GI4

In obese individuals, adipokines released from fat depots decrease the insulin sensitivity of

peripheral tissue. Increased peripheral insulin resistance causes post-prandial hyperglycemia,
which, in turn, increases insulin secretion. This hyperinsulinemia triggers lipid uptake as well
as lipogenesis within hepatocytes (non-alcoholic steatosis). The precursors
of triglycerides (e.g., fatty acids, glycerols) and the byproducts of lipid metabolism can cause
hepatocellular damage (non-alcoholic steatohepatitis, NASH) by inducing oxidative stress.
Chronic hepatocellular damage eventually leads to cirrhosis and increased risk of hepatocellular
carcinoma. NASH is only diagnosed in patients with no history of heavy alcohol use and after
other causes of chronic liver disease have been ruled out.

Primary biliary cholangitis (PBC; also known as primary biliary cirrhosis) is a chronic

progressive liver disease of autoimmune origin that is characterized by destruction of the
intralobular bile ducts. The pathogenesis of PBC is unclear; however, it primarily affects middle-
aged women and is frequently associated with other autoimmune conditions. In the early stages,
PBC is typically asymptomatic. Fatigue is the most common initial complaint. In advanced
disease, increased fibrotic changes lead to typical signs of cholestasis (e.g., jaundice) and portal
hypertension (e.g., ascites, gastrointestinal bleeding). Elevated cholestasis parameters (ALP, γ-
GT, bilirubin) as well as antimitochondrial antibodies (AMAs) help establish the diagnosis.
Management consists of slowing disease progression with ursodeoxycholic acid and relieving
symptoms. Liver transplantation is the only definitive treatment.

A combination of amoxicillin, clarithromycin, and omeprazole for a minimum of 7 days is used

for H. pylori eradication therapy. Multiple studies have demonstrated an association
between MALT lymphoma and H. pylori infection. In 60–80% of patients with H. pylori-
associated gastric MALT lymphoma, H. pylori eradication therapy causes complete regression of
the tumor.

Painless jaundice, together with a palpable gallbladder, should always raise suspicion

for pancreatic malignancy. This patient's smoking history is a risk factor for pancreatic
adenocarcinoma, which manifests with biliary tract obstruction as a late sign of infiltrative
disease. Dilated biliary and pancreatic ducts (the double duct sign) can be seen
on ultrasonography as a result of a stenosing tumor in the pancreatic head and subsequent
prestenotic dilation, as seen in this patient. Direct hyperbilirubinemia indicates obstructive
jaundice. The accumulation of serum bile acids, which causes pruritus, could explain the scratch
marks on this patient's extremities. His significant weight loss is another classic symptom of a
malignant process.

Abdominal x-ray is the preferred diagnostic modality for toxic megacolon and should be

ordered in all patients who present with bloody diarrhea, abdominal distention, and
signs of sepsis. Dilation of the transverse colon > 6 cm on plain abdominal x-
ray confirms the diagnosis. Loss of colonic haustration and multiple air-fluid levels
indicate colonic dilation and paralytic ileus. Patients with inflammatory bowel disease,
such as this patient, are at risk of developing toxic megacolon, especially early in the
course of disease (∼ 5% lifetime risk).

Zenker diverticulum is a pulsion-pseudodiverticulum and is caused by an inadequate relaxation

of the upper esophageal sphincter (UES) leading to increased intraluminal pressure that results in
outpouching of the pharyngeal wall. The condition usually forms in
the hypopharynx within Killian triangle, an area of weakness in the posterior pharyngeal wall.
This elderly man presents with classic symptoms of  Zenker diverticulum, including  dysphagia,
regurgitation of undigested food,  halitosis, and a  fluctuant  neck mass.

Furosemide was likely prescribed to this patient to treat her ascites. If administered in

excess, furosemide can lead to a profound diuresis with water and electrolyte depletion, resulting
in hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia, and ultimately the acute kidney
injury and metabolic alkalosis as seen in this patient. Hypokalemia and hypomagnesemia can
cause life-threatening arrhythmias, such as the ventricular tachycardia suffered by this patient. In
addition to correcting this patient's electrolyte levels, management would also include prompt
rehydration with intravenous fluids.

This patient with decompensated liver cirrhosis most likely has hepatorenal syndrome. As portal

hypertension worsens in patients with decompensated cirrhosis, vasodilatory mediators are
produced, leading to vasodilation of the splanchnic circulation. The altered hemodynamics result
in renal hypoperfusion, which in turn causes a decrease in GFR. Patients typically present with
gradual loss of kidney function, as seen in this patient who developed oliguria over a period of 1
month, an unremarkable urine sediment, and FENa < 1% and BUN/Cr ratio > 20. Treatment of
this condition includes administration of albumin, octreotide, and midodrine. A liver transplant is
the only curative option in advanced liver disease.