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Liver Disease
Lindsay Higgins
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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.
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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.
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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.
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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)
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Sympathetic Input

Hepatic Artery

Vasoconstriction



Portal Vein

α1
Vasodilation

β2

D1

Cholinergic
Vasoconstriction


α1
Vasodilation

β2
Note: β2 input also stimulates Glycogenolysis and Gluconeogenesis.
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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)
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Functions of the Liver:
Blood Cleansing/Immune Function

Kupffer cells lining the sinusoids are part of the monocytemacrophage (reticuloendothelial) system.

Phagocytosis (colonic bacteria, endotoxin, cellular debris, viruses
proteins, etc.)

Processing of antigens

Release of proteins, enzymes, cytokines
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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.
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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.
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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).
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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)
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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
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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
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P-450 Inhibitors

Inhibit yourself from drinking alcohol from a KEG. It will make
you a SICCO and give you crazy AIDS.

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
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Acute Alcohol
Ketoconazole
Erythromycin (& other Macrolides)
Grapefruit Juice
Sulfonamides
Izoniazid
Cimetidine
Chloramphenicol
Omeprazole
SSRI/SNRI
Antipsychotics
Ritonavir
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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
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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.
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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.
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Liver Dysfunction

2 types based on lab tests:

Parenchymal Disorders

Obstructive Disorders
Parenchymal
Obstructive
AST
Increased
Slightly Increased
ALT
Increased
Slightly Increased
Albumin
Decreased
Normal
PT
Increased
Increased
Bilirubin
Increased
Increased
Alkaline Phosphatase
Slightly Increased
Increased
5-Nucleotidase
Slightly Increased
Increased
Glutamyl Transpeptidase
Increased
Increased
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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
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Protein-Losing Enteropathy
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Prothrombin Time

Evaluates synthetic function

Normally 11-14 seconds
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Half life is 4-6 hours

Measures the activity of
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


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
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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
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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.
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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
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Effect of Anesthesia on the Liver:
Biliary Function

Opioids  spasm of the sphincter of Oddi

Incidence (highest to lowest)

Fentanyl
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Morphine
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Meperidine
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Butorphanol

Nalbuphine
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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
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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
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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
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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
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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
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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
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Chronic Hepatitis:
Intraoperative Considerations

Chronic Persistent Hepatitis and Chronic Lobular Hepatitis is
treated like acute hepatitis

Chronic Active Hepatitis is treated like Cirrhosis
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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
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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)
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Cirrhosis:
GI Considerations

Portal hypertension (greater than 10 mm Hg) leads to extensive portalsystemic venous collateral channels





Treatment of variceal bleed:





Gastroesophageal  major source of morbidity and mortality
Hemorrhoidal
Periumbilical
Retroperitoneal
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
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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
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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
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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
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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
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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
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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
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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