Chapter 41: Alterations of Digestive Function

Duodenal Ulcers

• A duodenal ulcer is a break in the duodenum's protective mucosal lining.
• H. pylori infection and NSAID use are the most common causes.
• Rare cases of idiopathic duodenal ulcers can stem from rapid gastric emptying or smoking.

Pathophysiology

• Acid in the duodenum facilitates H. pylori infection.
• Causative factors lead to high concentrations of acid and pepsin, which penetrate the mucosal barrier and cause ulceration.

Clinical Manifestations

• Chronic intermittent epigastric pain is common, occurring 30 minutes to 2 hours after eating or in the middle of the night.
• Pain is caused by sensorineural stimulation by acid or muscle spasm.
• Pain is typically relieved by food or antacids ("pain-food-relief" pattern).
• Older adults may experience no symptoms; hemorrhage or perforation may be the first sign.
• Bleeding can cause hematemesis or melena.

Diagnosis

• Endoscopic evaluation allows visualization of lesions and biopsy.
• Radioimmune assays determine gastrin levels to identify ulcers, associated with gastric carcinomas.
• H. pylori is detected using the urea breath test, serum antibody tests (IgG and IgA), and stool antigen levels.
• Gastric biopsy detects H. pylori and confirms eradication after treatment

Treatment

• The goal is to relieve hyperacidity and prevent complications.
• Antacids neutralize gastric acid, increase pH, inactivate pepsin, and relieve pain.
• Proton pump inhibitors or H2 receptor blockers suppress acid secretion.
• A combination of antibiotics eradicates H. pylori; probiotics may provide added benefit.
• Ulcer-coating agents (sucralfate and colloidal bismuth) promote healing.
• Anticholinergic drugs inhibit gastric secretion, suppress motility, and delay gastric emptying.
• A diet high in vitamin A, vitamin C, zinc, selenium, and fiber is recommended.
• Surgical resection may be needed for bleeding, perforation, obstruction, or peritonitis.

Complications

• Intestinal obstruction or perforation can cause constant pain.

Dysphagia

• Defined as difficulty swallowing or a sensation of obstruction during swallowing.

Pathophysiology

• Classified as oropharyngeal or substernal/esophageal based on the location of the sensation.
• Caused by mechanical obstruction of the esophagus or a functional disorder affecting esophageal motility.
• Mechanical obstruction is either intrinsic (tumors, strictures) or extrinsic (external compression).
• Functional dysphagia results from neural or muscular disorders affecting voluntary swallowing or peristalsis.
• Typical causes include dermatomyositis, stroke, multiple sclerosis, Parkinson's disease, ALS, or myasthenia gravis.
• Achalasia is a rare disorder involving the loss of inhibitory neurons, leading to smooth muscle atrophy.
• Loss of myenteric innervation causes loss of esophageal peristalsis and failure of LES relaxation, leading to functional obstruction.

Clinical Manifestations

• Vary depending on the location of the obstruction.
• Distention and spasm of esophageal muscles cause stabbing pain.
• Upper esophageal obstruction causes discomfort 2-4 seconds after swallowing.
• Lower esophageal obstruction causes discomfort 10-15 seconds after swallowing.
• Tumors initially cause difficulty swallowing solids, progressing to semisolids and liquids.
• Common symptoms include retrosternal pain, regurgitation, unpleasant taste, vomiting, and weight loss.

Diagnosis

• Diagnosis depends on history and clinical manifestations.
• Video fluoroscopy and ultrasound visualize contours and identify structural defects.
• Manometry documents motility disorders and abnormal pressure changes.
• A video-modified barium swallow evaluates motility in oropharyngeal dysphagia.
• Esophageal endoscopy examines mucosa, obtains biopsies, and may facilitate corrective surgery.

Treatment

• Symptoms can be managed by eating slowly, eating small meals, taking fluids with meals, and elevating the head of the bed.
• Medications may need to be formulated for easy swallowing; tube feedings may be necessary.
• Definitive treatments include dilation or surgical myomotomy of the LES and botulinum toxin injection.

Complications

• Aspiration of esophageal contents can lead to chronic cough and pneumonia.

GERD

• Defined as reflux of acid and pepsin or bile salts from the stomach into the esophagus causing esophagitis.
• Affects around 18% to 27% in North America.
• Risk factors include obesity, hiatal hernia, and drugs that relax the LES.
• May trigger asthma, chronic cough, or sinusitis.
• Nonerosive reflux disease (NERD) involves reflux symptoms without visible esophageal injury.

Pathophysiology

• GERD is caused by abnormalities in LES function, esophageal motility, and gastric motility or emptying.
• Resting tone of LES is lower than normal.
• Increased abdominal pressure from vomiting, coughing, lifting, obesity, or pregnancy can cause reflux esophagitis.
• Hiatal hernia weakens the LES.
• Delayed gastric emptying increases the risk of reflux esophagitis.
• Severity depends on the gastric content composition and esophageal mucosa exposure time.
• An acid pocket is an area of postprandial unbuffered gastric acid; enlarged in hiatal hernia.

Clinical Manifestations

• Heartburn, chronic cough, asthma attacks, laryngitis, sinusitis, and upper abdominal pain within 1 hour of eating.
• Dysphagia with weight loss can result from edema, fibrosis, esophageal spasm, or decreased motility.
• Alcohol or acidic foods can cause discomfort during swallowing.
• Symptoms worsen when lying down or with increased intraabdominal pressure.

Diagnosis

• Based on history and clinical manifestations.
• Esophageal endoscopy shows hyperemia, edema, erosion, and strictures.
• Dysplastic changes (Barrett esophagus) can be identified by biopsy.
• Impedance/pH monitoring measures the movement of stomach contents and acidity.

Treatment

• Proton pump inhibitors are the primary treatment for controlling symptoms and healing esophagitis.
• Other therapies include H2 receptor antagonists, prokinetics, and antacids.
• Lifestyle modifications include weight reduction, smoking cessation, elevating the head of the bed, and avoiding tight clothing.
• Laparoscopic fundoplication may be needed if medical treatment fails.

Complications

• Eosinophilic esophagitis is an idiopathic inflammatory disease characterized by esophageal infiltration of eosinophils.
• Precancerous lesions (Barrett esophagus) can progress to adenocarcinoma.

Hiatal Hernia

• Defined as the protrusion of the upper part of the stomach through the diaphragm into the thorax.

Type I: Sliding

• The proximal portion of the stomach moves into the thorax through the esophageal hiatus.
• Etiology: congenitally short esophagus, fibrosis, excessive vagal nerve stimulation, or weakening of the diaphragmatic muscles.
• Exacerbated by increased intraabdominal pressure (coughing, bending, tight clothing, obesity, pregnancy).
• Associated with GERD due to diminished LES pressure.

Type II: Paraesophageal (Rolling Hiatal Hernia)

• Herniation of the greater curvature of the stomach through a secondary opening in the diaphragm.
• The stomach protrudes through the opening into the thorax, lying alongside the esophagus.
• Gastroesophageal junction remains below the diaphragm.
• Reflux is uncommon.
• Congestion of mucosal blood flow can lead to gastritis and ulcer formation.
• Mechanical strangulation can cause vascular engorgement, edema, ischemia, and hemorrhage.

Type III: Mixed

• Includes elements of Types I and II.
• Tends to occur with other diseases (GERD, peptic ulcer, cholecystitis, chronic pancreatitis, diverticulosis).

Type IV

• The entire stomach and other abdominal organs slide into the thorax.
• Aggravated form of Type III.

Diagnosis

• Diagnosis is achieved with chest x-ray with oral barium, endoscopy, high-resolution manometry, and reflux monitoring.
• Chest x-ray shows protrusion of the stomach into the thorax (paraesophageal hiatal hernia).

Treatment

• Dietary modifications such as eating small, frequent meals and avoiding the recumbent position after eating.
• Avoid abdominal supports and tight clothing.
• Weight control is recommended for obese individuals.
• Proton pump inhibitors alleviate reflux esophagitis.
• Histamine 2 receptor agonists and antacids are less effective.
• Drugs that relax the LES are contradicted.
• Laparoscopic surgery may be performed for paraesophageal hiatal hernia or if medical management fails.

Gastroparesis

• Defined as delayed gastric emptying in the absence of mechanical gastric outlet obstruction.
• Most commonly associated with diabetes mellitus, surgical vagotomy, or fundoplication.
• May be idiopathic.
• Pathophysiology involves abnormalities of the autonomic nervous system, smooth muscle cells, enteric neurons, and GI hormones.
• Diabetic gastroparesis is a form of neuropathy involving the vagus nerve.
• Nausea, vomiting, abdominal pain, postprandial fullness occur.
• Treatment includes dietary management, prokinetic drugs, gastric electrical stimulation, and/or pyloroplasty.

Intestinal Obstruction

• Defined as any condition preventing normal flow of chyme or failure of intestinal motility.
• Occurs in the small or large intestine.
• Classified as simple or functional.
• Simple obstruction is a mechanical blockage of the lumen with preserved blood flow.
• Strangulated obstruction compromises blood flow, leading to ischemia.
• Paralytic ileus is a failure of motility after surgery, pancreatitis, or hypokalemia.
• Acute obstructions are caused by adhesions or hernias.
• Chronic or partial obstructions are caused by tumors or inflammatory disorders.

Common Causes of Intestinal Obstruction

• Herniation: Protrusion of intestine through abdominal muscles.
• Intussusception: Telescoping of one part of the intestine into another.
• Torsion (Volvulus): Twisting of the intestine, occluding blood supply.
• Diverticulosis: Inflamed herniations of the mucosa and submucosa.
• Tumor: Tumor growth into the intestinal lumen.
• Paralytic (Adynamic) Ileus: Loss of peristaltic motor activity.
• Fibrous Adhesions: Peritoneal irritation leads to adhesions.

Small Bowel Obstruction (SBO)

• Impaired absorption and increased secretion with fluid and gas accumulation.
• Distention decreases water and electrolyte absorption, increasing secretion.
• Dehydration leads to elevated hematocrit level, hypotension, and tachycardia.
• Severe dehydration can cause hypovolemic shock.
• Symptoms include colicky pains followed by nausea and vomiting.
• Pain intensifies as peristaltic wave meets obstruction.
• Ischemia causes constant pain; hypotension leads to sweating and tachycardia.
• Necrosis, perforation, and peritonitis lead to fever and leukocytosis.

Pyloric Obstruction or Obstruction High in Small Intestine

• Metabolic alkalosis develops due to excessive loss of hydrogen ions.
• Symptoms include early, profuse vomiting of clear gastric fluid.
• Obstruction in the proximal small intestine causes mild distention and vomiting of bile-stained fluid.
• Partial obstruction causes diarrhea or constipation; complete obstruction causes constipation only.
• Increased bowel sounds (tinkly) with peristaltic rushes and crampy pain.

Prolonged Obstruction or Obstruction in Lower Intestine

• Metabolic acidosis is more likely due to the inability to reabsorb bicarbonate.
• Hypokalemia can be extreme, leading to acidosis and atony of the intestinal wall.
• Lack of circulation causes buildup of lactic acid, increasing acidosis.
• Severe pressure occludes venous drainage and arterial circulation, leading to ischemia, necrosis, perforation, and peritonitis.
• Fever and leukocytosis result from bacterial overgrowth, ischemia, and bowel necrosis.
• Sepsis and multiple organ failure can occur due to proliferation and translocation of bacteria.

Large Bowel Obstruction (LBO)

• Caused by carcinoma, diverticulitis, inflammatory bowel disease, or volvulus.
• Symptoms include hypogastric pain and abdominal distention.
• Pain varies; vomiting occurs late.
• Small and large intestinal perforation causes acute pain, nausea, vomiting, and fever.
• Acute colonic pseudo-obstruction (Ogilvie syndrome) is a rare functional dilation of the large bowel.

Classification of Obstruction

• Onset: acute (sudden) or chronic (protracted).
• Extent: partial (incomplete) or complete.
• Location: small intestine or colon.
• Effects on intestinal wall: simple or strangulated.
• Causal factors: mechanical or functional (paralytic ileus).

Diagnosis & Treatment

• Diagnosis is based on clinical manifestations and imaging studies.
• Management includes fluid and electrolyte replacement and decompression of the lumen.
• Laparoscopic procedures release adhesions.
• Immediate surgical intervention is required for strangulation, complete obstruction, or perforation.
• Intravenous antibiotics, fluid resuscitation, and surgery are needed for intestinal perforation.

Ulcerative Colitis

• A chronic inflammatory disease causing ulceration of the colonic mucosa, most commonly in the rectum and sigmoid colon.
• Lesions appear in susceptible individuals between 20 and 40 years of age Less common in people who smoke; smoking may not improve the natural history of ulcerative colitis

Pathophysiology

• Primary lesion begins with inflammation at the base of the crypt of Lieberkühn
• Involves the rectum (proctitis) and may extend proximally to the entire colon (pancolitis)
• Inflammation involves infiltration and release of inflammatory cytokines from Th2-associated cytokines → activate neutrophils, lymphocytes, plasma cells, macrophages, eosinophils, and mast cells
• Inflammation → damages the epithelial mucosal barrier with leak of fluids into the gut
• Severe inflammation causes small erosions that form ulcers.
• Abscess formation occurs in the crypts, leading to necrosis and ulceration.
• Chronic disease causes inflammatory polyps (pseudopolyps).

Clinical Manifestations

• Intermittent periods of remission and exacerbation.
• Large volumes of watery diarrhea.
• Bleeding, cramping pain, and an urge to defecate are due to mucosal destruction.
• Frequent bloody diarrhea with passage of purulent mucus is common.
• Mild UC involves less mucosa and minimal symptoms.
• Severe UC involves the entire colon, with fever, elevated pulse, frequent diarrhea, urgency, bloody stools, cramps, dehydration, weight loss, and anemia.
• Extraintestinal manifestations include cutaneous lesions, polyarthritis, osteopenia, mouth ulcers, eye inflammation, and primary sclerosing cholangitis.
• May cause life-threatening microthrombi.

Diagnosis

• Based on medical history, clinical manifestations, imaging, and biopsy findings.
• Endoscopic evaluation shows inflamed and hemorrhagic mucosa.
• Radiologic assessment reveals loss of haustra, ulceration, and irregular mucosa.
• Laboratory data shows low hemoglobin, hypoalbuminemia, and low serum potassium. stool culture rules out infectious causes.

Treatment

• Mild disease: 5-aminosalicylic acid or sulfasalazine, followed by corticosteroids.
• Recurrent or serious disease: Azathioprine, cyclosporine, and TNF-blocking agents.
• Severe disease requires hospital admission and IV fluids.
• Extreme malnutrition may require intravenous hyperalimentation.
• Surgical procedures include total proctocolectomy, ileorectal anastomosis, or ileal pouch anal anastomosis (IPAA).
• Antibiotic treatment is used for pouchitis

Complications

• Anal fissures, hemorrhoids, and perirectal abscess.
• Severe hemorrhage is rare.
• Edema, strictures, or fibrosis can obstruct the colon.
• Perforation is an unusual complication.
• The risk of colon cancer increases after many years of ulcerative colitis.

Dumping Syndrome

• Defined as the rapid emptying of hypertonic chyme from the stomach into the small intestine after surgery.
• Occurs 10 to 20 minutes after eating (early dumping syndrome).
• Etiology: 5% to 10% of individuals who have undergone partial gastrectomy, bariatric surgical procedures, or pyloroplasty.
• Factors promoting early dumping include loss of gastric capacity and emptying control.

Pathophysiology

• Rapid gastric emptying creates a high osmotic gradient in the small intestine.
• Sudden shift of fluid from the vascular compartment to the intestinal lumen.
• Vasomotor responses include increased pulse rate, hypotension, weakness, pallor, sweating, and dizziness.
• Rapid distention of the intestine causes epigastric fullness, cramping pain, nausea, and vomiting.
• Diarrhea can occur.
• Late dumping syndrome occurs 1 to 3 hours after eating, causing weakness, diaphoresis, and confusion.
• Hypoglycemia occurs due to increased insulin secretion stimulated by hyperglycemia.

Treatment

• Responds to dietary management: frequent small meals high in protein and low in carbohydrates.
• Acarbose slows intestinal digestion of carbohydrates.
• Somatostatin analogs slow gastric emptying.
• Octreotide inhibits insulin and gut hormone release.
• Other measures include drinking fluids between meals and reclining on the left side after eating.
• Surgical intervention may be needed

Hepatitis

• Viral hepatitis is a systemic disease affecting primarily the liver.

Hepatitis A (HAV)

• RNA virus, transmitted fecal-orally.
• Incubation phase - 30 days
• Acute onset with fever, never chronic, and mild.
• Prevented with hygiene, immune serum globulin, and HAV vaccine.
• Fecal shedding is greatest 10 to 14 days before symptoms and during the first week of symptoms.
• Antibodies (anti-HAV) develop about 4 weeks after infection.
• Greatest for 10 to 14 days before the onset of symptoms and during the first week of symptoms, and up to 3 months after onset of symptoms (The disease is most contagious during this time)
• Prevented by hygiene, immune serum globulin, and HAV vaccine

Hepatitis B (HBV)

• DNA virus, transmitted parenterally, sexually.
• Incubation phase - 60-180 days
• Insidious onset, can be severe and prolonged or chronic
• Prevented with hygiene, HBV vaccine, and screening blood.
• Coinfection with HCV, HDV, and HIV is common.
• Mother-infant transmission is screened for and prevented with HBV vaccine and immunoglobulin.
• Major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
• Drug resistance and disease recurrence can occur.
• Vaccine prevents transmission and reduces hepatocellular carcinoma.
• 3 types of viral particles in HBV: larger Dane particle, Hepatitis B core antigen (HBcAg), The HBeAg

Hepatitis C (HCV)

• RNA virus, transmitted parenterally.
• Genotype specific
• Incubation phase - 30-180 days
• Insidious onset and severe
• Treat with: interferon-alpha or combined with ribavirin; treatment also related to HCV genotype cirrhosis
• Risk factors include intravenous drug use.
• Diagnosis involves detection of anti-HCV IgG.
• Clinical presentation includes persistent infection with recurring acute symptoms.
• Often undiagnosed as there may be no symptoms
• Progression to cirrhosis is the most common cause of hepatocellular carcinoma and liver transplant.
• No vaccine exists.

Hepatitis D (HDV)

• Occurs as a coinfection with hepatitis B.
• Incubation phase - 35-72 days
• Insidious onset
• Treatment with pegylated interferon alpha
• Risk factors include parenteral drug users.
• Diagnosis involves presence of antibodies against HDAg (anti-HD) and HDV RNA in serum.

Hepatitis E (HEV)

• RNA virus, transmitted fecal-orally.
• Incubation phase - 15-60 days
• Resembles HAV or progresses to acute liver failure.
• Most common in Asian and African countries
• Prevalent among adults and has the highest mortality in pregnant women
• Diagnosis involves detection of anti-HEV IgM
• Treatment includes ribavirin and pegylated interferon.

Pathophysiology of all types of Hepatitis

• Hepatic cell necrosis, scarring, Kupffer cell hyperplasia, and infiltration by mononuclear phagocytes occur.
• Cellular injury is promoted by cell-mediated immune mechanisms.
• Regeneration of hepatic cells begins within 48 hours of injury.
• Inflammatory process can damage and obstruct bile canaliculi → cholestasis and obstructive jaundice
• Hepatitis B can cause acute liver failure.

Clinical Manifestations

• nausea, malaise, abdominal pain, and jaundice; ranges from absence of symptoms to fulminating hepatitis, with rapid onset of liver failure and coma
• Serum aminotransferase values, aspartate transaminase (AST) and alanine transaminase (ALT) → elevated
• Consists of four phases: incubation, prodromal, icteric, and recovery phases
• The infection is highly transmissible during the prodromal phase.

Prodromal (Preicteric) Phase

• Begins about 2 weeks after exposure and ends after the appearance of jaundice
• Symptoms: fatigue, anorexia, malaise, nausea, vomiting, headache, hyperalgia, cough, and low-grade fever.

Icteric Phase (Jaundice)

• Begins about 1-2 weeks after prodromal phase & Lasts 2 to 6 weeks
• Symptoms before: dark urine and the stools clay colored (due to conjugated hyperbilirubinemia)
• Symptoms during: enlarged, smooth, tender liver
• The icteric phase is the actual phase of illness
• Stool can be lighter in color due to cholestasis

Recovery (Posticteric) Phase

• Begins with resolution of jaundice and lasts 6-8 weeks
• Liver may still be enlarged and tender, symptoms diminish
• Liver function test results return to normal within 2 to 12 weeks after the onset of jaundice

Treatment

• Recommended for healthcare workers, liver transplant recipients, and others who are at risk for contact with infected body fluids

Types of Diarrhea

• Defined as the presence of loose, watery stools with more than 3 in 24 hours (acute).
• Persistent diarrhea lasts longer than 14 to 30 days.
• Chronic diarrhea lasts longer than 30 days. Factors determining stool volume / consistency
• Factors determining stool volume / consistency: water content of colon, diet, presence of unabsorbed food, unabsorbable material, intestinal secretions

Pathophysiology

• Large-volume diarrhea is caused by excessive water or secretions in the intestines.
• Small-volume diarrhea is caused by excessive intestinal motility.

Osmotic Diarrhea

• A nonabsorbable substance draws water into the lumen by osmosis, increasing stool weight and volume.

Secretory Diarrhea

• Excessive mucosal secretion of chloride- or bicarbonate-rich fluid or inhibition of net sodium absorption.

Motility Diarrhea

• Excessive motility decreases transit time, mucosal surface contact, and opportunities for fluid absorption.

Clinical Manifestations

• Acute or chronic, depending on the cause.
• Prolonged diarrhea leads to dehydration, electrolyte imbalance, metabolic acidosis, and weight loss.
• Acute bacterial/viral infection causes fever.

Diagnosis

• Thorough history of onset, frequency, and volume of stools.
• Iatrogenic diarrhea is suggested by previous radiation therapy, intestinal resection, or drugs.
• Labs/Diagnostics: stool culture, polymerase chain reaction, examination of stool specimens for blood, microscopy for protozoal infections, abdominal roentgenograms, endoscopy, and intestinal biopsies →provide specific data

Treatment

• Restoration of fluid and electrolyte balance, antimotility medications, and treatment of causal factors.
• Natural bran and psyllium are effective for mild diarrhea.
• Probiotics are useful to prevent and treat C. difficile-associated diarrhea.
• Fecal transplantation is used for resistant cases.

Portal Hypertension

• Defined as abnormally high blood pressure in the portal venous system, with hepatic venous pressure above 5 mmHg.

Pathophysiology

• Caused by disorders obstructing blood flow through the hepatic portal system.
• Prehepatic causes involve thrombosis or narrowing of the hepatic portal vein.
• Intrahepatic causes result from vascular remodeling, thrombosis, inflammation, or fibrosis.
• Posthepatic causes occur from hepatic vein thrombosis or cardiac disorders causing right-sided heart failure.
• Cirrhosis of the liver is the most common cause.

Clinical Manifestations

• Vomiting blood from bleeding esophageal varices.
• Hemorrhoidal varices.
• Endoscopy and liver stiffness measurements (elastography) are used for diagnosis.

Treatment

• Nonselective beta-blockers prevent variceal bleeding.
• Endoscopic vein ligation
• Fluids, blood, antibiotics, and vasoactive drugs are used for emergency management.
• Transjugular intrahepatic portosystemic shunt (TIPS) decompresses varices but reduces hepatic blood flow.

Varices

• Distended, tortuous, collateral veins.
• Prolonged hepatic portal vein pressure causes collateral veins to open.
• Complication: rupture of varices can be life

Splenomegaly

• Enlargement of the spleen due to increased pressure in the splenic vein.
• Thrombocytopenia from platelet sequestration is a common symptom.

Hepatopulmonary Syndrome

• Respiratory complication of advanced liver disease and portal hypertension.
• Associated with intrapulmonary vasodilation, shunting, and hypoxia.

Ascites

• Accumulation of fluid in the peritoneal cavity.
• Complication of portal hypertension and cirrhosis.
• Portal hypertension, decreased albumin, splanchnic arterial vasodilation, and renal retention contribute.
• Clinical Manifestations: accumulation of ascitic fluid causes abdominal distention, increased abdominal girth, and weight gain
• Diagnosis of ascites: based on clinical manifestations and identification of liver disease
• Chest and abdominal x-rays, ultrasonography, or CT scans → evaluate cause and extent of the ascites and complications Treatment: if restoration of liver function is possible (ascites caused by viral hepatitis) → ascites diminishes spontaneously In some cases: Strong diuretics, dietary salt restriction and potassium-sparing diuretics Other procedures: peritoneovenous shunt (peritoneal fluid into veins) and transjugular intrahepatic portosystemic shunt (TIPS) Causes bacterial peritonitis

Hepatic Encephalopathy (Portosystemic Encephalopathy)

• Complex neurologic syndrome with impaired behavioral, cognitive, and motor function.
• Can develop rapidly, or slowly
• Encephalopathy is the result of a dysfunctional liver and collateral vessels that shunt blood around the liver to the systemic circulation -Leads to circulation of neurotoxins such as, inflammatory cytokines, short-chain fatty acids, serotonin, tryptophan, and false neurotransmitters End products of intestinal protein digestion (ammonia; as this cannot be converted to urea by the diseased liver) Ammonia is metabolized to glutamine in the brain, promoting permeability of the blood-brain barrier Clinical Manifestations: Subtle changes in personality, memory loss, irritability, lethargy, and sleep disturbances

Treatment

• Correction of fluid and electrolyte imbalances and withdrawal of depressant drugs.
• In the first steps: Manage cerebral edema, and dietary protein must be manage-tracked to reduce blood ammonia levels
• Prevent ammonia absorption by colon: with nonabsorbable disaccharides such as (lactulose)

Cirrhosis

• Irreversible inflammatory, fibrotic liver disease.
• Cirrhosis develops slowly over a period of years with severity and rate of progression depend on the cause.
• If alcohol is involved → rate of cell death and the severity of inflammation depend on the amount of alcohol Etiology: Alcohol abuse and HCV infection are the most common causes Structural changes result from injury and fibrosis. Patho: Chaotic fibrosis: alteration or obstruction of biliary channels and blood flow → jaundice and portal HTN. The formation of fibrous bands and regenerating nodules → distorts architecture of the liver parenchyma

Clinical Manifestations

• Multiple-system disease → hepatomegaly, splenomegaly, ascites, gastrointestinal hemorrhage, portal hypertension, hepatic encephalopathy, and esophageal varices
• Anemia → blood loss, malnutrition, and hypersplenism. Hepatorenal syndrome and portopulmonary syndrome → late complications
• Risk for infection is greater due to innate immune dysfunction

Treament

• Guidelines are available to guide treatment and predict clinical outcome
• Guidelines are available to guide treatment and predict clinical outcome
• Many complications are treatable, although No specific treatment available
• Slow disease progression: rest, a nutritious diet, corticosteroids, antioxidants, drugs that slow fibrosis, and management of complications such as ascites, gastrointestinal bleeding, anemia, infection, and encephalopathy

Alcoholic Liver Disease

• Severity related to the amount and duration of alcohol consumed and formation of acetaldehyde which has the following cellular effects: Oxidative stress and lipid peroxidation Disrupts cytoskeletal and membrane function Inhibits export of proteins from the liver → altered metabolism of vitamins and minerals → malnutrition Promotes liver fibrosis Spectrum of alcoholic liver disease: alcoholic hepatitis, and alcoholic cirrhosis Fat deposition (deposition of triglycerides) within the liver due to increased lipogenesis and decreased fatty acid oxidation and fat metabolism by hepatocytes

Treatment for Alcoholic Liver

• Reversible with abstinence
• mildest form of alcoholic liver disease; reversible with abstinence Steroids with and/or pentoxifylline; supported by abstinence of alchol

NonAlcoholic Fatty Liver Disease

• Can happen in non alchol drinkers/individuals that drink very little alcohol most common chronic liver disease in U.S. Treatment: lifestyle modification with diet and exercise Complications: individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH) Pioglitazone can be consdered for those with fibrosis

Biliary Cirrhosis

Differs from alcoholic cirrhosis → damage and inflammation leading to cirrhosis begin in bile canaliculi and bile ducts, rather than in the hepatocytes.

PRIMARY BILIARY CIRRHOSIS (PBC)

Cause: natural-killer T lymphocytes and highly specific antimitochondrial antibody destruction of the small intrahepatic bile ducts Patho: inflammation, destruction, fibrosis, and obstruction of the intrahepatic bile ducts Long-term treatment: ursodeoxycholic acid (UDCA) is highly effective Bezafibrate may be effective for UDCA nonresponsers Intramuscular injections of vitamins D and K → vitamin deficiency Liver transplant only option for those with progressive disease not responding to medical treatment

Secondary Biliary Cirrhosis

Prolonged partial or complete obstruction of the common bile duct or its branches. chronic obstruction to bile flow → increases pressure in the hepatic bile duct → accumulation of bile in the centrilobular spaces Treatment: Surgery or endoscopy relieves obstruction, prolongs survival, and diminishes or resolves symptoms

SCLEROSING CHOLANGITIS

Chronic inflammatory fibrotic disease of the hepatic bile ducts → secondary biliary cirrhosis Associated with proximal inflammatory bowel disease (75%) and primarily affects genetically susceptible young males; 305 of cases are women treatment: No effective sustaining medical or surgical therapy, and liver transplant is required for liver failure

Vomiting

Forceful emptying of stomach and intestinal content through the mouth VOMITING CENTER “the area postrema” Location: in the medulla oblongata; includes the reticular formation, tractus solitarius nucleus, and the parabrachial nucleus ANTAGONISTS (effective anti-emetics) Serotonin and neurokinin-1 antagonists → used to treat nausea and vomiting associated with postoperative vomiting and cancer chemotherapy TREATMENT: olanzapine → antagonist to serotonin and dopamine; corticosteroids (given in combination with other therapies) → prevent chemotherapy-induced nausea

• DOPAMINE D2 AGONISTS (cause nausea/vomiting) Apomorphine, levodopa, and bromocri