Ch. 25 - Liver Function Alterations During Disease Flashcards
The word juandice comes from the French word _____, which means “yellow”.
Jaune
The term used to describe the yellow discoloration of the skin, eyes, and mucous membranes most often resulting from the retention of bilirubin; however it may also occur due to retention of other substances.
Jaundice
A type of jaundice that is not visible to the naked eye.
Overt Jaundice
At what bilirubin levels will jaundice be visible?
3.0 - 5.0 mg/dL
This term is most commonly used in the clinical laboratory to refer to serum or plasma sample with a yellow discoloration due to an elevated bilirubin level.
Icteric
Enumerate the different classifications of jaundice based on the site of the infection.
Prehepatic
Hepatic
Posthepatic
A type of jaundice that is due to a problem with the liver itself (an intrinsic liver defect or disease).
Hepatic jaundice
This is a type of jaundice occurring prior to liver metabolism. Most commonly caused by an increased amount of bilirubin being presented to the liver (seen in acute and chronic hemolytic anemias)
Prehepatic jaundice
This disease causes an increased amount of red blood cell destruction and the subsequent release of increased amounts of bilirubin presenting to the liver for processing.
Hemolytic anemia
People that have prehepatic jaundice rarely have bilirubin levels that exceed ___ mg/dL because the liver is capable of handling the overload
5.0
Prehepatic jaundice may also be referred to as _____ because the fraction of bilirubin increased in this disease is the _____ fraction.
Unconjugated hyperbilirubinemia
Unconjugated
This fraction of bilirubin is: Not water soluble Bound to albumin Not filtered by the kidneys Not seen in the urine
Unconjugated fraction
This type of jaundice occurs when the primary problem causing the jaundice resides in the liver (Intrinsic liver defect or disease).
Hepatic jaundice
These are disorders of bilirubin metabolism and transport defects that can cause hepatic jaundice.
Crigler-Najjar syndrome
Dubin-Johnson syndrome
Gilbert’s disease
Neonatal physiologic jaundice of the newborn
These are hepatic causes of jaundice that result in elevations in unconjugated bilirubin.
Crigler-Najjar syndrome
Gilbert’s disease
Neonatal physiologic jaundice of the newborn
These are hepatic causes of jaundice that result in elevations in conjugated bilirubin.
Dubin-Johnson syndrome
Rotor syndrome
This is a benign autosomal recessive hereditary disorder that results from a genetic mutation in the gene UGT1A1.
Gilbert’s syndrome
This gene is located on chromosome 2; it produces UDPGT. It is the hepatic 1A1 isoform of UDPGT
UGT1A1
It is known as the most common cause of jaundice but has no morbidity or mortality in the majority of those affected and carries generally no clinical consequences.
Gilbert’s syndrome
The total serum bilirubin of patients with Gilbert’s syndrome fluctuates between ___ and 3.0 mg/dL, and rarely exceeds___ mg/dL.
1.5; 4.5
The liver’s conjugation system in this disease/syndrome is working at approximately 30% of normal.
Gilbert’s syndrome
Described as a syndrome of chronic nonhemolytic unconjugated hyperbilirubinemia and an inherited disorder of bilirubin metabolism resulting from a molecular defect within the gene involved with bilirubin conjugation.
Crigler-Najjar syndrome
A type of Crigler-Najjar syndrome where there is a complete absence of enzymatic bilirubin conjugation.
Type 1
A type of Crigler-Najjar syndrome where there is a mutation causing a severe deficiency of the enzyme responsible for bilirubin conjugation.
Type 2
Diseases that are characerized as primarily unconjugated hyperbilirubinemias.
Gilbert’s syndrome
Crigler-Najjar syndrome
Diseases that are characerized as primarily conjugated hyperbilirubinemias.
Dubin-Johnson syndrome
Rotor syndrome
This syndrome is a rare autosmoal recessive inherited disorder caused by a deficiency of the canalicular multidrug resistance/multispecifc organic anionic transporter protein (MDR2/cMOAT).
Dubin-Johnson syndrome
In this disease, the liver’s ability to uptake and conjugate bilirubin is functional; however, the removal of conjugated bilirubin from the liver cell and the excretion into the bile are defective. Results in accumulation of conjugated and unconjugated bilirubin.
Dubin-Johnson syndrome Posthepatic jaundice (Bilirubin is conjugated, but not excreted properly)
Conjugated bilirubin bound to albumin is referred to as _____. This type of bilirubin reacts as conjugated bilirubin in the laboratory method to measure conjugated or direct bilirubin.
Delta bilirubin
On a liver biopsy sample, this syndrome would have the appearance of dark-stained granules. It is also obstructive in narture.
Dubin-Johnson syndrome
What is the level of total bilirubin for a person with Dubin-Johnson syndrome?
Between 2 and 5 mg/dL
A syndrome that is clinically similar to Dubin-Johnson syndrome but its has an unknown cause. It is hypothesized to be due to a reduction in the concentration or activity or intracellular binding proteins such as ligandin.
Rotor syndrome
On a liver biopsy sample, this syndrome would have NO appearance of dark-stained granules.
Rotor syndrome
This disease is a result of a deficiency in the enzyme glucoronyl transferase, one of the last liver functions to be activated in prenatal life since bilirubin processing is handled by the mother of the fetus.
Physiologic jaundice of the newborn
It is the enzyme responsible for bilirubin conjugation. The deficiency of this enzyme results in rapid build-up of unconjugated bilirubin, which can be life threatening.
Glucoronyl transferase
When unconjugated bilirubin builds up in the neonate, it cannot be processed and it is deposited in the nuclei of the brain and degenerate nerve cells, causing _____. This often results in cell damage and death in the newborn.
Kernicterus
What are ways to treat infants suffering from Physiologic jaundice of the newborn?
Ultraviolet radiation to destroy the bilirubin as it passes through the capillaries of the skin
Exchange transfusion in extreme cases.
This classification of jaundice occurs as result from biliary obstructive disease, usually from physical obstructions (gallstones or tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi.
Posthepatic jaundice
In posthepatic jaundice, bile is not being brought to the intestines therefore stool loses its source of normal pigmentation and becomes _____ colored.
Clay
A clinical condition in which scar tissue replaces normal, healthy liver tissue. The scar tissue blocks the flow of blood through the organ an prevents the liver from functioning properly.
Cirrhosis
What are the signs and symptoms of cirrhosis that would appear after liver function deteriorates?
Fatigue, nausea, unintended weight loss, jaundice, bleeding from the gastrointestinal tract, intense itching and swelling in the legs and abdomen.
In the US, what is the most common cause of cirrhosis?
Chronic alcoholism
Enumerate other causes of cirrhosis aside from chronic alcoholism.
Chronic hepatitis B (HBV), C (HCV), and D (HDV) virus
Autoimmune hepatitis
Inherited disorders (α1-antitrypsin deficiency, Wilson disease, hemochromatosis, and galactosemia)
Nonalcoholic steatohepatitis
Blocked bile ducts
Drugs, toxins, and infections
What are the classifications of liver cancer?
Primary
Metastatic
_____ liver cancer is cancer that begins in the liver cells;
_____ cancer occurs when tumors from other parts of the body spread (metastasize) to the liver.
Primary;
Metastatic
Metastatic cancer is (more/less) common than primary liver cancer.
More
From what site does cancer in the liver usually originate from?
Colon
Lung
Breast
A type of benign tumor of the liver that occurs almost exclusively in females of child-bearing age.
Hepatocellular adenoma
A type of benign tumor of the liver that has masses of blood vessels with no known etiology.
Hemangiomas
A type of malignant tumor of the liver that is also known as hepatocarcinoma, and hepatoma.
Hepatocellular carcinoma (HCC)
Aside from HCC, it is another form of malignant tumor of the liver.
Bile duct carcinoma
This is the most common type of malignant tumor of the liver.
Hepatocellular carcinoma (HCC)
This is an uncommon hepatic malignancy of children.
Hepatoblastoma
It is a term used to describe a group of disorders caused by infectious, metabolic, toxic, or drug-induced disease found almost exclusively in children.
Reye syndrome
A condition wherein the cause is unknown.
Idiopathic
Although idiopathic, it is often preceded by a viral syndrome such as varicella (chicken pox), gastroenteritis, or an upper respiratory tract infection such as influenza.
Reye syndrome
It is an acute illness characterized by non-inflammatory encephalopathy and fatty degeneratioin of the liver, with a clinical presentation of profuse vomiting accompanied with varying degrees of neurological impairment such as fluctuating personality changes and deterioration in consciousness.
Reye syndrome
In Reye syndrome, the degeneration of the liver is characterized by a mild hyperbilirubinemia and threefold increases in _____ and _____.
Ammonia (NH3)
Aminotransferases (Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT))
It is the most common mechanism of toxicity in drug and alcohol related disorders. In this type of mechanism, the drug induces an adverse immune response directed against the liver itself and results in hepatic and/or cholestatic disease.
Immune-mediated injury to the hepatocytes
Of all the drugs associted with hepatic toxicity, what is the most important/valuble? It causes very mild, transient, and unnoticed injury to the liver; however, with heavier and prolonged consumption, it can lead to alcoholic cirrhosis.
Ethanol
Approximately how much of the alcohol absorbed from the stomach and small intestine is transported to the liver for for metabolism?
90%
What enzymes are required by the liver for the elimination of alcohol?
Alcohol dehydrogenase
Acetaldehyde dehydrogenase
The enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase converts alcohol to acetaldehyde and subsequently to _____. This can then be oxidized to water and carbon dioxide, or it may enter the citric acid cycle
Acetate
Alcohol induced liver injury may be categorized into three stages which are:
Alcoholic fatty acid liver
Alcoholic hepatitis
Alcoholic cirrhosis
This represents the mildest category of alcohol induced liver injury where very few changes in liver function are measurable. Characterized by slight elevations in AST, ALT and gamma-glutamyl transferase (GGT)
On biopsy, fatty infiltrates are noted in the vacoules of the liver. Affects young to middle aged people with moderate alcohol consumption.
Alcoholic fatty liver
An alcohol induced liver injury that presents with common signs and symptoms including fever, ascites, proximal loss
Laboratory evidence of liver damage: moderately elevated AST, ALT, GGT, and alkaline phosphate (ALP) and elevations in total bilirubin greater than 5 mg/dL
Serum proteins (albumin) is decreased, International normalized ratio is elevated
Alcoholic hepatitis
The most severe stage in an alcohol induced liver injury
Symptoms tend to be nonspecific and include weight loss, weakness, hepatomegaly, splenomegaly, jaundice, ascites, fever, malnutrition, and edema
Increased liver function tests (AST, ALT, GGT, ALP, and total bilirubin), decreased albumin, and prolonged prothrombin time
Liver biopsy is the only method by which a definitive diagnosis may be made.
Alcoholic cirrhosis
Alcoholic cirrhosis is (more/less) common in males than in females.
More
Give one of the most common drugs associated with serious hepatic injury.
Acetaminophen
A liver abnormality that is characteristic of alcoholic fatty liver with inflamation.
Steatohepatitis
A liver abnormality characterized by scar tissue formation
Hepatic fibrosis
A liver abnormality characterized by destruction of normal liver structure
Hepatic cirrhosis
An alcohol induced liver injury wherein the elevations in AST are more than twice the upper reference of normal but rarely exceed 300 IU/mL.
ALT are lower than AST, resulting in ALT/AST ratio (De Ritis ratio) greater than 2
Serum proteins, specially albumin, is decreased
International normalized ratio is decreased
Alcoholic hepatitis
The AST/ALT ratio is referred to as the _____.
De Ritis ratio
This is the ratio of the coagulation time in the patient compared with a normal coagulation time
International Normalized ratio (INR)
