VIVA: Physiology - Respiratory Flashcards
What are the initial physiological responses to high altitude?
3/5 to pass:
- Hyperventilation: decreases CO2 > O2
- Alkalosis: limited by movement of bicarbonate from CNS (1-2 days) and renal excretion of HCO3-
- Increased 2,3-DPG: R shift O2-Hb dissociation curve (early), then L shift at higher altitudes due to alkalosis
- Alveolar hypoxia induces pulmonary vasoconstriction, then pulmonary HTN
- Decreased work of breathing
What are the longer-term physiological effects of altitude exposure?
3 to pass:
- Polycythaemia
- Increased viscosity of blood
- Increased O2 carriage
- Pulmonary HTN resulting in RVH
- More capillaries
- Increased oxidative enzymes
- Increased mitochondria
Describe factors affecting airway resistance
In laminar flow, resistance is proportional to the length * of the tube and viscosity *, and inversely proportion to fourth power of the radius * of the tube (as per Poiseuille’s Law *: R = 8 x L x viscosity / n x radius^4)
- Turbulent flow is most likely to occur at high Reynold’s numbers: that is, when inertial forces dominate over viscous forces (Reynold’s number = density x diameter x velocity / viscosity)
- Resistance is highest in medium-sized bronchi and low in very small airways
- Airway resistance decreases as lung volume rises because the airways are then pulled open by radial traction
- Bronchial smooth muscle is controlled by the autonomic nervous system: stimulation of B-adrenergic receptors causes bronchodilation, reduced alveolar pCO2 causes increased resistance
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Define dynamic compression of airways and its effects on flow
- Intrapleural pressure > alveolar pressure causes airway compression
- Dynamic compression of airways limits airflow during forced expiration
How is carbon dioxide transported in the blood?
Percentages for arterial blood:
1. Dissolved (5-10%):
- CO2 20x more soluble than O2, therefore dissolved CO2 plays a significant role in its carriage
- 10% of gas evolved into the lung from blood is in dissolved form
2. Bicarbonate (90%) *:
- Formed by sequence CO2 + H20 <-> H2CO3 <-> H+ + HCO3- (first step aided by carbonic anhydrase)
3. Carbamino compounds (5%):
- Combination of CO2 with terminal amine groups in blood proteins
- Most important is globin in haemoglobin: reduced Hb binds more CO2 as carbaminohaemoglobin than HbO2
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What is the chloride shift?
Hamburger effect:
- Ionic dissociation of carbonic acid results in HCO3- and H+ formation within the red cell
- HCO3- diffuses out but H+ cannot as the cell membrane is relatively impermeable to cations
- To maintain electrical neutrality, Cl- ions move into the cell from the plasma
- Cl- levels thus lower in systemic venous blood than systemic arterial blood
Describe how respiration compensates for acid-base changes
- CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
- Rapid responder
- Respiratory centre responds to H+, mainly at peripheral chemoreceptors but also transferred to CSF by CO2
- Metabolic acidosis triggers increased ventilation, decreasing CO2 -> decreased H+ and HCO3- (base deficit)
- Metabolic alkalosis triggers decreased ventilation, increasing CO2 -> increased H+, increased HCO3- (base excess)
- In reality there is often no compensation
What clinical conditions might cause metabolic acidosis? Metabolic alkalosis?
Metabolic acidosis: DKA (due to lactic acid)
Metabolic alkalosis: vomiting (due to loss of acid)
Describe the factors that determine the airway resistance in the lung
Decreases with:
- Stimulation of B-adrenergic receptors causing bronchodilation
Increases with:
- Parasympathetic nerve stimulation causing bronchoconstriction
- Histamine
- Reduction in lung volume
- Decreased pCO2
- Increased density and viscosity of gas
With regard to lung compliance, give examples of diseases that reduce compliance
3 to pass:
- Pulmonary fibrosis
- Pulmonary oedema
- Pulmonary haemorrhage
- Atelectasis
- Loss of surfactants (e.g. respiratory distress syndrome)
What factors cause turbulent flow in airways?
Expressed by Reynold’s number:
- Reynold’s number = fluid density * x diameter * x velocity of flow * / viscosity *
- Laminar flow only occurs in small airways, transitional in most areas, turbulent in trachea (especially with rapid breathing)
*3/4 needed to pass
What factors affect the radius of the airway?
- Bronchial smooth muscle (under control of sympathetic and parasympathetic activity)
- Lung volume
Describe the symptoms of acute mountain sickness
- Headache
- Fatigue
- Dizzy
- Palpitations
- Nausea
- Loss of appetite
- Insomnia
What is the alveolar gas equation?
Useful formula to measure the relationship between the fall in pO2 and the rise in pCO2 that occurs in hypoventilation (a useful measure of the V/Q inequality)
PAO2 = FiO2 x (Patmos - PH2O) - (PaCO2 / RQ) + F
Where:
- PAO2 is the alveolar oxygen partial pressure
- PiO2 is the partial pressure of inspired oxygen (fraction of inspired oxygen 21% multiplied by difference between atmospheric pressure 760mmHg and water vapour pressure 47mmHg in the alveolus, usually comes to ~149mmHg)
- PaCO2 is the arterial CO2 partial pressure
- RQ is the respiratory quotient (CO2 production:O2 consumption, typically 0.8)
- F is a small correction factor for inert gases (typically 2mmHg and can be ignored)
How do you calculate the alveolar-arterial gradient?
Difference between PAO2 (alveolar oxygen partial pressure) and PaO2 (arterial oxygen partial pressure)
What is the physiological significance of the A-a gradient?
V/Q mismatch (e.g. shunting or dead space)
What is the role of central chemoreceptors in control of ventilation?
- Located near ventral surface of medulla
- Rise in blood CO2 increases CO2 in CSF *
- CSF has poor buffering capacity so pH changes rapidly
- Liberated H+ ions stimulate chemoreceptors (increasing pH has reverse effect) *
- Efferents stimulate medullary respiratory centre to increase ventilation and return CO2 to normal *
- Chronic CO2 elevation gives normal CSF pH and insensitivity
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What is the role of peripheral chemoreceptors?
3/5 to pass:
- Located in carotid and aortic bodies that have high blood flow
- Respond mostly to decrease in O2 below 100mmHg
- Impulses transmitted to respiratory centre to increase ventilation
- Responsible for all of the ventilatory response to hypoxaemia
- Also responsible for small but rapid response to rise in CO2 and decrease in pH (carotid bodies)
What is the role of red blood cells in CO2 transport?
1/3 to pass:
1. Carbonic anhydrase:
- Only found significantly in red cells
- Role in major buffer for CO2 and H+
2. Haldane effect:
- Hb (particularly deoxy) is also a major H+ buffer allowing increased/faster H+/HCO3- dissociation
- Cl- shift is mediated by Band 3 Cl- transporter in RBC membrane, and allows 70% HCO3- diffusion into plasma, maintaining ionic neutrality
3. Hb protein:
- Major carbamino protein (better when deoxyHb as more negative charge)
What is the Haldane effect?
- H+ + HbO2 <-> H+-Hb + O2
- DeoxyHb binds more H+ than oxyHb and forms carbamino compounds more readily
- Binding of O2 to Hb reduces its affinity for CO2
- Enhances removal of CO2 * from O2-consuming tissues (e.g. muscles) into the blood
- Promotes dissociation of CO2 from Hb in the presence of O2 * (e.g. the lungs) which is vital for alveolar gas exchange
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Draw and explain the carbon dioxide dissociation curve
What is pulmonary compliance?
- Compliance = volume change / pressure change *
- Maximal in mid-inspiration
- Lower at extremes
- Approximately 200ml/cm H2O
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What factors decrease or increase pulmonary compliance?
Decreased (3 examples):
- Alveolar oedema
- Pulmonary fibrosis
- Pulmonary venous hypertension
- Unventilated lung
Increased (1 example):
- Age
- Emphysema
What are the physiological effects of surfactant of the lung?
2/4 to pass:
- Increased lung compliance
- Reduced work of breathing
- Improved stability of alveoli
- Keeps alveoli dry
What are the main determinants of compliance of the thorax?
- Surface tension of the alveoli (2/3)
- Elastin/collagen fibres (1/3)
- Alveolar surface tension depends on alveolar pressure, alveolar radius, surfactant (Law of Laplace: P = 2 x T/R)
How does compliance vary throughout the upright lung?
Higher at the base than the apex, because apex is already more distended (hence better ability to ventilate base compared with apex)
Draw the pressure-volume curve of a normal lung
- Sigmoid curve of intrapleural pressure vs volume, does not reach 0% lung volume
- Shows lung volume is higher during deflation than inflation for any given pressure (hysteresis)
- Shows that lung contains residual air, without any expanding pressure (due to airway closure)
- Shows that compliance decreases at higher lung volumes (lung becomes stiffer due to reaching limits of elasticity)
Which areas of the brain control respiration?
2 to pass:
- Medulla: medullary respiratory centre (in particular the Pre-Botzinger Complex) generates intrinsic rhythm
- Pons (apneustic centre and pneumotaxic centre): may modulate activity of medulla
- Cerebral cortex: voluntary control
- Limbic system and hypothalamus: change respiration in response to emotions
What is the difference between a diffusion-limited and perfusion-limited gas?
Perfusion-limited gas:
- One where the partial pressure on both sides of the membrane equilibrates rapidly such that no further diffusion into the blood can occur from the alveoli unless the blood perfusion rate increases
- In the graph, there is no gap between the alveolar partial pressure of the gas at the time blood leaves the pulmonary capillary
- E.g. O2
Diffusion-limited gas:
- One where the partial pressure of the gas does not achieve equilibrium in the time that blood spends in the pulmonary capillaries
- In the graph, there is a gap between the partial pressure of the gas at the end of the pulmonary capillary perfusion time
- E.g. CO2
Draw a diagram that demonstrates the components of total lung volume
3/6 correctly labelled to pass:
- TLC, VC, FRC, TV, RV, ERV
Draw and describe the oxygen haemoglobin dossciation curve
Correct shape and labels with 2 points of saturation to pass
Describe the normal relationship between ventilation and perfusion in an upright lung
Pulmonary circulation is affected by gravity:
1. Apex:
- Less blood flow
- Larger alveoli
- Slightly less ventilation
- Ventilation > perfusion *
- High V/Q ratio *
2. Middle:
- Ventilation = perfusion
- V/Q = 1
3. Base:
- More blood flow
- Smaller alveoli
- More ventilation
- Perfusion > ventilation *
- Low V/Q ratio *
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