GASTRO 2: BOARDS AND BEYOND Flashcards
What demographic is primarily affected by autoimmune hepatitis (AIH)?
Women in their forties and fifties.
How is AIH commonly identified?
Through incidental findings of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels on blood work.
What are potential complications of AIH?
Chronic liver disease and, rarely, cirrhosis.
What are the diagnostic criteria for AIH?
Presence of antinuclear antibodies (ANA) for sensitivity and anti-smooth muscle antibodies (ASMA) for specificity, especially in type I AIH.
What is the management strategy for acute episodes of AIH?
Treatment typically involves steroids and immunosuppressants.
Are highly specific for systemic lupus erythematosus (SLE) and are believed to be implicated in the pathogenesis of lupus nephritis.
Anti-double stranded DNA antibodies
Are specific for CREST syndrome, a limited cutaneous form of systemic scleroderma. The five main features (as indicated by the acronym) are calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.
Anti-centromere antibodies
Are associated with drug-induced lupus. Common drugs implicated include procainamide, penicillamine, isoniazid, and methyldopa.
Anti-histone antibodies
Are found in patients with anti-phospholipid syndrome, a hypercoagulable state that causes thrombosis in arteries and veins. It causes a number of pregnancy-related complications, including miscarriage, stillbirth, preterm delivery, and preeclampsia.
Anti-cardiolipin antibodies
Are specific for primary biliary cholangitis. Like autoimmune hepatitis, this condition primarily affects middle-aged women. ANA antibodies are also sensitive markers for this disease. Unlike autoimmune hepatitis, patients generally present with signs and symptoms consistent with cholestasis, including itching, fatigue, and jaundice. Primary biliary cholangitis more often progresses to cirrhosis.
Anti-mitochondrial antibodies
What is a pyogenic liver abscess?
A walled-off infection of the liver.
What is the most likely cause of a pyogenic liver abscess in a patient with diverticulitis?
Seeding of the portal venous system with bacteria from the diverticulitis episode.
Which organisms are most commonly responsible for pyogenic liver abscesses?
Enteric flora, particularly gram-negative rods like E. coli and Klebsiella pneumoniae.
What characterizes acute alcoholic hepatitis?
Hepatitis occurring after acute binge drinking in individuals with a history of alcohol-use disorder.
What are common symptoms of acute alcoholic hepatitis?
Right upper quadrant abdominal pain, fever, and jaundice.
What is the main toxic by-product involved in the pathophysiology of acute alcoholic hepatitis?
Acetaldehyde, produced during alcohol metabolism.
How does acetaldehyde affect hepatocytes?
It damages intermediate filaments within the cells.
What is a classic histopathological finding in acute alcoholic hepatitis?
Mallory bodies, which are cytoplasmic inclusions representing damaged intermediate filaments in hepatocytes.
In alcoholic liver disease, nuclei may be pushed aside by fat accumulation with cells, but
Nuclear abnormalities are not a classic feature of alcoholic hepatitis.
An overabundance of microtubules can be seen in cardiac myocytes in patients with
Hypertrophic cardiomyopathy
Structural and functional alterations of the Golgi apparatus are seen in several neurodegenerative, diseases including
Amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s dementia, and Huntington’s disease.
What is Budd-Chiari syndrome?
Hepatic vein thrombosis leading to abdominal pain, ascites, and hepatomegaly.
How is Budd-Chiari syndrome diagnosed?
Doppler imaging showing obstruction of the hepatic vein.
What conditions are associated with Budd-Chiari syndrome?
Hepatocellular carcinoma, polycythemia vera, and hypercoagulable states.
What comprises the portal triad?
A bile duct, hepatic artery, and portal vein, surrounded by zone I (periportal).
Describe the zones of the liver acinus
Zone I (periportal), Zone II (midzone), Zone III (centrilobular).
What happens in Zone III during hepatic vein thrombosis?
Congestion occurs first, leading to potential hepatic necrosis.
Why is Zone III particularly susceptible to injury?
It is vulnerable to ischemic damage, fatty infiltration, and fibrosis.
What are common etiologies of cirrhosis?
Alcoholic liver disease, viral hepatitis, autoimmune conditions (e.g., autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis).
How does cirrhosis affect liver function?
It impairs synthetic functions like albumin and clotting factor production.
What laboratory findings would indicate cirrhosis?
Decreased serum albumin and prolonged prothrombin time (PT), partial thromboplastin time (PTT), and INR.
How are Factor VIII levels affected in chronic liver disease?
Factor VIII levels are usually normal or increased due to synthesis by endothelial cells outside the liver.
Where else is von Willebrand factor (VWF) synthesized?
By endothelial cells outside the liver, similar to Factor VIII.
Evidence of hypervolemia:
- Distended abdomen (ascites)
- Bilateral pitting edema
Cirrhosis Overview
- Vasodilation
- Low systemic vascular resistance (SVR)
Hemodynamic Changes in Cirrhosis
Low SVR activates:
- Sympathetic nervous system (SNS)
- Renin-angiotensin-aldosterone system (RAAS)
Results in:
- Sodium and water retention
- Hypervolemia
Cirrhosis: Activation of Compensatory Systems
Low albumin → decreased plasma oncotic pressure
Fluid leakage from capillaries →
Reduces circulating volume
Causes ascites and peripheral edema
Impact on Renal Blood Flow
Low circulating volume → decreased renal blood flow (RBF)
Increased serum antidiuretic hormone (ADH) levels
Plasma Oncotic Pressure in Cirrhosis
Total body sodium is increased in hypervolemia (e.g., cirrhosis, heart failure)
Serum sodium = sodium in blood
Can be elevated, normal, or low in hypervolemia
Hyponatremia risk:
Due to water retention and dilution of serum sodium
Total Body Sodium vs. Serum Sodium
- Activation of SNS and RAAS → sodium and water retention
- Excess fluid increases total body sodium
- Retention of water can lead to hyponatremia
Summary of Fluid and Sodium Dynamics
Internal hemorrhoids are a consequence of congestion of the
Superior rectal veins
In cirrhosis, venous collaterals form between the left gastric vein and the esophageal veins. Congestion of this vessel leads to
Esophageal varices
What are Varices?
- Dilated, tortuous veins
- Hallmark of end-stage liver disease and cirrhosis
Can rupture, leading to life-threatening hemorrhage
Cause of Varices
- Result from portal venous congestion
Secondary to obstructed blood flow in cirrhotic liver
Gastric Varices Explained
- Dilated veins due to congestion in short gastric veins
- Located along the greater curvature of the stomach
- Short gastric veins drain into the splenic vein, then the portal vein
Congestion in the splenic vein leads to dilation of short gastric veins
Visible during endoscopy
Risks of Bleeding Varices
- High morbidity and mortality in cirrhosis
- Screening endoscopy performed to evaluate and treat when bleeding risk is high
The superior rectal veins drain into the inferior mesenteric vein, which then drains to the portal vein. Note that the other rectal veins (middle and inferior rectal veins) bypass the portal-venous system. Blood from these veins eventually drains into the inferior vena cava.
Dilation of these vessels in portal hypertension does not occur.
The umbilical vein is present during fetal development. This structure closes after birth and becomes the
Ligamentum teres (also called the round ligament of the liver).
- Drug of choice for managing ascites in cirrhosis after salt and fluid restriction
- Aldosterone receptor antagonist
Spironolactone Overview
- Blocks aldosterone action at the distal tubule
Results in: - Decreased sodium and water retention
- Increased excretion of salt and water (diuresis)
- Improvement of ascites
Mechanism of Action: Spironolactone
- Spironolactone is a potassium-sparing diuretic
- Requires monitoring for hyperkalemia
Potassium-Sparing Diuretic: Spironolactone
Common ECG changes:
- Peaked T waves (classic finding)
Severe hyperkalemia can lead to:
- Broadening of QRS
- Absence of P-waves
- Conversion to sinusoidal wave pattern
Hyperkalemia Monitoring: Spironolactone
Polyuria and volume loss occurs with
Hypercalcemia
Tetany occurs in
Hypocalcemia
Calciphylaxis occurs in
Hyperphosphatemia
Parathyroid inhibition occurs in ?. Severe hypomagnesemia suppresses parathyroid hormone release, leading to hypocalcemia.
Marked hypomagnesemia
- Impairment of neuropsychiatric function due to impaired hepatic function
Often associated with hyperammonemia
Hepatic Encephalopathy Overview
Common in many cases of hepatic encephalopathy
Neurologic manifestations include:
- Asterixis
- Confusion
- Coma
Role of Hyperammonemia
Synthetic disaccharide and osmotic laxative
- Used to lower elevated serum ammonia in hepatic cirrhosis
Lactulose as Treatment
- Increases excretion of ammonia via the GI tract
- Fermented by colonic flora → release of fatty acids
Mechanism of Lactulose
- Increases free fatty acid and hydrogen ion concentration in the colon
- Acidifies colonic environment, converting NH3 to NH4+
- NH4+ cannot be reabsorbed and is excreted in stool
Effects of Lactulose Fermentation
- Ammonium excretion via stool lowers serum NH3 levels
- Helps improve symptoms of hepatic encephalopathy
Impact on Serum NH3 Levels
Increase in free fluid in the peritoneal cavity
- Defined as >25 ml of fluid
Definition of Ascites
Portal hypertension
Primary Cause of Ascites in Cirrhosis
Blood flows from the portal venous system → liver → hepatic veins → inferior vena cava
Normal Blood Flow Pathway
- Normal liver tissue is replaced by fibrous tissue
- Disrupted blood flow leads to portal hypertension
Changes in Cirrhosis
- Increased capillary hydrostatic pressure in the abdomen
- Fluid shifts from intravascular space to extravascular space
Mechanism of Ascites Formation
The most common cause of liver malignancy is metastasis. Common primary sites include the pancreas, breast, lung, and colon. Metastasis to the liver is more likely to present as multiple lesions, but a single lesion can also occur. Colonic adenocarcinoma is most likely in this case, given the
Coexisting microcytic anemia and heme positive stool.
Hepatocellular carcinoma (HCC) is less common than metastasis to the liver. HCC generally presents as a single lesion; however, this patient has no apparent risk factors. Risk factors include infection with ?.
hepatitis B, hepatitis C, cirrhosis, alcohol abuse, and exposure to aflatoxins
Hepatic adenomas are benign lesions that generally present as solitary nodules in the right lobe of the liver and occur in
Younger women on oral contraceptives.
Hepatic angiosarcomas are rare, highly malignant lesions whose primary risk factors include exposure to
Polyvinyl chloride or arsenic.
Rare, highly malignant primary tumor of the liver
- Vascular in nature
Hepatic Angiosarcoma Overview
- Atypical endothelial cells
- Disorganized vascular structures
Hepatic Angiosarcoma Histological Features
Death often secondary to rupture of liver nodules
Hepatic Angiosarcoma Cause of Death
Generally poor prognosis
- Less than one year from diagnosis
Hepatic Angiosarcoma Prognosis
Common metastasis to the lungs and spleen
Hepatic Angiosarcoma Metastatic Sites
Toxic exposures, notably:
- Polyvinyl chloride
- Arsenic
Hepatic Angiosarcoma Primary Risk Factors
Most common primary malignancy of the liver
Hepatocellular Carcinoma (HCC) Overview
- Alcohol use
- Cirrhosis
- Chronic hepatitis B
- Exposure to aflatoxins (e.g., from contaminated homegrown vegetables)
Hepatocellular Carcinoma (HCC) Risk Factors
- Commonly associated with polycythemia
- Elevated hematocrit due to secretion of erythropoietin (EPO)
Hepatocellular Carcinoma (HCC) Lab Abnormalities
- EPO increases bone marrow production of red blood cells
- Normally secreted by the kidney in response to anemia
Erythropoietin (EPO) in HCC
Is a tumor marker elevated in pancreatic cancer.
Ca 19-9
Is a tumor marker that is elevated in multiple malignancies including colonic, gastric, breast, lung, and medullary thyroid cancer.
Carcinoembryonic antigen (CEA)
This man has cirrhosis with no evidence of portal hypertension, such as ascites. Patients with cirrhosis of any cause are at increased risk for hepatocellular carcinoma (HCC). For this reason, abdominal imaging with
Ultrasound, CT scan, or MRI is performed at regular intervals, usually every six months.
A contrast agent, is injected into the rectum via enema to visualize the distal colon and rectum by X-ray. This can be useful in disorders of the distal colon, including colon cancer, inflammatory bowel disease, and Hirschsprung’s disease.
Barium
Occurs in end-stage liver disease when the liver can no longer synthesize sufficient clotting factors.
Coagulopathy with elevated prothrombin time
Alanine aminotransferase (ALT) is a liver enzyme. Its levels are elevated in many forms of liver disease, and may be low in ? when the liver is replaced by fibrous tissue.
Cirrhosis
Occurs in end-stage liver disease with liver failure when the liver can no longer perform gluconeogenesis.
Hypoglycemia
- Autosomal recessive disorder of copper metabolism
- Characterized by impaired copper transport and excretion in bile
Wilson’s Disease Overview
- Caused by mutation of the ATP7B gene on chromosome 13
- ATP7B is a copper transport protein
Genetic Cause of Wilson’s Disease
- Impaired function of ATP7B leads to copper accumulation in the liver and other organs
- Results in free radical production and tissue damage
Mechanism of Copper Accumulation
- Pathological hallmark of Wilson’s disease
- Corneal copper deposits along Descemet’s membrane at the limbus (corneoscleral junction)
Kayser-Fleischer Ring
Copper accumulation in the brain leads to symptoms such as:
- Ataxia (leading to falls)
- Difficulty speaking
Neurologic Impairment in Wilson’s Disease
Total body copper is increased compared to normal
Copper is trapped in organs (liver, brain, eye, kidneys)
Copper Metabolism in Wilson’s Disease
- Total serum copper is paradoxically decreased
- Ceruloplasmin (copper transport protein) is low due to impaired copper incorporation
Wilson’s D: Serum Copper and Ceruloplasmin Levels
- 24-hour urinary copper excretion is increased
- Increased free copper in serum is filtered at the glomerulus and excreted
Urinary Copper Excretion in Wilson’s Disease
Increased urinary copper excretion does not reverse total body copper accumulation in tissues
Impact of Urinary Excretion on Copper Accumulation
- Ceruloplasmin is the copper transport protein in serum
Levels are low because copper cannot be incorporated and released from the liver
Ceruloplasmin in Wilson’s Disease
- Hepatomegaly
- Increased serum aminotransferase levels
Clinical Features of Wilson’s Disease
- Oral chelation therapy with penicillamine
- Aids in copper excretion via the kidneys
Treatment for Wilson’s Disease
Condition characterized by excess total body iron
Hemochromatosis Overview
- Can be hereditary due to mutation of the C282Y gene
- Gene codes for the HFE protein
Genetic Cause of Hemochromatosis
- Can develop from excessive blood transfusions
Associated with disorders like: - Sickle cell anemia
- Beta thalassemia major
- Myelodysplastic syndromes
Acquired Causes of Hemochromatosis
Skin: Dark bronze discoloration from iron deposition
Pancreas: May lead to diabetes (“bronze diabetes”)
Heart: Common manifestation is dilated cardiomyopathy
Organ Systems Affected by Hemochromatosis
- New complaint of dyspnea on exertion
- Pitting edema
- Extra heart sound
Symptoms Supporting Dilated Cardiomyopathy
Enlarged cardiac silhouette due to increased size of the left ventricle
Chest X-ray Findings in Dilated Cardiomyopathy
Condition of iron overload with deposition in multiple organs
Hemochromatosis Overview
- Elevated serum iron
- Elevated ferritin
- Elevated transferrin saturation
- Transferrin levels may be decreased or normal
Iron Studies in Hemochromatosis
- Dilated cardiomyopathy (most common)
- Rarely, restrictive cardiomyopathy
Cardiac Manifestations of Hemochromatosis
Skin may turn bronze from iron interaction with melanin
Skin Changes in Hemochromatosis
- Iron deposition can lead to diabetes mellitus
- Often referred to as “bronze diabetes” due to concurrent skin changes
- Symptoms include polyuria and polydipsia
Pancreatic Effects of Hemochromatosis
Iron deposition may lead to:
- Hepatomegaly
- Abnormal liver function tests
- Cirrhosis
- Increased risk of hepatocellular carcinoma
Liver Complications in Hemochromatosis
arthralgias
Joint Symptoms in Hemochromatosis
- Erectile dysfunction and small testes indicate testicular atrophy
- Leads to decreased serum testosterone
Endocrine Effects in Hemochromatosis
- Increase in ferritin and hemoglobin A1C
- Decrease in serum testosterone
Expected Laboratory Changes in Hemochromatosis
Avoid Alcohol: Protects the liver.
Avoid Vitamin C: Increases iron absorption.
Dietary Recommendations for Hemochromatosis
Heme Iron: Found in red meat; easily absorbed.
Non-Heme Iron: Absorbed as Fe2+; enhanced by Vitamin C (converts Fe3+ to Fe2+).
Iron Absorption Forms
Avoid vitamin C to limit dietary iron absorption.
Implications for Hemochromatosis Patients
