SEM 1 - (CC) LIVER FUNCTION TEST 1 Flashcards
It is the chief metabolic organ in the body with lobules as its microscopic and function units.
Liver
Liver framework is composed of 3 systems, what are those 3?
Hepatocytic
Hepatobiliary
Reticuloendothelial
The liver receives _____ of blood per minute from the portal vein for filtration while it also delivers toxins to the liver for processing and detoxification.
15 mL
In the liver, to eliminate toxins such as alcohol, two enzymes are essential in the pathway, which are?
- alcohol dehydrogenase
and
2, acetaldehyde dehydrogenase.
a unique organ with the capacity to regenerate cells that have been damaged, injured, or removed.
liver
_______ of the remaining tissue in case of tissue injury due to biliary obstruction or toxic exposure is a distinguishing feature of the liver.
Hypertrophy
______ are the primary liver parenchymal cells and play complicated roles in fibrosis and cirrhosis;
Hepatocytes
In hepatocytes ; the targets for most hepatotoxic agents, including what?
hepatitis viruses, alcohol metabolites, and bile acids
Major Cell Types of Liver:
- Hepatocyte
- Kupfer Cell
major liver cell type that represents 80% of the volume of the liver; performs the major hepatic functions; responsible for
the regenerative property.
Hepatocyte
Major live cell type that has the phagocytic role; it is the hepatic macrophage, engulfing organisms and toxins.
Kupfer cell
5 Functions of the Liver:
- Synthetic Function
- Conjugation Function
- Detoxification and Drug Metabolism
- Excretory and Secretory Function
- Storage Function
Synthetic Function of the Liver:
- The liver secretes the ff….
- The normal liver produces about ______ of albumin daily,
- It is also involved in the metabolism of cholesterol into ______
- plasma proteins, carbohydrates, lipids, lipoproteins, clotting factors, ketone bodies, enzymes, and xenobiotics.
- 12 grams
- bile acids.
Conjugation Function of the Liver:
- ____ is the site of liver metabolism.
- ______ of bilirubin is produced daily in the healthy adult.
- Liver
- 200 to 300 mg
Detoxification and Drug Metabolism of Liver:
- Liver serves to protect the body from potentially injurious substances absorbed from the intestinal tract and toxic by-product of metabolism.
- ______ (toxic by-product) is converted to urea in the liver.
Ammonia
Excretory and Secretory Function of Liver
- Excretion of bile involves the elimination of _______, _______ and _____
- Bile acids (_______ and _____) are conjugated with the amino acids _____ and _____ to form bile salts.
- bile acids or salts, pigments, and cholesterol.
- cholic acid and chenodeoxycholic acid ; glycine and taurine
Storage function of liver:
- Storage site for all _____ and _____ vitamins.
- Liver is also the storage depot for ______, which is released when glucose is depleted.
- fat-soluble and water-soluble
- glycogen
MAJOR LIVER FUNCTION TESTS
- TESTS MEASURING THE HEPATIC SYNTHETIC FUNCTION
- TEST MEASURING CONJUGATION AND EXCRETION FUNCTION
- TEST FOR DETOXIFICATION FUNCTION
Liver function test that is useful in quantitating the severity of hepatic dysfunction.
TESTS MEASURING THE HEPATIC SYNTHETIC FUNCTION
In TESTS MEASURING THE HEPATIC SYNTHETIC FUNCTION ;
_____ and ________ provide the most useful indices for assessing severity of liver disease.
Serum albumin and the vitamin-K-dependent coagulation factors
Proteins are abundantly produced in liver except the _______
immunoglobulins
Routine Markers in TESTS MEASURING THE HEPATIC SYNTHETIC FUNCTION
Total protein, albumin, globulin, and albumin/globulin ratio
Secondary Markers in TESTS MEASURING THE HEPATIC SYNTHETIC FUNCTION
Prothrombin TIme
Analysis of proteins is important for assessing nutritional status and presence of severe diseases involving the liver, kidney, and bone marrow.
Total Protein
Plasma levels of total protein is _______ higher than serum due to _______
0.2 to 0.4g/dL ; fibrinogen.
Total protein and albumin are about ____ higher in ambulatory individuals.
10%
Transudates have a total protein of ______ (<50% of the serum total protein);
exudates has _____
<3.0g/dL ; >3g/dL.
Total protein measurement is usually performed in serum which has no _______ and no ________ that may slightly dilute proteins in plasma.
fibrinogen ; anticoagulant
In measuring total proteins in serum, ____ may not be required.
fasting
Total Protein Reference range: _________
6.5-8.3 g/dl
METHODS FOR TOTAL PROTEIN MEASUREMENT
- Kjeldahl Method
- Biuret Method
- Folin-Ciocalteu Method
- Lowry Method
5, Turbidimetric and Nephelometric Method
6, Ultraviolet Absorption Method - Refractometry
- Immunofixation Electrophoresis
- Salt Fractionation
a method for total protein measurement that is a reference method but not routinely used.
Kjeldahl Method
Kjeldahl Method is based on the measurement of __________
nitrogen content of protein.
Kjeldahl Method uses serum samples treated with _________, _______
tungstic acid, forming protein-free filtrate(PFF).
According to Kjeldahl, 1 gram of nitrogen is equivalent to ______ of proteins
6.54 grams
In kjeldahl method, the nitrogen content of proteins is about _____ to ______
15.1% to 16.8%.
Reagent in Kjeldahl Method and its end product
Reagent: Sulfuric acid (digesting agent)
End product: Ammonia
a method for total protein measurement that is most widely used method
Biuret Method
Biuret method of total protein measurement is recommended by the __________ expert panel.
International Federation of Clinical Chemistry (IFCC)
Principle: Cupric ions form a complex with the peptide bonds, forming a violet-colored chelate which is proportional to the number of peptide bonds present and reflects the total protein level at 545 nm.
Biuret Method
Biuret method requires at least two _______ and an _____ medium to measure total protein.
peptide bonds ; alkaline
It is preferred by automated analyzers since protein concentration as low as 10 or 15 mg/dL can be measured.
Biuret Method
_____ and _____ influence the Biuret method, causing falsely elevated total protein
Hemolysis and ictericia
Reagents in Biuret Method
Alkaline copper sulfate, Rochelle salt (Nak Tartrate), NaOH, and Potassium iodide
ref range in biuret method
6.5-8.3 g/dL
a method for total protein measurement that has the highest analytical sensitivity.
Folin-Ciocalteu Method
Principle: Oxidation of phenolic compounds, such a s tyrosine, tryptophan, and histidine, to give a deep blue color
Folin-Ciocalteu Method
Folin-Ciocalteu Method give a _____ color
deep blue
Folin-Ciocalteu Method main reagent and color enhancer
Main reagent: Phosphotungstic-molybdic acid o r phenol reagent
Color enhancer: Biuret reagent
a method for total protein measurement that utilizes the reagents of Folin-Ciocalteu method (phenol) and biuret method where the addition of phenol reagent to the biuret reagents improves the color formation.
Lowry Method
a method for total protein measurement that utilize sulfosalicylic acid and or trichloroacetic acid.
Turbidimetric and Nephelometric Method
Turbidimetric and Nephelometric Method Measurement depends on the formation of a uniform fine precipitate which scatters incident light in suspension (______) or block light (______).
nephelometry ; turbidimetry
Turbidimetric methods is also used in _____ and ______ specimens.
CSF and urine
Principle: The absorbance of proteins at 210 nm is due to the absorbance of the peptide bonds a t specific wavelength.
Ultraviolet Absorption Method
In Ultraviolet Absorption Method, absorption of proteins at 280 nm is due to _______, ______ and _______
tryptophan, tyrosine, and phenylalanine
Proteins absorb light at ________ and ______
210 nm and 280 nm.
a method for total protein measurement that is an alternative test to chemical analysis of serum total proteins.
Refractometry
Refractometry is based on measurement of _______ of solutes in serum.
refractive index
Refractive index is not applicable for _____ measurements because of increased concentration of solutes.
urine protein
a method for total protein measurement that characterizes the abnormal bands by adding specific antisera to each sample cell of the electrophoretic gel and
the immune complex is viewed by staining
Immunofixation Electrophoresis
Immunofixation Electrophoresis is used to diagnose and monitor different plasma cell dyscrasias such as _______ and _______
multiple myeloma and Waldenstrom’s
macroglobulinemia
Immunofixation Electrophoresis is preferred in detecting (not quantification) abnormal proteins such as the _________
M-spike in multiple myeloma
a method for total protein measurement that has higher analytical sensitivity compared to the conventional electrophoresis since it can measure small abnormalities such as the beta-gamma bridging in hepatic cirrhosis.
Immunofixation Electrophoresis
a method for total protein measurement where Globulins can be separated from albumin by salting-out procedures using sodium salts.
Salt Fractionation
Salt Fractionation reagent
sodium sulfate salt
The albumin that remains in solution in the supernatant can be measured by any of the routine _______ methods ; globulin is insoluble in ____ but not in _______
total protein ; water ; dilute salt solution
SOLUBILITY PROPERTY OF PROTEINS:
WHAT PROTEIN?
Soluble: Water, Conc. Salt Solution
Insoluble: Saturated Salt Sol, Highly Conc. Salt Sol, Hydrocarbon solvents
Albumin
SOLUBILITY PROPERTY OF PROTEINS:
WHAT PROTEIN?
Soluble: Weak Salt Sol, Hydrocarbon Solvents
Insoluble: Water Saturated Salt Sol, Conc. Salt Sol
Globulin
Principle: Migration of charged particles in an electric field
Serum Protein Electrophoresis (SPE)
The single most significant clinical application of SPE is the identification of __________ and differentiating them from _____________
monoclonal spike of immunoglobulins ; polyclonal hypergammaglobulinemia.
In SPE; _______ exhibits a pattern of acute inflammation associated with tissue injury producing elevated acute phase reactants (A.AT, haptoglobin, alpha-1 antichymotrypsin).
Myocardial infarction
Major proteins that contribute to electrophoresis:
albumin
a1-antitrypsin
a2-macroglobulin
haptoglobin
B-lipoprotein
transferrin
complement C3
fibrinogen
immunoglobulins
_______ proteins increase as a non-specific response to inflammation.
Alpha 1-globulin
Normal SPE Pattern (FASTEST TO SLOWEST)
- Albumin
- A1 Globulin
- A2 Globulin
- Beta-globulin
- Gamma-globulin
Fastest band in SPE
Albumin
2nd Fastest band in SPE
what does it include?
A1 Globulin
glycoproteins, AAT, AAG, thyroxine binding-globulin (TBG)
3rd fastest band?
what does it include/
A2 Globulin
haptoglobin, AMG, ceruloplasmin
4th band
what does it include?
Beta globulin
transferrin, beta-lipoprotein, hemopexin, complement (C3 and C4)
5th & slowest band
what does it include?
Gamma-globulin
immunoglobulin and CRP
REF VALUE FOR ALBUMIN
53-65% (3.5-5.0 g/dL)
REF VALUE FOR A1-GLOBULIN
2.5-5% (0.1-0.3g/dL)
REF VALUE FOR A2-GLOBULIN
7-13% (0.6-1.0 g/dL)
REF VALUE FOR B-GLOBULIN
8-14% (0.7-1.1 g/dL)
REF VALUE FOR GAMMA-GLOBULIN
12-22% (0.8-1.6 g/dL)
ABNORMAL SERUM ELECTROPHORETIC PATTERN AND ITS RELATED DISORDER:
GAMMA SPIKE
MULTIPLE MYELOMA
ABNORMAL SERUM ELECTROPHORETIC PATTERN AND ITS RELATED DISORDER:
B-GAMMA BRIDGING
HEPATIC CIRRHOSIS
ABNORMAL SERUM ELECTROPHORETIC PATTERN AND ITS RELATED DISORDER:
A2-GLOBULIN BAND SPIKE
NEPHROTIC SYNDROME
ABNORMAL SERUM ELECTROPHORETIC PATTERN AND ITS RELATED DISORDER:
A1-GLOBULIN FLAT CURVE
JUVENILE CIRRHOSIS (AAT DEFICIENCY)
ABNORMAL SERUM ELECTROPHORETIC PATTERN AND ITS RELATED DISORDER:
SPIKES OF A1, A2, AND B-GLOBULIN BANDS
INFLAMMATION
The presence of free hemoglobin will cause _____ in the late alpha-2o r early beta zone region.
“blip”
The presence of small spikes or striking elevation in the beta region is due to ______________
Iron deficiency anemia (transferrin).
Rheumatoid arthritis and malignancy would result in _____________ classified as __________
polyclonal gammopathy ; chronic inflammation.
Other Measurements for Total Proteins:
____________ Is for detection of proteins to as little as 1 ug.
Coomassie brilliant blue dye
Other Measurements for Total Proteins:
________, which develops a violet color by reacting with primary amines, is widely used for detection of peptides and amino acids after paper chromatography.
Ninhydrin
Other Measurements for Total Proteins:
________ utilized ion-exchange columns, while ________ detects drugs as part of the toxicology screens.
Amino acid analyses ; thin-layer chromatography
DISEASE WITH INCREASED TOTAL PROTEIN
- Malignancy
- Multiple myeloma
- Waldenstrom’s macroglobulinemia
DISEASE WITH DECREASED TOTAL PROTEIN
- Hepatic cirrhosis
- Glomerulonephritis
- Nephrotic syndrome
- Starvation
The concentration of this protein is inversely proportional to the severity of the liver disease.
Albumin
Plasma levels of albumin decline when severe hepatocellular disease lasts more than ______
3 weeks.
In hepatic circulatory disorder, _____ is used because its concentration reflects the shift of protein and fluid
into ascites, and its important contribution to the plasma oncotic pressure.
albumin
Decreased serum albumin concentration may be due to ________
decreased synthesis
Low total protein and low albumin: ________ and _______
Reference range of albumin: ______
Hepatic cirrhosis and nephrotic syndrome ; 3.5-5.0 g/dl
albumin methods: dye assays
1 . Bromcresol green (BCG) . most commonly used method 2. Bromcresol purple (BCP)- most specific method
3. Hydroxyazobenzene benzoic acid (HABA)
4. Methyl orange (MO)
Albumin can be measured by direct methods based on its _______
dye-binding property.
Albumin reversible binds many ________, including dyes that do not interact with the other serum
proteins.
small molecules
______ is used extensively in automatic analyzers for determining serum albumin parallel with Biuret
reagent for total protein
BCG
____ reacts almost only to albumin compared to BCG which has affinity with minor globulins
BCP
The presence of drugs, such as penicillin, and the use of hemolyzed and icteric samples affect measurement of ________
serum albumin
_____ is affectedby the presence of penicillin leading to false decrease of albumin.
BCG
BCG and BCP are not significantly affected by ______ sample
hemolyzed
HABA method is influenced by ________
hyperbilirubinemia
_______ are catioinic dyes and free from interference from bilirubin.
BCG and BCP
- Severe dehydration
- Prolonged tourniquet application artifactual hyperalbuminemia
Hyperalbuminemia
factors in hypoalbuminemia
- Reduced Synthesis
- Increased Loss
- Increased Catabolism
Chronic liver disease
Malabsorption syndrome
Malnutrition and muscle wasting disease
related to?
- Reduced Synthesis
Nephrotic syndrome (20-30g/day) - albumin excretion is increased when the glomerulus no longer functions to restrict the passage of proteins from the blood
Massive burns
Protein-losing enteropathy Orthostatic albuminuria
related to?
Increased Loss
Massive burns
Widespread malignancy Thyrotoxicosis
related to?
increased Catabolism
4 major fractions of globulin
A1, A2, Beta, Gamma
determined indirectly through the concentration of total protein.
Globulin
Indirect method of globulin and Ref. Range
IM: Total Protein - Albumin = Globulin
Ref. Range = 2.3-3.5 g/dL
It is determined to validate if globulin is higher than albumin.
Albumin/Globulin Ratio
If globulin is greater than albumin, the phenomenon is called the _________, as seen in _______ , ______, and ________
inverted A/G ratio ; cirrhosis, multiple myeloma, and Waldenstrom’s macroglobulinemia.
_____ and even _________ may help define the clinical situations related to the inverted A/G ratio.
Serum ; urine protein electrophoresis
ref range of A/G ratio
Reference range: 1.3-3:1
If the hepatic injury is less than ___, total regeneration will occur and the total protein, albumin, and even ammonia remain normal.
80%
In the case of hepatitis, the serum protein may be normal due to less severe hepatic damage but in __________,
regeneration of the liver tissue does not ensue due to more than 80% liver damage, thus, the total protein and albumin are both decreased.
panhepatic cirrhosls.
It is the hereditary absence of albumin or the inability to synthesize albumin.
Analbuminemia
- It is the presence oftwo albumin bands intead of a single band in electrophoresis.
Bisalbuminemia
- It is the presence of albumin with unusualmolecular characteristics in the blood.
Bisalbuminemia
It is associated with excess amounts of therapeutic drugs in serum.
Bisalbuminemia
It is the presence of two albumin bands instead of a single band in electrophoresis.
Kwashiorkor
It is the lack of amino acids in an individual’s diet due to severe malnutrition, resulting in the liver’s inability to synthesize proteins and eventually decreased plasma oncotic pressure.
Kwashiorkor
It differentiatesintrahepatic disorder (prolonged protime) from extrahepatic obstructive liver disease (normal protime).
Prothrombin Time (Vitamin K Response Test)
Prolonged protime, despite vitamin K administration, indicates _________ capacity to synthesize the proteins.
loss of hepatic
Vitamin K is administered ________, __ mg daily for __ to __ days.
intramuscularly ; 10 ; 1 to 3