Hepatic

Hepatic Overview

  • The liver is a vital organ, continuously processing blood and performing numerous functions that are essential for maintaining homeostasis and overall health.

  • This lecture focuses on liver function, failure, and its impact on the circulatory system.

Liver Function on a Good Day

  • The liver receives blood from two primary sources:

    • Arterial Supply: Oxygenated blood comes from the left ventricle of the heart via the aorta, providing oxygen necessary for organ and cell metabolism.

    • Venous Supply: Oxygen-poor but nutrient-rich blood is supplied from the digestive tract, stomach, intestines, spleen, and pancreas through the portal vein. This is unique because the liver is one of the few organs that processes venous blood before it returns to the heart.

  • The liver performs several crucial functions:

    • Metabolism:

    • Pharmacokinetics: Metabolizes drugs and pharmaceuticals.

    • Carbohydrate Metabolism: Stores glycogen and converts it to glucose as needed (glycogenolysis) or produces glucose from non-carbohydrate sources (gluconeogenesis).

    • Lipid and Protein Metabolism: Converts lipids and proteins into glucose.

    • Synthesis of Albumin: Essential for maintaining oncotic pressure in the vasculature.

      • Albumin affects drug binding and regulates fluid movement into blood vessels. Low albumin can lead to edema.

    • Clotting Factors: Produces proteins that are crucial for blood coagulation, preventing excessive bleeding and blood clots.

    • Detoxification:

    • The liver detoxifies blood by breaking down toxins, with ammonia being a major concern. Ammonia is converted into urea, which is excreted by the kidneys.

    • Storage:

    • Stores vitamins, minerals, and glycogen.

    • Production of Bile: Bile acids are synthesized to help digest fats in the digestive system.

Detecting Liver Failure

  • The liver function tests (LFTs) help identify liver dysfunction:

    • AST (Aspartate Aminotransferase): Elevated in liver cell injury but also seen in other conditions (not specific to liver).

    • ALT (Alanine Aminotransferase): More specific to liver damage; elevation indicates liver disease.

    • ALP (Alkaline Phosphatase) and GGT (Gamma-Glutamyl Transferase): Markers for biliary function. Elevation indicates biliary obstruction or dysfunction.

    • Bilirubin: Increased levels may indicate liver dysfunction or biliary obstruction.

    • Albumin Levels: Low levels indicate decreased synthetic function of the liver.

    • PT/INR (Prothrombin Time/International Normalized Ratio): Prolonged time indicates reduced clotting factor synthesis.

    • Ammonia Levels: Increased levels are linked to hepatic encephalopathy (confusion and altered mental status due to ammonia toxicity).

Consequences of Liver Failure on Circulatory System

  • Portal Hypertension: Blood flow obstruction leads to increased pressure in the portal vein, causing backflow effects:

    • Ascites: Fluid accumulation in the abdominal cavity (peritoneal space).

    • Splenomegaly: Enlargement of the spleen due to increased pressure, resulting in sequestration of blood products like platelets (thrombocytopenia).

    • Development of varices: Enlarged and fragile veins in the esophagus and stomach, which risk rupture and lead to serious bleeding.

    • Caput Medusa: Visible engorged veins above the abdomen due to increased venous pressure.

Conditions Leading to Liver Failure

  • Liver injuries can stem from:

    • Viral Infections: Such as hepatitis C.

    • Alcohol Abuse: Toxic to liver cells leading to fatty liver disease and scarring.

    • Non-alcoholic Fatty Liver Disease (NAFLD): Fat accumulation due to metabolic issues or diet.

    • Autoimmune Conditions: The body's immune system attacks liver cells leading to inflammation and scarring.

  • Most damaging processes lead to cirrhosis: fibrosis of the liver resulting from repeated injuries.

Pathophysiology of Ascites and Spontaneous Bacterial Peritonitis (SBP)

  • Ascites results from:

    • Portal hypertension (backed-up blood).

    • Low albumin synthesis.

    • Kidney dysfunction contributing to sodium retention.

  • Infections can occur in the ascitic fluid leading to SBP, which is a medical emergency requiring antibiotics.

  • Signs of SBP include fever, worsening abdominal pain, and altered encephalopathy.

Managing Hepatic Encephalopathy (HE)

  • HE results from ammonia toxicity when the liver fails to convert ammonia into urea, allowing it to cross the blood-brain barrier:

    • Symptoms begin as confusion and can escalate to coma if untreated.

    • Signs include asterixis (flapping tremors of the hands).

    • Monitor for precipitating factors: GI bleed, dehydration, infection, certain medications.

  • Management Strategies:

    • Lactulose: Binds ammonia and enhances its expulsion via stool (osmotic laxative).

    • Rifaximin: Non-absorbable antibiotic reducing intestinal bacterial colonization and thus lowering ammonia production.

Management of Portal Hypertension and Varices

  • Treatment aims at reducing portal vein pressure to prevent variceal rupture:

    • Beta-Blockers: Such as propranolol reduce heart rate and contractility, leading to lower systemic vascular resistance.

    • Octreotide: Vasoconstrictor that decreases blood flow to the portal system, helping control acute variceal bleeding.

Medications in Hepatic Dysfunction

  • Careful monitoring required, especially for drug interactions and adverse effects:

    • Prevent hypotension when combining medications that lower blood pressure.

    • Monitor for bradycardia and supervise fluid and electrolyte balance, particularly potassium.

    • Educate patients on potential side effects and when to seek help for symptoms of GI bleeding or changes in mental status.