functions of the liver Flashcards
What are the 5 possible fates of glucose that enter the liver from the bloodstream?
Glucose-6-phosphate is dephosphorylated to free glucose, which is exported to replenish blood glucose.
Glucose-6-phosphate not immediately needed to form blood glucose is converted into glycogen.
oxidized for energy (Normally, however, fatty acids are the preferred fuel for energy production in hepatocytes)
Excess is oxidised into acetyl-CoA, which is a precursor for the synthesis of lipids.
substrate for pentose phosphate pathway, yielding both reducing power (NADPH) needed for the biosynthesis of fatty acids and cholesterol, and ribose-5-phosphate, a precursor in nucleotide biosynthesis.
What are the 6 possible fates of the lipids that enter the liver from the bloodstream?
converted into liver lipids.
Fatty acids are the major oxidative fuel in the liver. Fatty acids may be oxidized to acetyl-CoA which is further oxidized via the citric acid cycle.
Excess acetyl-CoA released by oxidation of fatty acids is converted into ketone bodies, which are circulated in the blood to peripheral tissues, to be used as fuel for the citric acid cycle.
biosynthesis of cholesterol, which is required for membrane synthesis. Cholesterol is also the precursor of all steroid hormones and bile salts.
converted to phospholipids and triacylglycerols and transported as plasma lipoproteins. Cholesterol and cholesterol esters are also transported as lipoproteins.
Free fatty acids are bound to serum albumin and are carried in the blood to the heart and skeletal muscles, to be oxidised as a major fuel.
What are the 5 possible fates of the amino acids that enter the liver from the bloodstream?
as precursors for protein synthesis in hepatocytes. The liver is the site of biosynthesis of most of the plasma proteins and coagulation factors.
Amino acids may pass from the liver into the blood and thus to other organs, to be used as precursors in the biosynthesis of tissue proteins.
Certain amino acids are precursors in the biosynthesis of nucleotides, hormones, and other nitrogenous compounds in the liver and other tissues.
Amino acids not needed for biosynthesis are deaminated and degraded to yield pyruvate, acetyl-CoA or citric acid cycle intermediates.
4a. Acetyl-CoA may be oxidized via the citric acid cycle for energy
4b. Ammonia released is converted to urea.
In the periods between meals, expecially if prolonged, there is some degradation of muscle protein to amino acids.
Alanine is transported to the liver and deaminated.
The resulting pyruvate is converted by hepatocyte into blood glucose (via gluconeogenesis) and the ammonia is converted into urea for excretion.
The glucose returns to the skeletal muscle to replenish muscle glycogen stores.
Storage functions
Glycogen, Vitamins A, D, B12, Iron
Vitamin A is the vitamin stored in greatest quantity in liver.
When extra iron is available in body fluids, it combines with apoferritin (a protein found in large amounts in hepatocytes) to form ferritin, which is stored in hepatocytes.
Immunological function
The reticuloendothelial system of the liver contains many immunologically active cells.
Bacteria and other antigens carried to the liver from the gastrointestinal tract are phagocytosed and degraded by Kupffer cells.
Kupffer cells are activated by several factors eg. infection. They secrete interleukins, tumor necrotic factor (TNF), collagenase and lysosomal hydrolases.
Antigen are degraded without the production of antibody. Thus they are prevented from reaching other antibody-producing sites in the body and thereby prevent generalized adverse immunological reactions.
Hormone and drug inactivation
Hormones such as insulin, glucagon, oestrogens, growth hormone, glucocorticoids and parathyroid hormone are taken up by the liver, where they are inactivated and converted into highly polar metabolites.
Drugs, alcohol and other foreign substances are also metabolized by similar reactions.
define Liver function test
is it a reliable indicator of liver function ?
how should be interpreted ?
Refers to a panel of biochemical test that are often deranged in patients with liver diseases.
No single test is a reliable indicator of liver function – liver has many different functions and diversity of possible diseases.
Should be interpreted in the context of clinical scenario with understanding of the degree of reliability /specificity of the test.
The 4 various uses of liver function test:
Screening
Non invasive, sensitive screening for liver dysfunction
Helpful to recognise type of liver disease
Eg differentiate btw acute viral hepatitis and cholestatic disorders
Assess severity of certain diseases
Helpful in follow up of certain liver diseases
eg evaluating responses to therapy
Limitations of Liver function test
Lack sensitivity
LFT may be normal in certain liver diseases
Lack specificity
Serum albumin may be decreased in chronic liver diseases ( as Albumin is synthesized in the liver) and also in nephrotic syndrome.
Aspartate aminotransferases may be raised in cardiac diseases and hepatic diseases (When liver cells are damaged, AST leaks out into the bloodstream and the level of AST in the blood becomes higher than normal.)
Bilirubin
- what does it asses?
- What are prefix for conjugated?
- How to measure unconjugated?
- In urine what kind of bilirubin found?
- What is seen in Jaundice without bilirubinuria?
- examples of conditions?
- what does increased conjugated bilirubin in blood lead to?
- Assesses conjugated (H2O soluble) and unconjugated (lipid soluble) fractions
- Conjugated fraction (mono- and diglucuronide) also called direct- it gives a direct reaction with diazo reagent
- The unconjugated (indirect) is total minus direct
- Conjugated but not unconjugated bilirubin can be found in urine
- Jaundice without bilirubinuria leads to increased level of unconjugated bilirubin in blood– seen in haemolysis or failure of bilirubin uptake by liver
- increased conjugated bilirubin in blood leads to cholestasis (decrease in bile flow) (e.g. intrahepatic cholestasis of hepatitis)
Test of synthetic functions
Prothrombin time
Serum aspartate aminotransferase (Aspartate transaminase , AST)
Serum alanine aminotransferase (Alanine transaminase, ALT)
Serum alkaline phosphatase (ALP)
gamma-Glutamyltransferase
Serum albumin
- site of synthesis
- half life
- Is it a reliable indicator?
- when it decreases?
- Specificity for liver disease.
- when can hypoalbuninemia occur?
- Liver is the only site of synthesis
- Long half-life ~ 20 days
- Not reliable indicator in acute liver disease (acute hepatitis)
- decreases in chronic liver disease
normal range 35 – 45g/dl
Hypoalbuminemia not specific for liver disease .
May occur in protein malnutrition, nephrotic syndrome.
Prothrombin time
Major site of synthesis of most blood coagulation proteins
Results expressed in sec or as ratio of plasma prothrombin time to control plasma time.
Normal control 9-11 sec
Short half life of the factors makes this a sensitive marker for acute and chronic liver disease
Increased PT associated with liver disease may be due to
Hepatocellular dysfunction
Vit K deficiency
In cholestasis, impaired absorption of vit K, vit K dependent factors are not synthesised, ↑PT .
(Bile salt in GIT is necessary for absorption of fat soluble vitamin including vit K).
Treatment with Vit K will distinguish ↑PT due to cholestasis from that due to hepatocellular damage
Serum aspartate aminotransferase (Aspartate transaminase , AST)
- Occurs in ?
- specific
- present in
- High levels seen in
Occurs in cytosol and mitochondria of cells
Not specific to liver
Also present in heart, muscle, kidney and brain.
High levels seen in injury to any of these - hepatocellular disease, MI, muscle injury,
Serum alanine aminotransferase (Alanine transaminase, ALT)
- type of enzyme
- found primarily in?
- increases parallel to?
Is a cytosolic enzyme
Found primarily in liver – relatively specific to liver – raised only in liver cell damage
Increases parallel to AST in liver disease
