Download - Non-anion gap Metabolic Acidosis (NAGMA)
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Interesting Electrolyte Cases
Joel M. Topf, M.D.
Nephrology
248.470.8163
http://PBFluids.blogspot.com
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58 y.o. female with weakness and muscle aches
139 115 3.1 17
16
1.0
7.34 / 87 / 33 / 17
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Determine the primary acid-base disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
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Determine the primary acid-base disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
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Determine the primary acid-base disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the
same direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
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Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the
same direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
Metabolic Acidosis
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Predicting pCO2 in metabolic acidosis: Winter’s Formula• In metabolic acidosis the expected pCO2 can
be estimated from the HCO3
Expected pCO2 = (1.5 x HCO3) + 8 ± 2
• If the pCO2 is higher than predicted then there is an addition respiratory acidosis
• If the pCO2 is lower than predicted there is an additional respiratory alkalosis
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– Expected pCO2 = (1.5 x HCO3) + 8 ±2
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
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– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
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– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
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– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
Appropriately compensated metabolic acidosis
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• Metabolic acidosis is further evaluated by determining the anion associated with the increased H+ cation
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• Metabolic acidosis is further evaluated by determining the anion associated with the increased H+ cation
It is either chloride
Non-Anion GapMetabolic Acidosis
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• Metabolic acidosis is further evaluated by determining the anion associated with the increased H+ cation
It is either chloride
Non-Anion GapMetabolic Acidosis
Or it is not chloride
Anion GapMetabolic Acidosis
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• Metabolic acidosis is further evaluated by determining the anion associated with the increased H+ cation
• These can be differentiated by measuring the anion gap.
It is either chloride
Non-Anion GapMetabolic Acidosis
Or it is not chloride
Anion GapMetabolic Acidosis
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Anion gap
=
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Anion gap
=
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Anion gap
=
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Anion gap
=
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• Anion gap = Na – (HCO3 + Cl)
• Normal is 12
Calculating the anion gap
• Anion gap = 139 – (17 + 115)• Anion gap = 7
139 115 3.1 17
16
1.0
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• Anion gap = Na – (HCO3 + Cl)
• Normal is 12– Varies from lab to lab– Average anion gap in healthy controls is 6 ±3
• Improving chloride assays have resulted in increased chloride levels and a decreased normal anion gap.
Calculating the anion gap
• Anion gap = 139 – (17 + 115)• Anion gap = 7
– Varies from lab to lab– Average anion gap in healthy controls is 6 ±3
• Improving chloride assays have resulted in increased chloride levels and a decreased normal anion gap.
139 115 3.1 17
16
1.0
Appropriately compensated non-anion gap metabolic acidosis
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NAGMA: Loss of bicarbonate
GI loss of HCO3
Diarrhea
Surgical drains
Fistulas
Ureterosigmoidostomy
Obstructed ureteroileostomy
Cholestyramine
Renal loss of HCO3
Renal tubular acidosis
Proximal
Distal
Hypoaldosteronism
Saline infusionsDilutional acidosis
HCl intoxication
Chloride gas intoxication
Early renal failure
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NAGMA: Loss of bicarbonate
GI loss of HCO3
Diarrhea
Surgical drains
Fistulas
Ureterosigmoidostomy
Obstructed ureteroileostomy
Cholestyramine
Renal loss of HCO3
Renal tubular acidosis
Proximal
Distal
Hypoaldosteronism
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NAGMA: Loss of bicarbonate
GI loss of HCO3
Diarrhea
Surgical drains
Fistulas
Ureterosigmoidostomy
Obstructed ureteroileostomy
Cholestyramine
Renal loss of HCO3
Renal tubular acidosis
Proximal
Distal
Hypoaldosteronism
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140 102 4.4 24135 100 5.0 35135 50 5.0 90135 50 5.0 90
Plasma
Bile
Pancreas
Small intestines
Large intestines
110 90 35 40
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Urine pH=5.5 Serum pH=7.4
100 fold difference
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Ureterosigmoidostomy
Urine pH=5.5 Serum pH=7.4
100 fold difference
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Ureterosigmoidostomy Ureteroileostomy
Urine pH=5.5 Serum pH=7.4
100 fold difference
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Renal causes of non-anion gap
• Renal tubular acidosis is a failure of the kidney to reabsorb all of the filtered bicarbonate or synthesize new bicarbonate to keep up with metabolic demands.
• Daily acid load– Protein metabolism consumes bicarbonate
– This bicarbonate must be replaced
– Generally equal to 1 mmol/kg
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Bicarbonate handling• Normally 144 mmol of
bicarbonate per hour are filtered at the glomerulus– 24 mmol/L x 100 mL/min x 60
min/hour
– Equivalent to 3 amps of bicarb per hour or a bicarb drip running 1 liter per hour
3456 mmol/day 50-100 mmol/day
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Bicarbonate handling• Normally 144 mmol of
bicarbonate per hour are filtered at the glomerulus– 24 mmol/L x 100 mL/min x 60
min/hour
– Equivalent to 3 amps of bicarb per hour or a bicarb drip running 1 liter per hour
• The kidney must create 50-100 mmol per day of new bicarb-onate to replace bicarbonate lost buffering the daily acid load.
3456 mmol/day 50-100 mmol/day
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Proximal tubule: reabsorption of filtered bicarbonate
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Proximal tubule: reabsorption of filtered bicarbonate
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Proximal tubule: reabsorption of filtered bicarbonate
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Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
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Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
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Distal tubule, completion of reabsorption and replacing bicarbonate lost to the daily acid load.
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Fate of excreted hydrogen ion
The minimal urine pH is 4.5. This is a H+ concentration a 1000 times that of plasma.
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Fate of excreted hydrogen ion
The minimal urine pH is 4.5. This is a H+ concentration a 1000 times that of plasma.
ButIt still is only 0.04 mmol/L
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Fate of excreted hydrogen ion
The minimal urine pH is 4.5. This is a H+ concentration a 1000 times that of plasma.
ButIt still is only 0.04 mmol/L
In order to excrete 50 mmol (to produce enough bicarb-onate to account for the daily acid load) one would need to produce 1250 liters of urine.
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Fate of excreted hydrogen ion
Ammonium
Titratable acid
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Proximal RTA (Type 2)
• The Tm is the maximum plasma concentration of any solute at which the proximal tubule is able to completely reabsorb the solute.
• Beyond the Tm the substance will be incompletely reabsorbed and spill in the urine.
• In Proximal RTA the Tm for bicarbonate is reduced from 26 to 15-20 mmol/L.
Na+
H2OHCO3 Glucose
Amino Acids
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• Proximal RTA– Tm for bicarbonate at 15
• Serum bicarbonate above the Tm
Proximal RTA (Type 2)
24 mmol/L
15 mmol/L
pH 8
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• Proximal RTA– Tm for bicarbonate at 15
• Serum bicarbonate at the Tm
Proximal RTA (Type 2)
15 mmol/L
15 mmol/L
pH 5
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• Proximal RTA– Tm for bicarbonate at 15
• Serum bicarbonate below the Tm
Proximal RTA (Type 2)
12 mmol/L
12 mmol/L
pH 5
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Proximal RTA: etiologies
• Acquired– Acetylzolamide – Ifosfamide – Chronic hypocalcemia– Multiple myeloma– Cisplatin– Lead toxicity– Mercury poisoning– Streptozocin– Expired tetracycline
• Genetic– Cystinosis– Galactosemia– Hereditary fructose
intolerance– Wilson’s disease
• Hyperparathyroidism• Chronic hypocapnia
– Intracellular alkalosis
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Proximal RTA: consequences
• Hypokalemia• Bone disease
– Bone buffering of the acidosis
– Decreased 1,25 OH D leading to hypocalcemia and 2° HPTH
• Not typically complicated by stones
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Distal RTA (Type 1)
• A failure to secrete the daily acid load at the distal tubule is distal rta.
• A failure in any one of the three steps in urinary acidification can result in RTA
• Each step has been demonstrated to fail and has independent etiologies
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Distal RTA: Voltage dependent
• Only variety of distal RTA which is hyperkalemic
• Differentiate from type 4 by failure to respond to fludrocortisone.– Obstructive uropathy– Sickle cell anemia– Lupus– Triameterene– Amiloride
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Distal RTA: Voltage dependent
• Only variety of distal RTA which is hyperkalemic
• Differentiate from type 4 by failure to respond to fludrocortisone.– Obstructive uropathy– Sickle cell anemia– Lupus– Triameterene– Amiloride
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Distal RTA: Voltage dependent
• Only variety of distal RTA which is hyperkalemic
• Differentiate from type 4 by failure to respond to fludrocortisone.– Obstructive uropathy– Sickle cell anemia– Lupus– Triameterene– Amiloride
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Distal RTA: Voltage dependent
• Only variety of distal RTA which is hyperkalemic
• Differentiate from type 4 by failure to respond to fludrocortisone.– Obstructive uropathy– Sickle cell anemia– Lupus– Triameterene– Amiloride
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Distal RTA: H+ Secretion
• Called classic distal RTA
• Most common cause of distal RTA– Congenital– Lithium– Multiple myeloma– Lupus– Pyelonephritis– Sickle cell anemia– Sjögren’s syndrome– Toluene (Glue sniffing)– Wilson’s disease
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Distal RTA: Gradient defect
• Amphotercin B
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Distal RTA: consequences
• Bones– Chronic metabolic
acidosis results in bone buffering.
• Bicarbonate• Phosphate • Calcium
• Kidney stones– Calcium phosphate
stones• Due to hypercalciuria• Increased urine pH• Decreased urinary
citrateWell Mr. Osborne, it may not be kidney stones after all.
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Hypoaldosteronism
• Chronic hyperkalemia of any etiology decreases ammonia- genesis
• Without ammonia to convert to ammonium total acid excretion is modest
• Urinary acidification is intact
• Acidosis is typically mild without significant bone or stone disease
• Primary problem is with high potassium
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non-anion gap metabolic acidosis
Diagnosing the cause of:
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Ammonium
Titratable acid
To look for renal H+ clearance look for urinary ammonium
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Ammonium
Titratable acid
To look for renal H+ clearance look for urinary ammonium
NH4+
![Page 62: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/62.jpg)
Urinary anion gap: Urinary ammonium detector
(Na+ + K+) – Cl–
• In the presence of ammonium the chloride will be larger than the sum of Na and K.
• So a negative anion gap means ammonium in the urine.
• Ammonium in the urine means effective renal acid secretion
• Ammonium in the urine usually rules out RTA
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NAGMA and urinary anion gap• Diarrhea
![Page 64: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/64.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative
![Page 65: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/65.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline
15 mmol/L
15 mmol/L
pH 5
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NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
15 mmol/L
15 mmol/L
pH 5
![Page 67: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/67.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment
24 mmol/L
15 mmol/L
pH 8
![Page 68: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/68.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
24 mmol/L
15 mmol/L
pH 8
![Page 69: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/69.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load
12 mmol/L
12 mmol/L
pH 5
![Page 70: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/70.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load• Negative
12 mmol/L
12 mmol/L
pH 5
![Page 71: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/71.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load• Negative
• Distal RTA
![Page 72: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/72.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load• Negative
• Distal RTA:– Positive
![Page 73: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/73.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load• Negative
• Distal RTA:– Positive
• Type IV RTA
![Page 74: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/74.jpg)
NAGMA and urinary anion gap• Diarrhea
– Negative• Proximal RTA
– At baseline• Negative
– During treatment• Positive
– During acid load• Negative
• Distal RTA:– Positive
• Type IV RTA– Positive
![Page 75: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/75.jpg)
58 y.o. female with weakness and muscle aches
139 115 3.1 17
16
1.0
7.34 / 87 / 33 / 16
U/A pH 6.5
80 115 45
Urine electrolytes
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58 y.o. female with weakness and muscle aches
139 115 3.1 17
16
1.0
7.34 / 87 / 33 / 16
U/A pH 6.5
80 115 45
Urine electrolytes
Appropriately compensated non-anion gap metabolic acidosis due
to distal RTA
![Page 77: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/77.jpg)
74 y.o. female with 34 year history of DM c/o weakness
139 123 6.6 17
21
1.2
7.34 / 87 / 33 / 16
Albumin 1.8
![Page 78: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/78.jpg)
Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
![Page 79: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/79.jpg)
Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
![Page 80: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/80.jpg)
Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
![Page 81: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/81.jpg)
Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the
same direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
![Page 82: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/82.jpg)
Determine the primary disorder
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the same
direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
1. Acidosis or alkalosis– If the pH is less than 7.4 it is acidosis– If the pH is greater than 7.4 it is alkalosis
7.34 / 87 / 33 / 16pH / pO2 / pCO2 / HCO3
2. Determine if it is respiratory or metabolic– If the pH, bicarbonate and pCO2 all move in the
same direction (up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions (up and down) it is respiratory
Metabolic Acidosis
![Page 83: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/83.jpg)
– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
![Page 84: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/84.jpg)
– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
![Page 85: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/85.jpg)
– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
![Page 86: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/86.jpg)
– Expected pCO2 = (1.5 x HCO3) + 8 ±2– Expected pCO2 = 31-35– Actual pCO2 is 33, which is within the predicted range,
indicating a simple metabolic acidosis
Predicting pCO2 in metabolic acidosis: Winter’s Formula
7.33 / 87 / 33 / 17 pH / pO2 / pCO2 / HCO3
Appropriately compensated metabolic acidosis
![Page 87: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/87.jpg)
Calculating the anion gap
• Anion gap = Na – (HCO3 + Cl)
139 123 6.6 17
16
1.0
![Page 88: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/88.jpg)
Calculating the anion gap
• Anion gap = Na – (HCO3 + Cl)
139 123 6.6 17
16
1.0• Anion gap = 139 – (123 + 17)• Anion gap = -1
![Page 89: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/89.jpg)
Calculating the anion gap
• Anion gap = Na – (HCO3 + Cl)
139 123 6.6 17
16
1.0• Anion gap = 139 – (123 + 17)• Anion gap = -1A negative anion gap!That’s got to mean something!
![Page 90: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/90.jpg)
Hypoalbuminuria, hypophosphatemia• The “other anions” includes phosphate and albumin
• Hypoalbuminuria and hypophosphatemia lowers the anion gap
• If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap
![Page 91: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/91.jpg)
Hypoalbuminuria, hypophosphatemia• The “other anions” includes phosphate and albumin
• Hypoalbuminuria and hypophosphatemia lowers the anion gap
• If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap
![Page 92: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/92.jpg)
Hypoalbuminuria, hypophosphatemia• The “other anions” includes phosphate and albumin
• Hypoalbuminuria and hypophosphatemia lowers the anion gap
• If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap
Adjusted Normal Anion Gap
![Page 93: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/93.jpg)
Hypoalbuminuria, hypophosphatemia• The “other anions” includes phosphate and albumin
• Hypoalbuminuria and hypophosphatemia lowers the anion gap
• If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap
Adjusted Normal Anion Gap
![Page 94: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/94.jpg)
Hypoalbuminuria, hypophosphatemia• The “other anions” includes phosphate and albumin
• To estimate the normal anion gap for any individual multiply the albumin by 2.5 and add half the phosphorous
• Hypoalbuminuria and hypophosphatemia lowers the anion gap
• If one fails to adjust the upper and lower limit of the normal anion gap, altered albumin and phosphorous can hide a pathologic anion gap
Adjusted Normal Anion Gap
![Page 95: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/95.jpg)
Other causes of a low anion gap• Increased chloride
– Hypertriglyceridemia– Bromide– Iodide
• Decreased “Unmeasured anions”– Albumin– Phosphorous– IgA
• Increased “Unmeasured cations”– Hyperkalemia– Hypercalcemia– Hypermagnesemia– Lithium– Increased cationic paraproteins
• IgG
Albumin
Phos
IgA
Chloride
Bicarb
Sodium
Potassium
Calcium
Magnesium
IgG
Normalanion
gap
![Page 96: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/96.jpg)
Recent lab history
![Page 97: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/97.jpg)
non-anion gap metabolic acidosis with hyperkalemia
Diagnose the cause of:
![Page 98: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/98.jpg)
non-anion gap metabolic acidosis with hyperkalemia
Diagnose the cause of:
1. Type four RTA, hyporenin-hypoaldo
![Page 99: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/99.jpg)
non-anion gap metabolic acidosis with hyperkalemia
Diagnose the cause of:
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA
![Page 100: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/100.jpg)
A dipstick for aldosterone activity:The trans-tubular potassium gradientThe TTKG
![Page 101: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/101.jpg)
Trans-tubular Potassium Gradient(TTKG)• The ratio of tubular to
venous K indicates the level of aldosterone activity.
• In the presence of hyperkalemia the ratio should be > 10.
• In the presence of hypokalemia the ratio of < 4.
![Page 102: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/102.jpg)
Trans-tubular Potassium Gradient(TTKG)• The ratio of tubular to
venous K indicates the level of aldosterone activity.
• In the presence of hyperkalemia the ratio should be > 10.
• In the presence of hypokalemia the ratio of < 4.
![Page 103: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/103.jpg)
Trans-tubular Potassium Gradient(TTKG)• The ratio of tubular to
venous K indicates the level of aldosterone activity.
• In the presence of hyperkalemia the ratio should be > 10.
• In the presence of hypokalemia the ratio of < 4.
![Page 104: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/104.jpg)
Trans-tubular Potassium Gradient(TTKG)• The ratio of tubular to
venous K indicates the level of aldosterone activity.
• In the presence of hyperkalemia the ratio should be > 10.
• In the presence of hypokalemia the ratio of < 4.
![Page 105: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/105.jpg)
• The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts.
• This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD.
€
TTKG =KCCD
K plasma
KCCD =Kurine
OsmurineOsmplasma
TTKG =
Kurine
OsmurineOsmplasma
K plasma
TTKG =Kurine × OsmPlasma
K plasma × Osmurine
Trans-tubular Potassium Gradient(TTKG)
![Page 106: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/106.jpg)
• The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts.
• This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD.
€
TTKG =KCCD
K plasma
KCCD =Kurine
OsmurineOsmplasma
TTKG =
Kurine
OsmurineOsmplasma
K plasma
TTKG =Kurine × OsmPlasma
K plasma × Osmurine
Trans-tubular Potassium Gradient(TTKG)
![Page 107: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/107.jpg)
• The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts.
• This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD.
€
TTKG =KCCD
K plasma
KCCD =Kurine
OsmurineOsmplasma
TTKG =
Kurine
OsmurineOsmplasma
K plasma
TTKG =Kurine × OsmPlasma
K plasma × Osmurine
Trans-tubular Potassium Gradient(TTKG)
![Page 108: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/108.jpg)
• The trans-tubular potassium gradient adjusts the urine potassium for water loss in the collecting ducts.
• This allows the use of urinary potassium to calculate the ratio of potassium from the tubule to the interstitium in the CCD.
€
TTKG =KCCD
K plasma
KCCD =Kurine
OsmurineOsmplasma
TTKG =
Kurine
OsmurineOsmplasma
K plasma
TTKG =Kurine × OsmPlasma
K plasma × Osmurine
Trans-tubular Potassium Gradient(TTKG)
![Page 109: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/109.jpg)
– Urine osmolality > serum osmolality
• Pre-requisites to using the TTKG as a measure of aldosterone activity:
Trans-tubular Potassium Gradient(TTKG)
![Page 110: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/110.jpg)
– Urine osmolality > serum osmolality
• Pre-requisites to using the TTKG as a measure of aldosterone activity:
Fluid leaving the LoH has an osmolality of 100 mOsm/Kg
Trans-tubular Potassium Gradient(TTKG)
![Page 111: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/111.jpg)
– Urine osmolality > serum osmolality
• Pre-requisites to using the TTKG as a measure of aldosterone activity:
Fluid leaving the LoH has an osmolality of 100 mOsm/Kg
In the presence of ADH water leaves the DCT so that the tubular fluid becomes isosmotic
Trans-tubular Potassium Gradient(TTKG)
![Page 112: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/112.jpg)
– Urine osmolality > serum osmolality
• Pre-requisites to using the TTKG as a measure of aldosterone activity:
Fluid leaving the LoH has an osmolality of 100 mOsm/Kg
In the presence of ADH water leaves the DCT so that the tubular fluid becomes isosmotic
Trans-tubular Potassium Gradient(TTKG)
– Urine Na > 20 mmol/L
![Page 113: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/113.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA
Trans-tubular Potassium Gradient(TTKG)
Lets play low normal or high! TTKG and Aldo level
![Page 114: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/114.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA
Trans-tubular Potassium Gradient(TTKG)
1. Type four RTA, hyporenin-hypoaldo
• Low TTKG• Low aldosterone
Lets play low normal or high! TTKG and Aldo level
![Page 115: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/115.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA
Trans-tubular Potassium Gradient(TTKG)
1. Type four RTA, hyporenin-hypoaldo
• Low TTKG• Low aldosterone
2. Hyperkalemic Distal (Type 1) RTA, voltage dependent distal RTA
• Low TTKG• High aldosterone
Lets play low normal or high! TTKG and Aldo level
![Page 116: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/116.jpg)
4.7 5 5.2 5.4 5.76.6
3.8
1.8
-5
0
5
10
15
20
25
-5 -4 -3 -2 -1 0
BicarbonatePotassiumAlbuminAnion Gap
58 y.o. female with weakness and muscle aches
![Page 117: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/117.jpg)
4.7 5 5.2 5.4 5.76.6
3.8
1.8
-5
0
5
10
15
20
25
-5 -4 -3 -2 -1 0
BicarbonatePotassiumAlbuminAnion Gap
Both the bicarbonate and potassiumwere normal at admission. This ishospital acquired RTA (type 1 or 4)
58 y.o. female with weakness and muscle aches
![Page 118: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/118.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
Hospital acquired RTA really means drug induced RTA
![Page 119: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/119.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
Hospital acquired RTA really means drug induced RTALets play: Name that drug!
![Page 120: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/120.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
Hospital acquired RTA really means drug induced RTA
1. Type four RTA, hyporenin-hypoaldo
• Spironolactone• ACEi/ARB• Heparin
Lets play: Name that drug!
![Page 121: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/121.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
Hospital acquired RTA really means drug induced RTA
1. Type four RTA, hyporenin-hypoaldo
• Spironolactone• ACEi/ARB• Heparin
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
• Amiloride• Triamterene• Trimethoprim
Lets play: Name that drug!
![Page 122: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/122.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
58 y.o. female with weakness and muscle aches
![Page 123: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/123.jpg)
1. Type four RTA, hyporenin-hypoaldo
2. Hyperkalemic Distal (Type 1), voltage dependent distal RTA
58 y.o. female with weakness and muscle aches
Patient’s TTKG was 2.7 with a K of 5.7
Aldosterone was 22
The patient had been started on a high dose of TMP/SMX for a partially resistant urinary tract infection
![Page 124: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/124.jpg)
Two women with non-anion
gap metabolic acidosis
One with hypokalemia
One with hyperkalemia
Both with distal RTA
![Page 125: Non-anion gap Metabolic Acidosis (NAGMA)](https://reader038.vdocuments.mx/reader038/viewer/2022102700/554b5b0eb4c9051b458b4d67/html5/thumbnails/125.jpg)
Fin