SM 200a/201a - Acid Base Flashcards
What is Pendrin?
Which cells contain it?
Pendrin is an HCO3-/Cl- exchanger on the apical membrane of beta-intercalated cells of the collecting duct (secrete bicarb), and the basolateral membrane of alpha-intercalated cells of the collecting duct (reabsorb bicarb)
It functions to get HCO3- out of the cell, and Cl- into the cell
What is the effect of angiotensin II on HCO3- reabsorption and acid excretion?
Angiotensin II stimulates bicarbonate reabsorption and acid excretion
Angiotensin II -> kidney works to increase pH
(Angiotensin II is secreted in response to signals that indicate low volume; low volume -> hypoperfusion -> lactic acidosis -> decreased serum pH; kidney reacts by retaining bicarb and excreting acid)
What is citrate?
What is its role in acid-base balance?
Citrate is an organic anion
Citrate reabsorption is equivalent to base retention
- Main urinary base
- Reabsorbed and converted to CO2 and H2O
- This consumes H+ and generates OH-
- Chelates Ca2+
- Prevents precipitation with phosphate and oxalate ->
- *prevents kidney stones**
How does NH3 get across the membranes of the kidney tubule?
Diffusion
- Proximal convluted tubule
- Diffuses into the lumen
- Binds to H+ and becomes trapped
- Reabsorbed and recycled in the Loop of Henle
- Medullary collecting duct
- Diffuses into lumen
- Binds to H+ and becomes trapped and excreted
What is the differential for anion-gap metabolic acidosis?
MUDPILES: Acid add-on state
- Methanol
- Uremia
- Diabetic ketoacidosis (any ketoacidosis)
- Phenformin, paracetamol/acetaminophen, paraldehyde
- Iron, Isoniazid, Inborn errors of metabolism
- Lactic acidosis
- Ethanol/Ethylene glycol
- Saliclates/ASA/Aspirin
What is the Henderson-Hasselbach Equation for Biarbonate/Carbonic acid?
What acid-base transporters in the cell membrane protect the cell from changes in pH?
-
Na+/H+ exchanger
- Main mechanism
- Na+ dependent
- Cl-/HCO3- exhcanger
- Na+ independent
- Na+,HCO3-/H+,Cl- exchanger
- Na+ dependent
What is the effect of hypokalemia on HCO3- reabsorption and acid excretion?
Hypokalemia stimulates bicarbonate reabsorption and acid excretion
Hypokalemia -> kidney works to increase serum pH
In which tubules of the kidney is bicarbonate reabsorption driven by the Na+/H+ exhchanger?
Proximal tubule
Thick ascending limb of LOH
(Not the collecting tubule, although Na+ indirectly affects H+ secretion in the CT)
Where in the kidney tubule is NH4+ reabsorbed?
Loop of Henle
What is the equation for urine anion gap?
How do you use it?
[Na+] + [K+] + [NH4+] = [Cl-]
Useful in in ruling in/out RTA as a cause of hyperchloremic (non-AG) metabolic acidosis
- If [Na+] + [K+] > [Cl-], then there is no NH4+ in the urine
- If this is true while the patient is acidemic, the kidney tubules are not properly acidifying the urine
- If [Na+] + [K+] -], then there is NH4+ in the urine
- This is an indication of acid excretion, which means the metabolic acidosis is not likely to be caused by RTA
Why might does amiloride cause metabolic acidosis?
Amiloride blocks Na+ reabsorption in the collecting duct
- Decreased Na+ reabsorption
- -> Decreased Na+/H+ exchange
- -> Decreased H+ secretion
- -> Metabolic acidosis
Describe the pathophysiology of diabetic ketoacidosis
Lack of insulin
- -> Lipolysis and release of fatty acids
-
-> Accumulation of ketone bodies
- Acetoacetatic acid and beta-hydroxybutyric acid
-
-> Accumulation of ketone bodies
What is Type A lactic acidosis?
Increased lactic acid generation
- Due to tissue hypoxia
- Severe hypotension
- Cardiac arrest
- Sepsis
(Type B = decreased utilization of lactic acid)
A state of _______________ leads to the formation of glutamine in the liver
A state of metabolic acidosis leads to the formation of glutamine in the liver
What is the most frequent and severe cause of H+ build up in the circulation?
Lactic acidosis
Describe the transport of NH4+ (ammonia) in the kidney tubule
-
Glutamine –> NH4+ in the proximal tubule
- Glutamine into PCT epithelial cell through the basolateral membrane
- Glutamine –> NH4+ –> NH3 + H+
- H+ is secreted into the tubule via H+/Na+ exchanger
- NH3 diffuses into the tubule
- In the tubule, NH3 + H+ –> NH4+
-
NH4+ is reabsorbed in the Loop of Henle
- NH4+/K+ exchanger
- Na+/NH4+/Na+ exchanger
- NH4+ channel
-
NH3 diffuses into the medullary collecting duct, binds to H+ and is trapped as NH4+
- Acid (H+) secreted by collecting duct epithelial cells binds to NH3 and becomes trapped as NH4+
- This is how the body secretes acid while retaining bicarb
What is the differential for non-anion gap (hyperchloremic) metabolic acidosis?
USED CARS: Bicarb loss
- Uretrosigmoidostomy
- Saline administration (NaCl)
- In the face of renal dysfunction
- Endocrine (addison’s), Ethanol
- Diarrhea
- Carbonic anhydrase inhibitors
- Ammonium chloride
- Renal tublar acidosis
- Spironolactone
Meatabolic Acidosis is a primary disturbance characterized by _________________
Meatabolic Acidosis is a primary disturbance characterized by
a fall in blood bicarbonate levels
This leads to decreased pH
Why do you see hypokalemia in Distal RTA?
DRTA = the distal tubule (alpha-intercalated cells) cannot secrete H+
- Lumen is negatively charged due to Na+ reabsorption
- Pulls + charge in
- K+ is secreted instead
Describe the “classic presentation” of Distal RTA
- Hyperchloremic metabolic acidosis
- Inability to lower urinary pH below 5.5 despite acidemia
- Due to impaired H+ secretion
- Hypokalemia
- Lumen negatively charged due to Na+ reabsorption; if H+ cannot be secreted, K+ is secreted
- Nephrocalcinosis (increased Ca2+ in the kidney tubule)
- Lumen negatively charged due to Na+ reabsorption; if H+ cannot be secreted, Ca2+ is secreted
- Kidney stones
- Due to increased Ca2+
Describe the process of HCO3+ reabsorption in the proximal tubule
There is no “bicarbonate transporter” on the apical membrane
Na+ gradient into the cell is necessary to drive H+ secretion in the apical membrane via Na+/H+ exchanger
- H+ secreted into the lumen is important (Na+/H+ exchanger, H+ pump)
- HCO3- combines with H+ to form H2CO3
- H2CO3 breaks down into H2O and CO2 via carbonic anhydrase
- CO2 diffuses across the basolateral membrane
- H2O diffuses across the baslolateral membrane via AQP1
- CO2 combines with H2O to form H2CO3 via carbonic anhydrase
- H2CO3 dissociates into H+ and HCO3-
-
HCO3-/Na+ cotransporter (NBCe1a) transports Na+ and 3(HCO3-) into the interstitium
- This is the only difference from HCO3- reabsorption in the TAL
- The TAL has a HCO3-/Cl- exchanger instead
- Na+ gradient is maintained by Na+/K+ ATPase
What are the major causes of metabolic alkalosis?
- Loss of H+ ions
- GI
- Loss of gastric acid secretions
- Vomiting, NG tube
- Loss of gastric acid secretions
- Renal
-
Loop or thiazide diuretics
- More Na+ delivery to cortical collecting duct stimulates principal cells to reabsorb more Na+
- This creates a favorble charge gradient for alpha intercalated cells to secrete H+
-
Mineralcorticoid excess
- Aldosterone stimulates alpha intercalated cells to reabsorb bicarb and secrete H+
- Bartter and Gitelman syndromes
-
Loop or thiazide diuretics
- GI
- Retention of administered bicarbonate
- Milk Alkali syndrome
- Administration of NaHCO3
What is the effect of volume depletion on HCO3- reabsorption and acid excretion?
Volume depletion stimulates bicarbonate reabsorption and acid excretion
Volume depletion -> kidney works to increase pH
(Is this a response to the decreased perfusion and resulting acidosis associated with volume depletion?)
What is the major function of the alpha-intercalated cells in the collecting tubule?
Secrete acid (H+)
Reabsorb K+ (H+/K+ exchanger)
What are the two main urine buffers?
Phosphate (HPO42- )
H+ + HPO42- —> H2PO4-
Ammonia (NH3)
H+ + NH3 —> NH4+
What is the effect of volume expansion on HCO3- reabsorption and acid excretion?
Volme expansion inhibits bicarbonate reabsorption and acid excretion
Volume expansion -> kidney works to decrease pH
Why is ammonia production and excretion in the kidney important?
It is important for reabsorbing bicarbonate
What is the main pH regulatory transporter that protects the cell from acid load?
Na+/H+ exchanger
What is type B lactic acidiosis?
Decreased utilization of lactic acid
- Liver failure
- Drugs
- Malignancies
(Type A = Increased lactic acid generation)
What are the clinical features of proximal RTA?
- Fanconi syndrome
- Bicarb wasting
- Glycosuria
- Phosphauria
- Hyperuricosuria
- Aminoaciduria
- Hypokalemia
- No nephrocalcinosis or kidney stones
- Rickets
What are the 4 general mechanisms of metabolic acidosis
(a low HCO3 state)?
- Loss of HCO3- externally
- Diarrhea
- Proximal RTA
- Failure of the kidneys to excrete acid
- Distal RTA
- CKD
- Acid retained in the body uses up bicarb
- Addition of H+ which titrates HCO3-
- Drinking something with H+
- H+ buildup in the circulation
- Lactic acidosis
- Ketoacidosis
Metabolic Alkalosis is an acid-base disorder characterized by ________________
Metabolic Alkalosis is an acid-base disorder characterized by a primary increase in blood bicarbonate concentration
Primary = not in response to an acidosis
What compensatory mechanisms in the kidney are activated by metabolic alkalosis?
- Reduced bicarbonate reabsorption along the nephron
- Increased secretion of bicarbonate by beta-intercalated cells
What are the major functions of principal cells in the collecting tubule?
Reabsorb Na+
Secrete K+
If there is an excess bicarbonate load, which section of the kidney is responsible for secreting it?
Cortical collecting duct beta-intercalated cells
Secrete bicarb through upregulation of pendrin
Describe the process of HCO3+ reabsorption in the thick ascending limb
There is no “bicarbonate transporter” on the apical membrane
Na+ gradient into the cell is necessary to drive H+ secretion in the apical membrane via Na+/H+ exchanger
- H+ secreted into the lumen is important (Na+/H+ exchanger, H+ pump)
- HCO3- combines with H+ to form H2CO3
- H2CO3 breaks down into H2O and CO2 via carbonic anhydrase
- CO2 diffuses across the basolateral membrane
- H2O diffuses across the baslolateral membrane via AQP1
- CO2 combines with H2O to form H2CO3 via carbonic anhydrase
- H2CO3 dissociates into H+ and HCO3-
-
HCO3-/Cl- exchanger transports Cl- into the cell 3(HCO3-) into the interstitium
- This is the only difference between TAL and PCT (Na+/HCO3- cotransporter in the PCT)
- Na+ gradient is maintained by Na+/K+ ATPase
This is basically the same in the TAL, except there is a HCO3-/Cl- cotransporter on the basolateral membrane instead of a Na+/HCO3- exchanger
What is the effect of aldosterone on HCO3- reabsorption and acid excretion?
Aldosterone stimulates bicarbonate reabsorption and acid excretion
Aldosterone -> kidney works to increase pH
(Aldosterone II is secreted in response to signals that indicate low volume; low volume -> hypoperfusion -> lactic acidosis -> decreased serum pH; kidney reacts by retaining bicarb and excreting acid)
What process is occuring?
Is it adequately compensated?
- pH: 7.55 (7.36-7.42)
- pCO2: 52 (40)
- HCO3: 44 (NORMAL=24)
Metabolic alkylosis
- Comparing pH and pCO2: yes
- 55 is about equal to 52
- Comparing pCO2 and HCO3: yes
- ΔpCO2 = 12, which is about half of ΔHCO2 (20)
- Compensation: ΔpCO2 = 0.6 * ΔHCO3
How do you treat metabolic alkalosis?
Cl- administration
NaCl usually
KCl if the patient is hypokalemic
Based on pCO2 and HCO3- levels, how can we tell if an acid/base process is appropriately compensated?
Metabolic acidosis:
Metabolic alkalosis:
Chronic respiratory acidosis:
Chronic respiratory alkalosis:
Metabolic
-
Acidosis: pCO2 and HCO3- decrease about the same amount
- ΔpCO2 = 1.2 * ΔHCO3-
- Metabolic acidosis = Decreased pH, decreased pCO2
- Bicarb will be used up to neutralize extra acid?
-
Alkalosis: pCO2 inreases about twice as much as HCO3-
- ΔpCO2 = 0.6 * ΔHCO3-
- Metabolic alkalosis = Increased pH, increased pCO2
- Bicarb will be produced
Respiratory
-
Acidosis: Increase in HCO3- is about twice as much as increase in pCO2
- ΔHCO3- = 0.4 * ΔpCO2
- Respiratory acidosis = Decreased pH, increased pCO2
- Kidney will reclaim bicarb to compensate for low pH
-
Alkalosis: Decrease in HCO3- is about twice as much as decrease in pCO2
- ΔHCO3- = 0.5 * ΔpCO2
- Respiratory alkylosis = Increased pH, decreased pCO2
- Kidney will excrete bicarb to compensate for high pH
Why do you see kidney stones in patients with Distal RTA?
Distal RTA = problem secreting H+ in the distal convoluted tubule
- The lumen is negatively charged due to Na+ reabsorption
- If H+ cannot be secreted, Ca2+ and K+ are secreted instead
- Increased Ca2+ in the tubule -> kidney stones
What percentage of NH4+ produced in the proximal tubule is excreted in the urine?
100%
What is the major function of the beta-intercalated cells in the collecting tubule?
Secrete HCO3- (HCO3-/Cl- exchanger)
Secrete K+
How do you calculate the anion gap in an acid-base process?
Serum AG = [Na+] - [Cl-] - [HCO3-]
Urine AG = [Na+] + [K+] - [Cl-]
I like to think of this as [Na+] + [K+] + [NH4+] = [Cl-] to remember what it actually means
- Note on Urine AG
- If [Na+] + [K+] > [Cl-], then there is no NH4+ in the urine
- If this is true while the patient is acidemic, the kidney tubules are not properly acidifying the urine
- If [Na+] + [K+] -], then there is NH4+ in the urine
- This is an indication of acid excretion
- If [Na+] + [K+] > [Cl-], then there is no NH4+ in the urine
Why is Na+ important for protecting the cell from an acid load?
The Na+/H+ exchager (main intracellular pH regulator) depends on extracellular Na+ in order to get H+ out of the cell
Where in the kidney tubule is NH4+ formed?
Proximal tubule
Where is metabolic alkalosis generated?
Where is it maintained?
- Generated by the stomach
- Gastric fluid loss
- Decreased H+ secretion
- Maintained by the kidneys
- Increased bicarbonate reabsorption
What are the compensatory responses to metabolic alkalosis?
- Alkalemia is sensed by the peripheral chemoreceptors
- -> decreased respiration
- -> CO2 retention
- -> increased pCO2
- 0.6 mmHg for every 1 Meq/L increase in HCO3
- => +10 HCO3 = +6 pCO2
Note: There is a limit to respiratory compensation for metabolic alkylosis because too much of a decrease in ventilation would cause hypoxemia
What process allows for both reabsorption of HCO3- and H+ excretion?
De Novo Bicarbonate formation in the collecting duct
Requires the action of carbonic anhydrase
NH3 combines with H+ secreted into the lumen and traps it as NH4+ - this allows for H+ excretion without HCO3- excretion
