Fig. 33.1
Anatomy of the kidney and urinary system
Autonomic innervation of genitourinary tract consists of sympathetic fibers (originating from T8–L1) and parasympathetic fibers (vagal nerve and nerves originating from S2–4), which serve to modulate renal perfusion, peristalsis, and sphincter tone (Table 33.1). Efferent nerves for both parasympathetic and sympathetic innervation of genitourinary systems originate from the spinal cord as splanchnic nerves, combining at several major nerve plexus which then innervate visceral organs. Sympathetic stimulation serves to inhibit peristalsis and increase sphincter tone while parasympathetic stimulation serves the opposite functions. Innervation of the intra-abdominal components of the genitourinary system, the kidney, and the ureter is primarily thoracolumbar (T8–L2), while the nerve supply of the pelvic organs, the bladder, the prostate, the seminal vesicles, and the urethra is primarily lumbosacral with some lower thoracic input (T10). Nerve supply to the testicles is via the ilioinguinal nerve and genital branch of the genitofemoral nerve for the anterior scrotum. These nerve branches originate from T10 to L2. The posterior portion of the scrotum is innervated from S1–4.
Table 33.1
Autonomic and sensory innervation of the genitourinary system
Organ | Sympathetics | Parasympathetics | Spinal levels of pain conduction |
|---|---|---|---|
Kidney | T8–L1 | CN X (vagus) | T10–L1 |
Ureter | T10–L2 | S2–4 | T10–L2 |
Bladder | T11–L2 | S2–4 | T11–L2 (dome), S2–4 (neck) |
Prostate | T11–L2 | S2–4 | T11–L2, S2–4 |
Penis | L1–2 | S2–4 | S2–4 |
Scrotum | NS | NS | S2–4 |
Testes | T10–L2 | NS | T10–L1 |
Renal Physiology
The functions of the kidney are numerous including feedback mechanisms that maintain fluid balance, osmolarity, electrolyte content and concentration, and acidity within narrow limits. Extracellular solutes are tightly regulated, including sodium, potassium, hydrogen ion, bicarbonate, and glucose. The kidney also generates ammonia and glucose, and eliminates nitrogenous and other metabolic waste, including urea, creatinine, and bilirubin, as well as toxins and many classes of drugs. Finally, circulating hormones secreted by the kidney influence regulation of systemic blood pressure, red blood cell generation, and calcium homeostasis. The adrenal glands, sitting atop of the kidneys, are a major endocrine organ producing mineralcorticoid (aldosterone), glucocorticoids (cortisol), and sex steroids (androgens). The medulla of the adrenal glands is directly innervated by presynaptic sympathetic fibers and release systemic epinephrine in response to sympathetic stimulation.
Each kidney contains approximately one million nephrons, the functional units of the kidney (Fig. 33.2). The nephron is a tubular structure that is segmented into specialized parts, including the glomerulus, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and a collecting duct that drains into the renal pelvis and ureter. The glomerulus, a permeable tuft of capillaries, serves as the interface between blood and kidney. It is cupped by Bowman’s capsule, the most proximal component of the nephron, thereby, providing a large surface area for filtration of blood into the nephron. Blood flow to the glomerulus is regulated through the afferent and efferent arterioles, which adjust the glomerular filtration pressure. Depending on this filtration pressure, fluid (approximately 120 mL/min) is filtered into the Bowman’s capsule and then passes into the tubules.
Fig. 33.2
Structure and function of the nephron
The glomerular capillary endothelium, glomerular basement membrane, and visceral epithelium of Bowman’s capsule are responsible for creating the filtration barrier. All three layers are negatively charged and fenestrated. Filtration through the glomerulus is dependent on particle size and charge (cations readily filtered, while anions repelled and remain in the blood) and the hydrostatic pressure in the tuft (determined by afferent and efferent arterioles). Examples of molecules that are freely filtered are water, sodium, urea, glucose, and insulin. Larger molecules that are not filtered include hemoglobin and proteins (albumin). Injury to the kidney can result in disruption of the charge and fenestrations such that proteins are filtered, resulting in proteinuria.
The permeable large surface area of the glomeruli allows approximately 180 L of protein-free fluid to be filtered by the kidneys each day. However, almost 99 % of this filtrate is reabsorbed in the tubules of the nephrons. Unlike the glomerulus (which depends on perfusion pressure, particle size, and charge for passive filtration), the tubules depend on specialized active pumps to generate local environments of diffusion gradients. The tubule can be divided into several segments in which these local environments occur, allowing highly regulated solute and fluid absorption. Sodium is actively transported via triphosphate (ATP) pumps into the interstitium, while water follows passively across an osmolar gradient (Loop of Henle). Urine and plasma osmolality are regulated by a feedback mechanism in the loop of Henle: increased interstitial sodium concentrations which result from hypovolemia lead to an increased reabsorption of water and a decrease in urine output.
The glomerular filtration rate (GFR) describes the rate at which fluid is filtered by the kidneys.
Ideally the GFR is measured by clearance of a molecule that is freely filtered at the glomerulus, but neither secreted nor absorbed in the renal tubule. The gold standard molecule for GFR measurement is inulin (derived from Jerusalem artichoke, chicory, and dahlias), which is impractical for clinical use. Instead, due to ease of measurement, creatinine is used. Creatinine slightly overestimates true GFR because some creatinine is also secreted by renal tubules. Normal GFR is 120–130 mL/min/1.73 m2, with a decline with age by approximately 1 mL/min/1.73 m2 per year after the third decade. A GFR of 60 represents loss of approximately half of the adult level of normal kidney function.
Renal Blood Flow and Autoregulation
The kidneys are the best-perfused organ per gram of tissue in the body and receive 20 % of the cardiac output. Renal blood flow is heterogeneous with the renal cortex receiving approximately 80 % of renal blood flow, and the renal medulla receiving only about 20 %. As a result, the medulla is particularly susceptible to ischemia during periods of decreased renal blood flow. Several overlapping control mechanisms exist to regulate renal blood flow and GFR by altering tone of the afferent and efferent arterioles of the glomerulus and broadly include: autoregulation, the rennin–angiotensin–aldosterone system, and neurohumeral system.
Autoregulation
Global renal blood flow is autoregulated and is kept constant at a mean arterial pressure of 50–150 mmHg in normotensive patients. The mechanism for autoregulation is thought to be due to direct myogenic activity of the afferent arteriole in response to blood pressure. With increased blood pressure the afferent arteriole contracts (thereby reducing blood flow), and with reduced blood pressure the arteriole dilates, thereby, maintaining perfusion in low blood pressure states. Autoregulation fails when the mean arterial pressure falls below 50 mmHg at which point perfusion becomes pressure dependent.
Renin–Angiotensin–Aldosterone System
The renin–angiotensin –aldosterone system (RAAS) plays key role in salt and water reabsorption by the nephron (Fig. 33.3). The RAAS is regulated by the juxtaglomerular apparatus (JGA), a specialized group of cells adjacent to the afferent arteriole, and the macula densa, a specialized group of tubule cells located in the ascending limb of the loop of Henle. The JGA releases the enzyme renin in to the bloodstream which is responsible for production of angiotensin I in the liver. Angiotensin I is converted to active angiotensin II in the lung by angiotensin converting enzymes (ACE) which then stimulates aldosterone production by the adrenal gland. Aldosterone acts on tubule cells to increase intravascular volume and salt absorption. Therefore, renin catalyzes the rate limiting step in the production of angiotensin II; thus, it is plasma renin levels that determine angiotensin II levels. Cells of the macula densa act as chemosensors for filtrate passing through the tubule, and modulate the activity of JGA. The macula densa senses sodium chloride (NaCl) concentration, which is directly related to tubular flow rate (the higher the rate the higher the NaCl concentration). A decrease in NaCl concentration strongly stimulates secretion of renin from the JGA, thereby, increasing GFR.
Fig. 33.3
The renin–angiotensin–aldosterone system
In addition to its role in salt and water absorption, angiotensin II has significant effects on renal vasculature and GFR. Importantly, it causes increased vasoconstriction of the efferent arteriole relative to the afferent arteriole, which results in a higher hydrostatic pressure in the glomerulus, thereby, increasing filtration. However, in states of very high angiotensin II secretion, the differential in constriction of the afferent and efferent arterioles is lost, and GFR decreases. The stimulation of renin release during times of increased sympathetic activity is an important mechanism of maintaining GFR despite reduced renal blood flow resulting from catecholamine-induced vasoconstriction. In addition to the JGA-macula densa mechanism, renin secretion is also directly stimulated by a decrease in arterial pressure, which is thought to be due to direct stimulation of baroreceptors in the afferent arteriole responding to changes in wall stretch, and by circulating catecholamines which act on β-adrenergic receptors on the JGA cells.
Autonomic System
Catecholamines (norepinephrine and epinephrine) act on renal vascular α1 receptors leading to reduced renal blood flow by vasoconstriction. GFR is maintained during sympathetic activation by the RAAS activity, which disproportionately increases efferent arteriole constriction. The renal vasculature also contains dopaminergic receptors which cause vasodilation in response to activation. These dopaminergic receptors are the site of action of dopamine and fenoldopam, which are sometimes used to “protect” the kidney in times of high norepinephrine-induced vasoconstriction.
Prostaglandins
Prostaglandins are synthesized in the kidney and lead to afferent arteriole dilation. This dilation is an important mechanism of maintaining renal perfusion during systemic hypotension. Nonsteroidal inflammatory drugs (NSAIDs) block prostaglandin synthesis resulting in their nephrotoxic properties.
Atrial Natriuretic Peptide (ANP)
ANP is released by atrial myocytes in response to atrial stretch and beta receptor stimulation. ANP acts on the renal vasculature by dilating the afferent arteriole and possibly constricting the efferent arteriole of glomeruli, thereby, increasing GFR and promoting fluid elimination. ANP also antagonizes the action of aldosterone in the collecting duct, and the release of angiotensin, further reducing Na and H2O reabsorption.
Effects of Anesthesia on Renal Function
The primary effects of anesthesia and surgery on renal physiology occur through changes in GFR. Fluctuations in blood pressure can have a major effect on renal blood flow and GRF through vasodilation, which reduces renal blood flow when blood pressure falls below autoregulation range, and vasoconstriction (surgical stress), which induces sympathetic activation and alters renal perfusion by stimulating renin/angiotensin/aldosterone release. Clinical studies have failed to identify the superiority of one anesthetic technique over another in the general surgery population. Repeated insults from nephrotoxins in conjunction with ischemic injury or preexisting renal dysfunction are usually required to result in acute kidney injury.
Volatile anesthetics in general cause a decrease in GFR caused by a decrease in renal perfusion pressure either by decreasing systemic vascular resistance or cardiac output (e.g., halothane). This decrease in GFR is exacerbated by hypovolemia, and the release of catecholamines and antidiuretic hormone, as a response to painful stimulation during surgery. Some older inhalational anesthetics (methoxyflurane, enflurane) may, however, have a directly nephrotoxic effect from their metabolic breakdown to free fluoride ions. High intra-renal fluoride concentrations may impair the concentrating ability of the kidney and lead to non-oliguric renal failure. Sevoflurane is also associated with production of nephrotoxic Compound A (a vinyl ether), which is a degradation product formed during low flow anesthesia (<2 L/min) with interaction of sevoflurane with the carbon dioxide absorbent. Although nephrotoxic effects of compound A has been shown in animal models, they have not been shown to be significant in humans. Sevoflurane is considered safe even in patients with renal impairment as long as prolonged low-flow anesthesia is avoided. Isoflurane is metabolized to insignificant amounts of fluoride.
Opiates and benzodiazepines have minimal effect on renal function. Nonsteroidal anti-inflammatory drugs may be nephrotoxic through their inhibition of the production of prostacyclin. Some antibiotics commonly used during the perioperative period, particularly the aminoglycosides, can also be nephrotoxic. Aminoglycosides are filtered in the proximal tubule and bind to tubular membranes resulting in cellular injury. Toxicity is proportional to high trough levels of the drug. Other antibiotics such as β-lactams (penicillins, cephalosporins) can also cause interstitial nephritis.
Positive-pressure ventilation used during general anesthesia can decrease cardiac output leading to release of catecholamines, renin, and angiotensin II, which results in reduced renal blood flow and GFR. The use of regional anesthetic techniques that achieve a sympathetic block of levels T4–10 may be beneficial to patients with kidney disease, or those at high risk for postoperative kidney injury, as the sympathetic blockade attenuates catecholamine-induced renal vasoconstriction and suppresses cortisol and epinephrine release. However, care should be taken to maintain normovolemia and normotension to avoid decreases in renal perfusion associated with the regional anesthetic associated sympathetic blockade. Epidural anesthesia has minimal effects on renal blood flow in healthy volunteers as long as normotension and isovolemia are maintained.
Effects of Surgery on Renal Function
Surgical factors can have a significant impact on renal physiology. Insufflation of the abdomen during laparoscopic surgery can reduce venous return and cardiac output resulting in a decrease in renal blood flow and GFR. The increased intra-abdominal pressure during laparoscopic surgery also may be transmitted directly to the kidneys resulting in further reduction of renal blood flow. Aortic cross-clamping or occlusion of the inferior vena cava can drastically reduce renal blood flow. Suprarenal clamping of the aorta not only reduces blood flow to the kidneys but may also loosen aortic plaque resulting in renal embolism. Interestingly, there is also a reduction in renal blood flow with infra-renal aortic clamps, possibly through renal vasospasm or reduction in cardiac output resulting from the large increase in resistance due to clamping. Cardiopulmonary bypass is associated with renal dysfunction as a result of hypotension, microemboli, and inflammation. Use of off-pump coronary bypass grafting may cause renal injury comparable to cardio-pulmonary bypass, as the results of clinical trials have been equivocal.
The use of intravenous contrast during procedures which require angiograms can result in nephrotoxicity. Intravenous contrast induces renal injury through hemodynamic effects, direct contrast medium molecule tubular cell toxicity, and endogenous biochemical disturbances such as an increase in oxygen-free radicals and/or a decrease in antioxidant enzyme activity. Contrast-induced nephropathy is prevented by adequate hydration. Use of N-acetylcysteine (free radical scavenger) may help in preventing renal injury. Importantly, radiocontrast dye is an osmotic diuretic, which may increase urine output and actually worsening the renal injury through dehydration.
Renal Failure
Acute Kidney Injury
Approximately 1 % of patients undergoing general surgical procedures develop acute kidney injury (AKI). Patients developing perioperative AKI are more likely to be male, older, diabetic, and have a history of congestive heart failure, hypertension, ascites, or preoperative renal insufficiency. Emergency surgery doubles and intraperitoneal surgery more than triples the risk for postoperative AKI. Patients who develop AKI have a higher risk of postoperative morbidity and mortality. Additional patient and surgical risk factors for development of perioperative AKI are listed in Table 33.2.
Table 33.2
Risk factors for perioperative AKI
Preexisting renal insufficiency |
Congestive cardiac failure |
Hypertensive or diabetic nephropathy |
Sepsis, shock |
Nephrotoxic drugs—radiocontrast dye, aminoglycoside antibiotics, cyclosporin, NSAIDs |
Surgeries—kidney transplant, cardiopulmonary bypass, aortic cross-clamping |
Advanced age |
Acute kidney injury is characterized by an acute decline in GFR, associated with disturbances in fluid, electrolyte, and acid–base balance. Acute kidney injury commonly results from multiple insults and is often, but not always, reversible. A change in nomenclature from acute renal failure to acute kidney injury has allowed a more accurate characterization of the spectrum of disease from subclinical injury to complete organ failure. Classification of AKI is commonly described by the RIFLE or AKIN criteria. The RIFLE criteria for AKI contain five categories (risk, injury, failure, loss, and end-stage kidney disease rifle). The first three categories are defined by either percent change of serum creatinine or urine output criteria. The Acute Kidney Injury Network (AKIN) subsequently introduced a definition of AKI based on the observation that even smaller absolute changes of serum creatinine may affect morbidity and mortality.
Risk—serum creatinine 1.5 times the baseline, and urine output < 0.5 mL/kg/h for 6 h
Injury—serum creatinine 2 times the baseline, and urine output < 0.5 mL/kg/h for 12 h
Failure—serum creatinine 3 times the baseline, and urine output < 0.5 mL/kg/h for 24 h
Loss—persistent loss of renal function > 4 weeks
End-stage—persistent loss of renal function > 3 months
Acute kidney injury is commonly divided into three categories based on etiology (Table 33.3):
Table 33.3
Causes of acute kidney injury
Prerenal failure— State of low renal perfusion, nephron intact | – Hypovolemia (blood loss, dehydration) – Hypotension (Abdominal compartment syndrome) – Shock (CHF, Sepsis) – Unabated systemic/renal vasoconstriction (ACE inhibitors, NSAIDS, high sympathetic tone, high dose pressors) |
Intrinsic failure— State of nephron cell death from toxins/ischemia | – Vascular: Renal infarction, embolism – Tubular (ATN): Ischemia from prolonged prerenal state, nephrotoxins (aminogylcosides), rhabdomyolisis – Glomerular: Glomerulonephritis, vasculitis |
Postrenal failure— State of urinary flow obstruction | – Prostatic obstruction – Ureteral obstruction (stone, clot) or injury – Extraureteral obstruction |
1.
Prerenal (adaptive state to reduced perfusion through hypotension or dehydration, where structure and function of kidney remain intact)
2.
Intrinsic (cytotoxic injury with destruction of nephron anatomy and function)
3.
Postrenal (state of obstructive urine flow).
Renal failure also is classified according to urine flow rates, so the terms oliguric (<400 mL urine output in 24 h), nonoliguric (>400 mL urine output in 24 h), and polyuric renal failure are often encountered. Prerenal, intrinsic, and postrenal causes of failure can present as oliguric or non-oliguric failure, but more commonly present as oliguric failure. In some cases, patients with AKI may have normal or high (>2.5 L/day) urine flow rates, but have biochemical abnormalities that are similar to the abnormalities occurring in patients with low urine output. Their management is generally less complex than that of oliguric patients because fluid balance is easier to maintain.
Reversible prerenal AKI and acute tubular necrosis caused by medullary ischemia (intrinsic AKI) are two ends of a continuum. Initially, hypotension or dehydration leads to reduction in renal perfusion. Prerenal failure ensues and the kidney compensates by retention of solute and water leading to oliguria (<0.5 mL/kg/h) and a state of prerenal azotemia. This compensation increases tubular workload and decreases medullary blood supply. Prerenal azotemia is a reversible state; however, persistence of this state or an additional renal insult will eventually lead to irreversible ischemic injury and death of tubular cells characteristic of intrinsic renal failure. Urine output then decreases despite adequate intravascular volume, leading to accumulation of waste products. The traditional division of prerenal versus intrarenal azotemia is artificial, but may help guide treatment options, especially if further hydration may potentially reverse the condition.
Indices used to distinguish between prerenal and renal causes of AKI are provided in Table 33.4. The fractional excretion of sodium (FENa) is a commonly used to differentiate prerenal azotemia from acute tubular necrosis.
Table 33.4
Parameters used to distinguish between prerenal and renal causes of acute kidney injury
Parameters | Prerenal | Renal |
|---|---|---|
Fraction of sodium filtered | <1 % | >2 % |
Ratio of serumBUN/creatinine | >20 | <20 |
Urine sodium (meq/L) | <20 | >40 |
Urine osmolality (mosm/L) | >500 | <400 |
FENa is calculated as (UrineNa/PlasmaNa)∕(UrineCreatinine /PlasmaCreatinine)
A FENa <1 % is consistent with prerenal azotemia, while a FENa >3 % is consistent with the development of ATN. Notably, the calculation of a FENa is only useful in patients with oliguric renal failure, without preexisting renal failure, who have not received a diuretic. Urine sediment/microscopy is also useful in differentiating ATN from prerenal azotemia, where the presence of muddy brown casts and renal tubular epithelial cells is highly associated with development of ATN. The number of casts and epithelial casts per high power field may also be correlated with the degree of ATN. Once acute renal failure is established, there is no intervention that has proven beneficial to expedite the recovery of renal function. In most cases renal function recovers spontaneously within a few days. However, it is essential to avoid further renal injury and improve the impaired physiologic functions to prevent progression to chronic renal failure.
Prevention of Perioperative Kidney Injury
A number of strategies have been proposed to preserve renal function in the perioperative period. Most of these practices are based on tradition, anecdotal information, or extrapolation from animal studies rather than double blinded randomized controlled trials in humans. A summary of strategies to reduce or prevent the development of perioperative acute kidney injury is provided in Table 33.5.
Table 33.5
Strategies to reduce or prevent the development of perioperative acute kidney injury
Oxygen delivery maintenance | Maintaining hematocrit, cardiac output |
Prevention of vasconstriction | Maintaining adequate preload, use of ACE inhibitors |
Renal vasodilation | Measure atrial natriuretic peptide, use dopamine?
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