Transcript POTASSIUM BALANCE

POTASSIUM BALANCE
Ronen L, MD
NEPHROLOGY 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-KATPase 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 K+ IN
TUBULAR CELLS
INCREASED ACTIVITY OF H+K+-ATPase
DECREASED TUBULAR
EXCRETION OF K+
INCREASED REABSORPTION
OF K+
DECREASED URINARY EXCRETION OF K+
RENAL RESPONSE TO POTASSIUM LOADING
K+ LOAD
INCREASED ALDOSTERONE
SECRETION
K+
INCREASED IN TUBULAR
CELLS AND PLASMA
DECREASED ACTIVITY OF H+K+-ATPase
INCREASED TUBULAR
EXCRETION OF K+
DECREASED
REABSORPTION OF K+
INCREASED URINARY EXCRETION 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-angiotensinaldosterone 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
Collecting duct
Na
HCO3
proximal convuluted tubule
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
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
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)
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
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
Drugs affecting K secretion
Pseudohypoaldosteronism
RESISTANCE TO ALDOSTERONE: HYPERKALEMIA, HYPOTENSION OR
HYPERTENSION
* ACQUIRED: mostly
kidney.
in tubulointerstitial diseases of the
* CONGENITAL: RARE!
1. TYPE 1: salt wasting,
hypotension and hyperkalemia,
high levels of renin and aldosterone. Genetics: loss-offunction 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 insulin
b. NaHCO3 (esp. if acidotic)
c. β2-adrenergic agonists
Removal of excess K+ from the body:
a. Diuretics
b. Cation-exchange resin: kayexalate
c. Dialysis