Hepatic

Page 1

Structure of Hepatic Disorders Session

  • Revision of liver basics

    • Helps in understanding

  • Types of liver injury

    • Discussion and questions

  • Portal hypertension, ascites, hepatic encephalopathy, jaundice

    • Small group discussion

  • Alcohol and the liver, other toxicities

    • Final questions and discussion

  • Focus on information for communicating with patients

    • Understanding disease states

  • Emphasis on practical knowledge

    • Not overwhelmed by numbers or minor details

Dr. Rhonda J. Rosengren's Role

  • Facilitator to help understand content

    • Not to overwhelm with information

  • Available for discussions on campus

  • Additional information to support learning

    • Ignore if not helpful

Blood Flow to the Liver

  • Liver's role in filtering and storing blood

  • Metabolism and detoxification functions

  • Importance of bile formation and regeneration

Page 2

Enterohepatic Circulation

  • Process involved in drug metabolism

  • Component of pharmacology and toxicology

Liver Cell Types

  • Hepatocytes

    • Vital for liver functions

  • Kupffer Cells

    • Role in engulfing foreign material

  • Ito Cells

    • Store and release fat

  • Endothelial Cells

    • Release cytokines and inflammation mediators

Liver Structure and Cell Types

  • Illustration of liver structure with different cell types

Page 3

Types of Liver Injury

  • Necrosis (Hepatocyte death)

    • Common acute response

  • Fatty Liver (steatosis)

    • Response to alcohol, excess energy consumption

  • Cholestasis

    • Impaired bile formation

  • NAFLD

    • Non-alcoholic fatty liver disease

    • Can progress to NASH

Importance of Liver Histology

  • Understanding normal liver structure and function

Diagnostic Tests and Liver Injury

  • ALT and AST as indicators of liver injury

  • Paracetamol overdose as a common cause of severe liver failure

Questions for Discussion

  • Significance of vitamin A in excess and deficiency

  • Liver's regulation of vitamin A and processing of xenobiotics and hormones

Page 4

  • Types of Liver Injury

    • Cirrhosis is the end stage of chronic liver injury.

    • Liver is made up of scar tissue and some hepatocytes.

    • Cirrhosis leads to severe loss of liver function.

    • Complications can arise when these processes are disrupted.

  • Liver Cirrhosis

    • Characteristics include collagen staining, unhealthy hepatocytes, and fat accumulation.

    • Many cells are replaced by collagen and scar tissue in cirrhosis.

  • Hepatitis

    • Hepatitis A and B have vaccines.

    • Hepatitis C has no vaccine and is a leading cause of liver transplant in the USA.

    • Hepatitis B and C are leading causes of liver cancer.

  • Liver Cancer

    • Metastatic liver cancer is common due to blood flow to the liver.

    • Primary liver cancer can result from chronic Hep B or Hep C infection, NAFLD, cirrhosis, and exposure to aflatoxin.

Page 5

  • Aspergillus Flavus

    • Currently not present in NZ, but may increase with climate change.

  • Consequences of Chronic Liver Injury

    • Toxic insults from drugs and chemicals can lead to swelling and fibrous tissue.

  • Portal Hypertension

    • Abnormally high blood pressure in the hepatic portal venous system.

    • Can be caused by various disorders obstructing blood flow.

  • Long-term Portal Hypertension Consequences

    • Varices and ascites are common complications.

    • Varices can lead to life-threatening hemorrhage.

    • Ascites can cause abdominal distension, hernias, and bacterial peritonitis.

Page 6

  • More Consequences of Long-term Portal Hypertension

    • Hepatic encephalopathy can occur due to neurotoxins not being detoxified.

    • Jaundice is a common complication of cirrhosis.

  • Other Causes of Jaundice

    • Excessive hemolysis of RBCs can lead to jaundice.

    • Neonatal jaundice is common and usually transient.

  • Hepatic Kidney Failure

    • Seen in about 10% of patients hospitalized with liver failure.

    • Patients show signs of both liver and kidney dysfunction.

  • Alcohol in New Zealand

    • Alcohol-related harm is a significant issue in NZ.

    • Recommended alcohol consumption has decreased over the years.

    • Alcohol is a toxic substance normalized in society.

Page 7

  • Toxic Responses to Ethanol

    • Ethanol is a strong CNS depressant.

      • Effect is proportional to blood alcohol concentration.

      • Mild CNS depression at 0.05-0.1% or 50-100 mg/dl.

      • Coma and death can occur at > 0.5% or 500 mg/dl.

    • Liver can only clear 1 standard drink an hour.

      • Bolus alcohol intake can be deadly.

    • Toxic metabolite of ethanol.

      • Excess ethanol saturates aldehyde dehydrogenase (ALDH).

      • Acetaldehyde builds up, leading to nausea, vomiting, and hypotension.

    • Plasma markers related to alcohol.

      • Elevated GGT in the plasma is a marker of chronic alcohol.

      • GGT is needed for the utilization of glutathione (GSH).

      • Alcohol causes oxidative stress, increasing GGT.

Page 8

  • All livers are not equal

    • Genetic polymorphism affects enzyme activity.

      • Japanese or Chinese have highly active ADH.

      • Japanese, Chinese, and Vietnamese have less active ALDH.

    • Paracetamol liver injury – drug interaction with ethanol.

      • Ethanol increases CYP2E1 enzyme production.

      • Chronic drinking raises the chance of liver injury.

    • More textbook disagreements.

      • Health benefits of red wine are not universally accepted.

      • No safe levels of alcohol from a cancer standpoint.

      • Alcohol ingestion is medicinal in antifreeze or methanol poisoning.

Questions

  • Importance of a good diet for chronic drinkers

    • Why is it important?

  • Recommended foods for chronic drinkers

    • What should be deez nuts