Chapter 38 week 7

Liver Anatomy and Physiology Review

• Liver is the body's factory with numerous functions.
• Secretory Function:
  • Produces bile from cholesterol.
  • Conjugates bilirubin.
• Excretes exogenous dyes to help eliminate them from the body.
• Metabolic Function:
  • Involved in the metabolism of carbohydrates, fats, proteins, minerals, and vitamins.
• Production:
  • Produces albumin (important protein).
  • Produces alpha and beta globulins.
  • Produces clotting factors.
  • Produces transport proteins.
• Detoxification of substances.
• Storage Function: Stores B12 and vitamin A.

Liver Blood Supply and Metabolism

• Dual blood supply:
  • Portal blood from the pancreas, small and large intestines, spleen, and esophagus.
  • Hepatic artery.
• Portal vein carries blood from the GI tract to the liver for metabolism.
• Hepatic vein carries blood from the liver to the inferior vena cava, then to the right atrium.
• Nutrients absorbed from the intestine are metabolized in the liver before entering general circulation.

Categories of Liver Disease

• Hepatocellular Failure:
  • Failure inside the liver cells.
• Portal Hypertension:
  • Increased pressure in the portal vein system.

Consequences of Hepatocellular Failure

• Reversal of normal liver functions due to hepatocyte dysfunction.
  • Impaired bilirubin conjugation leading to jaundice.
  • Reduced production of clotting factors.
  • Decreased albumin production leading to hypoalbuminemia.
  • Decreased vitamin D and K levels, leading to:
    • Osteomalacia (insufficient calcium in bones) due to vitamin D deficiency.
    • Poor clotting factor production due to vitamin K deficiency.
    • Feminization due to impaired steroid hormone processing; increased estrogen levels occur.

Portal Hypertension and its Implications

• Backup of blood in the GI tract due to obstruction of flow to the liver.
  • GI congestion.
  • Development of esophageal or gastric varices.
    • Esophageal varices: dilated blood vessels in the esophagus.
    • Gastric varices: dilated blood vessels in the stomach.
  • Hemorrhoids: congestion in the rectal veins.
  • Splenomegaly: enlargement of the spleen.
  • Ascites: accumulation of fluid in the peritoneal cavity.

Clinical Manifestations of Liver Disease

• Jaundice: due to lack of bilirubin conjugation.
• Muscle wasting: liver's inability to process amino acids.
• Ascites:
  • Portal vein hypertension.
  • Low colloid osmotic pressure (low protein in the blood).
• Steatorrhea:
  • Poor fat absorption due to lack of bile production.
  • Deficiency in fat-soluble vitamins (A, D, E, K).
• Dyslipidemia and hypertriglyceridemia: due to impaired lipoprotein processing.
• Abnormalities in glucose storage and release lead to hyperglycemia or hypoglycemia.
• Decreased production of clotting factors leads to excessive bleeding.
• Edema: due to low oncotic pressure from reduced albumin production.
• Hormonal imbalances:
  • In men: gynecomastia, impotence, and testicular atrophy.
  • In women: irregular menses.
  • Palmar erythema and spider telangiectasia (distended blood vessels that look like spider webs).
• Impaired detoxification leads to increased levels of toxins and drugs in the body.
• Ammonia accumulation:
  • Liver cannot convert ammonia to urea.
  • Ammonia crosses the blood-brain barrier, causing brain injury and encephalopathy.

Bilirubin Metabolism

• Normal process:
  • Hemoglobin is broken down into heme and globin.
    • Globin becomes amino acids.
    • Heme becomes iron and porphyrin.
    • Porphyrin is converted to biliverdin, then to bilirubin (unconjugated bilirubin).
  • Unconjugated bilirubin is not water-soluble and binds to albumin for transport to the liver.
  • In the liver, bilirubin is conjugated (made water-soluble) by binding glucuronic acid.
  • Conjugated bilirubin is excreted in bile into the intestine.
  • In the intestine, bacteria convert bilirubin to urobilinogen.
    • Urobilinogen gives feces its brownish color.
  • Some urobilinogen is reabsorbed and enters the intrahepatic cycle (portal system), where the liver processes it back to bilirubin.
  • A small amount of urobilinogen is excreted in urine, giving it a yellowish color.
• Jaundice: Accumulation of bilirubin due to dysfunction anywhere along the bilirubin metabolism pathway.

Types of Jaundice

• Prehepatic:
  • Excessive hemolysis, ineffective erythropoiesis, or hematoma reabsorption leads to increased unconjugated bilirubin.
• Hepatic:
  • Transport protein deficiency (e.g., Gilbert's syndrome).
  • Immature UDPGT enzyme (e.g., in newborns) resulting in low conversion to conjugated bilirubin, causing increased unconjugated bilirubin.
  • Genetic mutations affecting the enzyme UDPGT, leading to high unconjugated bilirubin.
  • Problem with transport protein moving conjugated bilirubin into bile, leading to increased conjugated bilirubin.
• Posthepatic:
  • Obstruction of the gallbladder or biliary tree leads to increased conjugated bilirubin.

Patient Evaluation for Liver Disorders

• Complete History: Provides information about type of bilirubin disorder.
• Physical Exam:
  • Signs like telangiectasia, ascites, palmar erythema, gynecomastia, and testicular atrophy suggest hepatic jaundice.
  • Possible causes include alcohol consumption, drug reactions, or liver cancer.
• Blood Tests:
  • AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase):
    • ALT: more specific to the liver; increased levels suggest liver-specific diseases like viral hepatitis or hepatocellular cancer.
    • AST: found in the liver, pancreas, muscle, and brain; increased levels suggest alcohol-related issues.
  • Alkaline Phosphatase (ALP):
    • Increased ALP suggests cholestasis (bile congestion) due to intrahepatic or extrahepatic duct blockage.
• Liver Biopsy: To identify the specific disease.
• Imaging: Ultrasound, CT, and MRI.

Portal Hypertension

• Obstruction of blood flow in the portal vein leads to congestion of blood to the intestines, stomach, esophagus, and rectum.
• Caused by fibrosis due to cirrhosis or cancer.
• Sluggish blood flow increases pressure and causes a backup.
• Consequences:
  • Anorexia.
  • Varices (esophageal, gastric, anorectal).
  • Ascites.

Esophageal Varices

• Small submucosal veins in the esophagus drain into the azygos vein or portal vein.
• Obstruction of the portal vein causes backflow into the submucosal vein, leading to dilation (varices).
• Varices are located in the proximal stomach and distal esophagus.
• Thin walls of varices can rupture easily, leading to life-threatening GI bleeding (gastroesophageal varices), often painless.
• Bleeding Risk: determined by the size of the varice.
  • If bleeding occurs, there's a 50% risk of death without treatment.
  • Greatest risk for rebleeding is in the first three days after initial bleeding (due to decreased clotting factors). Hepatocytes can't produce clotting factors due to fibrosis blocking them from working correctly.
• Clinical Manifestations:
  • Hematemesis: vomiting blood.
  • Melena: blood in stool (dark feces).
  • Bright red rectal bleeding: due to hemorrhoids.
  • Anemia. Depending on blood loss leads to hypovolemic shock.
• Treatment:
  • Resuscitate with IV fluids (normal saline).
  • Correct coagulopathy with vitamin K, fresh frozen plasma, and platelets.
  • Vasopressin and nitroglycerin:
    • Vasopressin analog: octreotide acetate (better due to fewer cardiac side effects).
  • Metoclopramide, H2 blockers, and PPI injections.
  • Beta blockers.
  • Antibiotic therapy (prophylactic effect).
• Emergency Treatment:
  • Esophageal gastro duodenoscopy: inject sclerosis solution into the virus and it stimulates thromboses, stopping bleeding.
  • Ligation of esophageal varices to stop bleeding by applying a strong external pressure.
• Balloon tamponade (Sengstaken-Blakemore tube).
• Transjugular Intrahepatic Portosystemic Shunt (TIPS).
• Liver transplantation.
• Esophagectomy: removing part of the esophagus with varices (high risk and side effects).

Hepatic Encephalopathy

• Neuropsychiatric syndrome caused by excess ammonia in the blood.
• Normally, the liver converts ammonia to urea, which is excreted by the kidneys.
• In liver disease conversion impaired, leading to excess ammonia that can cross the blood-brain barrier and damage the brain.
• Two contributing factors:
  • Liver function impairment.
  • Increased protein metabolism.
• Increased ammonia results from either impaired hepatocyte function or increasing protein metabolism.
• Clinical Manifestation:
  • Dementia.
  • Psychotic symptoms.
  • Spastic myelopathy.
  • Asterixis (liver flap): tremor when extending wrist; classic sign.
  • Increased ammonia levels are a key indicator.
• Treatment:
  • Address precipitating factors (hemorrhage, protein consumption, liver function).
  • Restrict dietary protein to 60 g or less, compensating with carbohydrates.
  • Administer vitamins important in metabolism.
  • High fiber diet. Give fiber to increase peristaltic in GI to help produce a normal bowel movement.
  • Administer amoxicillin and rifaximin to break down gut flora to avoid protein break down.
  • Administer lactulose to eliminate nitrogen waste from stool by creating a toxic hyperosmotic medium that ammonia prefer.

Ascites

• Fluid accumulation in the peritoneal cavity.
• Two underlying causes:
  • Portal hypertension.
  • Low albumin and colloid osmotic pressure.
• Diagnosis: Paracentesis to examine the fluid for protein, albumin, bacteria, and cells.
• Treatment:
  • Restrict sodium intake because sodium and water are body buddies and travel together. Too much sodium = Too much water.
  • Administer diuretics.
  • Create shunts to redirect fluid back to the vena cava.

Viral Hepatitis

• Inflammation of liver parenchyma, caused mainly by hepatitis viruses (A, B, C, D, E).
• Can also be caused by cytomegalovirus and Epstein-Barr virus.
• Hepatitis A (HAV):
  • Transmission: Fecal-oral route.
  • Virus: RNA virus.
  • Incubation period: 3-5 weeks (range 2-7 weeks).
  • Symptoms: Jaundice, right upper quadrant pain, malaise, anorexia, low-grade fever.
  • Therapy: Self-limited, lifetime immunity achieved
  • Testing Anti-HAV to find prior infections and test IgG and IgM for infections too
  • Treatment: Supportive (rest, nutrition, diet, avoid alcohol, acetaminophen, and hepatotoxin).
  • Prevention: Wash hands, clean laundry carefully, and immunization through vaccination.
• Hepatitis B (HBV):
  • Virus: Double-stranded DNA virus.
  • Transmission: Parenteral contact (infected blood, blood products), sexual contact, needles.
  • Risk factors: Prenatal, healthcare setting, 3 percent if patient undergoes transfusion, dialysis 1% for accupuncture
  • Incubation period: 3-4 months (range 2-6 months).
  • Symptoms: Asymptomatic or pain in joints, rashes, angioedema, or jaundice.
  • Testing serologically.
    • Hep B surface antigen is for telling of virus and is first to be positive one with acute marker infection. positive for first antigens in infection.
    • IgM and IgG are for core antibodies with IgM happening with acute patients
    • IGg of antibody surface means it's a sigh of victory meaning the battle against the virus.
    • Ever time E antigen envelope present its coutagious
  • Treatment:Isolate in case of being contagious
    • Interferon alpha
    • 
      New: lamivudine, terbudine, adofirtenofir, entecav (treament of choice.
      High risk vaccinations are a good prevention mechanism.
• Hepatitis C (HCV):
  • Transmitted: with blood via needles or blood transfusion.
  • Acute v chronic one is most important acute can come chronic fast
  • The supportive medication is PKL aided interferon alfa
• Hepatitis D(HDV: Need someone with hepatitis B as well which the virus relies on it.

Chronic Active Hepatitis

• Inflammatory reaction lasting more than 6 months.
• Destroys hepatocytes and damages portal trial and lobules.
• Can progress to cirrhosis, results with fatigue, malaise, Nausea vomiting and a big liver can occur. You can test serology to find this.
• Diagnosis: biopsy only to know how to grade and stage it.

Cirrhosis

• Irreversible, late-stage liver disease from severe or chronic injuries.
• Causes: Severe acute hepatitis, chronic hepatitis (B, C), toxic hepatitis, metal storage diseases (hemochromatosis), alcoholism.
• The liver's surface is smooth, which gets a chronic inflammation and is then a collagen fibrosis around it.
• Fibrotic liver and nodular. This causes change in blood flow.

Other liver diseases

• Biliary Cirrhosis
  • Caused by continuous and ongoing inflammation from internal bile ducts.
    Diagnosis can come confused with what is going on. And blood test also help this way too so the best is biopsy
    Give ursodiol and methotrexate (colchicine)
    is help with the issue
• Fatty Liver
  • Two types alcoholic and nonalcoholic fatty liver
  • Alcoholics burn out the liver cell
• Mild symptoms of portal hypertensions for someone with an alcohol issue Hepatomegaly.
  • So they have defects with getting proper absorption in fat metabolism
  • Abstience from alcohol also can give better nuitrition to patient, while nonalcoholic steatohepatitis occurs with too much from people who are obese
  • Not treated by them so 15 can get cyrotic issues
• Toxic Liver Disorder: Acetemophrnine can get very toxic and harm u a lot it can happen just not helping it and you body may use an enzyme that gets to free radicla, also using glutithoine tranfers is important too as well to get that electrons stable! Give accetlyicsteine for them to help produce a high number and prevent free radicl destroying the patient and also get free radicals out.

Health Complicatiosn

• Hepatocellular carcinoma also known as a Hepatoma. People are very high risk and can have the fulminant of it but only when having B and C. Some classic signs:
  • This comes along the other issues hepatomegly and a bit of abdomeal pain and nausea all comes from it
  • Increase RBC and increase glygocen. Very elevated alkaline
    Alpha photoproten is very important for needle biopsy for that since normal biopsy is too aggressive.