Acid-Base Homeostasis Flashcards
The two major ways that the kidneys will regulate acids is via _ proximally and _ distally
The two major ways that the kidneys will regulate acids is via reabsorption of bicarbonate proximally and secretion of H+ distally
We reclaim bicarbonate in the proximal tubule primarily via _ exchangers
We reclaim bicarbonate in the proximal tubule primarily via Na/H exchanger on the lumen side and Na/K ATPase on the basolateral side
* These establish a gradient for the HCO3-/Na+ cotransporter
* This is an example of secondary active transport
The body has two main buffer systems _ and _
The body has two main buffer systems phosphate and ammonia
* HPO4(-2) and NH3
_ is our “titratable” acid buffer but it is in fact fixed and limited by dietary intake
Phosphate is our “titratable” acid buffer but it is in fact fixed and limited by dietary intake of phosphate
_ is our “fixed acid” aka non-titratable acid buffer that can be increased during times of increaed acid burden
Ammonium is our “fixed acid” aka non-titratable acid buffer that can be increased during times of increased acid burden
* We can undergo ammoniagenesis when we need increased production
The phosphate buffer is most active in _ region of the kidney
The phosphate buffer is most active in the distal tubule and collecting duct because phosphate is more concentrated in this region due to the reabsorption of water
Ammonia gets made in _ region of the kidney
Ammonia gets made in the proximal tubule
Under conditions of increased acid burden, the body relies on the ability to increase excretion of fixed acid via _
Under conditions of increased acid burden, the body relies on the ability to increase excretion of fixed acid via ammonia
Compensation never returns the pH to normal; thus if we see a normal pH consider _
Compensation never returns the pH to normal; thus if we see a normal pH consider that there may be a second primary acid/base disorder
Metabolic acidosis/alkalosis can be compensated via changes in _ ; this occurs in a matter of (hours/days)
Metabolic acidosis/alkalosis can be compensated via changes in ventilation ; this occurs in a matter of hours
* Compensation via the respiratory system is quick
Respiratory acidosis/alkalosis can be compensated via changes in _ ; this occurs in a matter of (hours/days)
Respiratory acidosis/alkalosis can be compensated via changes in bicarb reabsorption ; this occurs in a matter of days
* The kidneys are very slow to compensate
If you have a value that falls inside the shaded area, that means _
If you have a value that falls inside the shaded area, that means compensation occurs as expected
If you have a value that falls outside of the shaded area, in the middle regions, that means _
If you have a value that falls outside of the shaded area, in the middle regions, that means we have two primary acid/base disorders
Expected CO2 compensation for metabolic acidosis
Winter’s formula:
1.5 (bicarb) + 8 +/- 2
Expected CO2 compensation for metabolic alkalosis
0.7 (bicarb) + 20 +/-5
Expected bicarb compensation for respiratory acidosis
Acute 10:1
Chronic 10:4
In other words, for every 10 mmHg increase in PCO2, the HCO3- should increase by 1 mEq/L acutely (< 2 days) or 4 mEq/L chronically (2-5 days)
Expected bicarb compensation for respiratory alkalosis
Acute 10:2
Chronic 10:4
In other words, for every 10 mmHg decrease in PCO2, the HCO3- should decrease by 2 mEq/L acutely (< 2 days) or 4 mEq/L chronically (2-5 days)
Causes of non-AG metabolic acidosis
Diarrhea is a major cause of a normal anion gap metabolic acidosis
Causes of increased anion gap metabolic acidosis
GOLDMARK:
* Glycols (ethylene glycol, propylene glycol)
* Oxoproline (acetaminophen)
* L-lactate (hypoperfusion or medications)
* D-lactate (bacteria)
* Methanol posioning
* Aspirin toxicity
* Renal failure
* Ketoacidosis
Glycols and methanol toxicity will cause increased anion gap metabolic acidosis + osmol gap; however only _ will cause visual disturbances
Glycols and methanol toxicity will cause increased anion gap metabolic acidosis + osmol gap; however only methanol will cause visual disturbances
Aspirin toxicity can cause increased AG metabolic acidosis and _
Aspirin toxicity can cause increased AG metabolic acidosis and respiratory alkalosis
Causes of osmolar gap without metabolic acidosis
- Isopropyl alcohol poisoning
- Mannitol
- Dextran-40
- Glycine
- Sorbitol
Anion gap equation
AG = Na - Cl - bicarb
Osmol gap equation
Osmol gap = measured osmolality - expected osmolality
Differential for normal AG metabolic acidosis
Normal AG metabolic acidosis: ACCRUED
* Acute kidney disease
* Chronic kidney disease
* Carbonic anhydrase inhibitors
* Renal tubular acidosis *
* Ureteroenterostomy
* Expansion
* Diarrhea *
Causes of metabolic alkalosis
Metabolic alkalosis causes: BARFED
* Bartter/Gitelman syndromes
* Aldosteronism
* Fomiting (vomiting)
* Excess alkali
* Diuresis
There are two phases of metabolic alkalosis from vomiting _ and _
There are two phases of metabolic alkalosis from vomiting generation phase and maintenence phase
The generation phase involves the _ hypovolemia and loss of _ in the urine
The generation phase involves mild hypovolemia and loss of Na+, K+, HCO3- in the urine
Initially following a vomiting episode, we will see a loss of _ and the generation of _
Initially following a vomiting episode, we will see a loss of HCl, Na, H2O (from the stomach) and the generation of Na+, HCO3
During the generation phase, the body preferentially reaborbs (bicarb/ Cl-)
During the generation phase, the body preferentially reabsorbs Cl-
* WHY? because you lost lots of HCl in the vomit
* This means that bicarb is being lost
During the generation phase, _ electrolytes are being lost in the urine
Durine the generation phase, Na+, K+, and bicarb are being lost in the urine
The only time that there is a mismatch in urine Na+ and urine Cl- is during _
The only time that there is a mismatch in urine Na+ and urine Cl- is during generation phase of metabolic alkalosis
* Urine Na+ is high while urine Cl- is low
Urine pH during the generation phase of metabolic alkalosis (post vomiting) will be (acidic/basic/neutral)
Urine pH during the generation phase of metabolic alkalosis (post vomiting) will be neutral ~7
Explain the movement of electrolytes during the generation phase
- We must regain our Cl- supply so we sacrifice bicarb in exchange
- Bicarb (-) must take a positive (+) electrolyte with it to keep our urine neutral
- Na+ and K+ will go with the bicarb to keep the urine neutral (but we are losing these)
Urine electrolytes in generation phase of vomiting
Urine electrolytes in maintenance phase of vomiting
The maintenance phase of vomiting is characterized by a metabolic alkalosis with a paradoxical aciduria; explain
We would normally expect the kidneys to take care of a state of alkalosis by excreting base in the urine –> however, we have aciduria due to the bigger need to reclaim Na+
How do diuretics lead to metabolic alkalosis?
Loss of blood volume causes a secondary hyperaldosteronism (activated RAAS) which leads to increased secretion of H+ and alkalosis
Primary aldosteronism is a cause of metabolic alkalosis and hypertension; the body will combat the volume expansion via _
Primary aldosteronism is a cause of metabolic alkalosis and hypertension; the body will combat the volume expansion via
* Pressure natriuresis
* ANP
Once aldosterone increases the ECF above ~3L, _ occurs to prevent overload and edema
Once aldosterone increases the ECF above ~3L, pressure natriuresis occurs to prevent overload and edema
* We call this an “aldosterone escape” because we are escaping the effects of aldosterone
* New set point is established so that we are excreting sodium in balance with intake again
Three factors that contribute to the aldosterone escape:
Three factors that contribute to the aldosterone escape:
1. ANP is triggered by stretch and decreases sodium reabsorption in the collecting duct
2. Downregulation of the NaCl transporter in the DCT
3. Pressure natriuresis
Primary aldosteronism may present with metabolic alkalosis, hypokalemia and (high/low) urine Na+, Cl-
Primary aldosteronism may present with metabolic alkalosis, hypokalemia and high urine Na+, Cl-
* Due to aldosterone escape
The two main acid/base goals of the proximal tubule are:
The two main acid/base goals of the proximal tubule are:
1. Hold onto bicarb
2. Make ammonia to take care of H+
Proximal RTA (Type 2) is a _
Proximal RTA (Type 2) is a tubular defect in the HCO3 reabsorption
We expect urine pH to be _ in proximal RTA
We expect urine pH to be < 5.5 (distal acidification preserved) in proximal RTA
Proximal RTA is associated with (hypo/hyper) kalemia
Proximal RTA is associated with hypokalemia secondary to hyperaldosteronism that results from NaHCO3 loss
* Recall that bicarb is reclaimed on the basal membrane via the Na/Bicarb cotransporter
The acute insult of proximal RTA will result in _ urine pH and _ wasting
The acute insult of proximal RTA will result in urine pH > 6.5 and bicarb wasting
* Initially the problem with bicarb reabsorption will cause bicarb wasting in the urine and a basic pH
* This is the acute insult, before steady state is reached
Steady state conditions of a proximal RTA will result in _ urine pH and bicarb _
Steady state conditions of a proximal RTA will result in urine pH < 5.5 and total bicarb reabsorption
* All of the filtered HCO3 is now being reabsorbed, however, the amount of filtered HCO3 is just less
Proximal RTA can present as weakness, bone pain, bone fractures, and impaired growth; largely due to the wasting of _ and the decreased synthesis of _
Proximal RTA can present as weakness, bone pain, bone fractures, and impaired growth; largely due to the phosphate wasting and the decreased synthesis of active vitamin D
Proximal RTA is associated with lower levels of _ , the enzyme that is responsible for making active vitamin D
Proximal RTA is associated with lower levels of 1alpha-hydroxylase , the enzyme that is responsible for making active vitamin D, 1,25- dihydroxy vitamin D
What are the mechanisms by which we could end up with distal RTA?
Distal RTA can be due to:
1. Problem with H+ ATPase
2. Problem with ENaC
3. Problem with HCO3-/Cl- exchanger
Weakness, impaired growth in children, and calcium phosphate kidney stones, and CKD are common manifestations of _ RTA
Weakness, impaired growth in children, and calcium phosphate kidney stones, and CKD are common manifestations of distal RTA
RTA with decreased serum potassium and acidic urine (< 5.5) must be _
RTA with decreased serum potassium and acidic urine (< 5.5) must be proximal RTA
RTA with decreased serum potassium and basic urine (> 6) must be _
RTA with decreased serum potassium and basic urine (> 6) must be distal RTA
RTA with increased serum potassium and basic urine (> 6) must be _
RTA with increased serum potassium and basic urine (> 6) must be voltage-dependent hyperkalemic RTA
* Tubulointerstitial injury
* Drug that blocks ENaC
RTA with increased serum potassium and acidic urine (< 5.5) must be _
RTA with increased serum potassium and acidic urine (< 5.5) must be Type 4 RTA
* Problem with aldosterone
