Apex Unit 10 Liver

Function: Bile is produced by the hepatocytes.
It contains cholesterol and waste products including bilirubin and bile salts.
Half the bile runs directly into the duodenum and the half is stored in the gallbladder which is released in response to a meal.

Flow: Bile produced by hepatocytes drains into the canaliculi and then into the bile ducts.
The bile ducts converge to form the common hepatic duct (CHD).
Also joining the CHD are the cystic duct from the gallbladder and the pancreatic duct
The CHD empties into the duodenum, controlled by the sphincter of Oddi

Biliary obstruction:
Intrahepatic causes: Hepatitis, cirrhosis, TPN, hypoxia, ischemia, drugs including inhaled anesthetics and abx, sepsis.
Extrahepatic causes: Pancreatitis, gallstones, bile duct injury, malignancy, infection and biliary cirrhosis

Cholelithiasis (gallstones) is the most common cause of obstruction.
Physical obstruction causes a predominantly conjugated hyperbilirubinemia – jaundice
Normal serum bilirubin -0.2 – 1.2 mg/dL.
Jaundice may not be recognizable until levels reach 3 mg/dL

Chronic cholestasis, if unrelieved, may lead to cirrhosis.
Vitamin deficiency from malabsorption of fat-soluble vitamins A,D,E,K
In acute cholangitis, stasis can lead to bacteremia, septic shock, death.
Pts who undergo biliary tract sx for obstruction may develop postoperative acute oliguric renal failure from the release of nephrotoxic bile salts, pigments, endotoxins and inflammatory mediators.

3 tests of biliary obstruction
1. 5’-Nucleotidase (0-11 units/L) MOST SPECIFIC
2. Y Glutamyl transpeptidase (0-30 units/L)
3. Alkaline phosphatase (45-115 units/L) not very specific – also found in bone, placenta, tumors

Fun fact: Glucagon is administered during ERCP to relax the biliary sphincter (side effect – N/V)

Subtopic

Acute or Chronic
Most common cause of liver cancer and indication for liver transplant.
Caused by viruses, hepatotoxins, and autoimmune responses

In US, most common cause of hepatitis is from either hepatitis A, B, C, or D virus. Hepatitis E is rare in US
Other viral etiologies-herpes simplex, CMV, Epstein Barr
Viral hepatitis is usually silent for 2 weeks following infection.
Then signs and symptoms include fever, malaise,N/V, jaundice and usually last 2-12 weeks.

Hepatitis A
Incidence-50%
Fecal-oral transmission
Serum markers: Early- IgM, late-IgG
Does not cause cirrhosis or hepatocellular carcinoma
Prophylaxis after exposure- pooled gamma globulin, Hep A vaccine

Hepatitis B
Incidence-35%
Percutaneous or sexual transmission
Serum markers: HBsAG, Anti-HBcAg
Can cause cirrhosis/liver CA in up to 5% of adults and 80-90% of children
Prophylaxis after exposure- Hep B immunoglobulin, Hep B vaccine

Hepatitis C
Incidence-15%
Percutaneous transmission
Serum marker-Anti-HCV 1.5-9 months
Causes cirrhosis, liver CA in up to 75% of cases
Prophylaxis after exposure- Interferon + Ribavirin

Hepatitis D
Co-infection with type B
percutaneous transmission
Serum markers: late-Anti-HDV

Drug Induced Hepatitis
Associated with late onset, usually 2-6 weeks after insult, as long as 6 months.
Clinically indistinguishable from viral hepatitis. Requires lab confirmation.
A lot of hepatotoxic drugs but most important for us is acetaminophen, Halothane, and alcohol.

Chronic hepatitis
Inflammation that exceeds 6 months
Progressive destruction of liver tissue, cirrhosis, liver failure
most common cause is alcoholism folled by Hep C
Dx: increased liver enzymes and bilirubin, hitologic evidence of liver inflammation
S/sx: jaundice, fatigue, thrombocytopenia, glomerulonephritis, neuropathy, arthritis, myocarditis.
Prolonged PT, decreased albumin.

What is Cirrhosis?
-Hepatic cellular death, where healthy hepatic tissue is replaced by nodules and fibrotic tissue-> number of functional hepatocytes are reduced as well as the number of sinusoids.
-As the number of hepatocytes decrease the liver can’t carry out its essential functions.
-The number of blood vessels passing through the liver is reduced, therefore increasing the hepatic vascular resistance (portal hypertension).
-Body creates collateral blood flow to compensate for increased resistance= portosystemic shunts.
-This blood bypasses the liver, drugs and toxins (ammonia) remina in the systemic circulation for a longer period of time.

Scoring systems-> MELD and Child-Pugh Score:
MELD-> model of end-stage liver disease: uses a logarithmic calculation that examines 3 factors of hepatic function: bilirubin, INR and serum creatinine.
-Low risk= <10
-Intermediate risk= 10-15
-High risk= > 15
Child-Pugh Score: examines 5 factors of hepatic function: albumin, PT, bilirubin, ascites, and encephalopathy.
-Class A: 5-6 points-> 10% risk of periop mortality.
-Class B: 7-9 points-> 30% risk of periop mortality.
-Class C: 10-15 points= 80% risk of periop mortality.
-Patient with class A or B optimized- reasonable to proceed with surgery, patient in class C should be medically managed until hepatic function improves.

What’s the TIPS procedure??
-Transjugular intrahepatic portosystemic shunt- bypasses a portion of the hepatic circulation by shunting blood from the portal vein (hepatic inflow vessel) to the hepatic vein (hepatic outflow vessel). Portal pressure is reduced and minimizes back pressure on the splanchnic organs-> thus reduces the likelihood of bleeding from esophageal varices wich reduced the amount of ascites -> temporary treatment for hepatorenal syndrome.
-Hemorrhage is a significant risk during TIPS procedure.

Physiologic changes

1. CV-
A. Hyperdynamic circulation: portosystemic shunt & vasodilator release->
-drops SVR and BP-> dropped CO
-Increased RAAS activiation-> increases blood volume (patient may behave like he is hypovolemic)
-Increased peripheral blood flow (shunting)-> increased SvO2
-Decreased response to vasopressors
-Diastolic dysfunction
B. Portal HTN: increased hepatic vascular resistance-> increased backpressure to proximal organs, esophageal varices-> bleeding, Splenomegaly-> thrombocytopenia

C. Ascites: decreases oncotic pressure and protein binding, increased volume of distribution, and drainage-> leads to hypotension

2. Pulmonary-

A. Restrictive defect: Ascites and/or pulmonary effusion-> decreased compliance and atelectasis
B. Respiratory Alkalosis: Hypoxemia-> compensatory hyperventilation
C. Hepatopulmonary syndrome: pulmonary vasodilation-> intrapulmonary shunt (R to L)-> hypoxemia
D. Portopulmonary hypertension: PAP >25 mmHg in the setting of portal htn

3. CNS-
A.Hepatic encephalopathy: decreased hepatic clearance-> increased ammonia-> cerebral edema-> increased ICP (increased ammonia treated with lactulose, abx, and decreased protein intake.
-Bleeding-> blood reabsorption-> increased nitrogen load-> increased ammonia

4. Autonomic: Increased SNS and Increased RAAS and ANS reflex dysfunction

5. Renal:
A. Renal hypoperfusion-> decreased GFR-> Increased RAAS -> NA and H2O retention (dilutional hyponatremia may occur)
B. Hepatorenal syndrome-> decreased GFR-> renal failure )liver transplant is definitive tx)

6. Hematologic:
A. Anemia: decreased CaO2 d/t hemorrhage, folic acid deficiency, hemolysis, and bone marrow depression
B. Reduced factor production: decreased procoagulants and decreased anticoagulants -> bleeding or clot risk (depends on balance).
C. Thrombocytopenia: decreased thrombopoietin and bone marrow depression -> decreased platelet production. Splenomegaly-> increased platelet consumption.

Impaired liver function reduces prodution--prolonged Sux, and possibly ester LA, DOA

Spleen converts aged hemeglobin (120 days) to unconjugated bilirubin--which is neurotoxic.

The lipophilic bilirubin is transported to liver bound to albumin, where it is conjugated by glucoronic acid

Once conjugated, and made more hydrophilic, it is excreted with bile where it is metabolized by gut bacteria and eliminated via stool

Hyperglycemic induced insulin release stimulates conversion of excess carbohydrates (glucose) to glycogen (glyogenesis) in the liver. Liver impairment reduces glycogen stores and precipitates hypoglycemia

Deamination of amino acids allows conversion to carbohydrates and fats.

Deamination of AAs produces ammonia, which is converted to urea by the liver for renal clearance. Excess ammonia causes hepatic encephalopathy.

Conversion of lipids to energy storage molecules--triglycerides

Energy release via beta-oxidation of fatty acids (used in Krebs cycle)

Synthesizes cholesterol, lipoproteins, phospholipids

Produces all plasma proteins except Immunoglobulins

Albumin--acidic drugs

Alpha-a acid glycoprotein--basic drugs

When liver function is impaired, drugs that typically bind to these proteins will have a higher Vd

Factors II, XII, IX, X are Vitamin K dependent, which is absorbed in the presence of bile in the gut

Anticoagulants--antithromnbin, proteins C,S, and Z (also vitamin K dependent

Fibrinolytics (Plasminogen)

Thrombopoeitin--stimulates platelet production

Subtopic

Early: Tremors and disordered perception ( hallucinations and nightmares)
Late: Increased SNS activity ( Tachycardia, hypertension, dysrhythmias), N/V, insomnia, confusion and agitation.
Treatment: Alcohol, beta blockers, alpha 2 agonists

-Alcoholics are vitamin B1 deficient
-Disulfram is the treatment for alcoholics in recovery

-Occur 2-4 days without alcohol
S/S include grand mal seizures , tachycardia, hypertension or hypotension and combativeness.
Treatment: Diazepines and beta blockers

Subtopic

75% of liver blood flow, 50% of O2 content

Receives venous blood that has passed through the splanchnic circulation.

Portal Perfusion Pressure = Portal Vein Pressure - Hepatic Vein Pressure

25% of liver blood flow, 50% of O2 content

Hepatic Artery Perfusion Pressure = MAP - Hepatic Vein Pressure

*Hepatic Arterial Buffer Response - decrease in portal vein flow is compensated by an increase in hepatic artery flow. mediated by adenosine (potent vasodilator)

GA and Neuraxial can decrease liver blood flow due to decrease in MAP. Induction can decrease by 30-50%!