Acid Base Balance Flashcards
(starting at slide 12) What 2 basic ways does the kidney regulate [HCO3-]?
- Reabsorbing filtered HCO3-
- Generating new HCO3-
What do the 2 processes for kidney regulation of HCO3- depend on?
Active H+ secretion from tubule cells in lumen
Describe the mechanism for reabsorption of HCO3-; SEVEN steps !
- Active H+ secretion from tubule cells (coupled with passive Na+ reabsorption)
- Filtered HCO3- reacts with secreted H+ to form H2CO3; in presence of carbonic anhydrase on luminal membrane -> CO2 and H2O
- CO2 is freely permeable and enters cell
- Within cell, CO2 -> H2CO3 in presence of carbonic anhydrase which then dissociates to form H+ and HCO3-
- H+ ions are source of secreted H+
- HCO3- ions pass into peritubular capillaries with Na+
- Bulk of HCO3- reabsorption occurs in proximal tubule >90%
Why does it not matter that the HCO3- reabsorbed is not the same ion as was filtered?
The NET effect is the same; HCO3- is a large charged molecule, by converting it to CO2 it is much easier to save this valuable buffer
What is the importance of HCO3- reabsorption?
GFR = 180l/day
[HCO3-] = 24mmoles/l = 4320mmoles HC03- filtered per day
Must be reabsorbed, since failure to do so means adding H+ to the ECF
Is there any excretion of H+ ions during HCO3- reabsorption?
Nope
HCO3- reabsorption diagram
What is the range of urine pH in humans?
Minimum = 4.5-5.0
Maximum = ~8.0
Net production of H+ daily is 50-100 mmoles, if this was present as free H+ ions pH of 1L urine would be 1!; what acts as a buffer for urine? What is this process called?
Several weak acids and bases - mostly bibasic phosphate (HPO42-)
Also uric acid and creatinine
Process is called ‘titratable acidity’ because its extent is measured by the amount of NaOH needed to titrate urine pH back to 7.4 for a 24hr urine sample
What is the importance of the formation of titratable acidity?
It generates new HCO3- and excretes H+
What is titratable acidity only used for?
Acid loads
Give the methods in which ‘titratable acidity’ 1. removes H+ from body and 2. generates new HCO3-
- Na2HPO4 in lumen; one Na+ is reabsorbed in exchanged for secreted H+ - this monobasic phosphate removes H+ from body
- Source of new HCO3- is indirectly CO2 from blood; it enters tubule cells, combining with H2O to form carbonic acid in presence of carbonic anhydrase, which then dissociates to yield H+, used for secretion, and new HCO3-, which passes with Na+ into the peritubular capillaries
Where does titratable acidity principally occur?
In the distal tubule; this is where phosphate ions, not reabsorbed by the proximal tubule Tm mechanism, become greatly concentrated because of removal of up to 95% of the initial filtrate
What is the titratable acidity process dependent on?
PCO2 of blood
Diagram of titratable acidity 2 processes
Why is the distal tubule to site of formation of titratable acidity?
Because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate in proximal tubule and loop of Henle
What is ammonium excretion a major adaptive response to?
An acid load - generates new HC03- AND excretes H+
(ONLY used for acid loads)
What is the basis for ammonium excretion?
The difference in solubility between NH3 and NH4+
NH3 is lipid soluble and NH4+ is not
Give the process by which NH4+ is excreted
Glutamine in proximal tubule cells is metabolised to alpha-ketoglutarate and 2 amino groups
NH3 is produced by deamination of the amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells
NH3 moves out into tubule lumen, where it combines with secreted H+ ions in the distal tubule to form NH4+, which combines with Cl- ions (from NaCl) to form NH4Cl which is excreted
What is the source of secreted H+ for combination with NH3?
Again - CO2 from blood
Give the process by which new HCO3- is formed along with the excretion of ammonium
The alpha-ketoglutarate molecule is further metabolised to HC03-, which is transported into the blood (peritubular capillaries) along with Na+
How does NH4+ formed in cells in proximal tubule pass out into lumen?
There is an NH4+/Na exchanger
(net effect is the same)
Ammonium excretion in distal tubule
Ammonium excretion in proximal tubule
Activity of renal glutaminase is exquisitely dependent on what?
pH
When intracellular pH fallls = increase in renal glutaminase activity and therefore more NH4+ produced and excreted
Which is the MAIN adaptive response of the kidney to acid loads?
the ability to augment NH4+ production
Why does it take 4-5 days for augmentation of ammonium excretion in response to acid load to take effect?
Because of the requirements of increased protein synthesis
Normally only 30-50mmoles H+ per day are lost as NH4+, but this can increase to how much in the presence of severe acidosis?
250mmoles/l
It also takes time to swtich off the ability to make NH4+; in what situation is this done?
When there is excess of alkali
By the time an acid-base disturbance becomes evident as a change in plasma pH, are the body’s buffers effective?
NOPE
What do resp disorders affect?
PCO2
What do renal disorders affect? (PCO2 or HCO3)
[HCO3-]
What does respiratory acidosis result from?
Reduced ventilation and therefore retention of CO2
(alveolar hypoventilation)
Give 2 ACUTE causes of respiratory acidosis
- Drugs which depress the medullary resp centres e.g. barbiturates and opiates
- Obstruction of major airways
Give a CHRONIC cause of respiratory acidosis
Lung disease e.g. bronchitis, emphsyema, asthma
What is the physiological response to resp acidosis?
Need to protect the pH so need an increase in [HC03-]
Increased PCO2 -> increased secretion of H+ and increased HCO3-
Acid conditions stimulate renal glutaminase so get more NH3 produced, BUT, it takes time !
Increased generation of new HCO3 as well as increased reabsorption of HCO3 (the increased PCO2 will also increase the ability to reabsorb it)
Although renal compensation to increase the HCO3- protects the pH, it does not correct the original disturbance - what is the only thing that can do that?
Resoration of normal ventilation
(same in respiratory alkalosis)
What does this mean for blood gas values in chronic resp acidosis e.g. bronchitis?
Blood gas values are NEVER normalised
(they may be eg pH 7.32, Pco2 65mmHg (8.67 kPa), [HCO3-] 38 mmoles/l)
Patients with lung disease will always have aberrant PCO2 and [HCO3-], but as long as kidney function is not impaired pH can be maintained at a level compatible with life - problems arise when these patients develop renal dysfunction
What is the hallmark of respiratory acidosis (in terms of levels)?
Decreased pH with elevated bicarbonate levels
How does respiratory alkalosis occur?
Due to a fall in PCO2 and this can only occur through increased ventilation and CO2 blow-off
(alveolar hyperventilation)
Give 3 causes of ACUTE respiratory alkalosis
- Voluntary hyperventilation
- Aspirin
- First ascent to altitude
Give a cause of CHRONIC respiratory alkalosis
Long term residence at altitute (decreased PO2 to <60mmHg (8kPa) stimulates peripheral chemoreceptors to increase ventilation)
What should happen in resp alkalosis to protect pH?
[HCO3-] should decrease
How does breathing into a paper bag help to partially reverse the neurological symptoms caused by resp alkalosis in a patient who is hysterically hyperventilating due to anxiety?
The patient re-breathes exhaled CO2 which raises arterial PCO2 and corrects the problem
By which mechanism are alkaline conditions dealt with? What happens?
HCO3- reabsorptive mechanism
If PCO2 is decreased = less H+ is available for secretion therefore less of the filtered load of HCO3- is reabsorbed so HCO3- is lost in the urine
Metabolic acidosis must be due to what?
A decrease in [HCO3-]
Either due to increased buffering of H+ or direct loss of HCO3-
What must be done in metabolic acidosis to protect pH?
PCO2 must be decreased
Give 3 causes of metabolic acidosis
- Increased H+ production, as in ketoacidosis of a diabetic (acetoacetic acid, beta-hydroxybutyric acid) or in lactic acidosis
- Failure to excrete normal dietary load of H+ as in renal failure
- Loss of HCO3- as in diarrhoea (i.e. failure to reabsorb intestinal HCO3-)
What does the resulting metabolic acidosis stimulate?
Ventilation -> so that PCO2 falls
Increase in ventilation is in depth rather than rate - may be very striking, reaching a max of 30 l/min cf normal 5-6 l/min when the arterial pH falls to 7.0
This degree of hyperventilation = Kussmaul breathing = an established clinical sign of renal failure or diabetic ketoacidosis (v serious)
How is the disturbance normally corrected in acidosis?
Kidneys normally correct disturbance by restoring [HCO3-] and getting rid of H+ ions
What is the problem with the normal reaction to acidosis by the kidneys when in metabolic acidosis?
Source of H+ ions is the carbonic acid from CO2, but the resp compensation lowers the PCO2 to protect the pH !!!
Compensations for A/B disturbances are always in the same direction as what?
The initial disturbance
Remeber pH is defined as ration of [HCO3-]/PCO2
However they are never quite to the same extent i.e. not complete - so pH is not restored to 7.4
What is the survival of there not being complete compensation for A/B disturbance?
Complete compensation would remove the drive to correct the original disturbance
If there was no pressure to correct initial disturbance, a further preturbation may push the system so far that compensation can no longer be effective
Because of the decreased PCO2, the total amount of H+ secreted by the renal tubule will be less than normal in metabolic acidosis, but why does this not impact HCO3- reabsorption and titratable acid?
The plasma [HCO3-] and therefore filtered load of HCO3- is reduced to an even greater extent, so a smaller fraction of total H+ is needed for HCO3- reabsorption and therefore a greater proportion is available for excretion in the form of titratable acid and NH4+
How long does the renal compensation of metabolic acidosis take to reach full effectiveness?
A few days (so not usually seen in acute disturbances)
What occurs immediately with increased H+ within the body? What occurs within minutes?
Buffering in ECF and then ICF
Respiratory compensation
What reaction takes longer to develop its full response to increased metabolic H+? Why?
Renal correction of the disturbance takes longer to develop the full response to increased H+ excretion and generate new HCO3- because renal glutaminase takes 4-5 days to reach max
What happens once renal compensation occurs in metabolic acidosis?
As HCO3- starts to increase, resp compensation begins to wear off untul eventually get rid of all excess H+
So, resp compensation delays renal correction, but protects pH, which is much more important
What increases in metabolic alkalosis? What must then increase to protect pH?
[HCO3-] must have increased
PCO2 will increase to protect pH
Give 4 causes of metabolic alkalosis
- Increased H+ ion loss - vomiting - loss of gastric secretion
- Increased renal H+ loss - aldosterone excess, excess liquorice ingestion
- Excess administration of HCO3- -unlikely to produce a metabolic alkalosis in subjects with normal renal function, but may if renal function impaired
- Massive blood transfusions can lead to metabolic alkalosis - bank blood contains citrate to prevent coagulation, which is convered to HCO3-, but need at least 8 units to have this effect
How is metabolic alkalosis dealt with? (same a resp alkalosis)
- The greatly filtered load of HCO3- exceeds level of H+ secretion to reabsorb it, even in presence of increased PCO2, so the excess is lost in urine
- Again, resp compensation delays renal correction, but protects the pH
Give the H+ levels, pH levels, I° disturbance and compensation for: respiratory acidosis
H+ = increased
pH levels = decreased
I° disturbance = increased PCO2
Compensation = increased [HCO3-]
Give the H+ levels, pH levels, I° disturbance and compensation for: respiratory alkalosis
H+ = decreased
pH levels = increased
I° disturbance = decreased PCO2
Compensation = decreased [HCO3-]
Give the H+ levels, pH levels, I° disturbance and compensation for: metabolic acidosis
H+ = increased
pH levels = decreased
I° disturbance = decreased [HCO3-]
Compensation = decreased PCO2
Give the H+ levels, pH levels, I° disturbance and compensation for: metabolic alkalosis
H+ = decreased
pH = increased
I° disturbance = increased [HCO3-]
Compensation = increased PCO2
A decrease in pH (acidosis) is caused by one of what 2 things?
Decreased HCO3+
Increased PCO2
An increase in pH (alkalosis) is caused by one of what 2 things?
Increased HCO3-
Decreased PCO2
V IMPORTANT - for a given increase in PCO2, there is a smaller decrease in pH in which - chronic or acute? Why?
Smaller decrease in chronic
NH3 production has a considerable capacity to raise HCO3- but takes 4-5 days to be fully turned on so in chronic it is utilised and pH drops to a lesser extent
(similar diff in acute v chronic resp alkalosis - delay in turning off NH3 production)
In reality - A/B imbalance doesnt just occur in isolation and in otherwise healthy individuals; consider a badly controlled diabetic in ketoacidosis who also has chronic bronchitis and a haemhorrage - what would they then have in terms of A/B balances?
- Metabolic acidosis (ketoacidosis)
- Resp acidosis
- Lactic acidosis (haemhorrage)
= combined metabolic and respiratory acidosis
(BG values: pH = 6.99; PCO2 = 60mmHg (8kPa); HCO3- = 13mmoles/l)
What specifically does high acid cause (in terms of electrolyte imbalance)?
Hyperkalaemia (as H+ ions are buffered intracellularly in exchange for K+ ions); danger of ventricular fib
Homeostatic plateau
3 management strategies for hyperkalaemia?
- Insulin (+ glucose if non-diabetic) = stimulates cellular uptake of K+
- Calcium resonin - oral/pr = exchanges Ca2+ ions for K+ ions (24 hrs)
- Ca gluconate (iv) = reduces excitability of heart, stabilizes cardiac muscle cell membranes
(careful monitoring essential - risk of hypokalaemia)
Hyperkalaemia in acidosis and effect of management via insulin
How does a bad case of vomiting demonstrate the precedence that hypervolaemia takes over correction of metabolic alkalosis (or any acid/base imbalance)
Loss of NaCl and H2O -> hypovolaemia
loss of HCl -> alkalosis
Hypovolaemia stimulates aldosterone to increase distal tubule Na+ reabsorption - the main ion exchanged for Na+ is H+ (also due to loss of Cl-)
Resp compensation for metabolic alkalosis (increased PCO2) helps drive H+ secretion = exacerbates metabolic alkalosis by adding yet more HCO3- to plasma
Exacerbation of metabolic alkalosis via increased loss of H+ in correction of hypovolaemia
How do we restore volume and therefore allow metabolic alkalosis to be corrected in heavy vomiting?
Give NaCl
In vomiting and diarrhoea, although we lose both acid and alkali, why do we become alkalotic?
Decreased ECF volume = increased aldosterone = ‘contraction alkalosis’
What is the anion gap?
The difference between the sum of the principal cations (Na+ and K+) and the principal anions in the plasma (Cl- and HCO3-)
What is the normal anion gap?
14-18mmoles/L
i.e. (140+4) - (104-24) = 16mmoles/L (due to plasma proteins)
In what situation is it useful to measure the anion gap?
Metabolic acidosis
What are the 2 patterns of metabolic acidosis in terms of anion gap?
- No change from normal (acidosis due to loss of bicarbonate from gut - reduction of bicarb is compensated by an increase in chloride - no change in gap)
- Anion gap increases (e.g. lactic or diabetic acidosis, due to reduction in bicarb is made up by other anions such as lactate, acetoacetate, ß-OH butyrate - anion gap increases)
What is normal: pH, PCO2, HCO3-
pH = 7.4 (range 7.37-7.43)
PCO2 = 40mmHg/5.3kPa (range 4.8-5.9)
HCO3- = 24mmoles/l (range 22-26)
