lecture 12 - pulmonary infections Flashcards
What are the mechanisms of evading pulmonary defences
Attachment to and entry into epithelial cells in LRT
Release of toxins - enhance infection by impairing ciliary activity
Resistance to killing phagocytosis
Define URTI
Upper Respiratory Tract Infection
- sore throat, tonsillitis, pharyngitis, laryngitis, sinusitis and common cold
- mostly caused by viruses
Define LRTI
Lower Respiratory Tract Infections
- Infection of lung tissue -> pneumonia or TB
Mostly caused by bacteria some virus
Describe the etiology of pneumonia
Infection of lung tissue
- compromised immune system
- compromised local defences (loss or suppression of cough reflex, ciliary impairment, thick mucus obstruction, interference with phagocytes (macrophages), pulmonary congestion and edema, preceding URTI
Describe lobar pneumonia
Entire lung lobe affected
Describe bronchopneumonia
Infection in bronchi and bronchioles - spreads to adjacent lung tissue in patchy manner - no necessarily confined to one lobe or lung
Describe classification by etiological agent
- Determines treatment
- Can’t always be identified
Describe classification by clinical setting
- Narrows down suspected organisms
(CA, HA, Aspiration pneumonia, immunocompromised hosts)
Describe Community Acquired (CA) pneumonia
Bacterial or viral - follows URTI (viral) - lobar or broncho
- Streptococcus pneumoniae most common (90-95% cases)
- haemophilus influenza, staph aureus, mycoplasma pneumoniae
What are the stages of lobar pneumonia
- Congestion (day 1)
- Red hepatization (days 2-4)
- Grey hepatization (days 5-8)
- resolution
Describe the congestion stage
Dilated and congested capillaries in alveolar walls
Proteinaceous, fibrin rich fluid in alveolar spaces(increased permeability)
Describe the red hepatization stage
Fibrous exude, neutrophils and RBC in alveolar spaces (solid alveoli)
Capillaries still congested
Describe the grey hepatization stage
Fibrinous exudate has macrophages and few neutrophils
- Macrophages contain hemosiderin (brown haemoglobin derived pigment from phagocytosis of extravasated RBC)
Alveolar wall congestion subsided
Describe the resolution stage
Enzymatic digestion of exudate occurs - expectoration and phagocytosis (macrophages)
What ae the complication of bacterial pneumonia
In elderly and already ill
- pleural effusion
- empyema (puss build up)
- lung abscess (necrotic core)
- Respiratory and circulatory failure (ARDS)
What is Acute Respiratory Distress Syndrome (ARDS)
Rapid wide spread inflammation in lungs
- injury of pneumocytes and pulmonary endothelial cell activation -> increased capillary permeability and fibrin-rich fluid fills alveoli
- 40% mortality rate - decreased quality of life common
Describe Community Acquired (CA) viral pneumonia
- Usually cause URTI but may spread to LRT
- ‘atypical pneumonia’ (viruses) - inflammatory exude in alveoli walls rather than spaces and predominantly mononuclear cells instead of neutrophils (some bacteria may cause)
What are the predisposing factors of CA pneumonia
Extremes of age, malnutrition, chronic diseases
Describe Tuberculosis
Caused by Mycobacterium tuberculosis
- transmits through prolonged contact (cough, sneeze etc.) - latent or extrapulmonary TB can’t be transmitted
Describe Mycobacterium tuberculosis
- Aerobic bacillus (fast-acid - resists gram stain)
- Lipid capsule
- Visualised in Ziehl-Neelsen stain (pink)
- Better detected by PCR
Describe TB response 3 weeks after infection
T-cell mediated response
- Enter hilar (draining) lymph nodes - presented to APC and T cells differentiate into TH1 cells
- Produce IFN- gamma - activates macrophages and enhances bactericidal power
- Macrophages (‘epithelioid cells’)secrete TNF -> further monocyte and macrophage recruitment - aggregate to form TB granulomas
- Granulomas develop central caseous necrosis - tissue damage as result of immune response and cytokine release
Describe the TB granuloma
- Specific type of chronic inflammation (can be formed in reaction to foreign body)
- Persistent activation of T cell-mediated response by difficult to irradiate organism
What makes up a TB granuloma
Healing attempted around granuloma (fibrosis)
‘Collar’ of activated T lymphocytes
Activated macrophages (epithelioid cells)
Giant cells (fusion of multiple macrophages)
Necrosis - caseous necrosis
Describe primary infection of TB
Ghon focus - develops granulomas and caseating necrosis (TH1 response)
- Deep in midzone of lung
Hilar lymph nodes involved in initial infection also develop granulomas and caseation
Together Ghon complex
What are the 3 outcomes of primary TB infection
- Acquired immunity (90%) - TH1 response halts infection -> killing of organism and Ghon complex heals by fibrosis (calcified detection on X-ray)
- Latent TB - remain dormant waiting to reactivate when host immunity drops
- Progressive primary TB - infection progresses and ongoing immune response -> extensive caseation necrosis and lung tissue damage (mostly immunosuppressed/elderly)
What is secondary TB (chronic)
Reactivation or re-exposure to bacilli in previously sensitized host -> rapid mobilization of vigorous immune reaction
-> large granulomas with extensive tissue damage - massive central caseous necrosis surrounded by fibrosis
Where are secondary lesions usually
Apical parts of lungs - oxygen tension is highest (aerobic bacteria)
Why is secondary TB also called ‘cavitary’
extensive tissue destruction can destroy adjacent bronchial walls -> coughing up of bacteria-laden caseous material, leaving empty cavities in lungs
- ‘open’ lesions are infectious
Describe the diagnosis of active TB
- identifying M. tuberculosis in clinical sample (definitive)
- Clinical findings (cough, sputum, fever etc.)
- Chest X-ray (Indicative)
- Mantoux test (TST) or Interferon-Gamma Release Assay (IGRA)
Does the TST differentiated between latent and active
No - active diagnosed through presence of symptoms
Describe false negative/positive TST results
False-negative - viral infections, malnutrition or immunosuppression
False-positive - prior BCG vaccination
Go over IGRA
- blood test
- measures immune reactivity (TH1 cells) - produce interferon-gamma
- should remain positive after successful treatment
less likely to give false-positive
What is the treatment of TB
- multiple-drug therapy
- 2 phase for active
- intensive - bactericidal (4 drugs for 2 months)
- Confirmation - sterilization (2 drugs for 4 months)
- latent - one over 9 months (under 40)
- Second-line antibiotics available for multi-drug resistant TB
