This document discusses the physiology and pathophysiology of hypokalemia. It covers the normal distribution and regulation of potassium in the body, as well as causes of hypokalemia including decreased intake, extrarenal losses, and renal losses. Types of renal tubular acidosis that can cause hypokalemia are described. The approach to hypokalemia involves considering underlying causes like Bartter syndrome, Gitelman syndrome, Liddle's syndrome, and hypomagnesemia. Treatment principles for correcting hypokalemia are provided.

1. APPROACH TO
HYPOKALEMIA
KKKKKK
Dr AJMAL N M
Dr. V Jaswanth reddy
General medicine pg 1st year

2. PHYSIOLOGY OF POTASSIUM
• Major intracellular cation
. 1 mmol =1meq=40mg of k+
.Total body stores=50meq x BW
=3000meq
=2500meq stores in muscles
.Intracellular K+=120-140meq per lit
. The function of intracellualar k+ is for cell growth
and protein synthesis
. On an average daily 100 meq of k+ is required for
the body

3. .ECF ICF ratio of potassium is important in
maintaining the resting membrane potential
. 90-95% of k+ excreted by kidneys ( chief ion)
.buffering extra cellular pool by a much large
intracellular pool even on infusing 40meq after
1 hr sr. K+can raise only by 0.5meq per lit
.Intracellular accumulation of k+against its
electrochemical gradient made possible by Na+-
k+ ATPase .
.

4. .Digoxin and K+ compete for same binding site
on
Na+k+ATPase , so digoxin inhibits Na+k+ATPase
as a result K+ cannot come inside the cell and
causes hyperkalemia.
.Muscle-2500meq, RBC -250meq,Liver-250meq
Bone -300meq: BODY K+DISTRIBUTION
. K+shifts from blood to the cell (active)by insulin,
B2agonists , alkalosis,alphaantagonists,
Theophylline, barium , chloroquine,
hypokalemic periodic paralysis (ca2+
channelopathy)

5. Hypokalemic periodic paralysis
. It is a genetic thing , AD
. Classic paralysis/ severe muscle weakness
. Recurrent episodes
. PPT by carbohydrate meal / rest /stress

6. .k+ shifts from cell to blood(passive)
By:1) cell destruction ( hemolysis,
rhabdomylosis, rumor lysis)
2)Non selective B blockers
3) alpha agonists
4) acidosis
5) exercise
6) mannitol(water enters from cell to blood ,
which leads to shrinkage of the cell, and K+ moves
out and leads to hyperkalemia)

7. Renal handling of K+
• 90% of K+ is excreted by kidney
• 65-70% of K+ is reabsorbed by PCT(passive transport)
• ThAL reabsorb K+ via Na-K-2Cl symporter
• Principal cells of cortical collecting duct with the help
of aldosteron-reabsorb salt and water and excrete
out K+ and H+
• Alpha intercalated cells of cortical collecting duct has
H+-K+ atpase which excrete H+ and reabsorb K+

9. When to Suspect
• Muscle weakness- Flaccid paralysis with no sensory
involvement.
• Smooth muscle- constipation(paralytic ileus) and Bladder
dysfunction.
• Cardiac-Arrythmias
• Nephrogenic DI
• Rhabdomyolysis
• Respiratory failure

10. ECG changes
• 3-3.5meq/l: Flattening of T waves, Prominent
U waves and prolongation of QT or QU
interval
• <3meq/l: sagging of ST segment
• <2.5meq/l: widening of QRS, Prolongation of
PR interval,risk of arrythmias

13. .Normal sr. k+3.5-4.5 meq
<3.5=hypokalemia
<2 is significant almost due to renal
Loss
. Any hypokalemia un responsive to k+ think of
mg deficiency

14. Step wise Approach
Step:1
• Look at Urine spot potassium
>15
Renal loss of
potassium
<15
Nonrenal loss
1.Decreased intake
2. Extra Renal Loss
3.Transcellular shift

15. • Decreased Intake: 15meq/day K+ will be
excreted even in response to a K+ free diet.
• Eg: Anorexia nervosa,Alcoholism, Intestinal
malabsorption.
• Extra Renal Loss : 1) Sweating in large
amount, occuring as a part of exercise in hot
humid condition.
• 2) GI loss : Diarrhea and vomiting

16. Renal loss of Potassium (Step2)
ABG
Acidosis
RTA type1
RTA type 2
Alkalosis
Normal to low BP
BARTTER
GITELMANN
High BP
CONNS
LIDDLES
CUSHINGS
AME
GRA

17. Renal Potassium Wasting
• There is always a balanced reciprocal relationship
between distal load of Na and circulating
aldosterone which is the most important
mechanism for maintaining normal S.K+.

18. RENAL TUBULAR ACIDOSIS
• Group of disorders having defect in acidification
of urine due to tubular defect.
• Metabolic acidosis with alkaline urine.
• Normal anion gap metabolic acidosis with
high/+ve urine anion gap.

19. TYPES OF RTA
• Type 1 RTA: (Distal RTA): defect in alpha
intercalated cells of cortical collecting duct.
• Defect is in H+ ATPase or H+-K+ ATPase .
• Hence it is an H+ secretion defect.
• It is the most severe form of RTA
• Severe metabolic acidosis with alkaline urine of
pH>5.5

20. • Severe metabolic acidosis cause calcium
resorption from bone.
• Hence Hypercalcemia, hypercalcuria and renal
stones.
• Severe bone changes like short stature can also
occur.
• Severe Metabolic acidosis will decrease the
capacity of PCT to reabsorb salt and water
resulting in severe volume depletion – RAAS
activation - Worsen hypokalemia.

21. Causes
• Type 1 RTA: 1)Idiopathic (most common type)
2)Genetic(AR defect in H+ atpase).
3)Acquired causes: Sjogren syndrome, SLE,
Drugs (Ampho B)

22. Type 2 RTA (Proximal RTA)
• Type 2 RTA: Defect is in proximal convoluted tubule.
• Generalised proximal tubular dysfunction.
• Defect in bicarbonate reabsorption
• Less severe form of RTA.
• Since it is a generalised tubular dysfunction there will
be Glycosuria, Aminoaciduria and Phosphaturia.
(Fanconi syndrome).

23. • Less severe metabolic acidosis-hence less
bone resorption- hence less chance of stones.
• There will be loss of vit D through urine -
hence vit D deficiency/ Rickets/ osteomalacia.
• Less metabolisc acidosis- less volume
depletion – less RAAS activation - less
hypokalemia

24. • M/c cause : Fanconi Syndrome
• Fanconi syndrome can be Genetic or sporadic
or acquired.
• Genetic causes : Cystinosis, Wilsons disease
• Acquired causes: Multiple myeloma,
Hyperparathyroidism, drugs (outdated
tetracycline), Aminoglycoside,
topiramate,cyclofosfamide)
Causes of Type 2 RTA

25. • Type 3 RTA: Carbonic anhydrase 2 gene defect
• Rare form of RTA.
• Type 4RTA: RTA associated with
Hyperkalemia.
• Aldosterone defect: Aldosteron act on eNaC,
cause Na and water reabsorption and H+ & K+
excretion.
• Defect in this mechanism will cause metabolic
acidosis with hyperkalemia.

26. BARTTER SYNDROME
• Severe form of Inherited channelopathy
• AR mode of inheritance.
• Defect lies in ThAL : Inhibitory defect of Na-K-2Cl
channel.
• Simulating an aldosterone exess state.
• Presenting as Hypokalemia ,Alkalosis and high urine
chloride.

27. • Same channel is present in the ear for maintaining
endolymph concentration.
• Hence many have associated SNHL.
• Chronic use of loop diuretic can mimic Bartter.
• Other association is a paracellular pathway defect
where there is hypercalcuria and
hypermagnesuria hence can present as stone
disease.
• Serum Ca and Mg are normal because intestinal
absorption of Ca and Mg is normal.

28. GITELMANN SYNDROME
• Less severe form of inherited channelopathy.
• AR mode of inheritance.
• Defect is in DCT : inhibitory defect of Na-Cl symporter.
• Can simulate aldosterone excess state, Hence cause
Hypokalemia, Alkalosis and high urine Chloride.
• Chronic Thiazide use can mimic Gitelmann.

29. • Whenever there is volume depletion body try
to conserve more calcium, hence
Hypercalcemia and hypocalcuria.
• Same channel in intestine is also defective
hence absorption of Mg from intestine is
defective and hence Hypomagnesemia.

30. LIDDLES SYNDROME
• AD mode of inheritance
• Stimulatory defect of eNaC
• Hence called as PSEUDOHYPERALDOSTERONISM
• Chronic steroid usage can mimic Liddle.
• Treatment : Amiloride

31. Hypomagnesemia
• Think of hypomagnesemia when you have persistant
hypokalemia.
• Under normal circumstances intracellular Mg will inhibit
K+ excretion through ROMK channels of distal nephron.
• Low intacellular concentration of Mg
cause Hypokalemia refractory to Rx.
• Once hypomagnesemia gets corrected K+ will come
back to normal

33. ● Potassium chloride always give oral
● 750mg tablets contain 10meq
● Daily effective dose 40-100meq(75)
● 75meq can rise k+ by roughly 1meq after 1hr
● 2amp of KCL in 200ml NS run over 2hrs
● 1amp of KCL=10ml
● 1ml=2meq of k+
● 1amp=20meq
● 2amp of KCL=40meq rise k+by 0.5meq/L
● Max can given on a day =160meq
● Max dose that can be given through a
peripheral line =20meq/hr
Correction of Hypokalemia

34. • Suppose a patient have a S.K+ of 2.5 meq/l
• Target is 3-3.5meq/l
• Deficit is 0.5-1meq/l 2-4 amp of Kcl
• Given as 2amp of KCl in 500ml NS over 4-6hrs.
• If you have a central line then give 2amp KCl in
200ml NS over 2Hr.

35. •In life threatening conditions give 5-10meq
over 15mins
•severe(<2.5)/symptomatic=require I.V
•Prefee Dextrose free solution (NS)