Renal Handling of Calcium and Phosphate

Hi :) In this post we'll have a look at how the kidneys handle Calcium and Phosphate. We'll also look at diuretics, kidney failure, and hyperparathyroidism. 

 Calcium Balance

Calcium is critical to the function of all cells but is particularly important in the heart, muscles and bones. The amount of calcium in the blood is regulated through the kidneys, the digestive tract, bone and skin. Calcium can be added to the blood by the reabsorption of bone (bone is broken down) or by absorption through the digestive tract. Calcium can be removed from the blood plasma by the calcification of bone (bone is formed) or through filtration at the kidneys.

Calcium can be transported in the blood plasma in three ways: free as Ca2+, complexed with other ions, or bound to carrier proteins. Ionised and complexed Ca2+ can be freely filtered at the glomerulus in the kidney. Ninety-nine per cent of the Ca2+ which is filtered at the glomerulus is reabsorbed. The reabsorption which occurs at the loop of Henle and the distal tubule are under hormonal control.

It is important to remember that calcium balance is highly regulated by hormonal control. In particular, three hormone regulate plasma calcium levels:

1. Parathyroid Hormone (PTH): this is released from the parathyroid hormone in response to decreased plasma Ca2+ levels. PTH increases the amount of calcium in the blood by:
1. stimulating the resorption of bone
2. stimulating Ca2+ reabsorption in the ascending loop of Henle and distal tubules in the kidney.
3. Stimulating the action of Calcitriol at the kidneys. This promotes calcium reabsorption at the gastrointestinal tract (GIT) as well as reabsorption at the kidneys.  
2. Calcitriol (1,25-(OH)2D3): this is a steroid hormone synthesised from vitamin D3. It increases the absorption of calcium from the GIT as well as increasing the reabsorption in the distal nephron of the kidney.
3. Calcitonin: This is a hormone secreted by the thyroid gland and its secretion is triggered by hypercalcaemia (too much calcium in the blood). It increases the calcium uptake by the bone and decreases the renal calcium reabsorption. Its nett effect is to decrease plasma calcium levels. It plays a much less important role in calcium balance when compared to PTH and Calcitriol.

Now, the ratio between calcium and phospate concentrations is very important and ideally it should be 2:1. The close association between calcium and phosphate means that factors regulating calcium balance also affect phosphate balance. 

Parathyroid Hormone has a particularly important influence on plasma phosphate concentrations. PTH an opposing influence on the plasma phosphate concentrations. It promotes bone reabsorption to increase the concentration of phosphate in the blood. It also reduces the amount of phosphate reabsorbed and this promotes phosphate excretion. This causes the plasma phosphate concentration to remain stable despite a decreased plasma calcium concentration. 

Hyperparathyroidism

There are two types of hyerparathyroidism: primary and secondary. Primary occurs when the parathyroid works too hard and this increases PTH production. This leads to hypercalcaemia. Secondary involves a reaction of the parathyroid gland to a low calcium concentration in the blood. This leads to an increase in the amount of PTH. Overall, a loss of calcium from the bones is experienced and this leads to fragility and fractures, etc. There is also an abnormally low amount of phosphate in the blood plasma. 

The Effect of Diuretics

Diuresis is defined as the increased rate of urine output through increased excretion of solutes and therefore water. Hypokalaemia (reduced concentration of potassium in the blood) is a side effect of the long term use of diuretics. Two types of diuretics exist:

1. Loop Diuretics (Frusemide): These inhibit the Na+/K+/2Cl- symporter at the thick ascending loop of Henle. This decreases the medullary gradient for water reabsorption which results in an increased flow in the distal nephron. 
2. Potassium Sparing Diuretics (Spironolactone): these block the action of aldosterone in the late distal tubule and collecting duct. This causes the Na/K pump to not be induced which blocks Na reabsorption and K excretion. This results in diuresis because ADH release relies on the sodium concentration in the extracellular fluid.   

Kidney Failure 

Renal failure occurs when 75% of the nephrons of both kidneys fail to function. It is characterised by Isosthenuria and Azotaemia (Increased blood nitrogen levels). Acute renal failure is characterised by an abrupt decline in renal function which is usually due to an ischemic or toxic insult as well as an enlarged kidney. It may be reversible. Chronic renal failure occurs over weeks to years and the nephron damage is irreversible as it is replaced by fibrous tissue. It is characterised by a decrease in the size of the kidney.

That's it for this post, if you have any questions please feel free to ask :)