Renal handling of potassium ion

Question 1

Define the key elements to whole body potassium balance - effect on RMP, effect on ECG

Answer 1

effect on ECG

Note: In hypokalemia high U wave + T waves appear as QT prolongation

Hyperkalaemia in serum potasssium can result in ventricular fibrillation

Question 2

Functions of K+

Answer 2

Regulation of Cell volume
Regulation of intracellular pH
Synthesis of DNA, Protein growth
Enzyme function
Maintain RMP
Cardiac and Neuromuscular activities

Question 3

Potassium’s distribution between body compartments.

Answer 3

ECF : 3.5-5 mEq/L
ICF : 140-150 mEq/L
Serum potassium = 4-5 mEq/L

Question 4

Values of hyperkalaemia and hypokalaemia?

Answer 4

Hyperkalemia: ECF [K+]> 5.0 mEq/L
Hypokalemia: ECF [K+]<3.5 mEq/L

Question 5

Why is it critical for excitability of nerve and muscle cells?

Answer 5

High K+: Effect diastolic depolarization Phase. Inactivates fast Na channels

Low K+ Reduces excitability

Hyperkalemia causes the membrane potential to become less negative which decreases excitability by inactivating the fast sodium channels responsible for depolarizing phase of the action potential.

Hypokalemia hyperpolarizes the membrane potential & thereby reduces excitability.
So Consider,
If T wave is high: hyperkalemia, acute MI
T wave too small: hypokalemia, hypothyroidism, pericardial effusion. It is important to remember that it causes aappearance of U wave immediately after the T wave and may combine and contribute to the impression of QT prolongation.
Cardiac Arrhythmias are produced both by hyperkalemia & hypokalemia.

Question 6

Overview of K+ Homeostasis

Answer 6

Total Body K+= 3500 mEq
(In a 70 kg man)
2% located in ECF ie: 65-70 mEq

diet = 100 mEq intake/day

intestinal absorption = 90

ECF = 65 ; tissue stores 3435 (insulin, ep, aldosterone)

excretion from ECF in urine 90-95 mEq per day, by ADH, aldosterone

feces 5-10 mEq of K+/day

Question 7

K+ intake by

Answer 7

epinephrine
aldosterone
insulin

Question 8

Describe the causes of hypokalaemia.

Answer 8

1. Inadequate intake
   - inability to obtain or ingest food
   - Diet deficient in potassium
2. Excessive renal, gastrointestinal and skin losses
   - Diuretic therapy (thiazide and loop diuretics)
   - Increased aldosterone level (primary aldosteronism, stress-cortisol)
   - Increase sweating, vomiting and diarrhea
3. Transcellular shift
   - Administration of insulin (to treat diabetic ketoacidosis)
   - β-adrenergic agonist—-albuterol (bronchodilator)
   - Alkalosis

Question 9

Describe the effects of hypokalaemia.

Answer 9

1. Neuromuscular manifestations
   - Muscle flabbiness, weakness and fatigue
   - Muscle cramps and tenderness
   - Paresthesia and paralysis
2. Impaired kidney’s ability to concentrate the urine
   - polyuria, urine with low osmolality, polydipsia
3. Gastrointestinal manifestations
   - Anorexia, nausea, vomiting,
   - Constipation, abdominal distension, paralytic ileus
4. Cardiovascular manifestations
   - Arrhythmias, increased sensitivity to digitalis toxicity
5. Metabolic alkalosis (Mainly)

Question 10

Describe the causes of hyperkalaemia

Answer 10

1. Decreased renal elimination
   -Decreased renal function-renal failure
   -Treatment with potassium-sparing diuretics (Spironolactone - Aldosterone antagonist : Retains K+ in body)
   -Decreased aldosterone level
   [Adrenal insufficiency (Addison’s disease),
   Treatment with ACEI,
   Angiotensin II receptor blocker)
2. Movement of potassium from the ICF to ECF
   - Tissue injury such as burns and crushing injuries
   - Extreme exercise or seizures
   - Acidosis

Question 11

Describe the effects of hyperkalaemia

Answer 11

1. Gastrointestinal manifestations
   Anorexia, nausea, vomiting, intestinal cramps, diarrhea
2. Cardiovascular manifestations
   Ventricular fibrillation and cardiac arrest
3. Neuromuscular manifestations
   P- aresthesia (seen often in stroke survivors, brain injury patients)
   Weakness, tiredness (Seen in our case)
   Muscle cramps
4. Pronounced metabolic acidosis (Mainly)

Question 12

Describe the renal tubular handling of potassium.

Answer 12

Excretion = Intake; even when intake is as much as 10 fold

Overall excretion determined by DT and CCD

5%-10% of dietary K+ is lost through feces & Sweat: Is not regulated well

Cant reduce excretion as low as Na+ (0.2%)

Question 13

Mechanisms of Tubular K+ handling

Answer 13

Late PCT: passive paracellular reabsorption

Thick ascending LoH:
Mechanisms of Tubular K+ handling
+ loop diuretic sensitive, Na-K-2Cl cotransporter

DCT = principal cells = Type B intercalated cells => K+ secretion into lumen by fd, Na+ into cell by fd, Na-K ATPase brings in K+ first and Na out further.

Type A intercalated cells - reabsorb K+ by HKE in hypokalemia

Question 14

Cellular Mechanism of K+ secretion by Principal cells in DT & CD

Answer 14

Secretion prefers the Apical membrane Channel route rather than Baso lateral one

the rate of secretion of K+ by DCT & CCD cells: Na-K-ATPase –> ECG –> Kpermeability by fd

Question 15

**

Physiological Factors: (K+ uptake)

Answer 15

Acute stimulation: Insulin (Most Important) Adrenaline: (α- In release); β2 (Uptake)

Chronic Stimulation: Aldosterone

Question 16

Patho Physiological Factors Displacing K+ between compartments

Answer 16

1. Acid Base Balance
2. Plasma osmolality
3. Cell lysis
4. Exercise
5. ACIDOSIS => too much H+ in plasma, so H-K exchanger => leads to hyperkalaemia

ALKALOSIS => too less H+ in plasma, so H-K exchanger => leads to hypokalaemia

AND VV. hyperkalaemia => acidosis and
hypokalaemia => alkalosis

2. If ECF plasma osmolality increases, water out of cell, ICF K+ increases, so K+ moves out of cell through K+ channels = ECF K+ increased.
3. cell lysis in burns, rhabdomyolysis, chemotherapy
4. walking - 0.3 mEq/L ; vigorous exercise 2.0 mEq/L

Question 17

Exercise could be Life threatening:

Answer 17

a) Endocrine disorders b) Renal Failure

c) Certain Medications ( β2 adrenergic Blocker)

Question 18

Control of K+ secretion:
1. Increased plasma [K+]

2. Chronically elevated plasma Aldosterone
3. Urine Flow Rate (Pathophysiological factor)

Answer 18

↑ plasma K = ↑ intracellular K = ↑ Gradient across apical
membrane = K+ secreted by ICTypeA cell.

Hyperkalemia stimulates =
Na-K ATPase activity;
Permeability;
Aldosterone;
Flow rate of tubular fluid

2. Chronically elevated plasma Aldosterone

eg. Spironolactone (Aldosterone antagonist)
Retains K+ in body

aldosterone causes increased K+ permeability and leads to excretion of K+

3. Urine Flow Rate (Pathophysiological factor)

Increase in flow rate => INCREASES CILIA BENDING. => Ca2+ enters, Na+ enters => Increases K+ Gradient for K+ exit

Vm= Membrane Voltage & reduction of which increases the electrochemical driving force for K+

Question 19

K+ excretion by

Answer 19

aldosterone

ADH

Question 20

Acute and Chronic effect of Metabolic acidosis on K+ excretion

**Describe the control of renal potassium excretion.

Answer 20

acute:
DCT and CT-Principal cells = decrease K+ excretion

chronic:
skeletal muscle cell + PCT cell => increase aldosterone => DCT and CT PC => K+ excretion increase