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Lecture 18

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Biological Sciences
Stephen Reid

1    Lecture 18: Calcium Regulation, Glucose Regulation and Clearance 1. Calcium Regulation Calcium levels in the blood are regulated primarily by hormones. Calcium exchange occurs between the blood and the following calcium stores or reservoirs; bone, the gut and the kidney. We can absorb calcium from digested food in the gut or reabsorb it from the kidney (it was filtered in the first place). The rates of absorption from the gut or reabsorption from the kidneys can be regulated depending upon whether plasma calcium levels are high or low. We can take calcium from the bones and add it to the blood or deposit it from the blood back into the bone. Calcium removal from the bone is referred resorption whereas when calcium is deposited into the bones it is referred to as calcification or deposition. There are three primary hormones involved in these process: parathyroid hormone and calcitrol (both involved in raising plasma calcium levels), and calcitonin (involved in lowering them). Parathyroid hormone and calcitonin are both produced in the parathyroid and thyroid glands, respectively. 2    ++ Calcitonin is produced by the thyroid gland in response to high levels of Ca ions in the blood plasma - the role of calcitonin is to lower plasma calcium levels. Calcitonin causes the deposition of calcium into the bone and reduces the reabsorption of calcium by the kidneys. Parathyroid hormone produced by the parathyroid gland functions to raise plasma calcium levels when they fall below normal. It does this by stimulating the reabsorption of calcium in the kidneys and by stimulating the release of calcium from the bones to the blood. PTH also, indirectly, by helping to produce calcitrol (see below) causes calcium uptake from the gut to increase. 3    Calcitrol is produced when plasma calcium levels are too low. The process begins with the conversion of cholesterol into 7-dehydrocholesterol which, in turn, is converted to vitamin D3 by sunlight (as blood moves in vessels near the surface of the skin). Vitamin D3 is converted in the liver into 25-hydroxyvitamin D3. If plasma calcium levels are low, the kidneys are stimulated by parathyroid hormone to turn 25-hydroxyvitamin D3 into calcitrol. Calcitrol, like parathyroid hormone, increases calcium reabsorption in the kidney, but it also works upon the gut and increases the rate of uptake of calcium from the intestines into the blood. 4    2. Glucose Handling by the Kidney Normally, 100% of the filtered glucose is reabsorbed by the kidneys, passing through the tubular + epithelium via act+ve glucose/Na co-tr+ns+ort, and into the peritubular fluid via facilitated diffusion (the Na is reabsorbed via Na /K exchange). The filtered load of a particular solute is the amount that is filtered at the glomerulus. It is calculated by multiplying glomerular filtration rate by the concentration of the solute in the plasma. Filtered Load = GFR x [solute] plasma The transport maximum of a substance refers to the maximum operating capacity of the transport and carrier proteins that handle that particular substance. The renal threshold of a substance is the plasma concentration of a substance at which it begins to appear in the urine. When the filtered load is equal to the transport maximum, then the renal threshold for that substance has been met. In order to calculate the renal threshold for glucose (the point at which glucose levels in the plasma are so high that glucose begins to appear in the urine) we need to determine when the filtered load equals the transport maximum. The transport maximum for glucose is 375 mg/ml. This is a fact and not something that we calculate. The filtered load is equal to GFR (125 ml/min) multiplied by the concentration of glucose in the plasma (1 mg/ml). The filtered load is therefore 125 mg of glucose filtered every minute (mg/min). Filtered Load = GFR x [glucose] plasma 5    The renal threshold is achieved when the filtered load is equal to the transport maximum. Therefore, in the equation above we can replace filtered load with transport maximum and the [glucose] in the plasma can be replaced with renal threshold. This transforms the above equation into the following: Transport Maximum = GFR x Renal Threshold The renal threshold is therefore the transport maximum divided by GFR. We have values of 375 mg/ml for transport maximum and 125 ml/min for GFR. This means that the renal threshold for glucose is 3 mg/ml (300 mg/dL). In other words, when the concentratio
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