Renal Anatomy, Physiology, Pathophysiology, and Anesthesia Management

Chapter 29


Renal Anatomy, Physiology, Pathophysiology, and Anesthesia Management



The kidneys are paired organs that lie retroperitoneally on both sides of the vertebral column. They function to excrete the end products of bodily metabolism and thereby control the concentration of constituents of body fluids. A rich blood supply to these vital organs, coupled with the physiologic processes of filtration, reabsorption, secretion, and excretion, maintains homeostasis of the fluid that bathes each cell. For management of anesthetized patients to be optimal, clinicians must be familiar with physiologic mechanisms that allow the kidneys to control the body’s intracellular and extracellular environments.


This chapter addresses the effect of anesthesia and surgery on both the normal and the diseased kidney. After a discussion of the anatomic structure and physiologic mechanisms of the kidney, the effects of anesthesia on normal renal function are addressed. Pathophysiologic mechanisms associated with acute and chronic renal failure follow. Preoperative renal assessment and anesthetic considerations for patients with impaired renal function are emphasized, and pertinent anesthetic considerations for common urologic procedures are identified.



Structure of the Kidney


The kidneys are bean-shaped, reddish-brown organs located in the posterior part of the abdomen on both sides of the vertebral column (Figure 29-1). These organs extend from the 12th thoracic vertebra to the 3rd lumbar vertebra; each weighs approximately 125 to 170 g in men and 115 to 155 g in women. Each kidney is about 11.25 cm long, 5 to 7.5 cm wide, and 2.5 cm thick. The right kidney’s position is slightly lower than the left because of hepatic displacement. The kidneys and their vessels are embedded in fatty tissue (perirenal fat) and enclosed in renal fascia. Renal fascia and large vessels hold the kidneys in position (see Figure 29-1).



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FIGURE 29-1 Kidney position.


The anterior and posterior surfaces, upper and lower poles, and lateral margin of the kidney have convex contours. The medial margin is concave because of the presence of the hilus (recessed fissure). Structures that enter or leave the kidney through the hilus include the renal artery and vein, nerves, lymphatics, and ureters.


A longitudinal section of the kidney reveals two distinct regions—the outer cortex and the inner medulla (Figure 29-2). The medulla is divided into 8 to 18 triangular wedges called pyramids. The base of each pyramid is directed toward the renal cortex, and the apexes converge toward the renal pelvis. Pyramids have a striated appearance because they contain the loop of Henle and collecting ducts of the nephron. The apex of each pyramid, called the papilla, is composed of many collecting ducts, and those papillary ducts empty into a cup-shaped structure known as the minor calyx. Several minor calyces join to form major calyces, which come together as the renal pelvis. The renal pelvis is the major reservoir for urine. Ureters connect the renal pelvis to the bladder. 1




Nephron


The functional unit of the kidney is the nephron. Approximately 1,250,000 of these units are present in each kidney. The shape of the nephron is unique, unmistakable, and admirably suited for its function. Each area of the nephron is selective with regard to its performance. Nephrons hold the filtrate that has been filtered from the blood. End products of metabolism are excreted, and metabolically important substances such as water are reabsorbed as needed.


The nephron (Figure 29-3) begins in the cortex at the glomerulus and ends where the tubule joins the collecting duct at the papilla. The glomerulus is a tuft of capillaries derived from the afferent arteriole. Blood is brought to the glomerulus by the afferent arteriole; blood that is not filtered returns to the circulation by way of the efferent arteriole (see Figure 29-3). The filtrate from the glomeruli enters the Bowman capsule, or capsula glomeruli, flows through a tortuous tube, or proximal convoluted tubule, and then goes to the loop of Henle, distal convoluted tubule, and collecting duct.



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FIGURE 29-3 The nephron.


The nephron, which changes in shape and direction as it follows its course, is contained partly in the renal cortex and partly in the medulla (Figure 29-4). The cortex contains the Bowman capsule, glomerulus, and proximal and distal tubules. The thin, descending loop of Henle comes from the proximal tubule and extends toward the pyramid. The descending loop of Henle eventually bends on itself and forms an enlarged, ascending loop of Henle. The ascending limb joins the distal convoluted tubule.1



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FIGURE 29-4 Renal filtration.


The kidneys have two kinds of nephrons: cortical nephrons, which extend only partially into the medulla, and juxtamedullary nephrons, which lie deep in the cortex and extend deep into the medulla. One fifth to one third of the nephrons are juxtamedullary and play an important role in concentration of urine.



Renal Blood Supply


To understand how the kidneys function, it is essential to understand their blood supply. The kidneys are highly vascular. Although they represent only 0.5% of body weight, they receive 1100 to 1200 mL of blood per minute, or 20% to 25% of the cardiac output. Blood reaches these organs through the renal arteries. At the hilus of the kidney, the renal artery divides into several lobar arteries and then subdivides again into interlobar arteries, which run between the pyramids. When these vessels reach the corticomedullary zone, they make well-defined arches over the bases of the pyramids. These vessels, known as arcuate arteries, divide into a series of arteries known as interlobular arteries (see Figure 29-2). An interlobular artery may terminate as an afferent arteriole or as a nutrient artery to the tubule.


The afferent arterioles form the high-pressure capillary bed within the Bowman capsule called the glomerulus. Because little or no oxygen is removed in the glomerulus, the blood that is not filtered begins its passage to the venous system via the efferent arteriole. The efferent arteriole is smaller than the afferent arteriole, thereby affording some resistance to blood flow. The efferent vessel soon becomes a plexus of capillaries again, and this low-pressure bed is known as the peritubular capillary. The peritubular capillary bed winds and twists around the proximal and distal tubule. A few hairpin loops, called vasa recta, dip down among the loops of Henle. Anatomic arrangements of these capillary beds and the renal tubules set the stage for filtration, reabsorption, and concentration of urine.


After leaving the peritubular capillary, blood returns to the central circulation via the veins. Renal veins are named in reverse order of the arteries, and therefore are the interlobular, arcuate, interlobar, lobar, and renal veins. The renal vein leaves the kidney at the hilus and empties into the inferior vena cava.


The portion of the cardiac output that passes through the kidney is called the renal fraction. Because cardiac output in a 70-kg man is approximately 5600 mL/min, and blood flow through both kidneys is 1200 mL/min, the normal renal fraction is 21%. This flow may vary from 12% to 30%. Distribution of renal blood flow is to the renal cortex and the medulla, with the cortex receiving the larger amount. Values obtained from dogs indicate that 3 to 5 mL/g/min are distributed to the cortex, 1 to 2 mL/g/min to the outer medulla, and 0.3 to 0.6 mL/g/min to the inner medulla. Only a small portion of blood (1% to 2%) flows through the vasa recta in the medulla. 1



Regulation of Renal Blood Flow


Blood flow to any organ is determined by the arteriovenous pressure difference across the vascular bed and is given by the following relationship:


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where MAP is the mean arterial pressure, VP is the venous pressure, and VR is the vascular resistance. Renal blood flow is regulated by intrinsic autoregulation and neural regulation.


Autoregulation of renal blood flow implies that blood flow remains normal despite a considerable change in pressure. With a MAP between 50 and 180 mmHg, renal blood flow to both kidneys remains 1200 mL/min. If mean systemic blood pressure falls below 50 mmHg, filtration ceases. Afferent arteriole vasodilation and myogenic mechanisms are responsible for autoregulation.1


When renal blood flow decreases, glomerular filtration is reduced. A reduction in glomerular filtration leads to dilation of the afferent arteriole. An increase in blood flow to the glomerulus returns glomerular filtration to normal.


Myogenic mechanisms also play a role in renal autoregulation. When arterial pressure rises, the arterial wall is stretched, the vessel constricts, and blood flow remains normal. When arterial pressure decreases, the opposite effect occurs. Therefore renal blood flow remains constant over a wide range of pressure changes.


Neural regulation also has a role in renal blood flow. The sympathetic nervous system innervates both the afferent and efferent arterioles. Although autoregulation overrides the adrenergic system with mild stimulation, acute sympathetic stimulation with its associated vasoconstriction can decrease renal blood flow substantially. The parasympathetic nervous system is not physiologically significant.1



Renal Physiology


The kidneys maintain a steady state essential to life. This is accomplished through three major mechanisms: filtration, reabsorption, and tubular secretion. What is filtered or secreted but not reabsorbed is excreted as urine.



Filtration


Filtration, which results from pressures that force fluids and solutes through the glomerulus, is the first step in the formation of urine. The quantity of glomerular filtrate formed each minute in all nephrons is called the glomerular filtration rate (GFR). The filtration fraction is the quantity of renal plasma flow that becomes filtrate and is defined as GFR divided by the flow to one kidney. Because the GFR is approximately 125 mL/min, and the flow to one kidney is 650 mL/min, the filtration fraction is 125/650, or 19% (approximately one fifth) of plasma flow. Of the 125 mL/min (or 180 L/day) of this protein-free filtrate made, 99% is reabsorbed from the renal tubules, and the remaining small portion is excreted as urine.1



Regulation of Glomerular Filtration Rate


Glomerular filtration is also dependent on several physiologic factors:



The pressure inside the high-pressure glomerulus (60 mmHg) is an outward force, whereas the colloid osmotic pressure created by proteins in the glomerulus (28 mmHg) is an inward force that tends to hold fluid within the glomerulus. Pressure in the Bowman capsule (18 mmHg) opposes filtration. As illustrated in Figure 29-4, filtration pressure is the pressure that forces fluid through the glomerular membrane. It is equal to the glomerular pressure minus the sum of the glomerular colloid osmotic pressure and the capsular pressure. With the values given, the normal filtration pressure is 10 mmHg. Several factors can alter GFR. Increased renal blood flow, dilation of the afferent arteriole, and increased resistance in the efferent arteriole increase GFR. Afferent arteriole constriction and efferent arteriole dilation tend to decrease GFR.


A special structure called the juxtaglomerular complex regulates GFR. At the juxtaglomerular complex, the distal convoluted tubule lies between the afferent and efferent arterioles. Cells of the distal tubule coming into contact with the arterioles are dense and therefore are referred to as the macula densa. Smooth muscle cells of both the afferent and efferent arterioles consist of juxtaglomerular cells, which contain renin. Anatomically this structure is arranged to allow fluid in the distal tubule to alter afferent or efferent arteriolar tone and thus regulate GFR.


Decreased glomerular filtration causes overabsorption of sodium ions (Na+) and chloride ions (Cl−) in the ascending limb of the loop of Henle and therefore a reduction in the delivery of these ions to the macula densa. Decreases in the concentrations of sodium and chloride cause afferent arterioles to dilate and thus increase renal blood flow and GFR. Sympathetic stimulation and decreased delivery of both sodium and chloride to the macula densa also cause the juxtaglomerular cells to release renin. Renin clears angiotensinogen from the liver to form angiotensin I. In the lung, angiotensin I is changed into angiotensin II under the influence of a converting enzyme. In addition to having a generalized vasoconstricting effect, angiotensin II causes constriction of the efferent arteriole. This causes the pressure in the glomerulus to increase and the GFR to return to normal.1




Tubular Reabsorption and Secretion


Conversion of glomerular filtrate to urine is the result of filtration at the glomerulus, tubular reabsorption or transport from the tubular lumen to the renal cell, and secretion or transport from the renal cell to the filtrate. Of all that is filtered or secreted, 99% is reabsorbed as the filtrate moves along the nephron.


Tubular reabsorption permits conservation of essential substances such as water, glucose, amino acids, and electrolytes. Some substances, such as water and sodium, are reabsorbed throughout the nephron, whereas others, such as glucose, are completely reabsorbed when plasma concentrations are low. Certain substances have a reabsorption maximum value, and after that value is reached, excess filtered material is excreted, regardless of plasma concentration. This maximum value is termed maximum transport. Maximum transport occurs because of saturation of a carrier for a particular substance.


By the time the blood has reached the peritubular capillary, one fifth of the plasma has been filtered into the Bowman capsule. The hydrostatic pressure in this low-pressure capillary bed has dropped to 13 mmHg, whereas the osmotic pressure has increased to 30 to 32 mmHg. The peritubular capillaries are extremely porous compared with those in other body tissues, and their proximity to the proximal and distal tubule sets the stage for movement of water and solutes from the tubule to the peritubular capillary bed. Anatomic location and the colloid osmotic pressure of plasma proteins account for the rapid absorption required in this area.1



Transport Mechanisms


Basic mechanisms of transport through the tubular membrane can be divided into active transport and passive transport. Active transport is the net movement of particles across a membrane against an electrochemical gradient, generally at the cost of metabolic energy. Passive transport involves the movement of substances across membranes and relies on either concentration gradients or chemical gradients. Active transport can be further divided into primary active transport, which requires energy, and secondary active transport, which does not require energy. Most primary active transport is for sodium. Secondary active transport is a result of the movement of sodium from the tubular lumen to the interior of the cell. For example, the active transport of sodium pulls glucose and amino acids with it. Because a carrier protein in the membrane combines with sodium and glucose, the process is termed cotransport. In addition to glucose and amino acids, chloride, phosphate, calcium, magnesium, and hydrogen ions are co-transported.


Some substances are actively secreted into the renal tubule in exchange for other molecules. Hydrogen, potassium, and urate ions are secreted in this manner. Hydrogen and potassium are generally secreted in exchange for sodium in a process termed countertransport.


When substances are actively transported from the tubule to the peritubular capillary bed, a concentration gradient that causes passive absorption of water by osmosis is established. When positive ions are actively transported, negative ions follow to maintain electrical neutrality. Chloride ions and urea are examples of substances that are passively absorbed.1



Proximal Tubule


Each portion of the renal nephron is selective with regard to what is reabsorbed or secreted. Active transport of sodium is the primary function of the proximal tubule. Water, most electrolytes, and organic substances are cotransported with sodium. The osmotic force generated by active sodium transport promotes passive diffusion of water out of the tubules into the peritubular capillaries. Passive transport of water is further enhanced by the elevated osmotic pressure of the blood in the peritubular capillaries. Reabsorption of water leaves an increased concentration of urea within the tubular lumen, thereby creating a gradient for its passive diffusion into the peritubular plasma. As positively charged sodium ions leave the tubular lumen, negatively charged chloride ions passively follow to maintain electroneutrality. Hydrogen ions are actively secreted in exchange for sodium. Secretory transport of sodium also occurs in the proximal tubule.


As the filtrate passes along the proximal tubule, 60% to 70% of filtered sodium and water, 50% of urea, and potassium, calcium, phosphate, uric acid, and the bicarbonate (HCO3) form of carbon dioxide (CO2) have been reabsorbed. Glucose, proteins, amino acids, acetoacetate ions, and vitamins are completely or almost completely reabsorbed by active processes. Because protein molecules are too large to be reabsorbed by normal mechanisms, a special mechanism called pinocytosis is used to save proteins. In this process, the tubular membrane engulfs the protein and internalizes it. Once inside the cell, the protein is digested into amino acids that can then be absorbed into the interstitial fluid.



Loop of Henle


The primary function of the loop of Henle is to establish a hyperosmotic state within the medullary area of the kidney, a function vital to conservation of salt and water. Water conservation and the production of a concentrated urine involve a countercurrent exchange system in which a concentration gradient causes fluid to be exchanged across parallel pathways. The fluid moves up and down the parallel sides of the hairpin loop of Henle in the medulla. The longer the loop, the greater the concentration gradient, because the gradient increases from the cortex to the medulla. Sluggish blood flow in the vasa recta helps maintain the gradient.


Countercurrent exchange begins in the thick, ascending limb of the loop of Henle with the active transport of sodium and chloride out of the tubular lumen and into the medullary interstitium. Because the lumen in this area is impermeable to water, water cannot follow. The tubular fluid becomes hypoosmotic, and the medullary interstitium hyperosmotic. The descending limb of the loop is highly permeable to water but does not actively transport sodium and chloride. Sodium and chloride diffuse into the interstitium, the hypertonic interstitium causes water to move out, and the remaining fluid in the descending loop becomes concentrated at the tip of the medulla. As the tubular fluid rounds the loop and enters the ascending limb, water is retained, and sodium and chloride are removed. The filtrate therefore is very dilute as it reaches the distal tubule. The thick segment of the loop of Henle has a powerful role in renal mechanisms for diluting or concentrating the urine.1






Renal Hormones






Atrial Natriuretic Factor


Atrial natriuretic factor (ANF) is a peptide hormone synthesized, stored, and secreted by the cardiac atria.3 It acts on the kidney to increase urine flow and sodium excretion, and it may enhance renal blood flow and GFR. In addition, ANF antagonizes both the release and end-organ effects of renin, aldosterone, and ADH. The stimulus for ANF release is atrial distention, stretch, or pressure.4 ANF is one of the most potent diuretics known. Inhibition of plasma renin, angiotensin, and aldosterone can produce a dose-dependent decrease in blood pressure.





Renal Regulation of Acid-Base Balance


The kidneys, along with the body’s fluid buffers and respiratory system, play a major role in regulating acid-base balance. Epithelial cells of the proximal tubules, the thick portion of the loop of Henle, distal tubules, and collecting ducts secrete hydrogen into the tubular fluid. This secretory process actually begins with CO2 in the epithelial cells, where under the influence of carbonic anhydrase, CO2 combines with water to form carbonic acid (H2CO3). H2CO3 dissociates into HCO3 and hydrogen ions, and hydrogen ions are actively secreted into tubular fluid in exchange for sodium ions. This exchange maintains appropriate electrical balance between anions and cations in the tubular fluid.


An increase in HCO3 in alkalosis means that the filtered amount of HCO3 exceeds the amount of hydrogen secreted. Because excess HCO3 must react with hydrogen (HCO3− + H+ → H2CO3 → CO2− + H2O) and be absorbed as CO2, excess HCO3 ions are lost in the urine along with sodium. In this way, sodium and excess HCO3 are removed from the extracellular fluid.


In acidosis the concentration of hydrogen ions increases to a level far greater than that of HCO3 in the tubules. Excess hydrogen ions are lost in the urine through the phosphate or ammonia (NH3) buffer system.


The phosphate buffer is composed of hydrogen phosphate (HPO2−) and dihydrogen phosphate (H2PO4). Both of these ions become concentrated in the tubular fluid because of poor reabsorption. The quantity of HPO2− is normally fourfold that of H2PO4. Excess hydrogen ions entering the tubules combine with monohydrogen phosphate to form H2PO4, which is lost in the urine. A sodium ion is absorbed into the extracellular fluid in exchange for hydrogen. It combines with HCO3, which was formed in the process of secretion of the hydrogen, and sodium bicarbonate is added to the extracellular fluid.


NH3, which is synthesized by all epithelial cells except those in the thin segment of the loop of Henle, is also secreted into the tubules. NH3 reacts with hydrogen to form the ammonium ion (NH4). Ammonium ions are lost in the urine with chloride and other tubular anions.


The kidneys control extracellular fluid hydrogen concentration by excreting an acidic or basic urine. Excretion of acidic urine removes excess acid from the extracellular fluid, whereas loss of basic urine removes base from the extracellular fluid.



Concentration and Dilution of Urine


The kidneys have the ability to respond to the changing tonicity of body fluids by excreting dilute or concentrated urine. This function involves a countercurrent exchange system in which a concentration gradient causes fluid to be exchanged across parallel pathways (see Figure 29-6). In a countercurrent exchanger, reversal of flow in one stream results in the formation of a gradient that allows water and solutes to be exchanged along the length of the tube. The countercurrent exchanger in the kidney is the descending and ascending loop of Henle. The concentration gradient increases from the cortex to the tip of the medulla. The anatomic arrangement of this part of the nephron and sluggish blood flow in the vasa recta help maintain the gradient.


Plasma water filtered at the glomerulus is isotonic with plasma. The daily urinary output is approximately 1.5 L/day, and its osmolarity may vary from 40 to 1400 mOsm/L, depending on water intake or loss. This is possible because of the countercurrent mechanism.


Approximately two thirds of the tubular fluid is reabsorbed between the glomerulus and the end of the proximal tubule. The tonicity of the filtrate in this area is the same as that of the surrounding tissue, or 300 mOsm. As the filtrate leaves the proximal tubule, it passes through an increasingly more concentrated medulla. Changes in the thick ascending limb of the loop of Henle are responsible for the hypertonicity.


The thick ascending limb of the loop of Henle is responsible for the active transport of sodium and chloride into the medullary interstitium. In contrast to the descending limb of the loop of Henle, the tonicity of which is in equilibrium with that of the interstitium, the ascending loop has a low permeability to water. The active transport of sodium and chloride produces a gradient between the ascending loop of Henle on one side and the descending loop and interstitium of the renal medulla on the other. The descending limb is highly permeable to water but does not actively transport sodium and chloride. The hyperosmotic interstitium causes water to move out of the descending limb, and the filtrate in the descending tubule is concentrated to 1200 mOsm at the tip of the medulla. As the tubular fluid rounds the loop and enters the ascending limb, active transport of sodium and chloride and retention of water create a hypoosmotic fluid of 100 mOsm at the distal tubule.


The hypoosmotic fluid of the distal tubule is delivered to the collecting duct, where the final adjustments of urine volume and concentration take place. In the absence of ADH, water permeability is low, and water is not reabsorbed. Because sodium and chloride can be reabsorbed, the osmolality decreases to below that of the distal tubule, and the urine is dilute. When the need for water conservation arises, ADH is secreted, permeability of the collecting duct increases, and water diffuses out of the duct into the hyperosmolar environment of the medullary extracellular fluid. In this way urine is concentrated and its volume is reduced.


The sluggish blood supply of the vasa recta in the medulla allows blood to flow through the medullary tissue without disturbing the osmotic gradient. If blood flow were rapid, the medullary concentration gradient and the ability to concentrate the urine would be lost.1,5



Effects of Anesthesia on Normal Renal Function


Before considering anesthetic implications for patients with renal disease, it is important to review the effects of anesthesia and surgery on normal renal function. Numerous studies have attempted to identify the effects of anesthesia on renal function, and although some have contributed to a better understanding of this area, differences among the studies in premedication, depth of anesthesia, fluid regimens, and other aspects of the experimental protocol allow only the broadest comparisons.



Anesthetic Effects


General anesthesia is associated with a temporary depression of renal blood flow, GFR, urinary flow, and electrolyte excretion. Although similar changes occur after spinal and epidural anesthesia, the magnitude of change tends to parallel the degree of sympathetic block and blood pressure depression. This consistent and generalized depression of renal function has been attributed to a number of factors, including type and duration of surgical procedure, physical status of the patient, volume and electrolyte status, depth of anesthesia, and choice of agent.5


Anesthesia may alter renal function by direct or indirect effects. Indirect effects are mediated through changes in the circulatory, endocrine, or sympathetic nervous system. Anesthetic drugs alter the circulatory system by decreasing renal perfusion, increasing renal vascular resistance, or a combination of both. Drugs associated with catecholamine lead to vasoconstriction, an increase in renal vascular resistance, a decrease in renal blood flow, and a decrease in renal function. Volatile agents such as isoflurane cause a mild to moderate increase in renal vascular resistance as a compensatory response to decreased perfusion pressure secondary to alterations in cardiac output or systemic vascular resistance.6–10 Desflurane has been shown to produce hemodynamic effects comparable to those produced by isoflurane.11 It increases heart rate and decreases both mean arterial pressure and systemic vascular resistance while maintaining cardiac output. In some studies, but not all, desflurane maintains arterial pressure and systemic vascular resistance to a greater degree than equianesthetic concentrations of isoflurane. Otherwise, desflurane and isoflurane have similar effects on most vascular beds, including the renal circulation.


Although earlier studies suggested that renal blood flow was reduced with sevoflurane, no renal functional or morphologic defects were noted after administration of this agent. Issues regarding the renal effects of the release of free fluoride ion associated with sevoflurane metabolism have been debated. Historically, high fluoride ion concentrations in the range of 60 to 90 µmol/L after methoxyflurane metabolism have led to nephrotoxicity characterized by polyuria. This methoxyflurane polyuria was commonly referred to as high-output renal failure. Sevoflurane has not produced the expected toxicity in the same way as methoxyflurane even though significant levels of fluoride ion may result from prolonged administration. A few reasons have been theorized for the lack of nephrotoxicity of sevoflurane, even though levels of metabolically released fluoride ion can approach those of methoxyflurane. They include the fact that sevoflurane metabolism is largely hepatic rather than renal. Intrarenal production of inorganic fluoride may be a more important factor than hepatic metabolism for the nephrotoxicity produced by increased serum fluoride concentration. Sevoflurane also has a much lower blood solubility so that it undergoes rapid elimination Sevoflurane has not been associated with nephrotoxicity.12–15


Changes in renal function during barbiturate, opiate, and nitrous oxide anesthesia are similar to those observed during the administration of low-dose volatile anesthesia.16 Preoperative hydration, lower concentrations of volatile anesthetics, and maintenance of normal blood pressure attenuate reductions in renal blood flow and GFR.17


High levels of spinal or epidural anesthesia can impair venous return, diminish cardiac output, and reduce renal perfusion.18 Epidural blocks at thoracic levels with epinephrine-containing local anesthetics cause moderate reductions in renal blood flow and GFR that parallel the decrease in mean blood pressure.19 Epidural blocks performed with epinephrine-free solutions generate little change in systemic hemodynamics; however, absorption of local anesthetics is enhanced in uremic patients.20


In summary, virtually all anesthetics have the potential to alter the cardiovascular system and affect renal blood flow, GFR, and urinary output. Although systolic arterial blood pressure may not fall below 80 to 90 mmHg, renal blood flow may be decreased by 30% to 40% after the administration of various anesthetics. This suggests impairment of autoregulation. In most cases, changes in renal function are transient and reversible. If they persist into the postoperative period, the cause is often a combination of factors such as preexisting renal or cardiovascular disease, severe fluid imbalance, or mismatched blood, and the importance of the anesthetic effects is decreased.



Physiologic Responses


The renal vasculature is richly innervated by the sympathetic nervous system. Drugs or perioperative events that stimulate this system cause an increase in renal vascular resistance and a decrease in renal blood flow and glomerular filtration. Surgical stress also may alter autonomic and neuroendocrine responses. Norepinephrine from sympathetic postganglionic nerve fibers and epinephrine and norepinephrine from the adrenal medulla shift blood away from the cortical nephrons; this results in decreases in renal blood flow, GFR, electrolyte excretion, and urinary output. Catecholamines also stimulate the release of renin, which ultimately leads to the production of angiotensin II, a potent vasoconstrictor.


Endocrine changes associated with anesthesia and surgical stress involve ADH, aldosterone, and the renin-angiotensin-aldosterone system. Although the perioperative period is associated with high circulating levels of ADH and aldosterone, it is not clear whether anesthetics stimulate the release or the release is secondary to the surgical stress response. General anesthetics and narcotics are thought to be minor stimuli of the release of ADH, but laparoscopic surgical procedures have been shown to increase ADH levels.21 Clinical studies have specifically identified that pneumoperitoneum during laparoscopic surgery increases the level of ADH.22 Other studies indicate that patients undergoing anesthetics lasting long durations had significant increases in ADH, with the greatest increase occurring at emergence.23 Additional investigations have shown that ADH levels increase after the induction of anesthesia and is higher in subjects receiving lower concentrations of remifentanil-propofol anesthesia.24


It is clear that ADH release is modulated by blood volume changes that are sensed by stretch receptors in the atrial wall. Hemorrhage, positive pressure ventilation, and the upright position increase ADH release.25,26 A decrease in arterial pressure stimulates ADH release. Distention of a balloon in the atrium, negative pressure ventilation, and immersion in water up to the neck decrease ADH release.


Renin-angiotensin levels may be elevated during the perioperative period, but the role of anesthetics and stress is not clear. Some studies have reported large increases in plasma renin levels associated with the use of anesthetics, whereas others report variances dependent on type of anesthesia delivered as well as surgical procedure. Balanced anesthesia has been found to result in higher levels of epinephrine, norepinephrine, and adrenocorticotropic hormones than total intravenous anesthesia.27 The influence of renin-angiotensin on the renal effects of anesthetic agents needs further clarification. Renin levels have been shown to increase during laparoscopic surgery, as well as vasopressin, epinephrine, norepinephrine, and cortisol.28 Preoperative hydration is thought to be important in the intraoperative release of renin.


Aldosterone, a hormone released from the adrenal gland, is responsible for the precise control of sodium excretion. It is not known whether anesthetic agents act directly on the adrenal gland to cause aldosterone release. They probably act indirectly through the neuroendocrine system and the renin-angiotensin-aldosterone system. Stimulation of the sympathetic nervous system causes renal vasoconstriction, which is a trigger for the renin-angiotensin-aldosterone system. Aldosterone leads to sodium and water reabsorption and can be associated with decreased urinary output.



Nephrotoxicity of Anesthetic Agents


The kidneys are extremely vulnerable to toxicity because of their rich blood supply and the increase in the concentration of excreted compounds that occurs in the renal tubules during the process of reabsorption. Medullary hyperosmolality encourages concentration of all substances, including toxins. The amount of renal damage associated with nephrotoxic agents depends on the concentration of the toxins, the degree of toxin binding to plasma proteins and nonrenal versus renal tissue, and the length of exposure of the kidneys to the toxin. The nephrotoxicity of anesthetic agents became fully appreciated in 1966, when vasopressin resistant–polyuria renal insufficiency was reported in patients receiving prolonged methoxyflurane anesthesia for abdominal surgery.29 Evidence gathered indicated that the release of the inorganic fluoride ions (F−) in the metabolism of this fluorinated anesthetic was the causative agent in nephrotoxicity. Fortunately none of the modern inhalation anesthetics are nephrotoxic.



Fluoride Ion Toxicity


Fluoride alters renal concentration mechanisms by interfering with active transport of sodium and chloride in the medullary portions of the loop of Henle. It also acts as a potent vasodilator, resulting in increased blood flow in the vasa recta and washout of medullary solute. Fluoride is a potent inhibitor of many enzyme systems, including those involving ADH, which is necessary for distal nephron reabsorption of water. Proximal tubular swelling and necrosis associated with fluoride ions also contribute to nephrotoxicity. Signs and symptoms of fluoride nephrotoxicity include polyuria, hypernatremia, serum hyperosmolality, elevations in blood urea nitrogen (BUN) and serum creatinine levels, and decreased creatinine clearance. The extent of nephrotoxicity in general surgical patients has been correlated with dosage or maximum allowable concentration hours (MAC-hours), duration, and peak fluoride concentrations.29



Methoxyflurane


Methoxyflurane, an anesthetic no longer used, was the first anesthetic associated with serious nephrotoxicity. The serum fluoride concentration after methoxyflurane anesthesia showed positive correlation with the degree of renal dysfunction.30 Vasopressin-resistant polyuria similar to that seen after methoxyflurane anesthesia was later produced in Fischer 344 rats injected with sodium fluoride.31 After 2.5 to 3 MAC-hours of methoxyflurane anesthesia, fluoride concentration was 50 to 80 µmol, and subclinical toxicity evidenced by a delayed return to maximum preoperative urine osmolarity and decreased urate clearance were noted.


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May 31, 2016 | Posted by in ANESTHESIA | Comments Off on Renal Anatomy, Physiology, Pathophysiology, and Anesthesia Management

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