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(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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收件人： huweicheng@sdu.edu.cn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 hardAbility to analyse and solve problemsAbility to study independently

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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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(d) Over-dose of digitalis( 洋地黄 ) suppresses the Na+ - K+ ATPase, the excretion of K+ reduce.

(c) Some diuretics (e.g. spironolactone 螺内酯 , an antagonist of aldosterone) inhibit the sodium reabsorption and the secretion of K is reduced.

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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,

Muscle relaxants increase the K+ permeability of skeletal muscular cell membrane.

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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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Prolonged P-Q (P-R) interval 间期 Short Q-T interval

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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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A increased 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