Week 5 - Control of breathing, respiratory failure, asthma Flashcards
Define hypoxia
A fall in alveolar, thus arterial pO2
Define hypercapnia
A rise in alveolar, thus arterial pCO2
Define hypocapnia
A fall in alveolar, thus arterial pCO2
Define hyperventilation
Ventilation increases with no change in metabolism
Define hypoventilation
Ventilation decreases with no change in metabolism
What are the effects on plasma pH of hyperventilation?
- Hypocapnia and respiratory alkalosis
- If pH rises above 7.6 then free calcium concentration falls enough to produce fatal tetany
- – Ca2+ is only soluble in acid, so when pH rises, Ca2+ cannot stay in the blood
- – Nerves become hyper-excitable
What are the effects on plasma pH of hypoventilation?
- Hypercapnia and respiratory acidosis
- If pH falls below 7 then enzymes become lethally denatured
Define respiratory acidosis
Alveolar pCO2 rises, so [dissolved CO2] rises more than [HCO3-], producing a fall in plasma pH
- pH decreased, pCO2 increased, HCO3- normal or increased
Define compensated respiratory acidosis
If respiratory acidosis persists, the kidneys respond to low pH by reducing excretion HCO3-
- Thus restoring the ratio [dissolved CO2]/[HCO3-]
- Hence restoring the pH
Define compensated respiratory alkalosis
If respiratory alkalosis persists, the kidneys respond by excreting HCO3-
- The ratio [dissolved CO2]/[HCO3-] returns near to normal
Define metabolic acidosis
Metabolic production of acid displaces HCO3- from plasma as the acid is buffered, so the pH of blood falls
- pH decreased, pCO2 normal or decreased, HCO3- decreased
Define metabolic alkalosis
- Metabolic production of HCO3- –> plasma [HCO3-] rises, causing the pH of blood to rise
- pH increased, pCO2 normal or increased, HCO3- increased
Define compensated metabolic acidosis
The ratio [dissolved CO2]/[HCO3-] may be restored near to normal by lowering pCO2 (increased ventilation)
Define compensated metabolic alkalosis
The ratio [dissolved CO2]/[HCO3-] may be restored near to normal by raising pCO2 (decreased ventilation)
What happens if there is a decrease in inspired O2?
- Detected by peripheral chemoreceptors located in the carotid and aortic bodies
- These are stimulated by a decrease in oxygen supply relative to their own oxygen usage, which is small
- – So they only respond to large drops in O2
- Stimulation of the receptors:
- – Increases the tidal volume and rate of respiration
- – Changes in circulation directing more blood to the brain and kidneys
- – Increased pumping of blood by the heart
What happens if there is an increase in inspired CO2?
- Peripheral chemoceptors detect changes in pCO2, but are insensitive
- Central chemoreceptors in the medulla of the brain detect changes in arterial pCO2
- Small rises in pCO2 increase ventilation
- Small falls in pCO2 decrease ventilation
Describe how central chemoreceptors work
- Located on the ventral surface of the medulla
- Exposed to cerebro-spinal fluid
— Separated from the blood by the blood brain barrier, which allows free passage of CO2 but not hydrogen carbonate
— The pH of the CSF is determined by its own hydrogen carbonate/carbonic acid buffer system
— Contains no haemoglobin
— CSF [HCO3-] is determined by plasma pCO2 and controlled by choroid plexus cells
• Rapid changes in plasma pCO2 take time to influence CSF
— CSF pCO2 determined by arterial pCO2
• So falls in pCO2 lead to rises in CSF pH
• Rises in pCO2 lead to falls in CSF pH
— pH of CSF is determined by the ratio of [HCO3-] to pCo2
— In the short term, [HCO3] is fixed (can’t cross BBB) so falls in pCO2 → increase in pH, and rises in pCO2 → decrease in pH
— Persisting changes in pH can be compensated for via the choroid plexus cells altering CSF [HCO3-] - Respond to a fall in CSF pH
What are the different types of hypoxia?
- Hypoxaemic – low pO2 or low O2 saturation
- Anaemic – normal pO2 but insufficient Hb to carry O2
- Stagnant – reduced delivery of O2 due to poor perfusion
- Cytotoxic – O2 delivery is adequate but tissues are unable to utilise O2
Describe type 1 respiratory failure
- Not enough oxygen enters the blood
- CO2 removal not compromised
- pO2 of arterial blood low
Describe type 2 respiratory failure
- Not enough oxygen enters the blood
- Not enough CO2 leaves it
- pO2 in arterial blood
What are some of the causes of respiratory failure?
- Low pO2 in inspired air
— Everything is normal, the air breathed in just has low pO2 - Hypoventilation
— Always associated with increased pCO2 (Type 2 respiratory failure)
— Neuromuscular problems
• Respiratory depression due to opiate overdose
• Head injury
• Muscle weakness
— Chest wall problems
• Scoliosis/kyphosis
• Morbid obesity
• Trauma
• Pneumothorax
— Hard to ventilate lungs
— Airway obstruction
• COPD and asthma when the airway narrowing is severe and widespread
— Severe fibrosis - Diffusion impairment
— O2 diffuses much less readily than CO2, so is always first
— pCO2 is hence low/normal, so type 1 respiratory failure
— Structural changes
• Lung fibrosis causing thickening of alveolar capillary membrane
— Increased path length
• Pulmonary oedema
— Total area for diffusion reduced
• Emphysema
o Elastin breakdown in alveolar walls, so reduced elastic recoil, increasing compliance - Ventilation/perfusion mismatch
— O2 diffuses much less readily than CO2, so is always first
— pCO2 is hence low/normal, so type 1 respiratory failure
— Reduced ventilation of some alveoli
• Lobar pneumonia
— Reduced perfusion of some alveoli
• Pulmonary embolism - Abnormal right to left cardiac shunts
Define asthma
A chronic disorder characterised by:
- Variable airflow obstruction
- – Due to airway smooth muscle
- Airway wall inflammation and airway wall remodelling
- – Airways have thickened smooth muscle and basement membranes
- Increase in airway responsiveness to a variety of stimuli
- – Reduces airway radius, increasing resistance and hence reducing airflow
- – Triggers: muscarinic agonists, histamine, cold air, arachadonic acid metabolites
What inflammation is there is asthma?
- Mast cells:
- – Increased in asthma
- – Release prostaglandinds, histamine, etc
- Eosinophils
- – Large numbers in the bronchial wall and secretions of asthmatics
- Dendritic cells and lymphocytes
- – Dendritic cells have a role in the initial uptake and presentation of allergens to lymphocytes
- – T-helper lymphocytes release cytokines that plan a key part in the activation of mast cells
- – Th2 phenotype favour the production of antibody production by B lymphocytes to IgE
What remodelling is there is asthma?
- Epithelium
- – Stressed and damaged with a loss of ciliated columnar cells
- Basement membrane
- – Deposition of collages, causing it to thicken
- Smooth muscle
- – Hyperplasia causing thickening of the muscle
