Update in Anaesthesia Renal Physiology Katie Wallace Correspondence Email: [email protected] IntrOductION like extension of the tubule called the Bowman’s Summary The kidney is a complex organ with several different capsule The major functions of the functions. One way to remember these functions is to • The proximal convoluted tubule (PCT) kidneys can be identified think about a patient who has chronic renal failure. by knowledge of the The main features are: • The descending thin limb of the loop of Henle pathological changes • The ascending thin and thick limb of the loops of seen in renal failure. The 1. Salt and water retention with oedema and kidney has important Henle hypertension roles in salt and water, 2. Uraemia • The vasa recta, which is a series of specialised acid-base, electrolyte and calcium homeostasis. These 3. Hypercalcaemia and hyperphosphataemia capillaries which wrap around the loop of Henle functions are described, 4. Acidosis and hyperkalaemia • The distal convoluted tubule (DCT) including the role of the 5. Anaemia. countercurrent multiplier • The collecting duct. and exchange systems of The main functions of the kidney are therefore: The glomeruli sit within the renal cortex and drain the loop of Henle. Where into the PCT. This then drains into the descending relevant, clinical examples 1. Salt and water balance or homeostasis are used to demonstrate limb of the loop of Henle, which descends down 2. Toxin removal the multiple roles of the through the medulla. It then turns back on itself, kidney. 3. Calcium and phosphate homeostasis becoming the ascending limb, and returns to the 4. Acid–base homeostasis cortex before becoming the DCT. The DCT drains 5. Stimulation of erythropoesis Homeostasis means ‘maintenance of the internal environment’ of the body within closely regulated limits. The functions of the kidneys are necessary to maintain this constant environment despite great variation in oral intake and the external environment. BASIC STRUCTURE OF THE KIDNEYS The kidney has several layers starting from the outer renal cortex moving deeper to the outer medulla and then to the inner medulla. The specialised structure within the kidney is the nephron. Each kidney contains Katie Wallace approximately one million Specialist Trainee nephrons. Each nephron consists Department of Anaesthesia of: Royal Devon and Exeter • A glomerulus, which in turn NHS Foundation Trust consists of a capillary tuft and Devon EX5 5DW a specialised enclosed pouch Figure 1. Detailed anatomy of the kidney and nephron UK Update in Anaesthesia | www.worldanaesthesia.org page 60 into a collecting duct which descends back down through the medulla diuretics) this is one of the renal mechanisms for eliminating drugs so that urine can drain into the renal pelvis and ureter. Humans have from the body. The majority of renal elimination of drugs from the a mixture of short (cortical nephrons) and long (juxta-medullary) body however is by filtration. nephrons - eighty-five per cent are short in humans. In general the greater the proportion of long loops or length of loop the greater the Loop of Henle concentrating ability (for example dogs are able to concentrate urine The human body has no active pump for water, which can only move to greater than 3000mmosm.l-1, and some desert animals to greater across a membrane by osmosis. The role of the Loop of Henle is to than 5000 mmosm.l-1) create an increasing concentration gradient in the interstitial tissues as the loop passes deeper into the medulla. A gradient from about FUNCTIONS OF THE KIDNEY 285mosm.l-1 in at the beginning of the loop to 1200mosm.l-1 at the apex of the loop is achieved. The collecting ducts pass through this Glomeruli osmotic gradient and so, under the influence of antidiuretic hormone The glomerulus is the filter unit of the nephron. It passively lets (ADH), water can be retained. The loops of Henle constitute a water, amino acids, sodium and other free ions pass through its countercurrent system - the ascending and descending limbs of membranes and into the tubule system, but not charged proteins, each loop are parallel, counter to (i.e. opposite in flow) and in close large proteins or cells. The unique basement membrane, which is proximity to each other. at the interface of the capillaries and Bowman’s capsule, allows this to happen. Glomerular filtration produces up to 125ml filtrate per There are 3 sections to the loop of Henle: minute, most of which needs to be quickly reabsorbed. 1. Thin descending limb Proximal convoluted tubule (PCT) 2. Thin ascending limb The PCT is responsible for the majority of the reabsorption. There are four different mechanisms by which solute transport occurs: 3. Thick ascending limb 1. Passive diffusion which occurs across a membrane down an The countercurrent system consists of: electrochemical gradient, e.g. sodium and chloride ions. • A countercurrent multiplier (the loop of Henle) which sets up 2. Facilitated diffusion which is also passive but is more selective as an increasing gradient of osmolality as you go to the bottom of it requires the interaction between an ion and a membrane-bound the loop. specific carrier protein, e.g. sodium/amino acid cotransporter. • A countercurrent exchange (the vasa recta) which maintains this gradient. ADH acts to allow uptake of water from the collecting 3. Passive diffusion through a membrane channel or pore, e.g. ducts. The osmotic gradient would otherwise gradually diminish potassium in the collecting duct. as water is reabsorbed by osmosis. 4. Active transport against an electrochemical gradient by an energy requiring pump, e.g. the potassium-hydrogen ion antiporter in Countercurrent multiplier the collecting duct. Essentially, sodium and chloride (Na+ and Cl-) leave the ascending limb, which is impermeable to water which therefore cannot follow. Some transporters within the PCT are responsible for secretion Deep in the medulla, Na+ and Cl- leave by passive diffusion, however of weak acids and bases. As drugs can be weak acids or bases (e.g. this passive diffusion is not sufficient to maintain such a steep gradient, so in the thick ascending limb sodium is actively pumped Table 1. Substances reabsorbed in the PCT out into the interstitium. Water does move out of the descending limb into the interstitium by osmosis and this leaves the fluid within Substance Approximate % reabsorbed in PCT the descending limb gradually increasing in osmolality as it moves deeper into the medulla towards the apex of the loop. Water 65 It is only as tubular fluid enters the ascending loop that it starts to Sodium 60 become less concentrated as Na+ and Cl- are actively pumped out Potassium/Chloride/Bicarbonate 80 (which is where we started). In effect, Na+ and Cl- are circulating around the bottom part of the loop which generates the high Glucose 100 osmolality in the interstitium. Amino acids 100 Countercurrent exchange Calcium 60 The multiplier is self-perpetuating until ADH allows water to be reabsorbed, thereby lowering the osmolality in the interstitium. The Phosphate 80 vasa recta are also countercurrent in their lay-out and they act in a Urea 50 very similar way to maintain the hypertonicity of the interstitium at the bottom of the loop. page 61 Update in Anaesthesia | www.anaesthesiologists.org Figure 2. The function of the loop of Henle in concentration of urine Na+ and Cl- diffuse from the ascending vasa into the descending vasa 2. Different segments of the loop have different permeabilities to and recirculate around the lowest parts of the loops. At the same water and sodium. time water diffuses from the descending vasa across to the ascending 3. Reabsorbed water is rapidly removed from the interstitium into vasa. the systemic circulation via the vasa recta. The role of urea 4. Sodium which is reabsorbed is effectively ‘trapped’ in the The other major factor in generation of the hypertonic medulla interstitium. is the fact that the collecting ducts are impermeable to urea until 5. The ascending and descending limbs of the same nephron the portions deep within the medulla, by which time (after water run parallel to each other with the filtrate running in opposite reabsorption) the urea concentration is very high. When urea reaches directions. this part of the collecting duct, ADH sensitive urea channels allow it to move into the interstitum down a concentration gradient and this 6. The unique arrangement of the blood supply (the vasa recta) is an further increases the osmolality of the interstitium. Some of the urea essential component in this system. diffuses back into the filtrate in the thin limbs of the loop of Henle Distal convoluted tubule (DCT) and some stays within the interstitium. The DCT is where the final fine tuning of the reabsorption of many In summary the important points about the counter current ions such as sodium, calcium, phosphate, potassium, and acid base multiplier system are: balance is achieved. 1. It is driven by the active reabsorption of the sodium in the thick Collecting duct ascending limb. The collecting duct passes down through the concentration gradient Update in Anaesthesia | www.worldanaesthesia.org page 62 generated by the countercurrent system. It has varying permeability Altering the radius of either or both of these vessels will alter the to water depending on the amount of antidiuretic hormone present pressure within glomerulus. This is called autoregulation, and is and therefore is responsible for concentrating urine. It is also involved achieved with the help of the macula densa, a group of specialised with acid secretion (see below) cells which sit with in the distal part of the ascending limb of the loop of Henle. They are also in close proximity to the afferent and RENAL BLOOD FLOW efferent arterioles.