POTASSIUM BALANCE

Ronen L, MDNEPHROLOGY AND HYPERTENSION SERVICES HADASSAH

UNIVERSITY HOSPITAL

Internal regulation External regulation

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

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

Potassium Transport Along the Nephron

K Secretion in the CCD

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

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

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.

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.

RENAL RESPONSE TO POTASSIUM DEPLETION (LOW INTAKE OR NON RENAL LOSSES)

K+ DEPLETION

DECREASED ALDOSTERONE SECRETION

DECREASED TUBULAR EXCRETION OF K+

DECREASED K+ IN TUBULAR CELLS

INCREASED ACTIVITY OF H+-K+-ATPase

INCREASED REABSORPTION OF K+

DECREASED URINARY EXCRETION OF K+

RENAL RESPONSE TO POTASSIUM LOADING

K+ LOAD

INCREASED ALDOSTERONE SECRETION

INCREASED TUBULAR EXCRETION OF K+

INCREASED K+ IN TUBULAR CELLS AND PLASMA

INCREASED URINARY EXCRETION OF K+

DECREASED ACTIVITY OF H+-K+-ATPase

DECREASED REABSORPTION OF K+

HYPOKALEMIA

• DECREASED NET INTAKE• INCREASED ENTRY INTO

CELLS• INCREASED

GASTROINTESTINAL LOSSES• INCREASED URINARY

LOSSES• INCREASED SWEAT LOSSES• DIALYSIS• POTASSIUM DEPLETION

WITHOUT HYPOKALEMIA

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

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

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

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

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

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

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

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

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Hypokalemia– Sympatology

• Muscle weakness or paralysis

• Cardiac arrhythmias

• Rhabdomyolysis

• Renal dysFx

Impaired concentration abilityIncreased ammonia productionImpaired urinary acidificationIncreased bicarbonate reabsorptionRenal insufficiency

Hypokalemia– ECG

• ST depression• Decreases amplitude of T

wave• Increased amplitude of U

wave• Prolongation of PR

interval• Widening of the QRS

complex

Hypokalemia- diagnosis

ANAMNESIS

PHYSICAL EXAMINATION

URINARY K+ EXCRETION

ACID BASE STATUS

Hypokalemia– Treatment

• KCl: the most common supplement

• ADVANTAGES: 1. correction of alkalosis,2. remains extracellular, and corrects

membrane potential more effectively.

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 10-20 mEq/hr, AND AT LOW CONCENTRATION, UP TO 40-60 mEq/L.

Hypokalemia– Treatment

• CONTINUE MONITORING K+ PLASMA LEVELS.

• CONTINUE FOLLOWING CONTINUOUS LOSS OF K+

HYPERKALEMIA

Hyperkalemia- Etiology

• INCREASED INTAKE

• EXIT OF K+ FORM CELLS TO EXTRACELLULAR FLUID

• DECREASED URINARY EXCRETION

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.

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

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)

Major causes of hyperkalemia

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

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

Causes of hypoaldosteronism

Drugs affecting K secretion

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.

Hyperkalemia- symptoms

• MUSCLE WEAKNESS

• CARDIAC ARRHYTHMIAS

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)

ECG CHANGES IN HYPERKALEMIA

Hyperkalemia- Diagnosis

• ANAMNESIS

• PHYSICAL EXAMINATION

• CHECK FOR: pH, urea and creatinine, glucose, markers of tissue damage (LDH, CPK), ECG.

TTKG- transtubular potassium gradient

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

Hyperkalemia– Treatment

Antagonism of cardiac effects of hyperkalemia: i.v calcium gluconate

Increase K+ entry into cells:a. i.v glucose and insulinb. NaHCO3 (esp. if acidotic)c. β2-adrenergic agonists

Removal of excess K+ from the body:d. Diureticse. Cation-exchange resin: kayexalatef. Dialysis