Liver Flashcards
is a very large and complex organ responsible for performing vital tasks that impact all body systems.
Liver
is unique in the sense that it is a relatively resilient organ that can regenerate cells that have been destroyed by some short-term injury or disease or have been removed.
Liver
It has complex functions include metabolism of carbohydrates, lipids, proteins, and bilirubin; detoxification of harmful substances; storage of essential compounds; and excretion of substances to prevent harm
Liver
If the liver becomes completely nonfunctional for any reason, death will occur within approximately 24 hours due to
Hypoglycemia
The liver is a large and complex organ weighing approximately
1.2 to 1.5 kg in the healthy adult
It is located beneath and attached to the _______, is protected by the lower rib cage, and is held in place by ligamentous attachments.
Diaphragm -
It is divided unequally into two lobes by the
falciform ligament
the liver is an extremely vascular organ that receives its blood supply from two sources:
hepatic artery and the portal vein
a branch of the aorta, supplies oxygen-rich blood from the heart to the liver and is responsible for providing approximately 25% of the total blood supply to the liver.
Hepatic artery
It supplies nutrient-rich blood (collected as food is digested) from the digestive tract, and it is responsible for providing approximately 75% of the total blood supply to the liver
Portal vein
From the _______, blood flows to the central canal (central vein) of each lobule.
sinusoid
The two blood supplies eventually merge into the __________, which is lined with hepatocytes capable of removing potentially toxic substances from the blood.
hepatic sinusoid
The excretory system of the liver begins at the _____
bile canaliculi
The ________ are small spaces between the hepatocytes that form intrahepatic ducts, where excretory products of the cell can drain.
bile canaliculi
It is the major excretory system
bile canaliculi
The right and left hepatic ducts merge to form the common hepatic duct, which is eventually joined with the cystic duct of the gallbladder to form the _________
common bile duct
The liver is divided into microscopic units called
lobules
The ________ are the functional units of the liver
lobules
they are responsible for all metabolic and excretory functions performed by the liver
lobules
Each lobule is roughly a six-sided structure with a centrally located vein (called the central vein) with ________ at each of the corners
portal triads
Each portal triad contains a ________, _____ and a _____ surrounded by connective tissue.
hepatic artery, portal vein, and bile duct
The liver contains two major cell types:
Hepatocytes and Kupffer cells
The _________ making up approximately 80% of the volume of the organ, are large cells that radiate outward from the central vein in plates to the periphery of the lobule
Hepatocytes
These cells perform the major functions associated with the liver and are responsible for the regenerative properties of the liver.
Hepatocytes
_________ are macrophages that line the sinusoids of the liver and act as active phagocytes capable of engulfing bacteria, debris, toxins, and other substances flowing through the sinusoids
Kupffer cells
The liver performs four major functions:
- excretion/secretion
- metabolism
- detoxification
- storage.
One of the most important functions of the liver is the processing and excretion of endogenous and exogenous substances into the bile or urine such as the major heme waste product
Bilirubin
The ________ is the only organ that has the capacity to rid the body of heme waste products. Bile is made up of bile acids or salts, bile pigments, cholesterol, and other substances extracted from the blood.
Liver
The body produces approximately ____ of bile per day and excretes 1 L of what is produced
3 L
is the principal pigment in bile, and it is derived from the breakdown of red blood cells.
Bilirubin
Bilirubin is bound by albumin and transported to the liver. This form of bilirubin is referred to as
unconjugated or indirect bilirubin
This form of bilirubin is insoluble in water and cannot be removed from the body until it has been conjugated by the liver
unconjugated or indirect bilirubin.
is located in the hepatocyte, is responsible for transporting unconjugated bilirubin to the endoplasmic reticulum, where it may be rapidly conjugated.
Ligandin
The conjugation (esterification) of bilirubin occurs in the presence of the enzyme _______
uridyldiphosphate glucuronyl transferase (UDPGT)
uridyldiphosphate glucuronyl transferase (UDPGT), which transfers a glucuronic acid molecule to each of the two propionic acid side chains of bilirubin to form bilirubin diglucuronide, also known as
conjugated bilirubin
This form of bilirubin is water soluble and is able to be secreted from the hepatocyte into the bile canaliculi.
conjugated bilirubin
Most of the urobilinogen formed (roughly 80%) is oxidized to an orange-colored product called
Urobilin
The ________ is what gives stool its brown color
urobilin or stercobilin
it is responsible for metabolizing many biological compounds including carbohydrates, lipids, and proteins.
Liver
The metabolism of _________ is one of the most important functions of the liver
carbohydrates
When carbohydrates are ingested and absorbed, the liver can do three things:
(1) use the glucose for its own cellular energy requirements,
(2) circulate the glucose for use at the peripheral tissues, or
(3) store glucose as glycogen (principal storage form of glucose) within the liver itself or within other tissues.
The ______ is the major player in maintaining stable glucose concentrations due to its ability to store glucose as glycogen (glycogenesis) and degrade glycogen (glycogenolysis) depending on the body’s needs
Liver
when the supply of glycogen becomes depleted, the liver will create glucose from nonsugar carbon substrates like pyruvate, lactate, and amino acids and this process is called
gluconeogenesis
Almost all proteins are synthesized by the liver except for the ___________ and __________
immunoglobulins and adult hemoglobin.
The _______ plays an essential role in the development of hemoglobin in infants.
liver
One of the most important proteins synthesized by the liver is _________, which carries with it a wide range of important functions
albumin
The ________ serves as a gatekeeper between substances absorbed by the gastrointestinal tract and those released into systemic circulation
liver
Every substance that is absorbed in the gastrointestinal tract must first pass through the liver; this is referred to as _______
first pass
This is an important function of the liver because it can allow important substances to reach the systemic circulation and can serve as a barrier to prevent toxic or harmful substances from reaching systemic circulation.
first pass
The most important mechanism is the ___________ system of the liver.
drug-metabolizing
This system is responsible for the detoxification of many drugs through oxidation, reduction, hydrolysis, hydroxylation, carboxylation, and demethylation.
drug-metabolizing system
Many of these take place in the liver microsomes via the cytochrome __________
P-450 isoenzymes
is used to describe the yellow discoloration of the skin, eyes, and mucous membranes most often resulting from the retention of bilirubin;
Jaundice, or icterus
Although the upper limit of normal for total bilirubin is 1.0 to 1.5 mg/dL, jaundice is usually not noticeable to the naked eye (known as ______) until bilirubin levels reach 3.0 to 5.0 mg/dL.
overt jaundice
the term _______ is most commonly used in the clinical laboratory to refer to a serum or plasma sample with a yellow discoloration due to an elevated bilirubin level
icterus
Jaundice is most commonly classified based on the site of the disorder:
prehepatic, hepatic, and posthepatic jaundice
__________ occurs when the problem causing the jaundice occurs prior to liver metabolism. It is most commonly caused by an increased amount of bilirubin being presented to the liver such as that seen in acute and chronic hemolytic anemias
Prehepatic jaundice
The liver responds by functioning at maximum capacity; therefore, people with _______ rarely have bilirubin levels that exceed 5.0 mg/dL because the liver is capable of handling the overload.
prehepatic jaundice
This type of jaundice may also be referred to as ________________ because the fraction of bilirubin increased in people with prehepatic jaundice is the unconjugated fraction.
unconjugated hyperbilirubinemia
___________ occurs when the primary problem causing the jaundice resides in the liver (intrinsic liver defect or disease).
Hepatic jaundice
Gilbert’s disease, Crigler-Najjar syndrome, and physiologic jaundice of the newborn are hepatic causes of jaundice that result in elevations in ______________
unconjugated bilirubin
Conditions such as Dubin-Johnson and Rotor syndrome are hepatic causes of jaundice that result in elevations in ___________
conjugated bilirubin.
__________, first described in the early twentieth century, is a benign autosomal recessive hereditary disorder that affects approximately 5% of the U.S. population.
Gilbert’s syndrome
Gilbert’s syndrome results from a genetic mutation in the gene (UGT1A1) that produces ________, one of the enzymes important for bilirubin metabolism.
UDPGT
It is characterized by intermittent unconjugated hyper-bilirubinemia, underlying liver disease due to a defective conjugation system in the absence of hemolysis.
Gilbert’s syndrome
was first described by Crigler and Najjar in 1952 as a syndrome of chronic nonhemolytic unconjugated hyperbilirubinemia.9
Crigler-Najjar syndrome
like Gilbert’s syndrome, is an inherited disorder of bilirubin metabolism resulting from a molecular defect within the gene involved with bilirubin conjugation.
Crigler-Najjar syndrome
Crigler-Najjar syndrome may be divided into two types:
Type I and Type II
where there is a complete absence of enzymatic bilirubin conjugation
Type I
where there is a mutation causing a severe deficiency of the enzyme responsible for bilirubin conjugation.
Type II
is rare and is a more serious disorder that may result in death.
Crigler-Najjar syndrome
is a condition that is obstructive in nature, so much of the conjugated bilirubin circulates bound to albumin.
Dubin-Johnson
This type of bilirubin (conjugated bilirubin bound to albumin) is referred to as _______
delta bilirubin
This syndrome is relatively mild in nature with an excellent prognosis. People with __________ have a normal life expectancy, so no treatment is necessary.
Dubin-Johnson syndrome
________ often results in cell damage and death in the newborn, and this condition will continue until glucuronyl transferase is produced.
Kernicterus
It 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
is a clinical condition in which scar tissue replaces normal, healthy liver tissue.
Cirrhosis
Cancers of the liver are classified as
primary or metastatic.
__________ is cancer that begins in the liver cells while metastatic cancer occurs when tumors from other parts of the body spread (metastasize) to the liver
Primary liver cancer
a condition occurring almost exclusively in females of child-bearing age
Hepatocellular adenoma
masses of blood vessels with no known etiology is called
hemangiomas
What is the most common malignant tumor of the liver
Hepatocellular carcinoma
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
is an acute illness characterized by non-inflammatory encephalopathy and fatty degeneration of the liver, with a clinical presentation of profuse vomiting accompanied with varying degrees of neurologic impairment such as fluctuating personality changes and deterioration in consciousness.
Reye syndrome
AST means
aspartate aminotransferase
ALT means
alanine aminotransferase
The _______ is a primary target organ for adverse drug reactions because it plays a central role in drug metabolism.
liver
Of all the drugs associated with hepatic toxicity, the most important is _______
Ethanol
is a condition where bile cannot flow from the liver to the duodenum
CHOLESTASIS
Within the liver, the elimination of alcohol requires the enzymes alcohol ______ and ________ to convert alcohol to acetaldehyde and subsequently to acetate.
dehydrogenase and acetaldehyde dehydrogenase
Alcohol-induced liver injury may be categorized into three stages:
alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis
The reaction of bilirubin with a diazotized sulfanilic acid solution to form a colored product was first described by ______ in ______ using urine samples.
Ehrlich in 1883
When using the several methods described earlier, two of the three fractions of bilirubin were identified:
conjugated (direct) and unconjugated (indirect) bilirubin.
____________ is a nonpolar and water-insoluble substance that is found in plasma bound to albumin.
Unconjugated (indirect) bilirubin
_____________ is a polar and water-soluble compound that is found in plasma in the free state (not bound to any protein).
Conjugated (direct) bilirubin
This type of bilirubin will react with the diazotized sulfanilic acid solution directly (without an accelerator).
Conjugated (direct) bilirubin
It reacts in the absence of an accelerator
Conjugated bilirubin
It requires an accelerator
Unconjugated bilirubin
The third fraction of bilirubin is referred to as “_____” bilirubin
delta
__________ is conjugated bilirubin that is covalently bound to albumin.
Delta bilirubin
filtered by the glomerulus and excreted in the urine. This fraction of bilirubin, when present, will react in most laboratory methods as conjugated bilirubin. Thus, total bilirubin is made up of three fractions:
conjugated, unconjugated, and delta bilirubin
The three fractions together are known as
total bilirubin
A ________ is preferred as the presence of lipemia will increase measured bilirubin concentrations.
fasting sample
Total bilirubin methods using a ___________ may be performed on either serum or plasma.
diazotized sulfanilic acid solution
Serum, however, is preferred for the ______ because the addition of the alcohol in the analysis can precipitate proteins and cause interference with the method.
Malloy-Evelyn procedure
is very sensitive to and is destroyed by light; therefore, specimens should be protected from light
Bilirubin
Ireview mo lang
If left unprotected from light, bilirubin values may reduce by 30% to 50% per hour. If serum or plasma is separated from the cells and stored in the dark, it is stable for 2 days at room temperature, 1 week at 4°C, and indefinitely at −20°C.41
the __________ or Malloy-Evelyn procedure is the most frequently used method to measure bilirubin.
Jendrassik-Grof
Basahin
The Jendrassik-Grof method is slightly more complex, but it has the following advantages over the Malloy-Evelyn method:
• Not affected by pH changes
• Insensitive to a 50-fold variation in protein concentration of the sample
• Maintains optical sensitivity even at low bilirubin concentrations
• Has minimal turbidity and a relatively constant serum blank
• Is not affected by hemoglobin up to 750 mg/dL
The diazotized sulfanilic acid reacts at the central methylene carbon of bilirubin to split the molecule forming two molecules of _________.
azobilirubin
This method is typically performed at pH ____ where the azobilirubin produced is red-purple in color with a maximal absorption of 560 nm.
1.2
The most commonly used accelerator to solubilize unconjugated bilirubin is __________
methanol
is a colorless end product of bilirubin metabolism that is oxidized by intestinal bacteria to the brown pigment urobilin.
Urobilinogen
A small portion that is not taken up by the hepatocytes is excreted by the kidney as ______.
urobilinogen
Increased levels of urinary urobilinogen are found in hemolytic disease and in defective liver cell function, such as that seen in ______.
hepatitis
___________ reacts with p-dimethylaminobenzaldehyde (Ehrlich’s reagent) to form a red color, which is then measured spectrophotometrically.
Urobilinogen
_________ play an important role in the assessment of liver function because injury to the liver resulting in cytolysis or necrosis will cause the release of enzymes into circulation.
Liver enzymes
_________ also play an important role in differentiating hepatocellular (functional) from obstructive (mechanical) liver disease, which is an important clinical distinction because failure to identify an obstruction will result in liver failure if the obstruction is not rapidly treated.
Enzymes
Although many enzymes have been identified as useful in the assessment of liver function, the most clinically useful include the
aminotransferases (ALT and AST), the phosphatases (ALP and 5′-neucleotidase), GGT, and lactate dehydrogenase (LD).
The two most common aminotransferases measured in the clinical laboratory are
AST (formerly referred to as serum glutamic oxaloacetic transaminase [SGOT]) and ALT (formerly referred to as serum glutamic pyruvic transaminase [SGPT]).
________ is found mainly in the liver (lesser amounts in skeletal muscle and kidney), whereas AST is widely distributed in equal amounts in the heart, skeletal muscle, and liver, making ALT a more “liver-specific” marker than AST
ALT
is a phosphatase that is responsible for catalyzing the hydrolysis of nucleoside-5′-phosphate esters.
5′-Nucleotidase (5NT)
___________ is a membrane-localized enzyme found in high concentrations in the kidney, liver, pancreas, intestine, and prostate but not in bone.
γ-Glutamyltransferase (GGT)
___________ plays a role in differentiating the cause of elevated levels of ALP as the highest levels of GGT are seen in biliary obstruction.
γ-Glutamyltransferase
__________ is an enzyme with a very wide distribution throughout the body. It is released into circulation when cells of the body are damaged or destroyed, serving as a general, nonspecific marker of cellular injury.
Lactate Dehydrogenase
In particular, immunoglobulin G (IgG) and IgM levels are more consistently elevated in chronic active hepatitis; ________, in primary biliary cirrhosis; and ______, in alcoholic cirrhosis.
IgM, IgA
________ is commonly increased in liver disease because the liver is unable to manufacture adequate amounts of clotting factor or because the disruption of bile flow results in inadequate absorption of vitamin K from the intestine.
Prothrombin time
The ______ plays a major role in removing ammonia from the bloodstream and converting it to urea so that it can be removed by the kidneys.
liver
It implies injury to the liver characterized by the presence of inflammation in the liver tissue
Hepatitis
_________ also known as infectious hepatitis or short-incubation hepatitis, is the most common form of viral hepatitis worldwide.
HAV
It is the primary means of HAV transmission.
Fecal-oral route
Clinical markers for the diagnosis and the progression of HAV infection are measured through the presence of ___________
serologic antibodies
___________ has been used as the primary marker of acute infection.
IgM anti-HAV
It is the production of scar tissue replacement of the normal hepatocytes with the scarred tissue
Cirrhosis
Another method of detecting HAV infection is amplification of viral RNA by __________
reverse transcription–polymerase chain reaction (RT-PCR)
Known as serum hepatitis or long-incubation hepatitis,
Hepatitis B
It can cause both acute and chronic hepatitis and is the most ubiquitous of the hepatitis viruses.
Hepatitis B
the three major routes of transmission of HBV are:
parenteral, perinatal, and sexual
The ______ is the primary site of HBV replication.
liver
is a 42-nm DNA virus classified in the Hepadnaviridae family
Hepatitis B
This antigen is present only in the nuclei of hepatocytes during an acute infection with HBV
Hepatitis B Core Antigen
an antigen closely associated with the core of the viral particle, is detected in the serum of persons with acute or chronic HBV infection
Hepatitis B e Antigen
is used to detect HBV DNA in the blood and is another method used to measure disease progression
Nucleic acid hybridization or PCR technique
It may be used to monitor the effectiveness of antiviral therapy in patients with chronic HBV infection, but it supplements rather than replaces current HBV serologic assays
Nucleic acid hybridization or PCR technique
(originally “non-A non-B hepatitis”) is caused by a virus with an RNA genome that is a member of the Flaviviridae family.
Hepatitis C
is transmitted parenterally. Although the sexual and fecal–oral routes as modes of transmission have been documented, the virus is transmitted primarily by blood transfusion of inappropriately screened blood products.
Hepatitis C or HCV
The _________ is usually not detected in the first few months of infection but will almost always be present in the later stages.
hepatitis C antibody
Currently, two laboratory tests are commonly used to diagnose HCV infection in clinical practice:
- anti-HCV detection by EIA
- quantitative nucleic acid PCR assays for serum HCV RNA.
______ is a unique subviral satellite virus infection. It is a small, defective RNA-containing virus that cannot replicate independently but rather requires the HBsAg of HBV for replication.
HDV or Hepatitis D
is currently the therapy used for treating chronic HDV infection.
Interferon-α
__________ a nonenveloped RNA virus that is only 27 to 34 nm in diameter, is the sole member of the genus Hepevirus in the family Hepeviridae. After infection, the incubation period is short, generally between 21 and 42 days prior to the onset of symptoms.
Hepatitis E
is transmitted primarily by the fecal–oral route, and waterborne epidemics are characteristic of HEV in many developing countries.
Hepatitis E
________ is diagnosed when the presence of IgM anti-HEV is detected
Acute HEV
