Transcript 7.hyperkalemia

(g) Exercise
Exercise can promote K shift out of cells
through:
(1) opening of ATP-dependent K+ channels
(2) decrease Na+ -K+ ATPase activity due to ATP
depletion.

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抄送：
邮件主题：病生问题求解
发件日期：Sun, 16 Mar 2008 00:44:38 +0800 (CST)
胡老师: 您好,我是您病生的一名学生.那天那个ATP-dependent
K channel的问题. 我觉得应是指该离子通道的开放或关闭依赖
于胞浆内ATP的浓度----- 低开高关; 而非指其消耗ATP.不然与通
道不耗能就矛盾了. 不知道想得对不对.望老师答疑.谢谢~
Work hard
Ability to analyse and solve problems
Ability to study independently
2
Exercise can promote K shift out of cells through:
(1) opening of ATP-dependent K+ channels
三种钾通道:
电压依赖型的钾离子通道
依赖钙离子的钾离子通道
KATP通道
主要受细胞内的ATP浓度调节。在生理条件下细胞内ATP浓度约
为3-4 mmol.L-1, KATP通道基本处于关闭状态。游离ATP是KATP通
道最强而有效的内源性阻断剂，只有当心肌细胞发生缺血缺氧，能
量耗竭，胞内ATP浓度低于0.2 mmol.L-1时通道开放，K+外流，

其主要功能有：
（1）舒张血管，包括外周血管和冠状动脉:主要由于KATP激活，
K+外流，细胞复极化加速，使动作电位时程缩短，Ca2+内流减少，
血管舒张。
(2)Ca2+内流减少，使心肌收缩力减弱，产生心脏保护作用。 ?
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Hyperkalemia
(1) Concept

Serum [K+]>5.5mmol/L is defined as hyperkalemia.

If the increase of serum [K+] is caused by the
movement of potassium from ICF to ECF, the
hyperkalemia does not mean potassium excess.

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(2) Causes and mechanism
1) Increased potassium intake
2) Decrease of renal excretion potassium
3) Increased movement of potassium from
cells to ECF
4) Blood concentration
5) Pseudohyperkalemia
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1) Increased potassium intake
Before the intravenous administration of KCl , we
must make sure that the renal function is good
enough to eliminate potassium.(见尿补钾)
Too rapid intravenous administration of KCl leads
to a severe incident, which is fatal.
It takes time (> 15 hours, longer in diseases) to get
the balance of [K+]e and [K+]i.
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Accidents
1982.08.17.<光明日报>. 湖南浏阳永和镇医院治
疗小儿腹泻.医生处方为:推NaHCO3溶液,滴KCl溶液.
护士错滴NaHCO3溶液,推KCl溶液,小儿死亡。
县法院以过失罪,判有缓刑考验期的有期徒刑。
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Transfusion of blood in stock
---------------------------------------------------------- period of stock
increase of plasma [ K+]
 -----------------------------------------------------------
2 weeks
4~5 times

3 weeks
10 times
 -----------------------------------------------------------
 (2)Infusion
of Penicillin Potassium
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Oral administration of potassium can rarely
cause fatal hyperkalemia.

Less absorption in gut.

Vomiting & diarrhea

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2) Decrease of renal excretion potassium
(a) Normally 90% of potassium is excreted from
kidneys.
In renal failure (GFR<15ml/min) , the
renal K+ excretion will decrease.
In acute RF : oliguria
In chronic RF: less functional nephrons
(compensation)
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anuria
The serum [K+] increases 0.7 mmol/L
per day with anuria, and 10 days later, the
patient with anuria
will die from
hyperkalemia.
No K intake ??
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
(b) Decreased secretion of
aldosterone leads to reduced
excretion of potassium.
Usually hyponatremia occurs
first.
If there is increased Na intake,
more Na+-K+ exchange will be in
distal tubules. (no hyperkalemia)
If there is no increased Na intake,
less Na+-K+ exchange will be in
distal tubules. ( hyperkalemia)
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(c) Some diuretics (e.g. spironolactone螺内酯, an
antagonist of aldosterone) inhibit the sodium
reabsorption and the secretion of K is reduced.
(d) Over-dose of digitalis(洋地黄)
suppresses the
Na+ - K+ ATPase, the excretion of
K+ reduce.
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3) Increased movement of potassium from
cells to ECF
(a) Acidosis results in the shift of potassium out of
the cells.

(b) Cell destruction often occurs with tissue
trauma, burn, rhabdomyolysis, lysis of tumor cells by
cytotoxic agents and hemolysis.

(c) Insulin deficiency ,hyperglycemia and acidosis
results in the decreased entry of K+ into the cells by
inhibiting Na+ - K+ ATPase.

(d) Low ATP production caused by hypoxia

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(e) Medicines
β
–receptor blokages (e.g. 心得安) blocks the
inward movement of K+ by inhabiting Na+-K+
ATPase,
relaxants increase the K+ permeability of
skeletal muscular cell membrane.
 Muscle
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4) Familiar hyperkalemic periodic paralysis is a rare genetic
disease, in which the serum [K+] is suddenly increased, so
the paralysis occurs.
5) Blood concentration
6)Pseudohyperkalemia may occur if the RBC destruction
happens during draw of blood for lab investigation.
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For example: traffic accident.
(1) Increased potassium production by more endogenous K.
(2) Decrease of renal excretion potassium
Bleeding leads to renal ischemia and then oliguria.
(3) Increased movement of potassium from cells to ECF
1) Tissue injury
2) Tissue hypoxia, less ATP production , pump
dysfunction.
3) metabolic acidosis
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(3) Effect on the body
1) Effect on the neuromuscular irritability
2) Effect on the heart
3) Effect on acid-base balance
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1) Effect on the neuromuscular
irritability (Biphasic)

In mild hyperkalemia
(<7mmol/L),

In hyperkalemia, the
difference between [K+]i and
[K+]e is decreased, the resting
membrane potential (RMP) is
less negative (partial
depolarization), which means
that a smaller stimulus will
evoke an action potential (AP).

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The excitability ( irritability) of skeletal
muscles is increased at first.
 The manifestation of skeletal muscle at first ,
is stabbing pain
 abnormal sensation ( too sensitive for pain)
mild tremor
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In severe stage
(>7~8mmol/L),
RMP<=TMP
depolarizative block
Na+ channel will not open.
The excitability is decreased to
disappear.
The excitability ( irritability)
of skeletal muscles is then
decreased at last. (Biphasic)
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




Manifestation:
muscle weakness
weak tendon reflex even disappear
flaccid paralysis弛缓性麻痹.
from limbs to trunk (respiratory muscle)
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The excitability
( irritability) of smooth
muscles of GI tract is
increased at first, then
decreased at last. (Biphasic)

It may be manifested
by diarrhea, intestinal colic
( abdominal pain) and
abnormal sensitivity
(paresthesia) at first, then
abdominal distension.
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2) Effect on the heart




2001.05.14<参考消息>:在美国执行死刑(用毒针):
先注硫喷妥钠,
溴化双哌雄双酯,
再注KCl.
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(a) A gradual increase of serum [K+] produces
biphasic sequences of excitability of myocardiac
cells.

An initial increase of excitability is followed by a
decrease. Cardiac arrest occurs in diastolid state.
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(b) Potassium permeability (K conductance 钾电导)
of membrane of myocardiac cells is increased, which
accelerates the repolarization.

Shortening of refractory period
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②The conductivity of myocardiac cell
is reduced.
The rate and range of depolarization is reduced in
hyperkalemia, because the RMP is near the TMP.

The most dangerous to the body is severe heart
blocking and cardiac arrest.
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(c) The autorhythmicity is decreased,
because the membrane permeability to
potassium is increased, the outward
potassium current is increased and the
inward sodium current is relatively
decreased.
The autorhythmicity of sinoatrial node
in reduced, there will be progressive sinus
bradycardia even cardiac arrest may occur.
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Summary of the effect on the myocardiac
cells
The excitability is increased.
 Shortening of refractory period
 The conductivity is reduced.
 The autorhythmcity is reduced, sinus bradycardia
 All make it easy to form reciprocal excitation (折返
激动) and ventricular fibrillation (心室颤动).
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(d) The contractivity is reduced due to
decreased intracellular calcium.

The high [K+]e inhibits the inward
flow of calcium.

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(e) Changes of ECG
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T wave is peaked and tent-shaped because phase
3 is accelerated due to rapid outward of potassium
([K+]=6~7mmol/L).

P wave is prolonged and eventual disappear due
to the decreased conductivity and excitability in atrium
([K+]=8mmol/L).

QRS complex is widened due to the decreased
conductivity in ventricle ([K+]=10mmol/L).

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P-Q (P-R) interval 间期
 Short Q-T interval
 Prolonged
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ECG in ?
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Multiple factors can alter the effect of
hyperkalemia on the heart.

If the hyperkalemia develops slowly, the
cardiac manifestation is minimal.

If there are some other electrolytes
disturbances at the same time, the cardiac
manifestation will change.

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 3)
Effect on acid-base
balance
 (a)
extracellular acidosis and
(b) unusual alkalinuria.
(a) When [K+] of ECF is increased in
hyperkalemia, the K+ of ECF moves into the
cells, at the same time the H+ in IEF moves
into the ECF for electric neutrality. Then the
[H+] in ECF will be increased.
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Mechanism:
 (b)
unusual alkalinuria.

There are two kinds of ion exchange, K+-Na+
and H+-Na+ , in renal tubules.

In hyperkalemia, the K+--Na+ exchange is
increased, the H+--Na+ exchange will decrease, so
the excretion of H+ from kidneys is reduced,
which leads to and basic (alkaline) urine.
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Usually in acidosis, the elimination of H+ is
increased from kidneys, and the urine should be
acidic.

But in the acidosis caused by hyperkalemia,
the urine is alkaline, it is unusual, so it is called
unusual alkalinuria.
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(4) Principle of treatment
 1)
Complete restriction of exogenous

potassium intake.
 2) Control of the underlying disease

(etiologic treatment)
 3) Transport of the serum K+ into cells
(a) Administration of insulin and glucose to
transport the potassium from ECF into the cells.

(b) Bicarbonate infusion (alkaline solution)
can drive the potassium into the cells.
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4) Increase the elimination of potassium
(a) A sodium polystyrene sulfonate resin 聚苯乙
烯磺酸钠树脂 is used to remove potassium from
colon. (Na+-K+ exchange)
 (b) Peritoneal dialysis
 (c) Hemodialysis

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Peritoneal Dialysis
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Hemodialysis
• Blood is circulated through artificial cellophane
membrane that permits a similar passage of water and
solutes
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(5)Protection of cardiac cells
A increased [Ca2+]
may raise the threshold
potential, which may
reestablish the difference
between the resting and
threshold potential and
restores the excitability.
 (10% calcium gluconate
葡萄糖酸钙)

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Na+ will increase the inward sodium
current in phase 0 (depolarization) to increase the
excitability of heart muscle.

11.2% sodium lactate 乳酸钠
 A increased
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