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Kalani L. Raphael, MD Assistant Professor
Division of Nephrology Department of Internal Medicine
University of Utah & Salt Lake City VA HCS
Practical approach to disorders involving
Sodium,
Potassium,
Bicarbonate,
& a bonus case.
“Hey, we admitted a 24 F with generalized weakness. Her K was undetectable, bicarb was low and urine pH was high. We think she has an RTA. Can you see her? Thanks a lot!”
Exam: 115/52, HR 79, generalized weakness, hypotonia
141 14
< 1.6 0.8 103
112
16
Do you agree with their diagnosis of renal tubular acidosis?
1. Profound hypokalemia 2. Low bicarbonate 3. Normal anion gap (AG=13)
141 14
< 1.6 0.8 103
112
16
Other Labs
Ca 9.2
Phos 1.5
Mg 2.0
TSH 2.5
ABG
pH 7.41
pCO2 29
pO2 91
HCO3- 18
BE -5
What is the acid-base problem, if any?
1. Profound hypokalemia 2. Normal anion gap metabolic acidosis
Renal Loss Diuretics RTA type 1 & 2 Aldosterone Vomiting
Hypovolemia
Hyperaldosteronism
High urine flow Diabetes insipidus
Na delivery
GI Loss Diarrhea
Redistribution Insulin Beta agonist Alkalemia Hyperthyroidism Alpha blockers Exercise
Hypokalemia
Renal K+ loss Non-renal K+ loss • GI • Redistribution
Tells us what the kidney is doing with Na+
Is there a fractional excretion of K+?
FENa+ =
Urine Na+
Urine Cr
Serum Na+
Serum Cr
< 1%
> 2%
Renal Na+ retention
Renal Na+ loss
TTKG =
Urine K+
Urine Osm
Serum K+
Serum Osm
FENa+ =
Urine Na+
Urine Cr
Serum Na+
Serum Cr
Why use osmolality? • If urine is very concentrated, urine K+ will be higher suggesting renal K+ loss
• Corrects for the difference in osmolality between urine & serum.
If you can’t readily identify the cause of hypokalemia
check TTKG
Reflects what the collecting duct is doing with K
TTKG distinguishes renal vs. non-renal causes of
hypokalemia
Hypokalemia
Renal K+ loss Non-renal K+ loss • GI • Redistribution
TTKG < 3% TTKG > 7%
141 14
< 1.6 0.8 103
112
16
Problems 1. Profound hypokalemia
TTKG =
Urine K+
Urine Osm
Serum K+
Serum Osm
11.7
422
3.5
290
= = 2.3%
< 20 mEq/L suggests renal retention
24 hour urine K+ = 17 mEq
141 14
< 1.6 0.8 103
112
16
Problems 1. Profound hypokalemia 2. Normal anion gap metabolic acidosis
TTKG and 24 hr K low. Non-renal potassium loss
NORMAL ANION GAP
Renal Tubular Acidosis GI Bicarbonate Loss NaCl Infusion
HIGH ANION GAP
Methanol Uremia DKA Paraldehyde INH Lactic acidosis Ethylene Glycol Salicylates
Gain of chloride &
Loss of bicarbonate
Gain of non-chloride anion &
Loss of bicarbonate
Normal anion gap metabolic acidosis
Renal Etiology • Renal tubular acidosis
Non-renal etiology • GI bicarbonate loss • NaCl infusion
What should the kidneys do when there is too much acid?
How do the kidneys do this?
Urinary acid excretion = [NH4+] + [titratable acids] – [HCO3
-]
The primary means by which kidneys adapt to an increased acid load is by: A. Increasing excretion of NH4
+ B. Increasing excretion of titratable acids C. Reducing excretion of HCO3
-
If there is a metabolic acidosis and kidneys work normally there should be lots of NH4
+ in the urine.
NH4+ largely binds to Cl-
Urinary chloride, in the setting of normal anion
gap metabolic acidosis, estimates the urinary [NH4
+]
Test to order in normal anion gap metabolic acidosis Urine electrolytes – Na, K, Cl
Calculate urinary anion gap = (Na + K) - Cl
KIDNEY ETIOLOGY Renal Tubular Acidosis
If kidneys are the cause of normal anion gap metabolic acidosis
-Low urinary NH4Cl -Urinary Cl << Urinary Na + K -Urinary Anion Gap is POSITIVE
NON-KIDNEY ETIOLOGY
• GI Bicarb loss
• NaCl infusion
If kidneys are not the cause of normal anion gap metabolic acidosis
-Tons of urinary NH4Cl -Urinary Cl >> Urinary Na + K -Urinary Anion Gap is NEGATIVE
Normal anion gap metabolic acidosis
Renal Etiology • Renal tubular acidosis
Non-renal etiology • GI bicarbonate loss • NaCl infusion
UAG negative UAG positive
141 14
< 1.6 0.8 103
112
16
Problems 1. Profound hypokalemia 2. Normal anion gap metabolic acidosis
TTKG and 24 hr K low. Non-renal potassium loss
Urine Na = 54 K = 5 Cl = 68
UAG = - 9 Non-renal cause of acidosis
What is the diagnosis? 1. RTA 2. Hypokalemic periodic paralysis 3. Laxative abuse/diarrhea
Treatment
Correct potassium first
Then correct acidosis with sodium bicarbonate (IV or PO)
Acidosis raises serum K+
Correcting acidosis 1st will lower serum K+ further
141 14
< 1.6 0.8 103
112
16
Normal anion gap metabolic acidosis
Check urinary electrolytes and calculate urinary anion gap
▪ Positive UAG = renal tubular acidosis
▪ Negative UAG = GI bicarbonate loss or NaCl infusion
Hypokalemia
If unsure of etiology, check TTKG
▪ < 3% means kidney is holding on to K+
▪ > 7% means kidney is excreting K+ inappropriately
Hyperkalemia
TTKG > 10 : the kidney is responding to
hyperkalemia appropriately
▪ Non-renal cause of hyperkalemia
If TTKG < 7, the kidney is NOT responding
appropriately
▪ Renal cause of hyperkalemia
Hyperkalemia
Inappropriate renal K+
retention
Appropriate renal K+ excretion
TTKG > 10% TTKG < 7%
Reduced Renal Excretion
Renal Failure
Obstruction
Hypoaldosteronism (type
IV RTA)
NSAIDs
K-sparing diuretics
GI Gain Upper GI bleed Redistribution Acidemia Insulin deficiency Beta blockers Rhabdo Tumor lysis Pseudohyperkalemia Alpha agonists
54 year old
Na+ 120
What 3 TESTS do you order to determine
etiology of hyponatremia?
1. Serum Osmolality 2. Urine Osmolality 3. Urine Na
260
600
40
Hyponatremia
• Lipids
• Proteins • Glucose
• Mannitol
• Hyperosmolar
sucrose/mannitol
solutions (IVIg)
Everything else • Sorbitol
• Glycine
e.g. [Na] 120 meq/L
Hypo-osmolar Serum Osm < 280
Hyper-osmolar Serum Osm > 300 Serum Osm 280 - 300
Iso-osmolar
Pseudohyponatremia
STEP ONE: Look at serum osm
Serum Osm
1. High - Hyperglycemia, mannitol
2. Normal - Hyperlipidemia, paraprotein
3. Low – Everything else
WHICH IS MOST COMMON?
Serum Osm 260
Urine Osm 600
Urine Na 40
Hyponatremia
• Lipids
• Proteins • Glucose
• Mannitol
• Hyperosmolar
sucrose/mannitol
solutions (IVIg)
Everything else • Sorbitol
• Glycine
e.g. [Na] 120 meq/L
Hypo-osmolar Serum Osm < 280
Hyper-osmolar Serum Osm > 300 Serum Osm 280 - 300
Iso-osmolar
Pseudohyponatremia
Serum Osm 260
Urine Osm 600
Urine Na 40
If hypoosmolar hyponatremia… STEP TWO: Look at urine osm Urine Osm < 100 mosm/kg ADH inactive
Polydipsia
Beer potomania (low solute intake)
Urine osm > serum osm
Appropriate ADH activity
Inappropriate ADH activity
Serum Osm 260
Urine Osm 600
Urine Na 40
Na
Na
Na
Na
Na
Na
H20
H20
H20
H20
H20 H20
Collecting duct
Blood
Urea
Urea
Urea
Urea
Urea
Urea
Low Effective Arterial Blood Volume
Urine Osm Urine Na
ADH
AQP2
AQP2
AQP2
EABV
APPROPRIATE ADH SECRETION
AQP2
Na+
Na+
Na+
Aldosterone Na+
Renal water reabsorption >> Na
Hyponatremia Urine Na < 10 Urine Osm > Plasma
SIADH
ADH
Pt is not hypovolemic Pt is not hyperosmolar
Na
Na
Na
Na
Na
Na
H20
H20
H20
H20
H20 H20
Collecting duct Blood
Urea
Urea
Urea
Urea
Urea
Urea
Urea
AQP2
AQP2
AQP2
Urine Osm Urine Na (usually)
Since EABV is normal • Aldosterone activity is normal • Little Na reabsorption
Yet ADH is secreted, inappropriately
Hyponatremia Urine Na > 20 Urine Osm > Plasma
Na H20
If hypoosmolar hyponatremia & High urine osmolality STEP THREE: Look at urine Na+ Urine Na+ < 10 mEq/L Aldosterone active
Low effective arterial blood volume, sepsis, etc
> 20 mEq/L
SIADH
Serum Osm 260
Urine Osm 600
Urine Na 40
Serum Osm Urine Osm Urine Na
Hyperosmolal > 300
Isoosmolal 280-300
Hypoosmolal < 280
STEP 1 STEP 2 STEP 3 HYPONATREMIA
Serum Osm 260
Urine Osm 600
Urine Na 40
Serum Osm Urine Osm Urine Na
Hyperosmolal > 300
Isoosmolal 280-300
Hypoosmolal < 280
• Polydipsia < 280 < 100
STEP 1 STEP 2 STEP 3 HYPONATREMIA
Serum Osm 260
Urine Osm 600
Urine Na 40
Serum Osm Urine Osm Urine Na
Hyperosmolal > 300
Isoosmolal 280-300
Hypoosmolal < 280
• Polydipsia < 280 < 100
• SIADH < 280 > serum > 20
• EABV < 280 > serum < 10
STEP 1 STEP 2 STEP 3 HYPONATREMIA
When interpreting Urine Na+ always consider diuretic use and Na intake
Serum Osm 260
Urine Osm 600
Urine Na 40
Severely symptomatic (seizure, coma, etc) and symptoms due to hyponatremia (usually Na < 120)
Bolus 100mL 3% saline q 10 min up to 3 doses ▪ Each bolus raises Na by ~2
▪ Rapidly reduces cerebral edema
▪ Close monitoring of serum Na
General guide
Increase serum Na to 120 at correction rate of 1meq/hr
0.5 meq/hr correction rate thereafter
What fluid?
NS to restore blood volume
3% if relatively euvolemic
Diuretics? CHF, cirrhosis Fluid restrict, salt tabs for SIADH Vaptans Urea
Serum sodium (SNa) values during treatment with vaptans and urea.
Soupart A et al. CJASN 2012;7:742-747
©2012 by American Society of Nephrology
1. Correcting too quickly 2. Aggressive correction in people who aren’t
severely symptomatic 3. Forgetting to include potassium replacement in
correction formulas Can lead to overcorrection
K+
Na+
K+
Na+
Infuse K+
Na+ Na+
Infuse Na+
Na+
K+ Na+
4. Correcting SIADH with NS Can worsen hyponatremia
Na+ 155
What 1 test do you order to identify
the cause of hypernatremia?
Urine osmolality
Blood
AQP2
AQP2
AQP2 Na
Na
Na
Na
Na
Na
H20
H20
H20
H20
H20
Collecting duct
Urea
Urea
Urea
Urea
Urea
Urea
Urea
ADH
Hyperosmolarity
Osmoreceptors
AQP2
Urine osm
If ADH is secreted
& kidney is responding to it
Na H20
NORMAL RESPONSE TO HYPERNATREMIA
Hypernatremia
Renal water loss • Diabetes insipidus
Non-renal water loss • GI • Skin • Lungs
Urine Osm > Serum Osm ADH and kidney are doing the right thing
Most cases
Nonrenal hypotonic fluid loss: skin, GI, respiratory
Excessive Na intake (normal saline in the hospital)
Urine Osm < Serum Osm ADH activity is impaired
▪ Diabetes insipidus: central, nephrogenic
Urine Osm = Serum Osm Think diuretics
This is really what You want to rule in/out in hypernatremia
Hypernatremia
Renal water loss • Diabetes insipidus
Non-renal water loss • GI • Skin • Lungs
Urine Osm > Serum Osm Urine Osm < Serum Osm
Na 155 Urine osm = 900
Does this patient have diabetes insipidus?
40 yo M seen in clinic after pancreatitis. Improving, but has poor appetite, malaise, abdominal pain. PMH Congenital NDI Familial polycythemia Gout Rheumatoid arthritis Obstructive uropathy Recurrent pancreatitis
Meds Probenecid Amiloride/HCTZ Doxazosin Nitrofurantoin Finasteride Colchicine Methotrexate Acetaminophen KCl MVI
Exam 97° Lying 118/72, 114 beats/min Standing 109/71, 133 beats/min JVP 2cm below sternal angle 2+ edema
141 103 29
3.3 9 1.7 112
Anion gap = 29
Methanol Uremia Diabetic ketoacidosis Paraldehyde INH Lactic acidosis Ethylene glycol Salicylates Tox Screen
Serum Osm
Lactate
Ketones
141 103 29
3.3 9 1.7 112
ABG
pH 7.31
pCO2 13
pO2 88
HCO3- 7
More Labs
Serum Osm 307
Calc Osm 298
Lactate 0.6
Ketones Neg
EtOH Neg
Toxic alcohols Neg
Acetaminophen 38 μg/mL
Salicylate Neg
Anion gap = 29
Usual anion gap metabolic acidosis lab tests are normal
© 2000 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2
Depletion of glutathione
Glutathione
g-glutamyl cysteine
Glutathione synthetase
GGT g-glutamyl amino acid
5-oxoproline (pyroglutamic acid) 5-oxoprolinase
Glutamate
g-glutamyl cyclotransferase
g-glutamyl cysteine sythetase
Glycine
Glutathione
g-glutamyl cysteine
Glutathione synthetase
GGT g-glutamyl amino acid
5-oxoproline (pyroglutamic acid) 5-oxoprolinase
Glutamate
g-glutamyl cyclotransferase
g-glutamyl cysteine sythetase
Glycine
Acetaminophen
RATE LIMITING STEP
Urine pyroglutamic acid (5-oxoproline)
> 40,000 ug/mg Cr (< 70)
Glutathione
g-glutamyl cysteine
Glutathione synthetase
GGT g-glutamyl amino acid
5-oxoproline (pyroglutamic acid) 5-oxoprolinase
Glutamate
g-glutamyl cyclotransferase
g-glutamyl cysteine sythetase
Glycine
Pregnancy Malnutrition
Sepsis
Inherited disorders
Anion gap metabolic acidosis
Since excreted in urine, UAG can be positive
Treatment is largely supportive Stop acetaminophen
Usually something else going on (sepsis, etc)
HD used in case reports NAC, theoretically beneficial
Cyanide, Citrate Uremia Toluene Ethylene glycol Diabetic ketoacidosis
Isoniazid, Iron Methanol Pyroglutamic acid, propylene glycol, paraldehyde Lactic acid, D & L Ethanol Ketoacidosis Salicylates, starvation ketoacidosis, sodium thiosulfate
“I have a 29 yo Hispanic woman who came to the ER with burning pain in her feet. We were about to send her home, but then her labs came back.”
141 139 9
3.9 25 0.6 86
ABG
pH 7.41
pCO2 36
pO2 60
HCO3- 22
BE -1
Ca 9.5
142 139 9
3.6 24 0.6 84
Ca 9.7
Problems: 1. Hyperchloremia 2. Negative anion gap
Normal tests CBC LFT P, Mg Manganese Heavy metals Ceruloplasmin CSF studies including
VDRL, ACE Glutamic acid
decarboxylase Ab
Urine arsenic, thallium
mercury, iodine Hexosaminidase A Beta-HCG Ro & La Ab B12, folate ANA TSH UA + culture CK
3 years later
Spastic diplegia
Distal neuropathic pain & sensory loss
Walks with stiff-legged antalgic gait using a clawed cane
Problems: 1. Hyperchloremia 2. Negative anion gap 3. Irreversible neurotoxicity
What is the diagnosis?
Ulcerated Erythematous Nodules on the Dorsal Aspect of the Hands and Fingers.
BROMODERMA
Serum bromide: 170 mg/dL (21 mmol/L) Chloride by chlorometer: 107 & 109 meq/L 141 139 9
3.9 25 0.6 86
Anticonvulsant and sedative Substitutes for chloride in nerves/kidney
10-50 mg/dL: sedation 75-150mg/dL: therapeutic range for seizure control >150mg/dL: debilitating toxicity >300mg/dL: may be fatal
Social History: From Mexico, in US for 3 years No EtOH, tobacco, drugs Takes Maca (herbal supplement) Works in a furniture factory gluing styrofoam chair seats,
does not use protective equipment Another worker started “walking funny.”
What is Maca? 1-2 mg bromide/capsule
Occupational exposure? 1-bromopropane was a solvent used in the glue
Solvent introduced to replace chlorofluorocarbons ▪ CFC banned because these deplete ozone
Carcinogen
Used in dry cleaning
Other workers had elevated bromide levels
