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Section III.Disturbance of Potassium Balance Potassium Balance

(1) Content and distribution

(2) Function of potassium

(3) Regulation of K+ balance

Hypokalemia

Hyperkalemia

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1. Potassium Balance(1) Content and distribution

  The adult body contains about 45 mmol/Kg of BW. About 98% of potassium is within the cells, [K +] i= 140~160 mmol/L. About 2% of K + is in the ECF, [K +]e = 3.5~5.5 mmol/L. 3/4 of the intracellular K+ is in muscle cells.

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There are two forms of existence:

(1) free state of potassium, K+,

(2) the K combining to protein and glycogen.

Both are exchangeable.

(Na+)

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(2) Function of potassium

1) Metabolism

2) Membrane potential

3) Regulation of pH

4) Osmotic pressure of ICF

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1) Metabolism

(a) K+ is required for the activity of some intracellular enzymes e.g. the enzyme for ATP production.

(b) K+ is involved in anabolism.

1 g of glycogen contents 0.33~0.45 mmol,

The K+ moves into cells with glucose, during the synthesis of glycogen.

1 g of protein needs 30 mmol of K+.

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2) Membrane potential

The ratio of the intracellular to the extracellular potassium concentration ([K+]i∕[K+]e) constitutes the cellular resting membrane potential. Minimal change of [K+]e may affect the membrane potential obviously. K+ is important for normal neuromuscular irritability.

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3) Regulation of pH

Exchange of K+ and H+ crossing the cell membrane is important for acid-base balance. Changes of K+ concentration will lead to the changes of pH. When K+ moves out of the cells, H+ will move into the cells as an exchange for electrical neutrality. More H+ will lead to acidosis.

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4) Osmotic pressure

Potassium ion is the major intracellular cation, so K+ is important in the formation of osmotic pressure in the cell. To keep the volume of ICF.

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(3) Regulation of K+ balance

1) Equilibrium of K+ in ICF and ECF

2) Balance of intake and excretion

K excretion in kidney

K excretion in colon

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1) Equilibrium of K+ in ICF and ECF (transcellular potassium movement)

Equilibrium means to keep

[K+]i= 140~160 mmol/L;

[K+]e = 3.5~5.5 mmol/L

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Significance : After intake a bottle of orange juice (40 mmol/L of K+),

if all K+ stays in ECF, the [K+]e=4.5+2.4=6.9 mmol/L, which will lead to abnormal ECG. Abnormal ECG means the heart muscle is injured.

If all K+ is transported into ICF, the [K+]i=160+1.2=161.2 mmol/L.

Then the excessive K+ will be eliminated within several hours in the urine.

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Mechanism to keep the equilibrium:

The basic mechanism to the balance is “leak and pump”.

(Integrity of cell membrane and function of Na+-K+ pump)

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细胞内液细胞内液 [[KK++]]

140140 －－ 160mmo1160mmo1 ／／ LL

K+细胞内外移动的泵一漏机制（ Pump － leak mechanism ）

细胞外液细胞外液 [[KK++] ]

4.2mmol/L4.2mmol/L

钾的跨细胞转移调节钾的跨细胞转移调节

K+ K+

K+ 通道（漏）

Na+ Na+

K+ K+

Na+ - K+ 泵（泵）

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【影响钾的跨细胞转移的主要因素】

ECF [K+] 4.2mmol/L

ICF [K+]

140 － 160mmo1 ／L

钾代谢紊乱钾代谢紊乱

ECF [K+]

酸碱平衡状态

ECF [H+]↑ ， H+ 入细胞内，细胞内K+ 外移。 ECF 每 0.1 pH 变化大约引起0.6mmol/L 血清钾变化

ECF 渗透压↑ ↑ ，使细胞内 K+ 外移。渗透压

运动

可直接刺激 Na+ － K+ 泵活性，影响钾转移主要激素。

胰岛素 肾上腺素通过 cAMP 机制激活 Na+ － K+

泵活性，肾上腺能神经激活是促 K+ 自细胞内移出。 儿茶酚胺

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(a) Changes of pH

A decrease in pH of 0.1 units usually elevates the serum [K+] by about 0.6 mmol/L.

(alkalosis: pH ↑ 0.1, [K+] ↓ 0.6 mmol/L)

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(b) Extracellular K+ concentration

  A high [K+]e will stimulate the activity of Na+-K+ pump.

A low [K+]e will do in the converse way. 

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(c) Total K quantity in the body

When the total quantity of K in the body reduces, the loss of intracellular K+ is more than extracellular K+, but the ratio of extracellular K+ loss is more than intracellular K+ loss.

When the total quantity of K in the body increases , the increase of intracellular K+ is more than extracellular K+, but the ratio of extracellular K+ increase is more than intracellular K+ increase.

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(d) Regulation of hormone

Insulin promotes the movement of K+ into the liver cells and skeletal muscle cells by increasing sodium-potassium ATPase activity.

The β-adrenergic agonists also elevate Na+ -K+ pump activity to enhance K+ entry.

The α-adrenergic agents enhance the K+ transport out of cells.

Epinephrine stimulates α-recepter first,then β-recepter. (K+ )

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(e) Metabolism(anabolism; catabolism)

Increased anabolism (AA protein, glucose glucogen) elevates the [K+]i.

Increased catabolism (protein AA, glucogen glucose) reduces the [K+]i.

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f) Increased smotic pressure of ECF leads to increased [K+]e.

Increased osmolality of extracellular fluid draws the water out of cells with K+.

Decreased water in the cells elevates the [K+]i. The difference [K+]i and [K+]e increases, which leads to the shift of K+ out of cells increases.

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(g) Exercise

Exercise can promote K shift out of cells through:(1) opening of ATP-dependent K+ channels 与电压依赖型的钾离子通道不同，也与依赖钙离子的钾离子通道不

同，， 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。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，

游离 ATP 是 KATP 通道最强而有效的内源性阻断剂，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，降低心肌氧耗，产生心脏保护作用。

(2) decrease Na+ -K+ ATPase activity due to ATP depletion.

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(h) Integrity of cellular membrane

“Leak” indicates the moving of K+ out of the cell according to the gradient of [K+ ] between ICF and ECF, without expending ATP.

Leaking leads to the tendency to reduce the [K+]i. When the cell membrane is injured, the permeability of cell membrane to K+ is increased. More K+ move from cells into ECF.

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2) Balance of intake and excretion

(a) Intake: The common foods, like lean meat, milk and fruits content a lot of potassium. The average diet contains 60~100 mmol of potassium per day, which is enough for the daily body requirement. 90% of potassium in food is absorbed in small intestine.

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(b) Excretion

① Via kidney

About 90% or more potassium is eliminated from kidney. (12 字 )

The more K we eat, the more K is eliminated from kidneys. When the intake of potassium is decreased, the elimination from urine is decreased.

If no potassium intake, the kidneys will still secrete small amount of potassium (20~15 mmol/day). (Na+?)

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Potassium is freely filtered at the glomerulus. Almost all the potassium filtered is reabsorbed in proximal tubules via active transport. In loop of Henle: via Na+-K+-2Cl- contransporter. Most of the potassium in the urine is secreted from distal tubules and collecting ducts. No decrease of K+ filtration except severe reduction of GFR.

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(C)Regulation of renal loss in renal distal tubules and collecting ducts,

a) aldosterone Aldosterone activates

pump (Na+ /K+ pump) in basolateral membrane, the K+ transport from peritubular interstitial fluid into renal tubular cells will increase. Aldosterone increases the permeability of lumenal membrane, the K+ transport from renal tubular cells into tubules (urine) will increase.

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b) High [K+]e

High [K+]e activates pump (Na+ /K+ pump) in basolateral membrane, the K+ transport from peritubular interstitial fluid into renal tubular cells will increase.

High [K+]e increases the permeability of lumenal membrane, the K+ transport from renal tubular cells into tubules (urine) will increase.

High [K+]e decreases the [K+] difference between renal tubular cells and peritubular interstitial fluid, then decrease the back-flow of K+ from tubule.

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c) Volume and flow rate of urine in distal tubules and collecting ducts

Increased volume and flow rate of urine in distal tubules and collecting ducts reduce the [K+], increase the difference between the [K+] in urine and in tubule cells, increase the excretion of K.

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d) Acid-base balance

In acute acidosis, increased [H+] suppresses Na+-K+-ATPase, and the excretion of K+ decreases.

In alkalosis the excretion of K+ increases.

In chronic acidosis, the dominant effect is that increased [H+] suppresses the reabsorption of water and sodium in proximal tubule cells, urine volume increases, excretion of K+ increases.

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e) Electric field

If more negative charges in tubular fluid, more K+ will be excreted.

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② Via intestinal tract K excretion in colon

10% of K is excreted through the colon. The epithelial cells are just as the principal cells in the collecting duct, and affected by aldosterone.

K+ excretion via colon will increase in renal failure.

GFR↓↓↓ GFR↓↓↓ K excretion in colon to 1/3 of intake .

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③ Via sweating

Generally speaking, the loss of K+ with sweat is neglectful (5~10 mmol/L). This kind of loss may be significant some time (in plenty of sweat).