Acid Base Flashcards
body buffering
ECF buffer: major is HCO3, but also see plasma protein and inorganic phosphate buffering; ICF: hemoglobin in RBC, proteins, inorganic phosphate; bone: releases bicarb and phosphate in response to acidemia - accounts for 40% acute acid/base buffering
normal values for pCO2 and HCO3 and pH
pCO2 normal is 40 mmHg, HCO3 normal is 24 meq/L, pH is 7.35-7.45
what specific reaction does carbonic anhydrase catalyze?
hydration of CO2 -> H2CO3 (slow reaction). This is followed by the fast dissociation of carbonic acid into bicarb and proton
buffering timeline
50% extracelluar buffering complete w/in minutes, 50% intracellular buffering begins w/in minutes and completes in 6-8 hr
resp vs metabolic compensation for acidemia timeline
respiratory compensation = hyperventilation = begins w/in mins, complete in 12 hrs; renal compensation = H+ excretion and HCO3- production = takes up to 72 hrs
HCO3- reabsorption location
PCT reabsorbs 80% filtered load, TAL reabsorbs 10-15%, rest absorbed in DCT and distal nephron; fractional excretion < .01%
HCO3- generation location
both proximal and distal nephron (more in proximal)
urinary net acid excretion composed of? Which increases when the body is acidemic?
< plasma), not by changing TA excretion
renal response to acidemia
main: incr acid excretion by incr NH3 production; minor: upregulation of NaH exchanger, H-ATPase, HK ATPase activity
HCO3- reabsorption mechanism in PCT and TAL
H+ secreted through NaH antiporter (driven by low Na in cell established via basolateral NaK pump) and through H+ ATPase; H+ combines w/ HCO3- to form CO2 + water (reaction sped up by brush border CA); CO2 diffuses across membrane where it is turned back into HCO3 + H+ by intracellular CA; H+ is re-secreted to tubule while HCO3 is transported across basolateral membrane to plasma via Na/HCO3 synporter (full PCT and TAL) as well as Cl-HCO3 antiporter and K-HCO3 symporter in late PT and TAL
factors affecting PT HCO3 reabsorption (7)
HCO3 delivery to PT (incr filtered load = incr reabs) - this is dependent on GFR, tubular flow rate, and plasma HCO3 concentration; blood pH, HCO3, pCO2; CA activity; K balance (hypokalemia -> intracellular acidosis -> incr NaH exchanger activity -> incr HCO3 reabs); endothelin/catecholamines/glucocorticoids/insulin are incr w/ acidosis and stim NaH exchanger; ECF volume (decr V = more HCO3 reabs and H+ excr); PTH inhibits NaH exchange in PT acutely and stims H+ secr in distal nephron chronically
alpha vs beta intercalcated cells
alpha secretes acid and generates bicarb by secr H+ through H ATPase and through HK antiporter, this H+ combines w/ NH3 or w/ TA in the lumen and is excreted while the HCO3 formed in the creation of this H+ from CO2 is sent into the plasma via HCO3/Cl antiporter (net loss of acid/gain of base); beta is mirror image: basolateral HCO3-Cl antiporter is now apical, where it secretes HCO3 into lumen in exchange for chlorine (incr Cl in lumen leads to incr bicarb excr -> aka why we give KCl to alkalotic pts)
factors affecting distal H+ secretion (5)
aldo incr excr by H+ ATPase in alpha IC cells; neg lumen V est by Na reabs by primary cells (stimmed by aldo, also incr w/ thiazide and loop diuretics b/c more Na in distal tubule) incr H+ secr; more buffers (TA, NH3) leads to incr H+ excr; endothelin incr aldo, stims Na/H, stims H ATPase, stims ammoniagenesis and therefore incr acid excretion; PTH secretes phosphate and thus incr TA in tubule and thus incr acid secr
PTH effects on acid-base balance
PTH inhibits NaH exchange in PT acutely (decr HCO3 reabs) and stims H+ secr in distal nephron chronically (b/c stims Pi excretion, and phosphate is a TA) - PTH is acidotic acutely and alkalotic chronically
endothelin effects on acid-base balance
in response to acidemia, endothelin incr aldo synthesis, stims Na/H, stims H ATPase, stims ammoniagenesis and therefore incr acid excretion and HCO3 reabs
ECF volume effects on acid-base balance
low volume states make the kidney excrete acid: AgII stims NaH antiporter therefore more HCO3 reabs, Starling forces w/ volume contraction lead to incr water reabs and HCO3 follows via solvent drag, aldo stims H+ secretion – net acid excretion and HCO3 reabsorption
aldo effects on CD
principal cell: incr ENAC (apical Na reabs), incr K secr channel, incr basolateral NaK pump; alpha IC cell: incr apical H ATPase and basolateral Cl/HCO3 antiporter (net acid secretion and bicarb generation)
aldo effects on acid-base balance (4)
incr H ATPase therefore incr acid secr; incr Na reabs therefore make lumen more neg therefore incr acid secr; incr K secretion -> hypokalemia -> intracellular acidosis -> acid excretion and bicarb retention; also AgII stims NaH exchanger -> bicarb reabs; overall hyperaldo = alkalosis
ammoniagenesis
produced in PT from metablism of glutamine to glutamate and alpha-ketoglutarate, yielding 2 NH4 (-> lumen); alphaketoglutarate is metab to 2H+ and 2HCO3-, H+ are consumed in gluconeogenesis or oxidation while HCO3 are reabs to blood: net result is glutamine -> 2 NH4 (excreted) + 2 HCO3- (reabs)
ammonia movement in nephron
ammonia generated in PT, reabsorbed in TAL (instead of K in NK2CL) and deposited into medullary interstitium, this leads to high NH4 concentration in interstitium, NH3 diffuses down its gradient into CD where it combines w/ H+ to form trapped ammonia, ammonia enters cells on NaK pump and then is sent into lumen w/ H+; if H+ secr is impaired, NH4 excr will be impaired and NH4 will be reabs -> liver -> turned into urea, which consumes bicarb (net acid change = 0 bad!)
causes of metabolic acidosis (4 categories)
incr base loss from body (diarrhea, proximal RTA), failure to generate bicarb or excrete acid (reduced GFR, distal RTA, distal hyperkalemic RTA), incr generation of acid (lactic acidosis or ketoacidosis), addition of exogenous acid (methanol, ethylene glycol)
renal failure effects on acid-base balance (4)
early non-gap acidosis: decr ammonium synthesis (due to decr nephron mass and hyperkalemia), decr PT bicarb reabsorption (due to ECF V expansion from Na retention), decr distal H+ secr (due to hypoaldo b/c ECF V expansion); late high gap acidosis: retention of endogeneous acids (sulfuric, phosphoric)
proximal RTA (type II) - defect, plasma concentrations, urine concentrations
defect in bicarb reabsorption in PT due to reduced Tm for bicarb; body loses bicarb until plasma level is low enough that all filtered bicarb can be reabsorbed given reduced Tm; steady state urine is acidic b/c distal acidification - urine will have high bicarb at beginning of process but no bicarb at steady state (all bicarb reabsorbed if plasma level is low enough); plasma K is either low or normal while plasma bicarb is low
distal RTA (type I) - defect, urine
defect in distal H+ secretion (bicarb reabs in PT is normal); urine is alkaline (>5.5) regardless of plasma bicarb levels
distal hyperkalemic (type IV) RTA - defect, assoc w/, urine
aldo deficiency and/or resistance -> impaired distal tubule Na reabs and reduced NH4 synthesis (b/c hyperkalemia b/c no K secr) -> acidosis (decr H secr b/c no aldo, hyperkalemia, reduced ammonium synthesis); pts often have diabetes and advanced CKD; urine pH is variable (if urinary buffers like NH3 are low, urine can be acidic even w/ impaired distal H secretion)
proximal RTA causes (3)
defect in bicarb reabs in proximal tubule: CA dysfn (CA inhibitors like acetazolamide, genetic mutations); mutations in NaHCO3 transporter ; Fanconi syndrome (due to toxins like lead, cadmium, mercury, ifosfamide, valproic acid or due to diseases like cystinosis, galactosemia, fructose intolerance, Wilson’s, Lowe’s, multiple myeloma)
differentiating prox vs distal RTA
urine pH in steady state proximal RTA will be acidic b/c all bicarb reabs (lower plasma level) and b/c distal acidification is normal; urine pH in distal RTA will always be alkaline (>5.5) despite blood bicarb levels
distal RTA causes (5)
defect in acid excretion in distal nephron: H-ATPase defect (most common, both acquired and genetic); HK-ATPase defect (rare, from toxins like vanadium); incr H+ backleak (amphotericin B); CA mutation (us also has prox RTA); Cl-HCO3 cotransporter mutation (rare, genetic, assoc w/ deafness)
hypokalemia in distal and proximal RTA due to (4)
variable K concentration (us a bit low) due to: mild hyperaldosteronism b/c Na lost w/ HCO3; incr distal nephron delivery of Na and HCO3 stims K secr; defect in HK ATPase in some distal RTAs (less K reabs); incr membrane K permeability in dRTA assoc. w/ amphotericin B
proximal vs distal RTA: plasma K, plasma bicarb, Tm bicarb, fractional excr bicarb at normal plasma bicarb levels, urine pH, other abnormalities, tx
proximal has normal or low K, modest decr in plasma bicarb (us 14-18), low Tm bicarb, >15% FE bicarb at normal plasma bicarb levels, urine is acidic once steady state reached, assoc w/ Fanconi syndrome in some cases (glucosuria, amiunoaciduria, phosphaturia, uricosuria), tx is to give LOTS (>10 mEq/kg) of bicarb daily (since acidosis is mild, us. don’t even tx); dRTA has normal or low K, significant decr in plasma bicarb (can be 5,5), assoc w/ calcium in urine (nephrocalcinosis, nephrolithiasis), tx initial base defecit and then give small amt bicarb daily to compensate for daily acid load; overall, distal RTA is worse (more acidosis) but easier to tx than proximal RTA
hyperkalemia and NH4 synthesis
hyperK causes reduced ammoniagenesis: hyperkalemia sends H+ out of cells in exchange for K+ into cells; cell percieves an alkaline intracellular environment and so wants to conserve acid and thus doesn’t generate ammonia for excretion
anion gap definition and normal value
AG = [Na] - [HCO3] - [Cl]; normal 8-12 (10)
high gap acidosis causes (3)
endogeneous acids (lactic, ketones), exogeneous acids (methanol, ethylene glycol metabs), advanced kidney failure (retention of sulfuric/phosphoric acid)
normal gap acidosis causes (4)
diarrhea, RTA, dilutional acidosis, mild-moderate kidney failure (decr ammoniagenesis, decr H+ secr, decr bicarb reabs but not decr endogeneous acid excretion yet)
hyperchloremic metabolic acidosis
normal anion gap acidosis -> HCO3 is replaced in ECF by chloride
dilutional acidosis
due to large volume addition of bicarb-free IV fluids (i.e. normal saline) - results in dilution of existing bicarb in expanded total volume; commonly occurs in diabetic ketoacidosis (aggressive IV fluid administration incr urinary excretion of ketoacids which would normally be converted back to bicarb if left in body)
exogeneous acid administration timeline
at first, high osmolar gap but no anion gap (all present as methanol); as methanol is metabolized osmolar gap disappears but anion gap increases
normal anion gap in hypoalbuminemia
most of the normal AG (10) is due to albumin; if albumin is low, then AG should actually be lower and if it is still “normal” (10), then there is in fact a high gap acidosis; to correct, add 2.5 x (4.5 - patient’s albumin) to the calculated AG (normal albumin = 4.5)
causes of lactic acidosis (4 categories)
most commonly due to relative hypoxia (type A) due to hypotension, hypoxemia, sepsis, anemia; type B (no hypoxia) is less common: toxins (metformine, severe ethanol toxicity, NRTIs) cause excess lactate production due to incr glycoylsis due to low ATP, genetic disorders (G6PD deficiency) also cause excess production, liver failure causes decr lactate catabolism
primary ketoacid in alcoholic ketoacidosis
beta-hydroxybutyrate (nitoprusside test may thus be false negative b/c only detects acetoacetate and acetone); ketoacidosis occurs in alcoholism due to decr carb intake and due to incr NADH/NAD ratio that favors ketoacidosis
methanol and ethylene glycol systemic side effects
methanol -> formic acid -> blindness; ethylene glycol -> CNS and renal toxicity, calcium oxalate stones; both cause metabolic acidosis
aspirin acid-base disturbance
resp alkalosis due to central resp stimulation and sometimes high gap metabolic acidosis (esp in kids)
calculated Posm
2Na + BUN/2.8 + glucose/18
causes of high osmolar gap
ethanol most common cause (slightly high osm gap, no AG, no acidemia) but other alcohols (methanol, ethylene glycol) have very high osmolar gaps w/ high anion gaps and acidemia; DKA and AKA have slightly wide osmolar gaps
normal osmolar gap
5-10 mmol/L
delta delta
delta AG/ delta bicarb; if delta AG»_space; delta bicarb, then there must be concomitant metabolic alkalosis; if delta bicarb»_space; delta AG, then there is concomitant non-gap acidosis
Kussmaul respiration
deeper respirations in compensatory respiratory alkalosis (compensating for met acidosis) - depper, not necessarily faster
chronic acidemia consequences - kids (2), adults (3)
impaired growth and muscle development in kids; bone buffering in adults leads to osteopenia and hypercalcemia (-> kidney stones, nephrocalcinosis), muscle wasting occurs due to muscle catabolism to generate glutamine for ammoniagenesis in kidney
acute acidemia consequences (3)
impair cardiac function, acute hyperkalemia (less due to cellular shift of K, more due to concomitant kidney failure, tissue injury, cell lysis), systemic vasodilation (cerebral vasodilation -> incr intracranial pressure -> blurred vision, headache, restlessness, tremors, delirium, eventually lethargy and coma)
Winter’s formula: when to use, what is it
use Winter’s ONLY in metabolic acidosis to see if respiratory compensation is appropriate (if pCO2 is higher than expected, then concomitant resp acidosis, if it is lower than expected, then concomitant resp alkalosis); expected pCO2 = 1.5 x bicarb + 8 +/- 2 (use bicarb from ABG aka HCO3 not total CO2)
total CO2 vs HCO3
HCO3 from ABG, total CO2 from chem 7 (total CO2 = HCO3 + dissolved pCO2, where dissolved pCO2 = .03*pCO2)
tx metabolic acidosis
NaHCO3 or Na-citrate – normalize in chronic metbaolic acidosis, keep pH above 7.2 in acute metabolic acidosis (focus on fixing the primary problem and the acidosis will resolve itself - pts don’t die from acidemia, they us. die from underlying process)
causes of metabolic alkalosis (4)
assoc. w/ hypovolemia and chloride depletion: vomiting or NG tube, thiazide and loop diuretics, Barrter’s and Gitelman’s (mimic diuretics); assoc w/ hypervolemia: hyperaldosteronism
how does KCl correct alkalosis?
Cl- in distal tubule is exhcnaged for bicarb via apical Cl-HCO3 exchanger in beta IC cells
how does vomiting lead to alkalosis?
initial loss of H+ leads to metabolic alkalosis -> kidney attempts to correct alkalosis by secreting NaHCO3 (downregulates NaH exchanger, thus decr bicarb reabs and decr Na reabs by this exchanger) -> Na loss leads to hypovolemia -> hyperaldosteronism -> kidney conserves Na, secretes K, still secretes some bicarb to help restore pH balance -> K secretion leads to hypokalemia -> now kidney tries to conserve both K and Na, and thus can’t secrete bicarb (no cation) — now kidney is part of the alkalosis problem (maintenance) b/c it chooses maintaining volume over maintaining pH
vomiting urine: early, mid, late concentrations of Na, K, bicarb, Cl, pH
early: bicarb excretion high via NaH downregulation, which leads to high Na excretion, high urine pH, Cl is low b/c HCl lost in vomiting and kidney tries to conserve Cl, K is variable; mid: body is volume depleted therefore Na excr low, bicarb is still excreted but now K is secr w/ it due to hyperaldo, pH is still high, Cl is still low; late: body is volume depleted therefore no Na in urine, body is hypokalemic therefore little K in urine (some), no cation to secr w/ bicarb therefore little bicarb in urine (maintenance of alkalosis by kidney), pH is normal (acidic), chlorine still low
vomiting effects on K balance
hypokalemia: Na lost in urine as NaHCO3 leads to hypovolemia -> hyperaldo -> K excretion in urine
diuretics and acid-base balance
thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr; CA inhibitors induce metabolic acidosis (more bicarb excretion); osmotic diuretics induce metabolic acidosis (bicarb excreted via solvent drag?); K-sparing diuretics induce metabolic acidosis (Na not reabsorbed, therefore lumen not negative, therefore H+ not excreted)
Barrter’s and Gitelman’s mutations
Barrter’s = NK2CL mutation; Gitelmans = NaCl mutation
tx of metabolic alkalosis
for V depletion forms: correct Na deficit w/ NaCl, then correct alkalosis w/ KCl — removes stimulus for proximal bicarb reabs (downregulate NaH exchanger), removes hyperaldo (fixes hypovolemia), restores distal bicarb secretion by beta IC cells (incr Cl in lumen), fixes hypokalemia and thus fixes alkalosis; for hyperaldosteronism: correct cause
approach to acid base problems (6)
- what is the emia? 2. what is the osis (look at pCO2, HCO3) 3. is compensation appropriate (use Winter’s for met acidosis) - if inappopriate, is there another disturbance or is it just acute resp acidosis/alkalosis? 4. anion gap (if acidosis) 5. delta delta (if acidosis) 6. osmolar gap (if acidosis)
expected compensation for met acidosis, met alk, resp acid, resp alk
metabolic acidosis: use Winter’s, or 1.2 mm Hg pCO2 drop for every 1 mEq drop in bicarb; metabolic alkalosis: .7 mm Hg pCO2 rise for every 1 mEq rise in bicarb; resp acidosis: 1 (acute) or 3.5 (chronic) mEq bicarb rise for every 10 mm Hg pCO2 rise; resp alkalosis: 2 (acute) or 5 (chronic) mEq bicarb drop for every 10 mm Hg pCO2 drop (may correct pH to normal)
acute alkalemia consequences (5)
directly enhances neuromuscular excitability and modestly decr serum calcium -> paresthesias, numbness, twitching, tetany, cerebral vasospasm (-> decr cerebral blood flow -> dizziness, confusion, LOC… we induce resp alkalosis to tx intracranial P rises!)
causes of respiratory alkalosis (8)
anxiety/pain/fever, exercise, hypoxia, drugs (aspirin, theophylline, progesterone), liver failure/pregnancy (progesterone), gram neg sepsis (via TNF), intracerebral disease, excessive mechanical ventilation
categories of resp acidosis causes (2)
due to alveolar hypoventilation (i.e. from opiates); or due to severe ventilation-perfusion mismatch of the dead-space type (COPD, asthma)
causes of acute resp acidosis (3)
sedative drug ODs (opiates, benzos) is most common; severe acute exacerbation of any respiratory disease; suppression of the hypoxic drive to breath by administered O2 in pts w/ chronic resp disease
resp alkalosis + metabolic acidosis: pCO2/bicarb/pH levels, causes (2)
pCO2 low, bicarb low, pH variable (close to normal); aspirin OD (esp in kids), chronic liver disease (high prog -> resp alk) w/ sepsis (met acidosis)
resp alkalosis + metabolic alkalosis: pCO2/bicarb/pH levels, causes (2)
pCO2 low, bicarb high, pH v. high; caused by sepsis (resp alkalosis) after NG drainage (met alkalosis) or pain (resp alkalosis) w/ over-diuresis (met alkalosis)
resp acidosis + metabolic acidosis: pCO2/bicarb/pH levels, causes (3)
pCO2 high, bicarb low, pH v. low; caused by COPD (resp acidosis) w/ sepsis (met acidosis), cardiac arrest, RTA w/ severe K depletion (hypokalemia causes resp muscle weakness)
resp acidosis + metabolic alkalosis: pCO2/bicarb/pH levels, causes (2)
pCO2 high, bicarb high, pH variable (close to normal); caused by COPD (resp acidosis) w/ diuretics (met alkalosis) or by COPD (resp acidosis) over-ventilated w/ mech ventilation revealing compensatory metabolic alkalosis (post-hypercapneic alkalosis)
post-hypercapneic alkalosis
chronic resp acidosis (COPD) is compensated w/ renal alkalosis (incr bicarb generation, incr acid excretion, etc.). When COPD pt is mechanically ventilated (thus removing resp acidosis), renal alkalosis is revealed (not enough time to return to baseline w/o compensation)
