Acid base balance Flashcards
How do you calculate pH?
-log10[H+]
What is the broad pH range for fluids in the body?
6.8 - 8.0
What is the normal pH range for plasma?
7.35 - 7.45
What can changes in plasma pH affect? (3)
- Excitability of muscles and nerves
- Enzyme activity
- K+ levels
What happens to K+ levels during acidosis?
- K+ released from cells in exchange for H+
- Hyperkalaemia
What happens to K+ levels during alkalosis?
- H+ released from cells in exchange for K+
- Hypokalaemia
What is the net excess of H+ ions from diet/metabolism?
70 mmol/day
What 3 systems are involved in pH regulation?
- Blood and tissue buffers
- Respiration
- Renal
Where are buffers present in the body? (4)
- Blood
- Extracellular fluid
- Intracellular fluid
- Urine
What are examples of buffers? (4)
- Haemoglobin
- HCO3-
- Inorganic phosphate
- Weak acids/bases on proteins
What is the carbonic acid/bicarbonate equilibrium reaction?
CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-
What is H2CO3?
Carbonic acid
What is the Henderson - Hasselbalch equation?
pH = pK + log [HCO3-]/[H2CO3]
- H2CO3 ~ CO2 so usually divided by [CO2] instead of H2CO3
What is pK at 37°C?
6.1
What is normal pH?
7.4
What does acidosis mean?
Fall in pH
What does alkalosis mean?
Rise in pH
What is respiratory acidosis?
A problem with the lungs causes an increase in CO2 which reduces pH
What is hypercapnia?
Too much CO2
Which 3 conditions cause an increase in ventilation?
- Hypoxia
- Hypercapnia
- Acidosis
What are the 2 types of chemoreceptors?
- Peripheral
- Central
What are the peripheral chemoreceptors? (2)
Carotid and aortic bodies
Which nerves do the carotid and aortic bodies signal via? (3)
- Sinus nerve
- Vagus nerve
- Glossopharyngeal nerve
What is the main stimulus for the peripheral chemoreceptors?
Hypoxia
What is the main cell type in the peripheral chemoreceptors?
Glomus cell
What is the role of glomus cells?
Neuronal - fire action potentials
What are the 2 cell types in the carotid bodies?
- Glomus cells
- Type II cells
What is the role of type II cells?
Supporting cells
What is cranial nerve IX?
- Cranial nerve 9
- Glossopharyngeal nerve
Which divisions of the nervous system innervate the peripheral chemoreceptors?
Sympathetic and parasympathetic
What are BK K+ channels activated by?
Ca2+
What state are the BK K+ channels of the glomus cells in during normal oxygen conditions?
Open
What happens in the glomus cells when there is low O2/high CO2/low pH? (4)
- BK K+ channels inhibited
- Causes depolarisation, action potential fires
- Causes voltage gated Ca2+ channels to open = increased intracellular Ca2+
- Neurotransmitter released
What conditions trigger the glomus cells to fire action potentials? (3)
- Low oxygen (hypoxia)
- High carbon dioxide (hypercapnia)
- Low pH
Which neurotransmitters are released by glomus cells? (6)
- Acetylcholine
- Dopamine
- Noradrenaline
- 5-HT
- Substance P
- ANP
What causes the glomus cells to be more sensitive to changes in PO2? (2)
- Hypercapnia
- Low pH
What causes the glomus cells to be less sensitive to changes in PO2? (2)
- Low CO2
- High pH
What affects the glomus cells’ sensitivity to PCO2?
pH
What drives breathing under normal conditions?
Central chemoreceptors
What is the main stimulus for the central chemoreceptors?
Hypercapnia
Where are the central chemoreceptors located?
- Brain parenchyma
What are the central chemoreceptors surrounded by?
BECF (brain extracellular fluid)
How are central chemoreceptors separated from arterial blood?
Blood brain barrier
What are the features of the blood brain barrier? (2)
- Poor ion permeability (i.e. H+ and HCO3-)
- High CO2 permeability
Why does a small change in CO2 cause a big pH change in the BECF?
BECF doesn’t have many buffers
How does BECF cope with long term large changes in pH?
Can transport HCO3- from the blood into the BECF
Which kind of disorder changes the pH of BECF more?
Respiratory disorders
Why are central chemoreceptors less affected by metabolic disorders than respiratory?
Metabolic disorders could involve increases in H+ and the blood brain barrier has a low permeability to ions but a high permeability to CO2
Which brainstem nuclei contain central chemoreceptor neurons?
Ventrolateral medulla and other brainstem nuclei
What are the 2 neuronal types of central chemoreceptors?
- Acid activated (serotonin)
- Acid inhibited (GABA)
What is Kussmaul breathing?
Sever hyperventilation associated with metabolic acidosis
What are the 3 renal mechanisms involved in long-term acid base balance?
- HCO3- handling (reabsorption)
- Urine acidification
- Ammonia synthesis
Where in the nephron is HCO3- reabsorbed? (2)
- 90% proximal tubule
- 10% distal tubule
How is HCO3- reabsorbed in the proximal tubule cells? (6)
- H+ secreted across the apical membrane
- H+ bind with HCO3- in the filtrate to form H2CO3
- H2CO3 broken into H2O and CO2 by carbonic anhydrase on the apical membrane
- H2O and CO2 diffuse into the cell and recombine into H2CO3 via carbonic anhydrase
- H2CO3 dissociates into H+ and HCO3-
- HCO3- absorbed across the basolateral membrane via Na+ cotransporter
Which proteins are present in the basolateral membrane of proximal tubule cells? (3)
- Na+/K+ ATPase
- K+ channel
- HCO3-/Na+ cotransporter
What is the purpose of the Na+/K+ ATPase on the basolateral membrane of proximal tubule cells? (2)
- Sets a negative membrane potential and sets up an electrochemical gradient for Na+ to enter the cell on the apical membrane
- Pumps 3 Na+ out of the cell and 2 K+ in
Which proteins are present in the apical membrane of proximal tubule cells? (1)
Na+/H+ exchanger
What is base conservation? (2)
- 25% acidification of the urine
- 75% ammonia synthesis
What is urine acidification?
Alkaline salts in the urine are converted to acid salts in order to allow the body to excrete H+ without lowering the pH of the urine too much
What is the process of urine acidification involving alkaline phosphate? (3)
- Na2HPO (alkaline phosphate) becomes NaHPO4-, the Na+ is absorbed across the apical membrane
- H+ is secreted across apical membrane and binds to NaHPO4- to form NaH2PO4 (replaces Na+)
- NaH2PO4 (acid phosphate) is excreted in the urine
What is the formula for alkaline phosphate?
Na2HPO
What is the formula for acid phosphate?
NaH2PO4
What is NH3?
Ammonia
How is ammonia produced?
The metabolism of glutamine in the kidneys releases NH3 and H+
What is the product of glutamine metabolism?
Alpha keto-glutarate
What is NH4+?
Ammonium
Is ammonia permeable or impermeable?
Permeable
Is ammonium permeable or impermeable?
Impermeable
How is ammonia excreted?
- NH3 from glutamine metabolism diffuses into the tubular fluid
- H+ is secreted across the apical membrane
- H+ binds with NH3 to form NH4+ which is impermeable so is excreted in the urine
What is diffusion trapping?
- NH3 and H+ diffuse out of the renal cells and combine to form NH4+ which is impermeable and therefore trapped outside of the cells to be excreted
- NH3 acts as a buffer as it binds to H+ which removes them from the body without lowering the pH of the urine too much
How do the kidneys respond to acidosis? (4)
- Upregulation of H+ excretion
- No change in HCO3- handling (100% absorption)
- pH of urine decreases
- Causes plasma pH to increase back to normal
How do the kidneys respond to alkalosis? (4)
- Downregulation of H+ excretion
- Potential upregulation of HCO3- excretion
- pH of urine increases
- Causes plasma pH to decrease back to normal
What are the 2 types of acid base disorders?
- Respiratory acidosis/alkalosis
- Metabolic acidosis/alkalosis
What causes respiratory acidosis?
Increase in CO2 due to changes in lung function
What causes respiratory alkalosis?
Decrease in CO2 due to changes in lung function
What causes metabolic acidosis?
Increase in acid/decrease in base
What causes metabolic alkalosis?
Decrease in acid/increase in base
Which lung conditions can cause respiratory acidosis? (2)
- Emphysema
- Chronic bronchitis
What changes in the buffer system are caused by respiratory acidosis? (2)
- Increase in CO2 causes equilibrium to shift to the right so more H+ and HCO3- are produced
- This results in increase PCO2, increased HCO3- and low pH
What is the renal compensation for respiratory acidosis? (3)
- Increased H+ secretion
- Increased reabsorption of HCO3- (more been made)
- pH increases closer to normal at the expense of HCO3- levels being high
What changes in the buffer system are caused by respiratory alkalosis? (2)
- Decrease in CO2 causes equilibrium to shift to the left so H+ and HCO3- are used up
- This results in low PCO2, low HCO3- and high pH
What is the renal compensation for respiratory alkalosis? (3)
- Decreased H+ secretion
- Potential secretion of HCO3- (severe cases)
- pH drops closer to normal at the expense of low HCO3- levels
What diseases can cause metabolic acidosis? (3)
- Diarrhoea (loss of alkaline fluid)
- Cholera (diarrhoea)
- Diabetic ketoacidosis (generation of excess acid)
What changes in the buffer system are caused by metabolic acidosis? (2)
- Excess H+ bind with HCO3- forming H2CO3, H2O, CO2
- This results in low pH, low HCO3- and normal PCO2
What is the respiratory compensation for metabolic acidosis? (1)
Increased respiratory rate to decrease PCO2 (stimulation of chemoreceptors)
What is the renal compensation for metabolic acidosis? (2)
- Increased H+ secretion
- Increased reabsorption of new HCO3- (no change seen in HCO3- levels)
What changes in the buffer system are caused by metabolic alkalosis? (2)
- Loss of H+ causes equilibrium to shift to the right which generates H+ and more HCO3-
- This results in high HCO3-, high pH and normal PCO2
What issues can cause metabolic alkalosis? (2)
- Ingestion of alkaline fluid
- Vomiting (loss of acid)
What is the respiratory compensation for metabolic alkalosis? (2)
- Decreased respiratory rate to increase PCO2 (inhibition of chemoreceptors)
- More PCO2 causes more H+ and HCO3- to be made which bring pH down closer to normal
When is a mixed disorder life threatening?
When they are both of the same type e.g. respiratory and metabolic acidosis
When is a mixed disorder mild?
When they are of opposite types
What mixed disorder does an alcoholic patient have?
- Metabolic acidosis (breakdown of alcohol)
- Metabolic alkalosis (vomiting)
- Mild because they are opposite types
What mixed disorder does an asthma attack cause?
- Respiratory acidosis (can’t excrete CO2)
- Lactic (metabolic) acidosis (lack of O2)
- Life threatening because they are both acidosis
What mixed disorder do COPD patients who are treated with diuretics have?
- Respiratory acidosis (COPD, can’t get rid of CO2)
- Metabolic alkalosis (diuretics cause excretion of H+)
- Mild because they are opposite types
What mixed disorder does salicylate poisoning cause?
- Metabolic acidosis (ingested salicylic acid)
- Respiratory alkalosis (aspirin stimulates respiratory centre)
- Mild because they are opposite types
What is salicylate?
Aspirin (salicylic acid)
