—usually Aspergillus: mycetoma, invasive fungal infection
  • Foreign body (aspirated)
  • Post-traumatic (lung contusion)
  • Vasculitic syndromes, e.g. Goodpasture's syndrome
  • Iatrogenic - transbronchial lung biopsy and ablative procedures, Pulmonary artery perforation is a rare complication of pulmonary artery catheter placement, occur after pulmonary vein isolation using cryoballoon ablation for atrial fibrillation

  
• Cardiovascular causes of haemoptysis

  • Mitral stenosis
  • Pulmonary edema due to left heart failure
  • Coagulopathy (thrombocytopenia or use of anticoagulants)
• Common causes of massive hemoptysis

  • Lung cancer
  • Bronchiectasis
• Bleeding disorder


  Coagulopathy → ↓ clot formation during mild trauma to mucosal lining of respiratory airways → mild hemoptysis

  
• Trauma


  1. Blunt force trauma → pulmonary contusion and hemorrhage, rib fracture → pulmonary laceration

  2. Foreign body → direct trauma or local inflammation from an inhaled foreign body
• Tuberculosis


  1. Active tuberculosis → Bronchiolar ulceration → necrosis of adjacent blood vessels → hemoptysis, Rupture of Rasmusen's aneurysm (aneurysm of pulmonary artery)

  2. Prior tuberculosis → Erosion of healed calcified lymph node (broncholith) → through bronchial artery → into airway → hemoptysis, Structural lung damage → bronchiectasis → hemoptysis

  
• Primary lung carcinoma


  Invasion of mucosa → erosion of small friable mucosal vessels → hemoptysis, Large central tumour → malignant invasion of central pulmonary vessel → massive hemoptysis

  
• Mitral stenosis


  ↓ left ventricular inflow → ↑ left atrial pressure → backflow to pulmonary circuit → ↑ resistance in pulmonary veins → Reversal of blood into bronchial veins → Rupture of pulmonary capillaries and veins, Rupture of bronchial varix
• Pulmonary embolus


  Embolus gets lodged → pulmonary infarction distal to occlusion → bleeding
• Bronchiectasis


  Chronic airway inflammation → hypertrophy and tortuosity of bronchial arteries rupture of blood vessels → rapid hemoptysis
• Cocaine-induced pulmonary hemorrhage


  Rupture of bronchial or tracheal submucosal blood vessels, or from injury to the alveolar-capillary membrane → diffuse alveolar hemorrhage
• Mycobacterium tuberculosis complex


  M. tuberculosis (Koch's bacillus), M. bovis (TB in cows), M. africanum (rare causes of tuberculosis in Africa), M. microti, M canneti, M pinnepedii

  
• Nontuberculous mycobacteria (NTM)


  All the other mycobacteria which can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, disseminated disease

  
• Mycobacterium tuberculosis features


  • Slightly curved, rod shaped bacilli
  • 0.2-0.5 µ in Diameter, 2-4 µ in Length
  • Resists decolourization with acid & alcohol (Acid fast)
  • Highly Aerobic that's why prefers apex of lungs
  • Facultative intracellular pathogen (Macrophage)
  • Multiplies slowly (generation time of 20 hours vs E.coli generation time of 20 minutes)
  • Lipid Rich (Wax like) Cell Wall confers resistance
  • Non motile, nontoxic, no spore
  • Can remain dormant for decades
  • Can be stained with carbol fuchsin by either alkalinization (Kinyoun) or heat (Ziehl-Neelsen) methods + Fite Stain + Fluorescence method- auramine-rodamine dye
  • Only infect humans
  • Identified in clinical specimens as an acid-fast bacillus (AFB)

  
• Bacilli in small droplet nuclei (1 to 5 µm in diameter) remain suspended in air for long periods and once inhaled can reach the airways, where only 1 to 5 organisms are sufficient to cause infection. Laryngeal involvement renders the patient highly infectious. Direct cutaneous inoculation ("prosector's wart") does occur

  
• Mycobacterium tuberculosis pathogenesis


  1. Facultative intracellular organism avoids being destroyed by macrophages by disrupting the attachment of lysosomes to phagosomes which allows them to proliferate and multiply within macrophages

  2. Proteins Inhibiting Antimicrobial Responses of the Macrophage - increasing in the resistance to host toxic compounds, arrest of the normal progression of the phagosome, avoidance of the induction of apoptosis

  3. Lipid Rich (Wax like) Cell Wall responsible for Acid fastness, slow growth, virulence, and drug resistance - made up of mycolic acid, Cord Factor (trehalose 6,6'-dimycolate, TDM), Proteins in cell wall, Polysaccharides

  4. Can remain dormant for decades allowing reinfection when host defense is weak

  5. Proteases destroy tissue or modulate the immune response by inactivation of host defense molecules such as immunoglobulins and complement components, regulate nutrient for bacteria by hydrolyzing hosts proteins

  6. Cell Envelope Proteins provide a special barrier responsible for many of the physiological and disease-inducing aspects of mycobacteria

  
• Stages of Mycobacterium tuberculosis infection

  • Primary: first exposure + infection
  • Secondary tuberculosis (Post primary tuberculosis): Reinfection (2nd exposure) or Reactivation of primary infection (endogenous)
  • Active disease: infection + sign & symptoms
  • Latent tuberculosis infection (LTBI): infected person without sign and symptoms, bacteria remain dormant after primary infection

  
• The progression to clinical disease in a previously unexposed, immunocompetent person depends on three factors: (1) The number of M. tuberculosis organisms inhaled, (2) The virulence of M. tuberculosis, (3) The development of anti-mycobacterial cell-mediated immunity

  
• How diabetes mellitus predisposes to tuberculosis infection

  Affects chemotaxis of macrophages/monocytes, phagocytic activity & antigen presentation, Insulin deficiency → impaired processing of Fc receptor bond material, ↓ INF gamma production from T cells → ↓ activation of macrophages & destruction by free radicals and NO, Can affect the pharmacokinetics of anti-TB drugs, especially rifampicin, by reducing their plasma concentrations

  
• How HIV predisposes to tuberculosis infection


  Immune deficit prevents patient from containing initial infection, HIV infected acquire MTB → activate disease within 2 weeks → inc motility, Extra pulmonary TB more common, HIV multiply in CD4+ T cells → selectively destroy them → ↓ TB fighting lymphocytes → no or less cellular immune function

  
• Tests for diagnosis of tuberculosis

  • Mantoux tuberculin skin test with purified protein derivative (PPD)
  • Interferon-gamma release assay (IGRA) with antigens specific for Mycobacterium tuberculosis
  • Sputum Smear for Acid-fast bacilli (AFB)
  • Sputum Culture
  • GeneXPert (Nucleic Acid Amplification Testing – NAAT) which also tests for Rifampicin resistance

  
• Advantages of IGRA compared with PPD

  Only a single patient visit required, Ex vivo tests, No booster effect, Independent of BCG vaccination
• Advantages of IGRA compared with PPD

  • Only a single patient visit required
  • Ex vivo tests
  • No booster effect
  • Independent of BCG vaccination
• Sputum collection for TB diagnosis

  1. Patients suspected of having TB should submit sputum for AFB smear and culture

  2. Sputum should be collected in the early morning on 3 consecutive days

  3. In hospitalized patients, sputum may be collected every 8 hours
• Early morning sputum


  Ideal for initial investigation for presumptive TB patients for GeneXpert (Nucleic Acid Amplification Testing – NAAT) which also tests for Rifampicin resistance

  
• Acid-fast bacilli (AFB) smear


  Stain takes 10 mins but requires at least 10,000 bacilli per mL, now new labs use more sensitive auramine-rhodamine fluorescent stain (auramine O)
• Culture


  • Access to the organisms may require lymph node/sputum analysis, bronchoalveolar lavage, or aspirate of cavity fluid or bone marrow
  • Obtaining the test results is slow (3-8 wk), and they have a very low positivity in some forms of disease
• Tests to be ordered for all newly diagnosed TB cases

  • Full Blood Count WBC count
  • Baseline Urea, Electrolytes and Creatinine
  • Baseline Liver Function Tests (AST, ALT, Bilirubin levels)
  • Random or Fasting Blood Sugar levels
  • Consented HIV test after counseling by a certified counselor

  
• Blood cultures


  Using mycobacteria-specific, radioisotope-labeled systems help to establish the diagnosis of active TB, should be used for all patients with HIV infection who are suspected of having TB

  
• HIV serology


  In all patients with TB and unknown HIV status identifies HIV antigen and/or antibody generated as part of the immune response to infection with HIV
• Nucleic Acid Amplification Tests

  • Deoxyribonucleic acid (DNA) probes specific for mycobacterial ribosomal RNA identify species of clinically significant isolates after recovery
  • In tissue, polymerase chain reaction (PCR) amplification techniques can be used to detect M tuberculosis -specific DNA sequences and thus, small numbers of mycobacteria in clinical specimens
  • Ribosomal RNA probes and DNA PCR assays allow identification within 24 hours
• Chest X-ray


  • May be helpful in assessing the extent of lung damage in complicated cases
  • It is also important in the diagnosis of tuberculosis in children and extra-pulmonary TB
  • When difficult to interpret X-rays, a CT Scan may be necessary to confirm TB disease
  • PA + lordotic view helpful

  
• Chest radiograph findings


  • Patchy or nodular infiltrate
  • Cavity formation - Indicates advanced infection and is associated with a high bacterial load
  • Noncalcified round infiltrates - May be confused with lung carcinoma
  • Homogeneously calcified nodules (usually 5-20 mm) - Tuberculomas; represent old infection rather than active disease
  • Miliary TB - Characterized by the appearance of numerous small, nodular lesions that resemble millet seeds on chest radiography