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Physiology

Renal

Question 8 of 180

Where in the nephron is most K+ reabsorbed:

Answer:

Approximately 65 - 70% of filtered K+ is reabsorbed in the proximal tubule.

Potassium Handling

Potassium is the major intracellular cation. The potassium concentration inside cells is around 150 mmol/L, compared with around 4 mmol/L (3.0 - 4.5 mmol/L) in extracellular fluid. The K+ gradient across the cell membrane largely determines the electrical potential across that membrane. As this electrical potential influences the electrical excitability of tissues such as nerves and muscles, including the cardiac muscle, potassium levels must be precisely controlled within safe limits.

The average daily intake of potassium in the diet is around 40 - 120 mmol, but the kidney filters around 800 mmol each day. To maintain potassium balance, the kidney therefore excretes only 5 - 15% of the filtered potassium. Potassium is freely filtered in the glomerulus, almost entirely reabsorbed before the filtrate reaches the collecting tubules, and is then secreted into the collecting duct before being excreted in urine.

Renal Potassium Handling

K+ is freely filtered at the glomerulus.

Proximal tubule:

Approximately 65 - 70% of filtered K+ is reabsorbed in the proximal tubule. Potassium reabsorption is tightly linked to that of sodium and water. The reabsorption of sodium drives that of water, which may carry some potassium with it. The potassium gradient resulting from the reabsorption of water from the tubular lumen drives the paracellular reabsorption of potassium and may be enhanced by the removal of potassium from the paracellular space via the Na+/K+ ATPase pump. In the later proximal tubule, the positive potential in the lumen also drives the potassium reabsorption through the paracellular route.

Loop of Henle:

Some K+ moves into the filtrate in the thin descending limb of the loop of Henle, but this is counterbalanced by movement of K+ out of the loop and into the medullary collecting ducts. The net result is some recycling of this potassium across the medullary interstitium. Around 30% of filtered K+ is reabsorbed in the thick ascending limb of the loop of Henle, primarily via the luminal Na+/K+/2Cl- cotransporter, but there is also significant paracellular reabsorption, encouraged by the positive potential in the tubular lumen.

Distal tubule:

The distal tubule can reabsorb more potassium and 95% of filtered K+ is reabsorbed in a sodium-dependent fashion before the filtrate reaches the collecting ducts.

Collecting tubule and ducts:

In the distal nephron, the principal cells secrete potassium, whereas the intercalated cells reabsorb potassium; potassium secretion far outweighs its reabsorption in this part of the nephron, and it is here that regulation of potassium excretion primarily occurs (mainly as a result of changes in potassium secretion by the principal cells).

Reabsorption of K+ by intercalated cells is driven by the apical H+/K+ ATPase pump; K+ leaves these cells through basolateral potassium channels.

Secretion of K+ by principal cells is driven by the basolateral Na+/K+ ATPase pump; K+ is secreted into the lumen through apical K+ channels or via K+/Cl- cotransporters down a concentration gradient. The negative potential in the tubular lumen due to Na+ reabsorption also promotes K+ secretion (thus increased sodium reabsorption promotes potassium secretion). As potassium secretion is occurring down a concentration gradient, it can continue only if the concentration of potassium in the filtrate is kept low, hence an increased tubular flow rate results in increased K+ secretion and excretion (seen in hypokalaemia secondary to diuretic therapy).

Control of Renal Potassium Excretion

  • Aldosterone: A rise in [K+] in the extracellular fluid of the adrenal cortex directly stimulates aldosterone release. Aldosterone promotes the synthesis of Na+/K+ ATPases and the insertion of more Na+/K+ ATPases into the basolateral membrane, and also stimulates apical sodium and potassium channel activity, overall acting to increase sodium reabsorption and potassium secretion.
  • pH changes: Potassium secretion is reduced in acute acidosis and increased in acute alkalosis. A higher pH increases the apical K+ channel activity and the basolateral Na+/K+ ATPase activity – both changes that promote K+ secretion.
  • Flow rates: Increased flow rates in the collecting duct reduce K+ concentration in the lumen and therefore enhance K+ secretion. Increased flow also activates BK potassium channels, and ENaC channels which promote potassium secretion and sodium reabsorption respectively.
  • Sodium delivery: Decreased Na+ delivery to the collecting ducts results in less Na+ reabsorption and hence a reduced gradient for K+ secretion.
  • ADH: ADH reduces urinary flow rates that would reduce potassium secretion, however it also stimulates the apical potassium channel activity, which helps maintain normal potassium secretion.
  • Magnesium: Intracellular magnesium can bind and block K+ channels inhibiting K+ secretion into the tubules. Therefore magnesium deficiency reduces this inhibitory effect and so allows more potassium to be secreted into tubules and can cause hypokalaemia.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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