Pathophysiology

• Respiratory system & associated disorders

  • Lung tumour
  • Respiratory control centre
  • Stroke
  • Opiates
  • Tumours
  • Raised intra-cranial pressure
  • Head Injury
  • Neuro-muscular
  • Multiple sclerosis
  • Poliomyelitis
  • Lesions of motor neurons
  • Chest wall
  • Trauma
  • Pneumothorax
  • Surgery
  • Ventilation
  • Asthma
  • Bronchitis
  • Bronchiolitis
  • Cystic fibrosis
  • Inhaled foreign body
  • Gas transfer
  • Emphysema
  • Oedema
  • Pulmonary thromboembolism
  • Heart failure
  • Sickle cell anaemia
• Pathologies affecting the respiratory system
• Respiratory failure


  Respiratory system fails in one or both of its gas exchange functions: (oxygenation and carbon dioxide elimination) due to dysfunction of one or more essential components of the respiratory system
• Essential components of the respiratory system

  • Chest wall (including pleura and diaphragm)
  • Airways
  • Alveolar – capillary units
  • Pulmonary circulation
  • Neuromuscular interaction
  • CNS (brain stem)
• Respiratory failure not appropriately treated

  Progressive deterioration = cardiac arrest
• Hypoxemic respiratory failure (Type I)

  Most common type of respiratory failure, associated with acute diseases of the lung, PaO2 of less than 8 kPa (<60mmHg), PaCO2 either normal or low
• Common causes of hypoxemic respiratory failure

  • Cardiogenic pulmonary oedema
  • Non-cardiogenic pulmonary oedema (e.g. ARDS)
  • Pneumonia
  • Pulmonary embolism
  • Pulmonary hypertension
• Hypercapnic respiratory failure (type II)

  PaCO2 more than 6.7 kPa (>50mmHg), hypoxemia is also common if patients not on supplementary oxygen
• Common causes of hypercapnic respiratory failure

  • Severe asthma
  • Chronic bronchitis and emphysema (COPD)
  • Drug overdose – e.g. opiates
  • Neuromuscular diseases – myasthenia gravis
  • Chest wall abnormalities
• Types of respiratory failure

  • Acute
  • Chronic
  • Acute on chronic e.g. acute exacerbation of COPD
• Pathophysiological Events in Respiratory Failure

  • Ventilation/Perfusion (V/Q) mismatch
  • Shunting (Severe V/Q mismatch)
  • Diffusion limitation (i.e. respiratory membrane is thickened/destroyed)
  • Hypoventilation (decreased minute ventilation relative to demand due to airway failure)
• Ventilation-Perfusion (V/Q)


  Relationship between ventilation and perfusion in the alveolus
• In healthy lungs ventilation approximately matches perfusion
• Ventilation-Perfusion (V/Q) mismatch


  Any pathology affecting ventilation e.g. COPD can cause a mismatch between ventilation and perfusion (low V/Q), any pathology affecting perfusion e.g. heart failure can cause a mismatch between ventilation and perfusion (high V/Q)
• Shunt


  Under-ventilated areas of the lungs can lead to a shunt where venous blood returns to the heart without collecting its normal oxygen quota, hypoxemia caused by a shunt may be more difficult to correct by supplementary oxygen administration
• Causes of shunt


  • pneumonia
  • atelectasis
  • severe pulmonary oedema
• Normal lung with normal V/Q, oxygenated blood emerges from pulmonary capillaries
• Shunt in lung with low V/Q, deoxygenated blood emerges from some pulmonary capillaries reducing SATS
• Cardiogenic Pulmonary Oedema


  Left Ventricular Failure (LVF) - generally as a consequence of MI but can also be consequences of diseases of heart valves, failures in conduction system of the heart, neurogenic shock, a reduction in stroke volume (SV) triggers compensatory mechanisms
• Cardiogenic Pulmonary Oedema


  Compensatory mechanisms triggered by a fall in BP further damages the heart, the myocardium can become distended and contraction weakens, ejection fraction is reduced considerably so the left side of the heart becomes congested with blood, ventricular diastolic pressure increases and blood return from the lungs is impeded
• Poor pumping by damaged left ventricle causes blood to back-up pulmonary veins into lungs
• Increase in hydrostatic pressure results in pulmonary oedema
• Symptoms and Signs of Pulmonary Oedema

  • Difficulty breathing
  • Anxiety
  • Pale skin
  • Pink frothy sputum
  • Hypoxia
  • Orthopnoea (inability to lie down flat due to breathlessness)
  • Oedema of ankles in later stage
• Acute Respiratory Distress Syndrome (ARDS)


  ARDS is as a result of acute lung injury which lead to increased vascular permeability causing pulmonary oedema, ARDS is a form of non-cardiogenic pulmonary oedema that can quickly lead to acute respiratory failure, fluid accumulates in the lungs interstitium, alveolar space, and small airways, causing the lungs to stiffen, this impairs ventilation and gas exchange- Therefore, it reduces oxygenation of blood
• ARDS is a life-threatening clinical syndrome of progressive respiratory insufficiency associated with a high mortality rate
• ARDS


  Characterised by acute, severe hypoxia which is not caused by left ventricular heart failure, there is an imbalance of pro-and anti-inflammatory mediators causing acute inflammatory injury to the alveolar epithelium and blood vessels, neutrophils and their products have a crucial role in the pathogenesis of ARDS
• Causes of ARDS


  • Pneumonia
  • Aspiration of gastric secretion
  • Drowning
  • Pulmonary embolism
  • Trauma (severe chest injury)
  • Inhalation injury (e.g. smoke inhalation)
  • Sepsis
  • Massive blood transfusion reaction
  • Acute pancreatitis
  • Severe burns
• Phases of ARDS


  • Exudative phase (first 24 hrs) with hypoxaemia, leakage of fluid into the alveoli plus haemorrhage and infiltration of neutrophils
  • Proliferative phase (14 days after the injury) persistent hypoxaemia, and reduced lung compliance (decreased surfactant), thrombi form in the small blood vessels of the lungs
  • Fibrotic phase (3 weeks into injury) widespread pulmonary fibrosis, loss of the normal lung structure and worsening lung compliance
• Chest Radiograph of ARDS shows diffuse bilateral opacities, compared to a healthy lung
• Impaired defence mechanisms that may lead to Respiratory infection e.g. pneumonia

  • Loss or suppression of cough reflex
  • Too much mucus production and accumulation
  • Injury to the cilia
  • Interference with phagocytic action of alveolar macrophages
  • Pulmonary congestion and oedema
• Pneumonia


  Inflammation of the lung parenchyma, may affect a single lobe or many lobes (multi-lobular), or interstitial, alveolar space fill with exudate, inflammatory cells, and fibrin (Pus)
• Causes of Bacterial Pneumonia

  • Streptococcus pneumoniae (pneumococcal pneumonia)
  • Mycoplasma pneumoniae
  • Haemophilus influenzae
  • Klebsiella pneumoniae
  • Staphylococcus aureus
• Causes of Viral Pneumonia

  • Influenza virus
  • Respiratory Syncytial Virus (RSV)
• Symptoms of Pneumonia


  • Cough with phlegm (pus) often green/yellow or brown or blood-stained mucus, may be malodorous (esp. anaerobes)
  • Fever and chills (sweating and shivering)
  • Shortness of breathe/faster-shallow breathing
  • Chest pain which gets worse when breathing or coughing
• Complications of Pneumonia


  • Pleural effusion/pleurisy
  • Dyspnoea (breathing difficulties)
  • Sepsis (spread of the infection into blood)
• COPD


  Chronic Obstructive Pulmonary Disease, a progressive chronic respiratory diseases that limit air flow and gas exchange, usually progressive and is associated with inflammation of the lungs as they respond to noxious particles or gases, potentially preventable with proper precautions and avoidance of precipitating factors, treatment is more symptomatic
• Conditions included under COPD

  • Chronic Bronchitis (chronic inflammation of bronchi, excess mucus production, chronic productive cough)
  • Emphysema (abnormal permanent enlargement of the airspace distal to terminal bronchiole due to damage to alveolar wall, chronic cough)
• Smoking is the primary risk factor for COPD, long-term smoking is responsible for 80-90 % of cases, smokers are 10 times more likely to die of COPD compared to non-smokers
• Other Risk Factors for COPD

  • History of childhood respiratory infections
  • Possible genetic link to Alpha-1-antitrypsin deficiency
  • Increasing age
• COPD is one of the most common respiratory diseases in the UK, it usually starts to affect people over the age of 35, although most people are not diagnosed until they are in their 50s, an estimated 1.2 million people are living with diagnosed COPD