Short theoretic material - Гастроэнтерология (анг,рус) - Конспект лекций
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Гастроэнтерология (анг,рус)

Short theoretic material

 

Cirrhosis is a chronic diffuse condition characterized by replacement of liver cells by fibrotic tissue, which creates a nodular-appearing distortion of the normal liver architecture. This fibrosis represents the end result of a variety of etiologies of liver injury.

Hepatic Encephalopathy

Hepatic encephalopathy is the syndrome of disordered consciousness and altered neuromuscular activity that is seen in patients with acute or chronic hepatocellular failure or portosystemic shunting.

Mechanisms of Injury

The pathogenesis of hepatic encephalopathy is controversial, and numerous mediators have been implicated.

Precipitating factors include azotemia; acute liver failure; use of a tranquilizer, opioid, or sedative-hypnotic medication; GI hemorrhage; hypokalemia and alkalosis (diuretics and diarrhea); constipation; infection; high-protein diet; progressive hepatocellular dysfunction; and portosystemic shunts (surgical or TIPS).

Diagnosis

Presentation varies from subtle mental status changes to coma.

Asterixis (flapping tremor) is present in stages I-II of encephalopathy. This motor disturbance is not specific to hepatic encephalopathy.

The electroencephalogram shows slow, high-amplitude, and triphasic waves.

Determination of blood ammonia level is not a sensitive or specific test for hepatic encephalopathy.

Treatment

Diet

The rationale and benefit of dietary protein restriction is controversial. Once the patient is able to eat, a diet containing 30-40 g of protein per day is initiated. Special diets (vegetable protein or branched-chain amino acid enriched) may be beneficial in patients with encephalopathy that is refractory to the usual measures.

Medications

Medications include nonabsorbable disaccharides (lactulose, lactitol, and lactose in lactase-deficient patients) and antibiotics (neomycin, metronidazole, and rifaximin).

The initial dose of lactulose is 15-45 mL PO bid-qid. Maintenance dose should be adjusted to produce three to five soft stools per day. Oral lactulose should not be given to patients with an ileus or possible bowel obstruction.

Lactulose enemas (prepared by the addition of 300 mL lactulose to 700 mL distilled water) can also be administered.

Neomycin can be given by mouth (500-1,000 mg q6h) or as a retention enema (1% solution in 100-200 mL isotonic saline). Approximately 1%-3% of the administered dose of neomycin is absorbed, with the attendant risk of ototoxicity and nephrotoxicity. The risk of toxicity is increased in patients with renal insufficiency. Because lactulose is as effective as neomycin, it is preferred for initial and maintenance therapy.

Metronidazole (250 mg PO q8h) is useful for short-term therapy when neomycin is unavailable or poorly tolerated. Long-term metronidazole is not recommended due to its associated toxicities.

Rifaximin 400 mg is a new antibiotic with a very good safety profile that is used as an alternative to neomycin and metronidazole.

Combination therapy with lactulose and any of the antibiotics mentioned above should be considered in cases that are refractory to either agent alone.

Portal Hypertension

Portal hypertension is the main complication of cirrhosis, and is characterized by increased resistance to portal flow and increased portal venous inflow. Portal hypertension is established by determining the pressure difference between the hepatic vein and the portal vein (pressure gradient >10 mm Hg).

Direct and indirect clinical consequences of portal hypertension include esophageal and gastric varices, portal hypertensive gastropathy, ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis.

Etiology

Causes of portal hypertension in patients without cirrhosis include idiopathic portal hypertension, schistosomiasis, congenital hepatic fibrosis, sarcoidosis, cystic fibrosis, arteriovenous fistulas, splenic and portal vein thrombosis, myeloproliferative diseases, nodular regenerative hyperplasia, and focal nodular hyperplasia.

Diagnosis

Clinical Presentation

Portal hypertension frequently complicates cirrhosis and presents with ascites, GI bleeding from esophageal or gastric varices or portal hypertensive gastropathy, and splenomegaly.

Imaging

Ultrasonography, CT, and MRI showing cirrhosis, splenomegaly, collateral venous circulation, and ascites are suggestive of portal hypertension.

Diagnostic Procedures

Upper endoscopy showing varices (esophageal or gastric) or portal hypertensive gastropathy

Transjugular portal pressure measurements

 

Ascites

Ascites is the abnormal (>25 mL) accumulation of fluid within the peritoneal cavity. Causes of ascites besides cirrhosis include cancer (peritoneal carcinomatosis), heart failure, tuberculosis, pancreatic disease, nephrotic syndrome, surgery or trauma to the lymphatic system or ureters, and serositis.

Diagnosis

Clinical Presentation

Presentation ranges from ascites detected only by imaging methods to a distended, bulging abdomen on physical examination. Percussion of the abdomen reveals shifting dullness.

Imaging

Ultrasonography, CT, and MRI are sensitive methods to detect ascites.

Laboratory Studies

A serum to ascites albumin gradient (SAAG) that is >1.1 g/dL indicates portal hypertension-related ascites (97% specificity).

An SAAG of <1.1 g/dL is found in nephrotic syndrome, peritoneal carcinomatosis, serositis, tuberculosis, and biliary or pancreatic ascites.

Diagnostic Procedures

Paracentesis should be performed for diagnosis (e.g., new-onset ascites, suspicion of malignant ascites, or spontaneous bacterial peritonitis [SBP]) or as a therapeutic maneuver when tense ascites causes significant discomfort or respiratory compromise.

Routine diagnostic testing should include fluid cell and differential counts, albumin, total protein, and culture.

Amylase and triglyceride measurement, cytology, and mycobacterial smear/culture can be performed to confirm specific diagnoses.

Bleeding and intestinal perforation are possible complications.

Rapid large-volume paracentesis (>5 L) may lead to circulatory collapse, encephalopathy, and renal failure. Concomitant administration of IV albumin (5-8 g/L ascites removed) can be used to minimize these complications, especially in the setting of renal insufficiency or the absence of peripheral edema.

 

Treatment

Dietary

Dietary salt restriction (2 g salt or 88 mmol Na+/d) should be initiated and continued thereafter unless the renal ability to excrete sodium spontaneously improves.

In selected cases, it may be necessary to restrict sodium intake further.

The use of potassium-containing salt substitutes can lead to serious hyperkalemia.

Routine water restriction is not necessary. If dilutional hyponatremia (serum Na+ <120 mmol/L) occurs, fluid restriction to 1,000-1,500 mL/d usually suffices.

Medications

Diuretic therapy can be initiated along with salt restriction. The goal of diuretic therapy should be a daily weight loss of no more than 1.0 kg in patients with edema and approximately 0.5 kg in those without edema until ascites is adequately controlled. Diuretics should not be administered to individuals with an increasing serum creatinine level.

Spironolactone (100 mg PO in a single daily dose with food) is the diuretic of choice. The daily dose can be increased by 50-100 mg every 7-10 days until satisfactory weight loss, a maximum dose of 400 mg, or side effects occur. Hyperkalemia and gynecomastia are common side effects. Amiloride or triamterene (potassium-sparing diuretics) are substitutes that can be used in patients in whom painful gynecomastia develops.

Loop diuretics, such as furosemide (20-40 mg, increasing to a maximum dose of 160 mg PO daily) or bumetanide (0.5-2.0 mg PO daily), can be added to spironolactone.

Patients should be observed closely for signs of dehydration, electrolyte disturbances, encephalopathy, muscle cramps, and renal insufficiency. Nonsteroidal anti-inflammatory agents may blunt the effect of diuretics and increase the risk of renal dysfunction.

Nonoperative:TIPS has been proven effective in the management of refractory ascites (fluid overload that is nonresponsive to a sodium-restricted diet and high-dose diuretic therapy).

Complications include shunt occlusion, bleeding, infection, cardiopulmonary compromise, and hepatic encephalopathy.

Spontaneous Bacterial Peritonitis

SBP is an infectious complication of portal hypertension-related ascites. Risk factors for SBP include ascitic fluid protein concentration <1 mg/dL, variceal hemorrhage, and a prior episode of SBP.

Diagnosis

Clinical manifestations include abdominal pain and distention, fever, decreased bowel sounds, and worsening of hepatic encephalopathy. However, the disease may be present in the absence of specific clinical signs. Cirrhotic patients with ascites and evidence of any clinical deterioration should undergo diagnostic paracentesis to exclude SBP.

Laboratory: The diagnosis is likely when the ascitic fluid contains >250 neutrophils/microliter Gram stain reveals the organism in only 10%-20% of samples. A positive culture confirms the diagnosis.

Cultures are more likely to be positive when 10 mL ascitic fluid is inoculated into two blood culture bottles at the bedside.

The most common organisms are Escherichia coli, Klebsiella, and Streptococcus pneumoniae. Blood cultures are positive in approximately one-half of cases with SBP. Polymicrobial infection is uncommon and should lead to the suspicion of secondary bacterial peritonitis.

Treatment

In suspected cases (fever, abdominal pain, or tenderness) without more than 250 neutrophils/microliter, empiric antibiotic therapy with a third-generation cephalosporin (e.g., ceftriaxone, 1 g IV daily, or cefotaxime, 1-2 g IV q6-8h, depending on renal function; or a quinolone (ciprofloxacin, 400 mg IV q12h) is appropriate for 5 days. Paracentesis should be repeated if no clinical improvement occurs in 48-72 hours, especially if the initial ascitic fluid culture was negative.

Concomitant use of albumin 1.5 g/kg body weight at diagnosis and 1 g/kg body weight on day 3 improves survival and prevents renal failure in SBP.

Norfloxacin (400 mg PO daily) can be used as secondary prophylaxis by reducing the frequency of recurrent episodes of SBP. However, the use of antibiotic prophylaxis has not been clearly shown to improve survival and does select resistant gut flora.

Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is a unique form of functional renal impairment in the setting of acute or, more commonly, chronic liver disease. Common precipitating factors include systemic bacterial infections, SBP, and large-volume paracentesis without volume expansion.

Diagnosis

Major and minor diagnostic criteria are summarized in Table 17-4.

Type I HRS is characterized by the acute onset of rapidly progressive (<2 weeks), oliguric renal failure unresponsive to volume expansion. There is a doubling of the initial serum creatinine to a level >2.5 mg/dL or a 50% reduction in the creatinine clearance to a level <20 mL/min. Type II HRS progresses more slowly but relentlessly and often clinically manifests as diuretic-resistant ascites.

TABLE 17-4 Diagnostic Criteria of Hepatorenal Syndrome

Major criteria

Low glomerular filtration rate, as indicated by serum creatinine >1.5 mg/dL or 24-hr creatinine clearance <40 mL/min

Absence of shock, ongoing bacterial infection, fluid losses, and current treatment with nephrotoxic drugs

No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dL or increase in creatinine clearance to 40 mL/min) after diuretic withdrawal and expansion of plasma volume with 1.5 L of a plasma expander

Proteinuria <500 mg/dL and no ultrasonographic evidence of obstructive uropathy or parenchymal renal disease

Additional criteria

Urine volume <500 mL/d

Urine sodium <10 mEq/L

Urine osmolality greater than plasma osmolality

Urine red blood cells <50/high-power field

Serum sodium concentration <130 mEq/L

Note: All major criteria must be present for the diagnosis of hepatorenal syndrome. Additional criteria are not necessary for the diagnosis but provide supportive evidence.

Treatment

Medical

No clear or established treatments are available for HRS. Systemic vasoconstrictors including vasopressin analogs (terlipressin), somatostatin analogs (octreotide), and О±-adrenergic agonists (midodrine and norepinephrine) with plasma expansion have shown a beneficial role in uncontrolled studies.

Nonmedical

TIPS is a potential treatment alternative; however, data are limited.

Hemodialysis may be indicated in patients listed for liver transplantations.

Liver Transplantation

In suitable candidates, liver transplantation may be curative.

Prognosis

Without treatment, patients with type I HRS have a short-term fatal prognosis, with death occurring within 2-3 months of onset. Patients with type II HRS have a median survival of approximately 6 months.

 

 

 

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