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 high
preval 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 K
Ratio > 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?????