Unit II

Inborn Errors of metabolism – Phenylketonuria, alkaptonuria, albinism, tyrosinosis, maple syrup urine disease,

Sickle cell anemia. Disorders of liver and kidney – Jaundice, fatty liver, normal and abnormal functions of liver and kidney, Inulin and urea clearance.

Phenylketonuria

Alkaptonuria

Tyrosinosis

Maple syrup urine disease

JAUNDICE

Jaundice, also known as icterus,[1] is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes caused by high blood bilirubin levels.[2] This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid. Concentration of bilirubin in blood plasma is normally below 1.2 mg/dL(<25µmol/L). A concentration higher than approx. 3 mg/dL (>50µmol/L) leads to jaundice.[3] 

Jaundice is often seen in liver disease such as hepatitis or liver cancer. It may also indicate leptospirosis or obstruction of the biliary tract, for example by gallstones or pancreatic cancer, or less commonly be congenital in origin (e.g., biliary atresia).

Van den Bergh reaction is a chemical reaction used to measure bilirubin levels in blood.[1] More specifically, it determines the amount of conjugated bilirubin in the blood. The reaction produces azobilirubin.

Principle: bilirubin reacts with diazotised sulphanilic acid to produce purple coloured azo bilirubin.

Normal and abnormal functions of liver

Functions Test of Kidney

INULINE AND CLEARANCE TEST

InulinInulins are a group of naturally occurring polysaccharides produced by many types of plants,[1] industrially most often extracted from chicory.[2] 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,[11] 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.[3][4] Some articles considered the fractions with DP lower than 10 as short-chained fructooligosaccharides, and only called the longer-chained molecules inulin.[5]

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.[12] It can also improve the stability of foams and emulsions. [4]

Calculation of 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 intoBowman'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%.[43]

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.)