The other week we discussed some cardiac drugs and I mentions diuretics. So in this blog we are going to look at the kidneys and how different types of diuretics function.
Firstly, it is important to know the structure of the kidneys and most importantly the nephron. The role of the kidneys within the body is to filter the blood, regulate the pH, volume, pressure and osmolarity of the blood as well as producing hormones. The kidneys filter around 150 litres of blood every day, that’s filtering the entire blood volume of a human around 30 times each day. The kidneys are located around the T12 to L3 level and are retroperitoneal, meaning they are behind the peritoneal layer. The right kidney is slightly lower in the abdomen than the left kidney as the liver pushes it lower. From the image you can see the entrance of the renal artery, vein and ureter, this entrance point is known as the renal hilum. Inside the kidney, from outside to inside, there is the capsule and the renal cortex, then the medulla which is made up of around 10-18 renal pyramids. The urine will then drain into the minor calyces, then the major calyces before entering the renal pelvis and exiting the kidney via the ureter.
Each kidney contains around 1 million nephrons. The nephron fine tunes what is excreted into the urine and what is reabsorbed back into the blood via the peritubular capillaries. Each nephron contains various sections; the glomerulus, the proximal convoluted tubule (PCT), the loop of Henle, the distal convoluted tubule (DCT) and the collecting duct. Each of these sections has a slightly different role in the reabsorption of substances into the blood stream. The afferent arterioles are divisions from the cortical radiate arteries, and enter the glomerulus where small solutes are transported into the bowman’s space. Water and solutes pass through the endothelium of the capillary, through the basement membrane and the epithelium of the nephron and into the bowman’s space. The epithelium has cells called podocytes which have tiny gaps that act like a seize, allowing only the passage of small molecules such as water, glucose and ionic salts but blocks larger substances like red blood cells. From the glomerulus the fluid travels into the PCT where mainly water and sodium are reabsorbed but also glucose and bicarbonate. The descending loop of Henle is the main site of passive transport of water by increased medullary osmolarity. The more concentrated tubular fluid then travels around to the ascending loop of Henle where sodium is reabsorbed. The DCT reabsorbs the remaining sodium, water and bicarbonate and secretes potassium.
There is an area called the juxtaglomerular complex which is between the DCT and the afferent arteriole of the glomerulus. This helps regulate the blood pressure and the rate at which the glomeruli filters by regulating vasoconstriction or dilation of the afferent and efferent arterioles. This works on detecting the levels of sodium and chloride, when these are low can signal to produce renin which increases sodium reabsorption and increases the blood pressure.
There are many different type of diuretics but all of them have the main function of increasing the production of urine. Diuretics are given to patients that are fluid overloaded to try and eliminate this excess fluid from the body, in patients with heart failure for example. The most commonly used diuretics are loop, thiazide (-like) and potassium-sparing diuretics.
Loop diuretics e.g. furosemide – inhibit the sodium-potassium-chloride cotransporter in the ascending loop of Henle. Calcium and potassium are also lost in the urine through use of the loop diuretics.
Thiazide diuretics e.g. hydrochlorothiazide – inhibit the sodium-chloride cotransporter in the early DCT, increasing the excretion of sodium and chloride. This leads to greater loss of potassium and reduced effectiveness of the glomerular filtration rate. These drugs can cause hypokalaemia.
Potassium sparing diuretics e.g. spironolactone – inhibition of expression of sodium channels in the collecting duct (aldosterone receptor antagonist). This leads to decreased reabsorption of sodium and decreased secretion of potassium in the DCT and proximal collecting duct.
When starting patients on diuretics, close attention needs to be paid to the electrolytes especially potassium, in order to choose the right diuretic for that patient to prevent further harm.