Liver

Question 1

The _____ controls the flow of bile into the duodenum.

Answer 1

Sphincter of Oddi

Question 2

The liver receives about __% of the cardiac output (or ____ L/min).

Answer 2

30%; 1.5 L/min

Question 3

The portal vein provides _1__ of hepatic blood flow, and the hepatic artery supplies the remaining _2__. Each vessel contributes _3__% of the liver’s oxygen supply.

Answer 3

1. 70% (PV) (Portal veins are partially desaturated flow from the intestines)
2. 30% (HA)
3. 50% of oxygen supply

Question 4

T or F: Flow through the portal vein is autoregulated. So what?

Answer 4

(False) Flow through the portal vein is not autoregulated, making it susceptible to hypotension. When this happens, the hepatic arterial buffer response (through the washout of vasodilators such as adenosine) compensates by increasing flow through the hepatic artery. Liver disease and volatile anesthetics disrupt the hepatic arterial buffer response,
which predisposes the liver to ischemia.

Question 5

Common bedside tests of liver function can be divided into those that assess what four things?

Answer 5

Synthetic function
Hepatocellular integrity
Hepatic clearance
Biliary duct obstruction

Question 6

Synthetic function is commonly assessed by what two things? Which is a better indicator of acute injury and which is better for chronic injury?

Answer 6

Prothrombin time (acute)
Albumin (chronic impairment)

Question 7

The PT is very sensitive for acute injury, because factors ___ and ___ have short half-lives that are less than 24 hours.

Answer 7

5 and 7

Question 8

Albumin is a better measure of chronic liver impairment, because its half-life is ___.

A serum albumin concentration less than ___ suggests chronic liver dysfunction.

Answer 8

21- days

3 g/dl

Question 9

Hepatocellular integrity is measured by? Give two examples.

Answer 9

Serum aminotransferases such as:
Alanine aminotransferase (ALT - found in the liver)
Aspartate aminotransferase (AST - found in liver, eart, skeletal muscle, kidney, brain, RBCs).

Aminotranseases catbolize amino acids fr entry into the citric acid cycle.

Question 10

T or F: Enzymes spike in cases of extensive hepatocellular injury including acute viral hepatitis, ischemic hepatitis, and acute drug- or toxin-induced liver injury. These conditions are generally considered contraindications to elective surgery.

Answer 10

True

Keep in mind that serum aminotransferases can rise from other conditions that affect the liver such as systemic infection, heart failure, and cancer.

Question 11

What test helps us assess hepatic clearance?

Answer 11

Serum bilirubin

Question 12

What is the significance of measuring unconjugated vs conjugated bilirubin?

Answer 12

An increased conjugated bilirubin concentration suggests a hepatic or post-hepatic problem.

An elevated unconjugated bilirubin level suggests a pre-hepatic origin such as hemolysis or hematoma reabsorption.

Question 13

What three tests do we use to assess biliary duct obstruction? Which is most sensitive? Least?

Answer 13

Alkaline phosphatase, gamma glutamyl transpeptidase, and 5’-nucleotidase.

Alkaline phosphatase is the least specific indicator of biliary duct obstruction, while 5’-nucleotidase is the most specific.

Question 14

The Child-Turcotte-Pugh and MELD scoring systems predict what?

These systems require knowledge of the patient’s (1), (2), (3), (4), (5).

Answer 14

• The risk of surgery for patients with liver disease.
• International normalized ratio (INR)
  Plasma bilirubin level
  Plasma albumin level
  Degree of encephalopathy
  Volume of ascites

Question 15

What lab tests evaluates the liver’s synthetic function?

Answer 15

INR
Serum albumin
Other serum proteins

Hepatic synthetic function is easily assessed by measurement of plasma albumin and fibrinogen and determination of the prothrombin time or the INR.

Question 16

What lab test evaluates the liver’s excretory function?

Answer 16

Plasma bilirubin levels

Question 17

What lab tests evaluates the liver’s metabolic function?

Answer 17

Blood glucose
Cholesterol
Lipoprotein levels

Question 18

What lab test evaluates bile duct obstruction?

Answer 18

Plasma alkaline phosphatase

Question 19

What lab tests evaluates the hepatocellular injury?

Answer 19

Plasma aspartate aminotransferase
Plasma alanine aminotransferase levels

Question 20

The liver is a unique vital organ because it serves multiple, independent functions each of which is necessary for sustaining life. These include:

1. Synthesis of proteins required for coagulation (3 things) and fluid volume homeostasis (1 thing)
2. Conjugation and excretion of metabolic products (2 things)
3. Carbohydrate metabolism (2 things)
4. Drug metabolism ( 3 things +)
5. Defense from pathogens (1 thing).

Answer 20

1. Fibrinogen, prothrombin, factor VII ; Albumin
2. Bilirubin and ammonia
3. Glycogen storage and glucose release
4. Muscle relaxants, local anesthetics, narcotics, many others
5. Reticuloendothelial cells

Question 21

Patients with liver failure can develop abnormal neurologic function (1); altered cardiovascular performance and hemodynamics; altered metabolism with accumulation of waste products (2); accumulation of extracellular fluid volume (3); and compromised immune and endocrine function.

Some patients are at risk for acute renal failure (4) and altered pulmonary physiology (5) or portopulmonary hypertension [PPH].

Answer 21

1. Encephalopathy
2. Jaundice
3. Ascites
4. Hepatorenal syndrome
5. Hepatopulmonary syndrome [HPS]

Question 22

The branches of the vasculature and bile ducts demarcate the boundaries of the eight liver segments.

The hepatic acinus is the functional unit of the liver. It is elliptical in shape, centering along the vascular anastomoses connecting two portal triads and extending out toward the central hepatic venules.

Portal venule and hepatic arteriolar blood flows from the portal triads to the hepatic venules through the sinusoids (Figure 14-1).

Fibrosis leads to portal hypertension from compression of these blood vessels. Hepatocytes are described as being in zone 1, 2, or 3 based on their distance from the center of the acinus with its nutrient and oxygen supply. Those in zone 3 are at greatest risk of ischemic, viral, and toxic injury as they are more remote from their source of oxygen and nutrients. Zone 3 is the area of the hepatic acinus where bridging fibrosis first occurs following ischemic or metabolic injury.

Answer 22

Question 23

Review Table with Physiologic and Biochemical Functions of the Liver

Answer 23

Question 24

__(1)__ excretion is the final pathway for the hepatic elimination of heme, cholesterol, and drug metabolites cleared from the plasma.

The principal mechanism of hepatic excretion is the conversion of nonpolar, lipid-soluble compounds to polar, water-soluble compounds by means of __(2)__.

Answer 24

1. Bile
2. Conjugation with glucuronic acid

Question 25

Heme molecules are oxidized and eventually conjugated to form __(1)__.

Answer 25

1. Direct bilirubin Approximately 80% of bilirubin is derived from hemoglobin. The remainder comes from other heme molecules, such as those contained by myoglobin and cytochromes. Excretion of conjugated bilirubin at the canaliculi requires energy and is a rate-limited process that occurs against a concentration gradient. Transport failure leads to direct hyperbilirubinemia.

Question 26

Jaundice is more apparent with __(1)__ hyperbilirubinemia because this bilirubin is water soluble and diffuses easily through tissues. Jaundice can be prehepatic (a result of (__2__); hepatocellular (__3__); or cholestatic (__4__).

Answer 26

1. Conjugated 2. Hemolysis 3. Metabolic, toxic, viral, alcoholic, cirrhotic 4. Sex hormones, hepatobiliary-pancreatic malignancies, gallstones

Question 27

__(1)__ bilirubin is the primary component of hyperbilirubinemia with prehepatic disease, whereas __(2)__ hyperbilirubinemia is present with cholestatic disease. Both may be elevated with hepatic disease.

Answer 27

1. Unconjugated (indirect) 2. Conjugated (direct)

Question 28

Alcohol is metabolized by --(1)-- to --(2)--. --(3)-- is the rate-limiting step in eliminating (#2 above), but it can be overwhelmed when large amounts of alcohol are ingested. Alcohol can also be metabolized by the microsomal ethanol-oxidizing system, an alcohol-inducible P450 enzyme that also metabolizes acetaminophen.

Answer 28

1. Alcohol dehydrogenase 2. Acetaldehyde 3. Acetaldehyde dehydrogenase ( Acetaldehyde, when it cannot be rapidly eliminated, is toxic to a number of cellular components and can lead to zone 3 hepatic necrosis.)

Question 29

Look over the mechanism of acetaminophen toxicity.

Answer 29

Acetaminophen can be conjugated to a sulfate or a glucuronide prior to excretion. Alternatively, it can be oxidized to highly reactive compounds by P450 mixed-function oxidases. Binding to glutathione inactivates these toxic compounds. When glutathione is depleted, the reactive metabolites bind to hepatocellular macromolecules and cause cell necrosis. P450 enzyme activity is induced by chronic alcohol ingestion. Increased P450 enzyme activity can deplete glutathione and enhance the toxic binding to macromolecules. Acetylcysteine can augment glutathione and prevent hepatic necrosis if given early after the ingestion of a lethal dose of acetaminophen. Fulminant hepatic necrosis and acute liver failure can occur 2–3 days following an acetaminophen overdose. The outcome of acetaminophen-induced hepatic necrosis can be predicted by measuring the plasma level of acetaminophen 4 hours after ingestion. Blood levels greater than 300 μg/mL predict that hepatic necrosis will occur. Blood levels less than 120 μg/mL usually do not result in hepatic necrosis.

Question 30

In acute liver failure, why are plasma proteins not the best to use to determine severity of disease? What is a better indicator?

Answer 30

Plasma protein levels decrease late in the time course of the disease because of their long half-lives (albumin = 22 days). Factor VII, however, has a short half-life (approximately 4-6 hours) and is a better index of hepatocellular synthetic function in the face of acute hepatocellular injury following transplantation. Serum albumin and the prothrombin time are the standard tests of synthetic function and are used in the algorithm establishing the Child-Pugh score.

Question 31

The best laboratory tests of hepatic excretion are serum levels of --(1)--. These lab values are also used in the determination of the Child-Pugh score.

Answer 31

1. Indirect and direct bilirubin Although most forms of liver disease will eventually produce an elevation of bilirubin, it is most common with biliary obstruction or secondary autoimmune biliary disease.

Question 32

With any form of biliary obstruction, --(1)--, which is normally excreted in bile, leaks into the systemic circulation. As a result, patients with bile duct obstruction will develop elevated plasma levels of this before they develop hyperbilirubinemia.

Answer 32

1. Alkaline phosphatase

Question 33

Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic --(1)--. Elevated serum levels indicate --(2)-- from a variety of causes, including viral infection, alcohol abuse, and obesity. The highest elevations (approximately 50 times normal values) of the transaminases occur with ischemic or toxic liver injury and acute viral hepatitis. Gamma-glutamyl transpeptidase (γ-GT) and lactate dehydrogenase are enzymes that can be elevated in both hepatocellular injury and bile duct obstruction.

Answer 33

1. Mitochondrial enzymes 2. Hepatocellular injury The serum liver enzyme response to hepatocellular injury can be confusing because elevations occur in the early phase of injury. Decreasing enzyme levels may indicate either recovery or worsening to severe, irretrievable injury.

Question 34

Encephalopahy: Because encephalopathy can progress rapidly from subclinical findings to overt coma, it should be anticipated in any patient with cirrhosis undergoing surgery. Encephalopathy in chronic liver failure is associated with elevation of plasma --(1)--. 2. How does lactulose work?

Answer 34

1. Ammonia level (The encephalopathy can be improved in the short term by limiting protein in the diet; this will decrease the amount of nitrogenous waste and ammonia produced in the bowel.) 2. Lactulose is a nondigestible disaccharide sugar whose metabolism by gut bacteria increases the acid content of the colon.66 Acidification of the stool traps ammonia as ammonium ion in the gut contents, which facilitates its excretion. A third strategy is to reduce the number of bacteria producing ammonia from protein using an antibiotic such as neomycin.

Question 35

Why should a person with cronic liver disease be considered to have a cardiomyopathy if their cardac index (CI) is normal with cardiac catheterization?

Answer 35

The circulation in chronic liver disease is hyperdynamic and characterized by a markedly increased cardiac index, low systemic vascular resistance, mild tachycardia, a normal-to-increased stroke volume, a high mixed venous oxygen saturation, and a poor oxygen extraction ratio. The differential diagnosis should include ischemic cardiomyopathy, alcoholic cardiomyopathy, and cardiomyopathy secondary to hemochromatosis.

Question 36

Describe the two pulmonary sundromes noted in patients with advaned liver disease.

Answer 36

The first is HPS; the second is PPH. HPS: Portal hypertension can lead to the development of collateral circulation with large veins in the abdominal and chest walls, the mediastinum, stomach, and esophagus. In extreme cases, these venous collaterals can anastomose with pulmonary vessels, leading to portopulmonary shunting. This can produce a state of high blood volume, high blood flow with intrapulmonary shunts, producing the HPS. On the other hand, PPH is a high-pressure state similar to primary pulmonary hypertension. The right ventricle is often dilated, cyanosis is absent, the right ventricular ejection fraction is low, and systemic hypoxia is rare. These patients may acutely respond to inhaled nitric oxide.

Question 37

Liver