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Chapter 9. Disorders of Potassium metabolism

Nephrology Study
by

Hee Jung Jeon

on 18 April 2017

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Transcript of Chapter 9. Disorders of Potassium metabolism

Chapter 9. Disorders of Potassium metabolism
Conclusion
Thank you for your attention!
is here
Potassium Intake

Potassium distribution

Renal K Handling with Normal Renal Function

Renal K Handling in the Face of CKD
Clinical manifestation

Etiology

Diagnosis

Treatment
Clinical manifestation

Etiology

Diagnosis

Treatment
Normal physiology of
potassium metabolism
Hypokalemia
hyperkalemia
Contents
Normal physiology of potassium metabolism
Potassium intake
Potassium distribution
Renal K Handling with Normal Renal Function
Renal K Handling in the Face of CRF
Hypokalemia
Clinical manifestation/etiology/diagnosis/treatment
Hyperkalemia
Clinical manifestation/etiology/diagnosis/treatment
Essential for many cellular functions

Present in most foods & excreted primarily by the kidney
typical western diet: 70~150 mmol/day
efficiently absorbed in GI tract
Potassium Intake
Artichoke
Avocado
Sirloin steak
Cantaloupe
Grapefruit
Prunes
Raisins
Squash
Clinical Manifestations
Clinical Manifestations
Cardiovascular
hypoK increases BP by 5-10 mmHg
by stimulating Na retention -> intravascular vol. expansion
by sensitizing the vasculature to endogenous vasoconstrictors
expression of the kidney-specific isoform of WNK1
NCC-mediated Na reabsorption in distal convoluted tubule
ENaC- mediated Na reabsorption in cortical collecting duct

esp. digoxin, diuretic-induced hypoK
Increases the risk of Vent. arrhythmias, V.fib, and sudden cardiac death
Clinical Manifestations
Clinical Manifestations
Hormonal
hypoK
-> impair insulin release & induce insulin resistance
-> worsen glucose control in diabetic patients
Muscular
hyperpolarizes skeletal m. cells
-> impairing m. contraction
impairs local nitric oxide release
-> reduces skeletal m. blood flow
-> predispose to rhabdomyolysis during vigorous exercise
Renal
Tubulointerstitial and Cystic Changes
K depletion
stimulates intra-renal vasocontrictors
(AT-II & endothelin)
inhibits intra-renal vasodilators
(kallikrein, NO, prostaglandins) 
renal structural change (tubulointerstitial fibrosis)
HypoK predisposes to renal cyst formation
Acid Base : metabolic alkalosis
Polyuria
d/t increased renal net acid excretion
severe hypoK -> resp. m. weakness -> resp. acidosis
hypoK
-> impairs renal concentrating ability
-> causes mild polyuria, 2~3 liters/day
Hepatic Encephalopathy
hypoK
-> increases renal ammonia production
-> 1/2 to the systemic circulation via renal veins
-> may worsen hepatic encephalopathy
Etiology
(1) Pseudohypokalemia :
m/c cause : AML
large number of abnormal WBC can take up extracellular K if blood is stored for prolonged periods at room temp.
(2) Redistribution: Fig 9.3
hypokalemic periodic paralysis
genetic defect in dihydropyridine-sensitive Ca channel
hyperthyroidism
(3) Extra-renal K Loss : skin, GI tract
excessive sweating or chr diarrhea, vomiting, NG suction
(4) Renal K Loss
Drugs
- thiazide > loop diuretics (adjusted for natriuretic effect)
- penicillin analogues: carbenicillin
- amphotericin B : increases collecting duct K secretion
- aminoglycoside, cisplatin, toluene, licorice

Endogenous Hormone : Aldosterone, CAH
- K uptake into cells & renal K excretion

Mg depletion : inhibits renal K retention
- diuretic, aminoglycoside, cisplatin induced

Intrinsic Renal Defect
: Bartter, Gitelman’s, Liddle synd

Bicarbonaturia : increases K secretion
major intracellular cation
100~120 mmol/l in the cytosol
Total intracellular potassium content
3000~3500 mmol in healthy adults
Potassium Distribution
Only 1-2%
total body K+
Na+,K+-ATPase : active uptake
2 K+ ions into cells in exchange for extrusion of 3 Na+
 -> high intracellular K+, low Na+
Intracellular K/extracellular K ratio
major determinant of cell membrane potential
intracellular electronegativity

Serum K concentration : tightly regulated
“Feed forward” regulatory system
gut or portal potassium sensors  adjusts renal potassium excretion (independently changes in plasma potassium or aldosterone concentration)
Potassium Distribution
Cellular potassium shifts
Diagnosis
IV K
- rate: 10 mmol/h (peri), 20 mmol/h (cent)
- 20 mmol of KCl increases the serum K by ~0.25 mmol/l

If KCl is administered in destrose-containing solutions, the resulting increase in cellular K uptake may exceed the KCl replacement rate & may worsen the hypoK

Conditions requiring urgent therapy (rare)
hypokalemic periodic paralysis
severe hypoK pts requiring urgent surgery
AMI with significant ventricular ectopy
-> IV K given 5-20 mmol during 15-20 min

Hypomagnesemia can lead to refractoriness to K replacement
=> replacement with MgSO4, periodic measure of serum Mg
Treatment
Clinical Manifestations
Asymptomatic to life threatening

Alteration of cardiac conduction -> Fig 9.8

Skeletal m. weakness
"rubbery" or "spaghetti" legs
with severe hyperK, resp. failure may occur from paralysis of the diaphragm


Etiology
(1) Pseudohyperkalemia
hemolysis
RA
Infectious mononucleosis
Abnormal RBC memb K permeability
prolonged tourniquet time
severe leukocytosis, marked thrombocytosis
(2) Redistribution: Fig 9.3
(3) Excess Intake
if renal K excretion impaired
ex) enteral products, Fig 9.1
(4) Impaired Renal Potassium Secretions
intrinsic renal defect - Gordon's synd.
specific medications
24-hour urine K+ excretion : type of hyperK
- renal : K+ <20 mmol/l
 => fludrocortisone :
Aldo deficiency (u-K up to >40 mmol/l)
Aldo resistance (u-K remains <20 mmol/l)
- extrarenal: K+ >40 mmol/l

Urinary K+ measurements may be difficult to interpret since K+ excretion depends on multiple factors (GFR, tubular lumen flow, diuretic use, and water reabsorption) in the distal tubule 
=> TTKG check
Distinguishing renal & nonrenal mechanisms of hyperK
Treatment of hyperK
Should not include NaHCO3 unless the pt is frankly acidotic (pH<7.2) or unless substantial endogenous renal function is present
Precautions with IV Calcium

- NaHCO3-containing solutions should not be used, d/t CaCO3 precipitation can occur
- hyperCa may occur, it may potentiate digoxin-related myocardial toxicity

Most rapid (1-3min), last for 30-60min
Dose may be repeated within 5-10 min
Consider continuous calcium infusion
- IV insulin
with or wihout glucose coadminister
continuous infusion
4~10 U/hr with D10W
- b agonist : IV, inhaled, SC
dose requir 2-8 times greater than usual nebulizer

- in severe hyperK, combined therapy with insulin &
albuterol may be more effective than either alone
♥신장내과 화이팅 ♥
Nephrology Fighting
Acidosis d/t inorganic anions (NH4Cl, HCl)  -> hyperK
Mechanism is not fully understood
Acidosis d/t organic anions (lactic acid)
Generally, do not cause transcellular K shift

Insulin
Directly stimulate Na+,K+-ATPase
βb2 agonist
Intracellular cAMP↑  stimulate Na+,K+-ATPase
aα-agonist
Opposite of bβ2 agonist
Causes of cellular potassium shifts
Aldoterone -> lower serum K
Stimulate K movement into cell (redistribution)
Increase K excretion in the Kidney > the gut

Hyperosmolality  -> hyperK
Effective plasma osmole (hyperglycemia, mannitol)
 -> water movement out of the cells
 -> cell volume↓ & intracellular K ↑
 -> Feedback inhibition of Na+,K+-ATPase
 -> Shifting K from intracellular to extracellular
Causes of cellular potassium shifts
Exercise -> hyperK
By aα-adrenergic R activation
 -> shift K out of skeletal m. cell
 -> induced arterial dilation
 -> Increased skeletal m. blood flow (adaptive mechanism)
Simultaneous βb2-adrenergic R activation
 -> Stimulate skeletal m. cellular K uptake
 -> Minimizing severity of exercise-induced hyperK

(* In patients with pre-existing K depletion, post-exercise hypokalemia may be severe and rhabdomyolysis may occur.)
Causes of cellular potassium shifts
K homeostasis is relatively well preserved, and serum K usually remains normal until the GFR is severely reduced
d/t increased K excretion per nephron & increased GI tract K excretion
Aldosterone & subclinical serum K increases may contribute to this adaptation

Pts with CKD appear to tolerate hyperK with fewer cardiac & ECG abnormalities than pts with well-preserved or normal renal function who experience AKI
=> mechanism (?)
Renal K Handling in the Face of CKD
Descending loop of Henle : K secretion
Thick ascending loop of Henle (apical membrane)
reabsorption by apical Na+-K+-2Cl- cotransporter
 -> Net K reabsorption in loop of Henle
Reverse to secretion
loop diuretics or K loading











Distal tubule & collecting duct
Major site regulate K excretion
Active secretion and absorption
Renal K Handling c Normal Renal Fx
Glomerulus : Nearly completely filtered

Prox. Tubule : reabsorbs the majority (~ 65-70%)
Very little regulated by changes in K intake
Renal K Handling c Normal Renal Fx
Principal cell(cortical collecting duct) : secretes K


Regulation factor :
luminal flow rate,
distal Na delivery,
K sparing diuretics
loop or thiazide diuretics
extracellular K & pH
aldosterone,
Renal K Handling c Normal Renal Fx

Intercalated cell :
reabsorbs K through apical H+,K+-ATPase that actively secretes H+ into the luminal fluid in exchange for K reasorption

Metabolic acidosis can increase H+,K+-ATPase contributing to hyperkalemia
Renal K Handling c Normal Renal Fx
ENaC
ROMK
H+,K+-ATPase
secretion by principal cell & reaborption by intercalated cell
-> effective regulation of renal K excretion
WNK (with no lysine) kinase
Origins of Myofibroblasts
Modified from Madeleine A et. Semin Nephrol 2010 & Liu et. Nat Rev Nephrol 2011
Full transcript