Physiology 10 Flashcards
What is the alveolar gas equation?
PAO2 = PIO2 - PICO2 / RQ
RQ = respiratory quotient
RQ depends on mix of dietary intake but is commonly quoted as 0.8
What is the A-a gradient?
What is its normal value?
A-a gradient = PAO2 - PaO2
Under normal conditions this is <2 kPa
What factors affect O2 carrying capacity in the blood?
Hb
SaO2
PaO2
How is HbO2 carrying capacity calculated?
HbO2 carrying capacity = [Hb] x 1.39 x SaO2/100
How is dissolved oxygen in the blood calculated?
Dissolved O2 = 0.023 x PaO2 ml/100ml
What is the equation for calculating total blood O2 content?
O2 content = [Hb] x 1.39 x SaO2/100 + (0.023 x PaO2)
Regarding the HbO2 dissociation curve what is the P50 at pH 7.4?
3.5kPa
How is oxygen delivery to tissues (DO2) defined?
DO2 = blood O2 content x CO
Regarding the HbO2 dissociation curve what is the P75 at pH 7.4?
Why is this number important?
5.3 kPa
This is a typical value for mixed venous blood
How is VO2 derived?
VO2 = CO x (Ca02 - CvO2)
For a ‘normal’ person, what is the O2 content of 100% saturated blood?
Approx 20ml/100ml
Using normal values to calculate, what is a normal VO2?
VO2 = 5000 x (20 - 15)/100
= 250 ml/min
Outline the concept of tissue hypoxia
When intracellular PO2 is insufficient to sustain normal aerobic metabolism for cellular functions
How is tissue hypoxia classified?
- Hypoxic hypoxia (low PO2)
- Anaemic hypoxia (reduced or dysfunctional Hb)
- Ischaemic hypoxia (low CO or vascular abnormality)
- Histotoxic hypoxia (inability of cells to utilise available oxygen)
What are the phases of cellular metabolism?
Phase 1: Production of 2-carbon compounds
Phase 2: Citric acid cycle
Phase 3: Electron transport chain
Outline processes relevant to phase 1 metabolism
Glycolysis (Glucose 6c -> 2x Pyruvate 3c) - Produces 2 NADH2+ and [net] 2 ATP (4 -2)
Glycolysis occurs in the cytoplasm
Oxidative decarboxylation (Pyruvate 3c + CoA -> Acetyl CoA 2c + CO2) - Produces 2 NADH2+ Oxidative decarboxylation occurs in the mitochondria
Beta-oxidation of free fatty acids in mitochondria produces Acetyl CoA
Oxidation of amino acids produces Pyruvate, Acetyl CoA and other intermediates
Outline the key points of Phase 2 metabolism
Citric Acid Cycle
- Acetyl CoA combines with Oxaloacetate to form citrate
- Citrate goes through a series of reactions producing intermediary compounds, energy-containing compounds and CO2
- The cycle ends with oxaloacetate, allowing the cycle to start again.
- Per glucose molecule, 2 cycles will produce 2 ATP, 6 NADH2+, 2 FADH2 and 4 CO2
Outline the key points of phase 3 metabolism
Electron Transport Chain
- Reduced energy-containing compounds are re-oxidised producing electrons and energy, used to phosphorylate ADP -> ATP
- Each NADH2+ produces 3 ATP in the ETC
- Each FADH2+ produces 2 ATP in the ETC
- Oxygen is the final electron acceptor in the chain
What is the breakdown of net ATP production from one glucose molecule during aerobic respiration?
Glycolysis: 8 ATP (2 ATP + 2 NAHD2+)
Oxidative decarboxylation: 6 ATP (2 NADH2+)
Citric acid cycle: 24 ATP (2 ATP + 6 NADH2+ + 2 FADH2)
What is the breakdown of net ATP production from one glucose molecule during anaerobic respiration?
Glycolysis: 2 ATP
The NADH2+ is used in the metabolism of pyruvate to lactate.
NAD+ and FAD are not re-formed so the citric acid cycle cannot continue
Lack of oxygen means the ETC cannot operate
How long can the body’s supply of ATP last?
Approx 90 seconds
What is the lowest possible mitochondrial PO2 compatible with oxidative phosphorylation?
0.4 kPa
What are the main mechanisms by which cellular hypoxia causes loss of function?
- Fall in ATP levels
- Fall in pH
How does the body compensate for hypoxia?
- Early / Late
- Local / Ventilatory / Cardiovascular
Early local: Changes to HbO2 affinity, vasodilatation
Early ventilatory: Hypoxic (<7 kPa) / hypercarbic response
Early CV: Vasoconstriction, tachycardia (to ^CO/MAP)
Late: Polycythaemia (detectable in 3-5 days)
How does the cerebral circulation respond to hypoxia?
PO2 <7 kPa leads to exponential increases in cerebral blood flow due to vasodilatation
How does cardiac circulation respond to hypoxia?
Local arteriolar dilatation through vasoactive metabolites, direct O2 effect and myogenic reduction in tone
What are normal values for CO2 tension?
PICO2: 0 kPa
PaCO2: 4.7-5.3 kPa
PvCO2: 6.1 kPa
PACO2 is = to PaCO2 due to the rapid equilibration across the alveolar wall.
What are the main factors affecting CO2 exchange in the alveoli?
How is alveolar CO2 calculated?
- AMV
- CO2 production
%PACO2 = CO2 output / AMV
eg. 200ml/min / 4000ml/min = 5%
What are the main causes of hypercapnia?
- Increased FiCO2
- Primary respiratory
- Increased CO2 production
- Compensatory
What are the complications of hypercapnia?
- Neurological:
- Increased CBF
- Increased ICP
- Narcosis >12kPa (likely pH mediated)
- Autonomic effects - Respiratory
- Tachypnoea
- Pulmonary vasoconstriction (>7kPa)
- Bohr effect -> reduction in HbO2 affinity
- Alveolar dilution of O2 - Cardiovascular
- HR and contractility reduced (though overcome by catecholamines)
- Vasodilatation
- Arrhythmia due to myocardial intracellular acidosis and catecholamines - Biochemical
- Acidosis -> K+ leakage from cells -> hyperkalaemia
- Acidosis -> increase in relative UNionised Calcium
What changes in respiratory gas properties occur at altitude?
- Pressures decrease
- Fractional values stay the same
- Alveolar SVP of water stays the same
How would you calculate PIO2 at sea level?
PIO2 = FiO2 x (ambient pressure - SVP H20 37°C)
PIO2 = 0.21 x (101 - 6.3) = 19.9 kPa
What are the changes to inspired oxygen relevant to air travel?
At 35,000ft, cabins are pressurised to ~5-6,000ft, equivalent to breathing 17% O2 at sea level
At what altitude does PO2 = O kPa?
63,000 ft
What temperature does water boil at on the top of Everest?
69°C
What would happen if a sea level dweller ascended to Everest summit quickly?
Initial hypoxic respiratory drive but this only lasts ~1hr. Following this hypoxia will develop
How does the body acclimatize to low PO2 at altitude?
- Hyperventilation and hypocapnia
- Respiratory alkalosis -> renal HCO3- excretion -> metabolic acidosis -> increased AMV
- Increased haematopoeisis
- Increase in 2,3 DPG, though counteracted by alkalosis
Takes days to weeks
How is mountain sickness classified?
Acute (Mild/Severe) ; Chronic
Above what altitude may acute mountain sickness occur?
6000ft
What are the clinical features of mild acute mountain sickness?
- Dyspnoea
- Headache
- Nausea
- Fatigue
- Sleep disturbance
- Cheyne-Stokes respiration
What are the clinical features of severe acute mountain sickness?
- High-altitude pulmonary oedema (HAPO): Associated with exercise, caused by excessive pulmonary vasoconstriction. High untreated mortality.
- High-altitude cerebral oedema (HACO): Hallucinations/coma
How is acute mountain sickness treated?
NIfedipine / acetazolamide
Immediate descent
What are the features of chronic mountain sickness?
- Poor hypoxic ventilatory response
- Polycythaemia
- Cyanosis
- Clubbing
- CO2 retention
How can patients be tested before flying if concerned about altitude?
Those with SpO2 <92% on air can undergo a 15% hypoxic challenge
By how much does pressure increase with depth underwater?
1atm per 10m
What are the possible complications of rapid decompression?
- Barotrauma
- Arterial air embolus
- Neurological damage
- Bubbles in vessel-poor tissues (eg. cartilage) with subsequent AVN
Define hyperbaric O2 therapy
Delivery of 100% O2 at an ambient pressure of 2-3 atm. Usually for 1-2h per day over a course of days.
What physiological benefit does hyperbaric O2 therapy confer?
Arterial O2 content shows a modest increase (from 19 - 25 ml/dL) at pressure but venous oxygen content increases significantly. This forms the basis for treating tissue hypoxia.
What are current indications for hyperbaric O2 therapy?
CO poisoning
Anaerobic infections
Possibly MS and burns
What are the challenges associated with managing air transfer of an anaesthetised patient?
- Precipitation of hypoxia at altitude
- Expansion of air-filled spaces on takeoff
- Breathing system valves may stick
- Boiling point of volatiles reduced, though low temperatures reduce this effect
Where are the Hbα genes encoded?
How many a-as make up the Hbα molecule?
Chromosome 16
141 a-as
Where are the Hbβ genes encoded?
How many a-as make up the Hbβ molecule?
Chromosome 11
146 a-as
Describe the structure of haem
Composed of an organic part and an iron atom in its ferric (Fe2+) state
The organic part is a protoporphyrin ring.
The Fe2+ forms six bonds
- 4x bonds to N in the protoporphyrin ring
- 1x bond to ‘proximal histidine’ of associated globin molecule
- 1x bond to O2 molecule
Close to the O2 binding site, a ‘distal histidine’ residue prevents oxidisation of other haem groups and prevents CO from binding to the Fe2+
Outline the production of haem
Glycine + Succinyl CoA -> Protoporphyrin
Protoporphyrin + Fe2+ -> Haem
Outline the breakdown of haem
Protoporphyrin -> biliverdin
Biliverdin -> bilirubin
Bilirubin is bound to albumin and glucuronidated in the liver and excreted in bile
In the bowel, bilirubin -> stercobilin. Some is reabsorbed and excreted via the kidney as urobilinogen
What is Hufner’s constant?
Describes the O2 carrying capacity of Hb
In vivo value is 1.34 ml/g
Differs from the theoretical value of 1.39 ml/g is likely due to small percentages of HbA2, HbF and COHb
What is the P50 of HbA?
3.5 kPa
What is the P50 of HbF?
2.5 kPa
What is the ‘double Bohr effect’ seen in pregnancy?
Maternal uptake of CO2 from the foetal circulation shifts the maternal HbO2 curve to the right and the foetal HbO2 curve to the left.
How is 2,3-DPG formed?
As a product of glycolysis
Where does 2,3 DPG exert its effect on Hb?
β-globin chains
What situations may lead to abnormal oxidation of haem?
CO toxicity
Physiological NO scavenging by Hb
Treatment with NO
Prilocaine or nitrate therapy
What artificial means of increasing O2 delivery have been explored?
Stroma free Hb-based carriers
Synthetics eg. Perfluorocarbons
What are some of the problems associated with development of stroma-free Hb-based O2 carrying solutions?
- Free Hb dissociates into nephrotoxic α/β dimers
- Concerns re prion contamination of bovine Hb
- Free Hb has a short IV half-life -> bilirubin
- Excessive scavenging of NO may lead to hypertension
