METC Hepatobiliary System and Liver Function

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METC Hepatobiliary System and Liver Function

Bilirubin
Principle pigment in bile derived from the breakdown of hemoglobin
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Terms

Definitions

Bilirubin Principle pigment in bile derived from the breakdown of hemoglobin
Cirrhosis A complication of many of liver diseases that is characterized by abnormal structure and function of the liver
Extretory Discharge of waste from an organ (Liver)
Secretory Process by which substances are released from an organ for a particular purpose
Hepatitis Inflammation of the liver often caused by infections especially viral, radiation, drugs (medications), chemicals, or toxins
Jaundice The yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of bilirubin
Necrosis The death of living cells or tissues
Reticulendothelial System (RES) A group of cells having the ability to take up and sequester inert particles and vital dyes; it includes macrophages and macrophage precursors; a cluster of these cells are located in the sinusoids of liver
Lobules Are the microscopic funtional units of the liver. Are hexagonal bodies composed of plates of cuboidal hepatic cells. These cells are arranged in irregular radiating columns and plates around a central vein
Sinusoids Are branches of the portal vein and hepatic artery located between the plates of the hepatic cells. They represent the main blood supply to the liver
Kupffer Cells Are phagocytic cells that line the sinusoids and belog to the monocyte-macrophage system. Their function is to removebacteria and other foreign particles from the blood
Canaliculi Are interlobular bile ducts that form very small bile capillaries that join to form increasingly larger bile ducts until the common bile duct is reached
Biliary Tract Are the network of ducts that connect the liver, gallbladder, and duodenum.
Hepatic Bile The duct receives bile from the canliculi, and is the are where bile exits the liver.
Cystic Ducts Are ducts that deliver ile from the gallbladder, and joins with the hepatic bile duct to form the common bile duct
Common Bile Ducts Delivers bile to the doudenum which aids in digestion
Portal Vein Drains the blood from the digestive organs, and delivers blood rich in digestive end products to the liver, It is positioned between two capillary beds, one in the liver, and the other is in the digestive area. It is responsible for about two-thirds of the hepatic blood supply.
Hepatic Artery Delivers oxygen rich blood from the aorta to the liver. It provides approximately one-third of the liver's blood supply
Hepatic Vein Is in the area where blood exits the liver, and empties into the vena cava for delivery to the heart.
Identify the functions of the Heptabiliary System Excretory Function
Metabolism function and storage
Detoxification Function
Filtration Function
Synthesis
Excretory FunctionThe liver is responsible for the excretion of many substances to include bilirubin, cholesterol, and drugs.
Excretion of bile salts is essential for the digestion and absorption of fats. This includes fat-soluble vitamins in the intestine. Bile salts attach to large lipids which begins their breakdwon into smaller molecules.
Bilirubin is produced in the reticuloendothelial system (RES) from the catabolism of hemoglobin. At this point bilirubin is insoluble in water, it becomes soluble when linked to albumin for transportation in the blood to the liver.
Metabolism functionCarbohydrate metabolism plays an important role in maintaining blood glucose levels in the liver. It can either store glucose as glycogen or break glycogen down in response to decreased blood glucose concentrations.
In lipid metabolism, the liver can synthesize essential lipids, breakdown fatty acids, or converts excess dietary protein and carbohydrates to fats. The protein and carbohydrates can then be stored for future use in the liver.
In protein metabolism in the liver can make many different amino acids and is the center for urea formation. Nitrogen from ammonia form into urea for later excretion
Protein Storage Vitamin and mineral storage happens in the liver. The liver is one of the storage sites for fat-soluble vitamins (A,D,E, and K) and many other metallic ions (Fe, Cu, etc.)
Detoxification FunctionThe liver converts toxi and relatively insoluble compounds into forms that are less-toxic and/or more water-soluble for excretion by the kidney
Detoxification process may involve the gain or loss of functional groups or the conjugation with cerain amino acids, glucuronic acid, sulfate, or reduced by glutathione to enhance excretion.
Filtration Function The phagocytic action of Kupffer cells removes bacteria and particles from the blood. Kupffer cells line the sinusoids which ehlp remove bacteria and other foreign particles in the blood.
Function of Aspartate Aminotransferase (AST) Is a transferase class enzyme
Catalyzes the transfer of an amino group or amino acid between aspartate and alpha-keto acids.
Widely used enzyme that aids in the diagnosis of several liver pathologies
Tissue sources of Aspartate Aminotransferase Primary
Liver
Heart
Secondary
Skeletal Muscle
Kidney
Pancreas
Clinical Significance of Aspartate AminotransferaseIs useful for identifying necrosis or inflammation of the liver
Elevated activity seen in:
Chronice active or chronic persistent hepatitis
Cirrhotic Liver
Muscular dystrophy, dermatomyositis, and pulmonary emboli
Acute pancreaitis, crush injuries, gangrene, and hemolytic disease
If specimen is hemolyzed AST will be elevated.
Test Methodology of Aspartate AminotransferaseEnzymatic Analysis
Is assay through coupling reaction.
The change in absorbance at 340nm with time is due to the production of NAD+. This is directly proportional to the AST activity.
Specimen of choice for AST is serum
Fasting preferred specimen
Specimen should be non-hemolyzed
Specimen should be free of lipemia
Function of Alanine Aminotransferase (ALT) Is a transferase class enzyme.
Catalyzes the reversible transfer of an amine group from the amino acids alanine and glutamate to the alpha-keto acids, alpha-ketoglutarate and pyruvate.
Tissue source for Alanine Aminotransferase Liver is the main source
Also concentrated in the Kidney
Clinical Significance of Alanine AminotransferaseSerum ALT levels are more useful in acute viral Hepatitis and cholestatic disease, compared to AST, which is most useful in chornic or infilitrative lesions.
Increased rapidly during acute hepatitis 15 to 20 time's upper limit of normal along with AST
In acute deases, ALT elevates as high as or higher than AST. ALT is more specific liver enzyme marker than AST. Ast level are normally 2.5 times greater than ALT in the liver
Serum ALT is also useful for screening blood donors for viral heptatitis.
Cerain drugs and alcohol may also increase ALT activity.
Test Methodology of Alanine Aminotransferase Enzymatic analysis
ALT is determined by a coupled enzymatic reaction
The concentration of NADH is measure at 340nm by continuous monitoring.
Specimen of choice is serum
Fasting specimen is preferred
Specimen sould be non-hemolyzed (elevated results)
Specimen should be free of lipemia
Function of Gamma-glutamyltransferase (GGT) is a transferase class enzyme
Catalyzes the transfer of the gamma-glutamyl group from a glutamyl-peptide and an amino acid to a peptide to form a glutamyl-amino acid
Aids in the transport of amino acids through cell membranes
Is involved in glutathione metabolism
Tissue Source for Gamma-Glutamyltransferase Primary soure for the hepatobiliary system
The liver and renal tubules have the highest activity
Has been found in the pancrease, prostrate gland, salivary glans, seminal vesicles, brain and heart
Clinical Significance of Gamma-GlutamyltransferaseIs elevated activity seen in all forms of liver desease
Has the highest concentration seen in hepatic and post hepatic biliary obstructions
Is useful in identifying primary or secondary (metastatic) liver cancers
Is extremely sensitive, but non-specific indicator of liver disease.
Is used as a screening test for alcohol abuse, drug induced elevation of GGT precede other liver enzymes
Test Methodology of Gamma-GlutamyltransferaseEnzymatic analysis
The p-nitroaniline produced in the reaction is determined by its yellow color, which is measured spectrophotometrically at 405nm and 37 C
Specimen of choice is serum
Fasting specimen is preferred
Specimen should be non-hemolyzed for the GGT test ( if hemolyzed GGT will be elevated)
Specimen should be free of lipemia
Function of Alkaline Phosphatase (ALP) Is a hydrolase class enzyme (the addition of water)
is associated with bone calcification and lipid transport
The exact metabolic function is unknown at this time
In the lab it catalyzes the transphophorylation of p-nitrophenylphosphate (p-NPP) to be p-nitrophenol (p-NP) in the presence of the buffer 2-amino-2methyl-1-propanol (AMP)
Tissue source of Alkaline Phophatase Is present in practically all tissues in the body
Liver and bone are the main sources of ALP
Spleen, kidney and intestines are secondary sources for ALP
Placenta (2nd and 3rd trimester) due to growth of fetus elevates ALP
Clinical significance of Alkaline PhosphataseThe liver responds to biliary obstruction by synthesis of ALP
Marked elevations are seen in extra-hepatic obstructions such as stones
Bone disease shows the highest activities of ALP
Serum levels are increase in pregnancy, and during bone growth. The reference range in children is dependent upon age and whether active growth is occuring.
Test Methodology of Alkaline PhosphataseEnzymatic analysis
In the lab, ALP catalyzes the removal of phosphate from 4-nitrophenyl phosphate to produce a chromgenic product 4-nitrophenoxide. The production of nitrophenoxide is spectrophotometrically measure at 405nm
Specimen of choice is serum
Fasting preferred
Specimen should be non-hemolyzed
Specimen should be free of lipemia
Function of Lactate Dehydrogenaseis an oxidoreductase class enzyme
Catalyzes the reversible converstion of lactate to pyruvate with the use of NAD+ as the hydrogen acceptor.
Physiological importances of LD are five isoenzymes formed in the final step of glycolysis, glucose is oxidized to pyruvate and NADH is the by-product. During anaerobic conditions the cycle is either slowed or stopped. LD converts pyruvate to lactate so glycolysis can continue
Tissue Sources for Lactate Dehydrogenase Of the five LD isoenzymes LD5 is specific to the liver
Is found in the cytoplasm of the cells
Is a non-specific disease maker. It is found in the heart, lung spleen, RBCs, and muscle
Clinical Significance of Lactate DehydrogenaseCellular lysis results in the loss o cytoplasm which elevates LD serum levels
Massive platelet destruction and pulmonary embolism
Lymphatic system pathophysiology
Elevated LD5 isoenzyme is liver disease. LD5 is the isoenzyme that is predominately in the liver
Liver Disease
Cirrhosis
Hepatitis
Liver carcinoma
Muscle (LD 1 and 2)
Injuries which occur with extreme exercise or crushing injuries (car accidents)
Inflammatory or degenerative diseases such as muscular dystrophy
Multi-system disease or injuries
Hypoxia
Extreme hyperthermia
Albumin Is a small globular protein that represents the most abundant protein in blood. It is almost entirely by the liver.
Clinical Significance of AlbuminMay be measured as an indicator of liver's protein synthesis capability
It is a sensitive indicator of liver diseasebut non-specific
Low serum albumin can also be found in burns, severe infections, maluntrition, and renal disease
Low serum albumin with an increase prothrombin time usually indicated impaird liver protein synthesis
Correlates with the severity of functional liver impairment best in chronic diseases, rather than acute liver diseases.
Ammonia Is the toxic compound that is normaly formed in the body from the breakdwon of proteins by bacteria and amino acid, which naturally occur in the body.
Clinical Significance of Plasma Ammonia LevelsMeasurements are useful in diagnosis of Reye's syndrome
Increases in plasma are caused by the liver's inability to metabolize ammonia to urea usually due to cirrhosis or hepatitis
Increased plasma ammonia is associated with the develpment of hepatitis with decreased mental capacity, and eventually stupor, coma, and death.
Function of Bilirubin The breakdown of the heme portion of hemoglobin
Clinical Significance of BilirubinIncreases can cause Jaundice
Increased levels can also indicate conditions such as Gilbert's and Grigler-Najjar syndromes
Useful in testing Neonatal patients for physiological jaundice a typical condition resulting from short-term liver immaturity
Specimen of choice is serum
Fasting preferred
Specimen should be non-hemolyzed
Specimen should be free of lipemia
Protect specimen from light
Test Methods for Bilirubin Modified Evelyn-Malloy Method
Jendarassik and Grof Method
Direct Spectrophotometry (Neonatal Bilirubin)
Modified Evelyn-Malloy MethodSodium nitrite is added to sulfanilic acid to form diazo reagent. The diazo reagent reacts with conjugated bilirubin to form a red-violet azobilirubin, which is measured at 540nm on the spectrophotometer
Methanol reagent is then added to the mixture to develop the conjucated bilirubing. Total bilirubin can then be measured at 540nm
The procedure measures conjugated (direct) bilirubin, and total bilirubin. Unconjugated (indirect) is calculated by subtraction
This testing method is very susceptible to hemolysis, which interferes causing elevated test results
Jendrassik and Grof MethodTotal bilibrubin is measured by adding sodium benzoate-caffeine reagent (accelerator) to the specimen following by the addition of diazotized sulfanilic acid. During the incubation period, both conjugated and unconjugated bilirubinreacts with the diazo reagent to produce azobilirubin.
Ten minutes after the addition of diazoitized sulfanilic acid solution, ascorbic acid, alkaline titrate, and diluted HCl are added a color reaction takes place resulting in blue azobilirubin
The absorbance of the resulting blue azobilirubin is then measured at 600nm
This method is used in automation and is the most commonly used testing method in the clinical laboratory. it is less susceptible to hemolysis interference than the Evelyn Mally method
Procedure measures conjugated (direct) bilirubin, and total bilirubin. Unconjugated (indrect) is calculated by subtraction
Direct Spectrophotometry (Neonatal Bilirubin)The absorbance of serum bilirubin at 454nm is proportional to the concentration of bilirubin. The serum of neonates does not contain carotene and other pigments that increase the absorbance at 454nm
Hb, which also absorbs at 454nm, is corrected for by subtracting the absorbance at 540nm
Procedure measures total bilirubin only
Commonly used instrument in neonatal nurseries is the bilirubinometer
Use is limited to neonates because of strong interference from carotenoids (colors in the serum in older children and adults)
Identify disorders of the Liver Cirrhosis
Hepatitis
Hepatic Tumors
Drug and Alcohol related to Liver diseases
Cirrhosis diseaseLiver has a capacity for limited regeneration. Excessive hepatic damage an subsequent regeneration results in irreversible scarring with the formation of fibrotic connective tissue. This results in loss of functioning liver cells and impaired blood flow through the liver
Most commonly caused by alcohol abuse but also can be caused by primary biliary cirrhosis
Hepatitis diseaseInflammation of the liver caused by infections sepcifically viral, radiation, drugs, chemicals, or toxins,
Hepatitis has many forms, some of the most common are:
Acute Viral Hepatitis A transmitted by fecal-oral route either by contaminated food or water.
Acute Viral Hepatitis B transmitted by blood, body fluids, and sexual routes
Hepatic Tumors disease Cancerous tumors from the liver target primary sites such as lunch, pancreas, gastrointestinal tract, or ovary
Pre-existing cirrhosis or Hepatitis-B is often associated with primary liver carcinoma
Drug and Alcohol related to Liver DiseaseDrugs, chemical, and metabolites of both are toxic to the liver. Ethanol is most abused drug that affects the liver. Chronic or heavy use can lead to cirrhosis. Ethanol is the most common cause of cirrhosis in the United States.
Acetaminophen is just one of the toxic drugs that affect the liver. When taken in large doses it can produce fatal hepatic necrosis unless rapid treatment occurs.
Other drugs cause milder symptoms with elevated liver function tests

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