This document discusses potassium regulation and related disorders. It covers the normal ranges and functions of potassium in the body. It describes renal handling and factors regulating potassium excretion. Potassium homeostasis is achieved through short term regulation via transmembrane flux and long term regulation by the kidney and aldosterone. Abnormalities include hyperkalemia, caused by increased intake or redistribution from cells, and hypokalemia caused by redistribution into cells or renal/extra-renal losses. Both can cause cardiac and muscle effects.

1. Serum Potassium, Its
Regulation & Related
Disorders
Dr Ifat Ara Begum
Associate Professor
Dept of Biochemistry
Dhaka Medical College, Dhaka

2. Introduction to potassium
The major cation of ICF
Normal range in ECF: : 3.5-5 mmol/L
Normal range in ICF: 140-150 mmol/L
Serum K+
concentration
 Is little affected by alteration of water
balance
 A poor guide of body K+
content

Doesn’t change unless there is 10%
alteration of body K+
content

3. Function of Potassium
Maintains OP & volume of ICF
Maintenance of internal environment
Regulates
 RMP, AP & neuromuscular function
 Tissue excitability
 Cardiac impulse
 Acid base balance
Helps in NA/protein synthesis
Facilitates cell growth

4. Renal handling of Potassium
May be discussed under following
headlines:
I. Tubular load of potassium
II. Tubular reabsorption of potassium
III. Tubular secretion of potassium
IV. Renal excretion of potassium

5. i) Tubular load of potassium
Tubular load equals to GFR X Plasma
concentration
= 180 L/day X 4.0 mmol/L
= 700 - 800 mmol/day

6. ii) Tubular reabsorption of Potassium
More than 95% of tubular load
i. From PCT: 70 - 80% occurs passively
(by solvent drag)
ii. From ALH : 20 – 30% occurs
passively (by solvent drag) & actively.
<10% of filtered K+
reaches the distal
tubule

7. iii) Tubular secretion of Potassium
Done mainly by principal cells of CD
under influence of aldosterone

8. iii) Renal excretion of Potassium
It is 80 mmol/day (mostly secreted
K+
). But it may be as high as 1000
mmol/day
&
as low as 10 mmol/day

9. Contd
Factors regulating renal K+
excretion:
 1. Sodium delivery/load to distal
nephron: If sodium load increases,
renal potassium excretion increases,
[as increased sodium reabsorption
occurs in exchange of K+
excretion]
 2. Tubular flow rate of filtrate: If
increases, renal K+
excretion increases.

10. Contd
 3. Serum potassium concentration: If
increases, renal K+
excretion increases
& vice versa
 4. Body potassium status: If increases,
renal K+
excretion increases & vice
versa
 5. Aldosterone activity: Increases the
renal K+
excretion
 6. Acidemia: Decreases the renal K+
excretion

11. Contd
 7. Alkalemia: Increases the renal K+
excretion
 8. Presence of unreabsorbed anions
(like keto acids etc) in filtrate:
Increases the renal K+
excretion
 9. Glucocorticoids: In excess
concentration, it increases the renal K+
excretion

12. Contd
Remember, unlike Na+
, renal response
(excretion) to
K+
excess is very fast
but
to K+
deficit is very slow

13. Potassium homeostasis
May be discussed under following
headings:
 Body potassium content
 Compartmental distribution of
potassium
 Potassium balance
&
 Regulation of potassium balance/
potassium homeostasis

14. Body potassium content
3000 – 4000 mmol in adult
or
50 – 60 mmol/kg
[1 mmol of potassium= 39 mg]
Remember, K+
depletion/excess refer to
body K+
content
&
Hypo/hyperkalemia refer to serum K+
concentration

15. Compartmental distribution of
potassium
I. In ICF : 98% (about 3500 mmol)
mostly in skeletal muscles
II. In ECF : 2% (about 65 mmol) of this,
only 0.4% is found in plasma

16. Potassium balance
Intake: 50 – 100 mmol/day via diets
1 – 2 mmol/kg
[lemon , orange, banana, coconut
water etc are rich source of potassium]
Output: 50 – 100 mmol/day via
a) Urine: 90% (90 mmol/day
b) Feces: 5 – 10%
c) Sweat: <5%

17. Diet (100 mmol/day)
Absorption (90
mmol/day)
ECF (65 mmol/day)
Stool (10
mmol/da
y)
Cell
(3500
mmol/da
y
Urine (90 mmol/day)

19. Contd
Remember,
 As urinary route is the major route for
K+
excretion from body, urinary K+
excretion represents the dietary intake
of K+

Urinary K+
excretion may be 10 –
1000 mmol/day to match with the
wide range of K+
intake to keep the
body K+
normal

20. Contd
 Urinary K+
excretion doesn’t go below
10 mmol/day (obligate K+
loss) or
above 1000 mmol/day (limit of K+
excretion).
So, intolerable hyperkalemia usually
happens
a. If dietary K+
intake is 10 times/more
than the normal with normal kidney
function
b. Or if renal function (GFR) is reduced

21. Regulation of Potassium balance
(Regulation of K+
homeostasis)
Can be discussed as:
1. Short term regulation (internal K+
balance): Done by transmembrane K+
flux
2. Long term regulation (external K+
balance): Done by renal K+
handling & its
regulation

22. 1. Short term regulation of K+
balance
(Transmembrane K+
flux)
Flux of K+
(influx or efflux)across the cell
membrane to keep serum K+
concentration normal & thereby to
maintain optimum cardiovascular &
neuromuscular functions

23. Contd
 In K+
overload, K+
immediately moves in
to the cell (K+
influx)
 In K+
deficit, K+
immediately comes out
of the cell (K+
efflux)

24. Contd
Importance of transmembrane In K+
flux:
 Renal response starts late & takes
time to be completed.
 But body can’t tolerate hypo /
hyperkalemic assault even for a
shorter period of time as there is
higher chance to develop cardiac
arrest

25. Contd
 So, in K+
imbalance , transmembrane K+
flux occurs as a rapid measure to keep
serum K+
within normal before renal
response starts to calm the situation

26. Contd
Factors regulating transmembrane K+
flux:
Factors causing K+
influx , thereby
hypokalemia: Acute K+
excess, insulin,
alkalosis, α-blockers, β- agonist
(epinephrine), aldosterone etc
Factors causing K+
efflux , thereby
hyperkalemia: Acute K+
deficit,
glucagon, acidosis, α- agonist
(norepinephrine), β- blocker , ECF
hyperosmolarity

27. Contd
How ECF hyperosmolarity causes K+
efflux?
 ECF hyperosmolarity causes osmotic
flow of water out of the cell along with
K+
efflux by solvent drag
 Loss of water from cells causes very
high intracellular K+
concentration as
well, which accelerates K+
diffusion out
of cells

28. Contd
Remember,
 β- agonist activity predominates over
α- agonist, so their combined effect
leads to hypokalemia
 The combined effect of β- blocker with
α- blocker leads to hyperkalemia

29. 2. Long term regulation of K+
balance
(Renal handling of potassium)
Kidney responds appropriately either
by K+
excretion (if K+
overload) or by K+
retention (if K+
deficit) to bring the
body K+
content to normal.
Renal response starts late & takes
time to be completed.
Hormone involved: Aldosterone

30. Contd
In hyperkalemia: Aldosterone
increases renal K+
excretion to bring
the serum K+
concentration gradually
back to normal
In hypokalemia: There is reduction of
renal K+
excretion due to aldosterone
deficiency, which gradually brings the
serum K+
concentration back to normal

31. Aldosterone
Mineralocorticoid hormone & a part of
the renin–angiotensin system
A steroid hormone produced by the zona
glomerulosa of the adrenal cortex in
the adrenal gland.
It is essential for Na+
conservation in the
kidney, salivary glands, sweat glands and
colon.
It plays a central role in the regulation of
the plasma Na+
, K+
and arterial BP

32. Contd
Acts on the nuclear mineralocorticoid
receptors within principal cells of the DT &
CD of the nephron
Influences the reabsorption of Na+
and
excretion of K+
(from and into the tubular
fluids, respectively) of the kidney, thereby
indirectly influencing water retention or
loss, BP and blood volume
Exactly the opposite function of
the ANP secreted by the heart

34. Abnormalities of Potassium
homeostasis
2 types of abnormalities:
1. Hyperkalemia
2. Hypokalemia

35. 1. Hyperkalemia
The clinical state of increased serum
potassium concentration (>5.0
mmol/L)
It is less common than hypokalemia
but
it is more dangerous and kills the
individual without warning

36. Contd
Causes:
 Increased K+
intake: e.g. excess i/v
infusion of K+
 Redistribution of K+
: K+
efflux from
cells
 Tissue breakdown/cell lysis:
Hemolysis, rhabdomyolysis, massive
injury, severe burn etc

37. Contd
 Renal diseases: ARF, CRF, obstructive
uropathy etc
 Spurious/pseudo hyperkalemia:
Hemolysis after blood collection,
delayed serum separation from clot ,
severe thrombocytosis / leukocytosis

38. Contd
Consequences/effects/complications:

39. Contd
 Cardiac arrhythmia
 Cardiac arrest
 Tingling & paresthesis
 Paresis & paralysis
 Paralytic ileus
 Respiratory muscle paralysis

40. 1. Hypokalemia
The clinical state of decreased serum
potassium concentration (<3.5
mmol/L)
Causes:
 Redistribution of K+
: K+
influx in to the
cells
 Extra-renal K+
loss: Diarrhoea, vomiting, NG
suction, laxative abuse, intestinal fistula etc

41. Contd
 Renal K+
loss:
i. Renal causes: RTA, post obstructive
diuresis, salt losing nephropathies,
diuretic phase of ARF
ii. Extra-renal causes:
Hyperaldosteronism, cushing
syndrome etc

42. Contd
Acid base disorder in hypokalemia:
 Metabolic acidosis: Renal tubular
acidosis, lower GIT loss (diarrhoea,
intestinal fistula etc), salt losing
nephropathy etc
 Metabolic alkalosis: Upper GIT loss
(vomiting, NG suction etc), diuretic
abuse, steroid excess state
(hyperaldosteronism, cushing
syndrome etc)

43. Contd
Consequences/effects/complications:
 Cardiac arrhythmia
 Cardiac arrest
 Muscle cramp, myalgia, fatigue
 Paresis & paralysis
 Paralytic ileus
 Respiratory muscle paralysis
 Hypokalemic nephropathy

44. Contd
Hypokalemic nephropathy:
It is featured by
 Nephrogenic DI
 Nephrosclerosis
 Interstitial nephritis
 Renal insufficiency