InternalMed_Harrison

InternalMed_Harrison. interpretation of the 24-h urine results should take into account that the collections are usually performed on a weekend day when the patient is staying at home; an individual’s habits may differ dramatically (beneficially or detrimentally) at work or outside the home. Specialized testing, such as calcium loading or restriction, is not recommended as it does not influence clinical recommendations.


InternalMed_Harrison

InternalMed_Harrison. Stone composition analysis is essential if a stone or fragment is available; patients should be encouraged to retrieve passed stones. The stone type cannot be determined with certainty from 24-h urine results. Imaging The “gold standard” diagnostic test is helical CT without contrast. If not already performed during an acute episode, a CT should be considered to definitively establish the baseline stone burden. A suboptimal imaging study may not detect a residual stone that, if subsequently passed, would be mistaken for a new stone. In this instance, the preventive medical regimen might be unnecessarily changed as the result of a preexisting stone.


InternalMed_Harrison

InternalMed_Harrison. Recommendations for follow-up imaging should be tailored to the individual patient. While CT provides the best information, the radiation dose is substantially higher than from other modalities; therefore, CT should be performed only if the results will lead to a change in clinical recommendations. Although they are less sensitive, renal ultrasound or a KUB exam are typically used to minimize radiation exposure, with recognition of the limitations.


InternalMed_Harrison

InternalMed_Harrison. Prevention of New Stone Formation Recommendations for preventing stone formation depend on the stone type and the results of metabolic evaluation. After remediable secondary causes of stone formation (e.g., primary hyperparathyroidism) are excluded, the focus should turn to modification of the urine composition to reduce the risk of new stone formation. The urinary constituents are continuous variables, and the associated risk is continuous; thus, there is no definitive threshold. Dichotomization into “normal” and “abnormal” can be misleading and should be avoided.


InternalMed_Harrison

InternalMed_Harrison. For all stone types, consistently diluted urine reduces the likelihood of crystal formation. The urine volume should be at least 2 L/d. Because of differences in insensible fluid losses and fluid intake from food sources, the required total fluid intake will vary from person to person. Rather than specify how much to drink, it is more helpful to educate patients about how much more they need to drink in light of their 24-h urine volume. For example, if the daily urine volume is 1.5 L, then the patient should be advised to drink at least 0.5 L more per day in order to increase the urine volume to the goal of 2 L/day. RECOMMENDATIONS FOR SPECIFIC STONE TYPES Calcium Oxalate Risk factors for calcium oxalate stones include higher urine calcium, higher urine oxalate, and lower urine citrate. This stone type is insensitive to pH in the physiologic range.


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InternalMed_Harrison. Individuals with higher urine calcium excretion tend to absorb a higher percentage of ingested calcium. Nevertheless, dietary calcium restriction is not beneficial and, in fact, is likely to be harmful (see “Dietary Risk Factors,” above). In a randomized trial in men with high urine calcium and recurrent calcium oxalate stones, a diet containing 1200 mg of calcium and a low intake of sodium and animal protein significantly reduced subsequent stone formation from that with a low-calcium diet (400 mg/d). Excessive calcium intake (>1200 mg/d) should be avoided.


InternalMed_Harrison

InternalMed_Harrison. A thiazide diuretic, in doses higher than those used to treat hypertension, can substantially lower urine calcium excretion. Several randomized controlled trials have demonstrated that thiazide diuretics can reduce calcium oxalate stone recurrence by ~50%. When a thiazide is prescribed, dietary sodium restriction is essential to obtain the desired reduction in urinary calcium excretion. While bisphosphonates may reduce urine calcium excretion in some individuals, there are no data on whether this class of medication can reduce stone formation; therefore, bisphosphonates cannot be recommended solely for stone prevention at present. A reduction in urine oxalate will in turn reduce the supersaturation of calcium oxalate. In patients with the common form of nephrolithiasis, avoiding high-dose vitamin C supplements is the only known strategy that reduces endogenous oxalate production.


InternalMed_Harrison

InternalMed_Harrison. Oxalate is a metabolic end product; therefore, any dietary oxalate that is absorbed will be excreted in the urine. Reducing absorption of exogenous oxalate involves two approaches. First, the avoidance of foods that contain high amounts of oxalate, such as spinach, rhubarb, and potatoes, is prudent. However, extreme oxalate restriction has not been demonstrated to reduce stone recurrence and could be harmful to overall health, given other health benefits of many foods that are erroneously considered to be high in oxalate. Controversy exists regarding the most clinically relevant measure of the oxalate content of foods (e.g., bioavailability). Notably, the absorption of oxalate is reduced by higher calcium intake; therefore, individuals with higher-than-desired urinary oxalate should be counseled to consume adequate calcium. Oxalate absorption can be influenced by the intestinal microbiota, depending on the presence of oxalate-degrading bacteria. Currently, however, there are no


InternalMed_Harrison

InternalMed_Harrison. be counseled to consume adequate calcium. Oxalate absorption can be influenced by the intestinal microbiota, depending on the presence of oxalate-degrading bacteria. Currently, however, there are no available therapies to alter the microbiota that beneficially affect urinary oxalate excretion over the long term.


InternalMed_Harrison

InternalMed_Harrison. Citrate is a natural inhibitor of calcium oxalate and calcium phosphate stones. Higher-level consumption of foods rich in alkali (i.e., fruits and vegetables) can increase urine citrate. For patients with lower urine citrate in whom dietary modification does not adequately increase urine citrate, the addition of supplemental alkali (typically potassium citrate) will lead to an increase in urinary citrate excretion. Sodium salts, such as sodium bicarbonate, while successful in raising urine citrate, are typically avoided due to the adverse effects of sodium on urine calcium excretion.


InternalMed_Harrison

InternalMed_Harrison. Past reports suggested that higher levels of urine uric acid may increase the risk of calcium oxalate stones, but more recent studies do not support this association. However, allopurinol reduced stone recurrence in one randomized controlled trial in patients with calcium oxalate stones and high urine uric acid levels. The lack of association between urine uric acid level and calcium oxalate stones suggests that a different mechanism underlies the observed beneficial effect of allopurinol. Additional dietary modifications may be beneficial in reducing stone recurrence. Restriction of nondairy animal protein (e.g., meat, chicken, seafood) is a reasonable approach and may result in higher excretion of citrate and lower excretion of calcium. In addition, reducing sodium intake to <2.5 g/d may decrease urinary excretion of calcium. Sucrose and fructose intake should be minimized.


InternalMed_Harrison

InternalMed_Harrison. For adherence to a dietary pattern that is more manageable for patients than manipulating individual nutrients, the DASH (Dietary Approaches to Stop Hypertension) diet provides an appropriate and readily available option. Randomized trials have conclusively shown the DASH diet to reduce blood pressure. At present, only data from observational studies are available, but these demonstrate a strong and consistent inverse association between the DASH diet and risk of stone formation. Calcium Phosphate Calcium phosphate stones share risk factors with calcium oxalate stones, including higher concentrations of urine calcium and lower concentrations of urine citrate, but additional factors deserve attention. Higher urine phosphate levels and higher urine pH (typically ≥6.5) are associated with an increased likelihood of calcium phosphate stone formation. Calcium phosphate stones are more common in patients with distal renal tubular acidosis and primary hyperparathyroidism.


InternalMed_Harrison

InternalMed_Harrison. There are no randomized trials on which to base preventive recommendations for calcium phosphate stone formers, so the interventions are focused on modification of the recognized risk factors. Thiazide diuretics (with sodium restriction) may be used to reduce urine calcium, as described above for calcium oxalate stones. In patients with low urine citrate levels, alkali supplements (e.g., potassium citrate) may be used to increase these concentrations. However, the urine pH of these patients should be monitored carefully because supplemental alkali can raise urine pH, thereby potentially increasing the risk of stone formation. Reduction of dietary phosphate may be beneficial by reducing urine phosphate excretion.


InternalMed_Harrison

InternalMed_Harrison. uric Acid The two main risk factors for uric acid stones are persistently low urine pH and higher uric acid excretion. Urine pH is the predominant influence on uric acid solubility; therefore, the mainstay of prevention of uric acid stone formation entails increasing urine pH. While acidifying the urine is not easily done, alkalinizing the urine can be readily achieved by increasing the intake of foods rich in alkali (e.g., fruits and vegetables) and reducing the intake of foods that produce acid (e.g., animal flesh). If necessary, supplementation with bicarbonate or citrate salts (preferably potassium citrate) can be used to reach the recommended pH goal of 6 to 7 throughout the day and night.


InternalMed_Harrison

InternalMed_Harrison. Urine uric acid excretion is determined by uric acid generation. Uric acid is the end product of purine metabolism; thus reduced consumption of purine-containing foods can lower urine uric acid excretion. It is noteworthy that the serum uric acid level is dependent on the fractional excretion of uric acid and therefore does not provide information on urine uric acid excretion. For example, an individual with high uric acid generation and concurrent high fractional excretion of uric acid will have high urine uric acid excretion with a normal (or even low) serum uric acid level. If alkalinization of the urine alone is not successful and if dietary modifications do not reduce urine uric acid sufficiently, then the use of a xanthine oxidase inhibitor, such as allopurinol or febuxostat, can reduce urine uric acid excretion by 40–50%.


InternalMed_Harrison

InternalMed_Harrison. Cystine Cystine excretion is not easily modified. Long-term dietary cystine restriction is not feasible and is unlikely to be successful; thus the focus for cystine stone prevention is on increasing cystine solubility. This goal may be achieved by treatment with medication that covalently binds to cystine (tiopronin and penicillamine) and a medication that raises urine pH. Tiopronin is the preferred choice due to its better adverse event profile. The preferred alkalinizing agent is potassium citrate as sodium salts may increase cystine excretion. As with all stone types, and especially in patients with cystinuria, maintaining a high urine volume is an essential component of the preventive regimen.


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InternalMed_Harrison. Struvite Struvite stones, also known as infection stones or triple-phosphate stones, form only when the upper urinary tract is infected with urease-producing bacteria such as Proteus mirabilis, Klebsiella pneumoniae, or Providencia species. Urease produced by these bacteria hydrolyzes urea and may elevate the urine pH to a supraphysiologic level (>8.0). Struvite stones may grow quickly and fill the renal pelvis (staghorn calculi). Struvite stones require complete removal by a urologist. New stone formation can be avoided by the prevention of UTIs. In patients with recurrent upper UTIs (e.g., some individuals with surgically altered urinary drainage or spinal cord injury), the urease inhibitor acetohydroxamic acid can be considered; however, this agent should be used with caution because of potential side effects.


InternalMed_Harrison

InternalMed_Harrison. In general, the preventive regimens described above do not cure the underlying pathophysiologic process. Thus these recommendations typically need to be followed for the patient’s lifetime, and it is essential to tailor recommendations in a way that is acceptable to the patient. Because the memory of the acute stone event fades and patients often return to old habits (e.g., insufficient fluid intake), long-term follow-up is important to ensure that the preventive regimen has been implemented and has resulted in the desired reduction in the risk of new stone formation.


InternalMed_Harrison

InternalMed_Harrison. Follow-up imaging should be planned thoughtfully. Many patients with recurrent episodes of renal colic that lead to emergency room visits often undergo repeat CT studies. While CT does provide the best information, the radiation dose is substantially higher than that with plain abdominal radiography (KUB). Small stones may be missed by KUB, and ultrasound has a limited ability to determine size and number of stones. Minimizing radiation exposure should be a goal of the long-term follow-up plan and must be balanced against the gain in diagnostic information.


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InternalMed_Harrison. urinary tract Obstruction Julian L. Seifter Obstruction to the flow of urine, with attendant stasis and elevation in urinary tract pressure, impairs renal and urinary conduit functions and is a common cause of acute and chronic kidney disease (obstruc-tive nephropathy). With early relief of obstruction, the defects in func-343 tion usually disappear completely. However, chronic obstruction may produce permanent loss of renal mass (renal atrophy) and excretory capability, as well as enhanced susceptibility to local infection and stone formation. Early diagnosis and prompt therapy are, therefore, 1871 essential to minimize the otherwise devastating effects of obstruction on kidney structure and function.


InternalMed_Harrison

InternalMed_Harrison. Obstruction to urine flow can result from intrinsic or extrinsic mechanical blockade as well as from functional defects not associated with fixed occlusion of the urinary drainage system. Mechanical obstruction can occur at any level of the urinary tract, from the renal calyces to the external urethral meatus. Normal points of narrowing, such as the ureteropelvic and ureterovesical junctions, bladder neck, and urethral meatus, are common sites of obstruction. When obstruction is above the level of the bladder, unilateral dilatation of the ureter (hydroureter) and renal pyelocalyceal system (hydronephrosis) occurs; lesions at or below the level of the bladder cause bilateral involvement.


InternalMed_Harrison

InternalMed_Harrison. Common forms of obstruction are listed in Table 343-1. Childhood causes include congenital malformations, such as narrowing of the ureteropelvic junction and abnormal insertion of the ureter into the bladder, the most common cause. Vesicoureteral reflux in the absence of urinary tract infection or bladder neck obstruction often resolves with age. Reinsertion of the ureter into the bladder is indicated if reflux is severe and unlikely to improve spontaneously, if renal function deteriorates, or if urinary tract infections recur despite chronic antimicrobial therapy. Vesicoureteral reflux may cause prenatal hydronephrosis and, if severe, can lead to recurrent urinary infections and renal scarring in childhood. Posterior urethral valves are the most common cause of bilateral hydronephrosis in boys. In adults, urinary tract obstruction (UTO) is due mainly to acquired defects. Pelvic tumors, calculi, and urethral stricture predominate. Ligation of, or injury to, the ureter during pelvic or


InternalMed_Harrison

InternalMed_Harrison. boys. In adults, urinary tract obstruction (UTO) is due mainly to acquired defects. Pelvic tumors, calculi, and urethral stricture predominate. Ligation of, or injury to, the ureter during pelvic or colonic surgery can lead to hydronephrosis which, if unilateral, may remain undetected. Obstructive uropathy may also result from extrinsic neoplastic (carcinoma of


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InternalMed_Harrison. Tumor Cancer of prostate Infection Calculi Cancer of bladder Trauma Pregnant uterus Carcinoma of cervix, Trauma colon


InternalMed_Harrison

InternalMed_Harrison. Retroperitoneal fibrosis Aortic aneurysm Trauma Uterine leiomyomata Carcinoma of uterus, prostate, bladder, colon, rectum Lymphoma Pelvic inflammatory disease, 1872 cervix or colon) or inflammatory disorders. Lymphomas and pelvic or colonic neoplasms with retroperitoneal involvement are causes of ureteral obstruction. As many as 50% of men over 40 years old may have lower urinary tract symptoms associated with benign prostatic hypertrophy, but these symptoms may occur without bladder outlet obstruction. Functional impairment of urine flow occurs when voiding is altered by abnormal pontine or sacral centers of micturition control. It may be asymptomatic or associated with lower urinary tract symptoms such as frequency, urgency, urge and postmicturition incontinence, nocturia, straining to void, slow stream, hesitancy, or a feeling of incomplete emptying. A history should be sought for trauma, back injury, surgery, diabetes, neurologic or psychiatric conditions, and medications. Causes


InternalMed_Harrison

InternalMed_Harrison. void, slow stream, hesitancy, or a feeling of incomplete emptying. A history should be sought for trauma, back injury, surgery, diabetes, neurologic or psychiatric conditions, and medications. Causes include neurogenic bladder, often with adynamic ureter, and vesicoureteral reflux. Reflux in children may result in severe unilateral or bilateral hydroureter and hydronephrosis. Urinary retention may be the consequence of α-adrenergic and anticholinergic agents, as well as opiates. Hydronephrosis in pregnancy is due to relaxational effects of progesterone on smooth muscle of the renal pelvis, as well as ureteral compression by the enlarged uterus. Diagnostic tools to identify anatomic obstruction include urinary flow measurements and a postvoid residual. Cystourethroscopy and urodynamic studies may be reserved for the symptomatic patient to assess the filling phase (cystometry), pressure-volume relationship of the bladder, bladder compliance, and capacity. Pressure-flow analysis


InternalMed_Harrison

InternalMed_Harrison. studies may be reserved for the symptomatic patient to assess the filling phase (cystometry), pressure-volume relationship of the bladder, bladder compliance, and capacity. Pressure-flow analysis evaluates bladder contractility and bladder outlet resistance during voiding. Bladder obstruction is characterized by high pressures in women, whereas in men, a diagnosis of bladder outlet obstruction is based on flow rate and voiding pressures. A voiding cystourethrogram may be useful in evaluating incomplete emptying and bladder neck and urethral pathology.


InternalMed_Harrison

InternalMed_Harrison. The pathophysiology and clinical features of UTO are summarized in Table 343-2. Pain, the symptom that most commonly leads to medical attention, is due to distention of the collecting system or renal capsule. Pain severity is influenced more by the rate at which distention develops than by the degree of distention. Acute supravesical obstruction, as from a stone lodged in a ureter (Chap. 342), is associated with excruciating pain, known as renal colic. This pain often radiates to the ↑ Reabsorption of Na+, urea, water Vasodilator prostaglandins, nitric oxide ↓↓ GFR AVP-insensitive polyuria ↓ Concentrating ↑ Vasoconstrictor Natriuresis ability prostaglandins Hyperkalemic, hyperchlo- production ↓ Transport functions for Na+, K+, H+ Release of Obstruction Abbreviations: AVP, arginine vasopressin; GFR, glomerular filtration rate.


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InternalMed_Harrison. Release of Obstruction Abbreviations: AVP, arginine vasopressin; GFR, glomerular filtration rate. lower abdomen, testes, or labia. By contrast, more insidious causes of obstruction, such as chronic narrowing of the ureteropelvic junction, may produce little or no pain and yet result in total destruction of the affected kidney. Flank pain that occurs only with micturition is pathognomonic of vesicoureteral reflux. Obstruction of urine flow results in an increase in hydrostatic pressures proximal to the site of obstruction. It is this buildup of pressure that leads to the accompanying pain, the distention of the collecting system in the kidney, and elevated intratubular pressures that initiate tubular dysfunction. As the increased hydrostatic pressure is expressed in the urinary space of the glomeruli, further filtration decreases or stops completely.


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InternalMed_Harrison. Azotemia develops when overall excretory function is impaired, often in the setting of bladder outlet obstruction, bilateral renal pelvic or ureteric obstruction, or unilateral disease in a patient with a solitary functioning kidney. Complete bilateral obstruction should be suspected when acute renal failure is accompanied by anuria. Any patient with renal failure otherwise unexplained, or with a history of nephrolithiasis, hematuria, diabetes mellitus, prostatic enlargement, pelvic surgery, trauma, or tumor should be evaluated for UTO.


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InternalMed_Harrison. In the acute setting, partial, bilateral obstruction may mimic prerenal azotemia with concentrated urine and sodium retention. However, with more prolonged obstruction, symptoms of polyuria and nocturia commonly accompany partial UTO and result from diminished renal concentrating ability. Impairment of transcellular salt reabsorption in the proximal tubule, medullary thick ascending limb of Henle, and collecting duct cells is due to downregulation of transport proteins including the Na+, K+ adenosine triphosphatase (ATPase), NaK2Cl cotransporter (NKCC) in the thick ascending limb, and the epithelial Na+ channel (ENaC) in collecting duct cells. Consequences include failure to produce urine free of salt (natriuresis) and loss of medullary hypertonicity producing a urinary concentrating defect. In addition to direct effects on renal transport mechanisms, increased prostaglandin E2 (PGE2) (due to induction of cyclooxygenase-2 [COX-2]), angiotensin II (with its downregulation of Na+


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InternalMed_Harrison. defect. In addition to direct effects on renal transport mechanisms, increased prostaglandin E2 (PGE2) (due to induction of cyclooxygenase-2 [COX-2]), angiotensin II (with its downregulation of Na+ transporters), and atrial or B-type natriuretic peptides (ANP or BNP) (due to volume expansion in the azotemic patient) contribute to the decreased salt reabsorption along the nephron.


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InternalMed_Harrison. Dysregulation of aquaporin-2 water channels in the collecting duct contributes to the polyuria. The defect usually does not improve with administration of vasopressin and is therefore a form of acquired nephrogenic diabetes insipidus. Wide fluctuations in urine output in a patient with azotemia should always raise the possibility of intermittent or partial UTO. If fluid intake is inadequate, severe dehydration and hypernatremia may develop. However, as with other causes of poor renal function, excesses of salt and water intake may result in edema and hyponatremia.


InternalMed_Harrison

InternalMed_Harrison. Partial bilateral UTO often results in acquired distal renal tubular acidosis, hyperkalemia, and renal salt wasting. The H+-ATPase, situated on the apical membrane of the intercalated cells of the collecting duct, is critical for distal H+ secretion. The trafficking of intracellular H+ pumps from the cytoplasm to the cell membrane is disrupted in UTO. The decreased function of the ENaC, in the apical membrane of neighboring collecting duct principal cells, contributes to decreased Na+ reabsorption (salt-wasting), decreased electronegativity of the tubule lumen, and therefore decreased K+ secretion via K+ channels (hyperkalemia) and H+ secretion via the H+-ATPases (distal renal tubular acidosis [RTA]). Proximal tubule ammoniagenesis, important to the elimination of H+ as NH4+, is impaired. These defects in tubule function are often accompanied by renal tubulointerstitial damage. Azotemia with hyperkalemia and metabolic acidosis should prompt consideration of UTO.


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InternalMed_Harrison. The renal interstitium becomes edematous and infiltrated with mononuclear inflammatory cells early in UTO. Later, interstitial fibrosis and atrophy of the papillae and medulla occur and precede these processes in the cortex. The increase in angiotensin II noted in UTO contributes to the inflammatory response and fibroblast accumulation through mechanisms involving profibrotic cytokines. With time, this process leads to chronic kidney damage. FIGuRE 343-1 Diagnostic approach for urinary tract obstruction in unexplained renal failure. CT, computed tomography.


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InternalMed_Harrison. FIGuRE 343-1 Diagnostic approach for urinary tract obstruction in unexplained renal failure. CT, computed tomography. UTO must always be considered in patients with urinary tract infections or urolithiasis. Urinary stasis encourages the growth of organisms. Urea-splitting bacteria are associated with magnesium ammonium phosphate (struvite) calculi. Hypertension is frequent in acute and sub-acute unilateral obstruction and is usually a consequence of increased release of renin by the involved kidney. Chronic kidney disease from bilateral UTO, often associated with extracellular volume expansion, may result in significant hypertension. Erythrocytosis, an infrequent complication of obstructive uropathy, is secondary to increased erythropoietin production.


InternalMed_Harrison

InternalMed_Harrison. A history of difficulty in voiding, pain, infection, or change in urinary volume is common. Evidence for distention of the kidney or urinary bladder can often be obtained by palpation and percussion of the abdomen. A careful rectal and genital examination may reveal enlargement or nodularity of the prostate, abnormal rectal sphincter tone, or a rectal or pelvic mass.


InternalMed_Harrison

InternalMed_Harrison. Urinalysis may reveal hematuria, pyuria, and bacteriuria. The urine sediment is often normal, even when obstruction leads to marked azotemia and extensive structural damage. An abdominal scout film may detect nephrocalcinosis or a radiopaque stone. As indicated in Fig. 343-1, if UTO is suspected, a bladder catheter should be inserted. Abdominal ultrasonography should be performed to evaluate renal and bladder size, as well as pyelocalyceal contour. Ultrasonography is approximately 90% specific and sensitive for detection of hydronephrosis. False-positive results are associated with diuresis, renal cysts, or the presence of an extrarenal pelvis, a normal congenital variant. Congenital ureteropelvic junction (UPJ) obstruction may be mistaken for renal cystic disease. Hydronephrosis may be absent on ultrasound when obstruction is less than 48 h in duration or associated with volume contraction, staghorn calculi, retroperitoneal fibrosis, or infiltrative renal disease. Duplex Doppler


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InternalMed_Harrison. be absent on ultrasound when obstruction is less than 48 h in duration or associated with volume contraction, staghorn calculi, retroperitoneal fibrosis, or infiltrative renal disease. Duplex Doppler ultrasonography may detect an increased resistive index in urinary obstruction.


InternalMed_Harrison

InternalMed_Harrison. Recent advances in technology have led to alternatives and have largely replaced the once standard intravenous urogram in the further evaluation of UTO. The high-resolution multidetector row computed tomography (CT) scan in particular has advantages of visualizing the retroperitoneum, as well as identifying both intrinsic and extrinsic sites of obstruction. Noncontrast CT scans improve visualization of the urinary tract in the patient with renal impairment and are safer for patients at risk for contrast nephropathy. Magnetic resonance urography is a promising technique but, at this time, not superior to the CT scan and carries the risk of certain gadolinium agents in patients with renal insufficiency, i.e., nephrogenic systemic fibrosis. The intravenous urogram may define the site of obstruction and demonstrate dilatation of the calyces, renal pelvis, and ureter above the obstruction. The ureter may be tortuous in chronic obstruction. Radionuclide scans are able to give differential


InternalMed_Harrison

InternalMed_Harrison. and demonstrate dilatation of the calyces, renal pelvis, and ureter above the obstruction. The ureter may be tortuous in chronic obstruction. Radionuclide scans are able to give differential renal function but give less anatomic detail than CT or intravenous urography (IVU).


InternalMed_Harrison

InternalMed_Harrison. To facilitate visualization of a suspected lesion in a ureter or renal pelvis, retrograde or antegrade urography should be attempted. These procedures do not carry risk of contrast-induced acute renal failure in patients with renal insufficiency. The retrograde approach involves catheterization of the involved ureter under cystoscopic control, whereas the antegrade technique necessitates percutaneous placement of a catheter into the renal pelvis. Although the antegrade approach may provide immediate decompression of a unilateral obstructing lesion, many urologists initially attempt the retrograde approach unless the catheterization is unsuccessful. Voiding cystourethrography is of value in the diagnosis of vesicoureteral reflux and bladder neck and urethral obstructions. Postvoiding films reveal residual urine. Endoscopic visualization by the urologist often permits precise identification of lesions involving the urethra, prostate, bladder, and ureteral orifices.


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InternalMed_Harrison. UTO complicated by infection requires immediate relief of obstruction to prevent development of generalized sepsis and progressive renal damage. Sepsis necessitates prompt urologic intervention. Drainage may be achieved by nephrostomy, ureterostomy, or ureteral, urethral, or suprapubic catheterization. Prolonged antibiotic treatment may be necessary. Chronic or recurrent infections in a 1874 poorly functioning obstructed kidney may necessitate nephrectomy. When infection is not present, surgery is often delayed until acid-base, fluid, and electrolyte status is restored. Nevertheless, the site of obstruction should be ascertained as soon as feasible. Elective relief of obstruction is usually recommended in patients with urinary retention, recurrent urinary tract infections, persistent pain, or progressive loss of renal function. Benign prostatic hypertrophy may be treated medically with α-adrenergic blockers and 5α-reductase inhibitors. Functional obstruction secondary to neurogenic


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InternalMed_Harrison. or progressive loss of renal function. Benign prostatic hypertrophy may be treated medically with α-adrenergic blockers and 5α-reductase inhibitors. Functional obstruction secondary to neurogenic bladder may be decreased with the combination of frequent voiding and cholinergic drugs.


InternalMed_Harrison

InternalMed_Harrison. With relief of obstruction, the prognosis regarding return of renal function depends largely on whether irreversible renal damage has occurred. When obstruction is not relieved, the course will depend mainly on whether the obstruction is complete or incomplete and bilateral or unilateral, as well as whether or not urinary tract infection is also present. Complete obstruction with infection can lead to total destruction of the kidney within days. Partial return of glomerular filtration rate may follow relief of complete obstruction of 1 and 2 weeks’ duration, but after 8 weeks of obstruction, recovery is unlikely. In the absence of definitive evidence of irreversibility, every effort should be made to decompress the obstruction in the hope of restoring renal function at least partially. A renal radionuclide scan, performed after a prolonged period of decompression, may be used to predict the reversibility of renal dysfunction.


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InternalMed_Harrison. Relief of bilateral, but not unilateral, complete obstruction commonly results in polyuria, which may be massive. The urine is usually hypo-tonic and may contain large amounts of sodium chloride, potassium, phosphate, and magnesium. The natriuresis is due in part to the normal correction of extracellular volume expansion, the increase in natriuretic factors accumulated during the period of renal failure, and depressed salt and water reabsorption when urine flow is reestablished. The retained urea is excreted with improved GFR, resulting in an osmotic diuresis which increases the urine volume of electrolyte-free water. In the majority of patients, this diuresis results in the appropriate excretion of the excesses of retained salt and water. When extracellular volume and composition return to normal, the diuresis usually abates spontaneously. Occasionally, iatrogenic expansion of extracellular volume is responsible for, or sustains, the diuresis observed in the postobstructive period.


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InternalMed_Harrison. to normal, the diuresis usually abates spontaneously. Occasionally, iatrogenic expansion of extracellular volume is responsible for, or sustains, the diuresis observed in the postobstructive period. Replacement with intravenous fluids in amounts less than urinary losses usually prevents this complication. More aggressive fluid management is required in the setting of hypovolemia, hypotension, or disturbances in serum electrolyte concentrations.


InternalMed_Harrison

InternalMed_Harrison. The loss of electrolyte-free water with urea may result in hypernatremia. Serum and urine sodium and osmolal concentrations should guide the use of appropriate intravenous replacement. Often replacement with 0.45% saline is required. Relief of obstruction may be followed by urinary salt and water losses severe enough to provoke profound dehydration and vascular collapse. In these patients, decreased tubule reabsorptive capacity is probably responsible for the marked diuresis. Appropriate therapy in such patients includes intravenous administration of salt-containing solutions to replace sodium and volume deficits.


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InternalMed_Harrison. Approach to the Patient with Gastrointestinal Disease William L. Hasler, Chung Owyang ANATOMIC CONSIDERATIONS The gastrointestinal (GI) tract extends from the mouth to the anus 344 SEC Tion 1 and is composed of several organs with distinct functions. Specialized independently controlled thickened sphincters that assist in gut compartmentalization separate the organs. The gut wall is organized into well-defined layers that contribute to functional activities in each region. The mucosa is a barrier to luminal contents or a site for transfer of fluids or nutrients. Gut smooth muscle in association with the enteric nervous system mediates propulsion from one region to the next. Many GI organs possess a serosal layer that provides a supportive foundation but that also permits external input.


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InternalMed_Harrison. Interactions with other organ systems serve the needs both of the gut and the body. Pancreaticobiliary conduits deliver bile and enzymes into the duodenum. A rich vascular supply is modulated by GI tract activity. Lymphatic channels assist in gut immune activities. Intrinsic gut wall nerves provide the basic controls for propulsion and fluid regulation. Extrinsic neural input provides volitional or involuntary control to degrees that are specific for each gut region.


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InternalMed_Harrison. The GI tract serves two main functions—assimilating nutrients and eliminating waste. The gut anatomy is organized to serve these functions. In the mouth, food is processed, mixed with salivary amylase, and delivered to the gut lumen. The esophagus propels the bolus into the stomach; the lower esophageal sphincter prevents oral reflux of gastric contents. The esophageal mucosa has a protective squamous histology, which does not permit significant diffusion or absorption. Propulsive esophageal activities are exclusively aboral and coordinate with relaxation of the upper and lower esophageal sphincters on swallowing.


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InternalMed_Harrison. The stomach furthers food preparation by triturating and mixing the bolus with pepsin and acid. Gastric acid also sterilizes the upper gut. The proximal stomach serves a storage function by relaxing to accommodate the meal. The distal stomach exhibits phasic contractions that propel solid food residue against the pylorus, where it is repeatedly propelled proximally for further mixing before it is emptied into the duodenum. Finally, the stomach secretes intrinsic factor for vitamin B12 absorption.


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InternalMed_Harrison. The small intestine serves most of the nutrient absorptive function of the gut. The intestinal mucosa exhibits villus architecture to provide maximal surface area for absorption and is endowed with specialized enzymes and transporters. Triturated food from the stomach mixes with pancreatic juice and bile in the duodenum to facilitate digestion. Pancreatic juice contains the main enzymes for carbohydrate, protein, and fat digestion as well as bicarbonate to optimize the pH for activation of these enzymes. Bile secreted by the liver and stored in the gallbladder is essential for intestinal lipid digestion. The proximal intestine is optimized for rapid absorption of nutrient breakdown products and most minerals, whereas the ileum is better suited for absorption of vitamin B12 and bile acids. The small intestine also aids in waste elimination. Bile contains by-products of erythrocyte degradation, toxins, metabolized and unmetabolized medications, and cholesterol. Motor function of the


InternalMed_Harrison

InternalMed_Harrison. The small intestine also aids in waste elimination. Bile contains by-products of erythrocyte degradation, toxins, metabolized and unmetabolized medications, and cholesterol. Motor function of the small intestine delivers indigestible food residue and sloughed enterocytes into the colon for further processing. The small intestine terminates in the ileocecal junction, a sphincteric structure that prevents coloileal reflux and maintains small-intestinal sterility.


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InternalMed_Harrison. The colon prepares the waste material for controlled evacuation. The colonic mucosa dehydrates the stool, decreasing daily fecal volumes from 1000–1500 mL delivered from the ileum to 100–200 mL expelled from the rectum. The colonic lumen possesses a dense bacterial colonization that ferments undigested carbohydrates and short-chain fatty acids. Whereas transit times in the esophagus are on the order of seconds and times in the stomach and small intestine range from minutes to a few hours, propagation through the colon takes more than 1 day in most individuals. Colonic motor patterns exhibit a to-and-fro character that facilitates slow fecal desiccation. The proximal colon serves to mix and absorb fluid, while the distal colon exhibits peristaltic contractions and mass actions that function to expel the stool. The colon terminates in the anus, a structure with volitional and involuntary controls to permit retention of the fecal bolus until it can be released in a socially convenient


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InternalMed_Harrison. to expel the stool. The colon terminates in the anus, a structure with volitional and involuntary controls to permit retention of the fecal bolus until it can be released in a socially convenient setting.


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InternalMed_Harrison. GI function is modified by influences outside of the gut. Unlike other organ systems, the gut is in continuity with the outside environment. Thus, protective mechanisms are vigilant against deleterious effects of foods, medications, toxins, and infectious organisms. Mucosal immune mechanisms include chronic lymphocyte and plasma cell populations in the epithelial layer and lamina propria backed up by lymph node chains to prevent noxious agents from entering the circulation. Antimicrobial peptides secreted by Paneth cells in the intestine further contribute to the defense mechanisms against pathogens in the lumen. All substances absorbed into the bloodstream are filtered through the liver via the portal venous circulation. In the liver, many drugs and toxins are detoxified by a variety of mechanisms. Although intrinsic nerves control most basic gut activities, extrinsic neural input modulates many functions. Two activities under voluntary control are swallowing and defecation. Many


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InternalMed_Harrison. of mechanisms. Although intrinsic nerves control most basic gut activities, extrinsic neural input modulates many functions. Two activities under voluntary control are swallowing and defecation. Many normal GI reflexes involve extrinsic vagus or splanchnic nerve pathways. The brain-gut axis further alters function in regions not under volitional regulation. As an example, stress has potent effects on gut motor, secretory, and sensory functions.


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InternalMed_Harrison. GI diseases develop as a result of abnormalities within or outside of the gut and range in severity from those that produce mild symptoms and no long-term morbidity to those with intractable symptoms or adverse outcomes. Diseases may be localized to one organ or exhibit diffuse involvement at many sites. GI diseases are manifestations of alterations in nutrient assimilation or waste evacuation or in the activities supporting these main functions.


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InternalMed_Harrison. GI diseases are manifestations of alterations in nutrient assimilation or waste evacuation or in the activities supporting these main functions. Impaired Digestion and Absorption Diseases of the stomach, intestine, biliary tree, and pancreas can disrupt digestion and absorption. The most common intestinal maldigestion syndrome, lactase deficiency, produces gas and diarrhea after ingestion of dairy products and has no adverse outcomes. Other intestinal enzyme deficiencies produce similar symptoms after ingestion of other simple sugars. Conversely, celiac disease, bacterial overgrowth, infectious enteritis, Crohn’s ileitis, and radiation damage, which affect digestion and/or absorption more diffusely, produce anemia, dehydration, electrolyte disorders, or malnutrition. Gastric hypersecretory conditions such as Zollinger-Ellison


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InternalMed_Harrison. Approach to the Patient with Gastrointestinal Disease 1876 syndrome damage the intestinal mucosa, impair pancreatic enzyme activation, and accelerate transit due to excess gastric acid. Biliary obstruction from stricture or neoplasm impairs fat digestion. Impaired pancreatic enzyme release in chronic pancreatitis or pancreatic cancer decreases intraluminal digestion and can lead to malnutrition.


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InternalMed_Harrison. Altered Secretion Selected GI diseases result from dysregulation of gut secretion. Gastric acid hypersecretion occurs in Zollinger-Ellison syndrome, G cell hyperplasia, retained antrum syndrome, and some individuals with duodenal ulcers. Conversely, patients with atrophic gastritis or pernicious anemia release little or no gastric acid. Inflammatory and infectious small-intestinal and colonic diseases produce fluid loss through impaired absorption or enhanced secretion. Common intestinal and colonic hypersecretory conditions cause diarrhea and include acute bacterial or viral infection, chronic Giardia or cryptosporidia infections, small-intestinal bacterial overgrowth, bile salt diarrhea, microscopic colitis, diabetic diarrhea, and abuse of certain laxatives. Less common causes include large colonic villus adenomas and endocrine neoplasias with tumor overproduction of secretagogue transmitters like vasoactive intestinal polypeptide.


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InternalMed_Harrison. Altered Gut Transit Impaired gut transit may be secondary to mechanical obstruction. Esophageal occlusion often results from acid-induced stricture or neoplasm. Gastric outlet obstruction develops from peptic ulcer disease or gastric cancer. Small-intestinal obstruction most commonly results from adhesions but may also occur with Crohn’s disease, radiationor drug-induced strictures, and less likely malignancy. The most common cause of colonic obstruction is colon cancer, although inflammatory strictures develop in patients with inflammatory bowel disease, after certain infections such as diverticulitis, or with some drugs.


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InternalMed_Harrison. Retardation of propulsion also develops from disordered motor function. Achalasia is characterized by impaired esophageal body peristalsis and incomplete lower esophageal sphincter relaxation. Gastroparesis is the symptomatic delay in gastric emptying of meals due to impaired gastric motility. Intestinal pseudoobstruction causes marked delays in small-bowel transit due to enteric nerve or intestinal smooth-muscle injury. Slow-transit constipation is produced by diffusely impaired colonic propulsion. Constipation also is produced by outlet abnormalities such as rectal prolapse, intussusception, or dyssynergia—a failure of anal or puborectalis relaxation upon attempted defecation.


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InternalMed_Harrison. Disorders of rapid propulsion are less common than those with delayed transit. Rapid gastric emptying occurs in postvagotomy dumping syndrome, with gastric hypersecretion, and in some cases of functional dyspepsia and cyclic vomiting syndrome. Exaggerated intestinal or colonic motor patterns may be responsible for diarrhea in irritable bowel syndrome. Accelerated transit with hyperdefecation is noted in hyperthyroidism.


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InternalMed_Harrison. Immune Dysregulation Many inflammatory GI conditions are consequences of altered gut immune function. The mucosal inflammation of celiac disease results from dietary ingestion of gluten-containing grains. Some patients with food allergy also exhibit altered immune populations. Eosinophilic esophagitis and eosinophilic gastroenteritis are inflammatory disorders with prominent mucosal eosinophils. Ulcerative colitis and Crohn’s disease are disorders of uncertain etiology that produce mucosal injury primarily in the lower gut. The microscopic colitides, lymphocytic and collagenous colitis, exhibit colonic subepithelial infiltrates without visible mucosal damage. Bacterial, viral, and protozoal organisms may produce ileitis or colitis in selected patient populations.


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InternalMed_Harrison. Impaired Gut Blood Flow Different GI regions are at variable risk for ischemic damage from impaired blood flow. Rare cases of gastroparesis result from blockage of the celiac and superior mesenteric arteries. More commonly encountered are intestinal and colonic ischemia that are consequences of arterial embolus, arterial thrombosis, venous thrombosis, or hypoperfusion from dehydration, sepsis, hemorrhage, or reduced cardiac output. These may produce mucosal injury, hemorrhage, or even perforation. Chronic ischemia may result in intestinal stricture. Some cases of radiation enterocolitis exhibit reduced mucosal blood flow.


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InternalMed_Harrison. Neoplastic Degeneration All GI regions are susceptible to malignant degeneration to varying degrees. In the United States, colorectal cancer is most common and usually presents after age 50 years. Worldwide, gastric cancer is prevalent especially in certain Asian regions. Esophageal cancer develops with chronic acid reflux or after an extensive alcohol or tobacco use history. Small-intestinal neoplasms are rare and occur with underlying inflammatory disease. Anal cancers arise after prior anal infection or inflammation. Pancreatic and biliary cancers elicit severe pain, weight loss, and jaundice and have poor prognoses. Hepatocellular carcinoma usually arises in the setting of chronic viral hepatitis or cirrhosis secondary to other causes. Most GI cancers exhibit carcinomatous histology; however, lymphomas and other cell types also are observed.


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InternalMed_Harrison. Disorders Without Obvious Organic Abnormalities The most common GI disorders show no abnormalities on biochemical or structural testing and include irritable bowel syndrome, functional dyspepsia, functional chest pain, and functional heartburn. These disorders exhibit altered gut motor function; however, the pathogenic relevance of these abnormalities is uncertain. Exaggerated visceral sensory responses to noxious stimulation may cause discomfort in these disorders. Symptoms in other patients result from altered processing of visceral pain sensations in the central nervous system. Functional bowel patients with severe symptoms may exhibit significant emotional disturbances on psychometric testing. Subtle immunologic defects may contribute to functional symptoms as well.


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InternalMed_Harrison. Genetic Influences Although many GI diseases result from environmental factors, others exhibit hereditary components. Family members of inflammatory bowel disease patients show a genetic predisposition to disease development themselves. Colonic and esophageal malignancies arise in certain inherited disorders. Rare genetic dysmotility syndromes are described. Familial clustering is even observed in the functional bowel disorders, although this may be secondary learned familial illness behavior rather than a true hereditary factor. The most common GI symptoms are abdominal pain, heartburn, nausea and vomiting, altered bowel habits, GI bleeding, and jaundice (Table 344-1). Others are dysphagia, anorexia, weight loss, fatigue, and extraintestinal symptoms.


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InternalMed_Harrison. Abdominal Pain Abdominal pain results from GI disease and extra-intestinal conditions involving the genitourinary tract, abdominal wall, thorax, or spine. Visceral pain generally is midline in location and vague in character, whereas parietal pain is localized and precisely described. Common inflammatory diseases with pain include peptic ulcer, appendicitis, diverticulitis, inflammatory bowel disease, and infectious enterocolitis. Other intraabdominal causes of pain include gallstone disease and pancreatitis. Noninflammatory visceral sources include mesenteric ischemia and neoplasia. The most common causes of abdominal pain are irritable bowel syndrome and functional dyspepsia.


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InternalMed_Harrison. Heartburn Heartburn, a burning substernal sensation, is reported intermittently by at least 40% of the population. Classically, heartburn is felt to result from excess gastroesophageal reflux of acid. However, some cases exhibit normal esophageal acid exposure and may result from reflux of nonacidic material or heightened sensitivity of esophageal mucosal nerves. Nausea and Vomiting Nausea and vomiting are caused by GI diseases, medications, toxins, acute and chronic infection, endocrine disorders, labyrinthine conditions, and central nervous system disease. The best-characterized GI etiologies relate to mechanical obstruction of the upper gut; however, disorders of propulsion including gastroparesis and intestinal pseudoobstruction also elicit prominent symptoms. Nausea and vomiting also are commonly reported by patients with irritable bowel syndrome and functional disorders of the upper gut (including chronic idiopathic nausea and functional vomiting).


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InternalMed_Harrison. Altered Bowel Habits Altered bowel habits are common complaints of patients with GI disease. Constipation is reported as infrequent defecation, straining with defecation, passage of hard stools, or a sense of incomplete fecal evacuation. Causes of constipation include obstruction, motor disorders of the colon, medications, and endocrine diseases such as hypothyroidism and hyperparathyroidism. Diarrhea is reported as frequent defecation, passage of loose or watery stools, fecal urgency, or a similar sense of incomplete evacuation. The differential diagnosis of diarrhea is broad and includes infections, inflammatory causes, malabsorption, and medications. Irritable bowel syndrome produces constipation, diarrhea, or an alternating bowel pattern. Fecal mucus is common in irritable bowel syndrome, whereas pus characterizes inflammatory disease. Steatorrhea develops with malabsorption.


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InternalMed_Harrison. GI Bleeding Hemorrhage may develop from any gut organ. Most commonly, upper GI bleeding presents with melena or hematemesis, whereas lower GI bleeding produces passage of bright red or maroon stools. However, briskly bleeding upper sites can elicit voluminous red rectal bleeding, whereas slowly bleeding ascending colon sites may produce melena. Chronic slow GI bleeding may present with iron deficiency anemia. The most common upper GI causes of bleeding are ulcer disease, gastroduodenitis, and esophagitis. Other etiologies include portal hypertensive causes, malignancy, tears across the gastroesophageal junction, and vascular lesions. The most prevalent lower GI sources of hemorrhage include hemorrhoids, anal fissures, diverticula, ischemic colitis, and arteriovenous malformations. Other causes include neoplasm, inflammatory bowel disease, infectious colitis, drug-induced colitis, and other vascular lesions.


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InternalMed_Harrison. Jaundice Jaundice results from prehepatic, intrahepatic, or post-hepatic disease. Posthepatic causes of jaundice include biliary diseases, such as choledocholithiasis, acute cholangitis, primary sclerosing cholangitis, other strictures, and neoplasm, and pancreatic disorders, such as acute and chronic pancreatitis, stricture, and malignancy.


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InternalMed_Harrison. Other Symptoms Other symptoms are manifestations of GI disease. Dysphagia, odynophagia, and unexplained chest pain suggest esophageal disease. A globus sensation is reported with esophagopharyngeal conditions, but also occurs with functional GI disorders. Weight loss, anorexia, and fatigue are nonspecific symptoms of neoplastic, inflammatory, gut motility, pancreatic, small-bowel mucosal, and psychiatric conditions. Fever is reported with inflammatory illness, but malignancies also evoke febrile responses. GI disorders also produce extraintestinal symptoms. Inflammatory bowel disease is associated with hepatobiliary dysfunction, skin and eye lesions, and arthritis. Celiac disease may present with dermatitis herpetiformis. Jaundice can produce pruritus. Conversely, systemic diseases can have GI consequences. Systemic lupus may cause gut ischemia, presenting with pain or bleeding. Overwhelming stress or severe burns may lead to gastric ulcer formation.


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InternalMed_Harrison. Evaluation of the patient with GI disease begins with a careful history and examination. Subsequent investigation with a variety of tools designed to test gut structure or function are indicated in selected cases. Some patients exhibit normal findings on diagnostic testing. In these individuals, validated symptom profiles are used to confidently diagnose a functional bowel disorder.


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InternalMed_Harrison. The history of the patient with suspected GI disease has several components. Symptom timing suggests specific etiologies. Symptoms of short duration commonly result from acute infection, toxin exposure, or abrupt inflammation or ischemia. Long-standing symptoms point to underlying chronic inflammatory or neoplastic conditions or functional bowel disorders. Symptoms from mechanical obstruction, ischemia, inflammatory bowel disease, and functional bowel disorders are worsened by meals. Conversely, ulcer symptoms may be relieved by eating or antacids. Symptom patterns and duration may suggest underlying etiologies. Ulcer pain occurs at intermittent intervals lasting weeks to months, whereas biliary colic has a sudden onset and lasts up to several hours. Pain from acute inflammation as with acute pancreatitis is severe and persists for days to weeks. Meals elicit diarrhea in some cases of inflammatory bowel disease and irritable bowel syndrome. Defecation relieves discomfort in


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InternalMed_Harrison. as with acute pancreatitis is severe and persists for days to weeks. Meals elicit diarrhea in some cases of inflammatory bowel disease and irritable bowel syndrome. Defecation relieves discomfort in inflammatory bowel disease and irritable bowel syndrome. Functional bowel disorders are exacerbated by stress. Sudden awakening from sound sleep suggests organic rather than functional disease. Diarrhea from malabsorption usually improves with fasting, whereas secretory diarrhea persists without oral intake.


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InternalMed_Harrison. Symptom relation to other factors narrows the list of diagnostic possibilities. Obstructive symptoms with prior abdominal surgery raise concern for adhesions, whereas loose stools after gastrectomy or gallbladder excision suggest dumping syndrome or postcholecystectomy diarrhea. Symptom onset after travel prompts a search for enteric infection. Medications may produce pain, altered bowel habits, or GI bleeding. Lower GI bleeding likely results from neoplasms, diverticula, or vascular lesions in an older person and from anorectal abnormalities or inflammatory bowel disease in a younger individual. Celiac disease is prevalent in people of northern European descent, whereas inflammatory bowel disease is more common in certain Jewish populations. A sexual history may raise concern for sexually transmitted diseases or immunodeficiency.


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InternalMed_Harrison. For more than two decades, working groups have been convened to devise symptom criteria to improve the confident diagnosis of functional bowel disorders and to minimize the numbers of unnecessary diagnostic tests performed. The most widely accepted symptom-based Approach to the Patient with Gastrointestinal Disease 1878 criteria are the Rome criteria. When tested against findings of structural investigations, the Rome criteria exhibit diagnostic specificities exceeding 90% for many of the functional bowel disorders.


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InternalMed_Harrison. The physical exam complements information from the history. Abnormal vital signs provide diagnostic clues and determine the need for acute intervention. Fever suggests inflammation or neoplasm. Orthostasis is found with significant blood loss, dehydration, sepsis, or autonomic neuropathy. Skin, eye, or joint findings may point to specific diagnoses. Neck exam with swallowing assessment evaluates dysphagia. Cardiopulmonary disease may present with abdominal pain or nausea; thus lung and cardiac exams are important. Pelvic examination tests for a gynecologic source of abdominal pain. Rectal exam may detect blood, indicating gut mucosal injury or neoplasm or a palpable inflammatory mass in appendicitis. Metabolic conditions and gut motor disorders have associated peripheral neuropathy.


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InternalMed_Harrison. Inspection of the abdomen may reveal distention from obstruction, tumor, or ascites or vascular abnormalities with liver disease. Ecchymoses develop with severe pancreatitis. Auscultation can detect bruits or friction rubs from vascular disease or hepatic tumors. Loss of bowel sounds signifies ileus, whereas high-pitched, hyperactive sounds characterize intestinal obstruction. Percussion assesses liver size and can detect shifting dullness from ascites. Palpation assesses for hepatosplenomegaly as well as neoplastic or inflammatory masses. Abdominal exam is helpful in evaluating unexplained pain. Intestinal ischemia elicits severe pain but little tenderness. Patients with visceral pain may exhibit generalized discomfort, whereas those with parietal pain or peritonitis have directed pain, often with involuntary guarding, rigidity, or rebound. Patients with musculoskeletal abdominal wall pain may note tenderness exacerbated by Valsalva or straight-leg lift maneuvers.


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InternalMed_Harrison. Laboratory, radiographic, and functional tests can assist in diagnosis of suspected GI disease. The GI tract also is amenable to internal evaluation with upper and lower endoscopy and to examination of luminal contents. Histopathologic exams of GI tissues complement these tests.


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InternalMed_Harrison. Laboratory Selected laboratory tests facilitate the diagnosis of GI disease. Iron-deficiency anemia suggests mucosal blood loss, whereas vitamin B12 deficiency results from small-intestinal, gastric, or pancreatic disease. Either also can result from inadequate oral intake. Leukocytosis and increased sedimentation rates and C-reactive protein levels are found in inflammatory conditions, whereas leukopenia is seen in viremic illness. Severe vomiting or diarrhea elicits electrolyte disturbances, acid-base abnormalities, and elevated blood urea nitrogen. Pancreaticobiliary or liver disease is suggested by elevated pancreatic or liver chemistries. Thyroid chemistries, cortisol, and calcium levels are obtained to exclude endocrinologic causes of GI symptoms. Pregnancy testing is considered for women with unexplained nausea. Serologic tests can screen for celiac disease, inflammatory bowel disease, rheumatologic diseases like lupus or scleroderma, and paraneoplastic dysmotility syndromes.


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InternalMed_Harrison. women with unexplained nausea. Serologic tests can screen for celiac disease, inflammatory bowel disease, rheumatologic diseases like lupus or scleroderma, and paraneoplastic dysmotility syndromes. Hormone levels are obtained for suspected endocrine neoplasia. Intraabdominal malignancies produce other tumor markers including the carcinoembryonic antigen CA 19-9 and α-fetoprotein. Blood testing also monitors medication therapy in some diseases, as with thiopurine metabolite levels in inflammatory bowel disease. Other body fluids are sampled under certain circumstances. Ascitic fluid is analyzed for infection, malignancy, or findings of portal hypertension. Cerebrospinal fluid is obtained for suspected central nervous system causes of vomiting. Urine samples screen for carcinoid, porphyria, and heavy metal intoxication.


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InternalMed_Harrison. Luminal Contents Luminal contents can be examined for diagnostic clues. Stool samples are cultured for bacterial pathogens, examined for leukocytes and parasites, or tested for Giardia antigen. Duodenal aspirates can be examined for parasites or cultured for bacterial overgrowth. Fecal fat is quantified in possible malabsorption. Stool electrolytes can be measured in diarrheal conditions. Laxative screens are done when laxative abuse is suspected. Gastric acid is quantified to rule out Zollinger-Ellison syndrome. Esophageal pH testing is done for refractory symptoms of acid reflux, whereas impedance techniques assess for nonacidic reflux. Pancreatic juice is analyzed for enzyme or bicarbonate content to exclude pancreatic exocrine insufficiency.


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InternalMed_Harrison. Endoscopy The gut is accessible with endoscopy, which can provide the diagnosis of the causes of bleeding, pain, nausea and vomiting, weight loss, altered bowel function, and fever. Table 344-2 lists the most common indications for the major endoscopic procedures. Upper endoscopy evaluates the esophagus, stomach, and duodenum, whereas colonoscopy assesses the colon and distal ileum. Upper endoscopy is advocated as the initial structural test performed in patients with suspected ulcer disease, esophagitis, neoplasm, malabsorption, and Barrett’s metaplasia because of its ability to directly visualize as well as biopsy the abnormality. Colonoscopy is the procedure of choice for colon cancer screening and surveillance as well as diagnosis of colitis secondary to infection, ischemia, radiation, and inflammatory bowel disease. Sigmoidoscopy examines the colon up to the splenic flexure and is currently used to exclude distal colonic inflammation or obstruction in young patients not at


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InternalMed_Harrison. and inflammatory bowel disease. Sigmoidoscopy examines the colon up to the splenic flexure and is currently used to exclude distal colonic inflammation or obstruction in young patients not at significant risk for colon cancer. For elusive GI bleeding secondary to arteriovenous malformations or superficial ulcers, small-intestinal examination is performed with push enteroscopy, capsule endoscopy, or double-balloon enteroscopy. Capsule endoscopy also can visualize small-intestinal Crohn’s disease in individuals with negative barium radiography. Endoscopic retrograde cholangiopancreaticography (ERCP) provides diagnoses of pancreatic and biliary disease. Endoscopic ultrasound is useful for evaluating extent of disease in GI malignancy as well as exclusion of choledocholithiasis, evaluation of pancreatitis, drainage of pancreatic pseudocysts, and assessment of anal continuity.


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InternalMed_Harrison. Radiography/Nuclear Medicine Radiographic tests evaluate diseases of the gut and extraluminal structures. Oral or rectal contrast agents like barium provide mucosal definition from the esophagus to the rectum. Contrast radiography also assesses gut transit and pelvic floor dysfunction. Barium swallow is the initial procedure for evaluation of dysphagia to exclude subtle rings or strictures and assess for achalasia, whereas small-bowel contrast radiology reliably diagnoses intestinal tumors and Crohn’s ileitis. Contrast enemas are performed when colonoscopy is unsuccessful or contraindicated. Ultrasound and computed tomography (CT) evaluate regions not accessible by endoscopy or contrast studies, including the liver, pancreas, gallbladder, kidneys, and retroperitoneum. These tests are useful for diagnosis of mass lesions, fluid collections, organ enlargement, and, in the case of ultrasound, gallstones. CT and magnetic resonance (MR) colonography are being evaluated as alternatives to


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InternalMed_Harrison. for diagnosis of mass lesions, fluid collections, organ enlargement, and, in the case of ultrasound, gallstones. CT and magnetic resonance (MR) colonography are being evaluated as alternatives to colonoscopy for colon cancer screening. MR imaging assesses the pancreaticobiliary ducts to exclude neoplasm, stones, and sclerosing cholangitis, and the liver to characterize benign and malignant tumors. Specialized CT or MR enterography can assess intensity of inflammatory bowel disease. Angiography excludes mesenteric ischemia and determines spread of malignancy. Angiographic techniques also access the biliary tree in obstructive jaundice. CT and MR techniques can be used to screen for mesenteric occlusion, thereby limiting exposure to angiographic dyes. Positron emission tomography can facilitate distinguishing malignant from benign disease in several organ systems.


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InternalMed_Harrison. Scintigraphy both evaluates structural abnormalities and quantifies luminal transit. Radionuclide bleeding scans localize bleeding sites in patients with brisk hemorrhage so that therapy with endoscopy, angiography, or surgery may be directed. Radiolabeled leukocyte scans can search for intraabdominal abscesses not visualized on CT. Biliary scintigraphy is complementary to ultrasound in the assessment of cholecystitis. Scintigraphy to quantify esophageal and gastric emptying is well established, whereas techniques to measure small-intestinal or colonic transit are less widely used. Histopathology Gut mucosal biopsies obtained at endoscopy evaluate for inflammatory, infectious, and neoplastic disease. Deep rectal biopsies assist with diagnosis of Hirschsprung’s disease or amyloid. Liver


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InternalMed_Harrison. Approach to the Patient with Gastrointestinal Disease biopsy is indicated in cases with abnormal liver chemistries, in unexplained jaundice, following liver transplant to exclude rejection, and to characterize the degree of inflammation in patients with chronic viral hepatitis prior to initiating antiviral therapy. Biopsies obtained during CT or ultrasound can evaluate for other intraabdominal conditions not accessible by endoscopy.


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InternalMed_Harrison. Functional Testing Tests of gut function provide important data when structural testing is nondiagnostic. In addition to gastric acid and pancreatic function testing, functional testing of motor activity is provided by manometric techniques. Esophageal manometry is useful for suspected achalasia, whereas small-intestinal manometry tests for pseudoobstruction. A wireless motility capsule is now available to measure transit and contractile activity in the stomach, small intestine, and colon in a single test. Anorectal manometry with balloon expulsion testing is used for unexplained incontinence or constipation from outlet dysfunction. Anorectal manometry and electromyography also assess anal function in fecal incontinence. Biliary manometry tests for sphincter of Oddi dysfunction with unexplained biliary pain. Measurement of breath hydrogen while fasting and after oral monoor oligosaccharide challenge can screen for carbohydrate intolerance and small-intestinal bacterial overgrowth.


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InternalMed_Harrison. Management options for the patient with GI disease depend on the cause of symptoms. Available treatments include modifications in dietary intake, medications, interventional endoscopy or radiology techniques, surgery, and therapies directed to external influences.


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InternalMed_Harrison. Dietary modifications for GI disease include treatments that only reduce symptoms, therapies that correct pathologic defects, and measures that replace normal food intake with enteral or parenteral formulations. Changes that improve symptoms but do not reverse an organic abnormality include lactose restriction for lactase deficiency, liquid meals in gastroparesis, carbohydrate restrictions with dumping syndrome, and low-FODMAP (fermentable oligodi-monosaccharides and polyols) diets in irritable bowel syndrome. The gluten-free diet for celiac disease exemplifies a modification that serves as primary therapy to reduce mucosal inflammation. Enteral medium-chain triglycerides replace normal fats in short-gut syndrome or severe ileal disease. Perfusion of liquid meals through a gastrostomy is performed in those who cannot swallow safely. Enteral feeding through a jejunostomy is considered for gastric dysmotility syndromes that preclude feeding into the stomach. Intravenous


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InternalMed_Harrison. gastrostomy is performed in those who cannot swallow safely. Enteral feeding through a jejunostomy is considered for gastric dysmotility syndromes that preclude feeding into the stomach. Intravenous hyperalimentation is used for individuals with generalized gut malfunction who cannot tolerate or who cannot be sustained with enteral nutrition.


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InternalMed_Harrison. Several medications are available to treat GI diseases. Considerable health care resources are expended on over-the-counter remedies. Many prescription drug classes are offered as short-term or continuous therapy of GI illness. A plethora of alternative treatments have gained popularity in GI conditions for which traditional therapies provide incomplete relief.


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InternalMed_Harrison. Over-the-Counter Agents Over-the-counter agents are reserved for mild GI symptoms. Antacids and histamine H2 antagonists decrease symptoms in gastroesophageal reflux and dyspepsia, whereas antiflatulents and adsorbents reduce gaseous symptoms. More potent acid inhibitors such as proton pump inhibitors are now available over the counter for treatment of chronic gastroesophageal reflux disease (GERD). Fiber supplements, stool softeners, enemas, and laxatives are used for constipation. Laxatives are categorized as stimulants, osmotic agents (including isotonic preparations containing polyethylene glycol), and poorly absorbed sugars. Nonprescription antidiarrheal agents include bismuth subsalicylate, kaolin-pectin combinations, and loperamide. Supplemental enzymes include lactase pills for lactose intolerance and bacterial α-galactosidase to treat excess gas. In general, use of a nonprescription preparation for more than a short time for chronic persistent symptoms should be supervised by


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InternalMed_Harrison. intolerance and bacterial α-galactosidase to treat excess gas. In general, use of a nonprescription preparation for more than a short time for chronic persistent symptoms should be supervised by a health care provider.


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InternalMed_Harrison. 1880 Prescription Drugs Prescription drugs for GI diseases are a major focus of attention from pharmaceutical companies. Potent acid suppressants, including drugs that inhibit the proton pump, are advocated for acid reflux when over-the-counter preparations are inadequate. Cytoprotective agents rarely are used for upper gut ulcers. Prokinetic drugs stimulate GI propulsion in gastroparesis and pseudoobstruction. Prosecretory drugs are prescribed for constipation refractory to other agents. Prescription antidiarrheals include opiate drugs, anticholinergic antispasmodics, tricyclics, bile acid binders, and serotonin antagonists. Antispasmodics and antidepressants also are useful for functional abdominal pain, whereas narcotics are used for pain control in organic conditions such as disseminated malignancy and chronic pancreatitis. Antiemetics in several classes reduce nausea and vomiting. Potent pancreatic enzymes decrease malabsorption and pain from pancreatic disease. Antisecretory


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InternalMed_Harrison. malignancy and chronic pancreatitis. Antiemetics in several classes reduce nausea and vomiting. Potent pancreatic enzymes decrease malabsorption and pain from pancreatic disease. Antisecretory drugs such as the somatostatin analogue octreotide treat hypersecretory states. Antibiotics treat ulcer disease secondary to Helicobacter pylori, infectious diarrhea, diverticulitis, intestinal bacterial overgrowth, and Crohn’s disease. Some cases of irritable bowel syndrome (especially those with diarrhea) respond to nonabsorbable antibiotic therapy. Anti-inflammatory and immunosuppressive drugs are used in ulcerative colitis, Crohn’s disease, microscopic colitis, refractory celiac disease, and gut vasculitis. Chemotherapy with or without radiotherapy is offered for GI malignancies. Most GI carcinomas respond poorly to such therapy, whereas lymphomas may be cured with such intervention.


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InternalMed_Harrison. Alternative Therapies Alternative treatments are marketed to treat selected GI symptoms. Ginger, acupressure, and acustimulation have been advocated for nausea, whereas pyridoxine has been investigated for nausea of first-trimester pregnancy. Probiotics containing active bacterial cultures are used as adjuncts in some cases of infectious diarrhea and irritable bowel syndrome. Probiotics that selectively nourish benign commensal bacteria may ultimately show benefit in functional disorders as well. Low-potency pancreatic enzyme preparations are sold as general digestive aids but have little evidence to support their efficacy.


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InternalMed_Harrison. Simple luminal interventions are commonly performed for GI diseases. Nasogastric tube suction decompresses the upper gut in ileus or mechanical obstruction. Nasogastric lavage of saline or water in the patient with upper GI hemorrhage determines the rate of bleeding and helps evacuate blood prior to endoscopy. Enteral feedings can be initiated through a nasogastric or nasoenteric tube. Enemas relieve fecal impaction or assist in gas evacuation in acute colonic pseudoobstruction. A rectal tube can be left in place to vent the distal colon in colonic pseudoobstruction and other colonic distention disorders.


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InternalMed_Harrison. In addition to its diagnostic role, endoscopy has therapeutic capabilities in certain settings. Cautery techniques can stop hemorrhage from ulcers, vascular malformations, and tumors. Injection with vasoconstrictor substances or sclerosants is used for bleeding ulcers, vascular malformations, varices, and hemorrhoids. Endoscopic encirclement of varices and hemorrhoids with constricting bands stops hemorrhage from these sites, whereas endoscopically placed clips can occlude arterial bleeding sites. Endoscopy can remove polyps or debulk lumen-narrowing malignancies. Endoscopic mucosal resection and radiofrequency techniques can remove or ablate some cases of Barrett’s esophagus with dysplasia. Endoscopic sphincterotomy of the ampulla of Vater relieves symptoms of choledocholithiasis. Obstructions of the gut lumen and pancreaticobiliary tree are relieved by endoscopic dilatation or placement of plastic or expandable metal stents. In cases of acute colonic pseudoobstruction, colonoscopy


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InternalMed_Harrison. of the gut lumen and pancreaticobiliary tree are relieved by endoscopic dilatation or placement of plastic or expandable metal stents. In cases of acute colonic pseudoobstruction, colonoscopy is used to withdraw luminal gas. Finally, endoscopy is commonly used to insert feeding tubes.


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InternalMed_Harrison. Radiologic measures also are useful in GI disease. Angiographic embolization or vasoconstriction decreases bleeding from sites not amenable to endoscopic intervention. Dilatation or stenting with fluoroscopic guidance relieves luminal strictures. Contrast enemas can reduce volvulus and evacuate air in acute colonic pseudoobstruction. CT and ultrasound help drain abdominal fluid collections, in many cases obviating the need for surgery. Percutaneous transhepatic cholangiography relieves biliary obstruction when ERCP is contraindicated. Lithotripsy can fragment gallstones in patients who are not candidates for surgery. In some instances, radiologic approaches offer advantages over endoscopy for gastroenterostomy placement. Finally, central venous catheters for parenteral nutrition may be placed using radiographic techniques.


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InternalMed_Harrison. Surgery is performed to cure disease, control symptoms without cure, maintain nutrition, or palliate unresectable neoplasm. Medication-unresponsive ulcerative colitis, diverticulitis, cholecystitis, appendicitis, and intraabdominal abscess are curable with surgery, whereas only symptom control without cure is possible with Crohn’s disease. Surgery is mandated for ulcer complications such as bleeding, obstruction, or perforation and intestinal obstructions that persist after conservative care. Fundoplication of the gastroesophageal junction is performed for severe ulcerative esophagitis and drug-refractory symptomatic acid reflux. Achalasia responds to operations to relieve lower esophageal sphincter pressure. Operations for motor disorders have been introduced including implanted electrical stimulators for gastroparesis and electrical devices and artificial sphincters for fecal incontinence. Surgery may be needed to place a jejunostomy for long-term enteral feedings. The threshold for


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InternalMed_Harrison. stimulators for gastroparesis and electrical devices and artificial sphincters for fecal incontinence. Surgery may be needed to place a jejunostomy for long-term enteral feedings. The threshold for performing surgery depends on the clinical setting. In all cases, the benefits of operation must be weighed against the potential for postoperative complications.


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InternalMed_Harrison. In some conditions, GI symptoms respond to treatments directed outside the gut. Psychological therapies including psychotherapy, behavior modification, hypnosis, and biofeedback have shown efficacy in functional bowel disorders. Patients with significant psychological dysfunction and those with little response to treatments targeting the gut are likely to benefit from this form of therapy. Louis Michel Wong Kee Song, Mark Topazian Gastrointestinal endoscopy has been attempted for over 200 years, but the introduction of semirigid gastroscopes in the middle of the twentieth century marked the dawn of the modern endoscopic era. Since then, rapid advances in endoscopic technology have led to dramatic changes in the diagnosis and treatment of many digestive diseases. Innovative endoscopic devices and new endoscopic treatment modalities continue to expand the use of endoscopy in patient care.


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InternalMed_Harrison. Current flexible endoscopes provide an electronic video image generated by a charge-coupled device in the tip of the endoscope. Operator controls permit deflection of the endoscope tip; fiberoptic bundles or light-emitting diodes bring light to the tip of the endoscope; and working channels allow washing, suctioning, and the passage of instruments. Progressive changes in the diameter and stiffness of endoscopes have improved the ease and patient tolerance of endoscopy. FIGURE 345-1 Duodenal ulcers. A. Ulcer with a clean base. B. Ulcer with a visible vessel (arrow) in a patient with recent hemorrhage.


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InternalMed_Harrison. Upper endoscopy, also referred to as esophagogastroduodenoscopy (EGD), is performed by passing a flexible endoscope through the mouth into the esophagus, stomach, and duodenum. The procedure is the best method for examining the upper gastrointestinal mucosa. While the upper gastrointestinal radiographic series has similar accuracy for diagnosis of duodenal ulcer (Fig. 345-1), EGD is superior for detection of gastric ulcers (Fig. 345-2) and flat mucosal lesions such as Barrett’s esophagus (Fig. 345-3), and it permits directed biopsy and endoscopic therapy. Intravenous conscious sedation is given to most patients in the United States to ease the anxiety and discomfort of the procedure, although in many countries EGD is routinely performed with topical pharyngeal anesthesia only. Patient tolerance of unsedated EGD is improved by the use of an ultrathin, 5-mm diameter endoscope that can be passed transorally or transnasally.


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InternalMed_Harrison. Colonoscopy is performed by passing a flexible colonoscope through the anal canal into the rectum and colon. The cecum is reached in >95% of cases, and the terminal ileum can often be examined. Colonoscopy is the gold standard for imaging the colonic mucosa. Colonoscopy has greater sensitivity than barium enema for colitis (Fig. 345-4), polyps (Fig. 345-5), and cancer (Fig. 345-6). Computed tomography (CT) colonography is an emerging technology that rivals the accuracy of colonoscopy for detection of some polyps and cancer, although it may not be sensitive for the detection of flat lesions, such as serrated polyps (Fig. 345-7). Conscious sedation is usually given before colonoscopy in the United States, although a willing patient and a skilled examiner can complete the procedure without sedation in many cases. Flexible sigmoidoscopy is similar to colonoscopy, but visualizes only the rectum and a variable portion of the left colon, typically to 60 cm


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InternalMed_Harrison. Flexible sigmoidoscopy is similar to colonoscopy, but visualizes only the rectum and a variable portion of the left colon, typically to 60 cm FIGURE 345-2 Gastric ulcers. A. Benign gastric ulcer. B. Malignant gastric ulcer involving greater curvature of stomach. from the anal verge. This procedure causes abdominal cramping, but 1881 it is brief and is usually performed without sedation. Flexible sigmoidoscopy is primarily used for evaluation of diarrhea and rectal outlet bleeding.


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InternalMed_Harrison. Three endoscopic techniques are currently used to evaluate the small intestine, most often in patients presenting with presumed small-bowel bleeding. For capsule endoscopy, the patient swallows a disposable capsule that contains a complementary metal oxide silicon (CMOS) chip camera. Color still images (Fig. 345-8) are transmitted wirelessly to an external receiver at several frames per second until the capsule’s battery is exhausted or it is passed into the toilet. Capsule endoscopy enables visualization of the small-bowel mucosa beyond the reach of a conventional endoscope and, at present, is solely a diagnostic procedure.


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InternalMed_Harrison. Push enteroscopy is performed with a long endoscope similar in design to an upper endoscope. The enteroscope is pushed down the small bowel, sometimes with the help of a stiffening overtube that extends from the mouth to the small intestine. The proximal to mid-jejunum is usually reached, and the instrument channel of the endoscope allows for biopsy or endoscopic therapy. Deeper insertion into the small bowel can be accomplished by single-or double-balloon enteroscopy or spiral enteroscopy (Fig. 345-9). These instruments enable pleating of the small intestine onto an over-tube (see Video 346e-1). With balloon-assisted enteroscopy, the entire intestinal tract can be visualized in some patients when both the oral and anal routes of insertion are used. Biopsies and endoscopic therapy can be performed throughout the visualized small bowel (Fig. 345-10).


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InternalMed_Harrison. During ERCP a side-viewing endoscope is passed through the mouth to the duodenum, the ampulla of Vater is identified and cannulated with a thin plastic catheter, and radiographic contrast material is injected into the bile duct and pancreatic duct under fluoroscopic guidance (Fig. 345-11). When indicated, the sphincter of Oddi can be opened using the technique of endoscopic sphincterotomy (Fig. 345-12). Stones can be retrieved from the ducts (see Video 346e-15), biopsies can be performed, strictures can be dilated and/or stented (Fig. 345-13), and ductal leaks can be stented (Fig. 345-14). ERCP is often performed for therapy but remains important in diagnosis, especially for sphincter of Oddi dysfunction and for tissue sampling of ductal strictures.


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InternalMed_Harrison. EUS utilizes high-frequency ultrasound transducers incorporated into the tip of a flexible endoscope. Ultrasound images are obtained of the gut wall and adjacent organs, vessels, and lymph nodes. By sacrificing depth of ultrasound penetration and bringing the ultrasound transducer close to the area of interest via endoscopy, high-resolution images are obtained. EUS provides the most accurate preoperative local staging of esophageal, pancreatic, and rectal malignancies (Fig. 345-15), although it does not detect most distant metastases. EUS is also useful for diagnosis of bile duct stones, gallbladder disease, submucosal gastrointestinal lesions, and chronic pancreatitis. Fine-needle aspirates and core biopsies of masses and lymph nodes in the posterior mediastinum, abdomen, pancreas, retroperitoneum, and pelvis can be obtained under EUS guidance (Fig. 345-16). EUS-guided therapeutic procedures are increasingly performed, including drainage of abscesses, pseudocysts, and pancreatic


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InternalMed_Harrison. and pelvis can be obtained under EUS guidance (Fig. 345-16). EUS-guided therapeutic procedures are increasingly performed, including drainage of abscesses, pseudocysts, and pancreatic necrosis into the gut lumen (see Video 346e-2), celiac plexus neurolysis for treatment of pancreatic pain, ethanol ablation of pancreatic neuroendocrine tumors, treatment of gastrointestinal hemorrhage, and drainage of obstructed biliary and pancreatic ducts.


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InternalMed_Harrison. NOTES is an evolving collection of endoscopic methods that entail passage of an endoscope or its accessories into or through the wall of the gastrointestinal tract to perform diagnostic or therapeutic FIGURE 345-3 Barrett’s esophagus. A. Pink tongues of Barrett’s mucosa extending proximally from the gastroesophageal junction. B. Barrett’s esophagus with a suspicious nodule (arrow) identified during endoscopic surveillance. C. Histologic finding of intramucosal adenocarcinoma in the endoscopically resected nodule. Tumor extends into the esophageal submucosa (arrow). D. Barrett’s esophagus with locally advanced adenocarcinoma. FIGURE 345-5 Colonic polyps. A. Pedunculated colon polyp on a thick stalk covered with normal mucosa (arrow). B. Sessile rectal polyp.


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InternalMed_Harrison. FIGURE 345-5 Colonic polyps. A. Pedunculated colon polyp on a thick stalk covered with normal mucosa (arrow). B. Sessile rectal polyp. FIGURE 345-4 Causes of colitis. A. Chronic ulcerative colitis with diffuse ulcerations and exudates. B. Severe Crohn’s colitis with deep ulcers. C. Pseudomembranous colitis with yellow, adherent pseudo-membranes. D. Ischemic colitis with patchy mucosal edema, subepithelial hemorrhage, and cyanosis. FIGURE 345-6 Colon adenocarcinoma growing into the lumen. FIGURE 345-7 Flat serrated polyp in the cecum. A. Appearance of the lesion under conventional white-light imaging. B. Mucosal patterns and boundary of the lesion enhanced with narrow band imaging. C. Submucosal lifting of the lesion with dye (methylene blue) injection prior to resection.


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InternalMed_Harrison. interventions. Some NOTES procedures, such as percutaneous endoscopic gastrostomy (PEG) or endoscopic necrosectomy of pancreatic necrosis, are well-established clinical procedures (see Video 346e-2); others, such as per-oral endoscopic myotomy (POEM) and endoscopic full-thickness resection of gastrointestinal mural lesions (Fig. 345-17, see Video 346e-3), are emerging as viable clinical therapeutic options; and still others, such as endoscopic appendectomy, cholecystectomy, and tubal ligation, are in development, and their ultimate clinical application is presently unclear. NOTES is currently an area of intense innovation and endoscopic research. FIGURE 345-8 Capsule endoscopy image of jejunal vascular ectasia.


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InternalMed_Harrison. FIGURE 345-8 Capsule endoscopy image of jejunal vascular ectasia. Endoscopic mucosal resection (EMR) (see Video 346e-4) and endoscopic submucosal dissection (ESD) (Fig. 345-18, see Video 346e-5) are two commonly used techniques for the resection of benign and early-stage malignant gastrointestinal neoplasms. In addition to providing larger specimens for more accurate histopathologic assessment and diagnosis, these techniques can be potentially FIGURE 345-9 Radiograph of a double-balloon enteroscope in the small intestine. FIGURE 345-10 Nonsteroidal anti-inflammatory drug (NSAID)–induced proximal ileal stricture diagnosed by double-balloon endoscopy. A. Ileal stricture causing obstructive symptoms. B. Balloon dilatation of the ileal stricture. C. Appearance of stricture after dilatation.


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InternalMed_Harrison. curative for certain dysplastic lesions and focal intramucosal carcinomas involving the esophagus, stomach, and colon. Several devices are also available for closure of EMR and ESD defects, as well as gastrointestinal fistulas and perforations. Endoscopic clips deployed through the working channel of an endoscope have been used for many years to treat bleeding lesions, but the development of more robust over-thescope clips has facilitated endoscopic closure of gastrointestinal fistulas and perforations not previously amenable to endoscopic therapy (see Video 346e-6). Endoscopic suturing is also feasible, and the technique can be used to close perforations and large defects (Fig. 345-19, see Video 346e-7), anastomotic leaks, and fistulas. Other potential indications for endoscopic suturing include stent fixation to prevent its migration (Fig. 345-20), and endoscopic bariatric procedures. These technologies are likely to have an expanding role in patient care.


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InternalMed_Harrison. Medications used during conscious sedation may cause respiratory depression or allergic reactions. All endoscopic procedures carry some risk of bleeding and gastrointestinal perforation. The risk is small with diagnostic upper endoscopy and colonoscopy (<1:1000 procedures), but ranges from 0.5 to 5% when therapeutic procedures, such as EMR and ESD, control of hemorrhage, or stricture dilatation, are performed. Bleeding and perforation are rare adverse events with flexible sigmoidoscopy. The risk of adverse events for diagnostic EUS (without needle aspiration) is similar to that for diagnostic upper endoscopy. FIGURE 345-11 Endoscopic retrograde cholangiopancreatogra-phy (ERCP) for bile duct stones with cholangitis. A. Faceted bile duct stones are demonstrated in the common bile duct. B. After endoscopic sphincterotomy, the stones are extracted with a Dormia basket. A small abscess communicates with the left hepatic duct.


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InternalMed_Harrison. Infectious complications are uncommon with most endoscopic procedures. Some procedures carry a higher incidence of postprocedure bacteremia, and prophylactic antibiotics may be indicated (Table 345-1). Management of antithrombotic agents prior to endoscopic procedures should take into account the procedural risk of hemorrhage, the agent, and the patient condition, as summarized in Table 345-2. ERCP carries additional risks. Pancreatitis occurs in about 5% of patients undergoing the procedure and in up to 30% of patients with sphincter of Oddi dysfunction. Young anicteric patients with normal ducts are at increased risk. Post-ERCP pancreatitis is usually mild and self-limited, but may result in prolonged hospitalization, surgery, diabetes, or death when severe. Bleeding occurs in 1% of endoscopic sphincterotomies. Ascending cholangitis, pseudocyst infection, retroperitoneal perforation, and abscess formation may occur as a result of ERCP.


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InternalMed_Harrison. Percutaneous gastrostomy tube placement during EGD is associated with a 10–15% incidence of adverse events, most often wound infections. Fasciitis, pneumonia, bleeding, buried bumper syndrome, and colonic injury may result from gastrostomy tube placement. FIGURE 345-12 Endoscopic sphincterotomy. A. A normal-appearing ampulla of Vater. B. Sphincterotomy is performed with electrocautery. C. Bile duct stones are extracted with a balloon catheter. D. Final appearance of the sphincterotomy.


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InternalMed_Harrison. C. Bile duct stones are extracted with a balloon catheter. D. Final appearance of the sphincterotomy. FIGURE 345-13 Endoscopic diagnosis, staging, and palliation of hilar cholangiocarcinoma. A. Endoscopic retrograde cholangiopancreatography (ERCP) in a patient with obstructive jaundice demonstrates a malignant-appearing stricture of the biliary confluence extending into the left and right intrahepatic ducts. B. Intraductal ultrasound of the biliary stricture demonstrates marked bile duct wall thickening due to tumor (T) with partial encasement of the hepatic artery (arrow). C. Intraductal biopsy obtained during ERCP demonstrates malignant cells infiltrating the submucosa of the bile duct wall (arrow). D. Endoscopic placement of bilateral self-expanding metal stents (arrow) relieves the biliary obstruction. GB, gallbladder. (Image C courtesy of Dr. Thomas Smyrk; with permission.)


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InternalMed_Harrison. C courtesy of Dr. Thomas Smyrk; with permission.) Endoscopy is an important diagnostic and therapeutic technique for patients with acute gastrointestinal hemorrhage. Although gastrointestinal bleeding stops spontaneously in most cases, some patients will have persistent or recurrent hemorrhage that may be life-threatening. Clinical predictors of rebleeding help identify patients most likely to benefit from urgent endoscopy and endoscopic, angiographic, or surgical hemostasis. FIGURE 345-14 Bile leak (arrow) from a duct of Luschka after lapa-roscopic cholecystectomy. Contrast leaks from a small right intrahe-patic duct into the gallbladder fossa and then flows into the pigtail of a percutaneous drainage catheter.


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InternalMed_Harrison. Initial Evaluation The initial evaluation of the bleeding patient focuses on the severity of hemorrhage as reflected by the postural vital signs, the frequency of hematemesis or melena, and (in some cases) findings on nasogastric lavage. Decreases in hematocrit and hemoglobin lag behind the clinical course and are not reliable gauges of the magnitude of acute bleeding. This initial evaluation, completed well before the bleeding source is confidently identified, guides immediate supportive care of the patient, triage to the ward or intensive care unit, and timing of endoscopy. The severity of the initial hemorrhage is the most important indication for urgent endoscopy, since a large initial bleed increases the likelihood of ongoing or recurrent bleeding. Patients with resting hypotension or orthostatic change in vital signs, repeated hematemesis, or bloody nasogastric aspirate that does not clear with large-volume lavage, or those requiring blood transfusions, should be considered for


InternalMed_Harrison

InternalMed_Harrison. orthostatic change in vital signs, repeated hematemesis, or bloody nasogastric aspirate that does not clear with large-volume lavage, or those requiring blood transfusions, should be considered for urgent endoscopy. In addition, patients with cirrhosis, coagulopathy, or respiratory or renal failure and those over 70 years of age are more likely to have significant rebleeding.