complex acid-base disorders - internal medicine · pdf fileobjectives develop a standardized...
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Complex Acid-Base
Disorders
Robert M Centor, MD FACP
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Objectives
Develop a standardized approach to
diagnosing acid-base disorders
Differential dx of normal gap acidosis
Differential dx of increased anion gap
acidosis
Understand all the
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Case #1
A 50-year-old man admitted with worsening ascites
HIV with low CD4, Hep C cirrhosis
H/O diarrhea (3-5 stools daily) on lactulose, also takes spironolactone, furosemide and propranolol 135 112 12 93
3.8 16 0.8
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Case #1
Identify acid-base disorder:
135 112 12 93
3.8 16 0.8
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Case #1 – further studies
Laboratory data show that the patient actually has a respiratory alkalosis, secondary to pulmonary edema.
Note A-a gradient – room air ABG
pH 7.45 145 117 35 168
pCO2 27 3.1 15 1.0
pO2 63
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Morning Report guesses
Type IV RTA secondary to spironolactone
Diarrhea
Distal RTA secondary to cirrhosis
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Teaching Point #1
You cannot diagnosis acid-
base disorders without an
ABG
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Case #2
A 38 year-old woman with progressive quadriparesis
h/o joint pain, stiffness and Raynaud’s Laboratory data:
pH 7.23 137 115 48 112
pCO2 29 0.9 12 0.8
pO2
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Case #2
A 38 year-old woman with progressive quadriparesis
h/o joint pain, stiffness and Raynaud’s Laboratory data:
pH 7.23 137 115 48 112
pCO2 29 0.9 12 0.8
pO2
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11
Normal gap acidosis
This patient has a gap of 10
Remember to adjust “normal gap” for the
patient’s albumin level
11
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Expected anion gap
Classic formula
11 – (2.5*[4-serum albumin])
UAB quick formula
Serum albumin * 3
12
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The Differential Diagnosis of
Normal Anion Gap Acidosis
Bicarbonate wasting
Incomplete buffering
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Bicarbonate wasting
Proximal RTA
Fanconi’s syndrome
Acetazolamide
Diarrhea
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Incomplete buffering
CKD Stage III or IV
Type IV RTA
ACE, ARB, aldosterone antagonists
Distal RTA
Urine-bowel connections
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K+ impact
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Additional information in
this case.
Urine pH 7.5
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Final Diagnosis
Sjögren’s syndrome with distal RTA
Distal RTA causing severe hypokalemia
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Teaching Point #2
Understanding physiology helps us diagnose
normal gap acidosis
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Case #3
A 48-year-old female
s/p ileostomy, now admitted for increased
ileal output
Laboratory data:
pH 7.33 141 112 18 97
pCO2 25 4.3 15 0.7
pO2 103
calc HCO3 13
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Case #3
A 48-year-old female
s/p ileostomy, now admitted for increased
ileal output
Laboratory data:
pH 7.33 141 112 18 97
pCO2 25 4.3 15 0.7
pO2 103
calc HCO3 13
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Acid Base Disturbance
Low bicarbonate with a anion gap of 14
Patient had a serum albumin of 5.7
Thus, normal gap
Presumed diagnosis
Normal gap acidosis secondary to
increased ileal output
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Diarrhea Causing Acidosis
Diarrhea normally has a basic pH
Or
Stool is BASIC!
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Diarrhea Causing Acidosis
Diarrhea normally has a basic pH
With profound diarrhea (at least 2-3
liters/day), patients may develop an
acidosis
This is more common in the presence of
CKD
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Analyzing this patient
Urine sodium 10
Urine potassium 47
Urine chloride 72
The urine anion gap differentiates renal
and GI causes
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Urine Anion Gap
UAG = Urine ([Na+ + K+] – [Cl-] )
UAG = Urine ([Na+ + K+ + NH4+ ] – [Cl- ])
If NH4+ = 0
UAG + and renal cause
If NH4+ = large
UAG – and GI losses
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Final thoughts
Urine anion gap = 10 + 47 – 72 = -15
Confirms patient has GI losses
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Teaching Point #3
Use the urine anion gap to differentiate
between buffering problems and bicarbonate
losses
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Case #4
65-year-old man with h/o chronic
constipation
3 weeks PTA - exploratory lap - no
obstruction
5 days PTA - large volume watery diarrhea
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Case #4 - lab values
Laboratory values
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pH 7.44 143 102 19 109
pCO2 42 3.3 33 1.0
pO2 52
calc HCO3
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Case #4 - lab values
Laboratory values
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pH 7.44 143 102 19 109
pCO2 42 3.3 33 1.0
pO2 52
calc HCO3
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Case #4 solved
The patient has a metabolic alkalosis
Unexpected with large volume diarrhea
Diarrhea secondary to lactulose
Because lactulose acidifies the stool!
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Teaching Point #4
Lactulose works by acidifying the stool and
thus could cause a metabolic alkalosis.
All other diarrhea causes a metabolic
acidosis
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Case #5
A 28-year-old man found non-responsive.
The patient did not respond to naloxone.
Laboratory data:
pH 7.12 146 107 12 148
pCO2 30 4.7 14 1.6
pO2 71
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Case #5
A 28-year-old man found non-responsive.
The patient did not respond to naloxone.
Laboratory data:
pH 7.12 146 107 12 148
pCO2 30 4.7 14 1.6
pO2 71 AG 25
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Axiom
Gaps > 25 are usually explainable
Aggressively seek an explanation when > 25
Else use clinical judgment
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The Differential Diagnosis of Elevated
Anion Gap Metabolic Acidosis
Ketoacidosis
Ingestion
Lactic acidosis
Uremia
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Differential Diagnosis of
Ketoacidosis
Diabetic ketoacidosis
Alcoholic ketoacidosis (10% have
negative ketones)
Starvation ketosis (generally smaller
gap)
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Ingestions & increased
anion gap
Ethylene glycol and methanol
Salicylates
INH - rarely seen
Iron
Acetaminophen (oxoproline) - mostly in
elderly malnourished women
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Lactic acidosis
Type A – dying tissue
Type B – tumor secretion
Medications
metformin
nucleoside reverse transcriptase inhibitor
linezolid
Propylene glycol
D-lactic acidosis
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Uremia
Increased phosphate levels
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More equations for
complex problems
Winter’s equation
Delta gap
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The Winter’s Equation
pCO2 = 1.5 x (HCO3-) + 8 ± 2
Uses calculated bicarb from ABG
Albert MS, Dell RB, Winters RW. Quantitative displacement of acid-base
equilibrium in metabolic acidosis. Ann Intern Med. 1967;66:312-322.
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Delta Gap
Delta gap = (observed – expected)
anion gap
Here the observed anion gap is 25 and
the expected anion gap is 12; therefore,
the delta gap is 13
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Use of the Delta Gap
One adds the delta to the observed
bicarbonate
This estimates bicarbonate prior to the
elevated anion gap
In this case the patient started out with a
normal bicarbonate of 27
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Further Evaluation
Normal lactate
Serum and urine ketones negative
Measured osms = 354
Calculated osms = 303
Osm gap = 51
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Calcium Oxalate Crystals
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Final Diagnosis
Ethylene Glycol
Classically treated with dialysis and IV
alcohol
New medication – fomepizole
Often can obviate dialysis
Now generic ~$500 per dose
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Teaching Point #5
Anion gaps of 25 or greater deserve a
thorough evaluation
The Winter’s equation helps us determine
the appropriate respiratory response
We can use the Delta gap to diagnose a
“double” metabolic abnormality
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Case #6
62-year-old man, alcoholic, CAP
Transferred after 4 days (on respirator)
On 10 mg/h of IV Ativan
pH 6.9 137 102 8 109
pCO2 36 4.3 10 0.7
pO2 121
calc HCO3 10
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Case #6
62-year-old man, alcoholic, CAP
Transferred after 4 days (on respirator)
On 10 mg/h of IV Ativan
pH 6.9 137 102 8 109
pCO2 36 4.3 10 0.7
pO2 121 AG 25
calc HCO3 10
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Case #6 - solution
Increased anion gap - 25
Respiratory acidosis
Serum osms = 364
D-lactic acid is markedly increased
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Propylene glycol toxicity
Propylene glycol is used to dissolve several
IV drugs
Lorazepam (Ativan) - most important
Diazepam
Trimethroprim-sulfamethoxazole
Propylene glycol -> lactate and acetate
Increased osm gap -> increased AG -> AKI
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Teaching Point #6
To avoid propylene glycol toxicity
Limit IV lorazepam to under 7 mg/hr
If you must go above
Check serum osms q12
When osm gap increases find another option
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Case #7
41-year-old woman, s/p bariatric surgery
(100# wt loss), presents “feeling drunk”
Chronic diarrhea - short gut syndrome
Mild gait instability
pH 7.2 140 116 5 82
pCO2 13 3.8 9 0.8
pO2 138
calc HCO3 5
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Double metabolic acidosis
Anion gap = 17
Expected gap = 8 (2.5*3)
Expected HCO3 = 8 + 9 = 17
pH 7.2 140 114 5 82
pCO2 13 3.8 9 0.8
pO2 138
calc HCO3 5 Alb 2.5
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Case #7 double acidosis
Winter’s equation:
5 * 1.5 = 8 + 8 = 16
Use calc HCO3 , not measured HCO3
Therefore no respiratory problem
pH 7.2 140 114 5 82
pCO2 13 3.8 9 0.8
pO2 138
calc HCO3 5 Alb 2.5
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Case #7 - diagnosis
Lactic acid 2.4 (0.7-2.1), neg salicylate
normal osm gap
D-Lactic acid 6.62 (0.0-0.25)
Pt gave history of recurrent symptoms -
always after a high carbohydrate meal
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Case #8
A 58-year-old schizophrenic male was
brought to the hospital because of
strange behavior after “overdose”
Laboratory data:
pH 7.49 139 90 18 100
pCO2 15 4.7 14 1.0
pO2 169 on 2
liters
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Case #8
A 58-year-old schizophrenic male was
brought to the hospital because of
strange behavior after “overdose”
Laboratory data:
pH 7.49 139 90 18 100
pCO2 15 4.7 14 1.0
pO2 169 on 2
liters
AG 35 Delta
gap
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Evaluating a mixed acid-
base disorder
Elevated anion gap = 35
Delta Gap = 35 – 12 = 23
Revealed bicarbonate = 23 + 14 = 37
Anion gap acidosis & metabolic
alkalosis
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Continued Evaluation
pCO2 = 15 therefore, primary respiratory
alkalosis
triple disorder of an elevated anion gap
acidosis, metabolic alkalosis, and a
respiratory alkalosis
Alka-seltzer overdose.
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Teaching point #8
A systematic approach to electrolyte panels
and ABGs allow us to diagnose “triple” acid-
base disorders
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Metabolic acidosis - Rx
Acute
Increased anion gap
Normal gap
Chronic Kidney disease
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Acute increased anion gap
Experts differ on need for bicarbonate
Most suggest definitely treating pH <7.0
No good data
Do not treat if underlying disorder will correct
quickly
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Acute normal gap
Always treat
Goal bicarbonate 22
Estimate deficit:
(22 – pt’s bicarb)* TBW
TBW ~ 0.5 wt in kg
Add bicarbonate (50 mEq/amp) to D5/W =
usually 2 or 3 amps
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CKD with acidosis
Recent studies suggest
Correcting acidosis delays progression
Perhaps giving bicarb prior to acidosis will also
delay progression
One tablet with each meal – 650 mg = 7.7
mEq
Or 1 tbsp sodium citrate solution twice daily
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Summary
Reviewed importance of ABG
Differential diagnosis of normal gap acidosis
Differential diagnosis of increased gap
acidosis
Possibly expanded knowledge of iatrogenic
acid base disorders
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1. Albert MS, Dell RB, Winters RW. Quantitative displacement of acid-base
equilibrium in metabolic acidosis. Ann Intern Med. 1967;66:312-322.
2. Gabow PA, Kaehny WD, Fennessey PV, Goodman SI, Gross PA, Schrier RW.
Diagnostic importance of an increased serum anion gap. N Engl J Med.
1980;303:854-858.
3. Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA.
Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with
human immunodeficiency virus infection: a report of 12 cases. Clin Infect Dis.
2001;33:1914-1921.
4. Kopterides P, Papadomichelakis E, Armaganidis A. Linezolid use associated with
lactic acidosis. Scandinavian Journal of Infectious Diseases. 2005;37:153-154.
5. Fenves A. Increased Anion Gap Metabolic Acidosis as a Result of 5-Oxoproline
(Pyroglutamic Acid): A Role for Acetaminophen. Clinical Journal of the American
Society of Nephrology. 2006;1:441-447.
6. Brent J. Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med.
2009;360:2216-2223.
References