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Renal anatomy, pharmacology and physiology Anaesthetics in renal dysfunction James Hayward SHO Anaesthetics Worthing Anatomy Kidneys located either side of vertebral column: left kidney lies superior to right kidney superior surface capped by adrenal gland Typical kidney 10 cm long, 5.5 cm wide, and 3 cm thick Weighs about 150 g Kidney in cross section Main function of the kidneys. Regulation of the water and electrolyte content of the body. Retention of substances vital to the body such as protein and glucose Maintenance of acid/base balance. Excretion of waste products, water soluble toxic substances and drugs. Endocrine functions Renal blood flow Kidneys receive 20–25% of total cardiac output 1200 ml of blood flows through kidneys each minute 99% of the blood flow goes to the cortex and 1% to the medulla Regulation of water and electrolyte content Two capillary beds arranged in series, the glomerular capillaries which are under high pressure for filtering, and the peritubular capillaries which are situated around the tubule and are at low pressure This permits large volumes of fluid to be filtered and reabsorbed. The nephron Each kidney is made up of about 1,000,000 nephrons Consist of renal tubule and renal corpuscle Renal corpuscle Each renal corpuscle: 150–250 µm in diameter Bowman’s capsule and glomerulus The renal tubule The tubule is made up of a number of sections, the proximal tubule, the medullary loop (loop of Henle), and the distal tubule which finally empties into the collecting duct. Urine production Urine is formed as a result of a three phase process : Simple filtration Selective and passive reabsorption Excretion Filtration Blood pressure forces water and small solutes across membrane into capsular space . The driving pressure is controlled by the afferent and efferent arterioles. Filtration takes place through the semipermeable walls of the glomerular capillaries Almost impermeable to proteins and large molecules. The filtrate is thus virtually free of protein and has no cellular elements. GFR and Autoregulation About 20% of renal plasma flow is filtered each minute (125 ml/min). This is the glomerular filtration rate (GFR). In order to keep the renal blood flow and GFR relatively constant the hydrostatic pressure needs to be maintained. When there is a change in arterial blood pressure, there is constriction or dilatation of the afferent and efferent arterioles. Autoregualtion At the loop of Henle, there is greater time for reabsorption of sodium and chloride ions. A decrease in the number of sodium and chloride ions reaching the distal tubule is detected by the macula densa. This in turn decreases the resistance in the afferent arteriole which results in an increase in renal blood flow. It also increases renin release from the juxtaglomerular apparatus which stimulates angiotensin II production causing constriction of the efferent arteriole. This is a negative feedback system The juxtaglomerular complex consists of: Macula densa cells, which are special distal tubular epithelial cells which detect chloride concentration Juxtaglomerular cells, modified smooth muscle cells, in the walls of the afferent and efferent arteriole. These cells produce renin. Renin-angiotensin Renin is an enzyme which converts the plasma protein angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) which is formed in small quantities in the lungs, proximal tubule and other tissues, converts angiotensin I to angiotensin II Angiotensin II causes vasoconstriction and an increase in blood pressure. Angiotensin II also stimulates the adrenal gland to produce aldosterone which causes water and sodium retention which together increase blood volume. Selective and Passive Reabsorption The function of the renal tubule is to reabsorb selectively about 99% of the glomerular filtrate. The Proximal Tubule reabsorbs 60% of all solute 100% of glucose and amino acids 90% of bicarbonate 80-90% of inorganic phosphate and water. Reabsorption is by either active or passive transport. Active transport requires energy to move solute against an electrochemical or a concentration gradient. It is the main determinant of oxygen consumption by the kidney. Passive transport is where reabsorption occurs down an electrochemical, pressure or concentration gradient. Most of the solute reabsorption is active, with water being freely permeable and therefore moving by osmosis. Water moves because of osmotic forces to the area outside the tubule where the concentration of solutes is higher. Loop of Henle Urine is concentrated if necessary. This is possible because of the high concentration of solute in the substance or interstitium of the medulla. This high concentration of solutes is maintained by the counter current mechanism. The loop of Henle is a counter current multiplier and the vasa recta is the counter current exchanger. Counter-current mechanism Osmotic gradient is produced by a countercurrent mechanism located in the loop of Henle The countercurrent mechanism is based upon the Na pump; by pumping large quantities of Na into the interstitial fluid in the medulla a very high concentration is built up Distal Tubule and Collecting Duct: The final concentration of urine depends upon the amount of antidiuretic hormone (ADH) secreted by the posterior lobe of the pituitary. ADH is present the distal tubule and the collecting duct become permeable to water, the water moves out of the lumen of the duct and concentrated urine is formed. In the absence of ADH the tubule is minimally permeable to water so large quantities of dilute urine is formed. Hypothalamic control of ADH There is a close link between the hypothalamus and the posterior pituitary. Osmoreceptors within the hypothalamus, sensitive to changes in osmotic pressure of the blood. If there is low water intake, there is a rise in osmotic pressure of the blood, and vice versa. Nerve impulses from the hypothalamus stimulate the posterior pituitary to produce ADH when the osmotic pressure of the blood rises, causing water retention and an increase in circulating volume. Acid-base Normal extracellular fluid and arterial pH of 7.35-7.45 (34-46 nmol.l-1 H+ concentration). Carbon dioxide (CO2), when dissolved in the blood is an acid, and is excreted by the lungs. The kidney excretes fixed acid. Tubular secretion of acid Normal metabolism produces large amounts of CO2 continuously (about 14 moles/day) If this CO2 were not removed we would rapidly develop fatal acidosis Almost all of the CO2 is removed, as a gas, from the lungs If blood pH is low respiration is stimulated so that more CO2 is removed, raising the pH to the normal level Bicarbonate is adjusted in the kidney Most filtered bicarbonate is reabsorbed in the proximal tubule The kidneys also dispose of non-volatile acids produced in metabolism Additional processes are used by the kidney to regulate pH: Secretion of H ions Occurs in the proximal tubule and distal tubules Secretion into blood lowers the pH Secretion into the tubule raises the pH Production of new bicarbonate in distal tubule: The distal tubule has fine control over bicarbonate Secreted into the blood raises the pH Secretion into tubule lowers the pH indirectly Production of ammonia (NH3) in proximal tubule cells during acidosis Helps to remove excess H by forming ammonium ion (NH4+) in the tubule Excretion of waste products Filtration occurs as blood flows through the glomerulus. Some substances not required by the body, and some foreign materials (e.g. drugs) may not be cleared by filtration through the glomerulus. Such substances are cleared by secretion into the tubule and excreted from the body in the urine. Endocrine functions (1) - Renin Increases the production of angiotensin II which is released when there is a fall in intravascular volume e.g. haemorrhage and dehydration. Constriction of the efferent arteriole to maintain GFR, by increasing the filtration pressure in the glomerulus. Release of aldosterone from the adrenal cortex Increased release of ADH from the posterior pituitary Thirst Inotropic myocardial stimulation and systemic arterial constriction Endocrine functions (2) Aldosterone Aldosterone promotes sodium ion and water reabsorption in the distal tubule and collecting duct where Na+ is exchanged for potassium (K+) and hydrogen ions by a specific cellular pump. Aldosterone is also released when there is a decrease in serum sodium ion concentration. e.g. vomiting. Gastric fluid contains significant concentrations of sodium, chloride, hydrogen and potassium ions. Therefore it is impossible to correct the resulting alkalosis and hypokalaemia without first replacing the sodium ions using 0.9% saline solutions. Endocrine functions (3) - ADH Antidiuretic Hormone (ADH) increases the water permeability of the distal tubule and collecting duct, thus increasing the concentration of urine. Endocrine functions (4) – The rest Atrial Natruretic Peptide(ANP) is released when atrial pressure is increased e.g. in heart failure or fluid overload. It promotes loss of sodium and chloride ions and water chiefly by increasing GFR 1,25 dihydroxy vitamin D (the most active form vitamin D) which promotes calcium absorption from the gut. Erythropoietin which stimulates red cell production. Renal pharmacology Problems in renal dysfunction (1) Drug handling Protein bound drugs have increased freefractions due to acidosis and hypoalbuminaemia Lipid insoluble drugs are eliminated by the kidney and the hepatic metabolites of lipsoluble drugs are excreted renally Uraemia may cause denaturation of proteins and change of structure or binding site configuration and may affect drug action Problems in renal dysfunction (2) Fluid and electrolyte balance Hypervolaemic and hypertensive with overload Dehydrated with limited cardiovascular reserve post dialysis Metabolic acidosis with respiratory compensation. Hyperkalaemia Hypermagnesaemia Hypocalcaemia Problems in renal dysfunction (3) Conditions assosciated with uraemia Hypertension and arrythmias, cardiomegaly and failure Pericardial effusions IHD Pulmonary oedema, atelectasis, pneumonia and ARDS Immunosuppression Poor wound healing Coagulopathy Peptic ulceration Hiccups Nausea and vomiting Problems in renal dysfunction (4) Anaemia Normochromic, normocytic secondary to reduced erythropoetin secretion Multiple transfusions and associated infections. Increased risk of surgical, pericaridial ad surgical haemorrhage Effect of anaesthesia on renal function Most operations on well-hydrated patients cause little effect on renal function. Most patients with mild renal disease do well. Autoregulation is preserved but function will be imparied below MAP of 60mmHg Patients with pre-operative renal dysfunction are more likely to go on to develop renal failure Pre-operative Surgery should be 24hrs after haemodialysis Peritoneal dialysis can continue until surgery Blood transfusion is best done during dialysis Bloods Correct clotting abnormalities Note any fistulae Consider gastro-protection and RSI Peri-operative (1) Consider regional approach Duration of LAs may be reduced Caution with spinal or epidural Avoid any av fistulae which should be protected Avoid lactate and potassium containing solutions Use drugs that are not primarily renally excreted Propofol Atracurium, rocuronium or vecuronium are suitable Iso, sevo, or des + nitrous Sux is not absolutely contraindicated May have prolonged action Pre-existing neuropathy or hyperkalaemia Peri-operative (2) Caution with medications that accumulate Morphine Digoxin Aminoglycosides ACE inhibitors Careful fluid balance to avoid overload Doppler CVP Urine output > 0.5mls/kg//hr Volume expansion first over vasopressors Consider improving renal perfusion Dopamine Mannitol ?Frusemide Post-operative Observe for signs of fluid overload, dehydration and residual neuromuscular blockade Patients who have already needed dialysis should go to HDU/ITU or any location with ready access to dialysis Analgesia with cautious opiods, avoid NSAIDs