How is CO2 produced in the body?
CO2 is a waste product of aerobic respiration. It is mainly produced by the Krebs cycle, which oxidises acetyl-CoA into ATP, intermediaries NADH and FADH2, and CO2
Mitochondria in cells use glucose and O2 to produce ATP, with H2O and CO2 as byproducts
What happens to the CO2 produced by the cells?
CO2 is transported to the lungs for expiration. As CO2 is non-polar and lipid soluble, it diffuses through the cell membrane into nearby capillaries:
- ~90% diffuses into RBCs
~ 5% dissolves into plasma, ~ 5% binds to proteins (primarily haemoglobins)
In RBCs, CO2 is acted on by carbonic anhydrase:
CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻
Allows the continual uptake of CO2 into RBCs. The process is reversed at the alveoli and CO2 is exhaled
NB however that excess CO2 produces high amounts of H+ => acidosis
Normal CO2 levels
PaCO2 = 35-45mmHg
< 35mmHg hypocapnia
> 45mmHg hypercapnia
Excess CO2 can cause acidosis (lowers blood pH) If high levels of CO2 are due to hypoventilation (i.e. not breathing enough) or breathing a CO2-rich atmosphere –it is called respiratory acidosis
What can cause high levels of CO2?
Respiratory issues:
* Chronic lung diseases (e.g., COPD, emphysema)
* Respiratory depression (e.g., due to opioids, brain injury)
* Severe asthma
* Hypoventilation
* Obstructive sleep apnoea
High levels of CO2 via breathing CO2- rich air:
- Unventilated or poorly ventilated indoor areas eg submarines, spacecraft, bunkers/basements
- occupational settings eg firemen, welders
- some natural/extreme environments eg caves, volcanic areas
Describe some medical interventions for high CO2 exposure
Treatments aim to restore normal blood/gas chemistry:
- Improving ventilation (e.g. CPAP, mechanical ventilation, intubation)
- Treat underlying cause of hypoventilation
(e.g. use of bronchodilators)
- Oxygen therapy or bicarbonate therapy however both rarely used as they can suppress respiratory
drive / other side-effects
define different levels of CO2
- Elevated - our current atm ~ 425ppm (40% higher than pre-industrial life)
- High - 1000-3000ppm eg public transport, subways
- very high - 3000-5000ppm eg in submarines, space craft
What are some health effects of long CO2 exposure?
At high levels, (1000-2000ppm) ppl can experience drowsiness, difficulty concentrating, [inablity to text] and at very high levels, confusion, headaches, dizziness symptoms.
Even greater levels of CO2 can lead to altered breathing, discomfort. At 40,000ppm, has been identified as immediately dangerous to life/health followed to coma/death at ~50-80,000ppm
What are the physiological responses to high CO2 levels in the blood?
There are 4:
1. the bicarbonate buffer system
2. pulmonary compensation
3. Renal compensation
4. Osteological compensation
Describe the bicarbonate buffer system and how it helps to neutralise pH
The bicarbonate buffer system immediately neutralises excess acid or base (High CO2 leads to acidity). The bicarbonate buffer system can form H2CO3 or carbonic acid which buffers against excess acid. In situations of high pH, H2CO3 can dissociate to release H+
CO₂ + H₂O —> H₂CO₃ —> H⁺+ HCO₃⁻
Describe the pulmonary system in pH compensation
The body has 2 chemoreceptors which detect changes in the chemicla composition of the blood:
- Central chemoreceptors: located in the ventrolateral medulla and detect pH (H+
levels) of the CSF
- Peripheral chemoreceptors: located in the carotid and aortic bodies and primarily detect arterial blood O2, CO2 and H+ levels
Compare the way in which CO2 is sensed by the central and peripheral chemoreceptors
The Central chemoreceptors (CCR) sense H+ in the CSF while the Peripheral chemoreceptors (PCR) sense H+, CO2 as well as O2 levels in arterial blood.
As CO2 increases in the body, it diffuses across the BBB, increasing H+ in the CSF. This provides a a strong drive for ventilation via the CCR. In contrast, CO2 weakly drives ventilation via the PCR.
H+ increases in arterial blood drives ventilation by the PCR, while CCR does not react to H+ in arterial blood.
Describe renal compensation and how it helps to adjust the pH balance
The kidneys are responsible for excreting H+ or the reabsorption of HCO3- in cases of low pH or the excretion of HCO3- in cases of respiratory alkalinity (altitude)
- H⁺ secreted (apical) into the tubular lumen at the PCT via Na⁺/H⁺ exchangers. Some is excreted
- Some H⁺ in filtrate combines with HCO₃⁻ to form CO2 and H2O
- CO2 diffuses into tubule cell, combines with H2O, (catalysed) to produce H+ and HCO₃⁻
- H⁺ secreted again (1) and excreted while HCO₃⁻ is reabsorbed via Na⁺/ HCO₃⁻ exchangers (basal)
- Glutamine is metabolised into NH4+ and excreted (also removes H+) while HCO₃⁻ is reabsorbed via Na⁺/ HCO₃⁻ exchangers (basal)
Compare how renal compensation is assisted by acetazolamide and it’s mechanism of action
Acetazolamide works in the kidney’s proximal tubule by inhibiting the enzyme carbonic anhydrase, which is essential for the reabsorption of HCO₃⁻, Na⁺, and Cl⁻. By blocking this process, acetazolamide causes these ions, along with water, to be excreted in the urine (increases urine production/diuresis) and a decrease in blood pressure. This action also causes alkalinization of the urine and a more acidic blood pH due to increased HCO₃⁻ excretion.
What is a potential issue with long term renal compensation of high acidosis in the body?
Chronic renal compensation of CO2 in the blood can lead to calcification of kidney tissue (mechanisms not fully understood).
- H+ excretion is increased but some H+
is buffered by phosphate - This requires calcium (Ca²⁺) for excretion as
calcium phosphate - Ca²⁺ is also mobilized from bone to buffer acid
- High urinary phosphate + calcium can lead to
precipitation of calcium salts in kidney tissue
Describe the osteologial compensation for acidosis
Bones are made up of minerals that can help maintain normal blood pH (e.g. calcium carbonate (CaCO₃) and hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂)). Chronic acidosis causes bone
resorption –osteoclasts break down and release CO₃²⁻ and PO₄³⁻ to buffer excess H⁺ ions. Long term, this can contribute to osteopenia/osteoporosis
What occurs when humans are exposed to high levels of CO2 for short-term and long-term?
For short term (<hours) CO2 exposure, blood bicarbonate system (and potentially some
respiratory compensation) are enough and quickly returns to normal when elevated exposure stops..
Longer-term exposures (e.g. submarines/space craft) at higher levels of CO2 (<5,000ppm) can lead to renal and osteological impacts
Describe physiological impacts in high levels of CO2 (~1000ppm)
Physiology dictates that respiratory and renal compensations can cope (1000ppm requires a ventilatory compensation of 1.1% ie ~ 1 breath/10 mins).
However, studies in animals have indicated increased levels of anxiety, stress/corticosterone, hyperactivity/reduced engagement in learning/memory tasks, altered upper airway muscle composition.
Also reflected in humans, where there has been reports of reduced SMS performance, decision making and problem-solving abilities.
What are upper healthy levels of HCO₃⁻
The upper healthy level of HCO₃⁻ is currently 28.3mM for arterial blood and 30mM for venous blood
