L5 - Acid Base Balance Flashcards
Why is acid-base balance important?
A small change in pH can have a large effect on body function
Log scale – 1 unit change = x10 change in [H+]
What can fluctuations in plasma H+ concentrations have an effect on?
Excitability of muscle and nerve
Enzyme activities
K+ levels
pH at venous end of tubule?
7.35
pH at arterial end of tubule?
7.45
What are the different pH value around the body?
Gastric secretion – 0.7
Cerebrospinal fluid – 7.3
Pancreatic secretions – 8.1
Urine – 5.4
What are the different sources of acid and alkali?
Metabolism – large amounts of acid produced
- 15 moles/ day CO¬¬2
- 40 mmol/day H+ (western diet has an excess of H+)
Diet – alkali and acid in food
- 20 mmol/day H+
- Lose 10 mmol/day OH-
Overall excess 70 mmol/day H+
What are the 3 different systems involved in acid-base balance?
Blood and tissue buffers (seconds)
Respiration (minutes)
Renal (hours) – only mechanism for the extrusion of acid/alkali
Where are buffers present throughout the body?
Blood – plasma and red blood cells
Extracellular and intracellular fluid
Urine
E.g. haemoglobin, inorganic phosphate, weak acids/bases, HCO¬¬-3
Carbonic acid/bicarbonate ECF buffer
CO2 + H2O H2CO3 H+ + HCO3
What is the Henderson-Hasselbach equarion
pH = pK + log [HCO3]/[H2CO3]
pK is a constant of 6.1 at 37oC
Ratio of [HCO3]/[CO2] = 20:1
6.1+log 20 = 6.1+1.3 = 7.4
What does chemical control of ventilation control?
Controls blood gas composition – PO2, PCO2, pH
How is ventilation chemically controlled?
Peripheral and central chemoreceptors - negative feedback system
Stimulated by hypoxia, hypercapnia, acidosis – all increase ventilation
- Increase in PO2
- Decrease in PCO2
- Increase in pH
What are peripheral chemoreceptors triggered by?
Mainly stimulated by decreased PO2 – hypoxia
What do peripheral chemoreceptors do once triggered?
When activated send signals through the sinus, gloss-pharyngeal and the vagus nerve to the medulla
What is the structure of carotid receptors?
Small – 2mg
High blood flow (40X higher than the brain per unit mass)
High metabolic rate
Glomus cells
Parasympathetic/sympathetic cells – regulate blood flow Aortic receptors smaller and less well studied
What do glomus cells do?
Fire action potentials when O2 drops
Neural phenotype
Type II – supporting
What is the mechanism of glomus cells?
- Inhibition of BK K channels – decreased PO2, increased PCO2, decreased pH
- Depolarisation and action potential firing
- Ca channels open increasing intracellular Ca
- Ach, dopamine, 5-HT, substance P, noradrenaline released
- Some SIDS babies have higher concentration of carotid body noradrenaline and dopamine - Afferent nerve fibre stimulation
Sensitivity to PO2 changes with?
Acid/base status
Higher pH = less action potentials
Sensitivity to PCO2 changes with?
pH
Higher pH = less action potentials
What are central chemoreceptors stimulated by?
Increased CO2 - hypercapnia
Change in PCO2 from 40 - 45 mmHg - doubles ventilation
Same increase in ventilation only seen with 50% fall in PO2
What factor is actually measured that triggers central chemoreceptors?
pH
Perfused cerebral ventricles with acidic solution – observed hyperventilation
Where are central chemoreceptors located?
Within the brain parenchyma and bathed in brain extracellular fluid
Separated from arterial blood by the blood brain barrier
- BBB has poor ion permeability
- H+ and bicarbonate can’t cross
- CO2 can cross
Increase in arterial PCO2 = increase in brain extracellular fluid PCO2
Where are central chemoreceptor neurones located?
Ventrolateral medulla and other brainstem nuclei
What are the two types of central chemoreceptor neurone?
Acid activated – serotonin
Acid inhibited – GABA
What are the characteristics of central chemoreceptor neurones?
Less non-bicarbonate buffering power (fewer proteins) in the BECF, so larger fall in pH
- Some long term compensation via transport of HCO-3 from blood
Poor ion permeability
- Metabolic disorders change BECF pH by 35% of that observed with respiratory disorders for the same change in blood pH
- Respiratory disorders are better at stimulating the chemoreceptors
Do peripheral and central chemoreceptors respond at the same time?
Yes - integrated responses
How do peripheral and central chemoreceptors respond to respiratory acidosis?
Both central and peripheral chemoreceptors
Normoxic central 65-80%
Peripheral chemoreceptors respond faster
As PO2 falls response to PCO2 enhanced
How do peripheral and central chemoreceptors respond to metabolic acidosis?
Severe cases lead to hyperventilation (Kussmaul breathing)
Decreased PCO2
Peripheral chemoreceptors - acute response role
Central chemoreceptors - longer term role
What are the changes in acid-base balance when you breathe faster?
Decrease in CO2 = decrease in [H+] = increase in pH
Increased pH of body fluids = chemoreceptors = decreased breathing rate
What are the changes in acid-base balance when you breathe slower?
Increase in CO2 = increase in [H+] = decrease in pH
Decreased pH of body fluids = chemoreceptors = increased breathing rate
