Chapter 25: Liver Function

Three stages of liver injury due to excessive alcohol consumption

1) Alcoholic fatty liver 2) Alcoholic hepatitis 3) Alcoholic cirrhosis

Liver blood supply

1) Hepatic artery - 25% 2)Portal vein - 75%

How are cancers of the liver classified?

1) Location: Primary or metastatic 2) Severity: Benign or malignant

Bilirubin specimen collection and storage

1) May be performed on serum (preferred) or plasma 2) Fasting sample is preferred; hemolyzed should be avoided 3) specimen sensitive to light and should be protected after collection and during transport

characteristics of Reye's Syndrome

1) Noninflammatory encephalopathy 2) Fatty degeneration of liver 3) Clinical presentation of profuse vomiting 4) Neurologic impairment

Portal triad

1) Portal vein 2) Hepatic artery 3)Common bile duct

Three fractions of bilirubin

1) conjugated - direct 2) unconjugated - indirect 3) delta - bound to albumin

four major functions of the liver

1) excretion/ secretion 2) metabolism 3) detoxification 4. storage

Malignant liver tumors

1) hepatocellular carcinoma ( also known as hepatocarcinoma and hepatoma) 2) bile duct carcinoma

two major cell types of the liver

1) hepatocytes 2) Kupffer cells

Tests measuring hepatic synthetic ability

1) serum albumin 2) prothrombin time

Benign liver tumors

1. hepatocellular adenoma 2. hemangiomas

Liver weight

1.2 to 1.5 kg in healthy adult

How much bilirubin does the body produce per day?

200 to 300 mg

Bilirubin reference range

Adult ranges: 1. Total bilirubin: 0.2 - 1.0 mg/dL 2. Conjugated bilirubin: 0.0-0.2 mg/dL 3. Unconjugated bilirubin: 0.2 - 0.8 mg/dL

most severe stage of liver injury; poor prognosis

Alcoholic cirrhosis

mild stage of liver injury; recovery with removal of drug

Alcoholic fatty liver

stage of liver injury with evidence of liver damage

Alcoholic hepatitis

Where did the commonly used methods for measuring bilirubin stem from?

All commonly used methods for measuring bilirubin stem from technique described by Malloy and Evelyn in 1937.

Enzymes used to assess liver function

Aminotransferases 1. Aspartate aminotransferase (AST) 2. Alanine aminotransferase (ALT) Phosphatases 1. Alkaline phosphatase 2. 5'-Nucleotidase 3. Gamma-glutamyltransferase 4. Lactate dehydrogenase

Made up of bile acids or salts, bile pigments, cholesterol.

Bile

small spaces between hepatocytes that form intrahepatic ducts where excretory products of cell can drain

Bile canaliculi

Principal pigment in bile, derived from breakdown of red blood cells; most is eliminated in feces, some in urine.

Bilirubin

Based on reaction of bilirubin with a diazotized sulfanilic acid solution with a 50% methanol solution as an accelerator; Also quantified by bilirubinometry in neonatal population.

Bilirubin Analysis

How much bile does the body produce and excrete?

Body produces 3 L of bile per day and excretes 1 L.

Maintains stable glucose concentrations by storing it as glycogen; Degrading glycogen when needed by body.

Carbohydrate synthesis

1) Condition in which scar tissue replaces healthy liver tissue. 2) Scar tissue blocks blood flow and prevents proper functioning. Commonly caused by chronic alcoholism and hepatitis C infection. 3) Also: chronic Hep B and D; autoimmune disorders, inherited

Cirrhosis

Inherited disorder of bilirubin metabolism resulting from a molecular defect within the gene involved with bilirubin conjugation; Increase in unconjugated bilirubin

Crigler-Najjar syndrome

Liver prevents toxic or harmful substances from reaching systemic circulation by binding or chemical modification.

Detoxification and Drug Metabolism

accounts for 1/3 to 1/2 of all reported cases of acute liver failure in the United States; Most common mechanism of injury is adverse immune response to drug directed against liver.

Drug-induced liver disease

1) Increase in conjugated bilirubin 2) Inherited autosomal recessive disorder 3) Liver cannot remove conjugated bilirubin from liver cell and excrete in bile 4) Dark-stained granules seen on biopsy of liver

Dublin-Johnson disease

Are released into circulation after an injury that results in cytolysis or necrosis; Used to differentiate hepatocellular from obstructive liver disease

Enzymes

most significant cause of hepatic toxicity

Ethanol (alcohol)

1) Most common cause of hepatic jaundice 2) Autosomal recessive hereditary disorder that affects 5% of U.S. population 3) Intermittent hyperbilirubemia 4) Caused by UGT1A1 reduced expression 5) Increase in unconjugated bilirubin

Gilbert's syndrome

occurs when the primary problem causing the jaundice resides in the liver (intrinsic liver defect or disease)

Hepatic jaundice

Injury to liver characterized by inflammation in liver tissue

Hepatitis

1) Most common form of viral hepatitis worldwide 2) Transmitted via contaminated or improperly handled food (oral-fecal route)

Hepatitis A

1) Can cause both acute and chronic hepatitis 2) Transmitted via parenteral, perinatal, and sexual transmission 3) Serologic markers of infection: core antigen, surface antigen, e antigen

Hepatitis B

Transmitted via parenteral transmission (primarily by blood transfusion)

Hepatitis C

1) A unique subvirus satellite virus infection 2) Requires HbsAg of HBV for replication; can only occur in patients who already have hepatitis B

Hepatitis D

1) Transmitted primarily by fecal-oral route 2) Characterized by water-borne epidemics in developing countries

Hepatitis E

used to describe the yellow discoloration of the skin, eyes, and mucous membranes most often resulting from the retention of bilirubin

Jaundice or icterus

macrophages lining sinusoids; act as phagocytes, engulfing bacteria, debris, toxins

Kupffer cells

Liver breaks down fatty acids to form triglycerides, phospholipids, or cholesterol.

Lipid synthesis

Largest internal organ; functionally complex; Plays critical role in: 1. Metabolism 2. Digestion 3. Detoxification 4. Elimination of substances from body

Liver

Microscopic units that divide liver; Responsible for all metabolic and excretory functions; Six-sided structures with centrally located vein and portal triads

Lobules

liver location

Located beneath and is attached to diaphragm, protected by rib cage, held in place by ligamentous attachments

Liver cancer that occurs when tumors from other parts of the body spread (metastasize) to the liver

Metastatic liver cancer

Methods for bilirubin analysis

Most commonly used are Jendrassik-Grof or Malloy Evelyn

increased level occurs in liver failure

Plasma ammonia

Tests measuring nitrogen metabolism

Plasma ammonia level

results from biliary obstructive disease, usually from physical obstructions (gallstones or tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi

Posthepatic jaundice

occurs when the problem causing the jaundice occurs prior to liver metabolism

Prehepatic jaundice

Liver cancer that begins in the liver

Primary liver cancer

Almost all proteins are synthesized by the liver except for the immunoglobulins and adult hemoglobin.

Protein synthesis

Commonly increased in liver disease

Prothrombin time

1) A group of disorders caused by infectious, metabolic, toxic, or drug-induced disease found predominantly in children 2) Often preceded by viral syndrome such as varicella, gastroenteritis, or upper respiratory tract infection (influenza) 3) Associated with ingestion of aspirin during viral syndrome

Reye's Syndrome

1) Cause is unknown but hypothesized to be due to reduction of activity of intracellular binding proteins like ligandin. 2) Less common than Dublin-Johnson 3) Increase in conjugated bilirubin 4) Dark-stained granules not seen on liver biopsy

Rotor's syndrome

Decreased level may be caused by decreased liver protein synthesis

Serum albumin

90% to 95% of hepatic malignancies are metastatic, not originating in liver cells (primary); may be benign or malignant

Tumors

complete absence of enzymatic bilirubin conjugation

Type 1 Crigler-Najjar Syndrome

mutation causing a severe deficiency of the enzyme responsible for bilirubin conjugation; more rare and can be fatal

Type 2 Crigler-Najjar Syndrome

colorless end product of bilirubin metabolism that is oxidized by intestinal bacteria to brown pigment

Urobilinogen

Rarely performed because methods are very complex. Patterns of individual bile acids and their state of conjugation are examined.

analysis of serum bile acids

How is jaundice classified?

based on the site of the disorder: 1. prehepatic 2. hepatic 3. posthepatic

Absence of urobilinogen from urine and stool is seen on what disease state?

complete biliary obstruction

divides the liver unequally into two lobes

falciform ligament

masses of blood vessels with unknown etiology

hemangiomas

Increased levels of urobilinogen in urine are found in what disease states?

hemolytic disease and defective liver cell function

Where do the two blood supplies of the liver merge?

hepatic sinusoids

occurs almost exclusively in females of childbearing age

hepatocellular adenoma

large cells radiating outward from central vein. Comprise 80% of the volume of the organ and perform the major functions associated with the liver and are responsible to regenerative properties

hepatocytes

Hepatitis symptoms

jaundice, dark urine, fatigue, nausea, vomiting, abdominal pain

Hepatitis E virus characteristics

nonenveloped RNA virus that is only 27 to 34 nm in diameter

Quantitative methods for measuring urobilinogen

reaction of urobilinogen with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to form a red color

Hepatitis causes

viral, bacterial and parasitic infections, radiation, drugs, chemicals, autoimmune diseases, and toxins

Test results: Post-hepatic

↑ total bilirubin, ↑ conjugated bilirubin, ↑ unconjugated bilirubin

Test results: Dublin-Johnson syndrome

↑ total bilirubin, ↑ conjugated bilirubin, ↔ unconjugated bilirubin

Test results: Rotor's syndrome

↑ total bilirubin, ↑ conjugated bilirubin, ↔ unconjugated bilirubin

Test results: Crigler-Najjar syndrome

↑ total bilirubin, ↓ conjugated bilirubin, ↑ unconjugated bilirubin

Test results: Gilbert's Disease

↑ total bilirubin, ↔ conjugated bilirubin, ↑ unconjugated bilirubin

Test results: Jaundice of newborn

↑ total bilirubin, ↔ conjugated bilirubin, ↑ unconjugated bilirubin

Test results: Pre-hepatic jaundice

↑ total bilirubin, ↔ conjugated bilirubin, ↑ unconjugated bilirubin