Flashcards in Respiratory Path Tute 2 Deck (6)
Autosomal recessive disease characterised by mutations to the CFTR gene on chromosome 7.
This gene encodes for Cl- transporter proteins – results in defects in Cl- transport.
CFTR also affects other ion channels and cellular processes on a tissue-specific basis.
Affect on lung
Other mucous membranes – e.g. GIT = constipation
Failure to reach growth milestones due to malnutrition
Salty Sweat noticed by mother
Caused by TB bacilli: Mycobacterium
• Micobacterium Bovis
• Micobacterium Africanum
• Mycobacterium Microti
Acid-fast bacilli, aerobil, non-motile, usually G+
THICK CELL WALL
TB is characterised by stages of ‘Primary Infection’ and ‘Post Primary’ progression or re-activation.
TB-causing bacteria is usually inhaled.
Is phagocytosed by macrophages, but not easily lysed due to its thick outer cell wall. Replicates in phagosomes. Lyes there for around 3-4 weeks.
Then, there is a Th1 response – Antibody formation (at theis stage mantoux testing is positive) – recruitment of macrophages. Because difficult to lyse, the body’s response is granulomatous formation.
Fibrocalcific nodules are formed aroung the central lesion of caseous necrosis. The causative agent may eventually die out (in which case all that remains is a scar) or remain viable in the caseous necrotic core of the granulomatous lesion
Primary TB is often asymptomatic in most people. May involve mild constitutional symptoms.
If immunosuppressed, may proress directly to post-primary TB. Only 5-10% of people progress to post-primary. Usually occurs later on in life when patient becomes immunocompromised. Post-Primary TB associated with higher mortality rate – 50%.
Post-primary TB: involves florid inflammatory response with the re-activation of previously latent bacilli. The reaction involves enlargement of the Primary lesion, and can lead to cavitation. The infection can spread, causing widespread parenchymal damage. The associated caseous necrosis may be coughed up, and sputum can contain the bacilli.
Post primary TB is associated with more serious symptoms, such as malaise, fever, night sweats, anorexia, haemoptysis, weight less, etc.
If infection not contained, the continued inflammation response and infection spread will cause extensive, and potentially irreversible (e.g. in the case of cavitation) lund damage.
Primary TB, if presents at all, may present with mild constitutional symptoms.
Post-primary TB tends to present with more serious symptoms, such as those just described.
Chest radiographs may show evidence of the dense caseous necrosis. Or of cavitating lesions.
Mantoux or tuberculin testing, etc.
Treatment: tends to be aggressive and prolonged. Primary TB may be treated with single Abx, but post-primary tends to be treated with multiple Abx. Recurrent TB has longer treatment: up to 24 months.
Maco and Micro Features
Pneumonia is characterised by the inflammation of the alveoli, leading to exudation of fluid into the interstitium and air spaces, leading to consolidation
Classification of Pneumonia:
Bronchopneumonia: Often affects more than one lobe. Areas of inflammation are patchy and diffuse, mainly centred around bronchi. Usually occurs in the very young or very old
Lobar Pneumonia: Tends to affect the whole lobe. Occurs more commonly in adults.
Pathogenesis (reflects macro appearance)
Consolidation phase: Within 24 hours. Acute inflammatory response causes outpouring of protein rich fluid into the alveolar air spaces. Neutrophils are also present. Associated with venous Congestion.
Red Hepatisation: Last a few days. Massive accumulation of neutrophils, fibrin and extravasated RBCs. This gives a red appearance. Lung is red, consolidated (form, airless) – appears like a liver
Grey Hepatisation: Lysis of RBCs, further fibrin accumulation. Grey, solid looking, congested lung
Resolution: Typically occurs 8-10 days after onset. Involves reabsorption of exudates and debris by macrophages. Exudate may also be coughed up. Failure to cough up / absorb exudate can lead to organisation and fibrosis.
Macro: Whole-lobe (lobar) or diffuse, patchy, surrounding bronchi (bronchopneumonia) consolidation. Red hepatisation is red, grey hepatisation is grey. In both the lung appears solid, firm and airless.
Microscopic appearance: Exudate, protein rich fluids, neutrophils, macrophages (later, when absorbing the exudate).
ARDS and DAD.
Macro and Micro Features
Aetiology of ARDS:
ARDS is characterised by an acute onset of dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. ARDS occurs in response to any form of diffuse / severe lung injury.
Aetiology: severe lung injury. E.g. due to DIC, sepsis, trauma, inhaling hot fumes/smoke/ash.
Histologically, ARDS is defined as DAD – Diffuse Alveolar damage.
The lung injury is mediated by an acute inflammatory response, which causes damage to the alveolar walls and or capillaries. The inflammatory response involves endothelial activation, increased vascular permeability, sequestration of neutrophils. Loss of diffusion capacity occurs as a result of the diffuse damage to alveolar walls and capillaries. Surfactant loss occurs as a result of damage to Type II Alveolar cells. The resultant exudate from the response, and tissue diffuse tissue destruction, normally results in scarring, producing chronic disease
DAD: Micro: Alveolar walls become lined with wax hyaline membranes. Fibrin Deposition. Inflammatory cell infiltrate. Organisation of the fibrin exudate normally results in intra-alveolar fibrosis. Marked thickening of the alveolar septae. Resolution is rare.
Macro: consolidated, oedematous lung.
Clinical course: Mortality aroung 40-60%. Hospitalisation is usually already occurring due to underlying cause. Profound tachypnoea and dyspnoea, cyanosis, hypoxia, respiratory failure, bilateral infiltrates.
**Acute Interstitial Pneumonia = DAD without known cause
Classification of Lung Cancers
Maco and Micro Features
Classification of Lung Cancers are broadly divided into Small Cell Lung Cancer (SCLC) and Non Small Cell Lung Cancer (NSCLC).
SCLC = only SCLC
NSCLC includes squamous cell carcinoma, adenocarcinma and large cell carcinoma.
The distinction is important because the treatment differs.
Squamous Cell = Arises from squamous cells (thus associated with smoking, arising due to squamous metaplasia). Associated with bronchi, more proximally.
Adenocarcinoma = Arises from glandular tissue. Arises peripherally.
Large cell = Undifferentiated tumours arising from transformed epithelial cells
Small cell = Undifferentiated tumour arising from primitive looking cells (very little cytoplasm)
Most Lung Cancers arise proximally in association with the larger bronchi. The exception is Adenocarcinoma which arises more peripherally.
Regardless of histological subtype = irregular, homogenous tumours grey, yellow, white in colour. Mucin and haemorrhage may be associated, and necrosis. Infiltration into surrounding tissue is common. Downstream consolidation oneumonia may occur secondarily to bronchial obstruction.