Oxygen & Carbon Dioxide Regulation Flashcards
What are the causes and consequences of hypoxia/hypocapnia/hypercapnia?
Hypoxia (Type 1 or 2 respiratory failure) = respiratory acidosis
Hypocapnia (hyperventilation) = respiratory alkalosis
—> reduction in ionised [Ca2+] (plasma proteins ionised due to increase in pH and can bind more calcium) —> hypocalcaemic tetany (twitch, tingles, characteristic posture)
Hypercapnia (hypoventilation, Type 2 respiratory failure) = respiratory acidosis —> enzymes lethally denatured
Define hypo/hyperventilation.
Hypoventilation = reduction in ventilation (slow, shallow breathing) with no change in metabolism causing hypercapnia & hypoxia
Hyperventilation = increase in ventilation (rapid breathing) with no change in metabolism (i.e. exercise does not cause hyperventilation) causing hypocapnia & hyper-oxia
Is it more important to maintain pO2 or pCO2?
pCO2
pCO2 affects pH; sigmoidal curve of Hb means pO2 has to fall significantly before tissue oxygenation is affected
What are the causes and consequences of metabolic acidosis/alkalosis?
Metabolic acidosis = reduction in [HCO3-]plasma —> lowered pH
e.g. due to increased production of acid from tissues
Metabolic alkalosis = increase in [HCO3-]plasma —> raised pH
e.g. due to reduction in acid content of blood (alkaline tide)
pH of blood plasma depends on the RATIO of [HCO3-]:pCO2 (not on the absolute values)
How are changes in pO2 sensed and regulated?
PERIPHERAL CHEMORECEPTORS
Monitor large decreases in arterial pO2 (when chemoreceptors themselves do not have sufficient O2 for metabolism)
- found in carotid bodies (bifurcation of common carotid) & aortic bodies (sit in and are supplied by the aorta) - high blood flow compared to size
- a large decrease in pO2 will stimulate increased ventilation, divert bloodflow to the brain, and increase heart rate (via the medulla)
How are changes in pCO2 sensed and regulated?
CENTRAL CHEMORECEPTORS
Monitor arterial pCO2 indirectly (by monitoring the pH of the CSF which is determined by [HCO3-]:pCO2)
Located in the medulla
Short-term:
[HCO3-]CSF is constant, so changes in the pH of the CSF are altered by changing the ventilation rate (changes ratio by altering pCO2; pCO2 can cross blood-brain barrier directly)
Long-term:
[HCO3-]CSF is altered in order to “reset” the baseline CSF pH which activates the central chemoreceptors (either as a result of persistent hypercapnia or persistent hypoxia)
How is CSF produced? What are the major constituents of CSF? How does CSF interact with the circulation?
Produced constantly by choroid plexus cells (amount produced can be altered very rapidly; normal amount ~500ml/day)
HCO3- can enter the CSF via the choroid plexus cells (cannot pass through the blood-brain barrier)
Flows through the ventricles of the brain and enters the venous circulation
CSF protects and nourishes the brain ([Na+][Cl-] in greater conc. than plasma, lower conc. of glucose, proteins, calcium, potassium, etc.)
Separated from the blood by the blood-brain barrier
note: not a physical/visible barrier; refers to selective permeability of the blood vessels of the brain
- permeable to O2, CO2, H2O, glucose, alcohol, general anaesthetics
- impermeable to HCO3-, H+, Na+, K+ (active transport required)
Give some examples of scenarios where the central chemoreceptors are reset to respond to a higher pCO2.
V/Q mismatch caused by changes to alveolar wall (O2 diffusion more affected than CO2) —> hypoxia
Short-term: Increased ventilation —> reduced pCO2 —> reduced ventilation
Long-term: Reduction in pCO2 compensated for by reduction in [HCO3-]CSF —> increases ventilation
Chronic bronchitis: poor ventilation causes hypoxia & hypercapnia
Short-term: reduction in pH of plasma & CSF—> increased ventilation —> breathlessness
Long-term: increased [HCO3-]CSF —> increase in pH of CSF —> breathlessness disappears
What is the difference between ventilation and perfusion?
VENTILATION = ensures oxygen enters blood at the same rate as it is utilised by metabolism & carbon dioxide leaves blood at the same rate as it is produced by metabolism
i.e. respiratory
PERFUSION = ensures oxygen is delivered to tissues & carbon dioxide is removed from the tissues
i.e. cardiovascular
Explain the movement of oxygen from the air to respiring tissues. Give some examples of diseases which affect the different areas.
AIR ——-> Airways —> Alveolar gas —> Alveolar membrane —>
Arterial blood —> Regional arteries —> Capillary blood —> TISSUES
Air: low inspired air
Air -> Airways: muscle/chest wall problems
Airways: obstructive airway disease
Alveolar membrane: fibrosis
Alveolar membrane -> Arterial blood: pulmonary oedema, V/Q mismatch
Arterial blood: anaemia
Arterial blood -> regional arteries: shock
Regional arteries: peripheral arterial disease
How does the V/Q change in the lung? What is the ideal V/Q?
Apex of lung: reduction in blood flow due to gravity increases V/Q
Base of lung: increase in alveolar ventilation & increase in blood flow due to gravity decreases V/Q
Ideal V/Q = 1
How is an arterial blood gas performed?
Use syringe coated with heparin (prevents sample clotting and clogging the blood gas analyser), seal the tube to prevent exchange of gases with the atmosphere (accurate measurement of blood gases), keep on ice to limit gas diffusion.
Arterial stab, usually via radial artery.
How can diffusion of gases be impaired in the lung? What does this cause?
Fibrotic lung disease: thickened alveolar membrane slows gas exchange (pCO2 normal as CO2 crosses alveolar membrane more easily than O2)
e. g. alveolitis (fibrosing alveolitis or extrinsic allergic alveolitis)
e. g. asbestosis (needle-shaped fibres engulfed by macrophages which subsequently burst —> release of inflammatory mediators —> inflammation)
e. g. pneumoconiosis
Pulmonary oedema: increase in diffusion resistance/distance due to presence of fluid between alveoli and capillaries (pCO2 normal as CO2 is more soluble than O2)
Emphysema: reduced surface area for gas exchange due to destruction of alveoli (normal pCO2 as CO2 crosses the alveolar membrane more easily than O2)
Diffusion impairment causes Type 1 respiratory failure (reduced pO2 but normal pCO2)
Define respiratory failure. How can it be categorised?
Not enough oxygen enters blood/not enough carbon dioxide leaves blood
TYPE 1: reduced pO2 but normal pCO2
- poor perfusion in some alveoli e.g. pulmonary embolism (can be compensated for by increased oxygen uptake in perfused alveoli)
- poor ventilation in some alveoli e.g. pneumonia, consolidation, early stages of acute asthma
(cannot be compensated for by increased oxygen uptake in other alveoli: Hb fully saturated) - impairment of diffusion of gases between alveoli and capillaries e.g. fibrotic lung disease, pulmonary oedema
acute respiratory distress syndrome, COPD, emphysema
+ low inspired O2 fraction, low barometric pressure, alveolar hypoventilation, V/Q mismatch, right to left shunt
TYPE 2: reduced pO2 and raised pCO2; caused by ineffective respiratory effort
- respiratory depression e.g. adverse drug reaction to narcotics, muscle weakness (upper or lower motor neurone problem)
- chest wall problems e.g. scoliosis/kyphosis, trauma, pneumothorax
- increased airway resistance making ventilation difficult e.g. COPD, asthma
+ bronchiecstasis, acute asthma, obstructive sleep apnoea, flail chest, ruptured diaphragm, abdominal distension, morbid obesity, coma, raised intracranial pressure, head injury, opioids/sedatives, cervical cord lesions (trauma, tumours), spinal cord (poliomyelitis), peripheral nerves (Guillain-Barre, diptheria, critical illness polyneuropathy) muscular dystrophy, NMJ (myasthenia gravis, organophosphate poisoning, botulism)
What are the symptoms associated with the different types of respiratory failure?
Type 1:
- breathlessness
- exercise intolerance
- central cyanosis
Type 2:
Acute: breathlessness (partially compensated; poor ventilation prevents full compensation)
Chronic: hypercapnia causing breathlessness reduced by “reset” of central chemoreceptors (reduced respiratory drive), so persisting hypoxia drives respiration via the peripheral chemoreceptors
- pulmonary circulation hypoxia causes pulmonary hypertension (vasoconstriction of pulmonary arterioles), right-sided heart failure, cor pulmonale
- increased oxygen transport due to increased Hb (polycythaemia) - increases blood viscosity - and increased 2,3-BPG
- obstruction traps air in lungs -> increases residual volume -> breathing at higher lung inflation -> more work needed to breathe -> exhaustion
