01-13 Acid-Base I, II & III Flashcards
1) Define the different types of acid-base disorders 2) Relate aspects of renal tubular physiology and pathophysiology to renal acid-base homeostasis 3) Integrate compensatory mechanisms in a stepwise approach to simple and mixed acid-base disorders 4) Utilize the concepts above to assess acid-base status in clinical vignettes and begin to contemplate management options
Give the Bronsted-Lowry definition of an acid and a base (proton viewpoint)?
Acids are H+ donors
Bases are H+ acceptors
Name three physiologically important buffers.
1) bicarb ([HCO3] >100,000X > [H+] !!)
2) albumin (and other protein)
3) phosphate (mostly in bone)
Buffering with phosphate (HPO4^2-)
—occurs when bicarb overwhelmed
—resulting in bone loss
Albumin as buffer
—albumin is negatively charged and @ physio pH binds Ca2+ and Na+
—acidemia → Na+ & Ca2+ displaced
—alkalemia → hypocalcemia
—A 13 year old boy has a proximal renal tubular acidosis, a chronic form of metabolic acidosis
—He develops a diarrheal illness and presents acutely with tachypnea and respiratory distress
—A CXR to evaluate his resp distress notes low bone mineral density, but clear lungs.
—Why resp distress?
—Why low BMD?
Resp distress: blowing off CO2 from acute metab acidosis
Low BMD: HPO42- is buffering chronic metab acidosis
How does one calculate the anion gap?
—What is normal?
AG = [Na+] – ([Cl-] + [HCO3-])
—Ref range: ~12mEq/mL
You have a patient with elevated AG but normal bicarb. Is this patient experiencing an acidosis?
Yes, the anion gap is due to organic anions. Whenever the gap is widened, you have an acidosis going on.
When might you have a low anion gap?
- hypoalbuminemia, most commonly
—the ~12mEq/mL is largely due to albumin - excess cations: ↑ Ca2+/Mg2+/Li+ or light chains
- excess buffering: ↑ HCO3-
-osis v -emia
- osis: process that favors a condition
- emia: actual elevated serum levels
—There can be multiple (metab) acidoses and alkaloses happening simultaneously.
—For acidemia or alkalemia, “There can be only one.”
—This is b/c resp d/o are defined solely by pCO2, it is not possible to have simultaneous resp acidosis and resp alkalosis whereas metab are defined by both HCO3- and A.G.
Is it possible to have an acidosis if a pt’s pH is 7.4?
Yes, recall that -osis just means there is a process going on that favors an -emia.
—This could occur if a pt had a concomitant metabolic alkalosis w/ their acidosis.
—A compensation by itself, however (e.g. decreased RR, or increased renal acid wasting), will not achieve normal pH.
What is an acidosis? How is it manifested?
Process favoring development of acidemia
Manifested as disturbances of HCO3-/CO2
—Low HCO3- (consumed by excess H+)
—High CO2 (produces carbonic acid)
What is an alkalosis? How is it manifested?
Process favoring development of alkalemia.
Also manifested as ∆s in HCO3-/CO2:
—High HCO3- (opposite acidosis)
—Low CO2 (opposite acidosis)
A 43 year old woman is found in the park, confused and brought to the nearest health facility.
—Resp rate is normal.
—Serum: Na+144 | K+ 4.0 | Cl- 102 | HCO3- 22
—Arterial pH is 7.41
—bicarb low
—AG = 144 - (102 + 22) = 20 → high
—pH so close to normal this is likely a metab acidosis (per AG) w/ concomitant metab alkalosis
—??this is my guess
Compensation for respiratory acidosis?
Lungs are retaining CO2, so HCO3- buffers and kidney makes more & retains HCO3-
—This response is slower than the lung and takes 2-3 days to really rev up to chronic compensation.
—Acute: ↑ HCO3- 1mEq/10mmHg pCO2
—Chronic: ↑ HCO3- 3-4mEq/10mmHg pCO2
**If compensation for a respiratory acidosis looks really “good” and you know the onset was acute, you should suspect a concomitant metab alkalosis
**Remember that compensation is never complete or over-compensating!
Compensation for metabolic acidosis?
Increased RR
How do you define whether a acid-base d/o is respiratory or metabolic?
Ask yourself:
—Is there pCO2 derangement? → respiratory
—Is there HCO3- or AG derangement? → metab
A 15 yo girl presents non-responsive. She has shallow respirations. Her parents are worried she may have gotten to their “sleep” medications earlier that day
—VS: T 36.8, HR 55, RR 6
—ABG: pH 7.18 | pCO2 72 | HC03 28
What is her acid-base disturbance?
respiratory acidosis
Causes of hypoventilation (and thus respiratory acidosis)?
Central (e.g. brain damage, benzo poisoning, etc.)
Pulmonary (e.g. COPD, PE)
Peripheral (respiratory muscle weakness; MG, poliomyelitis)
A (different) 15 yo girl presents non-responsive. She has shallow respirations. Her parents are worried she may have gotten to their “sleep” medications earlier that day
—VS: T 36.8, HR 55, RR 6
—ABG: pH 7.31 | pCO2 72 | HC03 36
What is her acid-base disturbance?
pH: low → acidemia, reflected by…
CO2: high → acute respiratory acidosis, however…
HCO3-: high, too…
—So there is likely an underlying metabolic alkalosis going on here as well.
Dx: “Mixed Acute Resp Acidosis with Acute Metabolic Alkalosis”
10 month old boy with history of 3 days of watery diarrhea
—VS: T 37.2; HR 136; RR 30; BP 80/46
—PE: cranky, clinging to mother, but
good perfusion, nl abdomen
—Labs: Na 136; K 3.6; Cl 110; HCO3 16; BUN 18; Cr 0.4
—ABG- pH 7.30 pCO2 30
What is his acid base disturbance?
pH: low → acidemia
pCO2: also low
HCO3-: also low
A.G.: high (136 - [110 + 16] = 10)
Acute metab acidosis (losing bicarb in stool)
w/ Respiratory compensation (RR = 30)
Causes of Metab acidosis?
Generation, ingestion or retention of acid —Generation: e.g. DKA ,lactic acidosis —Ingestion: e.g. ASA O.D. —Retention: e.g. distal RTA Loss of HCO3-. —Diarrhea, pancreatic fluid losses —Proximal RTA
How do you estimate if respiratory compensation is adequate?
—What more accurate tool could you look-up on epocrates?
XX YY rule: pH 7.XX ~= pCO2 YY
—e.g pH 7.30; pCO2 30
Or…look up Winter’s Formula
Factors that increase the anion gap?
MUDPILES Methanol Urea DKA Paraldehyde (anti-epileptic) Isoniazid (INH Lactic Acidosis (Li?) Ethylene Glycol Salicylates
—3 y/o ♂ found semi-comatose in family garage —BMP: Na- 132, K- 4.2, Cl- 104, HCO3- 8, glucose 90, BUN- 28, Cr 0.8 —ABG- pH- 7.25, PCO2- 24, HCO3- 8 —POsm= 309 mOsm/kg —Lactic acid - mildly elevated What is the acid base disturbance? What is the anion gap? What is osmolar gap?
pH: 7.25 = acidemia pCO2: low (respiratory depression/compensation?) A.G.: 132 - (8 + 104) = 20 (HIGH) HCO3-: metab acidosis O.G. = 264 + 10 + 5 = 279
Dx: high AG metab acidosis w/ mildly elevated Lactic Acid and high osmolal gap
—Together with history—suspect an intoxication/ingestion
Calculated osmolality equation?
—Ref range?
Osmolar gap equation?
—Ref range?
Calc. osmolality: 2[Na+] + BUN/2.8 + Gluc/18
—RR: 275–295 mOsm/kg (mmol/kg).
Osmolar gap = Observed - Estimated
—RR: OG < 10-15mOsm/kg
**you can estimate whether the OG is due to one suspected ingestion or > 1 ingestion, e.g. EtOH is common w/ MeOH & ethylene glycol ingestion
Changes in the anion gap and bicarbonate are not mutually exclusive.
—If an elevated anion gap is present, how do we assess for other concurrent metabolic disorders?
Delta∆-Delta∆!
—For every 1 meq/L increase in the anion gap, [HCO3-] should fall by 1 meq/L
—If not, some other process is occuring
What’s the equation for Delta∆-Delta∆?
—Interpretation
∆∆ = ∆[anion gap] - ∆[HCO3-] =
= (XX -12) - (24 - YY)
—Always calculate when you find an AG acidosis
[-]negative result: HCO3 has ∆ed more than AG
—means there’s an additional hyperchloremic acidosis making the AG acidosis WORSE
[+]positive result: AG has ∆ed more than AG
—means there’s a concurrent metabolic alkalosis making the overall acidosis IMPROVED compared to the gap acidosis alone
zero (i.e. ∆AG = ∆HCO3) → high AG acidosis is sole metab d/o
What processes causes hyperchloremic acidosis?
—loss of HCO3- —retention of H+ \_\_\_\_\_\_\_\_\_\_\_\_\_\_ (Also: High Cl- solutions such as NX volume resuscitation or hyperalimentation can also cause hyperchloremic acidosis —High Cl- intake at expense of HCO3- —Usually evident by Hx & review of IVFs)
How does one lose HCO3-?
—how do you differentiate between causes
GI losses
—cause usually evident!
renal excretion
—Do a urinalysis if unsure re: GI v. renal
—Inability to reabsorb HCO3- = proximal RTA
—If unsure
distal RTA vs. proximal RTA?
—Which is which “Type”?
Inability to excrete H+ = distal RTA (Type I)
How does kidney get rid of H+?
—How do we measure it?
Kidney secretes H+ in the form of NH4Cl
—hard to measure NH3 b/c it’s volatile
—therefore, we infer it from urine [Cl-]
Equation from Urine Anion Gap
Urine AG = ([Na+] + [K+]) – [Cl-]
—↑ NH4Cl excretion ↑s [Cl-] but not Na+ or K+
If you have a metabolic acidosis, what to you expect the urine anion gap to be if kidney is functioning correctly?
If kidney is functioning correctly, you expect it to dump more H+ in the form of NH4Cl.
—Therefore expect ↑ urine [Cl-]
—Therefore expect [-]negative urine AG
If you have a metabolic acidosis, and the kidney is NOT functioning correctly what to you expect the urine anion gap will be?
—If this kidney problem were due to an RTA, which kind would it be?
If kidney is NOT functioning correctly, you expect it to dump LITTLE H+ secretion as NH4Cl.
—Therefore expect ↓ urine [Cl-]
—Therefore expect [+]positive urine AG
—This would be DISTAL RTA
34 year old man with cancer, receiving ifosfamide, has his serum chemistries assessed
—Na 138; K 3.1; Cl 115; HCO3 10; Cr 1.1
—ABG: pH 7.25; pCO2 24
—Urine Lytes: Na 84; K 27; Cl 58
1. What is his acid-base disturbance?
2. What is his urine anion gap?
3. So is he excreting acid in his urine? Should he be?
Low HCO3, low pH, low CO2
—AG = 138 - (115 + 10) = 13
1.Non-gap metab acidosis (right?)
Urine AG: (84 + 27) -58 = 53
- No, he is not excreting acid in his urine. Yes, he should be!
Type I (Distal) RTA —Definition —Etiology(ies) —Labs —Tx
DEFINITION
α-intercalated cells in CD are not secreting H+ properly
ETIOLOGIES
1°: idio/sporadic, familial, AD, AR
2°:
—Auto-imm: Sjogren’s, Autoim hepatitis/1° biliary cirrhosis, SLE, RA
—Drugs: Ifosfamide, Amphotericin B, Lithium, Toluene inhalation
—Hypercalcuric conditions: Hyperparathyroidism, Vit D intoxication, Sarcoidosis, Idiopathic hypercalciuria
—Other: edullary sponge kidney, Obstructive Uropathy, Renal transplant rejection, Wilson’s disease, Sickle Cell Disease
LABS
—Urine AG: [+]Positive
—Urine [HCO3] low
—Urine pH: > 5.5 (i.e. not maximally acidified (e.g. can go down to ~4)
—Hypokalemia generally present (Has to excrete K+ to reabsorb Na+ in distal nephron b/c it can’t excrete H+)
TX
—tx underlying cause, if any
—supplement bicarb (or veg diet!)
Type II (Proximal) RTA —Definition —Etiology(ies) —Labs —Provocative Test? —Tx
DEFINITION
—inability to reabsorb HCO3- in PT
ETIOLOGIES
—N+/H+ exchanger in PT broken
—need to pump H+ into lumen to combine w/ HCO3- b/c H2CO3 —C.A.→ CO2 + H2O b/c CO2 is reabsorbed what’s reabsorbed
(there’s both a luminal C.A. and intracellular)
—idiopathic/sporadic
—familial (inborn errors of metab: byproducts damage cells)
—heavy metals
—Rx (CA inhibs, aminoglycosides)
—M-Protein disorders (MM, amyloidosis)
—Vitamin D def
—Paroxysmal nocturnal hemoglobinuria
LABS
—Urine pH < 5.5
—Urine A.G. should be negative at steady state
—Moderately low serum [HCO3-]
—Hypokalemia is generally present (as w/ Type I; b/c bicarb travels through nephron as sodium bicarb and so ↑ Na+ delivery to distal tubule = more K+ excretion)
PROVOCATIVE TEST
—Give bicarb load and then do serial UAs
—Expect pt to pee out all the new bicarb even when acidotic
TX
—Tx underlying cause, if possible
—Lots of bicarb (b/c they pee it all out) supplementation
Fanconi syndrome
generalized PT dysfunction (i.e. proximal RTA + glycosuria, aminoaciduria, phosphaturia, etc)
Describe the concept of bicarb steady state in Type II RTA.
—Bicarbonaturia halts when serum bicarbonate (filtered bicarbonate) falls below the new transport maximum (Tmax) → new steady state reached
—Distal acidification mechanisms are still intact
Type III RTA
A combination of both Type I and Type II RTA pathophysiology
—The physiologic state of the neonate
—The designation has generally fallen out of favor
—Neonates are born with various renal tubular
processes with decreased transport maximal
capacities compared to the mature kidney
—Bicarbonate reabsorption AND acid excretion are
below transport maximums compared to older children and adults
Type IV RTA —Definition —Etiology(ies) —Labs —Tx
DEFINITION
Lack of aldosterone effect in cortical CD
—low aldosterone
—aldosterone resistance
ETIOLOGY
—Not only does Aldo stim Na+ reabs and K+ secretion in the CCD, it also revs the H+-ATPase which pumps H+ into urine
-—Reduced Aldo—- —Low Renin (renal dz, NSAIDs, calciuneurin inhibs, volume expansion as w/ acute GN —ACEIs/ARBs/DRIs —1° Adrenal insufficiency —Familial
-—Aldo Resistance—-
—eNac inhib (K-sparers, abx like bactrim)
—Pseydohypoaldosteronism type 1
—Acquire/Congenital defects in eNac (obstructive uropathy, SCD, SLE)
LABS —Low serum [HCO3-] —hyperkalemia —near nl Cr ——hyperchloremic acidosis w/ mild hyperkalemia ——hyperK+ is often more marked finding ——(most other acidoses have HYPO-K+) —low urine K+, despite hyperkalemia
TX If hypoaldosteronism: fludrocortisone —Not used in hyporeninemic hypoaldosteronism or pseudo-hypoaldosteronism b/c of HTN —NaHCO3 supplements; K+ restriction —Furosemide or Thiazide can be given in specific conditions—can ↑ K+ and H+ excretion —be wary of excess volume depletion —esp if etiology is MR def!
Make table for Types I, II, IV w/ —Primary Defect —Plasma HCO3- —Urine pH —Plasma K+
see slide 88
A 2 y/o ♂ w/ fever and persistent cough has a metabolic panel drawn which shows serum HCO3 of 16
—PE: tachypnea and ↓ breath sounds on right
—ABG: pH 7.48, PCO2 22, PO2 78, HCO3 15
—What is the primary acid base disorder for this patient?
High pH with low pCO2 but low bicarb
—resp acidosis w/ renal compensation
—Shows importance of assessing pH and PCO2; not just basing things on a serum HCO3
2 y/o ♂ w/ fever and persistent cough has a serum HCO3 of 16
—PE: tachypnea & ↓ breath sounds on right
—ABG: pH 7.48, PCO2 22, PO2 78, HCO3 15
—What is the 1° acid base d/o for this pt?
—Does he have chronic resp alkalosis w/ appropriate compensation?
—Does he have acute resp alkalosis w/ concurrent
acute metab acidosis?
Alkalemia (pH = 7.48)
—low pCO2
—low pO2
—low bicarb
Chronic resp alkalosis b/c bicarb has fallen significantly down ~8 from nl
Dx: ASA toxicity
ASA toxicity
1° resp alkalosis & an ↑ A.G. acidosis both present
This combination should always prompt testing for salicylate toxicity
Salicylate toxicity represents a special case in acid-base disorders.
—Salicylic acid causes an elevated anion gap metabolic acidosis.
—The body responds by increasing minute ventilation, lowering pCO2.
—Aspirin also directly stimulates the respiratory center, further lowering pCO2 and causing a superimposed respiratory alkalosis.
Often, a primary respiratory alkalosis and an elevated anion gap acidosis are both present.
This combination should always prompt testing for salicylate toxicity
6 week old boy with projectile vomiting and weight loss
—Labs: Na+ 133, K+ 3.2, Cl- 88, HCO3- 36, Cr 0.3
—ABG: pH-7.48, PCO2- 50, HCO3- 35
What is the acid base disturbance?
alkalemia b/c pH is 7.48 (7.XX) —HCO3 high —pCO2 high at 50 (YY) —XX ~= YY therefore appropriate compensation —AG: 133 - (88 + 36) = 9
Metab alkalosis w/ compensatory resp acidosis
Metabolic Alkalosis
—Definition
—Causes
DEFINTION
—High pH, high HCO3-
CAUSES
Results from net loss of HCl from the body
—GI H+ losses (e.g. vomiting, NG suction)
——loss of H+ → ↑ HCO3-
——loss of Cl- inhibs HCO3- secretion in DT βs
—Renal H+ losses (e.g. hyperaldo, hypoK+)
—Alkali ingestion (e.g. milk-alkali syndrome)
—Volume depletion (“contraction alkalosis”)
How do you estimate if respiratory compensation to metab alkalosis is appropriate?
Quick but less accurate formula also applies here:
pH: 7.XX ; pCO2: XX e.g pH 7.50; pCO2 50
Milk-alkali syndrome
—Definition
—Cause
—Tx
Ingestion of HCO3- or CO32- alone is rarely sufficient to cause alkalosis.
—kidney can normally excrete the HCO3- load.
—Hypercalcemia inhibits HCO3- excretion
—Ingesting large amounts of dairy products
and/or CaCO3 (Tums) → hyperCa2+ & metab alk
—Tx by stopping ingestion!
Contraction Alkalosis
—Definition
—Causes
Loss of non-HCO3 containing fluids → “contraction” of the blood volume around a fixed mass of HCO3-
CAUSES
—Vomiting and diuretics are common causes
—Volume depletion stimulates RAAS
—Angiotensin II stimulates PT HCO3- reabs
—HyperAldo → hypokalemia and H+ secretion
How does hyperAldo cause metab alkalosis?
—Stimulates Na+ reabsorption
—Stimulates K+ secretion
—Stimulates H+ secretion, generating HCO3- because H+ came off of H2CO2 leaving HCO3- inside tubular cell
All of the above promote alkalosis
How does hypokalemia cause metab alkalosis?
Causes K+ shift: cells → plasma
—H+ shifts into cells to maintain electroneutrality
—Resulting intracellular acidosis stimulates NH3 generation and H+ secretion
How do you treat metab alkalosis 2°to vomiting, contraction alkalosis, and/or
hypokalemia?
replete volume, K+ and Cl-
—breaks cycle of ↑ aldo, intracellular acidosis, and HCO3- reabsorption
—These causes are sometimes called “chloride
responsive” for this reason
Liddle’s Syndrome?
—Tx?
ENaC constitutively active
—mimics hyperALDO
—Tx w/ amiloride
Treating metab alkalosis 2°to 1° hyperaldosteronism or its mimickers (e.g. Liddle’s, black licorice)?
Cl- and K+ repletion won’t correct problem
—These causes are sometimes called “chloride
unresponsive”
—Tx involves removing the source of
abnormal hormone or blocking the affected renal tubular transporters
Approach to Acid/Base Problems
- Acidemia or alkalemia?
- Determine the pCO2 and HCO3-
—Is there acidosis and/or alkalosis contributing to the 1° d/o or balancing it out? (XX = YY?)
—Is it a simple d/o w/ comp, or mixed d/o?
***Remember Compensation is never complete! - Always check A.G.! (if there is, check ∆∆)
- Check Hx/PE
- DDx
—GAP ACIDOSIS? think MUD PILES
—HYPER[CL-] ACIDOSIS? check urine AG & pH
——Is [-] urine AG? look for HCO3 wasting (diarrhea or proximal RTA)
——hyperkalemic?, consider Type IV RTA
—METAB ALK? assess volume status and serum K+
——GI losses or diuretics usu evident by hx
——If appropriate replete volume, K+, and Cl-
——If the alkalosis persists (esp w/ concurrent HTN), consider hyperALDO or its mimickers
Go over cases using blank PDF
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