potassium balance ronen l, md nephrology and hypertension services hadassah university hospital
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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
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