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What does it all mean? (Interpreting
Liver function tests)
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Your Liver Functions
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The Liver
The characteristic
structure and organization of the liver enables it to perform vital roles in
regulating, synthesizing, storing, secreting, transforming, and breaking
down many different substances in the body. In addition, the liver's ability
to regenerate lost tissue helps maintain these functions, even in the face
of moderate damage. This section of the module focuses on the structural
aspects of the liver and its ability to regenerate.
Liver Functions
The body depends on the liver to perform a number of vital functions ,
and although there is substantial overlap, they can be divided into three
basic categories:
regulation, synthesis, and secretion of many substances important in
maintaining the body's normal state
storage of important nutrients such as glycogen (glucose), vitamins, and
minerals, purification, transformation, and clearance of waste
products, drugs, and toxins
Disease or traumatic injury can greatly reduce the liver's ability to carry
out these normal activities. Thus, most of the clinical manifestations of
liver dysfunction (discussed later in this module) stem from cell damage and
impairment of the normal liver capacities. For example, viral hepatitis
causes damage and death of hepatocytes. In this case, manifestations may
include increased bleeding (due to decreased synthesis of clotting factors),
jaundice (yellow pigmentation due to decreased clearance of
bilirubin ), and increased levels of circulating hepatocyte enzymes
(released from dead liver cells).
1. Regulations, Synthesis, and Secretion. Hepatocytes are
metabolically active cells that serve many functions. For example, they take
up glucose, minerals, and vitamins from portal and systemic blood and store
them. In addition, hepatocytes can produce many important substances needed
by the body, such as blood clotting factors, transporter proteins,
cholesterol, and bile components. Finally, by regulating blood levels of
substances such as cholesterol and glucose, the liver helps maintain body
homeostasis.
a. Glucose. The liver plays a major role in maintaining blood
concentrations of glucose, by storing or releasing glucose as needed.
b. Proteins. Most blood proteins (except for antibodies) are
synthesized and secreted by the liver. One of the most abundant serum
proteins is albumin. Impaired liver function that results in
decreased amounts of serum albumin may lead to edema, swelling due to fluid
accumulation in the tissues.
The liver also produces most of the proteins responsible for blood
clotting, called coagulation or clotting factors. If the blood cannot clot
normally due to a decrease in the production of these factors, excessive
bleeding may result.
c. Bile. Bile is a greenish fluid synthesized by hepatocytes and
secreted into biliary ducts. It then leaves the liver to be temporarily
stored in the gallbladder before emptying into the small intestine. The
major components of bile include cholesterol, phospholipids, bilirubin (a
metabolite of red blood cell hemoglobin), and bile salts. Importantly, bile
salts act as "detergents" that aid in the digestion and absorption of
dietary fats. Liver damage or obstruction of a bile duct (e.g., gallstone)
can lead to cholestasis, (the blockage of bile flow, which causes the
malabsorption of dietary fats), steatorrhea (foul-smelling diarrhea
caused by non-absorbed fats), and jaundice.
d. Lipids. Cholesterol, a type of lipid, is a substance found in
cell membranes that helps maintain the physical integrity of cells. The
liver synthesizes cholesterol, which is then packaged and distributed to the
body to be sued or excreted into bile for removal from the body. Increased
cholesterol concentrations in bile may predispose to gallstone formation.
The liver also synthesizes lipoproteins, which are made up of
cholesterol, triglycerides (containing fatty acids), phospholipids, and
proteins. Lipoproteins circulate in the blood and shuttle cholesterol and
fatty acids (an energy source) between the liver and body tissues. Most
liver diseases do not significantly affect serum lipid levels, with the
exception of cholestatic diseases, which may be associated with increased
levels.
2. Storage. As mentioned above, the liver is designed to store
important substances such as glucose (in the form of glycogen). The liver
also stores fat-soluble vitamins (vitamins A, D, E and K), folate, vitamin B
12 , and minerals such as copper and iron. However, excessive
accumulation of certain substances can be harmful. For example, patients
with an inherited condition known as Wilson's disease cannot secrete
copper into bile normally and usually have a low blood level of the
copper-binding protein ceruloplasmin. Retained copper accumulates in
the liver (leading to cirrhosis and in the central nervous system
(resulting in neuropsychiatric symptoms).
3. Purification, Transformation, and Clearance. The liver removes
harmful substances (such as ammonia and toxins) from the blood and then
breaks them down or transforms them into less harmful compounds. In
addition, the liver metabolizes most hormones and ingested drugs to either
more or less active products.
a. Ammonia. The liver converts ammonia to urea, which is excreted
into the urine by the kidneys. In the presence of severe liver disease,
ammonia accumulates in the blood because of both decreased blood clearance
and decreased ability to form urea. Elevated ammonia levels can be toxic,
especially to the brain, and may play a role in the development of hepatic
encephalopathy.
b. Bilirubin. Bilirubin is a yellow pigment formed as a breakdown
product of red blood cell hemoglobin. The spleen, which destroys old red
cells, releases "unconjugated" bilirubin into the blood, where it circulates
in the blood bound to albumin (Figure
7). The liver efficiently takes up bilirubin and chemically modifies it
to "conjugated," or water-solube, bilirubin that can be excreted into bile.
Increased production or decreased clearance of bilirubin results in
jaundice, a yellow pigmentation of the skin and eyes from bilirubin
accumulation.
c. Hormones. Since the liver plays important roles in hormonal
modification and inactivation, chronic liver disease may cause hormonal
imbalances. For example, the masculinizing hormone testosterone and the
feminizing hormone estrogen are metabolized and inactivated by the liver.
Men with cirrhosis, especially those who abuse alcohol, have increased
circulating estrogens relative to testosterone derivatives, which may lead
to body feminization.
d. Drugs. Nearly all drugs are modified or degraded in the liver.
In particular, oral drugs are absorbed by the gut and transported via the
portal circulation to the liver. In the liver, drugs may undergo first-pass
metabolism, a process in which they are modified, activated, or inactivated
before they enter the systemic circulation, or they may be left unchanged.
Alcohol is primarily metabolized by the liver, and accumulation of its
products can lead to cell injury and death.
In patients with liver disease, drug detoxification and excretion may be
dangerously altered, resulting in drug concentrations that are too low or
too high or the production of toxic drug metabolites. Therefore, medications
that are metabolized by the liver must be used with caution in patients with
hepatic disease; these patients may need lower doses of the drug.
e. Toxins. The liver is generally responsible for detoxifying
chemical agents and poisons, whether ingested or inhaled. Pre-existing liver
disease may inhibit or alter detoxification processes and thus increase the
toxic effects of these agents. Additionally, exposure to chemicals or toxins
may directly affect the liver, ranging from mild dysfunction to severe and
life-threatening damage.
Summary
From its sheltered position in the abdominal cavity, the liver filters
blood from both the portal and systemic circulations. The body depends on
the liver to regulate, synthesize, store, and secrete many important
proteins and nutrients and to purify, transform, and clear toxic or unneeded
substances. To carry out these functions, hepatocytes are organized for
optimal contact with sinusoids (leading to and from blood vessels) and bile
ducts. A special feature of the liver is its ability to regenerate, but this
capacity can be exceeded by repeated or extensive damage.
The liver is the largest
gland in the body (approximately 1500 grams) and is located in the right
upper quadrant of the adodomen.
It is glossy in appearance and dark red in color from the rich supply of
blood flowing through it. Approximately 25% of the cardiac output flows to
the liver. It performs many important functions:
1) the uptake, storage, and disposal of nutrients (protein, glucose and
fat), drugs and toxins and 2) the production of synthesis proteins critical
for blood clotting) and metabolism of substances produced by the body
(Vitamins A, B, D, B-12, K).
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Anatomy of the Liver
The anterior surface of the liver is triangular
in shape, made of two lobes. The right lobe is the larger of the two,
measuring 6 to 7 inches in length. The left lobe is closer to 3 inches in
length.
Click on Image to Enlarge
Ligaments connect the upper surface of the liver to the diaphragm and the
abdominal wall and the under surface to the stomach and duodenum. The gall
bladder is located on the under surface of the right lobe of the liver.
Neighboring organs include the colon, the intestines, and the right kidney.
The Liver Up Close
When viewed under a microscope, the liver is seen as large network of
units called hepatic lobules. The hepatic lobule is very small and looks
like a six-sided cylinder
Click on Image to Enlarge
The lobule itself is surrounded by connective tissue and has 5 to 7
clusters of vessels around its edges. These vessels
include a branch of the portal vein, a branch of the
hepatic artery, and a bile
duct.
A central vein runs through the middle of the lobe and is surrounded by
cords of liver cells that radiate out in all directions. Between these cords
are wide thin-walled blood vessels called sinusoids.
Digestive Function of the Liver
Sometimes referred to as the "great chemical factory" of the body, the
liver creates, regulates, and stores a variety of substances used by the
gastrointestinal system , and it serves a
number of important digestive functions.
Click on Image to Enlarge
The main digestive chemical synthesized by the liver is bile. During a
meal, bile is secreted by liver cells and travels through the hepatic duct
system into the small intestine where it is used to break down fat
molecules.
Between meals, bile is stored in the gall bladder. Bile further serves as
a waste disposal system for toxins removed from the blood by the liver.
The liver also plays a major role in the regulation of blood glucose
(blood sugar). The liver synthesizes, dissolves, and stores amino acids,
protein, and fat. It stores several important vitamins like B-12 and Vitamin
A. The liver also disposes of cellular waste and breaks down harmful
substances like alcohol, disposing of them into the bile.
Circulatory Function of the Liver
While the liver is technically part of the gastrointestinal system, it
also plays an important role in blood circulation. The liver has been called
the "antechamber of the heart" because it collects and processes all of the
gastrointestinal blood through the portal vein and delivers it to the right
side of the heart. The liver receives blood through two vascular systems,
the portal vein and hepatic artery.
Click on Image to Enlarge
The portal vein is formed by multiple branches of veins (superior and
inferior mesenteric, splenic) that supply the small and large intestine.
Thus, all blood leaving the intestine will flow into the portal vein and
then into the liver. This helps to explain how colon cancer cells leave the
intestine and travel, via the portal vein, to the liver and then grow into
tumors. About 75% of the total blood flow to the liver comes from the portal
vein.
Click on Image to Enlarge
The hepatic artery arises from a branch (celiac) of the aorta (the main
artery leading from the heart). The hepatic artery supplies "oxygen-rich"
blood to the liver and represents 25% of the total blood flow to the liver.
The blood drains from the liver into the hepatic veins. These veins drain
into the inferior vena cava and finally into the right atrium of the heart.
The liver processes so much blood that at one time more than 25% of the
total blood output from the heart is flowing through its tissues!
The liver is a complex and unique organ serving many functions vital to
sustaining life. From digestion to circulation, the liver is constantly
processing blood for use by the rest of the body.
The liver is the most resilient of all of the body's organs. It is
capable of regenerating itself. When part of the liver is removed, a healthy
organ will often grow back to its original size.
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Liver Glossary
abdomen
largest body cavity that contains the stomach, small
intestines, colon, rectum, liver, spleen, pancreas, gall bladder,
bladder, kidneys and appendix
abdominal
relating to the abdomen
acetaminophen
pain reliever and aspirin substitute found in
over-the-counter drugs like Tylenol
acute
happening suddenly over a short period of time
anemia
decrease in the normal level of red blood cells in the
bloodstream
anterior
at or toward the front
Albumin [al BYOO min]: a protein in the serum that transports
substances such as drugs and prevents leakage of fluid into the
surrounding tissues.
Alkaline phosphatase [AL kuh lin FAHS fah tays]: protein found
in bile duct cell membranes; blood levels may be increased in any liver
disease, but more markedly with cholestasis.
Alhph 1 - antitrypsin [AL fah -1 an tigh TRIP sin]:
plasma protein produced by the liver that inhibits the activity of
trypsin and other proteolytic enzymes; inherited deficiency leads to
emphysema and sometimes cirrhosis.
alimentary canal
continuous tube that extends from the mouth to the anus
in which food is processed and eliminated
Aminotransferase [ah MEE noh TRANS fir ays]: hepatocyte enzyme
that modifies proteins; blood levels increase in the setting of
hepatocellular necrosis (hepatocyte death). The two aminotransferases
important in liver disease are AST (aspartate aminotransferase) and ALT
(alanine aminotransferase).
Antibodies: proteins produced in response to a specific
antigen, which can then combine with that antigen and neutralize it.
Antigens: a molecule with a specific configuration that is
recognized by the immune system; usually part of a protein or sugar. It
stimulates the formation of a specific antibody and can elicit an
allergic reaction, or otherwise trigger an immune response.
artery
a muscular tube that carries blood away from the heart
and to all of the other organs of the body
Ascites [uh SIGH teez]: accumulation of fluid in the abdominal
cavity, usually secondary to liver scarring and increased sinusoidal
pressure. Intractable ascites is unresponsive to treatment and
continually recurs.
asymptomatic
without symptoms
Autoimmunity [AW toh im MEWN it ee]: a state or disease in
which the body's immune system attacks the body's own tissues.
benign
not cancerous; does not spread to other parts of the
body; the opposite of malignant
Bile: greenish fluid formed by the liver and emptied into the
small intestine via the bile ducts; contains bilirubin, bile salts,
phospholipids, and cholesterol.
bile duct
tube that carries bile from the gallbladder to the
duodenum
Bilirubin [BIL ee roo bin]: a bile pigment cleared from the
bolld by the liver; formed as a breakdown product of old red blood
cells; marked increase in blood levels can lead to jaundice from
deposition of bilirubin in skin, mucous membranes, and whites of the
eyes.
Board Certified
certification from the American Board of Surgery that the
surgeon has the skills necessary to specialize in surgery
Caput medusae [KAP ut muh DOO see]: literally "Medusa's head";
dilated, varicose veins around the umbilicus, which may be seen in
patients with cirrhosis of the liver.
capillaries
smallest blood vessels of the circulatory system that
connect arteries and veins; also referred to as capillary beds and
network of capillaries
carcinogen
any substance that is known to cause cancer
catheter
a flexible tube inserted into the body to transfer fluids
Ceruloplasmin [suh ROO loh
PLAZ min]: copper transporter protein; blood levels are usually
decreased in Wilson's disease.
circulatory system
network of tissues that transports blood through out the
body; consists of blood vessels and the heart
chemotherapy
treatment of cancer with anti-cancer drugs
Cholestasis [hoh luh STAY
sis]: blockage or suppression of bile flow, from either intrahepatic
or extrahepatic causes.
chronic
an illness lasting a long time or recurring
Cirrhosis [sur ROH sis]: pathologically-defined disease
characterized by diffuse, irreversible fibrosis of the liver surrounding
regenerative nodules.
Coagulopathy [koh AG yoo LAH puh thee]: increased bleeding
tendency due to decreased hepatic synthesis of clotting factors.
colorectal
relating to the colon and the rectum
contrast dye
special dye usually injected into the body to stain
certain cells making them easier to image and interpret
Decompensation: failure of the liver to compensate for damage
or injury, resulting in a decrease in liver functions.
digestive tract
group of organs in the body that together provide
digestive functions; consists of the mouth, the pharynx, the esophagus,
the stomach, the small intestine, the large intestine and the anus
DNA
deoxyribonucleic acid; nucleic acid found in the
chromosomes in cells that transmits hereditary information when the
cells reproduce
duodenum
first section of the small intestine
Dysplasia [dis PLAY zhuh]:
alteration in size, shape, and organization of cells; may be
precursor of cancer.
Encephalopathy [en SEF uh LAH puh thee]: alteration in sleep
patterns and mental status, ranging from forgetfulness and mild
confusion to coma; may be caused by circulating gut-derived brain-toxic
proteins not cleared by a dysfunctional liver.
endothelial cells
flattened cells joined together to form a membrane; found
in the lining of the heart, blood vessels and lymphatic vessels, on the
surface of the rain and spinal cord and in the eye
estrogen
a female sex hormone
falciform ligament
band of strong fibrous tissue that connects the right
lobe and the left lobe of the liver
Fibrosis [figh BROH sis]: the formation of fibrous tissue, or
scarring.
Fulminant: running a speedy course, with rapid worsening.
gastrointestinal system
consists of the esophagus, stomach, liver, small and
large intestines
general anesthetic
a drug that puts the patient to sleep
Hemochromatosis [HEE moh KROH mah TOH sis]: toxic accumulation
of iron in organs leading to dysfunction, including cirrhosis; may be
genetic (inherited increase in gut iron absorption) or a result of
massive blood transfusions.
hemoglobin
a protein in red blood cells that carries oxygen from the
lungs to the rest of the body
hepatic artery
blood vessel that carries oxygen-rich blood to the liver
from the heart
hepatic portal vein
blood vessel that carries oxygen-poor blood from the
liver back to the heart
Hepatitis [HEP uh TIGH tis]: inflammation and damage to the
liver; generally considered acute if duration is less than 6 months,
chronic if greater than 6 months.
Hepatocellular necrosis: localized tissue death of hepatic
cells.
Hepatocellular carcinoma (HCC): a primary liver tumor more
common in patients with cirrhosis.
Hepatocytes: liver cells.
Hepatorenal [HEP uh togh REE nahl] syndrome: poorly understood
terminal kidney failure in the setting of hepatic disease.
Homeostasis [HOH mee oh STAY sis]: tendency of the body to
maintain a stable internal environment, using a variety of
counterbalancing control systems.
Hyperbilirubinemia [HIGH pur BIL ee roo bin EE mee uh]:
abnormally high levels of bilirubin in the blood.
Hodgkin's Disease
rare form of cancer that affects the lymphatic system
ibuprofen
pain reliever and anti-inflammatory found in over the
counter drugs like Advil and Motrin
Icterus: see Jaundice.
Idiopathic [ID ee oh PATH
ik]: autoimmune chronic active hepatitis (IACAH): chronic hepatitis
of unknown origin; associated with a variety of anti-self antibodies;
progresses to cirrhosis and decompensation unless treated with
corticosteroids.
implants
a small container of radioactive material placed near
cancer cells
inferior vena cava
large vein that returns blood to the heart from all of
the organs below the diaphragm
intraarterially
injected into an artery
intravenously
injected into a vein
Jaundice [JAHN dis]: hyperbilirubinemia, with deposition of
bile pigment in the skin, mucous membraes, and sclerae (whites of eyes),
resulting in a yellow appearance of the patient; also called icterus.
Kayser-Fleischer rings: golden-brown rings in the corneas due
to copper deposition in Wilson's disease.
Kupffer cells: "scavenger" cells that remove foreign matter,
worn-out blood cells, and bacteria from the liver
lesion
generally, a wound; can refer to an injury, infection or
a tumor
ligament
strong fibrous tissue that connects bones, cartilage and
muscle
Limiting plate: layer of hepatocytes surrounding each portal
triad and separating it from the surrounding sheets of hepatocytes.
local anesthetic
a drug that blocks pain and deadens the area where it is
applied
Lobule [LAHB yool]:
"structural" unit of the liver; shaped like a hexagon on cross section,
with six portal triads at the periphery and a central vein.
lymph nodes
small glands located throughout the lymphatic system that
store cells that help fight infection and disease
lymphatic system
the tissues and organs that produce, store and transfer
cells that help fight disease and infection; consists of bone marrow,
lymph nodes, spleen, thymus and the lymphatic vessels
malaise
vague feeling of discomfort like the onset of an illness
malignant
cancerous; cancer cells that may spread to other parts of
the body
metastases
cancer cells that have spread from a primary site to
another location in the body
metastatic
adjective used to describe cancer cells that have spread
from a primary site somewhere else in the body
non-Hodgkin's lymphoma
cancer of the lymphatic system that is not Hodgkin's
noninvasive
adjective used to describe a procedure that is external
and that minimizes side effects; refers to all procedures that do not
"break the skin"
oncologist
physician specializing in the treatment of cancer
oral contraceptives
pills used by women to provide birth control
palliative
the process of relieving the symptoms of disease without
curing it; the act of making the patient more comfortable
peritoneum
the tissue the lines the inside of the abdominal cavity
platelets
special blood cells that cause blood to clot and stop
bleeding
Portal hypertension [POR tahl HIGH per TEN shun]: abnormal
increase in portal blood pressure, usually due to obstruction of, or
increased resistance to, portal blood flow.
Portal system: includes all the veins that drain the small and
large intestines, stomach, and spleen and that converge into the portal
vein to drain into the liver.
Portal triad (or tract): consists of three components: branch
of the hepatic artery, branch of the portal vein, and a biliary duct,
all held tightly together by a limiting plate of hepatocytes at the
periphery of the lobule.
Portosystemic [POR toh sis TEM ick] shunting: development of
blood vessels that connect the portal and systemic circulation while
bypassing the liver.
primary tumor
the first mass of cancer cells to develop in the body
primary care physician
the physician one visits for physical exams and minor
illnesses
Prognosis: prediction as to the probable outcome of a disease.
Prothrombin [proh THRAHM bin] time (PT): laboratory test that
measures the clotting of blood in seconds; abnormally increased PT
signifies bleeding risk due to deficient synthesis of clotting proteins.
Pruritus: itching.
radiation
process of releasing energy as particles or waves from a
central source outward
radiation oncologist
physician specializing in the use of radiation therapy to
treat cancer
radiation therapy
treatment that uses x-rays to kill cancer cells; also
called radiotherapy
radioactivity
release of alpha and beta particles and gamma rays when
atoms of one element change to atoms of another element
radiologist
physician specializing in making and interpreting
pictures of the inside of the body
red blood cells
blood cells that carry oxygen from the lungs to the rest
of the body
resectable
surgical removal of a section of an organ is a feasible
option
resection
surgical removal of a section of an organ
Seroconversion: appearance of specific antibodies in the
blood, indicating recovery from infection or successful vaccination.
Sinusoids: tunnels through hepatic tissue allowing exchange of
nutrients and other substances between blood and hepatocytes.
Spider angiomas: red capillary tufts in the skin that blanch
on pressure; often found in patients with cirrhosis.
Spontaneous bacterial peritonitis (SBP): bacterial infection
of ascitic fluid.
sonographer
technician who specializes in the operation of ultrasound
equipment
Steatorrhea [STEE uh toh REE uh]: decreased absorption of
dietary fats, resulting in their passage to the distal bowel which
causes foul-smelling diarrhea; can be caused by deficiency of bile
salts.
systemic
affecting the entire body; as in systemic treatment that
treats every cell of the body
testosterone
a male sex hormone
tomography
the use of x-rays to produce images of one specific layer
of tissue
Transaminase: see Aminotransferase.
tumor
an abnormal growth of cells in a lump or mass
unresectable
surgical removal of a section of an organ is not a
feasible option
Varices [VAYR ih seez]: dilated veins; lower esophageal
varices form as collaterals from portal hypertension and can rupture,
leading to massive bleeding.
vasculature
relating to the vessels that carry blood throughout the
body
vein
tube that carries blood to the heart from all of the
other organs in the body
vessel
duct or tube that carries a body fluid; arteries and
veins are vessels
viral hepatitis
inflammation of the liver caused by a virus like the
Hepatitis B Virus or the Hepatitis C Virus
Wilson's disease:
inherited metabolic disorder in which copper accumulates in the liver
and in the central nervous system, causing hepatitis, cirrhosis, and
neuropsychiatric symptoms
white blood cells
blood cells that fight infection and disease in the body;
formed in the bone marrow
x-rays
acute invisible high-frequency electromagnetic waves that
can penetrate certain substances like skin |
FAQ
THE FUNCTION OF THE LIVER
Q. What does the liver do?
A. The liver:
- Stores iron reserves, as well as vitamins and minerals
- Makes bile to help digest food
- Detoxifies poisonous chemicals, including alcohol, beer, wine, and
drugs - prescribed and over-the-counter as well as illegal substances
- Stores energy by stockpiling sugar (carbohydrates, glucose and fat)
until you need it
- Makes your blood
- Manufactures new proteins
- Makes clotting factors to help blood clot
- Removes poisons from the air, exhaust, smoke and chemcials we breathe.
THE LIVER AND NUTRITION
Q. What does nutrition have to do with your liver?
A. Everything we eat, breathe and absorb through our skin
must be refned and detoxified by the liver, so special attention to
nutrition and diet can help keep the the liver healthy.
Q. Why is the liver so important in nutrition?
A. 85-90% of the blood that leaves the stomach and
intestines caries important nutrients to the liver where they are converted
into substances the body can use.
Q. Can poor nutrition cause liver disease?
A. It is actually much more likely that poor nutrition is
the result of chronic liver disease, not the cause. On the other hand, good
nutrition - a balanced diet with adequate calories, proteins, fats, and
carbohydrates - can actually help the damaed liver to regenerate new liver
cells.
For more information on this topic, see: Our detailed
page
Nutrition
HEPATITIS
Q. What is viral hepatitis?
A. Hepatitis means inflammation of the liver. Viral
hepatitis refers to several common contagious diseases caused by viruses
that attack the liver. The most important types of viral hepatitis are
hepatitis A, hepatitis B, and hepatitis C.
Q. What causes hepatitis A?
A. Hepatitis A is caused by eating food or drinking water
that has been contaminated with human excrement. Symptoms similar to the flu
and fatigue may occur; however, the disease is rarely life threatening.
Q. What is hepatitis B?
A. Hepatitis B is more common and much more infectious than
AIDS; there are approximately 300,000 new cases each year in the United
States. Hepatitis B may develop into a chronic form in up to 10% of
patients. Chronic hepatitis B may lead to scarring of the liver, called
cirrhosis, and cancer of the liver.
Q. What is hepatitis C?
A. Hepatitis C affects approximately 170,000 Americans each
year. It may develop into a chronic form in more than 75 to 85% of patients.
GALLSTONES
Q. What are the most important risk factors for developing
gallstones?
A. The three most important risk factors are body weight,
increasing age and being female.
Q. What is the gallbladder and what does it do?
A. The gallbladder is a small pear-shaped organ that
averages three to six inches in length. It lies underneath the liver in the
upper right side of the abdomen. The gallbladder serves as a reservoir for
bile, the fluid utilized by the body to digest fatty foods and assist in teh
absorption of certain vitamins and minerals.
Q. What are gallstones and how are they formed? A..
Gallstones are lumps of solid material that form within the gallbladder. The
two major types are cholesterol gallstones and pigment gallstones.
ALCOHOL AND LIVER DISEASE
Q. Does alcohol cause liver disease?
A. Yes, but it is only one of many causes, and the risk
depends on how much you drink and over how long a period.
Q. How much alcohol can I safely drink?
A. Because some people are much more sensitive to alcohol
than others, there is no single right answer for everyone. Generally,
doctors recommend that if you drink, don't drink more than two drinks per
day.
Q. Can "social drinkers" get alcoholic hepatitis?
A. Unfortunately, yes. Alcoholic hepatitis is frequently
discovered in alcoholics, but it also occurs in people who are not
alcoholics.
Q. Are men or women more likely to get alcoholic hepatitis?
A. Women appear to be more likely to suffer liver damage
from alcohol.
LIVER TRANSPLANTATION
Q. Which liver diseases are most commonly treated by
transplantation?
A. In adults, cirrhosis, the death of liver cells because
of chronic hepatitis, is the most common disease for which liver
transplantation is done. In children, the disease most often treated by
liver transplantation is biliary atresia, a failure of bile ducts to develop
normally to drain bile from the liver.
Q. Are there alternative treatments for liver diseases?
A. There are effective medicines for some liver diseases,
while for others only treatment for complications is available.
Q. What are the overall chances of surviving a liver
transplant?
A. This depends on many factors but overall 60-75% of adult
patients and 80-90% of children survive and are discharged from the
hospital.
Q. Where do donated livers come from?
A. Livers are donated, with the consent of the next of kin,
from individuals who have brain death, usually as the result of a head
injury or brain hemorrhage.
Q. How can I donate my organs?
A. If you wish to be an organ donor, carry an organ donor
card and place an organ donor sticker on your medical identification card.
For more information on liver transplantation, see:
"FAQ on Liver Transplantation."
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What does it all mean? (Interpreting Liver Function Tests)
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Considerations in Interpreting Liver Function Tests.
Author/s: David E. Johnston
Issue: April 15, 1999
A number of pitfalls can be encountered in the interpretation
of common blood liver function tests. These tests can be normal
in patients with chronic hepatitis or cirrhosis. The normal
range for aminotransferase levels is slightly higher in males,
nonwhites and obese persons. Severe alcoholic hepatitis is
sometimes confused with cholecystitis or cholangitis.
Conversely, patients who present soon after passing common bile
duct stones can be misdiagnosed with acute hepatitis because
aminotransferase levels often rise immediately, but alkaline
phosphatase and g-glutamyltransferase levels do not become
elevated for several days. Asymptomatic patients with isolated,
mild elevation of either the unconjugated bilirubin or the g-glutamyltransferase
value usually do not have liver disease and generally do not
require extensive evaluation. Overall hepatic function can be
assessed by applying the values for albumin, bilirubin and
prothrombin time in the modified Child-Turcotte grading system.
The commonly used liver function tests (LFTs) primarily
assess liver injury rather than hepatic function. Indeed, these
blood tests may reflect problems arising outside the liver, such
as hemolysis (elevated bilirubin level) or bone disease
(elevated alkaline phosphatase [AP] level).
Abnormal LFTs often, but not always, indicate that something
is wrong with the liver, and they can provide clues to the
nature of the problem. However, normal LFTs do not always mean
that the liver is normal. Patients with cirrhosis and bleeding
esophageal varices can have normal LFTs. Of the routine LFTs,
only serum albumin, bilirubin and prothrombin time (PT) provide
useful information on how well the liver is functioning.
The general subject of LFTs1,2 and the differential diagnosis
of abnormal LFTs in asymptomatic patients3-5 have been well
reviewed. This article discusses some common pitfalls in the
interpretation of LFTs. Hints for interpreting these tests are
presented in Table 1.
Markers of Hepatocellular Injury
The most commonly used markers of hepatocyte injury are
aspartate aminotransferase (AST, formerly serum
glutamic-oxaloacetic transaminase [SGOT]) and alanine
aminotransferase (ALT, formerly serum glutamate-pyruvate
transaminase [SGPT]). While ALT is cytosolic, AST has both
cytosolic and mitochondrial forms.
Hepatocyte necrosis in acute hepatitis, toxic injury or
ischemic injury results in the leakage of enzymes into the
circulation. However, in chronic liver diseases such as
hepatitis C and cirrhosis, the serum ALT level correlates only
moderately well with liver inflammation. In hepatitis C, liver
cell death occurs by apoptosis (programmed cell death) as well
as by necrosis. Hepatocytes dying by apoptosis presumably
synthesize less AST and ALT as they wither away. This probably
explains why at least one third of patients infected with
hepatitis C virus have persistently normal serum ALT levels
despite the presence of inflammation on liver biopsy.6,7
Patients with cirrhosis often have normal or only slightly
elevated serum AST and ALT levels. Thus, AST and ALT lack some
sensitivity in detecting chronic liver injury. Of course, AST
and ALT levels tend to be higher in cirrhotic patients with
continuing inflammation or necrosis than in those without
continuing liver injury.
As markers of hepatocellular injury, AST and ALT also lack
some specificity because they are found in skeletal muscle.
Levels of these aminotransferases can rise to several times
normal after severe muscular exertion or other muscle injury, as
in polymyositis,8 or in the presence of hypothyroidism, which
can cause mild muscle injury and the release of
aminotransferases. In fact, AST and ALT were once used in the
diagnosis of myocardial infarction.
Slight AST or ALT elevations (within 1.5 times the upper
limits of normal) do not
necessarily indicate liver disease. Part of this ambiguity
has to do with the fact that unlike the values in many other
biochemical tests, serum AST and ALT levels do not follow a
normal bell-shaped distribution in the population.9 Instead, AST
and ALT values have a skewed distribution characterized by a
long "tail" at the high end of the scale (Figure 1).5 For
example, the mean values for ALT are very similar from one
population to another, but the degree to which the distribution
is skewed varies by gender and ethnicity. The ALT distributions
in males and nonwhites (i.e., blacks and Hispanics) tend to have
a larger tail at the high end, so that more values fall above
the upper limits of normal set for the average population.10,11
AST and ALT values are higher in obese patients, probably
because these persons commonly have fatty livers.12 ALT levels
have been noted to decline with weight loss.13 Depending on the
physician's point of view, the upper limits of normal for AST
and ALT levels could be set higher for more obese persons.
Rare individuals have chronically elevated AST levels because
of a defect in clearance of the enzyme from the circulation.14
For both AST and ALT, the average values and upper limits of
normal in patients undergoing renal dialysis are about one half
of those found in the general population.15 Mild elevations of
ALT or AST in asymptomatic patients can be evaluated efficiently
by considering alcohol abuse, hepatitis B, hepatitis C and
several other possible diagnoses (Table 2).5
Various liver diseases are associated with typical ranges of
AST and ALT levels (Figure 2). ALT levels often rise to several
thousand units per liter in patients with acute viral hepatitis.
The highest ALT levels-often more than 10,000 U per L-are
usually found in patients with acute toxic injury subsequent to,
for example, acetaminophen overdose or acute ischemic insult to
the liver. AST and ALT levels usually fall rapidly after an
acute insult.
Lactate dehydrogenase (LDH) is less specific than AST and ALT
as a marker of hepatocyte injury. However, it is worth noting
that LDH is disproportionately elevated after an ischemic liver
injury.16
It is especially important to remember that in patients with
acute alcoholic hepatitis, the serum AST level is almost never
greater than 500 U per L and the serum ALT value is almost never
greater than 300 U per L. The reasons for these limits on AST
and ALT elevations are not well understood. In typical viral or
toxic liver injury, the serum ALT level rises more than the AST
value, reflecting the relative amounts of these enzymes in
hepatocytes. However, in alcoholic hepatitis, the ratio of AST
to ALT is greater than 1 in 90 percent of patients and is
usually greater than 2.17 The higher the AST-to-ALT ratio, the
greater the likelihood that alcohol is contributing to the
abnormal LFTs. In the absence of alcohol intake, an increased
AST-to-ALT ratio is often found in patients with cirrhosis.
The elevated AST-to-ALT ratio in alcoholic liver disease
results in part from the depletion of vitamin B6 (pyridoxine) in
chronic alcoholics.18 ALT and AST both use pyridoxine as a
coenzyme, but the synthesis of ALT is more strongly inhibited by
pyridoxine deficiency than is the synthesis of AST. Alcohol also
causes mitochondrial injury, which releases the mitochondrial
isoenzyme of AST.
Patients with alcoholic hepatitis can present with jaundice,
abdominal pain, fever and a minimally elevated AST value,
thereby leading to a misdiagnosis of cholecystitis. This is a
potentially fatal mistake given the high surgical mortality rate
in patients with alcoholic hepatitis.19
Markers of Cholestasis
Cholestasis (lack of bile flow) results from the blockage of
bile ducts or from a disease that impairs bile formation in the
liver itself. AP and g- glutamyltransferase (GGT) levels
typically rise to several times the normal level after several
days of bile duct obstruction or intrahepatic cholestasis. The
highest liver AP elevations-often greater than 1,000 U per L, or
more than six times the normal value-are found in diffuse
infiltrative diseases of the liver such as infiltrating tumors
and fungal infections.
Diagnostic confusion can occur when a patient presents within
a few hours after acute bile duct obstruction from a gallstone.
In this situation, AST and ALT levels often reach 500 U per L or
more in the first hours and then decline, whereas AP and GGT
levels can take several days to rise.
Both AP and GGT levels are elevated in about 90 percent of
patients with cholestasis.20 The elevation of GGT alone, with no
other LFT abnormalities, often results from enzyme induction by
alcohol or aromatic medications in the absence of liver disease.
The GGT level is often elevated in persons who take three or
more alcoholic drinks (45 g of ethanol or more) per day.21 Thus,
GGT is a useful marker for immoderate alcohol intake.
Phenobarbital, phenytoin (Dilantin) and other aromatic drugs
typically cause GGT elevations of about twice normal. A mildly
elevated GGT level is a typical finding in patients taking
anticonvulsants and by itself does not necessarily indicate
liver disease.22,23
Serum AP originates mostly from liver and bone, which produce
slightly different forms of the enzyme. The serum AP level rises
during the third trimester of pregnancy because of a form of the
enzyme produced in the placenta. When serum AP originates from
bone, clues to bone disease are often present, such as recent
fracture, bone pain or Paget's disease of the bone (often found
in the elderly). Like the GGT value, the AP level can become
mildly elevated in patients who are taking phenytoin.22,23
If the origin of an elevated serum AP level is in doubt, the
isoenzymes of AP can be separated by electrophoresis. However,
this process is expensive and usually unnecessary because an
elevated liver AP value is usually accompanied by an elevated
GGT level, an elevated 5[acute accent]-nucleotidase level and
other LFT abnormalities.
In one study,24 isolated AP elevations were evaluated in an
unselected group of patients at a Veterans Affairs hospital.
Most mild AP elevations (less than 1.5 times normal) resolved
within six months, and almost all greater elevations had an
evident cause that was found on routine clinical evaluation.
Persistently elevated liver AP values in asymptomatic
patients, especially women, can be caused by primary biliary
cirrhosis, which is a chronic inflammatory disorder of the small
bile ducts. Serum antimitochondrial antibody is positive in
almost all of these patients.
Indicators of How Well the Liver Functions
Bilirubin
Bilirubin results from the enzymatic breakdown of heme.
Unconjugated bilirubin is conjugated with glucuronic acid in
hepatocytes to increase its water solubility and is then rapidly
transported into bile. The serum conjugated bilirubin level does
not become elevated until the liver has lost at least one half
of its excretory capacity. Thus, a patient could have
obstruction of either the left or right hepatic duct without a
rise in the bilirubin level.
Because the secretion of conjugated bilirubin into bile is
very rapid in comparison with the conjugation step, healthy
persons have almost no detectable conjugated bilirubin in their
blood. Liver disease mainly impairs the secretion of conjugated
bilirubin into bile. As a result, conjugated bilirubin is
rapidly filtered into the urine, where it can be detected by a
dipstick test. The finding of bilirubin in urine is a
particularly sensitive indicator of the presence of an increased
serum conjugated bilirubin level.
In many healthy persons, the serum unconjugated bilirubin is
mildly elevated to a concentration of 2 to 3 mg per dL (34 to 51
[micro sign]mol per L) or slightly higher, especially after a
24-hour fast. If this is the only LFT abnormality and the
conjugated bilirubin level and complete blood count are normal,
the diagnosis is usually assumed to be Gilbert syndrome, and no
further evaluation is required. Gilbert syndrome was recently
shown to be related to a variety of partial defects in uridine
diphosphate-glucuronosyl transferase, the enzyme that conjugates
bilirubin.25
Mild hemolysis, such as that caused by hereditary
spherocytosis and other disorders, can also result in elevated
unconjugated bilirubin values, but hemolysis is not usually
present if the hematocrit and blood smear are normal. The
presence of hemolysis can be confirmed by testing other markers,
such as haptoglobin, or by measuring the reticulocyte count.
Severe defects in bilirubin transport and conjugation can
lead to markedly elevated unconjugated bilirubin levels, which
can cause serious neurologic damage (kernicterus) in infants.
However, no serious form of liver disease in adults causes
elevation of unconjugated bilirubin levels in the blood without
also causing elevation of conjugated bilirubin values.
When a patient has prolonged, severe biliary obstruction
followed by the restoration of bile flow, the serum bilirubin
level often declines rapidly for several days and then slowly
returns to normal over a period of weeks. The slow phase of
bilirubin clearance results from the presence of delta-bilirubin,
a form of bilirubin chemically attached to serum albumin.26
Because albumin has a half-life of three weeks, delta-bilirubin
clears much more slowly than bilirubin-glucuronide. Clinical
laboratories can measure delta-bilirubin concentrations, but
such measurements are usually unnecessary if the physician is
aware of the delta-bilirubin phenomenon.
Albumin
Although the serum albumin level can serve as an index of
liver synthetic capacity, several factors make albumin
concentrations difficult to interpret.27 The liver can
synthesize albumin at twice the healthy basal rate and thus
partially compensate for decreased synthetic capacity or
increased albumin losses. Albumin has a plasma half-life of
three weeks; therefore, serum albumin concentrations change
slowly in response to alterations in synthesis. Furthermore,
because two thirds of the amount of body albumin is located in
the extravascular, extracellular space, changes in distribution
can alter the serum concentration.
In practice, patients with low serum albumin concentrations
and no other LFT abnormalities are likely to have a nonhepatic
cause for low albumin, such as proteinuria or an acute or
chronic inflammatory state. Albumin synthesis is immediately and
severely depressed in inflammatory states such as burns, trauma
and sepsis, and it is commonly depressed in patients with active
rheumatic disorders or severe end-stage malnutrition. In
addition, normal albumin values are lower in pregnancy.
Prothrombin time
The liver synthesizes blood clotting factors II, V, VII, IX
and X. The prothrombin time (PT) does not become abnormal until
more than 80 percent of liver synthetic capacity is lost. This
makes PT a relatively insensitive marker of liver dysfunction.
However, abnormal PT prolongation may be a sign of serious liver
dysfunction. Because factor VII has a short half-life of only
about six hours, it is sensitive to rapid changes in liver
synthetic function. Thus, PT is very useful for following liver
function in patients with acute liver failure.
An elevated PT can result from a vitamin K deficiency. This
deficiency usually occurs in patients with chronic cholestasis
or fat malabsorption from disease of the pancreas or small
bowel. A trial of vitamin K injections (e.g., 5 mg per day
administered subcutaneously for three days) is the most
practical way to exclude vitamin K deficiency in such patients.
The PT should improve within a few days.
Blood ammonia
Measurement of the blood ammonia concentration is not always
useful in patients with known or suspected hepatic
encephalopathy. Ammonia contributes to hepatic encephalopathy;
however, ammonia concentrations are much higher in the brain
than in the blood and therefore do not correlate well.28
Furthermore, ammonia is not the only waste product responsible
for encephalopathy. Thus, blood ammonia concentrations show only
a mediocre correlation with the level of mental status in
patients with liver disease. It is not unusual for the blood
ammonia concentration to be normal in a patient who is in a coma
from hepatic encephalopathy.
Blood ammonia levels are best measured in arterial blood
because venous concentrations can be elevated as a result of
muscle metabolism of amino acids. Blood ammonia concentrations
are most useful in evaluating patients with stupor or coma of
unknown origin. It is not necessary to evaluate blood ammonia
levels routinely in patients with known chronic liver disease
who are responding to therapy as expected.
Grading Liver Function by Child-Turcotte Class
In communicating among themselves, many physicians use the
Child-Turcotte class as modified by Pugh, often termed the
"Child class," to convey information about overall liver
function and prognosis (Table 3).29 This grading system can be
used to predict overall life expectancy and surgical mortality
in patients with cirrhosis and other liver diseases.30
For elective general abdominal surgery, perioperative
mortality is in the neighborhood of several percent for patients
who fall into the Child class A, 10 to 20 percent for those in
class B and approximately 50 percent for those in class C.31
These percentages must be balanced by prognostic considerations
when transplantation becomes an option. The presence of
cirrhosis by itself is not an indication for liver
transplantation, and transplantation is rarely performed in
patients who fall into Child class A. For example, the 10-year
survival rate is as high as 80 percent in patients with
hepatitis C and cirrhosis who have Child class A liver function
and no variceal bleeding.32 However, once patients with any type
of liver disease fall into the Child-Turcotte class B or class C
category, survival is significantly reduced and transplantation
should be considered.
REFERENCES
1.Kaplan MM. Laboratory tests. In: Schiff L, Schiff ER, eds.
Diseases of the liver. 7th ed. Philadelphia: Lippincott,
1993:108-44.
2.Kamath PS. Clinical approach to the patient with abnormal
liver function test results. Mayo Clin Proc 1996;71:1089-94.
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Reviewed May 1 2004
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