Acid Base

Question 1

body buffering

Answer 1

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

Question 2

normal values for pCO2 and HCO3 and pH

Answer 2

pCO2 normal is 40 mmHg, HCO3 normal is 24 meq/L, pH is 7.35-7.45

Question 3

what specific reaction does carbonic anhydrase catalyze?

Answer 3

hydration of CO2 -> H2CO3 (slow reaction). This is followed by the fast dissociation of carbonic acid into bicarb and proton

Question 4

buffering timeline

Answer 4

50% extracelluar buffering complete w/in minutes, 50% intracellular buffering begins w/in minutes and completes in 6-8 hr

Question 5

resp vs metabolic compensation for acidemia timeline

Answer 5

respiratory compensation = hyperventilation = begins w/in mins, complete in 12 hrs; renal compensation = H+ excretion and HCO3- production = takes up to 72 hrs

Question 6

HCO3- reabsorption location

Answer 6

PCT reabsorbs 80% filtered load, TAL reabsorbs 10-15%, rest absorbed in DCT and distal nephron; fractional excretion < .01%

Question 7

HCO3- generation location

Answer 7

both proximal and distal nephron (more in proximal)

Question 8

urinary net acid excretion composed of? Which increases when the body is acidemic?

Answer 8

< plasma), not by changing TA excretion

Question 9

renal response to acidemia

Answer 9

main: incr acid excretion by incr NH3 production; minor: upregulation of NaH exchanger, H-ATPase, HK ATPase activity

Question 10

HCO3- reabsorption mechanism in PCT and TAL

Answer 10

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

Question 11

factors affecting PT HCO3 reabsorption (7)

Answer 11

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

Question 12

alpha vs beta intercalcated cells

Answer 12

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)

Question 13

factors affecting distal H+ secretion (5)

Answer 13

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

Question 14

PTH effects on acid-base balance

Answer 14

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

Question 15

endothelin effects on acid-base balance

Answer 15

in response to acidemia, endothelin incr aldo synthesis, stims Na/H, stims H ATPase, stims ammoniagenesis and therefore incr acid excretion and HCO3 reabs

Question 16

ECF volume effects on acid-base balance

Answer 16

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

Question 17

aldo effects on CD

Answer 17

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)

Question 18

aldo effects on acid-base balance (4)

Answer 18

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

Question 19

ammoniagenesis

Answer 19

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)

Question 20

ammonia movement in nephron

Answer 20

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!)

Question 21

causes of metabolic acidosis (4 categories)

Answer 21

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)

Question 22

renal failure effects on acid-base balance (4)

Answer 22

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)

Question 23

proximal RTA (type II) - defect, plasma concentrations, urine concentrations

Answer 23

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

Question 24

distal RTA (type I) - defect, urine

Answer 24

defect in distal H+ secretion (bicarb reabs in PT is normal); urine is alkaline (>5.5) regardless of plasma bicarb levels

Question 25

distal hyperkalemic (type IV) RTA - defect, assoc w/, urine

Answer 25

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)

Question 26

proximal RTA causes (3)

Answer 26

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)

Question 27

differentiating prox vs distal RTA

Answer 27

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

Question 28

distal RTA causes (5)

Answer 28

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)

Question 29

hypokalemia in distal and proximal RTA due to (4)

Answer 29

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

Question 30

proximal vs distal RTA: plasma K, plasma bicarb, Tm bicarb, fractional excr bicarb at normal plasma bicarb levels, urine pH, other abnormalities, tx

Answer 30

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

Question 31

hyperkalemia and NH4 synthesis

Answer 31

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

Question 32

anion gap definition and normal value

Answer 32

AG = [Na] - [HCO3] - [Cl]; normal 8-12 (10)

Question 33

high gap acidosis causes (3)

Answer 33

endogeneous acids (lactic, ketones), exogeneous acids (methanol, ethylene glycol metabs), advanced kidney failure (retention of sulfuric/phosphoric acid)

Question 34

normal gap acidosis causes (4)

Answer 34

diarrhea, RTA, dilutional acidosis, mild-moderate kidney failure (decr ammoniagenesis, decr H+ secr, decr bicarb reabs but not decr endogeneous acid excretion yet)

Question 35

hyperchloremic metabolic acidosis

Answer 35

normal anion gap acidosis -> HCO3 is replaced in ECF by chloride

Question 36

dilutional acidosis

Answer 36

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)

Question 37

exogeneous acid administration timeline

Answer 37

at first, high osmolar gap but no anion gap (all present as methanol); as methanol is metabolized osmolar gap disappears but anion gap increases

Question 38

normal anion gap in hypoalbuminemia

Answer 38

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)

Question 39

causes of lactic acidosis (4 categories)

Answer 39

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

Question 40

primary ketoacid in alcoholic ketoacidosis

Answer 40

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

Question 41

methanol and ethylene glycol systemic side effects

Answer 41

methanol -> formic acid -> blindness; ethylene glycol -> CNS and renal toxicity, calcium oxalate stones; both cause metabolic acidosis

Question 42

aspirin acid-base disturbance

Answer 42

resp alkalosis due to central resp stimulation and sometimes high gap metabolic acidosis (esp in kids)

Question 43

calculated Posm

Answer 43

2Na + BUN/2.8 + glucose/18

Question 44

causes of high osmolar gap

Answer 44

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

Question 45

normal osmolar gap

Answer 45

5-10 mmol/L

Question 46

delta delta

Answer 46

delta AG/ delta bicarb; if delta AG >> delta bicarb, then there must be concomitant metabolic alkalosis; if delta bicarb >> delta AG, then there is concomitant non-gap acidosis

Question 47

Kussmaul respiration

Answer 47

deeper respirations in compensatory respiratory alkalosis (compensating for met acidosis) - depper, not necessarily faster

Question 48

chronic acidemia consequences - kids (2), adults (3)

Answer 48

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

Question 49

acute acidemia consequences (3)

Answer 49

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)

Question 50

Winter's formula: when to use, what is it

Answer 50

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)

Question 51

total CO2 vs HCO3

Answer 51

HCO3 from ABG, total CO2 from chem 7 (total CO2 = HCO3 + dissolved pCO2, where dissolved pCO2 = .03*pCO2)

Question 52

tx metabolic acidosis

Answer 52

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)

Question 53

causes of metabolic alkalosis (4)

Answer 53

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

Question 54

how does KCl correct alkalosis?

Answer 54

Cl- in distal tubule is exhcnaged for bicarb via apical Cl-HCO3 exchanger in beta IC cells

Question 55

how does vomiting lead to alkalosis?

Answer 55

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

Question 56

vomiting urine: early, mid, late concentrations of Na, K, bicarb, Cl, pH

Answer 56

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

Question 57

vomiting effects on K balance

Answer 57

hypokalemia: Na lost in urine as NaHCO3 leads to hypovolemia -> hyperaldo -> K excretion in urine

Question 58

diuretics and acid-base balance

Answer 58

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)

Question 59

Barrter's and Gitelman's mutations

Answer 59

Barrter's = NK2CL mutation; Gitelmans = NaCl mutation

Question 60

tx of metabolic alkalosis

Answer 60

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

Question 61

approach to acid base problems (6)

Answer 61

1. 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)

Question 62

expected compensation for met acidosis, met alk, resp acid, resp alk

Answer 62

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)

Question 63

acute alkalemia consequences (5)

Answer 63

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!)

Question 64

causes of respiratory alkalosis (8)

Answer 64

anxiety/pain/fever, exercise, hypoxia, drugs (aspirin, theophylline, progesterone), liver failure/pregnancy (progesterone), gram neg sepsis (via TNF), intracerebral disease, excessive mechanical ventilation

Question 65

categories of resp acidosis causes (2)

Answer 65

due to alveolar hypoventilation (i.e. from opiates); or due to severe ventilation-perfusion mismatch of the dead-space type (COPD, asthma)

Question 66

causes of acute resp acidosis (3)

Answer 66

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

Question 67

resp alkalosis + metabolic acidosis: pCO2/bicarb/pH levels, causes (2)

Answer 67

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)

Question 68

resp alkalosis + metabolic alkalosis: pCO2/bicarb/pH levels, causes (2)

Answer 68

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)

Question 69

resp acidosis + metabolic acidosis: pCO2/bicarb/pH levels, causes (3)

Answer 69

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)

Question 70

resp acidosis + metabolic alkalosis: pCO2/bicarb/pH levels, causes (2)

Answer 70

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)

Question 71

post-hypercapneic alkalosis

Answer 71

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)