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Liver Disease

Lindsay Higgins

+Anatomy

The Falciform Ligament separates the right and left anatomic lobes.

Blood supply distinguishes the surgical lobes by the bifurcation of the right and left Hepatic Artery and Portal Vein. There are a total of 8 surgical segments.

+Anatomy (cont.)

50-100,000 lobules. Hepatocytes are arranged

cylindrically around a central vein.

4-6 portal tracts (hepatic arterioles, portal venules, bile canaliculi, lymphatics, and nerves) surround each lobule.

+Anatomy (cont.)

The functional unit of the liver is the acinus, with the portal tract in the middle and the central veins in the periphery.

Zone 1 is closest to the portal tract and receives the most O2.

Zone 3 is closest to the central vein, receives the least O2 and is the most susceptible to ischemia.

+Vascular Supply

Blood Flow (30% of cardiac output) 75% Portal Vein 25% Hepatic Artery

Oxygen Supply 55% PORTAL VEIN (O2 saturation is 85%) 45% Hepatic Artery

Hepatic Artery flow is dependent on autoregulation postprandially (not during fasting).

Portal Vein blood flow is dependent on spleen and GI tract flow. Some compensation between Portal Vein and Hepatic Artery

(decrease in flow from one increases flow from the other)

+Sympathetic Input

Hepatic Artery Vasoconstriction

α1 Vasodilation

β2 D1 Cholinergic

Portal Vein Vasoconstriction

α1 Vasodilation

β2

Note: β2 input also stimulates Glycogenolysis and Gluconeogenesis.

+Functions of the Liver: Blood Reservoir Portal Vein pressure is normally 7-10 mm Hg, but the

low resistance of the hepatic sinusoids allows large blood flows/volumes in the portal veins small changes in hepatic venous tone causes large changes in hepatic blood volume

Decrease in CVP (hemorrhage) Decrease in hepatic venous pressure shifts blood from liver into circulation (300 mL)

Increase in CVP (CHF patients) Increase in hepatic venous pressure blood accumulates in the liver (1L)

+Functions of the Liver:Blood Cleansing/Immune Function Kupffer cells lining the sinusoids are part of the

monocyte-macrophage (reticuloendothelial) system. Phagocytosis (colonic bacteria, endotoxin, cellular debris,

viruses proteins, etc.) Processing of antigens Release of proteins, enzymes, cytokines

+Liver Functions:Carbohydrate Metabolism Only the liver (and to some extent the muscle) are able to store

glycogen Insulin enhances glycogenesis. Epinephrine and Glucagon enhance glycogenolysis.

Glycogen stores are depleted after 24 hours of fasting (after that the body is dependent on gluconeogenesis (de novo synthesis of glucose).

Only the liver and kidney can form glucose from lactate, pyruvate, amino acids and glycerol. Gluconeogenesis is vital for the maintenance of a normal blood glucose. Glucocorticoids, Catecholamines, Glucagon, and thyroid hormone

enhance gluconeogenesis. Insulin inhibits gluconeogenesis.

+Liver Function:Carbohydrate Metabolism (cont.) Final products of carbohydrate metabolism are

galactose, glucose, and fructose. All cells turn glucose ATP

Citric Acid Cycle (aerobic) Glycolysis (anaerobic) Phosphogluconate (only in the liver and adipose tissue)

Liver and kidney can turn lactate, pyruvate, amino acids, and glycerol into glucose.

+Liver Function:Fat Metabolism When carbohydrate stores are saturated, the liver

converts the excess carbohydrates (and proteins) into fat (fatty acids), which can be used directly as fuel or stored in the liver or adipose tissue.

Only RBCs and the renal medulla can utilize only glucose (even neurons can switch to fatty acid breakdown products – ketone bodies – after several days of starvation).

+Liver Function:Protein Metabolism The liver performs CRITICAL steps in protein metabolism.

Without this function, death occurs in a matter of days. Deamination of amino acids (converts them to carbs and fats –

“transamination”) Formation of Urea (formed from ammonia) Interconversions between nonessential amino acids Formation of plasma proteins

Nearly all plasma proteins (except for immunoglobulins) Albumin ALL COAGULATION FACTORS (except for Factor VIII and

vWF) Vit K: Factors II, VII, IX, X

Plasma Cholinesterase (pseudocholinesterase)

+Liver Function:Drug Metabolism Most drugs undergo hepatic biotransformation. End products are inactivated or more soluble (more easily

excreted in kidney or by bile) Phase I: via oxidases and P-450

Oxidation Reduction Deamination Sulfoxidation Dealkylation Methylation

Phase II: conjugation

+P-450 Inducers

Queen Barb Steals Phen-Phen and Refuses Greasy Carbs, Chronic Alcohol, and Glucose Quinidine Barbituates/Benzodiazepines St. John’s Wart Phenytoin Rifampin Griseofulvin Carbamazepine Chronic Alcohol Glucocorticoids

+P-450 Inhibitors

Inhibit yourself from drinking alcohol from a KEG. It will make you a SICCO and give you crazy AIDS. Acute Alcohol Ketoconazole Erythromycin (& other Macrolides) Grapefruit Juice Sulfonamides Izoniazid Cimetidine Chloramphenicol Omeprazole SSRI/SNRI Antipsychotics Ritonavir

+Liver Function:Other Metabolic Functions Converts T4 T3 Degradation of Thyroid Hormone, Insulin, Estrogen,

Aldosterone, Cortisol, Glucagon, ADH Storage of Vitamins A, B12, E, D, and K Production of transferrin, haptoglobin, and

ceruloplasmin

+Liver Function:Bile Formation and Excretion Bile is important for absorption of fat and excretion of

bilirubin, cholesterol, and drugs. Hepatocytes secrete bile salts, cholesterol,

phospholipids, conjugated bilirubin into bile canaliculi. Bile salts allow the absorption of fat soluble vitamins

(A, D, E, and K). Vitamin K deficiency manifests as a coagulopathy due to impaired formation of Factors VII, IX, and X.

+Hepatic Synthetic Function Tests Serum Albumin Prothrombin Time Cholesterol Pseudocholinesterase AST/ALT measure hepatocellular integrity rather than

function. Due to the liver’s large functional reserve, cirrhosis

may be present without lab abnormalities.

+Liver Dysfunction

2 types based on lab tests: Parenchymal Disorders Obstructive Disorders

Parenchymal ObstructiveAST Increased Slightly

IncreasedALT Increased Slightly

IncreasedAlbumin Decreased NormalPT Increased IncreasedBilirubin Increased IncreasedAlkaline Phosphatase Slightly

IncreasedIncreased

5-Nucleotidase Slightly Increased

Increased

Glutamyl Transpeptidase Increased Increased

+Albumin

Half life is 2-3 weeks, so may initially be normal with acute liver disease

Normally is 3.5-5.5 g/dL If less than 2.5 g/dL is indicative of:

Chronic Liver Disease Acute Stress Severe Malnutrition Nephrotic Syndrome Protein-Losing Enteropathy

+Prothrombin Time

Evaluates synthetic function Normally 11-14 seconds Half life is 4-6 hours Measures the activity of

Fibringogen Prothrombin Factors V, VII, and X

Prolonged PT (greater than 3-4 seconds or INR 1.5) usually reflects severe liver disease unless Vitamin K deficiency is present

+Effect of Anesthesia on the Liver:Hepatic Blood Flow Hepatic blood flow is decreased

All volatiles decrease portal blood flow in proportion to MAP and CO Most with Halothane Least with Isoflurane

Neuraxial anesthesia decreases blood flow by lowering arterial BP

Controlled positive pressure ventilation and high peak airway pressures decrease hepatic blood flow by decreasing venous return

Decrease liver blood flow: Hypoxemia (via sympathetic stimulation) Surgical procedures near the liver can decrease blood flow 60% Beta blockers, α1 agonists, H2 receptor blockers and vasopressin

Low dose Dopamine may increase liver blood flow

+Effect of Anesthesia on the Liver:Metabolic Functions Stress response from surgery increased

catecholamines, glucagon, and cortisol Mobilization of glucose stores hyperglycemia Mobilization of protein stores negative nitrogen

balance

This can be reduced by regional anesthesia, deep general, or blockade of the sympathetic system.

+Effect of Anesthesia on the Liver:Drug Metabolism Halothane has been reported to inhibit hepatic

metabolism of drugs (phenytoin, warfarin, and ketamine), but this is likely due to the resulting decrease in hepatic blood flow

+Effect of Anesthesia on the Liver:Biliary Function Opioids spasm of the sphincter of Oddi

Incidence (highest to lowest) Fentanyl Morphine Meperidine Butorphanol Nalbuphine

+Effect of Anesthesia on the Liver:Liver Tests Mild postoperative liver dysfunction in healthy people is

not uncommon and it is likely due to decreased hepatic blood flow.

When the results of LFTs are elevated postoperatively, it’s usually due to underlying liver disease or the surgical procedure itself.

Postoperative jaundice is most commonly from overproduction of bilirubin due to resorption of a large hematoma or red cell breakdown following a transfusion

+Halogenated Anesthetics

“Halothane Hepatitis” Due to hepatotoxic intermediates? Immune

hypersensitivity? Consider Viral hepatitis, CMV, EBV, and Herpes Incidence of fatal hepatic necrosis is 1:35,000 Risk factors: obesity, middle age, female, repeat

exposure to halothane (esp within 28 days)

Also with Methoxyflurane, Enflurane, and Isoflurane

+Acute Hepatitis

Viral Hepatitis A, B, C, D, or E, EBV, herpes, CMV, or

Coxsackieviruses Chronic hepatitis: 3-10% with Hep B and 50% with Hep C

Drug Induced Alcoholic is the most common Acetaminophen (25 grams is usually fatal dose) Halothane

+Acute Hepatitis:Preoperative Evaluation Patients with acute hepatitis should have any elective procedure

postponed until the acute phase has resolved (normalized LFTs). Risk of deterioration of hepatic function, encephalopathy, coagulopathy, or

hepatorenal syndrome Acute viral hepatitis: Morbidity 12% and Mortality 10% Alcohol withdrawal: Mortality 50%

BUN, CMP, PT, platelet count, HBsAg

Transaminases don’t correlate with disease severity Persistent elevation of PT after Vitamin K is indicative of severe liver disease Determine the cause and extent of liver disease

Drug exposures Recent Transfusions Prior Anesthetics

May need Vitamin K or FFP to correct coagulopathy

+Acute Hepatitis:Intraoperative Considerations Avoid factors that are detrimental to the liver Avoid factors that are known to decrease blood

flow to the liver (hypotension, excessive sympathetic activation, high mean airway pressures)

Inhalational agents are preferred to IV because they don’t require metabolism by the liver Isoflurane

Standard doses of induction agents can be used because termination of their effect is due to redistribution not metabolism

+Chronic Hepatitis

Elevated transaminases for 6 months (note that transaminases correlate poorly with severity of disease)

3 Types Chronic Persistent Hepatitis – resolves Chronic Lobular Hepatitis – resolves but has recurrent

exacerbations Chronic Active Hepatitis – destruction of normal cellular

architecture on biopsy 20-50% have Cirrhosis Most commonly due to Hepatitis B and C

+Chronic Hepatitis:Intraoperative Considerations Chronic Persistent Hepatitis and Chronic Lobular

Hepatitis is treated like acute hepatitis Chronic Active Hepatitis is treated like Cirrhosis

+Cirrhosis

Most common cause in the US is alcohol Hepatocyte necrosis is followed by fibrosis and nodular

regeneration Distortion of the liver’s normal cellular and vascular

structure leads to portal hypertension Impairment of synthetic functions lead to multisystem

disease

Clinical signs and symptoms often do not correlate well with severity of disease

+Cirrhosis:Possible Complications Variceal hemorrhage from portal hypertension Intractable fluid retention (ascites and hepatorenal syndrome) Hepatic encephalopathy or coma 10% also develop at least one episode of spontaneous

bacterial peritonitis

A few diseases can cause hepatic fibrosis without necrosis: Schistosomiasis Idiopathic Portal Fibrosis Congenital Hepatic Fibrosis Budd Chiari Syndrome (obstruction of the portal vein)

+Cirrhosis:GI Considerations Portal hypertension (greater than 10 mm Hg) leads to extensive portal-

systemic venous collateral channels Gastroesophageal major source of morbidity and mortality Hemorrhoidal Periumbilical Retroperitoneal

Treatment of variceal bleed: Reduce the rate of blood loss

Vasopressin Somatostatin Propranolol

Fluids/Blood Products Balloon Tamponade Endoscopic Sclerosis

TIPS may decrease portal hypertension but increases risk of encephalopathy

+Cirrhosis:Hematological Considerations Anemia – due to blood loss increased destruction, bone

marrow suppression, nutritional deficiencies Splenomegally

Thrombocytopenia Leukopenia

Decreased synthesis of coagulation factors coagulopathy

Excessive blood transfusions can increase nitrogen load and worsen encephalopathy

Consider platelet transfusions if less than 100,000

+Cirrhosis:Circulatory Considerations Hyperdynamic state Generalized peripheral vasodilation AV shunting + decreased viscosity 2/2 anemia =

increased CO Cirrhotic Cardiomyopathy: CO is dependent on higher

than normal filling pressures and below normal SVR Intravascularly depleted

+Cirrhosis:Respiratory Considerations Hyperventilation respiratory alkalosis Hypoxemia due to left-right shunting (up to 40% of CO)

Pulmonary AV shunts V/Q mismatching

Elevation of the diaphragm from ascites decreases lung volumes, especially FRC and predisposes to atelectasis

Ascites causes a restrictive effect Consider paracentesis if severe ascites

+Cirrhosis:Renal Considerations Ascites

Portal hypertension increases hydrostatic pressure Hypoalbuminemia decreases oncotic pressure Renal sodium and water retention due to relative hypovolemia and secondary

hyperaldosteronism

Edema Electrolyte Disturbances: hyponatremia and hypokalemia Hepatorenal Syndrome: Usually follows GI bleeding, aggressive duresis, sepsis

or surgery. Progressive Oliguria Sodium retention Azotemia Ascites Very high mortality Treatment is supportive; usually unsuccessful unless liver transplantation

+Cirrhosis:CNS Considerations Hepatic Encephalopathy

AMS Fluctuating CNS signs: asterixis, hyperreflexia, inverted plantar reflex EEG changes: symmetric high voltage, slow wave activity Increased ICP (some)

Related to the amount of hepatic damage and the amount of blood shunted away from the liver directly into systemic circulation

Toxins: Ammonia, Mercaptans, short chain fatty acids, phenols Increased permeability of BBB Precipitate encephalopathy: GI bleeding, increased dietary protein, hypokalemic

alkalosis (vomiting or diuresis), infections Treat aggressively

Lactulose – osmotic laxative and inhibits GI bacterial ammonia production Neomycin – inhibits GI bacterial ammonia production

+Cirrhosis:Intraoperative Considerations Drug Responses

Increased Vd (expanded ECF): Need higher loading doses Changes in CNS sensitivity Decreased protein binding Decreased drug metabolism Decreased drug elimination

Anesthetic Technique Barbituate or Propofol followed by Isoflurane (avoid

Halothane) Opioid supplementation (caution b/c decreased metabolism) Cisatricurium RSI: Ketamine or Etomidate with SCh

+Cirrhosis:Intraoperative Considerations Monitoring

Aline May require PEEP (if intrapulmonary shunts) CVP or Pulmonary Artery Catheter (monitor volume status) Follow UOP closely (mannitol) Preop, usually are sodium restricted, but intraop

preservation of intravascular volume is the priority Following the removal of large amounts of ascites often

requires subsequent colloid replacement to prevent hypotension and renal failure

Blood transfusions citrate toxicity (normally metabolized by the liver) hypocalcemia