Hypokalemia
Transcript of Hypokalemia
Approach to etiology of Hypokalemia
Dr.M.Emmanuel Bhaskar
Associate Professor in Medicine
Sri Ramachandra Medical College
Chennai,India
Approach……???????
Approach to hypokalemia
All you need to do is to have a CLOSER LOOK!
Learning objectives
1.To understand a concept based clinical approach to diagnose cause of hypokalemia
2.Understand the clinical relevance of common investigations used in the setting of hypokalemia
Plan for Interaction
Brief Introduction
Presentation of scenario
Discussion by audience
Discussion by presentor
Questions by audience
Answers by the faculty ?
How does body maintain a normal serum K?
Gennari et al NEJM 1998;339:451-458
Case-1
36 year old male admitted with pneumonia with septic shock. Admission labs shows Na-142, K-3, Cl-98, Hco3- 19. On Imipemem,nor-epinephrine,dopamine, pantoprazole , enoxaparin, I.V 0.9% Saline at 125cc/hr.
Day 5 develops Na-138,K-2.2,Cl-106,Hco3-17. Urine K- 30 meq/l .ABG- Ph-7.36 , Hco3-15, Pco2-26mmHg.. Mg-1.2 , Ca-9.6
K-improved to 3.2 with 80 meq /dy of i.v Kcl.
Case-1: Issues ?
Approach?
Case-1: Issues
Septic shock on Ionotropes and saline
Hospital acquired hypokalemia
Urinary K-excretion- ?
Metabolic acidosis with resp alkalosis
Marginally low serum Mg with normal Na,Cl,Ca
Diagnostic protocol based on our observation in 76 cases of hypokalemia [ K<2 meq/l]
Study period: May 2005-May 2009
5 Questions to fix the cause of Hypokalemia !
Is there an obvious gastro-intestinal loss
Is it drugs
How is renal handling of K
Unexplainable Metabolic acidosis/alkalosis
How is serum Mg, Na, Cl, Calcium
Case 1
Is there an obvious gastro-intestinal loss
Is it drugs ???
How is renal handling of K- ??loss
Unexplainable Metabolic acidosis/alkalosis
How is serum Mg [?low] ,Na,Cl,Calcium
Case 1
Is it drugs ???
Renal loss ???
Hypomagnesemia???
Drugs and Hypokalemia ?
Drugs and Hypokalemia
Insulin
Salbutamol, Theophylline
Diuretics
Drugs and Hypokalemia
Insulin
Salbutamol, Theophylline
Diuretics
Nor-Epinephrine, high dose dopamine
Fludrocortisone, high dose corticosteroids
Amphotericin-B , Beta-lactum antibiotics
Bicarbonate therapy
Case 1
Is it drugs ??? - YES
Renal loss ???
Hypomagnesemia???
How to assess renal handling of K?
Renal loss of K
Intrinsic renal disorders: Inherited/acquired
Hormonal effects : Hyperaldosteronism
How to assess renal handling of K?
Urinary K excretion- spot or 24 hours
Urinary K / Urinary creatinine ratio
TTKG [ Trans-tubular potassium gradient]
Urinary potassium excretion
A normal kidney should retain most of
the potassium in the setting of hypokalemia.
Spot K <10-15meq/l is normal
Spot K >20 meq/l indicates renal loss
Spot Urinary Potassium excretion
Limitations Poor validity in critically ill patients when considered in isolation due to highpreval of secondary hyperaldosteronism
Extra-renal loss may be associated with elevated spot urinary K !
Reimann et al. Nephrol dial transpt 1999;14:2957-2961
Urinary K/Urinary creatinine ratio
More meaningful test.
Excretion rates are similar during ↓K Ratio <1.5 indicates renal conservation of KRatio > 1.5 indicated renal wasting of K
Factors interfering creatinine secretion.Unclear role in critical illness
Groeneveld et al . Q J Med 2005;98:305-316
What is TTKG?
What is TTKG?
Most disliked term in the chapter on hypokalemia !
What is TTKG?
Soriano et al.J Am Soc Nephrol 2002;13:2160-2170
TTKG
Ratio between K concentration in the collecting duct and the peri-tubular cap
Tells about the behaviour of distal nephron during hypokalemia .
TTKG
Based on one time sample
Most useful test
TTKG
Based on one time sample
Most useful test
NOT AVAILABLE IN MOST CENTRES
TEST REQUIRES OSMOMETER
How to assess renal handling of K?
Urinary K excretion
Urinary K / Urinary creatinine ratio
TTKG [ Trans-tubular potassium gradient]
ALL HAVE SIGNIFICANT LIMITATIONS
How to assess renal handling of K?
Urinary K excretion
Urinary K / Urinary creatinine ratio
TTKG [ Trans-tubular potassium gradient]
ALL HAVE SIGNIFICANT LIMITATIONS
Interpretation in isolation may lead to
CONFUSION
Potassium wasting Renal disorders……loose potassium
They often also loose chloride,
sodium,bicarbonate,magnesium,
water and calcium
Potassium wasting renal disorders
Look beyond urinary K !
Case 1
Is it drugs ???- YES
Renal loss ???- ? YES [ ?aldosterone]
Hypomagnesemia???
Case 1
Is it drugs ???- YES
Renal loss ???- ? YES [ ?aldosterone]
Hypomagnesemia???
Secondary hyperaldosteronism produces
↓K much earlier than Met.alkalosis
How to identify clinically significant hypomagnesemia
How to identify clinically significant Hypomagnesemia?
Hypokalemia refractory to therapy
Serum Mg <1 mg/dl
Associated hypocalcemia [ < 7 mg/dl]*
Metabolic alkalosis
*Agus et al J Am Soc Nephrol 1999;10:1616-1622
What is the relation between magnesium and calcium
What is the relation between magnesium and calcium?
Hypomagnesemia causes impaired PTH release and increased PTH resistance.
Impaired PTH leads to renal loss of Mg
Resolution -Case 1
Is it drugs - YES [ Noradrenaline]
Renal loss ??? – ?YES[?aldosterone]
Hypomagnesemia??? - NO
Case 2
A 23 year old female presented with fatigue
for 3 months which worsened over the last
10 days. Clinical exam was unremarkable
except for a power of 4/5 in all limbs. Labs
showed a Na-134 meq/L,K-1.8 meq/l, Cl-110
meq/l and Hco3-15 meq/l. S.Creatinine-1.1
mg/dl, BUN-14 mg/dl, ABG: Ph- 7.31, Pco2-
30 mmHg, Hco3-14 meq/l, S.Mg-1.1mg/dl
Ca-8.8 mg/dl , Spot urine K-60 meq/l . ECG
showed U waves with QRS widening. Urine
Ph-6, Sp-gravity-1.010, sugar-nil,prot-nil, 5-6
pus cells and no casts.
Case 2 issues ?
Approach?
Case 2 issues
Hypokalemia
Partially compensated metabolic acidosis
Elevated spot urine K-80 meq/l
Mild hypomagnesemia, high normal Cl
5 Questions to fix the cause of Hypokalemia !
Is there an obvious gastro-intestinal loss
Is it drugs
How is renal handling of K
Unexplainable Metabolic acidosis/alkalosis
How is serum Mg, Na, Cl, Calcium
Case 2 :Where to begin?
Is there an obvious gastro-intestinal loss
Is it drugs
How is renal handling of K- loss
Metabolic acidosis/alkalosis
How is serum Mg↓, Na, Cl↑, Calcium
Case 2 :Where to begin?
Is there an obvious gastro-intestinal loss
Is it drugs
How is renal handling of K- loss
Metabolic acidosis/alkalosis
How is serum Mg, Na, Cl, Calcium
Hypokalemia with metabolic acidosis
Possibilities to consider
Hypokalemia with metabolic acidosis
Acute and chronic diarrheal disorder
Recovery phase of acute tubular necrosis
Renal tubular acidosis [distal , proximal]
Acetazolamide therapy
Met acidosis unrelated to hypokalemia
How to evaluate possible RTA?
Evaluation of possible RTA
Early morning first void urine pH
Confirm kidneys ability to acidify urine
Check for glycosuria, hypophosphatemia
Evaluation of urine pH
Good screening test
Urine ph >5.5 : possible distal [type-1] RTA
Urine ph <5.5 : possible proximal
[type-2]RTA
Analyzed Ideally within 30 minutes
Evaluate kidneys ability to acidify urine
Acid load test : ideal but rarely done
Frusemide test
Frusemide test for RTA-1
Principle
Frusemide increases distal delivery of Na
A normal distal nephron secretes H ion in response to this producing acidic urine
Type-1 RTA nephron fails to do this
Frusemide test: Protocol
Test urine pH
Administed 40 mg of frusemide preferably i.v
Repeat urine pH 1 to 2 hour later
Failure to produce acid urine indicates
Distal [type-1] RTA
Soriano et al. J Am Soc Nephrol 2002;13:2160-2170
Proximal[type-2]RTA
Often associated with additional tubular loss of glucose, phosphate and uric acid
Osteomalacia and rickets may occur
Urinary acidification intact
Isolated proximal bicarbonate loss possible
Case 2
Urine ph in routine sample- 6
Urine pH in first void sample-7
Frusemide test was abnormal
DISTAL RENAL TUBULAR ACIDOSIS
Often there is a diagnostic delay in RTA
Metabolic acidosis is often mild
Becomes severe only during intercurrent illness
Case 3
A 45 year old male presented with confusion
And irritablity for 7 days which was not
associated with fever. Patient is a known
diabetic for 8 years on OHAs. Current
alcoholic and smoker.On exam vitals were
stable and marked disorientation was
present. Labs showed a Na-141 meq/L,
K-1.4 meq/l, Cl-78 meq/l and Hco3-32 meq/l.
S.Creatinine-0.9 mg/dl, BUN-18 mg/dl,
ABG: Ph- 7.49, Pco2- 49 mmHg, Hco3-32
meq/l, S.Mg-0.7mg/dl,Ca-6.4 mg/dl , Spot
urine K-80 meq/l . ECG showed ST
depression ,T-U waves with QRS widening.
Urine Ph-5, Sp-gravity-1.010, sugar-nil,prot-
nil, 5-6 pus cells and no casts.
Case 3 issues?
Approach?
Case 3 issues?
Diabetic , alcoholic
Altered mentation
Hypokalemia, Elevated urinary K loss
Metabolic alkalosis
Hypochloremia,hypomagnesemia,
hypocalcemia, normal Na
Case 3 : Where to begin?
Diabetic , alcoholic
Altered mentation
Hypokalemia, Elevated urinary K loss
Metabolic alkalosis
Hypochloremia,hypomagnesemia,
hypocalcemia, normal Na
Case 3 : Where to begin?
Diabetic , alcoholic
Altered mentation
Hypokalemia, Elevated urinary K loss
Metabolic alkalosis
Hypochloremia,hypomagnesemia,
hypocalcemia, normal Na
Hypokalemia with metabolic alkalosis
Possibilities to consider
Hypokalemia with metabolic alkalosis
Vomiting
Diuretics
Secondary hyperaldosteronism
Acquired Hypomagnesemia
Barters/Gittelman/Liddle syndrome
Hypokalemia per se
Hypokalemia with metabolic alkalosis
Vomiting
Diuretics
Secondary hyperaldosteronism
Acquired Hypomagnesemia
Barters/Gittelman/Liddle syndrome
Hypokalemia per se
What are the acquired causes of Hypomagnesemia?
Acquired causes of ↓Mg
Alcoholism , Diabetes
Chronic diarrhea , vomiting, diuretic use
Diuretic phase of ATN
Rapid refeeding
Amphotericin B, Aminoglycosides
Vit D deficiency
Late pregnancy
Agus et al. J Am Soc Nephrol 1999;10:1616-1622
Hypomagnesemia:features
Serum value may not reflect real picture
CNS effects
Hypokalemia refractory to therapy
Metabolic alkalosis, hypochloremia
Hypocalcemia
Sodium not affected in acquired causes
Inherited tubular disorders
A birds eye view
NEJM 1999;340:1177-1187
Inherited tubular disorders vs Acquired Hypomagnesemia
Disorder Bp ↓Mg Na ↓Ca U .Ca
Barter N or low Yes-mild low variable
N or High
Gittel man N or low Yes-sev low no Low
Liddle High no N or High no N
↓ Mg N - N yes variable
Scheinmann NEJM 1999;340:1177-1187
Inherited tubular disorders vs Acquired Hypomagnesemia
Disorder Bp ↓Mg Na ↓Ca U .Ca
Barter N or low Yes-mild low variable N or High
Gittel man N or low Yes-sev low N Low
↓ Mg N - N yes variable
Inherited tubular disorders vs Acquired Hypomagnesemia
Disorder Bp ↓Mg Na ↓Ca U .Ca
Barter N or low Yes-mild low variable N or High
Gittel man N or low Yes-sev low N Low
Case 3:resolution
Severe Hypomagnesemia [acquired]
1. risk factors- alcoholism, diabetes
2. Hypokalemia which was refractory
3. Hypocalcemia
4. Metabolic alkalosis, normal Na
Case 4
A 25 year old female presented acute
weakness of all extremities .She had 2
similar episodes in the past. On exam vitals
were stable.Power was 1/5 all limbs. Labs
showed a Na-138 meq/L, K-1.6 meq/l, Cl-98
meq/l and Hco3-25 meq/l. S.Creatinine-0.9
mg/dl, BUN-18 mg/dl,ABG: Ph- 7.38, Pco2-
38 mmHg, Hco3-22 meq/l,
S.Mg-1.7mg/dl,Ca-9 mg/dl , Spot
urine K-8 meq/l . ECG showed ST
depression ,T-U waves with QRS widening.
Urine Ph-5, Sp-gravity-1.010, sugar-nil,prot-
nil, 5-6 pus cells and no casts.
Case 4: issues?
Approach?
Case 4: Issues
Hypokalemia
Extremity weakness
Normal renal handling of K
Normal acid-base status
Normal Na,Cl,Mg and Ca
Case 4: Where to begin?
Hypokalemia
Extremity weakness
Normal renal handling of K
Normal acid-base status
Normal Na,Cl,Mg and Ca
Case 4: Where to begin?
Hypokalemia
Extremity weakness
Normal renal handling of K
Normal acid-base status
Normal Na,Cl,Mg and Ca
Hypokalemic paralysis with normal acid-base status
Possibilities
Two patients with serum K-1.5
One having paralysis and the other having normal power .Is it
possible?
Two patients with serum K-1.5
One having paralysis and the other having normal power .Is it
possible?............yes
The serum K level does not primarily decide occurrence of
weakness!
What decides weakness in hypokalemia?
Ratio of ICF/ ECF
Normal 38/1
Conditions that lower both cellular and extracellular K may not produce weakness
Conditions rapidly shift large amount of K
into the cells ↑ ratio and cause weakness
Severe hypokalemia with paralysis and normal ABG
Periodic paralysis [familial or sporadic]
Thyrotoxic periodic paralysis
Suicidal Insulin over dose
Groeneveld et al . QJM;2005;98:305-316
Case 4
Sporadic periodic paralysis
1. Recurrence
2. Normal renal handing of K
3. Normal acid-base status
4. Normal thyroid function
In summary………
5 Questions to fix the cause of Hypokalemia !
Is there an obvious gastro-intestinal loss
Is it drugs
How is renal handling of K
Unexplainable Metabolic acidosis/alkalosis
How is serum Mg, Na, Cl, Calcium
Conclusion
Do not consider urinary K excretion in isolation
ABG is a desirable starting point while evaluating mod-severe hypokalemia
Look at Na,Cl,Mg and Ca
My guide and mentor…….
Prof.S.Shivakumar M.D
Prof & HOD of Medicine[retd]
Govt.Stanley Medical College
Chennai
Questions?????