24 Update in Anaesthesia a 45 degree caudad angle (towards the feet) and kg should not exceeded. Other local anaesthetic slightly posterior angle. The angle of approach is agents like lignocaine or prilocaine may be used. important to avoid accidental intravascular or intrathecal injection. The needle is then advanced Complications carefully until a paraesthesia is elicited. A click l Inadvertent epidural or subarachnoid injection may be detected as the needle passes through the is a potentially serious complication resulting prevertebral fascia. This usually occurs at the from incorrect needle placement. superficial level. The use of a nerve stimulator with a special insulated needle is very helpful in l Vertebral artery injection, this can result in confirming the correct placement of the needle and convulsions and loss of consciousness. performing the interscalene block accurately. l Phrenic nerve block is frequently produced, Correct stimulation produces twitching below the this complication precludes bilateral use of shoulder. Stimulation of the diaphragm indicates this technique. too anterior an approach. Once paraesthesia is Recurrent laryngeal, vagus, and cervical obtained, the needle is stabilised and after negative l sympathetic nerves are sometimes blocked. aspiration for , 20 to 30mls of the local anaesthetic is injected slowly and carefully. l Pneumothorax is rare but can happen with deep placement of the needle and in unskilled Local anaesthetic solution Bupivacaine 0.375- hands. 0.5% solution may be used safely in the volumes between 20-40mls, but the maximum dose of 2 mg/

PHYSIOLOGY OF THE Dr. P. Stewart the medulla. These nephrons have a greater Sydney concentrating ability, the mechanism being Australia explained below. The kidney is unique as it has two beds arranged in series, the glomerular The Functions of the Kidney which are under high pressure for l Regulation of the and content filtering, and the peritubular capillaries which are of the body. situated around the tubule and are at low pressure l Retention of substances vital to the body (figure 1). This permits large volumes of fluid to be such as and filtered and reabsorbed. l Maintenance of acid/base balance. Afferent arteriole Efferent arteriole l Excretion of waste products, water soluble toxic substances and drugs. Glomerulus l Endocrine functions. Regulation of the water and electrolyte content Bowman's of the body Capsule The kidney allows a person to eat and drink Peritubular Capillaries according to their habits without changing the composition of their fluid compartments. Renal Blood Supply is normally is about 20% of the cardiac output. Approximately 99% of the blood flow goes to the cortex and 1% to the medulla. The cortex is the outer part of the kidney containing most of the nephrons. The medulla is the inner part The Nephron: Each kidney consists of about one of the kidney and contains the specialised nephrons million nephrons. The nephron is made up of a in the juxta-medullary region, immediately next to glomerulus and its tubule (figure2). The tubule is Update in Anaesthesia 25 made up of a number of sections, the proximal autoregulation of renal blood flow and a feedback tubule, the medullary loop (loop of Henle), and the mechanism known as “ glomerular tubular balance”. distal tubule which finally empties into the collecting Glomerular Tubular balance. When there is a duct. decrease in GFR, there is a resulting decrease in the fluid flow rate within the Nephron: tubule. At the loop of Henle, Distal there is greater time for H O NaCI Tubule 2 reabsorption of sodium and More chloride ions. Therefore there Glomerlus hypotonic is a decrease in the number of + + Isotonic K H + Proximal Na + H2O Na sodium and chloride ions Tubule K+ 'Bulk H+ reaching the distal tubule which Reabsorber' Hypotonic is detected by the macula densa. (C) Collecting Duct This in turn decreases the (A) Urea resistance in the afferent arteriole which results in an

H2O increase in renal blood flow. It Na+CI- Isotonic H O 2 also increases release Hypertonic Hypertonic from the juxtaglomerular (B) apparatus which stimulates Loop of Henle angiotensin II production causing constriction of the efferent arteriole. is formed as a result of a three phase process These both act to increase the hydrostatic pressure - simple , selective and passive in the glomerular capillary bed and return GFR to reabsorption and excretion. normal (table 1). Filtration The juxtaglomerular complex consists of macula Filtration takes place through the semipermeable densa cells, which are special distal tubular walls of the glomerular capillaries which are almost epithelial cells which detect chloride concentration impermeable to and large molecules. The and modified smooth muscle cells, juxtaglomerular filtrate is thus virtually free of protein and has no cells, in the walls of the afferent and efferent cellular elements. The glomerular filtrate is formed arteriole. These cells produce renin. Renin is an by squeezing fluid through the glomerular capillary enzyme which converts the plasma protein bed. The driving hydrostatic pressure (head of angiotensinogen to angiotensin I. Angiotensin pressure) is controlled by the afferent and efferent converting enzyme (ACE) which is formed in small arterioles, and provided by arterial pressure. About Table 1 20% of renal plasma flow is filtered each minute (125 ml.min-1). This is the glomerular filtration rate (GFR). In order to keep the renal blood flow and GFR relatively constant hydrostatic pressure in the glomerulus has to be kept fairly constant. When there is a change in arterial blood pressure, there is constriction or dilatation of the afferent and efferent arterioles, the muscular walled vessels leading to and from each glomerulus. This process is called autoregulation. Autoregulation of GFR is achieved by 26 Update in Anaesthesia quantities in the lungs, proximal tubule and other the substance or interstitium of the medulla. This tissues, converts angiotensin I to angiotensin II high concentration of solutes is maintained by the which causes vasoconstriction and an increase in counter current multiplier. A counter current blood pressure. Angiotensin II also stimulates the multiplier system is an arrangement by which the adrenal gland to produce which causes high medullary interstitial concentration of solute water and sodium retention which together increase is maintained, giving the kidney the ability to blood volume. concentrate urine. The loop of Henle is the counter This is a negative feedback system. In other words current multiplier and the vasa recta is the counter the initial stimulus is a fall in blood volume which current exchanger, the mechanism being described leads to a fall in perfusion pressure in the kidneys. below. When blood volume, renal perfusion and GFR Actions of different parts of the loop of Henle improve the system feeds back to switch off or turn A The descending loop of Henle is relatively down the response to the stimulus. impermeable to solute but permeable to Selective and Passive Reabsorption water so that water moves out by , The function of the renal tubule is to reabsorb and the fluid in the tubule becomes hypertonic. selectively about 99% of the glomerular filtrate. B The thin section of the ascending loop of The Proximal Tubule reabsorbs 60% of all solute, Henle is virtually impermeable to water, but which includes 100% of glucose and amino acids, permeable to solute especially sodium and 90% of bicarbonate and 80-90% of inorganic chloride ions. Thus sodium and chloride ions phosphate and water. move out down the concentration gradient, Reabsorption is by either active or passive transport. the fluid within the tubule becomes firstly Active transport requires energy to move solute isotonic then hypotonic as more ions leave. against an electrochemical or a concentration Urea which was absorbed into the medullary gradient. It is the main determinant of oxygen interstium from the collecting duct, diffuses consumption by the kidney. Passive transport is into the ascending limb. This keeps the urea where reabsorption occurs down an electrochemical, within the interstitium of the medulla where pressure or concentration gradient. it also has a role in concentrating urine. Most of the solute reabsorption is active, with water C The thick section of the ascending loop of being freely permeable and therefore moving by Henle and early distal tubule are virtually osmosis. When the active reabsorbtion of solute impermeable to water. However sodium and from the tubule occurs, there is a fall in concentration chloride ions are actively transported out of and hence osmotic activity within the tubule. Water the tubule, making the tubular fluid very then moves because of osmotic forces to the area hypotonic. outside the tubule where the concentration of solutes is higher. The Loop of Henle is the part of the tubule which dips or “loops” from the 300 350 cortex into the medulla, H O 2 Solute 300 (descending limb), and 600 600 Medullary Solute H O Interstitium then returns to the cortex, 2 Solute 600 Solute mosm/l (ascending limb). It is this 800 800 Solute 900 H2O part of the tubule where Solute 1200 1000 1000 urine is concentrated if 1200 necessary. This is possible because of the high concentration of solute in Vasa Recta Update in Anaesthesia 27

The Vasa Recta (figure 3) is a portion of the or removal of hydrogen ions results in minimal peritubular capillary system which enters the change to pH, the purpose of the buffer. medulla where the solute concentration in the l The pH is the negative log to base 10 of the interstitium is high. It acts with the loop of Henle hydrogen ion concentration [H+] and indicates to concentrate the urine by a complex mechanism the acidity of the solution. The more acid the of counter current exchange. If the vasa recta did solution the higher the H+ concentration but not exist, the high concentration of solutes in the the lower the pH. The pH in the body is kept medullary interstitium would be washed out. Solutes under tight control as almost all enzyme diffuse out of the vessels conducting blood towards activities in the body are dependent on the pH the cortex and into the vessels descending into the being normal. medulla while water does the opposite, moving from the descending vessels to the ascending vessels. The lungs and kidneys work together to produce a This system allows solutes to recirculate in the normal and arterial pH of 7.35- medulla and water, in effect, to bypass it. 7.45 (34-46 nmol.l-1 H+ concentration). Carbon

dioxide (CO2), when dissolved in the blood is an Distal Tubule and Collecting Duct: The final acid, and is excreted by the lungs. The kidney concentration of urine depends upon the amount of excretes fixed acid and performs three functions to antidiuretic hormone (ADH) secreted by the achieve this:- posterior lobe of the pituitary. If ADH is present the distal tubule and the collecting duct become 1. Tubular secretion of acid (figure 4): The permeable to water. As the collecting duct passes buffer sodium bicarbonate, is filtered by the through the medulla with a high solute concentration glomerulus and then reabsorbed in the proximal in the interstitium, the water moves out of the tubule. The sodium is absorbed by a sodium/ lumen of the duct and concentrated urine is formed. hydrogen ion pump (Na+/H+) exchanging Na+ for In the absence of ADH the tubule is minimally H+ on the luminal proximal border of the tubular permeable to water so large quantities of dilute . A sodium/potassium pump (Na+/K+) forces urine is formed. Na+ through the cell from tubular fluid in exchange for potassium. There is a close link between the hypothalamus of the brain and the posterior pituitary. There are cells Bicarbonate Reabsorption: within the hypothalamus, osmoreceptors, which are sensitive to changes in osmotic pressure of the Interstial Proximal Tubular blood. If there is low water intake, there is a rise in Fluid Renal Tubular Cell Urine osmotic pressure of the blood, and after excess Na+ + CO + H O intake of water, the reverse. Nerve impulses from K 2 2 CO + H O the hypothalamus stimulate the posterior pituitary Na+ / K+ ATPase 2 2 to produce ADH when the osmotic pressure of the Carbonic Anthydrase (in brush border) blood rises. As a result water loss in the kidney is CO 2 H CO reduced because ADH is secreted, and water 2 3 reabsorbed in the collecting duct. Na+ H+ Na+/H+ Acid/Base Function HCO - + H+ 3 Antiporter l Acid: a substance that can release hydrogen ions in solution. l Base: a substance that can accept 2. Glomerular filtration of buffers which hydrogen ions in solution. combine with H+ : l Buffer: a substance whose pKa (the pH at a) The majority of the filtered bicarbonate is which half is in the ionised form and half reabsorbed (90% in the proximal tubule). unionised) is close to the pH of its The H+, released as the Tubular Secretion of environment. In those circumstances, addition Acid (above), forms carbonic acid with the - + bicarbonate (HCO3 ). H + HCO3 = H2CO3 28 Update in Anaesthesia

Carbonic anhydrase, found in the proximal Aldosterone promotes sodium ion and water tubular cells, catalyses the reaction to carbon reabsorption in the distal tubule and collecting duct + + dioxide (CO2) and water (H2O) (figure 4). where Na is exchanged for potassium (K ) and

The CO2 diffuses into the cell where it again hydrogen ions by a specific cellular pump. forms carbonic acid in the presence of Aldosterone is also released when there is a decrease carbonic anhydrase. The carbonic acid ionises in serum sodium ion concentration. This can occur, + - + to H and HCO3 . The H is then pumped out for example, when there are large losses of gastric of the cell back to the lumen of the tubule by juice. Gastric juice contains significant the Na+/H+ pump (1 above) and the sodium concentrations of sodium, chloride, hydrogen and is returned to the plasma by the Na+/K+ pump potassium ions. Therefore it is impossible to correct (1 above). Water is absorbed passively. the resulting alkalosis and hypokalaemia without b) Other buffers include inorganic phosphate first replacing the sodium ions using 0.9% saline - . (HPO4 ), urate and creatinine ions which are excreted in urine as acid when combined with Atrial Natruretic Peptide(ANP) is released when H+ ions secreted in the distal nephron atrial pressure is increased e.g. in failure or 3. Ammonia is produced enzymatically from fluid overload. It promotes loss of sodium and glutamine and other amino acids, and is chloride ions and water chiefly by increasing GFR.

secreted in the tubules. Ammonia (NH3) Antidiuretic Hormone (ADH) increases the water combines with secreted H+ ions to form a permeability of the distal tubule and collecting - non-diffusible ammonium ion (NH4 ) which duct, thus increasing the concentration of urine. In is excreted in the urine. Ammonia production contrast, when secretion of ADH is inhibited, it is increased by a severe metabolic acidosis to allows dilute urine to be formed. This occurs mainly as much as 700 mmol.day-1. when plasma sodium concentration falls such as following drinking large quantities of water. This Excretion of waste products fall is detected by the osmoreceptors (above). The Filtration occurs as blood flows through the hormones interact when blood loss or dehydration glomerulus. Some substances not required by the occurs to maintain intravascular volume. The flow body, and some foreign materials (e.g. drugs) may diagram in Table 2 illustrates this. not be cleared by filtration through the glomerulus. Other Substances Produced by the kidney Such substances are cleared by secretion into the 1,25 dihydroxy vitamin D (the most active form tubule and excreted from the body in the urine. vitamin D) which promotes calcium absorption Hormones and the Kidney from the gut. Renin (see above) increases the production of angiotensin II which is released when there is a fall which stimulates red cell production in intravascular volume e.g. haemorrhage and dehydration. This leads to: Both of these decrease in renal failure. l Constriction of the efferent arteriole to maintain GFR, by increasing the filtration pressure in the Table 2. glomerulus. l Release of aldosterone from the adrenal cortex l Increased release of ADH from the posterior pituitary l Thirst l Inotropic myocardial stimulation and systemic arterial constriction The opposite occurs when fluid overload occurs.