1. Ischemic hepatic injury, or shock liver
    • The hallmark of ischemic hepatopathy is a rapid and massive increase in the transamlnases with modest accompanying elevations in total bilirubin and alkaline phosphatase.
    • In patients who survive the underlying cause of their hypotension (e.g. septic shock, heart failure), liver enzymes typically return to normal within one to two weeks.
  2. Approach to a patient with Jaundice
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  3. Cholestasis Jaundice
    • The next appropriate step in management for patients with predominantly cholestatic pattern is to obtain an abdominal ultrasound to assess hepatic parenchyma and biliary ducts.
    • The presence of biliary dilatation is suggestive of extrahepatic cholestasis; the absence of biliary dilatation suggests intrahepatic cholestasis.
  4. Rotor's syndrome.
    • a rare, benign hereditary condition with chronic or fluctuating conjugated hyperbilirubinemia due to a defect in hepatic secretion of conjugated bilirubin into the biliary system.
    • It Is typically discovered in childhood but sometimes goes undiagnosed. Liver function tests are otherwise normal, and treatment is unnecessary.
  5. Bilirubin metabolism
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    • Following hemoglobin breakdown, the majority (95%) of bilirubin is in the unconjugated form, which undergoes hepatic conjugation.
    • Conjugated bilirubin then goes into the intestines, where it is predominantly deconjugated and recycled (enterohepatic circulation) to be reconjugated in the liver.
    • Alternatively, some of its metabolism products are excreted in feces as urobilinogen, with -1% of urobilinogen being renally excreted.
    • Unconjugated bilirubin (tightly bound to albumin) is highly insoluble, so it cannot be excreted in urine.
    • Excess unconjugated bilirubin (eg, hemolysis) undergoes the regular conjugation pathway with eventual production of urobilinogen, and the resultant excess urobilinogen is primarily recycled; however, a higher than normal amount of urobilinogen is excreted in feces or urine, leading to a positive urine urobilinogen assay.
    • On the other hand, conjugated bilirubin (loosely bound to albumin) is water soluble, so it can be excreted in urine.
    • Despite this, no bilirubin is normally seen on urinalysis (negative urine bilirubin assay) because conjugated bilirubin is usually degraded In the intestines.
    • However. when there is hepatic dysfunction, biliary obstruction, or a defect in hepatic bilirubin secretion, there is plasma buildup of conjugated bilirubin, which leaks into urine. This results in dark urine and a positive urine bilirubin assay.
  6. Lactose Intolerance
    • Lactase is a brush border enzyme that hydrolyses lactose.
    • Its concentration declines steadily as one ages into adulthood, especially in people of non European ancestry.
    • When there is an Inability to absorb lactose found in milk and dairy products, the condition is called lactose Intolerance. This is most commonly seen in Asian-Americans (90% ).
    • Patients typically manifest with osmotic diarrhea, abdominal cramps, bloating and flatulence after ingestion of such products.
    • The lactose tolerance test is cumbersome and time consuming.
    • Currently, the lactose hydrogen breath test has largely replaced the lactose tolerance test.
    • A positive hydrogen breath test is characterized by a rise in the measured breath hydrogen level after the ingestion of lactose, thus indicating bacterial carbohydrate metabolism.
  7. Factitious diarrhea
    • has a female predominance, patients are employed
    • in the health care field and have a history of multiple hospitalizations.
    • C/F: Diarrhea associated with laxative abuse is typically described as watery, frequent (10-20 bowel movements dally), and voluminous. Nocturnal bowel movements and abdominal cramps are present.
    • Labs: Hypokalemia is due to increased loss of potassium in the stool. This then impairs chloride reabsorption and results in decreased activity of the chloride-bicarbonate exchange, increasing serum bicarbonate concentrations (metabolic alkalosis).
    • Patients may also have hypermagnesemia if a magnesium-containing laxative Is used.
    • Diagnosis is supported by a positive stool screen for diphenolic (eg, bisacodyl) or polyethylene-containing laxatives.
    • Diagnosis is further suggested by: colonoscopy finding of melanosis coli, which is dark brown discoloration of the colon with pale patches of lymph follicles that can give the appearance of alligator skin.
    • Melanosis coli can develop within a few months of the onset of regular laxative Ingestion and can similarly disappear if laxative use is discontinued. If melanosis coli is not seen on gross inspection, histological examination may demonstrate the pigment in the macrophages of the lamina propria.
  8. Common Cancer Syndromes
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  9. Lynch syndrome (eg, hereditary nonpolyposis colorectal cancer)
    • is an autosomal dominant cancer syndrome that predisposes individuals to colorectal cancer and other malignancies.
    • Genetic testing should be performed in patients with a strong family history of colon cancer (eg, ~3 relatives involving multiple generations).
    • The condition is due to a germ line mutation in a DNA mismatch repair gene.
    • Once the diagnosis of Lynch syndrome is established, patients should undergo screening for colon cancer with colonoscopy.
    • In addition to colon cancer, patients are at extremely high risk for endometrial carcinoma.
    • Endometrial cancer screening with annual endometrial biopsy should begin at age 30-35.
    • Ovarian cancer risk is also increased and may present at a relatively younger age.
    • Therefore. prophylactic hysterectomy and bilateral oophorectomy is recommended at age 40 or earlier if childbearing is complete.
  10. Mallory-Weiss tear
    • Etiology:
    • • Sudden increase in abdominal pressure (eg, forceful retching)or abdominal trauma
    • • Longitudional Mucosal tear in esophagus or stomach (submucosal arterial or venous plexus bleeding)
    • • Risk factors: Hiatal hernia, alcoholism
    • Clinical presentation:
    • • Vomiting, retching
    • • Hematemesis
    • • Epigastric pain
    • Diagnosis: • Longitudinal laceration on endoscopy
    • Treatment:
    • • Most heal spontaneously(90%)
    • • Endoscopic therapy for persistent bleeding by electrocoagulation or local injection of epinephrine.
  11. Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
    • Such lymphomas may regress after the eradication of H. pylori using antibiotic therapy.
    • Antibiotic therapy still remains as the most accepted and recommended management of gastric MALT lymphoma without any metastasis.
    • Chemotherapy typically plays a role in the management of patients with MALT lymphoma if eradication of H. Pylori falls to produce regression of the lymphoma.
    • Such therapeutic regimens usually include CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) or CHOP + Bleomycin.
  12. Management of Upper GI Bleeding
    • Initial evaluation should begin with the ABCs: airway, breathing, and circulation.
    • If a patient has depressed level of consciousness, it is a set up for aspiration, which could quickly exacerbate her already tenuous clinical status, endotracheal intubation would be indicated at this time to secure her airway.
    • Put two large bore IV cannulas to begin aggressive fluid resuscitation, and a type and screen should be performed since the patient will likely need a blood transfusion.
    • Platelet transfusion Is not generally Indicated until levels fall below 50, 000/mm~.
    • Bleeding may be exacerbated by if patient has elevated INR for which FFP could be considered, but it is often of minimal effectiveness in cirrhotic patients receiving aggressive fluid resuscitation.
    • Administration of prophylactic antibiotics, and possibly a somatostatin analog such as octreotlde, should also be considered.
  13. Solid liver masses
    • Focal nodular hyperplasia:
    • • Associated with anomalous arteries
    • • Arterial now & central scar on imaging
    • Hepatic adenoma:
    • • Women on long-term oral contraceptives
    • • Possible hemorrhage or malignant transformation
    • Regenerative nodules:
    • • Acute or chronic liver injury (eg, cirrhosis)
    • Hepatocellular carcinoma:
    • • Systemic symptoms
    • • Chronic hepatitis or cirrhosis
    • • Elevated alpha-fetoprotein
    • Liver metastasis:
    • • Single/multiple lesions
    • • Known extrahepatic malignancy
  14. Metastatic Liver Disease
    • Metastatic disease is the most common cause of liver mass and is much more common than primary liver cancer.
    • Undiagnosed colorectal cancer (CRC) is likely n this patient with a solitary liver mass, probable iron deficiency anemia (low mean corpuscular volume), and positive fecal occult blood screen.
    • Gastrointestinal malignancies such as colorectal or pancreatic cancer, are the most frequent source of liver metastases as their venous drainage is through the portal system directly to the liver.
    • Lung, breast, and skin cancers (melanoma) often also spread to the liver.
    • The liver is a common site of metastatic disease due to its dual blood supply (systemic and portal) and hepatic sinusoidal fenestrations allowing for easier metastatic deposition.
    • Liver metastases are often clinically silent unless pressure on the liver capsule or obstruction of the biliary tree causes pain or jaundice.
    • Results of hepatobiliary laboratory testing (eg, alkaline phosphatase) may be normal or mildly elevated, even in the setting of heavy tumor burden.
    • Multiple hepatic nodules are typically seen in metastatic disease; however, solitary lesions are not uncommon.
    • If a primary tumor is identified (eg, with colonoscopy), liver biopsy Is usually not needed.
    • Colorectal cancer is the most common source of liver metastases: (as blood from the colon moves through the portal circulation directly to the liver)
  15. Pellagra ("rough skin" In Italian vernacular):
    • is due to niacin deficiency and is characterized by the "3 Ds": dermatitis, diarrhea, and dementia
    • • Dermatitis is primarily on sun-exposed areas of the body and is characterized by rough, hyperpigmented, scaly skin.
    • • Diarrhea is often associated with abdominal pain, nausea, and loss of appetite.
    • • Dementia Is due to neuronal degeneration in the brain and spinal cord and can lead to memory loss. affective symptoms (eg. depressed mood ), and psychosis.
  16. Niacin Deficiency
    • Niacin is present in a broad variety of foods and can be synthesized endogenously from tryptophan. In developing countries, niacin deficiency is seen in populations that subsist primarily on corn products (niacin in corn occurs in a bound, unabsorbable
    • form).
    • In developed countries, it is primarily seen in patients with impaired nutritional intake (eg, alcoholism, chronic Illness).
    • Pellagra can also be seen occasionally In those with carcinoid syndrome (due to depletion of tryptophan) or Hartnup disease (congenital disorder of tryptophan absorption).
    • Prolonged isoniazid therapy can interfere with metabolism of tryptophan and occasionally lead to pellagra.
  17. Nonalcoholic fatty liver disease
    • Definition:
    • • Hepatic steatosis on imaging or biopsy
    • • Exclusion of significant alcohol use
    • • Exclusion of other causes of fatty liver
    • NAFLD has risen along with the increase in obesity
    • A/W metabolic syndrome (eg, central obesity, diabetes mellitus, hyperlipidemia, hypertension )
    • Clinical features:
    • • Mostly asymptomatic
    • • Metabolic syndrome , Increased AST and ALT
    • • +/- Steatohepatitis (AST/ALT ratio <1)
    • • Hepatomegaly, Hyperechoic texture on ultrasound
    • Diagnosis: Liver Biopsy
    • Treatment:
    • • Diet & exercise, Statins, Decrease Obesity
    • • Consider bariatric surgery if BMI >35
    • Control metabolic risk factors
  18. Mechanism of NAFLD
    • NAFLD can be due to increased transport of free fatty acids (FFA) from adipose tissue to the liver, decreased oxidation of FFA in the liver, or decreased clearance of FFA from the liver (due to decreased VLDL production).
    • It is frequently related to peripheral insulin resistance leading to increased peripheral lipolysis, triglyceride synthesis, and hepatic uptake of fatty acids.
    • Hepatic FFA Increases oxidative stress and production of proinflammatory cytokines (eg, tumor necrosis factor-alpha).
  19. Clinical features of malignant biliary obstruction
    • Etiologies:
    • • Cholangiocarcinoma
    • • Pancreatic or hepatocellular carcinoma
    • • Metastatic cancer (eg, colon, gastric)
    • Clinical presentation:
    • • Jaundice (can be painless)
    • • Pruritus, weight loss. acholic stools with dark urine
    • • Examination: Can be normal or show right upper- quadrant mass, tenderness, or hepatomegaly
    • • Laboratory: Increased Direct bilirubin, Increased alkaline phosphatase & gamma-glutamyl transpeptidase & normal to increased AST &ALT
    • Evaluation:
    • • Abdominal imaging (ultrasound or computed tomography)
    • • Magnetic resonance cholangiopancreatogram or endoscopic retrograde cholangiopancreatogram if Imaging is nondiagnostic
  20. Pancreatic carcinoma
    • Clinical Presentation:Depends on tumor location. Most commonly presents with a dull upper abdominal pain that radiates to the back, weight loss, or jaundice.
    • Tumors located in the pancreatic body or tall: are most likely to present with abdominal pain and weight loss
    • Tumors located in the pancreatic head(60%-70%): are most likely to present with steatorrhea, weight loss, jaundice, pruritus, pale stools, dark urine.
    • As these tumors expand, they compress the pancreatic duct and common bile duct (leading to painless jaundice), sometimes seen on imaging as the double duct sign.
    • Physical examination: is often unremarkable aside from jaundice, with an abdominal mass or ascites present in only 20% of patients with pancreatic cancer.
    • Classic findings: include a nontender but palpable gallbladder at the right costal margin in a jaundiced patient (Courvoisier's sign) or left supraclavicular adenopathy (Virchow's node) in a patient with metastatic disease.
    • Laboratory evaluation: Increased serum bilirubin an d alkaline phosphatase in conjunction with a mild anemia.
    • Imaging: Abdominal ultrasound is usually the initial imaging performed on patients with jaundice.
    • When the ultrasound Is nondiagnostic, the next step is to obtain an abdominal CT scan.
    • Commonly, CT scan is effective in detecting bile and pancreatic duct dilation, mass lesions within the pancreas, and indications of extrahepatic spread (eg, metastases or ascites).
  21. Risk Factors for Pancreatic Carcinoma
    • Major risk factors for pancreatic cancer
    • Hereditary:
    • • First-degree relative with pancreatic cancer
    • • Hereditary pancreatitis
    • • Germline mutations (eg, BRCA1, BRCA2, Peutz-Jeghers syndrome)
    • Environmental:
    • • Cigarette smoking (most significant)
    • • Obesity, low physical activity
    • • Nonhereditary chronic pancreatitis
    • Insulin and insulin secretagogues (eg, sulfonylureas) are associated with an increased risk of Pancreatic cancer, whereas metformin is associated with a lower risk.
    • Cigarette smoking Is the most consistent reversible risk factor for pancreatic cancer.
  22. Duodenal Ulcer
    • Clinical Features: Epigastric pain and intermittent melena d/t UGI bleeding ,pain
    • Abdominal pain of is often worse on an empty stomach (possibly due to unopposed gastric acid emptying Into the duodenum) and improves with food (due to alkaline fluid secretion into the duodenum).
    • By contrast, the pain of gastric ulcers is often worse after eating due to increased acid secretion.
    • Etiology: Helicobacter pylori infection or nonsteroidal anti-Inflammatory drugs (NSAIDs).
    • Malignant ulceration should be considered with gastric ulcers but would be very unlikely in this young patient with DU.
    • Investigation: H pylori infection can be confirmed with endoscopic biopsy or urea breath test.
    • Management of DU due to H pylori requires the following:
    • • Antisecretory therapy, preferably a proton pump inhibitor (PPI) (eg. omeprazole. pantoprazole ), and
    • • Antibiotic eradication (eg, amoxlcillin plus clarithromycin)
  23. Medication-induced esophagitis
    • Antibiotics: Tetracyclines
    • Anti-inflammatory: Aspirin & many nonsteroidal agents anti-inflammatory drugs
    • Bisphosphonates: Alendronate, risedronate
    • Others: Potassium chloride, iron
  24. Pill esophagitis
    • Pill esophagitis is due to a direct effect of certain medications on esophageal mucosa.
    • Mucosal injury in pill esophagitis can be due to
    • Acid effect: (eg, tetracyclines),
    • osmotic tissue injury: (eg, potassium chloride), or disruption of normal gastroesophageal protection: (eg, nonsteroidal anti-inflammatory drugs).
    • Patients usually do not have prior esophageal disease, although pill esophagitis can be worse in those with concurrent gastroesophageal reflux.
    • Typical symptoms of pill esophagitis: Include sudden-onset odynophagia and retrosternal pain that can sometimes cause difficulty swallowing.
    • It is most common in: the mid-esophagus due to compression by the aortic arch or an enlarged left atrium.
    • The diagnosis is usually made: clinically but can be confirmed on endoscopy, which shows discrete ulcers with relatively normal-appearing surrounding mucosa.
    • Treatment: includes primarily stopping the offending medication to prevent future injury.
  25. Porcelain Gallbladder
    • Definition: It is a term used to describe the calcium-laden gallbladder wall with bluish color and brittle consistency often associated with chronic cholecystitis.
    • Pathogenesis: of the condition remains unclear, but it is thought that calcium salts are deposited intramurally due to the natural progression of chronic inflammation or chronic irritation from gallstones.
    • Clinical Features: Patients can be asymptomatic, have right upper quadrant pain, or have a firm and nontender right upper quadrant mass on examination.
    • Plain x-rays: can show a rimlike calcification in the area of the gallbladder, and CT scan typically reveals a calcified rim In the gallbladder wall with a central bile-filled dark area.
    • Porcelain gallbladder has been associated with increased risk for gallbladder adenocarcinoma (2%-5% In some studies).
    • Treatment: Cholecystectomy is typically considered for patients with porcelain gallbladder, particularly if they are symptomatic or have incomplete mural calcification.
  26. Primary biliary cholangitis (previously called primary biliary cirrhosis)
    • Pathogenesis:
    • • Autoimmune destruction of intrahepatic bile ducts leading to bile stasis and cirrhosis
    • Clinical features:
    • • Affects middle-age women
    • • Insidious onset of fatigue & pruritus
    • • Progressive jaundice, hepatomegaly, cirrhosis
    • • Cutaneous xanthomas & xanthelasmas due to accumulation of lipid-filled macrophages in the dermis
    • Laboratory Findings:
    • • Cholestatic pattern of liver injury
    • ( Marked increased alkaline phosphatase, Increased aminotransferases)
    • • Antlmltochondrial antibody
    • • Severe hypercholesterolemia ( elevation of HDL out of proportion to LDL and does not appear to significantly increase the risk for atherosclerosis.)
    • Treatment:
    • • Ursodeoxycholic acid (delays progression)
    • • Liver transplantation for advanced disease
    • Complications:
    • • Malabsorption, fat-soluble vitamin deficiencies
    • • Metabolic bone disease (osteoporosis, osteomalacia): (Calcium and vitamin D levels in these patients are typically normal, suggesting that the bone disease is not due to malabsorption)
    • • Hepatocellular carcinoma
    • PBC is often associated with other autoimmune disorders (eg, autoimmune thyroid disease).
  27. Evaluation of serum alkaline phosphatase
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  28. Ursodeoxycholic acid (UDCA)
    • Is used in a number of cholestatic disorders and is the drug of choice in PBC.
    • UDCA is a hydrophilic bile acid that decreases biliary injury by the more hydrophobic endogenous bile acids. It also increases biliary secretion and may have additional anti-inflammatory and immunomodulatory effects.
    • UDCA delays histologic progression in PBC and may improve symptoms and possibly survival.
  29. Primary sclerosing cholangitis
    • Definition: a chronic, progressive disorder of unknown etiology characterized by Inflammation, fibrosis, and stricturing of intrahepatic and extrahepatic bile ducts.
    • Clinical features:
    • • Fatigue & pruritus
    • • Majority or patients asymptomatic at time of diagnosis
    • • About 90% of patients have underlying inflammatory bowel disease, mainly ulcerative colitis
    • Laboratory/Imaging:
    • • Cholestatic liver function test pattern (serum aminotransferases typically <300 U/L) ( predominantly elevated alkaline phosphatase levels with smaller increases in serum aminotransferases)
    • • Multifocal stricturing/dilation of intrahepatic &/or extrahepatic bile ducts on cholangiography
    • Other nonspecific findings:
    • Include elevated inflammatory markers (eg, erythrocyte sedimentation rate), increased lgM, and positive perinuclear antineutrophil cytoplasmic antibodies.
    • Liver biopsy:
    • • Fibrous obliteration of bile ducts with concentric replacement by connective. tissue in an "onion-skin" pattern
    • ERCP/MRCP: multlfocal narrowing with intrahepatic and extrahepatic duct dilation
    • Complications:
    • • Intrahepatic &/or extrahepatic biliary stricture
    • • Cholangitis & cholelithiasis (cholesterol &/or pigment stones)
    • • Cholangiocarcinoma (10%-15% lifetime risk)
    • • Cholestasis (eg, Decreased fat-soluble vitamins, osteoporosis), ESLD, Portal HTN
    • • Colon cancer
  30. Small intestinal bacterial overgrowth
    • Etiology:
    • • Anatomical abnormalities (eg, strictures, fistulas, anastomosis, surgery)
    • • Motility disorders (eg, diabetes mellitus,radiation enteritis, scleroderma)
    • • Other causes (eg, end-stage renal disease, AIDS, cirrhosis, advanced age, acid suppression, Chronic Pancreatitis, immunodeficiency)
    • Signs/symptoms:
    • • Abdominal pain, diarrhea, bloating, excess flatulence, malabsorption, weight loss, anemia, & nutritional deficiencies
    • Diagnosis:
    • • Endoscopy (gold standard) with jejunal aspirate showing> 10/5 organisms/ml
    • • Glucose breath hydrogen testing,using lactulose, show an early peak in hydrogen levels due to rapid lactulose metabolism in the small bowel (normally broken down in the colon).
    • Common organisms:
    • • Streptococci, Bacteroides, Escherichia, Lactobacillus
    • Treatment:
    • • 7-10-day course of antibiotics (eg, maximin, amoxicillin-clavulanate)
    • • Avoid antimotility agents (eg, narcotics)
    • • Dtetary changes (eg, high-fat, low-carbohydrate)
    • • Trial of promotility agents (eg, metoclopramide)
  31. Spontaneous bacterial peritonitis
    • Definition: an ascitic fluid infection without an obvious intraabdominal surgical etiology.
    • Pathogenesis: SSP is most likely due to either intestinal bacterial translocation directly into the ascitic fluid or hematogenous spread to the liver and ascitic fluid (due to other bacterial infections).
    • Clinical presentation:
    • • Temperature ~37.8 c (100 F)
    • • Abdominal pain/tenderness
    • • Altered mental status (abnormal connect-the numbers test)
    • • Hypotension, hypothermia, paralytic ileus with severe infection
    • Fever and subtle changes in mental status are the most common symptoms, while abdominal pain often less prominent than in peritonitis due to other causes.
    • • Hypotension, hypothermia, paralytic ileus with severe infection
    • Diagnosis from ascitic fluid:
    • • PMNs more than or equal to 250/mm3
    • • Positive culture, often gram-negative organisms (eg, Escherichia coli, Klebsiella)
    • • Protein < 1 g/dl
    • • SAAG more than or equal to 1.1 g/dl
    • Treatment:
    • • Empiric antibiotics - third-generation cephalosporins (eg, cefotaxime)
    • • Fluoroquinolones for SBP prophylaxis
  32. Whipple's disease
    • Is a rare multi-systemic illness.
    • etiology: It is an infectious disease caused by the bacillus Tropheryma whippelil.
    • Common in: It is most commonly seen in white men in the fourth-to-sixth decades of life and often presents with weight loss.
    • Gastrointestinal symptoms: include abdominal pain, diarrhea, and malabsorption with distension, flatulence, and steatorrhea.
    • Extraintestinal manifestations: migratory polyarthropathy, chronic cough, and myocardial or valvular involvement leading to congestive failure or valvular regurgitation.
    • Later stages of the disease may be characterized by dementia and other central nervous system findings, such as supranuclear ophthalmoplegia and myoclonus.
    • Intermittent low grade fever, pigmentation and lymphadenopathy may also be occasionally seen.
    • Biopsy: PAS-positive material in the lamina propria of the small intestine Is a classical biopsy finding.
  33. Wilson's disease (hepatolenticular degeneration)
    • rare, autosomal recessive disease most often identified in younger individuals aged 5 to 40 years.
    • Genetic mutations: associated with Wilson's disease hinder copper metabolism by reducing the formation and secretion of ceruloplasmin and by decreasing the secretion of copper into the biliary system.
    • Copper is a pro-oxidant, and as it accumulates in greater quantities within the liver, it causes damage to the hepatic tissue through the generation of free radicals.
    • Eventually copper leaks from injured hepatocytes into the blood to be deposited in various tissues, including the basal ganglia (hepatolentlcular degeneration) and cornea.
    • Liver involvement In Wilson's disease may present as asymptomatic liver function abnormalities, chronic hepatitis, fulminant hepatitis, portal hypertension, or macronodular cirrhosis.
    • Neuropsychiatric symptoms: can include Parkinsonian like tremor, rigidity, ataxia, slurred speech, drooling, personality changes, depression, paranoia, and catatonia.
    • Wilson's disease is also associated with Fanconi syndrome, hemolytic anemia, and neuropathy.
    • The gold standard for diagnosis: is liver biopsy that demonstrates a quantitative hepatic copper level >250 mg/gram dry weight.
    • More commonly, diagnosis is confirmed by the presence of low serum ceruloplasmin (particularly <20 mg/dL) in conjunction with increased urinary copper excretion or Kayser-Fleischer rings.
    • Treatment: must be adhered to for the patient's lifetime and focuses on removing accumulated copper in the tissues and preventing re-accumuJation.
    • First line medications include copper chelators liked-penicillamine or trientine.
    • Oral zinc is also recommended as it prevents copper absorption.
    • Liver transplantation may be the only option for those with fulminant hepatic failure or decompensated liver disease that does not respond to pharmacotherapy.
  34. Zenker's (pharyngoesophageal) diverticulum (ZD)
    • ZD Is most common In elderly patients, particularly men.
    • It occurs in the posterior lower cervical esophagus near the cricopharyngeus muscle.
    • Pathogenesis: ZD develops immediately above the upper esophageal sphincter with posterior herniation between the fibers of the cricopharyngeal muscle.Upper esophageal sphincter dysfunction and esophageal dysmotility are believed to cause ZD
    • Patients may complain of oropharyngeal dysphagia, neck mass, regurgitation and foul-smelting breath (halitosis) secondary to pooling of material in the diverticulum.
    • If particularly large, the diverticula may be palpable. Patients with ZD are at risk for aspiration pneumonia.
    • Contrast esophagram: will clearly show the diverticulum, it is the diagnostic test of choice.
    • It is indicated to diagnose ZD unless the patient has severe swallowing difficulty.
    • Other options to visualize the esophagus: including endoscopy, are associated with very serious risks of complications such as esophageal perforation.
    • Treatment: ZD is usually repaired surgically (Open/endoscopic surgery, Cricopharyngeal myotomy)
    • Complications: Potential complications include tracheal compression, ulceration with bleeding, regurgitation, and pulmonary aspiration
  35. Clinical manifestations of trace mineral deficiencies
    • Chromium:
    • • lmpaired glucose control in diabetics
    • Copper:
    • • Brittle hair
    • • Skin depigmentation
    • • Neurologic dysfunction (eg, ataxia, peripheral neuropathy)
    • • Sideroblastic anemia
    • • Osteoporosis
    • Iron:
    • • Microcytic anemia
    • Selenium:
    • • Thyroid dysfunction
    • • Cardiomyopathy
    • • Immune dysfunction
    • Zinc:
    • • Alopecia
    • • Pustular skin rash (perioral region & extremities)
    • • Hypogonadism
    • • Impaired wound healing
    • • Impaired taste
    • • Immune dysfunction
  36. Zinc deficiency
    • Zinc is a trace mineral that is obtained from meat, nuts, and fortified cereal in the diet.
    • It is an essential component of numerous enzymes in the body and plays an important role in gene transcription and cell division.
    • Clinical manifestations of zinc deficiency: include hypogonadism, impaired wound healing, impaired taste, and immune dysfunction.
    • Characteristic physical examination findings: Alopecia as well as a skin rash consisting of erythematous pustules around body orifices (eg, mouth) and on the extremities.
    • Zinc is absorbed mostly in the duodenum and jejunum, and deficiency can be due to malabsorption (eg, Crohn disease, celiac disease), bowel resection, gastric bypass, or poor nutritional Intake.
    • In addition, patients dependent on parenteral nutrition (PN) are at risk for trace mineral deficiency (eg, zinc, selenium, copper, chromium) due to inadequate supplementation of parenteral intake.
    • Comorbid diarrhea and malabsorption further increase the risk of trace mineral deficiency in patients on PN due to excessive gastrointestinal losses.
  37. Suspected Gastrinoma
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  38. gastrinoma (Zollinger-EIIison syndrome (ZES))
    • ZES is usually sporadic but is found in conjunction with multiple endocrine neoplasia type 1 (MEN-1) in 20% of cases, 80% are sporadic
    • Gastrinomas usually occur in patients age 20-50 with dyspepsia, reflux symptoms, abdominal pain, weight loss, diarrhea, or frank gastrointestinal bleeding.
    • Endoscopy often shows: thickened gastric folds, multiple peptic ulcers, refractory ulcers despite proton pump inhibitor (PPI) use, or ulcers distal to the duodenum in the jejunum (suggesting excess gastric acid that cannot be fully neutralized in the duodenum).
    • Fasting serum gastrin level (off PPI therapy for 1 week) should be checked in suspected gastrinoma: a level <110 pg/ml rules it out, and a level >1000 pg/mL is diagnostic
    • If gastrin is elevated, gastric pH should also be measured as gastrin may also be elevated due to failure of gastric acid secretion (achlorhydria).
    • A gastrin level of 110-1000 pg/ml is non-diagnostic and requires a follow-up by secretin stimulation test. Secretin stimulates the release of gastrin by gastrlnoma cells.
    • Normal gastric G cells are inhibited by secretin; therefore, secretin administration should not cause a rise in serum gastrin concentrations in patients with other causes of hypergastrinemia.
    • Calcium Infusion study: is usually reserved for patients who have gastric acid hypersecretion and are strongly suspected of having gastrinoma despite a negative secretin test. Calcium infusion can lead to an increase in serum gastrin levels in patients with gastrinoma.
    • CT/MRI & somatostatin receptor scintigraphy: for tumor localization
  39. Why diarrhea in ZES?
    The excess gastric acid in the small intestine can cause diarrhea and steatorrhea due to inactivation of pancreatic enzymes and injury to the mucosal brush border.
  40. Liver Disease in Pregnancy
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  41. Intrahepatic cholestasis of pregnancy (ICP):
    • ICP Is a functional disorder of bile formation that develops in the second and third trimesters.
    • Etiology: is unclear, but it is thought that hormonal (eg, higher levels of estrogen or progesterone later in pregnancy), genetic, and environmental factors influence its development
    • Clinical manifestations: intense, often intolerable, generalized pruritus that is especially significant on the palms and soles and worsens at night. Evidence of skin excoriations may be present on examination. Fewer than 10% of patients have jaundice.
    • Investigations:
    • Serum total bile acids are typically increased and may be the only abnormal laboratory finding.
    • Liver function studies are sometimes suggestive of cholestasis with alkaline phosphatase and the total and direct bilirubin increased (although alkaline phosphatase Is elevated In normal pregnancy).
    • Serum aminotransferases may be 10 times normal (sometimes >1000 U/L), which requires that viral hepatitis be ruled out.
    • Treatment: is based on symptom relief, and pruritus resolves in the weeks following delivery. Ursodeoxychollc acid is commonly prescribed to increase bile flow and relieve itching.
    • Maternal prognosis is generally good.
    • However, early delivery is recommended once fetal maturity is achieved to avoid fetal complications (eg, intrauterine demise, neonatal respiratory distress syndrome).
  42. Acute mesenteric ischemia
    • Presentation:
    • • Rapid onset of periumbilical pain (often severe)
    • • Pain out of proportion to examination findings
    • • Hematochezia (late complication)
    • • If bowel infarction occurs, patients may develop more focal abdominal tenderness (due to local inflammation/infarction), peritoneal signs (eg, guarding, rebound tenderness), rectal bleeding, and sepsis.
    • Risk factors:
    • • Atherosclerosis (acute on chronic)
    • • Cardiac embolic events in the setting of atrial fibrillation, valvular disease (eg, infective endocarditis) or cardiovascular aneurysms
    • • Acute thrombosis due to peripheral arterial disease or low cardiac output states
    • • Hypercoagulable disorders
    • Laboratory findings:
    • • Leukocytosis
    • • Elevated hemoglobin (hemoconcentration)
    • • Elevated amylase & phosphate levels
    • • Metabolic acidosis (elevated lactate)
    • Diagnosis:
    • • CT (preferred) or MR angiography
    • • Mesenteric angiography, if diagnosis unclear
    • Treatment:
    • Treatment includes open embolectomy with vascular bypass or endovascular thrombolysis. In addition, patients should be started on broad-spectrum antibiotics and, in the absence of active bleeding, anticoagulation to reduce the risk of clot expansion
  43. Pancreatic Pseudocysts
    • Definition:
    • are mature walled-off pancreatic fluid collections (usually no necrosis or solid material) surrounded by a thick fibrous capsule and containing enzyme-rich fluid, tissue, and debris.
    • They can leak amylase-rich fluid into the circulation and increase serum amylase.
    • Complications: include spontaneous infection, duodenal or biliary obstruction, pseudoaneurysm (due to digestion of adjacent vessels), pancreatic ascites, and pleural effusion.
    • Diagnosis: CT scan showing a round, well circumscribed, encapsulated fluid collection in the pancreatic bed
    • Treatment:
    • In patients with minimal or no symptoms and without complications (eg, pseudoaneurysm), expectant management (eg, symptomatic therapy, nothing by mouth) is preferred initially.
    • Endoscopic drainage is typically reserved for those with significant symptoms (eg, abdominal pain, vomiting), infected pseudocyst, or evidence of pseudoaneurysm (usually embolized before drainage procedure).
  44. Gallstone Pancreatitis
    • AL T >150 U/L has a 95% positive predictive value for diagnosing gallstone pancreatitis.
    • Early cholecystectomy is recommended for medically stable patients who recover from acute pancreatitis and are surgical candidates.
    • Cholecystectomy can markedly reduce the risk of recurrent gallstone pancreatitis.
  45. Anal Cancer
    • Anal cancer develops primarily from squamous epithelial cells due to human papillomavirus (HPV) infection.
    • Risk is greatest in: men who have receptive anal intercourse and those with advanced HIV (due to Immunosuppression and increased prevalence of multiple HPV serotypes).
    • Rectal bleeding: is the most common manifestation of anal cancer and may be falsely attributed to hemorrhoids if the tumor is located above the anal sphincter, hiding it from view.
    • Patients also commonly have anal pain and/or a sensation of anal pressure.
    • Examination: may show a mass or an ulcerated anal lesion; spread via the lymphatic system may result in firm, nontender inguinal or femoral lymphadenopathy.
    • Diagnosis: requires a biopsy of the lesion.
  46. Anal fissures
    • Anal fissures are characterized by longitudinal tears in the anal canal distal to the dentate line
    • Pathophysiology: Spasm of the sphincter contributes to the pain and creates tension across the wound, leading to a chronic fissure
    • Etiology:
    • • Local trauma (eg, constipation, prolonged diarrhea, anal sex)
    • • Inflammatory bowel disease {eg, Crohn disease)
    • • Malignancy
    • Clinical presentation:
    • • Pain with bowel movements, the pain may be so severe that patients withhold bowel movements. exacerbating the constipation
    • • Bright red blood on toilet paper or stool surface
    • • Most common at posterior anal midline
    • • Chronic fissure may have skin tag at distal end (sentinel pile).
    • Treatment:
    • • High-tiber diet & adequate fluid intake
    • • Stool softeners
    • • Sitz baths to increase blood flow to the injured mucosa
    • • Topical anesthetics & vasodilators (eg, nifedipine, nitroglycerin) can be used to reduce pressure in, and increase blood flow to, the anal sphincter, facilitating healing.
  47. Acute Appendicitis
    • typically begins as a vague periumbilical visceral pain caused by stretching of the appendiceal wall. Eventually the peritoneum becomes inflamed and the pain becomes sharp and localizes to the RLQ.
    • Patients typically will have pain with palpation at McBurney point in the RLQ and Rovsing sign (RLQ pain with deep palpation of the LLQ).
    • Laboratory studies can show leukocytosis but may be normal.
    • Diagnosis based on classic clinical and laboratory features of appendicitis.
    • It does not warrant further imaging before surgery as this may delay treatment and lead to complications, including perforation.
    • However, patients who do not have the typical features of appendicitis or those with other possible causes of RLQ pain (eg, diverticulitis, Ileitis, inflammatory bowel disease) should have appropriate imaging with computed tomography or ultrasonography to confirm the diagnosis.
  48. Appendicular Abscess
    • Patients who have a delayed presentation with a longer duration of symptoms (>5 days) often have appendiceal rupture with a contained abscess.
    • These patients will generally have significant fever and leukocytosis, but findings on anterior palpation of the abdomen may be unrevealing.
    • In such cases, maneuvers that assess the deep abdominal spaces (eg, psoas sign, obturator sign, rectal examination) may be more informative.
    • In particular, the psoas sign: suggests the presence of an abscess posterior to the appendix adjacent to the psoas muscle (or possibly an unruptured retrocecal appendix).
    • Computed tomography imaging can confirm the diagnosis in these cases.
    • Patients with a contained appendiceal abscess have a very high complication rate from immediate surgery due to the mass of inflamed, infected, and friable debris and adhesions.
    • If they are otherwise clinically stable, these patients should be managed with intravenous antibiotics, bowel rest and possibly percutaneous drainage of the abscess.
    • They can return in 6-8 weeks for appendectomy on an elective basis ("interval appendectomy").
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  49. Dumping syndrome
    • Symptoms
    • • Abdominal pain, diarrhea, nausea
    • • Hypotension/tachycardia
    • • Dizziness/confusion, fatigue, diaphoresis
    • Timing
    • • 15-30 minutes after meals
    • Pathogenesis:
    • • DS is a common postgastrectomy complication. It is caused by loss of the normal action of the pyloric sphincter due to injury or surgical bypass and leads to rapid emptying of hypertonic gastric contents into the duodenum and small intestine.
    • • This causes fluid shifts from the intravascular space to the small intestine, leading to hypotension, stimulation of autonomic reflexes, and release of intestinal vasoactive polypeptides
    • Initial management:
    • • Small/frequent meals and eat slowly
    • • Replace simple sugars with complex carbohydrates
    • • Incorporate high-fiber & protein-rich foods
    • • Drink fluids between rather than during meals
    • A minority of patients with refractory symptoms may benefit from a trial of octreotide or require reconstructive surgery
  50. Splenic Injury, Liver Injury And Aortic Injury
    • Splenic injury is most likely in the setting of abdominal pain, tachycardia, and left chest wall and shoulder pain without evidence of abnormalities of the shoulder (likely referred pain due to phrenic nerve irritation from splenic hemorrhage).
    • The next step in evaluation should Include a focused assessment with sonography for trauma (FAST) examination to identify signs of hemorrhage.
    • Aortic Injury: most common mechanisms resulting in significant aortic injury are rapid deceleration injuries such as motor vehicle collisions at speeds >50 kmlhr (30 mph), falls from >3m (10ft), or severe crush injuries. Moreover, patients with aortic trauma frequently have significant comorbid injuries such as fractures, neurological deficits, cardiac murmurs, and upper extremity hypotension.
    • Liver Injury: Hepatic laceration is one of the most common solid organ injuries due to blunt abdominal trauma. Common manifestations include hypotension, free intraperitoneal fluid, right upper quadrant pain and bruising, and right shoulder pain due to phrenic nerve irritation.
Card Set
Alcoholic liver Disease