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TEJASVI NAVADHITAMASTU
“Let our (the teacher and the taught) learning be radiant”
Let our efforts at learning be luminous and filled with joy, and endowed with the force of purpose
Paper XII: CLINICAL AND DIAGNOSTIC BIOCHEMISTRY
Dr. Prabhakar Singh. D.Phil. Biochemistry
Department of Biochemistry, VBSPU, Jaunpur
Disorders of liver and kidney – Jaundice, fatty liver, normal and abnormal functions of liver
and kidney, Inulin and urea clearance.
DISORDERS OF LIVER AND KIDNEY
Normal /abnormal functions of liver
JAUNDICE
Summary of bilirubin metabolism
(UDP-GlcUA—UDP-glucuronic acid)
3. Obstructive (Regurgitation) Jaundice
This is due to an obstruction in the bile duct that prevents the passage of bile into the intestine.
The obstruction may be caused by gall stones, tumors etc.
Due to the blockage in bile duct, the conjugated bilirubin from the liver enters the
circulation. Obstructive jaundice is characterized by
1. Increased concentration of conjugated bilirubin in serum.
2. Serum alkaline phosphataseis elevated as it is released from the cells of the damaged bile duct.
3. Dark coloured urine due to elevated excretion of bilirubin and clay coloured feces due to
absence of stercobilinogen.
4. Feces contain excess fat indicating impairment in fat digestion and absorption in the absence
of bile (specifically bile salts).
5. The patients experience nausea and gastrointestinal pain.
FATTY LIVER
KIDNEY (RENAL) FUNCTION TESTS
The kidneys are the vital organs of the body, performing the following major functions.
1. Maintenance of homeostasis :The kidneys are largely responsible for the regulation of
water, electrolyte and acid-base balance in the body.
2. Excretion of metabolic waste products : The end products of protein and nucleic acid
metabolism are eliminated from the body. These include urea, creatinine, creatine, uric
acid, sulfate and phosphate.
3. Retention of substances vital to body :The kidneys reabsorb and retain several
substances of biochemical importance in the body e.g. glucose, amino acids etc.
4. Hormonal functions :The kidneys also function as endocrine organs by producing
hormones.
• Erythropoietin: a peptide hormone, stimulates hemoglobin synthesis and formation
of erythrocytes.
• Calcitriol (1,25-Dihydroxycholecalciferol)– the biochemically active form of vitamin
D – is finally produced in the kidney. It regulates calcium absorption from the gut.
• Renin,a proteolytic enzyme liberated by kidney, stimulates the formation of
angiotensin II which, in turn, leads to aldosterone production. Angiotensin II and
aldosterone are the hormones involved in the regulation of electrolyte balance.
Inulin
Inulins are a group of naturally occurring polysaccharides produced by many types of
plants, industrially most often extracted from chicory. The inulins belong to a class of dietary
fibers known as fructans. Inulin is used by some plants as a means of storing energy and is
typically found in roots or rhizomes. Most plants that synthesize and store inulin do not store
other forms of carbohydrate such as starch.
Chemical structure and properties
Inulin is a heterogeneous collection of fructose polymers. It consists of chain-
terminating glucosyl moieties and a repetitive fructosyl moiety, which are linked by β(2,1) bonds. The
degree of polymerization (DP) of standard inulin ranges from 2 to 60. After removing the fractions
with DP lower than 10 during manufacturing process, the remaining product is high performance
inulin. Some articles considered the fractions with DP lower than 10 as short-chained
fructooligosaccharides, and only called the longer-chained molecules inulin.
Because of the β(2,1) linkages, inulin is not digested by enzymes in the human alimentary system,
contributing to its functional properties: reduced calorie value, dietary fiber and prebiotic effects.
Without color and odor, it has little impact on sensory characteristics of food products. Oligofructose
has 35% of the sweetness of sucrose, and its sweetening profile is similar to sugar. Standard inulin
is slightly sweet, while high performance inulin is not. Its solubility is higher than the classical fibers.
When thoroughly mixed with liquid, inulin forms a gel and a white creamy structure, which is similar
to fat. Its three-dimensional gel network, consisting of insoluble submicron crystalline inulin particles,
immobilizes large amount of water, assuring its physical stability.It can also improve the stability of
foams and emulsions.
INULIN & GLOMERULAR FILTRATION RATE
Inulin is uniquely treated by nephrons in that it is completely filtered at the glomerulus but neither
secreted nor reabsorbed by the tubules. This property of inulin allows the clearance of inulin to be
used clinically as a highly accurate measure of glomerular filtration rate (GFR) — the rate of plasma
from the afferent arteriole that is filtered into Bowman's capsule measured in mL/min.
It is informative to contrast the properties of inulin with those of para-aminohippuric acid (PAH). PAH
is partially filtered from plasma at the glomerulus and not reabsorbed by the tubules, in a manner
identical to inulin. PAH is different from inulin in that the fraction of PAH that bypasses the
glomerulus and enters the nephron's tubular cells (via theperitubular capillaries) is completely
secreted. Renal clearance of PAH is thus useful in calculation of renal plasma flow (RPF), which
empirically is (1-hematocrit) times renal blood flow. Of note, the clearance of PAH is reflective only of
RPF to portions of the kidney that deal with urine formation, and, thus, underestimates the actual
RPF by about 10%.
The measurement of GFR by inulin or sinistrin is still considered the gold-standard. However, it has
now been largely replaced by other, simpler measures that are approximations of GFR. These
measures, which involve clearance of such substrates as EDTA, iohexol, Cystatin C, 125I-
iothalamate (sodium radioiothalamate), the chromium radioisotope 51Cr (chelated with EDTA),
and creatinine, have had their utility confirmed in large cohorts of patients with chronic kidney
disease.
For both inulin and creatinine, the calculations involve concentrations in the urine and in the serum.
However, unlike creatinine, inulin is not naturally present in the body. This is an advantage of inulin
(because the amount infused will be known) and a disadvantage (because an infusion is necessary.)
Prabhakar singh  iv sem-paper-disorders of liver and kidney
Prabhakar singh  iv sem-paper-disorders of liver and kidney
Prabhakar singh  iv sem-paper-disorders of liver and kidney
Prabhakar singh  iv sem-paper-disorders of liver and kidney

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Prabhakar singh iv sem-paper-disorders of liver and kidney

  • 1. TEJASVI NAVADHITAMASTU “Let our (the teacher and the taught) learning be radiant” Let our efforts at learning be luminous and filled with joy, and endowed with the force of purpose Paper XII: CLINICAL AND DIAGNOSTIC BIOCHEMISTRY Dr. Prabhakar Singh. D.Phil. Biochemistry Department of Biochemistry, VBSPU, Jaunpur Disorders of liver and kidney – Jaundice, fatty liver, normal and abnormal functions of liver and kidney, Inulin and urea clearance.
  • 2. DISORDERS OF LIVER AND KIDNEY Normal /abnormal functions of liver
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  • 5. JAUNDICE Summary of bilirubin metabolism (UDP-GlcUA—UDP-glucuronic acid)
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  • 8. 3. Obstructive (Regurgitation) Jaundice This is due to an obstruction in the bile duct that prevents the passage of bile into the intestine. The obstruction may be caused by gall stones, tumors etc. Due to the blockage in bile duct, the conjugated bilirubin from the liver enters the circulation. Obstructive jaundice is characterized by 1. Increased concentration of conjugated bilirubin in serum. 2. Serum alkaline phosphataseis elevated as it is released from the cells of the damaged bile duct. 3. Dark coloured urine due to elevated excretion of bilirubin and clay coloured feces due to absence of stercobilinogen. 4. Feces contain excess fat indicating impairment in fat digestion and absorption in the absence of bile (specifically bile salts). 5. The patients experience nausea and gastrointestinal pain.
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  • 16. KIDNEY (RENAL) FUNCTION TESTS The kidneys are the vital organs of the body, performing the following major functions. 1. Maintenance of homeostasis :The kidneys are largely responsible for the regulation of water, electrolyte and acid-base balance in the body. 2. Excretion of metabolic waste products : The end products of protein and nucleic acid metabolism are eliminated from the body. These include urea, creatinine, creatine, uric acid, sulfate and phosphate. 3. Retention of substances vital to body :The kidneys reabsorb and retain several substances of biochemical importance in the body e.g. glucose, amino acids etc. 4. Hormonal functions :The kidneys also function as endocrine organs by producing hormones. • Erythropoietin: a peptide hormone, stimulates hemoglobin synthesis and formation of erythrocytes. • Calcitriol (1,25-Dihydroxycholecalciferol)– the biochemically active form of vitamin D – is finally produced in the kidney. It regulates calcium absorption from the gut. • Renin,a proteolytic enzyme liberated by kidney, stimulates the formation of angiotensin II which, in turn, leads to aldosterone production. Angiotensin II and aldosterone are the hormones involved in the regulation of electrolyte balance.
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  • 20. Inulin Inulins are a group of naturally occurring polysaccharides produced by many types of plants, industrially most often extracted from chicory. The inulins belong to a class of dietary fibers known as fructans. Inulin is used by some plants as a means of storing energy and is typically found in roots or rhizomes. Most plants that synthesize and store inulin do not store other forms of carbohydrate such as starch. Chemical structure and properties Inulin is a heterogeneous collection of fructose polymers. It consists of chain- terminating glucosyl moieties and a repetitive fructosyl moiety, which are linked by β(2,1) bonds. The degree of polymerization (DP) of standard inulin ranges from 2 to 60. After removing the fractions with DP lower than 10 during manufacturing process, the remaining product is high performance inulin. Some articles considered the fractions with DP lower than 10 as short-chained fructooligosaccharides, and only called the longer-chained molecules inulin. Because of the β(2,1) linkages, inulin is not digested by enzymes in the human alimentary system, contributing to its functional properties: reduced calorie value, dietary fiber and prebiotic effects. Without color and odor, it has little impact on sensory characteristics of food products. Oligofructose has 35% of the sweetness of sucrose, and its sweetening profile is similar to sugar. Standard inulin is slightly sweet, while high performance inulin is not. Its solubility is higher than the classical fibers. When thoroughly mixed with liquid, inulin forms a gel and a white creamy structure, which is similar to fat. Its three-dimensional gel network, consisting of insoluble submicron crystalline inulin particles, immobilizes large amount of water, assuring its physical stability.It can also improve the stability of foams and emulsions.
  • 21. INULIN & GLOMERULAR FILTRATION RATE Inulin is uniquely treated by nephrons in that it is completely filtered at the glomerulus but neither secreted nor reabsorbed by the tubules. This property of inulin allows the clearance of inulin to be used clinically as a highly accurate measure of glomerular filtration rate (GFR) — the rate of plasma from the afferent arteriole that is filtered into Bowman's capsule measured in mL/min. It is informative to contrast the properties of inulin with those of para-aminohippuric acid (PAH). PAH is partially filtered from plasma at the glomerulus and not reabsorbed by the tubules, in a manner identical to inulin. PAH is different from inulin in that the fraction of PAH that bypasses the glomerulus and enters the nephron's tubular cells (via theperitubular capillaries) is completely secreted. Renal clearance of PAH is thus useful in calculation of renal plasma flow (RPF), which empirically is (1-hematocrit) times renal blood flow. Of note, the clearance of PAH is reflective only of RPF to portions of the kidney that deal with urine formation, and, thus, underestimates the actual RPF by about 10%. The measurement of GFR by inulin or sinistrin is still considered the gold-standard. However, it has now been largely replaced by other, simpler measures that are approximations of GFR. These measures, which involve clearance of such substrates as EDTA, iohexol, Cystatin C, 125I- iothalamate (sodium radioiothalamate), the chromium radioisotope 51Cr (chelated with EDTA), and creatinine, have had their utility confirmed in large cohorts of patients with chronic kidney disease. For both inulin and creatinine, the calculations involve concentrations in the urine and in the serum. However, unlike creatinine, inulin is not naturally present in the body. This is an advantage of inulin (because the amount infused will be known) and a disadvantage (because an infusion is necessary.)