Introduction, Major functions of liver, Tests to assess liver function, Classification of liver function tests, Interpretation of results (Medicinal biochemistry & Clinical pharmacy)
the following document contains various diagnostic test for screening liver function. and interpretation of results, which may confirm the presence of a disease or disorder
Liver function tests are recommended in the following situations
To check dage from liver infections (hepatitis)
To monitor the side effects of certain medications that affect liver
In alcohol consumers
If already have a liver disease , to monitor the disease
For gall bladder disease
Person experiencing symptoms of liver disorder
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
the following document contains various diagnostic test for screening liver function. and interpretation of results, which may confirm the presence of a disease or disorder
Liver function tests are recommended in the following situations
To check dage from liver infections (hepatitis)
To monitor the side effects of certain medications that affect liver
In alcohol consumers
If already have a liver disease , to monitor the disease
For gall bladder disease
Person experiencing symptoms of liver disorder
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
Liver function test (LFT) includes a group of blood tests commonly performed to evaluate the function of the liver. This test measures the level of liver enzymes, proteins, and bilirubin in the blood.
For more details, visit:
https://www.1mg.com/labs/test/liver-function-test-2562
Renal function tests are very useful for effective clinical evaluation of renal failure for effective management. So it is useful for medical and allied professional students and clinical practitioners.
This is an introduction to Pharmacology, which is very helpful for nursing students. This presentation tells about classification, sources, pharmacokinetics, and pharmacodynamics of drugs.
A test in which blood or urine samples are checked for the amounts of certain substances released by the kidneys. A higher- or lower-than-normal amount of a substance can be a sign that the kidneys are not working the way they should. Also called kidney function test.
Creatinine clearance may be used as indicator for GFR because:
Creatinine is endogenously produced.
Creatinine is released into body fluid at constant rate.
Its plasma level maintained within narrow limits.
Its plasma level not affected by dietary factors
Liver function test (LFT) includes a group of blood tests commonly performed to evaluate the function of the liver. This test measures the level of liver enzymes, proteins, and bilirubin in the blood.
For more details, visit:
https://www.1mg.com/labs/test/liver-function-test-2562
Renal function tests are very useful for effective clinical evaluation of renal failure for effective management. So it is useful for medical and allied professional students and clinical practitioners.
This is an introduction to Pharmacology, which is very helpful for nursing students. This presentation tells about classification, sources, pharmacokinetics, and pharmacodynamics of drugs.
A test in which blood or urine samples are checked for the amounts of certain substances released by the kidneys. A higher- or lower-than-normal amount of a substance can be a sign that the kidneys are not working the way they should. Also called kidney function test.
Creatinine clearance may be used as indicator for GFR because:
Creatinine is endogenously produced.
Creatinine is released into body fluid at constant rate.
Its plasma level maintained within narrow limits.
Its plasma level not affected by dietary factors
1.Detect presence of liver disease.
2.Distinguish among different types of liver diseases.
3.Estimate the extent of known liver damage.
4.Follow the response of treatment
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RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
2. OUTLINE:
• Introduction
• Major functions of liver
• Tests to assess liver functions
• Classification of liver function tests
• Reference/bibliography
3. INTRODUCTION:
Liver:
Liver is the largest gland of the body weighing 1.2-1.5 kg in an adult
human.
It is situated in the abdominal cavity, just below the diaphragm and
has 2 lobes.
The hepatic lobules are the structural and functional units of liver
containing hepatocytes, arranged in the form of cords.
Liver secretes bile which is alkaline, yellowish green fluid. It has no
enzymes but help in emulsification of fats due to the presence of bile
salts.
4. MAJOR FUNCTIONS OF LIVER:
1. Metabolic functions: Liver actively participates in carbohydrate, lipid,
protein, mineral and vitamin metabolisms.
2. Excretory functions: Bile pigments, bile salts and cholesterol are
excreted in the bile into intestine.
3. Protective functions and detoxification: Kupffer cells of liver perform
phagocytosis to eliminate foreign compounds. Ammonia is detoxified to
urea. Liver is responsible for metabolism of xenobiotic (detoxification).
4. Haematological functions: Liver participates in the formation of blood
(particularly in the embryo), synthesis of plasma proteins (including
blood clotting factors) & destruction of erythrocytes.
5. Storage functions: Glycogen, vitamins A, D & B12 and trace elements are
stored in liver.
5. TESTS TO ASSESS LIVER FUNCTION:
The liver function tests (LFTs) are the biochemical investigation
to assess the capacity of the liver to carry out any of the functions it
performs. LFT will help to detect the abnormalities and the extent of
liver damage. Two important facts should borne in mind while carrying
out LFT:
1. Liver is a large size factory of safety. Therefore, it can perform many
of it's functions almost normally, despite of the damage.
2. Selection of the right test is important in LFT. This is due to the fact
that since liver participates in several functions, the function that is
measured in LFT may not be the one that is adversely affected.
6. CLASSIFICATION OF LIVER FUNCTION
TESTS:
They are classified based on the major functions of liver.
1. Tests based on excretory function: Measurement of bile pigments, bile
salts, Bromosulphthalein test.
2. Tests based on serum enzymes: Determination of transaminases (ALT,
AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase, 5’-
nucleotidase and others.
3. Tests based on synthetic function: Serum proteins (albumin, globulins),
prothrombin time.
4. Tests based on metabolic capacity: Galactose tolerance test, antipyrine
clearance.
5. Tests based on detoxification: Hippuric acid synthesis.
7. 1. TESTS BASED ON EXCRETORY
FUNCTION:
a) Bilirubin: Bilirubin is a bile pigment and is the excretory end product of
heme degradation. It is conjugated in the liver to form bilirubin diglucuronide
and excreted in bile.
Normal range:
The normal concentration of serum bilirubin is in the range of 0.2-
1.0mg/dl. Of this, the conjugated bilirubin (diglucuronide 75%;
monoglucuronide 25%) is about 0.2-0.4mg/dl, while the unconjugated
bilirubin is 0.2-0.6mg/dl.
Van den Bergh reaction:
This is a specific reaction to identify the increase in serum bilirubin.
Normal serum gives a negative Van den Bergh reaction.
9. CONTD…
Mechanism of the reaction:
Van den Bergh reagent is a mixture of equal volumes of sulfanilic
acid (in dilute Hcl) & sodium nitrite. The principle of the reaction is that
diazotised sulfanilic acid reacts with bilirubin to form a purple coloured
azobilirubin.
Direct and indirect reaction:
Bilirubin as such is insoluble in water while the conjugated
bilirubin is soluble. Van den Bergh reagent reacts with conjugated
bilirubin and gives a purple colour immediately (normally within 30
seconds). This is referred to as “direct positive Van den Bergh reaction”.
10. CONTD…
Addition of methanol (or alcohol) dissolves the unconjugated
bilirubin which then gives the Van den Bergh reaction (normally within
30 minutes) positive and this is referred to as “indirect positive”.
If the serum contains both conjugated and unconjugated bilirubin
in high concentration, the purple colour is produced immediately (direct
positive) which is further intensified by the addition of alcohol (indirect
positive). This type of reaction is known as biphasic.
11. CONTD…
Uses:
This reaction is highly useful in understanding the nature of jaundice.
This is due to the fact that the type of jaundice is characterised by increased
serum concentration of unconjugated bilirubin (haemolytic), conjugated
bilirubin (obstructive) or both of them (hepatic). Therefore, the response of
Van den Bergh reaction can differentiate the jaundice as follows.
Indirect positive - Haemolytic jaundice
Direct positive - Obstructive jaundice
Biphasic - Hepatic jaundice
The conjugated bilirubin, being water soluble, is excreted in urine.
This is in contrast to unconjugated bilirubin which is not excreted. Bilirubin
in urine can be detected by “Fouchet's test” or “Gmelin's test”.
12. CONTD…
b) Bromosulphthalein test:
Bromosulphthalein is a dye used to assess the excretory function of
liver. It is a non-toxic compound and exclusively excreted by the liver
(through bile).
BSP is administered intravenously (5mg/kg body weight) and it's
serum concentration is measured at 45 minutes and at 2 hours. In
normal individuals, less than 5% of the dye is retained at the end of 45
minutes.
Any impairment in liver function causes an increased retention of the
dye. This test is quite sensitive to assess liver abnormality with
particular reference to excretory function.
13. 2. TESTS BASED ON SERUM ENZYMES:
Liver cells contain several enzymes which may be released into the
circulation in liver damage. Measurement of selected enzymes in serum is
often used to assess the liver function. It must be noted that there is no single
enzyme that is absolutely specific to liver alone. Despite this fact, serum
enzymes provide valuable information for LFT. Some of these enzymes are:
a) Transaminases (SGOT/AST & SGPT/ALT)
b) Alkaline phosphatase (ALP)
c) Gamma glutamyl transpeptidase (GGT)
d) 5’-nucleotidase
e) Others
14. CONTD…
a) Transaminases:
The activities of two enzymes namely- serum glutamate pyruvate
transaminase (SGPT; recently called as alanine transaminase-ALT) and
serum glutamate oxaloacetate transaminase (SGOT; recently known as
aspartate transaminase-AST) are widely used to assess the liver function.
ALT is a cytoplasmic enzyme while AST is found in both cytoplasm and
mitochondria. The activity of these enzymes is low in normal serum (ALT
5-40IU/L; AST 5-45IU/L). Serum ALT and AST are increased in liver
damage. However, ALT is more sensitive and reliable for the assessment of
LFT.
Estimation of serum transaminases cannot identify the causes of hepatic
damage. Further, they don't have much prognostic value.
15. CONTD…
b) Alkaline phosphatase (ALP):
It is mainly derived from bone and liver (the cells lining the bile
canaliculi). A rise in serum ALP (normal 3-13 KA units/dl), usually
associated with elevated serum bilirubin is an indicator of biliary
obstruction (obstructive/post hepatic jaundice). ALP is also elevated in
cirrhosis of liver and hepatic tumours.
Liver is not the sole source of alkaline phosphatase. Therefore, it's
measurement has to be carefully viewed before arriving at any
conclusion. The liver and bone isoenzymes of ALP can be separated
by electrophoresis.
16. CONTD…
c) Gamma glutamyl transpeptidase (GGT):
This is a microsomal enzyme widely distributed in body tissues,
including liver. Measurement of GGT activity provides a sensitive
index to assess liver abnormality.
The activity of this enzyme almost parallels that of transaminases in
hepatic damage. Serum GGT is highly elevated (normal 5-40IU/L) in
biliary obstruction and alcoholism.
Further, several drugs (e.g. phenytoin) induce and increase this
enzyme in circulation).
17. CONTD…
d) 5’-nucleotidase:
The serum activity of 5’-nucleotidase (normal 2-15U/L) is
elevated in hepatobiliary decrease and this parallels ALP. The advantage
with 5’-nucleotidase is that it is not altered in bone disease.
e) Others:
Serum isocitrate dehydrogenase and isoenzymes of lactate
dehydrogenase (LDH4 and LDH5) are also useful in LFT.
18. CONTD…
Interpretation of result:
Very often, a combination of serum enzyme estimations (instead of a
single one) is used for a better understanding of liver functions.
For instance, a large increase in transaminases (particularly ALT)
relative to a small increase in alkaline phosphatase indicates
hepatocellular damage.
On the other hand, a small increase in transaminases and a large
increase in alkaline phosphatase shows biliary obstruction.
19. 3. TESTS BASED ON SYNTHETIC
FUNCTION:
a) Serum proteins:
Albumin is solely synthesized by the liver. It has a half-life of about
20-25 days, therefore it is a good marker to assess chronic (and not acute)
liver damage. Low serum albumin is commonly observed in patients with
severe liver damage. It must be noted that the serum albumin concentration is
also decreased due to other factors such as malnutrition.
Functional impairment of liver is frequently associated with increased
synthesis of globulins. Cirrhosis of the liver causes a reversal of
albumin/globulin ratio (A/G ratio). Serum electrophoresis of proteins reveals
increased albumin and decreased gamma globulin concentration. This may
not have much diagnostic importance since several diseases are associated
with altered electrophoretic pattern of serum proteins.
20. CONTD…
b) Prothrombin time:
The liver synthesizes all the factors concerned with blood clotting. A
decrease in concentration of plasma clotting factors is found in the
impairment of liver function. This can be assessed in the laboratory by
measuring prothrombin time which is prolonged in patients with liver
damage, compared to normal. The half-lives of clotting factors are relatively
short (5-72 hrs.), therefore, changes in prothrombin time occur quickly.
Hence, this test is useful to assess acute as well as chronic liver damages;
besides it's help in the prognosis.
Vitamin K is required for the synthesis of blood clotting factors II, VII,
IX and X. Therefore, vitamin K deficiency can also cause prolonged
prothrombin time which must be ruled out, before drawing conclusions on the
liver functions. This is done by measuring prothrombin time before and after
administration of vitamin K.
21. 4. TESTS BASED ON METABOLIC
CAPACITY:
Galactose tolerance test:
Galactose is a monosaccharide, almost exclusively metabolized
by the liver. The liver function can be assessed by measuring the
utilisation of galactose. This is referred to as galactose tolerance test.
Procedure:
The subject is given intravenous administration of galactose
(about 300mg/kg body weight). Blood is drawn at 10-minute intervals
for the next 2 hours and galactose estimated. In the normal individuals,
the half-life of galactose is about 10-15 minutes. This is markedly
elevated in hepatocellular damage (infective hepatitis, cirrhosis).
22. 5. TESTS BASED ON DETOXIFICATION:
Hippuric acid synthesis:
The liver is the major site for the metabolism of xenobiotics
(detoxification). Measurement of hippuric acid synthesis is an ideal test for
assessing the detoxification function of liver. Hippuric acid is produced in the
liver when benzoic acid combines with glycine.
Procedure:
About 6g of sodium benzoate (dissolved in about 250ml water), is orally
given to the subject, after a light breakfast (usually 2hrs later) and after
emptying the bladder.
Urine collections are made for the next 4 hours and the amount of hippuric
acid excreted is estimated. Theoretically, 6g of sodium benzoate should
yield 7.5g of hippuric acid.
In the healthy persons, about 60% of sodium benzoate (equivalent to 4.5g
hippuric acid) is excreted in urine. A reduction in hippuric acid excretion
(particularly <3g) indicates hepatic damage.
23. CONCLUSION:
The choice of biochemical tests to measure liver functions mostly
depends on the purpose of the investigation. The clinical history of the
subject is often a guiding factor in this regard. A single test in isolation
may have a little diagnostic value.
Frequently, a combination of laboratory investigations are
employed in LFT. These include serum bilirubin (conjugated and
unconjugated), ALT, AST, ALP, GGT and proteins (albumin, globulins).
24. REFERENCE/BIBLIOGRAPHY:
1. A text book of Biochemistry by U. Satyanarayana; U. Chakrapani:
page no. 453-458.
2. A text book of Clinical pharmacy practice; Essential concepts and
skills by Dr. G. Parthasarathi.
3. www.slideshare.net