4. Pathophysiology of Respiratory Conditions Flashcards
Possible sites of impaired respiratory function
- Lung & chest wall
- Airways
- Blood gas interface
- Control of breathing
Examples of impaired respiratory function
Elastic behaviour of lungs: Respiratory distress syndrome
Airway resistance:
- Airway obstruction: COPD
- Bronchial smooth muscle tone: Asthma
Diffusion: Pulmonary oedema
Regulation of ventilation: Hyper- & hypoventilation
Ventilation/perfusion mismatch - shunt, pneumonia
Partial pressure of blood gases - hypoxemia
Gas transport & the oxyhemoglobin equilibrium - anaemia
Blood gas interface: Ventilation & Perfusion
Ventilation & Perfusion must be well matched to ensure blood gases & tissue oxygenation
What if the Pip is not “negative”?
A collapsed lung occurs due to the loss of the negative intrathoracic pressure - results in loss of elastic recoil function: PNEUMOTHORAX
Clinical example: Open pneumothorax (collapsed lung) secondary to trauma
The negative intrathoracic pressure generated on inspiration causes air to flow into the lungs through the airway & into the intrapleural space through the chest wall defect
Air in the pleural space will press on the lung, which can then partially or fully collapse causing dyspnoea
If air builds up in the pleural space, it can push against the heart or the aorta - tension pneumothorax: MEDICAL EMERGENCY
Compliance
High compliance means that the lung & chest wall expand easily
Low compliance means they resist expansion
Compliance is related to elasticity & surface tension
Lungs normally have high compliance & expand easily because elastic fibres in lung tissue stretch easily & surfactant in alveolar fluid reduces surface tension
Decreased compliance - Lung are more difficult to expand
Common feature of pulmonary conditions:
- With scarred lung tissue (e.g. tuberculosis)
- That cause lung tissue to become filled with fluid (e.g. pulmonary oedema)
- That produce a deficiency in surfactant, or
- With impeded lung expansion (e.g. paralysis of the intercostal muscles
Respiratory distress syndrome
A deficiency in surfactant in premature infants causes respiratory distress syndrome
The surface tension of alveolar fluid is greatly increased, so that many alveoli collapse at the end of each exhalation
Great effort is then needed at the next inhalation to reopen the collapsed alveoli
- Surfactant reduces surface tension at the next inhalation to reopen the collapsed alveoli
- The more premature the newborn, the greater the change that RDS will develop
- Treated prior to birth by giving mother steroids to mature lungs
Increased work of breathing - Restrictive diseases
Elastic work increased e.g. fibrosis, pulmonary congestion
Elastic work refers to the work of the intercostal muscles, chest wall & diaphragm
Resistance to airflow (R)
- R varies inversely with airway radius
- So R is highest in airways of smallest r
- But flow is spread amongst many small airways in parallel
- So TOTAL R is lowest in smallest airways
Asthma
Bronchiolar constriction (small r), therefore increased R, and this, increased P to achieve VT - Increased muscular effort i.e. WORK
Triggers of an asthma attack:
- Exposure to an allergen (pollen, dust mites, cockroaches)
- Irritants in the air (smoke, chemical fumes, strong odours)
Zones in the respiratory system
Conducting zone: Generations 0 - 16
- Cartilaginous (0 - 11)
- Non-cartilaginous (12 - 16)
Respiratory Zone: Generations 17 - 23
- Respiratory bronchioles (17 - 19)
- Alveolar ducts (20 - 22)
- Alveolar sacs (23)
Chronic Obstructive Pulmonary Disease (COPD)
Emphysema: Destruction of lung tissue around alveoli makes them collapse on expiration
Bronchitis: Increased mucus build up in the airways due to cilia loss/impairment
Work of breathing is increased
Emphysema
- Destruction of elastic tissue & structural elements in the lungs so the lungs are more compliant
- Loss of lung elasticity (stiffness) results in compromised passive deflation of lungs (expiration)
Hypo- & Hyper-Ventilation
- Controlled by arterial chemoreceptors that sense PaCO2, with voluntary control occurring as well
- Chemoreceptors are located in the aortic arch & the central brainstem
Mis-matches in ventilation can cause hypoxemia & respiratory acid/base disturbances
Blood gas interface - hypoventilation:
Consequences of hypoventilation:
Diminution of O2 in the alveoli
- Decrease of PAO2 & therefore PaO2
Accumulation of CO2 in the alveoli
- Increase of PA CO2 & PaCO2
- Decrease of arterial pH: Respiratory acidosis
+ Eventually: Acidotic coma
Drug induced hypoventilation:
- Reduced rate & depth of breathing - therefore a mismatch with metabolic demand
- Results in hypoxemai - reduced arterial blood oxygen
- May be induced inadvertently by drugs, such as morphine
Blood gas interface - hyperventilation
Consequences of hyperventilation:
Accumulation of O2 in the alveoli
- Increase of PAO2 & PaO2
Decrease of CO2 in the alveoli
- Decrease of PACO2 & PaCO2
- Increase of arterial pH: Respiratory alkalosis
+ Eventually: Alkalotic coma
Diffusion between Alveolar Air & Blood
Pulmonary oedema: Fluid in the interstitial space increases the diffusion distance between the alveoli & pulmonary capillaries
V̇O2 = DL x (PAO2 - PCO2)
Ventilation-Perfusion Ratio - Gravitational effects
Blood flow: When standing blood flow from the base (bottom) to the apex (top) of the lungs due to gravity
Ventilation: Decreases from the base to the apex of the lung but to a much lesser extent than blood flow due to gravity
Ventilation-Perfusion Ratio
V̇/Q ratio takes into account regional variations in V̇A & capillary perfusion
Blood flow:
- At the apex, low arterial pressure in the pulmonary circulation tend to collapse the small vessels: Increase in resistance & Decrease in blood flow
- At the base, higher pressure distends vessels: Decrease in resistance & Increase in blood flow
Shunt: Ventilation-Perfusion mismatch
“Shunt” is when blood enters the arterial system without going through the ventilated areas of the lung
Results in hypoxaemian
Very large shunt
- Usually only a very small % of total cardiac output (Qs/QT)
- Venous to arterial (right to left) circulatory shunts may result in severe hypoxaemia
- Most commonly arises from congenital heart abnormalities
Regional decrease in ventilation
Decrease in ventilation in a group of alveoli will result in PCO2 increasing & PO2 decreasing
Pulmonary hypoxic vasoconstriction
Decreased tissue PO2 around under ventilated alveoli constricts their arterioles, diverting blood to better ventilated arterioles
Transport of O2 in blood bound Hb
- Hb molecule made up of 4 subunits (2 alpha & 2 beta globins) each with 1 ham (porphyrin compound) at the centre
- Each haem contains a Fe2+ iron atom that can combine with O2
- Exists as oxyhemoglobin, de-oxyhaemoglobin
- [Hb]blood = ~150 g/L
- Mw = 64.5 kD
- Therefore ~2mM (Mw x Molarity = g/L)
Oxygen transport: In lung capillaries (flat region)
Oxygen dissociation curve: Hb is well saturated across a wide PAO2 range
Oxygen transport: In tissues (steep region)
Capillaries offload large volume of O2 with only a small drop in Po2
Transport of O2 in Blood Bound Hb - Rightward shift
Shifted to the right by:
- Increase in temp
- Decrease in pH (i.e. increased [H+]
- Decrease in PCO2
- Increase of 2,3-DPG (result of chronic hypoxia)
Rightward shift in curve increases off-loading of O2 in tissues - all occur during exercise
Oxygen content of blood
O2 content is the sum of the O2 combined with Hb + O2 that is physically dissolved
What is the O2 content of arterial blood from a healthy person with [Hb] of 150 g L-1? (PaO2 ~100 mmHg)
Physical dissolved = 3 mL O2 L blood-1 100 mm Hg-1
Bound to Hb = 1.34 mL O2 g-1 Hb (x 150)
Total O2 Content = 204 mL Lblood-1
Transport of CO2 in the blood
~7% as CO2 in simple solution
~23% as HbCO2 (carbaminohaemoglobin)
As H2CO3 {CO2 + H2O ⇌ H2CO3} with carbonic anhydrase (CA)
~70% as HCO3- {H2CO3 ⇌ H+ HCO3-}
COVID-19 Acute Respiratory Syndrome
- The lungs of COVID-19 patients consist of severe endothelial injury associated with the presence of intracellular virus & disrupted cell membranes
- Some patients will develop ARDS & require mechanical ventilation
- COVID-19 patients with reduced respiratory system compliance combined with increased D-dimer concentrations have high mortality rates
- D-dimer is released when a blood clot breaks down
