Approach to hypokalemia, pathophysiology of hypokalemia

1. Approach to
Hypokalemia
Dr Garima Aggarwal
22.09.2014

2. APPROACH TO HYPOKALEMIA
PATHOPHYSIOLOGY
 CLINICAL APPROACH
TREATMENT

4. Potassium homeostasis
.
 The ratio of intracellular to extracellular
potassium determines the cellular membrane
potential.
 Small changes - profound effects on the function
of the cardiovascular and neuromuscular systems.

5. Cellular K+ Content
 Intracellular K+ affects intra to extracellular K+
 With K+ depletion ,
K+ loss from ECF > ICF loss
causing increased Ki + / Ke+
 K+ depletion : hyperpolarization
 K+ retention : depolarization

8. Na+ K+ ATPase

9. Factors modifying transcellular
K+ distribution
 Acid base status
 Pancreatic hormones : insulin , glucagon
 Catecholamines
 Aldosterone
 Plasma Osmolality
 Exercise
 Cellular K+ content

10. Acid Base Status
Alkalemia promotes K+ uptake by cells
Acidemia diminishes K+ uptake by cells
H+ K+
K+ H+
ACIDOSI
S
ALKALOSIS
An oversimplification in acidosis

12. Exercise
 Recurrent contraction increases K+ egress from muscle
 Modest exercise : high K+ in ECF in local environment
produces vasodilatation & thereby increased regional blood
flow
 Severe exercise : increase plasma K+ modestly
 Physical training increases Na+K+ATPase activity in skeletal
muscle which helps skeletal muscle to take up K+ again

13. RENAL ADAPTATION
 Kidneys adapt to both acute and chronic
alterations in potassium intake.
 obligatory renal losses are 10-15 mEq/d.
 Maintain potassium homeostasis until the glomerular
filtration rate drops to less than 15-20 mL/min.
 In the presence of renal failure, the proportion of
potassium excreted through the gut increases.
 However, as renal function worsens, the kidneys may not
be capable of handling an acute potassium load.

14. Renal Handling of K+
 Glomerulus: freely filtered
 PCT, Thick As limb LOH :
reabsorbed
 DCT, CNT, CCD – secreted

18. INTERCALATED CELLS

19. RENAL ADAPTATION
Excretion is increased by
 (1) aldosterone,
 (2) high sodium delivery to the collecting duct (eg, diuretics),
 (3) high urine flow (eg, osmotic diuresis),
 (4) high serum potassium level

20.  Invitro studies
 Aldosterone stimulates Na+K+ATPase and thereby activating
Na + influx
Aldosterone

21. Hypokalemia
 Defined as plasma concentration of K+ < 3.5 mEq/L
 Mild Hypokalemia : 3.0 – 3.5 mEq/L : asymptomatic
 Moderate Hypokalemia < 3.0 mEq/L : symptomatic
 Severe Hypokalemia <2.5 mEq/L
Clinical manifestations of hypokalemia vary greatly between
individual patients &
their severity depends on degree of hypokalemia

22. Hypokalemia
Decreased intake
Redistribution
into cells
Increased loss
Renal Extra renal

23. PSEUDOHYPOKALEMIA
-spurious
 "pseudohypokalemia" occurs in acute myelogenous
leukemia
 large number of leucocytes in the blood specimen (stored at
room temperature)
 sponge-up the extracellular potassium => artefactually low
serum potassium reading

24. Decrease K intake
 Dietary – starvation, clay ingestion
 IV therapy

25. Redistribution into cells
 Alkalosis
 Insulin Excess
 Beta-2 agonist
 Alpha antagonist
 Hypokalemic
periodic paralysis
 Anabolic state-vit.
B 12, folic
acid
•GM CSF
•Total parenteral nutrition
•Hypothermia
•Barium toxicity
•Pseudohypokalemia

26. GI LOSS of K+
 Secretory diarrhea
 GIT fistula or small bowel enterostomy
 malabsorption syndrome
 excessive, voluminous vomiting
 laxative abuse

27. Transtubular potassium gradient
(TTKG)
 To account for the potentially confounding effect of urine
concentration on the interpretation of the urine potassium
 the serum-to-tubular fluid ratio of potassium at the level of the
cortical collecting tubule, where potassium is secreted.
 TTKG = (Urine potassium/urine osmolality : serum potassium
/serum osmolality)
 A value less than 3 suggests that the kidney is not wasting
excessive potassium, while a value greater than 7 suggests a
significant renal loss..

28. DISTAL K+ SECRETION (TTKG>4)
With normal or low blood pressure
1.With alkalosis – Diuretic therapy, Bartters and gitelmans
syndrome
2. With acidosis – RTA type 1& 2, carbonic anhydrase inhibitor
therapy
3. With variable pH – post obstructive diuresis, Recovery after
ATN,Mg depletion,amphotericine B

29. Barrter’s Syndrome
 Site of lesion – TAL
 Abnormal
NKCC2,ROMK,Cl channel
 Na wasting,volume
contraction
 RAASNa reabs by
CT
 K&H secretion,met
alkalosis,hypokalemia

30. Gitelman’s syndrome
 Autosomal recessive
 Abnormal NCCT
 Na wasting RAAS
activation
 K & H secretion
metabolic
alkalosis,hypokalemia

31. DISTAL K+ SECRETION (TTKG>4)
With Hypertension
1.Hyperaldosteronism-
Primary - Conns syndrome
Secondary - Renal ischemia, malignant HTN,hypovolemia,
renin secreting tumours
2. Other forms of mineralocorticoids receptor activation - cushing
syndrome, apparent min. excess
3. Liddles syndrome

32. Hypokalemia,Hypertension &
Alkalosis
Disease S.aldost
erone PRA
S.cortisol Response
to
steroids
Primary
aldosteronism
   No
GRA    Yes
AME    Yes
Liddle’s synd     No
Adr enz def    Yes

33. HYPOKALEMIA
TREATMENT

34. HYPOKALEMIA-TREATMENT
(1) decreasing potassium losses,
 (2) replenishing potassium stores,
 (3) evaluating for potential toxicities,
 (4) determining the cause in order to
prevent future episodes.

35. HYPOKALEMIA-TREATMENT
 In treating hypokalemia, the first step is to identify
and stop ongoing losses of potassium.
 Discontinue diuretics/laxatives.
 Use potassium-sparing diuretics if diuretic therapy is
required (eg, severe heart failure).
 Treat diarrhea or vomiting.
 Use H2 blockers to decrease nasogastric suction losses.
 Control hyperglycemia if glycosuria is present.

36. HYPOKALEMIA-TREATMENT
 Repletion of potassium losses is the second step.
 As a first approximation, for every decrease in serum
potassium of 1 mEq/L, the potassium deficit is
approximately 200-400 mEq..
 Oral potassium is absorbed readily.
 Relatively large doses can be given safely.

37. HYPOKALEMIA-TREATMENT
 if the hypokalemia is mild-moderate => po
administration potassium chloride should
occur more slowly over several days at 80 -
160 meq/day in divided doses .

38. HYPOKALEMIA-TREATMENT
 Intravenous potassium is less well tolerated because
it can be highly irritating to veins and can be given
only in relatively small doses, generally 10 mEq/h.
 Under close cardiac supervision in emergent
circumstances, as much as 40 mEq/h can be
administered through a central line.
 Oral and parenteral potassium can be used safely
simultaneously.
 Take ongoing potassium losses into consideration

39. HYPOKALEMIA-TREATMENT
 avoid glucose-containing parenteral fluids to
prevent an insulin-induced shift of potassium into
the cells.
 If the patient is acidotic, correct the potassium first
to prevent an alkali-induced shift of potassium into
the cells.
 Replete magnesium if low.
 Digoxin , liver disease –keep at 4.0 meq/l

40. Potassium replacement
therapy
 - cardiac monitoring is necessary in patients with
profound hypokalemia (< 2.5 meq/L), or if cardiac
arrhythmias are present, if IV potassium is planned
 - rapid IV bolus administration of potassium is
usually contra-indicated - the body has a limited
ability to rapidly absorb potassium and lethal
cardiac arrhythmias may result

41. Potassium replacement
therapy
 - IV potassium diluted in saline solution the
maximum concentration is 40 meq/L (peripheral
lines) or 60 meq/L (central lines)
10 - 20 meq/hour (in the average-sized adult) for
hypokalemia - if po potassium replacement therapy
cannot be tolerated or if a malabsorption syndrome
is suspected

42. IV infusion rate for severe or
symptomatic hypokalemia
 10 - 20 meq/hour Standard IV replacement rate
 20 - 40 meq/hour Serum potassium < 2.5 meq/L or
moderate-severe symptoms
 > 40 meq/hour Serum potassium < 2.0 Meq/L or life-threatening
symptoms

43. Thank you for your
attention