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
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
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
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