potassium balance and potassium imbalance. part Ⅰ

Potassium Balance and Potassium Imbalance

Part Ⅰ

Potassium BalancePotassium Balance

Ⅰ Ⅰ Content and Distribution of Content and Distribution of

Potassium in the BodyPotassium in the Body

Ⅱ Ⅱ Intake and Excretion of PotassiumIntake and Excretion of Potassium

Dietary K intake

70~100mmol/day

ECF 2%

Serum [K+] round 4.5mmol/L

K+

Skin trivial normallyColon 10%

Kidneys > 80% More ingested, more excreted Less ingested, less excreted Not ingested, excretion goes on

Content, distribution, intake and excretion of K Content, distribution, intake and excretion of K

Ex

cretio

n

ICF

[K+] 160mmol/L

98% of the total body potassium

Total body K content

31~57mmol/Kg body weight

Ⅲ Ⅲ Maintenance of Potassium HomeostasisMaintenance of Potassium Homeostasis

— —Distribution of KDistribution of K++ across the cell across the cell

membrane and Regulation of renal membrane and Regulation of renal

KK++ excretion excretion

Distribution of Potassium across Distribution of Potassium across the Cell Membrane the Cell Membrane

The NaThe Na++/K/K++ATPase membrane pump ATPase membrane pump and permeability of ion channelsand permeability of ion channels

1.Hormones — 1.Hormones — insulininsulin, glucagon, , glucagon, catecholaminescatecholamines, thyroid hormone, thyroid hormone

2.Serum [K2.Serum [K++]]

3.pH of ECF and plasma 3.pH of ECF and plasma osmolalityosmolality

4.Others — rate of cell breakdown, 4.Others — rate of cell breakdown, hypoxia, hypothermia, exercisehypoxia, hypothermia, exercise

Influencing Factors Influencing Factors

[K[K++]]↑↑

NaNa++

NaNa++/K/K++--ATPaseATPase

KK++

KK++ HH++

CatecholamineCatecholamine

Insulin Insulin

Regulation of Renal Potassium ExcretionRegulation of Renal Potassium Excretion

Filtration, reabsorption and Filtration, reabsorption and secretionsecretion

of potassiumof potassium

The nephron and collecting tubuleThe nephron and collecting tubule

Cl-

NaNa++//KK++ATPase(MgATPase(Mg22

++ activated activated) )

NaNa++/K/K++ATPaseATPase

HH++-- KK+ + ATPaseATPase


Filtration, reabsorption and secretion

of potassiumSecretion of potassium in the distal and

collecting tubules

principal cells, with Na+/K+ATPase membrane pump, for secretion of K+

lumenlumen

Principal CellPrincipal Cell

bloodblood

K+

Na+

Na+

K+

Cl-

Cl-K+

CO2

HCO3-

Cl-Cl-

H+

K+

CO2

Intercalated CellIntercalated Cell


Filtration, reabsorption and secretion

of potassiumSecretion of potassium in the distal and

collecting tubules

Reabsorption of K in the distal and collecting tubules, intercalated cells, with H+/K+-ATPase (proton pump) for reabsorption of K+


Filtration, reabsorption and secretion of potassium Secretion of potassium in the distal and collecting tubules Reabsorption of K in the distal and collecting tubules

intercalated cells, with H+/K+-ATPase

(proton pump) for reabsorption of K+

Factors influencing excretion of K+ by the distal and collecting tubules

Factors Influencing Excretion of KFactors Influencing Excretion of K++ by by the Distal and Collecting Tubulesthe Distal and Collecting Tubules

Aldosterone — activates NaAldosterone — activates Na++//KK++ATPase, ATPase, increase membrane permeability to Kincrease membrane permeability to K

[K[K++] in the ECF] in the ECF Flow rate of tubular fluid in the distal tubuleFlow rate of tubular fluid in the distal tubule pH of ECF —pH of ECF —↓↓pH inhibits NapH inhibits Na++//KK++ATPaseATPase

+

lumenlumen bloodblood

Principal CellPrincipal Cell

K+

Na+

Na+

K+

Cl-

Cl-

K+ [K+ ]↑

②③

CO2HCO3

-

Cl-Cl-

H+

K+

CO2

Intercalated CellIntercalated Cell

[H+ ]↑

①flow rate

Factors Influencing Excretion of KFactors Influencing Excretion of K++ by the by the

Distal and Collecting Tubules Distal and Collecting Tubules

+

+

Ald+

++

++ -

http://images.google.com/imgres?imgurl=ist-socrates.berkeley.edu/~jmp/adrenal.jpg&imgrefurl=http://ist-socrates.berkeley.edu/~jmp/JeremyLO2.html&h=300&w=348&prev=/images%3Fq%3Dadrenal%2Bgland%2B%26svnum%3D10%26hl%3Dzh-CN%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8%26sa%3DG

Maintenance of Potassium HomeostasisMaintenance of Potassium Homeostasis

Distribution of potassium across the cell Distribution of potassium across the cell

membranemembrane

Regulation of renal potassium excretionRegulation of renal potassium excretion

Excretion of K by the Colon also controlled Excretion of K by the Colon also controlled

by aldosteroneby aldosterone

Function of Potassium in the BodyFunction of Potassium in the Body

ⅣⅣFunction of Potassium in the BodyFunction of Potassium in the Body

The part K+ plays in metabolism

Maintenance of the resting membrane potential of excitable cells

Maintenance and regulation of osmotic pressure and acid-base balance both in ICF and ECF

Part Ⅱ

Potassium Imbalance

---abnormal changes in [K+] in ECF

Hypokalemia

Serum [K+]<3.5mmol/L,may or may not be

associated with K deficit

ECF 2%

Dietary intake

Serum [K+] < 3.5mmol/L

G.I losses---diarrhea, vomiting

Renal losses---diuretics, some diseases of the kidney

Losses from the skin---profuse sweating, burns

Exce

ssive

losses

ICF

[K+] may or may not be decreased

Total body K content

— decreased (K deficit)

shifting

— normal

Crude cotton seed oil poisoning

or

Etiology and PathogenesisEtiology and Pathogenesis


Ⅰ. Inadequate Intake Fasting, anorexia, inability to eat,

prolonged IV alimentation without K

supplementation, alcoholism

Ⅱ. Excessive Losses 1.Gastrointestinal losses

Diarrhea →extrusion of large amount of

alkaline liquid stool with a high content

of K→K depletion, acidosis, ECF volume

contraction →↑secretion of aldosterone

Vomiting →mainly increased renal excretion

of K+ due to metabolic alkalosis caused by

loss of gastric acid, contraction of ECF

volume

Etiology and PathogenesisEtiology and Pathogenesis Ⅰ. Inadequate Intake

Ⅱ. Excessive Losses 1.Gastrointestinal losses

2.Excessive renal losses (1)Diuretics→increased flow rate and delivery of Na+,Cl- and water to the distal tubule → increased Na+-K+ exchange; volume contraction →increased aldosterone → renal K excretion↑



Cl-






ⅠⅠ. Inadequate Intake. Inadequate Intake

ⅡⅡ. Excessive Losses. Excessive Losses 1.Gastrointestinal losses1.Gastrointestinal losses

2.Excessive renal losses2.Excessive renal losses (1) Diuretics (1) Diuretics (2) Some diseases of the kidney(2) Some diseases of the kidney Renal tubular acidosisRenal tubular acidosis

Excessive Renal Losses

(1) Diuretics(1) Diuretics(2) Some diseases of the kidney(2) Some diseases of the kidney Renal tubular acidosisRenal tubular acidosis Diuretic recovery phase of acute renal failureDiuretic recovery phase of acute renal failure

(3) Antibiotics (3) Antibiotics (4) Excess of adrenocortical hormones(4) Excess of adrenocortical hormones Aldosteronism, Cushing’s syndromeAldosteronism, Cushing’s syndrome

(5) Magnesium deficiency(5) Magnesium deficiency

Diuretic recovery phase of acute renal failureDiuretic recovery phase of acute renal failure



Cl-





A female patient, 42 years old, was admitted to the affiliated A female patient, 42 years old, was admitted to the affiliated hospital of the Sichuan Med.College as an emergency case on hospital of the Sichuan Med.College as an emergency case on April 4 1978, with a chief complaint of decreased food intake, April 4 1978, with a chief complaint of decreased food intake, nausea and frequent vomiting for 20 days. She had a history of nausea and frequent vomiting for 20 days. She had a history of diabetes mellitus for 3 years.diabetes mellitus for 3 years.

Diagnosis: Diabetic ketoacidosis, which is a medical emergency. Diagnosis: Diabetic ketoacidosis, which is a medical emergency. She was treated with insulin, with success. She was also found to She was treated with insulin, with success. She was also found to have infection of the urinary tract as well as severe have infection of the urinary tract as well as severe

hypokalemia (the serum [Khypokalemia (the serum [K++] was around 2mmol/L). Therefore ] was around 2mmol/L). Therefore she was given large doses of gentamycin for 33 days. KCl was she was given large doses of gentamycin for 33 days. KCl was also administered, both by mouth and IV instillation, in large also administered, both by mouth and IV instillation, in large doses, for 41 days. However, hypokalemia persisted doses, for 41 days. However, hypokalemia persisted (2.55mmol/L). (2.55mmol/L).

Case Report

To the surprise of the doctor, the patient suddenly developed To the surprise of the doctor, the patient suddenly developed spastic rigidity of the limbs. It was until then, 41days after spastic rigidity of the limbs. It was until then, 41days after

admission, the doctor examined the serum [Mgadmission, the doctor examined the serum [Mg22++], it was very ], it was very low:0.2mmol/L!(The normal range of serum [Mglow:0.2mmol/L!(The normal range of serum [Mg22++] being ] being 1.5~2.5mmol/L). IV MgSO1.5~2.5mmol/L). IV MgSO4 4 was immediately given, and also was immediately given, and also

for several days, with complete success! The doses of KCl was for several days, with complete success! The doses of KCl was

reduced, however, the serum [Kreduced, however, the serum [K+] rose to normal levels within ] rose to normal levels within

3 days! Serum [Mg3 days! Serum [Mg22++] also turned normal. No adverse ] also turned normal. No adverse reactions.(reactions.( 《中华内科杂志》《中华内科杂志》 19801980 年年 11 月月 ))

Questions:1. What is the cause or what are the causes of

hypokalemia and hypomagnesemia in this patient?

2. Why did the doctor fail to diagnose

hypomagnesemia earlier?

Excessive Renal Losses

(1) Diuretics(1) Diuretics(2) Some diseases of the kidney(2) Some diseases of the kidney Renal tubular acidosisRenal tubular acidosis Diuretic recovery phase of acute renal failureDiuretic recovery phase of acute renal failure

(3) Antibiotics (3) Antibiotics (4) Excess of adrenocortical hormones(4) Excess of adrenocortical hormones Aldosteronism, Cushing’s syndromeAldosteronism, Cushing’s syndrome

(5) Magnesium deficiency(5) Magnesium deficiency(6) Alkalosis(6) Alkalosis

Etiology and PathogenesisEtiology and PathogenesisⅠ.Inadequate Intake

Ⅱ.Excessive Losses

1. Gastrointestinal losses

2. Excessive renal losses 3. Excessive losses from the skin Profuse sweatings, burns or scalds

Etiology and PathogenesisEtiology and PathogenesisⅠ.Inadequate IntakeⅡ.Excessive LossesⅢ.Shifting of K+ from the ECF

to ICF 1.Overdose of insulin 2.-adrenergic agonist

overdose

NaNa++


KK++

KK++ HH++

AlbuterolAlbuterol

Insulin Insulin

Etiology and PathogenesisEtiology and PathogenesisⅠⅠ.Inadequate Intake.Inadequate Intake

ⅡⅡ.Excessive Losses.Excessive Losses

ⅢⅢ.Shifting of K.Shifting of K++ from the ECF to ICF from the ECF to ICF

1.Overdose of insulin1.Overdose of insulin

2.2.-adrenergic agonist overdose-adrenergic agonist overdose

3.Alkalosis 3.Alkalosis

4.Barium poisoning4.Barium poisoning

5.Familial hypokalemic periodic paralysis5.Familial hypokalemic periodic paralysis

NaNa++


KK++

KK++ HH++

AlbuterolAlbuterol

Insulin Insulin


ⅠⅠ.Inadequate Intake.Inadequate Intake

ⅡⅡ.Excessive Losses.Excessive Losses

ⅢⅢ.Shifting of K.Shifting of K++ from the ECF to ICF from the ECF to ICF

Crude Cotton Seed Oil poisoningCrude Cotton Seed Oil poisoning

Effects on the BodyEffects on the Body

— factors influencing the effects: the underlying diseases, the degree of hypokalemia and rapidity of its development, the ratio of [K+]i / [K+] e

Effects on Neuromuscular ExcitabilityEffects on Neuromuscular Excitability

The Resting Membrane Potential (RMP) and Action Potential The Resting Membrane Potential (RMP) and Action Potential (AP) of a skeletal muscle cell in the normal state(AP) of a skeletal muscle cell in the normal state

+35

0

-60

-90

Millivolts

Milliseconds

Threshold

Nernst equation ENernst equation Emm= -60lg[K= -60lg[K++]]icf icf / [K/ [K++]]ecfecf (mv) (mv)

Acute HypokalemiaAcute Hypokalemia

[K[K++]]ii / [K / [K++]]e e ↑↑ RMP more negative than normal

hyperdepolarization block, excitability↓

muscle weakness, flaccid paralysis, smooth muscle symptoms

-120

-90

-60

-30

0

30

Normal Low [K+] High [K+]

TMP

RMP

Action potential (AP)

The effects of serum K+ concentration on cellular membrane excitability

mv

ratio of [K+]i to [K+]e may be normal,

RMP and excitability unchanged, interfering

with cellular metabolism and vasodilation of

muscles during exercise

Chronic Hypokalemia

Effects on the HeartEffects on the Heart

A Brief Review of the Bioelectric A Brief Review of the Bioelectric

Phenomena of the HeartPhenomena of the Heart

a: effective refractory period; b: relative refractory period

c: supranormal period

RMP and AP of a Ventricular Muscle Cell of the HeartRMP and AP of a Ventricular Muscle Cell of the Heart

40

+20

0

-20

40

60

80

100

4

0

12

3

4

3

4

0

12

4

RMPmax.diast.potential

Atrial muscle Purkinje’s fiber

The Membrane Potential of Atrial Muscle, The Membrane Potential of Atrial Muscle, and Purkinje’s Fiber and Purkinje’s Fiber

1.Effects on excitability1.Effects on excitability

RMP<-90mv, excitability

Ca2+ inflow plateau, ERP shortened

Phase 3, SNP prolonged

AP prolongedAP prolonged

Effects of low serum [KEffects of low serum [K++] on the action potential ] on the action potential

of the myocardial cellof the myocardial cell

normal

normal

low [K+]e

Threshold potential

repolarization prolonged

a.mus. v.mus.

2. Effects on autorhythmicity2. Effects on autorhythmicity

K channel conductance of the cell

membrane of the fast response autonomic

cells acceleration of spontaneous

diastolic depolarization, autorhythmicity

The Membrane Potential of Purkinje’s FiberThe Membrane Potential of Purkinje’s Fiber

3

4

0

1

2

4

max.diast.potential

normalnormal

hypokalemiahypokalemia

3. Effects on conductivity3. Effects on conductivity

Amplitude and rapidity of phase 0

depolarization smaller than normal

conductivity

Cardiac arrhythmias due to increased excitability, shortened ERP, prolonged

SNP, increased autorhythmicity and

decreased conductivity

The conducting system of the heartThe conducting system of the heart

a: effective refractory period; b: relative refractory period

c: supranormal period

RMP and AP of a Ventricular Muscle Cell of the HeartRMP and AP of a Ventricular Muscle Cell of the Heart

conductivity and cardiac arrhythmias

—— reentry of excitation

Schematic diagram showing reentry of excitation Schematic diagram showing reentry of excitation in a Purkinje’s fiber-ventricular muscle circuitin a Purkinje’s fiber-ventricular muscle circuit

(1) normal (2) conduction slowed down (3) monodirectional block

stalk stalk stalk

ventricular muscle ventricular muscle ventricular muscle

stalk stalk

branch A

branch B

ventricular muscle

conduction slowed down

monodirectional block

++(4)

Ventricular premature excitation resulted from reentry of excitation

action potential

monodirectional block

reentry of excitation

ECG

4.Effects on contractility4.Effects on contractility

increased in acute hypokalemia,

decreased in chronic hypokalemia

Effects on the KidneyEffects on the Kidney

functional and mosphological changes

Effects on MetabolismEffects on Metabolism

carbohydrate metabolism, protein metabolism, acid-base balance

Effects on the Nervous SystemEffects on the Nervous System

documented symptoms,

contradictory reports

Principles of Prevention and TreatmentPrinciples of Prevention and Treatment

Ⅰ . Measures against the causes

Ⅱ. Replacement therapy with potassium

1.Oral replacement: 40~120mmol of K/day

2.IV instillation: KCl≤40mmol/L, ≤10mmol

of K/h

Never inject! Never inject! Monitor serum [K+] and ECG

HyperkalemiaHyperkalemia

serum [Kserum [K++]>5.5mmol/L,]>5.5mmol/L,

a medical emergencya medical emergency


Inadequate excretion of K

Renal failure, hypoaldosteronism, K sparing diureticsRedistribution of K in the body

tissue injury, acidosis, insulin deficiency,

familial hyperkalemic periodic paralysis Increased intake of K—rapid IV K administration


Ⅰ.Effects on neuromuscular excitability In mild to moderate hyperkalemia the ratio

of [K+]i to [K+]e RMP less negative than normal, excitability abnormal sensibility (paresthesia), diarrhea

Severe hyperkalemia, RMP decreased to level of TMP, depolarization block muscle weakness, paralysis, dizziness, coma

Ⅰ.Effects on neuromuscular excitability

Ⅱ.Effects on the heart

1.Effects on excitability

In mild to moderate cases, excitability , phase 0 upstroke smaller and slower;

Phase 2 plateau prolonged, phase 3 repolarization shortened

In severe cases, no AP can be induced

cardiac arrest






2. Effects on autorhythmicity

K channel conductance ,

autorhythmicity




2. Effects on autorhythmicity

3.Effects on conductivity

a smaller and slower phase 0 upstroke

conductivity


Ⅰ.Effects on neuromuscular excitabilityⅡ.Effects on the heart 1.Effects on excitability 2. Effects on autorhythmicity 3.Effects on conductivity 4.Effects on contractility high serum [K+] inflow of [Ca2+] contractility


Ⅰ. Effects on neuromuscular excitability

Ⅱ. Effects on the heart

Ⅲ. Effects on acid-base balance

ECF [K+] secretion of insulin and aldosterone ECF [K+] shifted into cells while [H+] move out

ECF [K+] Na+-K+ exchange in renal distal tubules and secretion of H+

ECF [K+] renal NH4 production,

acid retention

metabolic acidosis

Effects on the BodyEffects on the BodyEffects on Acid-Base BalanceEffects on Acid-Base Balance

Principles of Prevention and TreatmentPrinciples of Prevention and Treatment

Restriction of K intake, control of

underlying diseases, insulin + glucose, use of

Ca2+ and Na+ to counteract K, bicarbonate

infusion, ion-exchange resin, dialysis