Physiology
Renal
Regarding calcium, which of the following statements is CORRECT:
Answer:
The normal range of total serum calcium is 2.1 - 2.5 mmol/L. Only unbound ionised calcium is physiologically active. Of total plasma calcium, 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. Of dietary calcium, about 25 - 30% is absorbed by the gut.Calcium Handling
Physiology / Endocrine / Calcium and Bone / Renal / Calcium Balance
Last Updated: 26th July 2024
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).
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 |
