Podcast
Questions and Answers
What is the consequence of unconjugated bilirubin in the serum?
What is the consequence of unconjugated bilirubin in the serum?
How is unconjugated bilirubin transported to the hepatocyte?
How is unconjugated bilirubin transported to the hepatocyte?
Which factor would NOT be a cause of increased conjugated bilirubin levels?
Which factor would NOT be a cause of increased conjugated bilirubin levels?
What defines the process of conjugating bilirubin in the liver?
What defines the process of conjugating bilirubin in the liver?
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What does an elevation in serum bilirubin indicate?
What does an elevation in serum bilirubin indicate?
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What is one potential risk associated with a MAFLD diagnosis compared to NAFLD?
What is one potential risk associated with a MAFLD diagnosis compared to NAFLD?
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Why is under-reporting of alcohol ingestion significant in the context of NAFLD diagnosis?
Why is under-reporting of alcohol ingestion significant in the context of NAFLD diagnosis?
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Which statement accurately describes the relationship between MAFLD and metabolic syndrome?
Which statement accurately describes the relationship between MAFLD and metabolic syndrome?
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What percentage of individuals with a fatty liver do not meet any criteria for MAFLD?
What percentage of individuals with a fatty liver do not meet any criteria for MAFLD?
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How does the diagnosis of MAFLD benefit clinical treatment compared to NAFLD?
How does the diagnosis of MAFLD benefit clinical treatment compared to NAFLD?
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What common factor is associated with both obesity and insulin resistance in patients with fatty liver?
What common factor is associated with both obesity and insulin resistance in patients with fatty liver?
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Which of the following conditions is NOT indicated as being worsened by a MAFLD diagnosis?
Which of the following conditions is NOT indicated as being worsened by a MAFLD diagnosis?
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What does the MAFLD diagnostic criterion help avoid compared to NAFLD?
What does the MAFLD diagnostic criterion help avoid compared to NAFLD?
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What is a consequence of increased adipocyte-derived free fatty acid liberation?
What is a consequence of increased adipocyte-derived free fatty acid liberation?
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Why do obesity, insulin resistance, and fatty liver tend to cluster together?
Why do obesity, insulin resistance, and fatty liver tend to cluster together?
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What is the best therapeutic option for managing MAFLD?
What is the best therapeutic option for managing MAFLD?
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Which statement correctly describes the role of adiponectin in relation to fatty liver disease?
Which statement correctly describes the role of adiponectin in relation to fatty liver disease?
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What impact does exercise have on conditions like steatosis and fibrosis in individuals with obesity or type II diabetes?
What impact does exercise have on conditions like steatosis and fibrosis in individuals with obesity or type II diabetes?
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What is the most common cause of death in patients with Non-Alcoholic Fatty Liver Disease?
What is the most common cause of death in patients with Non-Alcoholic Fatty Liver Disease?
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Which of the following is a characteristic feature of Nonalcoholic Steatohepatitis (NASH)?
Which of the following is a characteristic feature of Nonalcoholic Steatohepatitis (NASH)?
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What is required for the diagnosis of NAFLD?
What is required for the diagnosis of NAFLD?
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Which of the following conditions is NOT a metabolic driver for MAFLD?
Which of the following conditions is NOT a metabolic driver for MAFLD?
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What role do liver enzymes play in diagnosing NAFLD?
What role do liver enzymes play in diagnosing NAFLD?
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Which feature is typically observed in cirrhosis related to NAFLD?
Which feature is typically observed in cirrhosis related to NAFLD?
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What common symptom may occur in some patients with Non-Alcoholic Fatty Liver Disease?
What common symptom may occur in some patients with Non-Alcoholic Fatty Liver Disease?
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What is one method used for determining the degree of inflammation and fibrosis in NAFLD?
What is one method used for determining the degree of inflammation and fibrosis in NAFLD?
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What is the primary purpose of elastography in the assessment of liver conditions?
What is the primary purpose of elastography in the assessment of liver conditions?
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Which scoring system is primarily based on blood tests and clinical data to predict the presence of fibrosis?
Which scoring system is primarily based on blood tests and clinical data to predict the presence of fibrosis?
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What is a common factor typically associated with both anorexia nervosa and bulimia?
What is a common factor typically associated with both anorexia nervosa and bulimia?
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Which psychological factor is NOT mentioned as a contributing factor to the etiology of eating disorders?
Which psychological factor is NOT mentioned as a contributing factor to the etiology of eating disorders?
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What complication is associated with malnutrition due to eating disorders?
What complication is associated with malnutrition due to eating disorders?
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Which of the following conditions is NOT a consequence of purging in eating disorders?
Which of the following conditions is NOT a consequence of purging in eating disorders?
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What factor is commonly recognized as a trigger for developing eating disorders?
What factor is commonly recognized as a trigger for developing eating disorders?
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Which of the following systems is primarily linked to the regulation of appetite and eating behaviors?
Which of the following systems is primarily linked to the regulation of appetite and eating behaviors?
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Which of the following statements about MAFLD is false?
Which of the following statements about MAFLD is false?
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What does a persistent elevation in ALT typically indicate in liver health assessments?
What does a persistent elevation in ALT typically indicate in liver health assessments?
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What does an increased PT/INR indicate in relation to blood clotting?
What does an increased PT/INR indicate in relation to blood clotting?
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Which vitamin deficiency is most commonly associated with increased clotting times?
Which vitamin deficiency is most commonly associated with increased clotting times?
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In liver function tests indicating acute hepatocellular injury, which enzyme is typically elevated more than the other?
In liver function tests indicating acute hepatocellular injury, which enzyme is typically elevated more than the other?
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What liver lab pattern is indicative of cholestasis?
What liver lab pattern is indicative of cholestasis?
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What pattern is observed in liver function tests for hepatitis B?
What pattern is observed in liver function tests for hepatitis B?
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Which condition is characterized by an AST:ALT ratio of 2 or greater?
Which condition is characterized by an AST:ALT ratio of 2 or greater?
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Which imaging technique is considered the best for examining larger biliary ducts and the gallbladder?
Which imaging technique is considered the best for examining larger biliary ducts and the gallbladder?
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What does a normal or modestly elevated ALP and GGT indicate in chronic hepatocellular injury?
What does a normal or modestly elevated ALP and GGT indicate in chronic hepatocellular injury?
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What test is definitive in diagnosing liver disease that is difficult to assess non-invasively?
What test is definitive in diagnosing liver disease that is difficult to assess non-invasively?
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In cases of Gilbert's syndrome, which laboratory result is typically elevated?
In cases of Gilbert's syndrome, which laboratory result is typically elevated?
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Study Notes
Liver Pathology Part III - MAFLD
- MAFLD is "metabolic dysfunction associated fatty liver disease".
- NAFLD is the most common cause of liver disease in the US.
- Estimated prevalence of NAFLD is up to 40% of the population.
- NAFLD includes simple hepatic steatosis and steatosis complicated by inflammation.
- Progression to NASH (non-alcoholic steatohepatitis) is uncommon.
- NASH progresses to cirrhosis in 10-20% of cases.
- In those progressing to cirrhosis, liver cancer incidence can be as high as 1-2% per year.
NAFLD - Pathologic Findings
- Initial findings include hepatocyte ballooning, lobular inflammation, and steatosis (fat accumulation).
- Progressive disease leads to more fibrosis, eventually causing cirrhosis.
- Strongly linked to obesity and the metabolic syndrome.
NAFLD - Pathophysiology
- "Two-hit" model
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- Hepatic fat accumulation.
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- Increased oxidative stress.
- Free radicals cause lipid peroxidation of accumulated intracellular fat.
- Obesity is associated with reduced intestinal barrier function and inflammation in the liver.
- Movement of microbes from the gut to the portal circulation.
Cirrhosis Pathogenesis
- Cirrhosis is the diffuse remodeling of the liver into parenchymal nodules surrounded by fibrous bands and a variable degree of vascular shunting.
- Stellate cells become activated and differentiate into highly fibrogenic myofibroblasts.
- Activated by inflammatory cytokines (e.g., TNF-alpha), toxins, and reactive oxygen species.
- Signals implicated include PDGF, TGF-beta, and IL-17.
- ECM deposition into the space of Disse and fibrous septae formation occur in regions of hepatocyte loss.
- Hepatocytes regenerate in nodules, but the architecture of the acinus is disrupted by fibrosis.
MAFLD vs. NAFLD
- Both require a 5% level of hepatic steatosis.
- MAFLD requires the presence of metabolic drivers of hepatic steatosis and inflammation (e.g., T2DM, obesity).
- A metabolic dysfunction composite score may be considered, further details are available on subsequent slides.
- NAFLD diagnosis requires excluding other liver diseases (significant alcohol use, hemochromatosis, etc.) as possible causes.
MAFLD and NAFLD Diagnostic Criteria
- MAFLD diagnostic criteria include 2 out of 7 metabolic risk factors.
- Elevated waist circumference
- Blood pressure > 130/85 (or use of BP meds)
- Elevated triglycerides (> 1.7 mmol/L)
- Low HDL cholesterol
- Prediabetes
- Elevated HOMA insulin resistance score
- Elevation in CRP
- NAFLD does not consider metabolic risk factors.
Why Diagnostic Differences Matter
- Clearer diagnoses can specify chronic viral hepatitis complicating NASH.
- Better diagnostics allow for targeted treatments.
- A MAFLD diagnosis increases the risk of diabetes, chronic kidney disease, and worsened lung function compared to NAFLD.
- MAFLD is often associated with increased "wear and tear" from metabolic dysregulation, while NAFLD may not be as strongly linked to this.
- MAFLD diagnostic criteria can mitigate issues with underreporting of alcohol consumption, a potential issue in patients with NAFLD.
MAFLD and NAFLD Pathophysiology
- Obesity and insulin resistance cluster frequently as they cause increased FFA liberation from adipocytes, converting them into triglycerides that are stored in hepatocytes.
- Elevated glucose and insulin leads to hepatic triglyceride synthesis.
- Adiponectin, an adipokine released by visceral fat, increases glucose utilization and fatty acid oxidation.
- Declines in adiponectin are associated with increased intra-abdominal fat.
MAFLD - Counteracting Pathology
- Weight loss via lifestyle modification is the best approach.
- Weight loss can reduce steatosis and improve fibrosis in patients with type 2 diabetes.
- Exercise may improve fibrosis and steatosis.
An Approach to Hepatic Investigations
- Blood tests assessing liver enzymes (ALT, AST), liver function (albumin, PT/INR), and bilirubin help diagnose liver damage severity and etiology.
Laboratory Analysis of Liver
- The different transaminases (ALT, AST), ALP, bilirubin, albumin, and PT/INR can be used for liver damage & etiology assessment
- Liver enzyme tests (ALT and AST), liver function tests (albumin and PT/INR), and bilirubin tests help determine liver pathology.
General Patterns and Concepts
- Damage to hepatocytes or biliary tree releases enzymes into the bloodstream.
- Elevated liver enzymes indicate damage.
- Hepatic function is assessed through serum albumin (maintains oncotic pressure) and bilirubin values.
- Bilirubin is a breakdown product of heme in the biliary tree, and increases signify damaged or impaired hepatic function.
- A PT/INR increase signifies time to clot increases and signifies impaired hepatic function.
- Hepatocellular pattern = increased AST and ALT, normal to mildly elevated ALP and GGT.
- Cholestatic pattern = increased ALP and GGT, normal or moderately elevated AST and ALT.
Liver Enzyme Tests
- ALT: Alanine aminotransferase, found primarily in hepatocytes, is a good indicator of hepatocyte damage.
- AST: Aspartate aminotransferase, found in hepatocytes and other cells, is less specific for hepatocyte damage than ALT.
- ALP: Alkaline phosphatase is found in hepatocytes and bone, increased levels often indicate biliary tract problems.
- GGT: Gamma-glutamyl transpeptidase is found in hepatocytes and other cells, increased levels often indicate biliary tract problem or alcohol use disorder.
Liver Function Tests
- Bilirubin: Two forms (unconjugated and conjugated) assess liver function, particularly the conjugation, transport, and excretion of bilirubin.
- Albumin: Levels help establish oncotic pressure and indicate long-term protein synthesis deficiencies.
- PT/INR: Prothrombin time (PT) or international normalized ratio (INR) evaluate the liver's ability to produce clotting factors and indicate liver dysfunction.
Liver Imaging- FYI Review
- Ultrasound is best for evaluating biliary ducts and gallbladder.
- MRI and CT provide insight into liver masses and fibrosis.
- MRCP is a specialised MRI technique to evaluate the biliary system.
- Liver biopsy is often needed as a definitive diagnosis for fibrosis or cirrhosis.
Liver Investigations in MAFLD
- Elastography is used to measure liver fibrosis.
- Elastography can have false positives.
- MRI is helpful for detailed views of the biliary system and fibrosis assessment.
- Ultrasound is a potentially cheaper and accurate way to assess steatosis.
- Liver biopsy is necessary to definitively diagnose steatosis and fibrosis.
MAFLD Screening Tests
- FIB-4 score, NAFLD fibrosis score and ELF test are some useful tests to calculate.
Etiology of Eating Disorders
- Anorexia nervosa and bulimia are complex disorders with multiple factors contributing to their etiology.
- Psychological factors include OCD traits, cognitive rigidity, heightened emotional sensitivity, impulsivity, and a history of developmental stress, trauma, and challenging interpersonal relationships.
- Body dissatisfaction and engagement in diets and strenuous athletic training are important behavioral factors.
- Biological factors include genetic effects, and dysfunction in serotonin, dopamine, norepinephrine, opioid, and cholecystokinin systems.
Complications of Eating Disorders
- All-cause mortality is 2-10 times higher than general populations of similarly aged individuals with similar demographic backgrounds.
- Independent of weight; vitamin and mineral deficiencies, stunted growth, reduced gastric motility, increased discomfort from fullness and avoidance to eat are all common.
- Consequences of malnutrition; Bradycardia, hypotension, orthostasis, hypothermia, metabolic alkalosis, hypochloremia, increased bicarbonate, osteopenia and myopathies.
- Consequences of purging; esophageal tears, intractable vomiting, hematemesis, metabolic acidosis (laxatives), hypokalemia and cardiomyopathies.
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Description
Test your knowledge on Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD) and its relationship with Non-Alcoholic Fatty Liver Disease (NAFLD). This quiz covers key concepts such as pathology, findings, and pathophysiology related to liver health. Assess your understanding of liver diseases and their progression.
