Acid/base Flashcards
Sources of H+
All from metabolism Carbonic acid (volatile, H2CO3) - excreted at lungs - H+ produced - need CA -reversed at lungs
Non-carbonic acids (non-volatile, HCl, H2SO4)
- metabolism of proteins, sulfates, phosphates
- daily acid load
- 50-100 mEq/day on normal diet
- buffered by HCO3-
Buffering systems for H+
Intracellular: inorganic phosphates, cystosolic proteins, hemoglobin/RBC
Extracellular: HCO3-/CO2 (primary mechanism), plasma proteins, inorganic phosphates
Bone: important in acidosis, takes up H+, dissolve bone mineral, breaks down carbonate –> bicarb and releases bicarb as buffer
Respiratory compensation for metabolic acidosis
- due to increase in H+ or decrease in bicarb
- causes decrease in HCO3- concentration
- increased ventilation –> decrease pCO2, rectifies ([H+] is proportional to pCO2/[HCO3-])
- H+ ion concentration in plasma determined by pCO2
- should not be able to completely resolve acidosis
Kusmall breathing: fast, deep –> diabetic ketoacidosis
Rule of thumb: for every decrease in 1 unit of bicarb, should also see 1 unit of decrease in pCO2, otherwise other acid-base issue in play
Respiratory compensation for metabolic alkalosis
Decreased ventilation
Not able to fully compensate for alkalosis
Renal compensation for respiratory acidosis
decreased ventilation –> increase pCO2
increase renal retention of bicarb
reabsorption of bicarb paired with production & excretion of ammonia
Renal compensation for respiratory alkalosis
increased ventilation –> decreased pCO2
increased excretion of bicarbonate
Henderson-Hasselbach
pH = 6.1 + log [HCO3-]/0.03(pCO2)
Renal compensation for H+ load
regenerates bicarbonate by eliminating H+
for every H+ eliminated, one HCO3- added to ECF
eliminated 50-100 mEq H+ / day
Renal resorption of all filtered bicarbonate
Hydrogen ion excretion:
- not filtered at glomerulus
- HCO3- filtered at glomerulus
- H+ secreted by PT and CD into lumen
HCO3- reabsorption
- all consequence of H+ secretion
- ~4300 mEq/day filtered
- almost all reabsorbed - 90% at PT, rest at LOH, CD
Reabsorption of bicarb at PT
water –> H+ and OH- in cell
H+ secreted into lumen through Na/H exchanger (gradient by Na/K ATPase)
Lumen: H+ + HCO3- –> H2CO3 –> H2O + CO2
CO2 and H2O passively reabsorbed into cell
Cell: CO2 + OH - –> HCO3- by CA
HCO3- goes to blood by HCO3-/Na+ exchanger
Reabsorption of bicarb at CD
H2O --> OH- and H+ in cell H+ secreted into lumen via H+ ATPase H+ + HCO3 --> H2CO3 --> CO2 + H2O (CA) passively resorbed into cell CO2 + OH- --> HCO3- by CA HCO3- moved out of cell into blood via HCO3-/Cl- exchanger
Renal excretion of H+
Combination of H+ + titratable acids
Generation of ammonium
Excretion of H+ with titratable acids
phosphates
gets used up quickly
once pH < 5.5, all phosphate is in H2PO4- form
PT and CD
Excretion of H+ with phosphate in PT
water –> H+ + OH-
H+ secreted through Na+/H+ exchanger
H+ combines with titratable phosphate in lumen –> H2PO4-, excreted
OH- generated in cell combines with CO2 –> HCO3 via CA
HCO3- moves into blood via HCO3-/Na+ exchanger
Excretion of H+ with phosphate in CD
water –> OH- + H+ in cell
H+ secreted to lumen via H+ ATPase
OH- + CO2 –> HCO3- via CA in cell
HCO3- moved to blood with HCO3-/Cl- exchanger
Excretion of H+ through ammonium
Accounts for ~50% fixed acid load excretion
can increase in response to acid load
NH4+ cant get trapped right away because it isn’t acidic enough
want to avoid losing NH4+ to blood
1) ammonium formation
- hydrolysis of glutamine in PT –> ammonium + alpha-KG
- ammonium excreted into lumen via Na+/NH4+ exchanger
- NH4+ in lumen is in equilibrium with NH3
- AKG –> HCO3- by CA, moved out by HCO3-/Na+ exchanger
2) ammonium reabsorption and recycling
- TAL: ammonium moved into cell in place of K+ through NKCC2
- NH4+ –> NH3 inside cell, NH3 accumulates in interstitium
3) Buffer in CD
- NH3 diffuses from interstitium –> cell –> lumen
- H2O –> OH- + H+
- H+ pumped to lumen via H+ ATPase
- lumen: H+ + NH3 –> NH4+
- NH4+ trapped in urine, excreted
- OH- in cell generates bicarbonate, moved to blood via HCO3-/Cl- exchanger
pH threshold
7.4 - above: alkalosis, below: acidosis
Bicarbonate threshold
Low <12
low pH + low bicarb = metabolic acidosis
high pH + low bicarb = compensation for respiratory alkalosis
anion gap
Anion gap = [Na+] - [Cl-] - [HCO3-]
Normal add 3 to AG (same threshold)
Clinical utility of AG
differentiating between different causes of metabolic acidosis
Anion-gap metabolic acidosis causes
MUDPILES Methanol Uremia Diabetic ketoacidosis Paraldehyde/metformin Iron/isoniazid Lactic acidosis Ethylene glycol, ethanol Salicylates
Presence of acids
Ketoacidosis
Lactic acidosis
- type A: impairment in tissue oxygenation
- type B: no impairment in tissue oxygenation (meds, malignancy, alcoholism, cirrhosis)
renal failure
toxins
Non-anion gap metabolic acidosis causes
Loss of bicarbonate
GI loss from diarrhea Renal tubular acidosis - impaired reabs at PT - defective H+ excretion at PT - aldosterone deficiency/resistance Dilution acidosis due to rapid ECFV expansion
Sx of metabolic alkalosis
Confusion/change in mental status paresthesias seizures muscle cramps/ tetany Sx related to causes - e.g. vomiting
DDx of elevated serum bicarb
Metabolic alkalosis
Respiratory acidosis with compensatory metabolic alkalosis
Differentiate with arterial pH:
- low pH = respiratory acidosis with compensatory metabolic alkalosis
- high pH = metabolic alkalosis
Presentation of metabolic alkalosis
increased serum bicarb
increased arterial pH
increased PaCO2 (compensatory respiratory acidosis)
hypokalemia, hypochloremia, hypovolemia also often present
Kidney’s role in alkalosis
Perpetuates - stimulation of H+ secretion = stimulate bicarb reabsorption, can perpetuate alkalosis
Indirect resorption via H+ secretion/Na+ resorption
- H+ secretion promoted by electronegative lumen
- Na+ resorption promoted by low ECFV, activation of RAAS
New HCO3- generated via glutamine metabolism
CCD: alpha/beta intercalated cells control bicarb resorption
- alpha: H+ secretion
- beta: HCO3- secretion
Initiation of metabolic alkalosis
1) H+ loss/HCO3- gain
2) Intracellular shift of H+
3) Alkali administration
4) contraction alkalosis
Vomiting/nasogastric irritation
- HCl lost
- parietal cells secrete H+ into stomach, HCO3- into blood
- loss of neutralization of pancreatic bicarb
- less Cl- available in urine to exchange with HCO3- in tubular lumen for excretion
- hypokalemia: alpha-intercalated cell of CCD promotes H+ secretion to take up K+ from lumen, promotes HCO3- return to blood
- volume depletion: active RAAS promotes hypokalemia - promote Na+ resorption in CCD, increase K+ secretion
- Na+ resorp –> H+ secretion –> bicarb resorption
- RAAS also promotes H+ secretion distally, promoting HCO3- resorption
renal loss of H, K, Cl
- Diuretics (most common cause of metabolic alkalosis)
- Primary aldosteronism: hypokalemia, Na+ resorption
- Bartter’s and Gitelman’s: diuretic-like
- Posthypercapnic alkalosis: bicarb generated by body due to chronic increase in pCO2 - once pCO2 is corrected, end up with metabolic alkalosis
- Post-correction alkalosis : give bicarb to treat severe metabolic acidosis –> bicarb load
Intracellular shift of H+
To compensate for hypokalemia: K+ shifts from ICF –> ECF
to maintain electroneutrality, H+ moves into cell, producing extracellular alkalosis
Causes intracelluar acidosis in PT, promoting HCO3- production, perpetuates metabolic alkalosis
Alkali administration
Post-correction metabolic alkalosis
Post-hypercapnic metabolic alk
Citrate excess: metabolized to bicarb in liver - massive transfusion
Contraction alkalosis/Cl-depletion alkalosis
Reduction of ECF with HCO3- staying relatively stable
Also caused by hypochloremia
RAAS
Most common initiators of metabolic alkalosis
Diuretics
GI loss
Post-hypercapnia
Bicarb administration
Maintenance of met alk
1) effective circulating vol depletion
2) hypokalemia
3) chloride depletion
Effective circulating vol depletion
lowered GFR - less HCO3- filtered
RAAS activation
- AngII: upreg of H+ ATPase in PCT and CCD
- aldosterone: ENaC in CCD - electronegative lumen, H+/K+ secretion
Hypokalemia - maintenance
Leads to intracellular acidosis
increased distal resorption of K+ in CCD
- H/K ATPase
- secretion of H+
Chloride depletion - maintenance
luminal hypochloremia
- stimulates RAAS
- reduced activity of Cl/HCO3- exchanger
AII in acid-base
activated by low ECFV or reduced NaCl concentration in ultrafiltrate
increase activity of Na/H antiporter in apical PT
increased activity of Na/3HCO3- antiporter in basolateral PT
H+ secretion, HCO3- reabsorption
Aldosterone in acid-base
increase Na/K ATpase in basolateral side of DT and CD, creating Na+ gradient –> increase Na resorption
electronegative lumen = secrete K+, H+
H+ secretion, HCO3- reabsorption
Cortisol in acid-base
release stimulated by acidosis
H+ secretion, HCO3- retention
PTH in acid-base
stimulated by acidosis
increases inorganic phosphate excretion in urine, promoting H+ excretion
