1. NEPHROLOGY AND HYPERTENSION SERVICES HADASSAH UNIVERSITY HOSPITAL
POTASSIUM BALANCE
Ronen L, MD
NEPHROLOGY AND HYPERTENSION SERVICES HADASSAH UNIVERSITY HOSPITAL

2. Internal regulation
External regulation

5. Role of Insulin and β-adrenergics on the Distribution of K

6. Shift of K Out of cells in Metabolic Acidosis
Monocarboxylic acids enter the cells in an electorneutral fashion. Therefore they do not cause a change in cell voltage.
H load of inorganic acid is titrated by HCO3 in the ECF→ ↓ cell voltage→ K shifts out of cell

8. Potassium Transport Along the Nephron

12. K Secretion in the CCD

13. Factors Affecting Potassium Secretion From the Tubular Cell to the Lumen
K+ concentration gradient across the luminal membrane
Electrical gradient across the tubular cell
K+ permeability of the luminal membrane

14. Effects of aldosterone actions in principal cells
Increases the permeability of the luminal membrane to Na by increasing the number of open ENaC→ increases electrical gradient across the tubular cell
Increases the permeability of the luminal membrane to K by increasing the number of open K channels
Enhances the activity of the Na-K-ATPase at the basolateral membrane→ increases cell K concentration

15. Regulation of Potassium Secretion- Serum Potassium Concentration
Direct effects: enhances Na+-K+-ATPase activity, increases luminal permeability to K+ and Na+.
Indirect effect: increases aldosterone secretion.

16. Regulation of Potassium Secretion- Distal Flow Rate
Increase in distal flow rate enhances K+ secretion.
It dilutes K+ secreted from the tubular cells to the lumen, and by doing so increases the K+ CONCENTRATION GRADIENT.
High flow rate also delivers more Na+ to the distal tubule, more Na+ is reabsorbed, and the gradient across the tubular cells rises, promoting K+ SECRETION.

17. RENAL RESPONSE TO POTASSIUM DEPLETION (LOW INTAKE OR NON RENAL LOSSES)
K+ DEPLETION
DECREASED ALDOSTERONE SECRETION
DECREASED K+ IN TUBULAR CELLS
INCREASED ACTIVITY OF H+-K+-ATPase
DECREASED TUBULAR EXCRETION OF K+
INCREASED REABSORPTION OF K+
DECREASED URINARY EXCRETION OF K+

18. RENAL RESPONSE TO POTASSIUM LOADING
K+ LOAD
INCREASED ALDOSTERONE SECRETION
DECREASED ACTIVITY OF H+-K+-ATPase
INCREASED K+ IN TUBULAR CELLS AND PLASMA
INCREASED TUBULAR EXCRETION OF K+
DECREASED REABSORPTION OF K+
INCREASED URINARY EXCRETION OF K+

19. HYPOKALEMIA DECREASED NET INTAKE INCREASED ENTRY INTO CELLS
INCREASED GASTROINTESTINAL LOSSES
INCREASED URINARY LOSSES
INCREASED SWEAT LOSSES
DIALYSIS
POTASSIUM DEPLETION WITHOUT HYPOKALEMIA

20. Major causes of hypokalemia
Decrease potassium intake
Increased entry into cells
An elevation in extracellular pH
Increased availability of insulin
Elevated β-adrenergic activity- stress or administration of beta agonists
Hypokalemic periodic paralysis
Marked increase in blood cell production
Hypothermia

21. Major causes of hypokalemia
Increased gastrointestinal losses
*Diarrhea
*Lower GI losses due to villous ademoma, VIPoma
Laxative abuse
* usu. Decreased intake and volume depletion leading to increased aldosterone contribute

22. Major causes of hypokalemia
Increased urinary losses
Diuretics
Primary mineralocorticoid excess
Loss of gastric secretions
Nonreabsorbable anions
Renal tubular acidosis
Salt-wasting nephropathies - including Bartter's or Gitelman's syndrome
Liddle’s syndrome
Amphotericin B
Hypomagnesemia
Polyuria

23. Causes of Mineralocorticoid Excess
PRIMARY HYPERALDOSTRONISM
A. Adenoma
B. Hyperplasia
C. Carcinoma
CUSHING DISEASE
LIDDLE’S SYNDROME
CHRONIC INGESTION OF EXOGENOUS MINERALOCORTICOID
HYPERRENINISM
A. Renal artery stenosis
B. Renin secreting tumor
HYPERSECRETION OF DEOXYCORTICOSTERONE OR OTHER MINERALOCORTICOID
LICORICE or CABENOXOLONE INGESTION- inhibits 11b-hydroxysteroid dehydrogenase which converts cortisol to cortisone
APPARENT MINERALOCORTICOID EXCESS

24. Liddle’s syndrome
Autosomal dominant. Characterized by activating mutation in collecting duct Na+ channel with enhanced sodium reabsorption. Low renin, low aldosterone levels.
The clinical picture mimics primary hyperaldosteronism: hypertension, hypokalemia and alkalosis

25. Barrter’s and Gitelman’s syndromes
Impairment in one of the transporters involved in sodium chloride reabsorption in the loop of Henle (Bartter’s) and distal tubule (Gitelman’s)
The tubular defects in sodium chloride transport are almost identical to that seen with chronic ingestion of a loop diuretic (mimicking Bartter syndrome) or a thiazide diuretic (mimicking Gitelman syndrome).
Impaired sodium chloride reabsorption leads to mild volume depletion and activation of the renin-angiotensin-aldosterone system.
The combination of secondary hyperaldosteronism and increased distal flow and sodium delivery enhances potassium and hydrogen secretion at the secretory sites in the connecting tubules and collecting tubules, leading to hypokalemia and metabolic alkalosis

26. Barrter’s syndrome
Bartter syndrome is an autosomal recessive disorder that often presents in childhood and may be associated with the following clinical features:
Growth and mental retardation
Hypokalemia
Metabolic alkalosis
Polyuria and polydipsia due to decreased urinary concentrating ability
Normal to increased urinary calcium excretion
Normal or mildly decreased serum magnesium concentration

27. Gitelman’s syndrome
Gitelman syndrome is an autosomal recessive disorder that presents with hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and normal blood pressure
Manifestations include::
Cramps of the arms and legs, due at least in part to hypokalemia and hypomagnesemia
Fatigue, which may be severe
polyuria and nocturia

28. proximal convuluted tubule
Collecting duct Na
HCO3

29. Hypokalemia– Sympatology
Muscle weakness or paralysis
Cardiac arrhythmias
Rhabdomyolysis
Renal dysFx
Impaired concentration ability
Increased ammonia production
Impaired urinary acidification
Increased bicarbonate reabsorption
Renal insufficiency

30. Hypokalemia– ECG ST depression Decreases amplitude of T wave
Increased amplitude of U wave
Prolongation of PR interval
Widening of the QRS complex

31. Hypokalemia- diagnosis
ANAMNESIS
PHYSICAL EXAMINATION
URINARY K+ EXCRETION
ACID BASE STATUS

33. Hypokalemia– Treatment
KCl: the most common supplement
ADVANTAGES:
correction of alkalosis,
remains extracellular, and corrects membrane potential more effectively.

34. Hypokalemia– Treatment
KCL CAN BE GIVEN ORALY OR I.V.
ORALLY- CAN BE GIVEN IN LARGE DOSES BUT CAN CAUSE GASTRIC ULCERS.
I.V SHOULD BE GIVEN VERY SLOWLY UP TO mEq/hr, AND AT LOW CONCENTRATION, UP TO mEq/L.

35. Hypokalemia– Treatment
CONTINUE MONITORING K+ PLASMA LEVELS.
CONTINUE FOLLOWING CONTINUOUS LOSS OF K+

36. HYPERKALEMIA

37. Hyperkalemia- Etiology
INCREASED INTAKE
EXIT OF K+ FORM CELLS TO EXTRACELLULAR FLUID
DECREASED URINARY EXCRETION

38. Hyperkalemia– Etiology: Increased Intake
Rare as a cause for hyperkalemia when renal K+ excretion is intact.
Acute K+ load, oral or IV. Can cause transient hyperkalemia.

39. Major causes of hyperkalemia
Increase potassium release from cells
Pseudohyperkalemia
Metabolic acidosis
Insulin deficiency, hyperglycemia, hyperosmolality
Increased tissue catabolism
Beta adrenergic blockade
Exercise
Hyperkalemic periodic paralysis
other
Overdose of digitalis or related digitalis glycosides
Red cell transfusion
Succinylcholine

40. Major causes of hyperkalemia
Reduced urinary potassium excretion
hypoaldosteronism
Acute and chronic kidney disease
Effective arterial volume depletion
Type IV renal tubular acidosis
Selective impairment of potassium excretion (normal renin and aldosterone, no Na wasting, normal antinatriuretic response to exogenous mineralocorticoids)

41. Causes of hypoaldosteronism
Aldosterone deficiency
Primary
Primary adrenal insufficiency
Congenital adrenal hyperplasia (21- hydroxylase deficiency)
Isolated aldosterone synthase deficiency
Heparin and low molecular weight heparin
Hyporeninenmic hypoalsdoteronism
Renal disease, most often diabetic nephropathy
Volume expansion, such in acute glomerulonephritis
Angiotensin inhibition (ACEI, ARB, DRI)
NSAIDS
Cyclosporine
HIV infection
Some cases of obstructive uropathy

42. Causes of hypoaldosteronism
Aldosterone resistance
Drugs which close the collecting tubule sodium channel
Amiloride
Spironolactone
Triamterene
Trimethoprim (high dose)
Pentamidine
Tubulointerstitial disease
Pseudohypoaldosteronism
Distal chloride shunt

43. Drugs affecting K secretion

44. Pseudohypoaldosteronism
RESISTANCE TO ALDOSTERONE: HYPERKALEMIA, HYPOTENSION OR HYPERTENSION * ACQUIRED: mostly in tubulointerstitial diseases of the kidney. * CONGENITAL: RARE! 1. TYPE 1: salt wasting, hypotension and hyperkalemia, high levels of renin and aldosterone. Genetics: loss-of-function mutations in MR, or mutations in subunits of ENaC. 2. TYPE 2: Gordon’s syndrome: hypertension, hyperkalemia, metabolic acidosis. genetics: mutation in WNK4 or gain-of-function mutation in WNK1.

45. Hyperkalemia- symptoms
MUSCLE WEAKNESS
CARDIAC ARRHYTHMIAS

46. Hyperkalemia- ECG PEAKED, NARROWED T WAVES
SHORT QT INTERVAL PRLONGATION OF PR INTERVAL
WIDENING OF QRS COMPLEX
LOSS OF P WAVE
SINE-WAVE PATTERN (QRS COMPLEX MERGES WITH THE T WAVE)

47. ECG CHANGES IN HYPERKALEMIA

48. Hyperkalemia- Diagnosis
ANAMNESIS
PHYSICAL EXAMINATION
CHECK FOR: pH, urea and creatinine, glucose, markers of tissue damage (LDH, CPK), ECG.

50. TTKG- transtubular potassium gradient

51. Hyperkalemia– Treatment
LOOK FOR ECG CHANGES!
IF ANY ECG CHANGES ARE SEEN, ONE SHOULD ACT URGENTLY!
I.V. TREATMENT AND CONTINUOUS ECG MONITORING ARE INDICATED.
BE READY WITH EXTERNAL PACEMACKER

52. Hyperkalemia– Treatment
Antagonism of cardiac effects of hyperkalemia:
i.v calcium gluconate
Increase K+ entry into cells:
i.v glucose and insulin
NaHCO3 (esp. if acidotic)
β2-adrenergic agonists
Removal of excess K+ from the body:
Diuretics
Cation-exchange resin: kayexalate
Dialysis