Liver Function
What is the diagnostic criteria for autoimmune hepatits?
1. Immunoglobulins - high. 2. Positive autoantibodies. 3. Biopsy 4. Viral serologies (Negative for hep A, B, C). Identification can be difficult.
Cholestatic type of Hepatic Jaundice
1. Simulates post hepatic jaundice very closely; 2. Also called "intra hepatic cholestasis" a term that describes the fact that bile flow into the duodenum is inhibited by intrahepatic disease.
Bilirubin was first demonstrated in the serum
by Vanderbergh and Muller. They found that serum from patients with jaundice caused by hemolysis gave the indirect reaction (reacted with Ehrlich's diazo reagent only in the presence of alcohol.) While in the serum of pts with jaundice due to obstruction of the biliary tract - the increased serum bilirubin levels gave the direct reaction (reacted to diazo reagent without the addition of alcohol)
What are some causes of minor elevation of AST and ALT (less than 100 U/L)?
chronic hep C, chronic hep B, hemochromatosis, fatty liver
The total serum globulin level is often elevated in patients with
cirrhosis.
The exclusion of bilirubin from the duodenum results in
clay-colored feces and very low levels of urobilinogenin feces and urine
The bile duct carries bile from the liver to the gallbladder which when stimulated by cholecystokinin does what?
contracts and releases bile through its duct, termed the cystic duct. This joins the common hepatic duct to for the common bile duct.
Most commonly used method for analyzing total serum bili is done by
converting bilirubin into a diazo dye intensity of the color being proportional to the quantity of the bilirubin
Laboratory findings in chronic Wilson's disease include
decreased ceruloplasmin, free plasma copper, total plasma copper, and urine copper.
The liver produces bile which aids in the
digestion of fats and the absorption of fat-soluble
Important role of the liver is the removal of toxic endogenous and exogenous substances from the blood and then
excretion into the bile conversion to products for excretion by Kidneys or Lungs
Indirect bilirubin is
free or unconjugated bound to albumin en route to the liver from the R.E. system. It is not soluble in water.
An increased level of fecal urobilinogen is evidence of
hemolysis.
Increased levels of urine urobilinogen are observed in
hemolytic jaundice and with subsiding hepatitis.
Bilirubin does not appear in the urine in
hemolytic jaundice.
High values of alpha-fetoprotein are almost always diagnostic of
hepato cellular carcinoma in adults. In children, such high values may reflect teratoblastomas of the testes and ovary.
less common causes of acute viral hepatitis include
herpes virus , cytomegalovirus, parvovirus B6 (in children), Varicella zoster and Epstein-Barr.
Crigler-Najjar syndrome which causes
hyperbilirubinemia with kernicterus.
In cirrhosis of the liver, a constant finding is
impaired glucose tolerance in association with hyper-insulinemia. Glucose uptake and glycogen synthesis will be impaired resulting in decreased glycogen storage in the liver.
A marked increase in amino acids is found only
in Severe liver damage. The increased plasma levels also lead to increased urinary excretion. In severe liver disease the increase in amino acid excretion in the urine may be sufficient to cause the formation or leucine and tyrosine crystals in urinary sediment.
Hepatocellular jaundice results from
injury to the parenchyma. Examples are: viral hepatitis, toxic hepatitis, cirrhosis.
Bilirubin is excreted by the hepatocytes and passes with the bile into the
intestines where it is reduced by bacterial action to urobilinogen.
Most common causes of elevated AST and ALT activities are either
ischemic or toxic liver, especially from drugs and toxins.
The liver has a great reserve capacity which means
it can nearly be removed without seriously affecting its function
Prothrombin is formed by the
liver cells which require vitamin K for the process.
GGT elevation is also associated with
non-alcohol-related diseases and is not a specific biomarker when used by itself.
Fecal urobilinogen decreased levels are characteristic of
obstructive (post-hepatic) jaundice but may also be found in patients with hepatocellular jaundice
In general cholesterol is normal or depressed in hepato cellular jaundice and elevated in
obstructive jaundice
In acute viral hepatitis, AST and ALT activities
peak before the appearance of jaundice, but decrease more gradually to normal levels within 3-5 weeks.
Urine Urobilinogen: Levels are decreased in
post hepatic jaundice.
Serum haptoglobin is elevated in patients with
post-hepatic jaundice and lower in those with hepatocellular disease.
Most used method to test for urine bilirubin
tablets or dipsticks impregnated with diazo reagent.
Urine Bilirubin: The presence of bilirubin in the urine of a patient with jaundice shows
that the hyperbilirubinemia is of the conjugated type
Ceruloplasmin is what?
the Copper containing protein in plasma. Its main function is to transport copper. A low serum concentration of ceruloplasmin occurs in about 95% of patients who are homozygous and in about 10% of subjects who are heterozygous for Wilson's disease, which has a defect in the synthesis of this protein
Total Serum Bilirubin: this level is useful in evaluating
the depth and progress of jaundice.
One of the most important roles of the liver is
the detoxification of injurious substances.
In Post-hepatic Conjugated jaundice, obstruction of the biliary tree produces jaundice by preventing
the entry of bilirubin that has been conjugated into the duodenum. The bilirubin is backed up into the blood, raising the level of direct bili which then appears in the urine. The exclusion of bilirubin from the duodenum results in clay-colored feces and very low levels of urobilinogenin feces and urine
The major portion of the urobilinogen is excreted in
the feces. Some is reabsorbed into the blood and re-excreted by the liver.
Alpha-fetoprotein (AFP) is present in moderate amounts in the serum of
the fetus , infant and normal pregnant female. Therefore not a good test for liver disease in the population.
Serum Protein Electrophoresis is useful to demonstrate
the globulin fraction, which is elevated in active macronodular cirrhosis and in chronic active hepatitis hyperglobulinemia represents large increases in the immunoglobulins of the gamma globulin fraction.
An extremely low level of fecal urobilinogen is evidence that
the jaundice is post hepatic
Plays an active role in detoxification of drugs and other harmful substances and in the metabolism of drugs
the liver
What is the primary organ responsible for the metabolism of carbohydrates, proteins, lipids, porphyrins, and bile acids
the liver
Also has an important role in production of some substances necessary for bleed coagulation metabolism and storage of iron plus the formation and breakdown of hemoglobin
the liver coag metabolism
Carbohydrate Metabolism
the liver plays an important role in controlling carbohydrate metabolism by maintaining glucose concentrations in a normal range. This is achieved by a tightly regulated system of enzymes and kinases regulating either glucose breakdown or synthesis in the hepatocytes. In liver disease, alterations in hepatic glucose metabolism following carbohydrate ingestion occur.
Central role in metabolism of carbs and in formation of proteins
the liver role
Amino acid metabolism, urea synthesis, and protein metabolism occur in
the liver.
Fibrinogen is produced exclusively by
the liver. This is not a sensitive liver test since in very severe forms of liver disease the fibrinogen content of the blood is not altered greatly from normal values.
Post-hepatic Conjugated obstructive is commonly called obstructive jaundice. What is it usually the result of?
the obstruction of the common duct or hepatic duct.
Degree of prolongation of the PT in a patient with parenchymal hepatic disease is a useful measure of
the severity of the hepatic injury. In acute hepatitis marked prolongation of the value is a sign that may bring a fatal outcome
The liver is involved in many phases of lipid metabolism including
the synthesis, esterification and excretion of cholesterol.
Even in severe hepatocellular disease, the ability to conjugate remains unimpaired and as such
there is a distinct increase in the direct bilirubin in the urine
Gilbert Syndrome characteristics include
transport deficit in sinusoidal membrane of the hepatocyte. Very little or no conjugation of bilirubin.
In patients with hepatitis, the serum cholesterol may be mildly decreased or normal, but the level of esterified cholesterol is
usually moderately decreased.
In severe cirrhosis the serum cholesterol is
very low
Tool to predict fibrosis and cirrhosis in chronic hepatitis C patients - AST to platelet ratio index.
APRI = AST level (U/L) / Platelet count. Scores less than 0.5 had a negative predictive value of 86%, where scores greater than 1.5 had a positive predictive value of 88% for identifying fibrosis and subsequent cirrhosis. APRI is also used based on observation that AST is elevated whereas platelet counts are reduced in patients with alcoholic hepatitis. (APRI will be elevated)
What is formed by the breakdown of hemoglobin by the cells of the RE system (Spleen, Bone Marrow, Kupffer cells of the liver)?
Bilirubin
What is one mechanism by which the liver detoxifies injurious substances?
Chemical reactions to form substances that are less toxic or more readily excreted by the kidneys through conjugation with glucuronic acid, glycine or other compounds.
This type of jaundice is seen most commonly with certain drug reactions; it is thought to occur as a result of Viral hepatitis or it may be idiopathic.
Cholestatic type of Hepatic Jaundice
Serum Bile Acids are products of
Cholesterol metabolism, the primary bile acids are conjugated with glycine and taurine prior to their transport into bile. During the fasting state, the conjugated primary bile acids, after secretion into the bile, are stored in the gallbladder. During digestion, they are excreted into the lumen of the GI tract.
The serum globulin level is often elevated in patients with
Chronic hepatic disease and chronic hepatitis, representing mainly immunoglobulins or gamma globulin fractions.
Most frequently used markers of alcohol consumption are
GGT, ALT and AST with the RBC MCV.
Hepatic Unconjugated Jaundice includes which syndromes we discussed?
Gilbert syndrome and Crigler-Najjar syndrome. Characteristics are fecal and urine urobilinogen are normal. Resembles hemolytic in that it is mostly unconjugated bili.
Characteristics of Unconjugated Jaundice
High fecal urobilinogen. High urine urobilinogen.
Autoimmune hepatitis (ATH) is generally a unresolved inflammation of the liver of unknown origin. What population is it highly prevalent in?
Highly prevalent in young and middle-aged women with a female to male ratio of 3.6:1.
Prothrombin can be reduced in two ways
I) in obstructive jaundice - the absence of bile salts severely reduces the absorption of Vit k from the intestines 2)In severe liver damagethe liver is less able to form prothrombin even in the presence of adequate amounts of the vitamin.
Levels of bile acids are what in the blood and urine of patients with obstructive jaundice?
Increased
The serum albumin level is an index of
Severity and prognosis in patients with chronic hepatic disease. Patients who show a rise of serum albumin have a better prognosis than those whose levels remain low
Bilirubin circulates in the blood bound to
albumin then goes to the liver. A small amount of bilirubin is excreted by the Kidneys
What are some causes of moderate elevation of AST and ALT (100-300 U/L)?
alcoholic hepatitis, non-alcoholic hepatitis, autoimmune hepatitis, Wilson's disease.
AST/ALT ratio greater than 1 in 92% of patients and greater than 2 in 70% of patients with
alcoholic liver disease
Serum Haptoglobin - This protein migrates with the
alpha 2 globulins
What are some causes of major elevation of AST and ALT (greater than 1000 U/L)?
autoimmune hepatitis, acute viral hep, ischemic or toxic injury
What percent of serum bilirubin is Unconjugated?
At least 80% of serum bilirubin is indirect
In some cases of liver damage from drugs or toxins, liver injury may not be evident until as much as
12 month following initiation of treatment. Common drugs falling into this category are non-steroidal anti-inflammatory drugs, Antibiotics anti-epileptic drugs, anti - TB drugs, and some herbal supplements.
Acetaminophen poisoning accounts for almost one-half of all cases of acute liver failure in the US. In 90% of acetaminophen-induced liver injury, AST + ALT are greater than
3000 U/L and peaks within 24 hours after admission and decline rapidly and reach near normal within 7 days following onset of injury.
AST/ALT ratio in non-alcoholic fatty liver is usually
<1.0. An AST/ALT ratio of greater than 1 indicates an advanced fibrotic form.
Jaundice is caused by
An increased bilirubin concentration in the blood stream
Can indirect bili be excreted in the urine?
It is tightly bound and cannot be filtered at the glomerulus so it is not excreted in the urine
What is the gold standard for diagnosis of non-alcoholic fatty liver?
Liver biopsy
Prehepatic Unconjugated Jaundice (hemolytic)
Liver function may be relatively normal, but it is not able to cope bilirubin production. This type can also result from any genetic or acquired types of hemolytic disease. (Such as *sickle cell*)
Extraction of foreign dyes from the blood by the liver can be applied to the testing of hepatic function. Three dyes have been used for this purpose:
Rose, Bengal sulfobromophtalein (BSP), and indocyanine green (IGG).
Liver Function Testing
No one measurement or test of liver function is sufficient for clinical analysis of most problems. A profile is most applicable to a particular problem should be selected. These tests along with radiographic, endoscopic, and liver biopsy should permit diagnosis of almost all patients with hepatic disease
Function and physiology of the liver
One of the largest organs; B. Made up of hepatocytes. Functions include: 1. Metabolism; 2. Synthesis of critical components; 3. Bile formation; 4. Endocrine function
Principal storage site of Lipids and Vitamins is where?
The liver.
Non-alcoholic fatty liver disease has 4 types:
Type 1 - fat alone, Type 2 - fat plus inflammation, Type 3 - Fat plus ballooning degeneration, Type 4 - Fat plus fibrosis
Prothrombin Time and Vitamin K response
Used chiefly for the control of anticoagulant and for liver function test
Direct (conjugated bili) is polar/nonpolar? Can it be excreted in urine?
a polar compound (water soluble). It reacts directly with diazo reagent and appears in the urine when serum levels are increased.
Alpha-1-antitrypsin is a genetic liver disease is characterized by
a very low plasma level of alpha-1-antitrypsin. The manifestations of the condition include liver disease of the infant, childhood, or even maturity.