Transcript K +

Potassium Balance and
Potassium Imbalance
Part Ⅰ
Potassium Balance
Ⅰ Content and Distribution of
Potassium in the Body
Ⅱ Intake and Excretion of Potassium
Dietary K intake
Serum [K+] round 4.5mmol/L
70~100mmol/day
ECF 2%
K+
ICF
[K+] 160mmol/L
Excretion
98% of the total
body potassium
Total body
K content
31~57mmol/Kg
body weight
Skin trivial normally
Colon 10%
Kidneys > 80%  More ingested, more excreted
 Less ingested, less excreted
 Not ingested, excretion goes on
Content, distribution, intake and excretion of K
Ⅲ Maintenance of Potassium Homeostasis
—Distribution of K+ across the cell
membrane and Regulation of renal
K+ excretion
Distribution of Potassium across
the Cell Membrane
The Na+/K+ATPase membrane pump
and permeability of ion channels
Influencing Factors
1.Hormones — insulin, glucagon,
catecholamines, thyroid hormone
2.Serum
K+
Na+/K+ATPase
[K+]
[K+]↑
Catecholamine
3.pH of ECF and plasma
osmolality
4.Others — rate of cell breakdown,
hypoxia, hypothermia, exercise
Na+
Insulin
K+
H+
Regulation of Renal Potassium Excretion
 Filtration,
Cl- and secretion
reabsorption
of potassium
Na+/K+ATPase(
Mg2+ activated)
The nephron and collecting tubule
Na+/K+ATPase
H+- K+ ATPase
Regulation of Renal Potassium Excretion
 Filtration,
reabsorption and secretion
of potassium
 Secretion of potassium in the distal and
collecting tubules
principal cells, with Na+/K+ATPase
membrane pump, for secretion of K+
lumen
blood
Na+
Cl-
Na+
K+
ClK+
K+
Principal Cell
CO2
H+
K+
CO2
HCO3Cl-
Intercalated Cell
Cl-
Regulation of Renal Potassium Excretion
 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+
Regulation of Renal Potassium Excretion

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 K+ by
the Distal and Collecting Tubules
— activates Na+/K+ATPase,
increase membrane permeability to K
 [K+] in the ECF
 Flow rate of tubular fluid in the distal tubule
 pH of ECF —↓pH inhibits Na+/K+ATPase
 Aldosterone
Factors Influencing Excretion of K+ by the
Distal and Collecting Tubules
lumen
+
Na+
Na+
Cl-
+
flow rate
+
ClK+
K+
+
[K+ ]↑
K+
CO2
HCO3-
+
Ald
K+
+
①
②
③
Principal Cell
H+
blood
Cl-
Intercalated Cell
CO2
Cl-
[H+ ]↑
+
Maintenance of Potassium Homeostasis
 Distribution
of potassium across the cell
membrane

Regulation of renal potassium excretion

Excretion of K by the Colon also controlled
by aldosterone
Function of Potassium in the Body
 The
part
K+
Ⅳ
plays in metabolism
 Maintenance
of the resting membrane
potential
of excitable
cells in the Body
Function
of Potassium
 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
Etiology and Pathogenesis
Dietary intake
Serum [K+] < 3.5mmol/L
ECF 2%
Excessive losses
shifting
ICF
[K+] may or may
not be decreased
Total body
K content
— decreased
(K deficit)
or
— normal
G.I losses---diarrhea, vomiting
Renal losses---diuretics, some diseases of the kidney
Losses from the skin---profuse sweating, burns
Crude cotton seed oil poisoning
Etiology and Pathogenesis
Ⅰ. Inadequate Intake
anorexia,
inability to eat,
Ⅱ. Fasting,
Excessive
Losses
prolonged IV alimentation
without K
1.Gastrointestinal
losses
supplementation,
alcoholism
Vomiting
→mainly
increased
excretion
Diarrhea
→extrusion
of largerenal
amount
of
+ due to metabolic alkalosis caused by
of
K
alkaline liquid stool with a high content
loss
of gastric
acid,acidosis,
contraction
ECF
of K→K
depletion,
ECFofvolume
volume
contraction →↑secretion of aldosterone
Etiology 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↑
Regulation of Renal Potassium Excretion
ClNa+/K+ATPase
Na+/K+ATPase(
Mg2+ activated)
The nephron and collecting tubule
H+- K+ ATPase
Etiology and Pathogenesis
Ⅰ. Inadequate Intake
Ⅱ. Excessive Losses
1.Gastrointestinal losses
2.Excessive renal losses
(1) Diuretics
(2) Some diseases of the kidney
Renal tubular acidosis
Excessive Renal Losses
(1) Diuretics
(2) Some diseases of the kidney
Renal tubular acidosis
Diuretic recovery phase of acute renal failure
(3) Antibiotics
(4) Excess of adrenocortical hormones
Aldosteronism, Cushing’s syndrome
(5) Magnesium deficiency
Regulation of Renal Potassium Excretion
ClNa+/K+ATPase
Na+/K+ATPase(
Mg2+ activated)
The nephron and collecting tubule
H+- K+ ATPase
Case Report
A female patient, 42 years old, was admitted to the affiliated
hospital of the Sichuan Med.College as an emergency case on
April 4 1978, with a chief complaint of decreased food intake,
nausea and frequent vomiting for 20 days. She had a history of
diabetes mellitus for 3 years.
Diagnosis: Diabetic ketoacidosis, which is a medical emergency.
She was treated with insulin, with success. She was also found to
have infection of the urinary tract as well as severe hypokalemia
(the serum [K+] was around 2mmol/L). Therefore she was
given large doses of gentamycin for 33 days. KCl was also
administered, both by mouth and IV instillation, in large doses,
for 41 days. However, hypokalemia persisted (2.55mmol/L).
To the surprise of the doctor, the patient suddenly developed
spastic rigidity of the limbs. It was until then, 41days after
admission, the doctor examined the serum [Mg2+], it was very
low:0.2mmol/L!(The normal range of serum [Mg2+] being
1.5~2.5mmol/L). IV MgSO4 was immediately given, and also
for several days, with complete success! The doses of KCl was
reduced, however, the serum [K+] rose to normal levels within
3 days! Serum [Mg2+] also turned normal. No adverse
reactions.(《中华内科杂志》1980年1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
(2) Some diseases of the kidney
Renal tubular acidosis
Diuretic recovery phase of acute renal failure
(3) Antibiotics
(4) Excess of adrenocortical hormones
Aldosteronism, Cushing’s syndrome
(5) Magnesium deficiency
(6) Alkalosis
Etiology and Pathogenesis
Ⅰ.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 Pathogenesis
Ⅰ.Inadequate Intake
Ⅱ.Excessive Losses
Ⅲ.Shifting of K+ from the
ECF to ICF
1.Overdose of insulin
2.-adrenergic agonist
overdose
K+
Na+/K+ATPase
Na+
Albuterol
Insulin
K+
H+
Etiology and Pathogenesis
Ⅰ.Inadequate Intake
Ⅱ.Excessive Losses
Ⅲ.Shifting of K+ from the ECF
to ICF
1.Overdose of insulin
2.-adrenergic agonist overdose
3.Alkalosis
4.Barium poisoning
5.Familial hypokalemic periodic
paralysis
K+
Na+/K+ATPase
Na+
Albuterol
Insulin
K+
H+
Etiology and Pathogenesis
Ⅰ.Inadequate Intake
Ⅱ.Excessive Losses
Ⅲ.Shifting of K+ from the ECF to ICF
Crude Cotton Seed Oil poisoning
Effects 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 Excitability
Nernst equation
Em= -60lg[K+]icf / [K+]ecf (mv)
+35
Millivolts
0
-60
Threshold
-90
Milliseconds
The Resting Membrane Potential (RMP) and Action Potential
(AP) of a skeletal muscle cell in the normal state
Acute Hypokalemia
[K+]i / [K+]e ↑
RMP more negative than normal
hyperdepolarization block, excitability↓
muscle weakness, flaccid paralysis,
smooth muscle symptoms
mv
30
0
Action potential (AP)
-30
-60
TMP
-90
RMP
-120
Normal
Low [K+]
High [K+]
The effects of serum K+ concentration
on cellular membrane excitability
Chronic Hypokalemia
ratio of [K+]i to [K+]e may be normal,
RMP and excitability unchanged, interfering
with cellular metabolism and vasodilation of
muscles during exercise
Effects on the Heart
A Brief Review of the Bioelectric
Phenomena of the Heart
RMP and AP of a Ventricular Muscle Cell of the Heart
a: effective refractory period;
b: relative refractory period
c: supranormal period
The Membrane Potential of Atrial Muscle,
and Purkinje’s Fiber
40
+20
Purkinje’s fiber
Atrial muscle
1
1
2
2
0
-20
40
0
3
0
3
60
80
100
4
RMP
4
4
4
max.diast.potential
1.Effects on excitability
RMP<-90mv, excitability
Ca2+ inflow
plateau, ERP shortened
Phase 3, SNP prolonged
AP prolonged
normal
low [K+]e
a.mus. v.mus.
Threshold
potential
repolarization
normal
prolonged
Effects of low serum [K+] on the action potential
of the myocardial cell
2. 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 Fiber
1
2
normal
0
4
max.diast.potential
3
hypokalemia
4
3. 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 heart
RMP and AP of a Ventricular Muscle Cell of the Heart
a: effective refractory period;
b: relative refractory period
c: supranormal period
conductivity and cardiac arrhythmias
—— reentry of excitation
(2) conduction
slowed down
(1) normal
stalk
stalk
ventricular muscle
stalk
ventricular muscle
stalk
(3) monodirectional block
stalk
branch A
branch B
monodirectional block
ventricular muscle
Ventricular premature
excitation resulted from
reentry of excitation
action potential
ECG
ventricular muscle
(4) conduction
slowed down
+
monodirectional
block
reentry of excitation
Schematic diagram showing reentry of excitation
in a Purkinje’s fiber-ventricular muscle circuit
4.Effects on contractility
increased in acute hypokalemia,
decreased in chronic hypokalemia
Effects on the Kidney
functional and mosphological changes
Effects on Metabolism
carbohydrate metabolism, protein
metabolism, acid-base balance
Effects on the Nervous System
documented symptoms,
contradictory reports
Principles 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! Monitor serum [K+] and ECG
Hyperkalemia
serum [K+]>5.5mmol/L,
a medical emergency
Etiology and Pathogenesis
 Inadequate
excretion of K
Renal failure, hypoaldosteronism, K sparing
diuretics
 Redistribution of K in the body
tissue injury, acidosis, insulin deficiency,
familial hyperkalemic periodic paralysis
 Increased intake of K—rapid IV K
administration
Effects on the Body
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
Effects on the Body
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;
In severe cases, no AP can be induced
cardiac arrest
Phase 2 plateau prolonged, phase 3
repolarization shortened
Effects on the Body
Ⅰ.Effects on neuromuscular excitability
Ⅱ.Effects on the heart
1.Effects on excitability
2. Effects on autorhythmicity
K channel conductance ,
autorhythmicity
Effects on the Body
Ⅰ.Effects on neuromuscular excitability
Ⅱ.Effects on the heart
1.Effects on excitability
2. Effects on autorhythmicity
3.Effects on conductivity
a smaller and slower phase 0 upstroke
conductivity
Effects on the Body
Ⅰ.Effects on neuromuscular excitability
Ⅱ.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
Effects
Effects
on on
Acid-Base
the BodyBalance
ECF [K+]
secretion of insulin and
Ⅰ.
Effects
on
neuromuscular
excitability
+
aldosterone
ECF [K ] shifted into cells
+] move out
while
[H
Ⅱ. Effects on the heart
 ECF [K+]
Na+-K+ exchange in renal
Ⅲ. Effects on acid-base balance +
distal tubules and secretion of H
 ECF [K+]
renal NH4 production,
acid retention
metabolic acidosis

Principles 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