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97

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Physiology

Renal

Question 117 of 180

Regarding calcium handling by the kidneys, which of the following statements is CORRECT:

Answer:

Calcium that is not protein bound is freely filtered in the glomerulus, and there is reabsorption along the nephron.
  • About 70% is reabsorbed in the proximal tubule.
  • About 20% is reabsorbed in the thick ascending limb of the loop of Henle.
  • This reabsorption is mainly passive and paracellular and driven by sodium reabsorption. Sodium reabsorption causes water reabsorption, which raises tubular calcium concentration, causing calcium to diffuse out of the tubules. The positive  lumen potential also encourages calcium to leave the tubule.
  • About 5 - 10% is reabsorbed in the distal convoluted tubule.
  • Less than 0.5% is reabsorbed in the collecting ducts.
  • Calcium reabsorption in the distal nephron is active and transcellular and is the major target for hormonal control.
Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.
  • Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+ entry channels in the apical membrane and the Ca2+ ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).
  • Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ ATPase pump (and to increase phosphate reabsorption).
  • Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

Normal Values of Calcium and Rationale for Corrected Calcium Values

RCEM defines the normal value for total serum calcium as 2.1 - 2.5 mmol/L. This is the sum of free ionised calcium and calcium bound to albumin.

This total serum calcium measurement must be adjusted for albumin levels (as patients with a low albumin have total serum calcium lower than the reference range yet have normal free ionised calcium and vice versa). 0.02 mmol/L should be added to the calcium concentration for every g/L that albumin is below 40 and 0.02 mmol/L should be subtracted for every g/L that albumin is above 40.

Corrected calcium = Measured calcium + [(40 g/l - albumin) x 0.02]

Calcium Absorption

Calcium rich foods include: cheese, milk, yoghurt, fish and some vegetables and nuts. Of dietary calcium, about 25 - 30% is absorbed by the gut. Ca2+ is absorbed throughout the small intestine but mainly in the duodenum and proximal jejunum. Absorption occurs by a transcellular process involving intracellular calcium-binding proteins called calbindins. Gut absorption is increased by activated vitamin D.

Physiological Actions of Calcium

Calcium is essential for:

  • enzymatic reactions
  • intracellular signalling
  • nerve conduction
  • skeletal, cardiac and smooth muscle contraction
  • the release of neurotransmitters
  • the release of hormones
  • secretion from exocrine glands
  • blood clotting
  • bone mineralisation

Transport of Calcium in the Blood

Only unbound ionised calcium is physiologically active.

Free intracellular Ca2+ must be maintained at a very low level; most is bound to proteins or stored in the endoplasmic reticulum and mitochondria.

Blood calcium levels in the extracellular fluid are kept within a very narrow range to maintain normal physiological processes:

  • about 45% of serum calcium is bound to albumin
  • about 5% is complexed to other ions and
  • about 50% is free ionised Ca2+.

Ionised calcium binds to negatively charged sites on protein molecules, competing with hydrogen ions for the same binding sites on albumin and other calcium-binding proteins. This binding is pH dependent and alters the level of ionised calcium in the blood. An increase in pH, alkalosis, promotes increased protein binding, which decreases free calcium levels. Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels.

Renal Calcium Handling

Calcium that is not protein bound is freely filtered in the glomerulus, and there is reabsorption along the nephron.

  • About 70% is reabsorbed in the proximal tubule.
  • About 20% is reabsorbed in the thick ascending limb of the loop of Henle.
  • This reabsorption is mainly passive and paracellular and driven by sodium reabsorption. Sodium reabsorption causes water reabsorption, which raises tubular calcium concentration, causing calcium to diffuse out of the tubules. The positive  lumen potential also encourages calcium to leave the tubule.
  • About 5 - 10% is reabsorbed in the distal convoluted tubule.
  • Less than 0.5% is reabsorbed in the collecting ducts.
  • Calcium reabsorption in the distal nephron is active and transcellular and is the major target for hormonal control.

Regulation of Renal Calcium Handling

Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.

  • Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+ entry channels in the apical membrane and the Ca2+ ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).
  • Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ ATPase pump (and to increase phosphate reabsorption).
  • Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

By Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. (OpenStax College) [CC BY 3.0 , via Wikimedia Commons

Calcium Handling. (Image by Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. (OpenStax College) [CC BY 3.0 , via Wikimedia Commons)

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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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