Metabolic acid base balance Flashcards
Describe normal pH and define acidosis and alkalosis
- normally pH is 7.4 and very tightly regulated within a normal range
- if higher than 8 or lower than 6.8 it is incompatible with life
- if pH is 7.35 or lower, this is termed acidosis (which depresses the CND, and leads to extreme conditions such as coma and respiratory failure)
- if pH is 7.45 or higher, this is considered alkalosis (stimulates SNS, and leads to extreme conditions such as muscle seizures and convulsions)
- Therefore, acidosis starts at an alkaline pH, but is acidic relative to the reference scale
What are the consequences of metabolic acidosis and alkalosis?
- acidosis (which depresses the CND, and leads to extreme conditions such as coma and respiratory failure)
- alkalosis (stimulates SNS, and leads to extreme conditions such as muscle seizures and convulsions)
Describe sources of acid input and output
input: diet and cellular metabolism
- output: hydrogen ions, handled by kidneys, and carbon dioxide, handled by the lungs
- layers of defence against pH disturbances: chemical buffering, pre-respiratory and renal responses (See also [[Physiology Lecture 6])] for buffers)
What is the role of the kidney in acid base balance?
Kidneys excrete and reabsorb H and HCO2
- kidneys are responsible for 25% compenstation of acids not handled by lungs
- they do this via direct and indirect mechanisms
- directly: excreting or reabsorbing hydrogen ions
- indirectly: excreting or reabsorbing bicarbonate buffer
Describe the actions of the kidney in acidosis and alkalosis
In acidosis the kidneys do two things:
- secrete hydrogen ions by primary and secondary active transport mechanisms. Examples include:
- buffering protons with ammonia and phosphate
- making new bicarbonate ions from carbon dioxide and water
- synthesise ammonia (HCO3 is a by-product of this process)
In alkalosis:
- processes are reversed: excrete the bicarbonate and reabsorb hydrogen ions (to help bring down the alkaline pH)
True or false: renal compensation is the fastest mechanism of acid-base balance
FALSE - renal compensation is the slowest mechanism of acid-base balance
List the transporters involved in renal handling
- Na+/H+ antiporter
- Na+/HCO3- symporter
- H+-ATPase
- H+/K+-ATPase
- Na+/NH4+ antiporter
- Na+/K+-ATPase
- HCO3-/Cl- antiporter
What are the components of net urinary acid excretion?
NAE = excreted hydrogen ions bound to phosphate, uric acid and creatinine (filtered buffer, not synthesised by kidney) + excreted protons bound to ammonia (Synthesised buffer) - excretion of filtered bicarbonate ions
Define titratable acid
The primary urinary buffer is phosphate (although there are others, a.k.a filtered buffers).
The urinary buffers are collectively referred to as titratable acids.
- protons transported into tubule using pump (H-ATPase or H/K ATP-ase)
- proton comes from carbonic anhydrase reaction (H2CO3–> Hco3- and H+)
- hydrogen ions binds with buffer in tubular fluid, to be excreted
Describe reabsorption of bicarbonate and how it is regulated
- all HCO3 is essentially reabsorbed
- modulated by hydrogen ion/ proton secretion
- additionally, it is regulated by H concentration gradient: more H, more efficient
- activity and expression of key H and HCO3 transporters is also regulated and affects efficiency e.g. by acidity levels
- in acidosis (secretion is favourable, therefore) increased H- ATPase in collecting duct, and Na/H antiporter and Na/3HCO3 expression and activity is increased in proximal tubule
- in alkalosis (retention is favourable, therefore) the reverse effects, decreased H-ATPase in collecting duct and decreased Na/H and Na/3HCO3 expression and activity ^[in addition to any other effects?]
Describe the relationship between plasma bicarbonate and urine bicarbonate
- similar to glucose pattern
- filtered and reabsorbed levels proportional to a point of saturated, then appear in urine i.e. excreted
- note threshold of plasma bicarbonate concentration before significant HCO3 appearance in urine is equivalent to normal plasma concentration
- therefore kidneys are well placed to excrete excess HCO3, minimising alkalosis
Why are kidneys well placed to excrete excess bicarbonate?
- similar to glucose pattern
- filtered and reabsorbed levels proportional to a point of saturated, then appear in urine i.e. excreted
- note threshold of plasma bicarbonate concentration before significant HCO3 appearance in urine is equivalent to normal plasma concentration
- therefore kidneys are well placed to excrete excess HCO3, minimising alkalosis
Describe reabsorption of bicarbonate
- proton concentration in tubule is key
- h2co3 formed
- ca on tubular side, results in co2 formed
- h2co3 reformed in cell
- ca leads to regeneration of hco3
- na/hco3 and cl/hco3 export HCO3 into blood
- Note: Na/K/ATPase contributes to exchanger function
Does secretion of bicarbonate normally occur? If so, how?
Secretion of HCO3 in collecting duct
NOTE: ONLY in alkalosis
- co2 diffuses into cell
- hco3 exchanged for cl
- h pumped with ATPase into interstitial space and blood, helping to correct
Describe the process of formation of new HCO3
For acid-base balance to be maintained, the kidneys must replenish any lost HCO3-
- This is achieved via 2 mechanisms
- Some of the HCO3- is produced during titration of urinary buffers in collecting duct
- note: not regulated by body’s requirement to maintain normal pH– non-specific process, simple buffering)
- 2nd mechanism is regulated
- synthesis of ammonia, producing bicarbonate
- occurs in early proximal tubule
- in mitochondria
- glutamine taken up from interstitial or tubule
- glutamine to glutamate
- glutamate to aKG
- both steps generate ammonium
- aKG to glucose requires protons, OH reacts with CO2 to form HCO3
- one glutamine = 2HCO3
- ammonium dissociates into ammonia, freely diffuses, h pumps out, forms ammonium again in tubule lumen
