This document discusses several topics related to biochemistry. It summarizes 1) the synthesis of thyroid hormones from tyrosine residues, 2) biochemical changes that occur in obstructive jaundice including increased bilirubin and ALP levels, 3) the Krebs cycle which generates most of the body's ATP through oxidation of acetyl CoA, and 4) respiratory alkalosis caused by hyperventilation and the kidney's compensatory response. It also briefly outlines gluconeogenesis, catecholamine synthesis, tumor markers, cellulose structure and function, electrophoresis techniques, vitamin D metabolism, and calcium distribution and regulation in the body.
This document discusses several topics related to biochemistry. It summarizes 1) the synthesis of thyroid hormones from tyrosine residues, 2) biochemical changes that occur in obstructive jaundice including increased bilirubin and ALP levels, 3) the Krebs cycle which generates most of the body's ATP through oxidation of acetyl CoA, and 4) respiratory alkalosis caused by hyperventilation and the kidney's compensatory response. It also briefly outlines gluconeogenesis, catecholamine synthesis, tumor markers, cellulose structure and function, electrophoresis techniques, vitamin D metabolism, and calcium distribution and regulation in the body.
This document discusses several topics related to biochemistry. It summarizes 1) the synthesis of thyroid hormones from tyrosine residues, 2) biochemical changes that occur in obstructive jaundice including increased bilirubin and ALP levels, 3) the Krebs cycle which generates most of the body's ATP through oxidation of acetyl CoA, and 4) respiratory alkalosis caused by hyperventilation and the kidney's compensatory response. It also briefly outlines gluconeogenesis, catecholamine synthesis, tumor markers, cellulose structure and function, electrophoresis techniques, vitamin D metabolism, and calcium distribution and regulation in the body.
This document discusses several topics related to biochemistry. It summarizes 1) the synthesis of thyroid hormones from tyrosine residues, 2) biochemical changes that occur in obstructive jaundice including increased bilirubin and ALP levels, 3) the Krebs cycle which generates most of the body's ATP through oxidation of acetyl CoA, and 4) respiratory alkalosis caused by hyperventilation and the kidney's compensatory response. It also briefly outlines gluconeogenesis, catecholamine synthesis, tumor markers, cellulose structure and function, electrophoresis techniques, vitamin D metabolism, and calcium distribution and regulation in the body.
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1.
SYNTHESIS OF THYROID HORMONES
● Thyroxin [tetraiodo-thyronine] ● Triiodothyronine-are synthesized from the tyrosine residues of the protein THROGLOBULIN and activated iodine. ● Iodination of tyrosine ring occurs to produce mono- and diiodotyrosine from which triiodothyronine [T3] and thyroxine [T4] are synthesized. ● The protein thyroglobulin undergoes proteolytic breakdown to release the free hormones, T3 and T4. 2. BIOCHEMICAL CHANGES IN OBSTRUCTIVE JAUNDICE. ● Jaundice is characterized by yellow coloration of sclera [of eyes] and skin. This is due to elevated serum bilirubin level, beyond 2mg/dl [normal <1mg/dl]. ● Obstructive [regurgitation] jaundice: This is due to an obstruction in the bile duct that prevents the passage of bile into the intestine. It may be caused by gall stones, tumors. ● Due to the blockage in the bile duct, the conjugated bilirubin from the liver enters the circulation. ● Obstruction is caused by, - Increased concentration of conjugated bilirubin in serum. - Serum ALP is elevated as it is released from the cells of damaged bile duct. - Dark coloured urine is due to excretion of bilirubin and clay coloured feces due to absence stercobilinogen. - Feces contain excess fat indicating impairment in fat digestion and absorption in the absence of bile [bile salts]. - Patient’s experience nausea and gastro intestinal pain. 3. KREB’S CYCLE. ● The citric acid cycle or tricarboxylic acid-TCA cycle is the most important metabolic pathway for the energy supply of the body. ● About 65-70% of the ATP is synthesized in kreb’s cycle. Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O. This cycle utilizes about two-third of total oxygen consumed by the body. ● Location – the enzyme of TCA cycle are located in mitochondrial matrix. 4. RESPIRATORY ALKALOSIS ● Primary abnormality in respiratory alkalosis is a decrease in H2CO3 concentration. ● This may occur due to prolonged hyperventilation resulting in increased exhalation of CO2 by the lung. ● Hyperventilation is observed in conditions such as hysteria, hypoxia, raised intracranial pressure, excessive artificial ventilation and the action of certain drugs [salicylate] that stimulate respiratory centre. ● The renal mechanism tries to compensate by increasing the urinary excretion of HCO3. 5. GLUCONEOGENESIS ● Synthesis of glucose from non-carbohydrate is known as gluconeogenesis. The major substrate/ precursors for lactate, pyruvate, glucogenic amino acid, propionate and glycerol. ● Location- Occurs mainly in the CYSTOL, although some precursors are produced in Mitochondria. It mostly takes place in the LIVER [about 1kg glucose synthesized everyday] and kidney matrix [about one-tenth of liver capacity]. ● Importance – Brain and CNS, erythrocytes, testes and kidney medulla are dependent on glucose for continuous supply of energy. ● Human brain alone requires about 120g/ day, out of about 160g needed by the entire body. ● Glucose is the only source that supplies energy to the skeletal muscle, under anaerobic conditions. ● In fasting even more than a day, gluconeogenesis must occur to meet the basal requirements of the body for glucose and to maintain the intermediates of citric acid cycle. This is essential for the survival of humans and animals. ● Certain metabolites produced in the tissues accumulate in the blood, [eg- lactate, glycerol, propionate etc]. Reactions of gluconeogenesis: It closely resembles the reversed pathway of glycolysis, although it is not the completely reversal of glycolysis. ● Three reactions of glycolysis are irreversible. The seven reactions are common for both glycolysis and gluconeogenesis. ● The three irreversible steps of glycolysis are catalyzed by the enzyme – hexokinase, phosphofructokinase and pyruvate kinase Gluconeogenesis from amino acids- ● The carbon skeleton of glucogenic amino acids [except leucine and lysine] result in formation of pyruvate.
Gluconeogenesis from lactate [cori cycle]-
● Lactate produced by active skeletal muscle is a major precursor for gluconeogenesis. Under anaerobic conditions, pyruvate is reduced to lactate by LDH. 6. SYNTHESIS OF CATECHOLAMINES ● The name catechol refers to the dihydroxylated phenyl ring. The amine derivatives of catechol are called catecholamines. ● Tyrosine is the precursor for the synthesis of catecholamines, namely dopamine, nor-epinephrine [noradrenaline], epinephrine [adrenaline]. ● The conversion of tyrosine to catecholamines occurs in adrenal medulla and CNS. Functions of catecholamines- ● Norepinephrine and epinephrine regulate carbohydrate and lipid metabolisms. ● They stimulate the degradation of triacylglycerol and glycogen. They cause an increase in the blood pressure. ● Dopamine and norepinephrine serve as neurotransmitter in the brain and ANS.
8. TUMOUR MARKER AND ITS IMPORTANCE.
● Biochemical indicators employed to detect the presence of cancers are collectively referred to as tumor markers. ● These are abnormally produced molecules of tumor cells such as surface antigen, cytoplasmic proteins, enzymes and hormones. It can be measured in serum [or plasma]. ● In theory the tumor markers must ideally be useful for screening the population to detect cancers. As such, the tumor markers support the diagnosis of cancers. ● It is useful for monitoring the response to theory and for the early detection of recurrence. 9. ROLE OF CELLULOSE. ● It occurs exclusively in plants and it is the most abundant organic substance in plant kingdom. ● It is a predominant constituent of plant cell wall. Cellulose is totally absent in animal body. ● Cellulose is composed of beta-D-glucose units linked by beta- [1 4] glycosidic bonds. ● It cannot be digested by mammals- including man- due to lack of the enzyme that cleaves beta- glycosidic bonds. ● Hydrolysis of cellulose yields a disaccharide cellobiose, followed by beta-D-glucose. ● Cellulose, though not digested, has great importance in human nutrition. It is a major constituent of fiber, the non- digestable carbohydrate. ● The functions of dietary fiber include decreasing the absorption of glucose and cholesterol from the intestine, besides increasing the bulk of feces. 10. ELECTROPHROSIS ● The movement of charged particles [ions] in an electric field resulting in their migration towards the oppositely charged electrode is known electrophoresis. ● Molecules with a net positive charge [cations] move towards the negative charge [anions] migrate towards positive anode. ● Electrophoresis is a widely used analytical technique for the separation of biological molecules such as plasma proteins, lipoproteins and immunoglobulins. ● The rate of migration of ions depends on several factors- shape, size, net charge and solvation of the ions, viscosity of the solution and magnitude of the current employed. Types of electrophoresis: 1. Zone electrophoresis: A simple and modified method of moving boundary electrophoresis is the zone electrophoresis. ● Inert supporting material- paper / gel Paper electrophoresis: ● In this technique, the sample is applied on a strip of filter paper wetted with desired buffer solution. ● The ends of the strip are dipped into the buffer reservoirs in which the electrodes are placed. The electric current is applied allowing the molecules migrate for sufficient time. ● The paper is removed, dried and stained with a dye that specifically colours the substance to be detected. The coloured spots can be identified. ● The serum proteins are separated into five distinct bands- albumin, alpha 1, 2, beta and delta-globulins. Gel electrophoresis- ● This technique involves the separation of molecules based on their size, in addition to the electrical charge. ● The movement of large molecules is slow in gel electrophoresis. ● Commonly used gels- agarose, polyacrylamide, sodium dodecyl sulfate [SDS]. 2. Isoelectric focusing- ● This is primarily based on the immobilization of the molecules at isoelectric PH during the electrophoresis. ● It can be conveniently used for purification of protein. 3. Immunoelectrophorosis- ● This technique involves combination of the principles of electrophoresis and immunological reactions. ● It is useful for the analysis of complex mixture of antigens and antibodies. ● The antibodies diffuse and, when they come in contact with antigens, resulting in the formation of precipitin bands.
11. Vitamin-D and calcium metabolism.
● Vitamin-D: It is a fat soluble vitamin. It resembles sterols in structure and functions like a hormone. ● Metabolism: vitamins D2 and D3 as such are not biologically active. They are metabolized identically in the body and converted to active forms of vitamin D. ● Synthesis of 1,25-DHCC: Metabolism and biochemical function: CALCIUM [also qns. no-22] It is the most abundant among the minerals in the body. ● Total content of calcium in an adult man- 1 to 1.5kg. As much as 99% present in bones and teeth. A small fraction [1%] found outside the skeletal tissue.
● Plasma calcium- Most of the blood Ca is present in the
plasma since the blood cells contain very little of it. ● Normal conc. Of plasma / serum Ca is 9-11mg/dl. Factors regulating plasma Ca level:- The hormones – Calcitriol, PTH and Calcitonin are the major factors that regulate the plasma calcium within the narrow range. Calcitriol- stimulates Ca uptake by osteoblasts of bone and promotes calcification or mineralization and remodeling. PTH- Primary function of PTH is to elevate serum Ca level. It has 3 independent tissues- Bone- it causes decalcification or demineralization of bone, a process carried out by osteoclasts. Kidney- it increases the Ca reabsorption by kidney tubules. Intestine- it increases the intestinal absorption of Ca by promoting the synthesis of calcitriol. Calcitonin- it promotes calcification by increasing the activity of osteoblasts. CT decreasing the influence of blood calcium. DISEASE STATE- Hypercalcemia, hypocalcemia, rickets, renal rickets, osteoporosis, osteopetrosis [marbal bone disease]. 12. ISOENZYMES. ● The multiple forms of an enzyme catalyzing the same reaction are isoenzymes or isozymes. Explanation for the existence of isoenzymes: ● It is synthesized from different genes [eg- malate dehydrogenase of cytosol is different from that found in mitochondria]. ● Oligomeric enzymes consisting of more than one type of subunits. ● An enzyme may be active as monomer or oligomer. ● In glycoprotein enzymes, difference in carbohydrate content may be responsible for isoenzymes. ● Isoenzymes of LDH: Systemic name is L-lactate- NAD+ oxidoreductase catalyses the interconversion of lactate and pyruvate. Diagnostic importance of LDH: ● Diagnosis of heart and liver disorders. In healthy individuals, the activity of LDH2 is higher than that of LDH1 in serum. ● In case of ‘myocardial infraction’, LDH1 is much greater than LDH2 and this happens within 12 to 24 hours after infraction. ● Increased activity of LDH5 in serum is an indicator of ‘liver diseases’. LDH activity in the RBC is 80-100 times more than that in serum. Isoenzymes of creatine phosphokines: ● Creatine kinase [CK] or CPK catalyses the inter-conversion of phosphor-creatine to creatine.
CPK exists as 3 isoenzymes-
● In healthy individuals, the CPK is undetectable in serum.
After the MI within the first 6-18hrs, CPK2 increases in the serum to as high as 20%. It is not elevated in skeletal muscle disorders. ● CPK2 [MB] is the earliest reliable indication of MI. Isoenzymes of ALP: ● Six isoenzymes of ALP have been identified. It is the monomer it is due to the difference in the carbohydrate content. ● Most important- Increase in alpha2- heat labile ALP- hepatitis, pre-beta ALP indicates bone diseases. Isoenzymes of alcohol dehydrogenase: ● It is a 2 heterodimer isoenzymes- alpha beta1, [orientals] alpha beta2. ● Accumulation of acetaldehyde is associated with tachycardia and facial flushing among orientals which is not commonly seen in whites. 13. PHOSPHO LIPIDS. ● These are complex or compound lipids containing phosphoric acid, in addition to fatty acids, nitrogenous base alcohol. Two classes: 1. Glycerophospholipids- contain glycerol as the alcohol. 2. Sphingophospholipids- contain sphingosine as the alcohol. ● Functions: In association with proteins, phospholipids form the structural components of membranes and regulate membrane permeability. ● Phospholipids [lecithin, cephalin, and cardiolipin] in mitochondria are responsible for maintaining the conformation of electron transport chain components and cellular respiration. ● Phospholipids participate in the absorption of fat from the intestine. ● These are essential for the synthesis of different lipoproteins, and thus participate in the transport of lipids. ● Accumulation of fat in liver [fatty liver] can be prevented by phospholipids- lipotropic factors. ● Arachidonic acid, an unsaturated fatty acid liberated from phospholipids, serves as a precursor for the synthesis of eicosanoids [prostaglandins, prostacyclins, thromboxans]. ● Phospholipids participate in the reverse cholesterol transport and help in removal of cholesterol from the body. ● Phospholipids act as a surfactant. Respiratory distress syndrome in infants is associated with insufficient production of this surfactant. ● Cephalins, an important group of phospholipids participate in blood clotting. ● Phospholipids are involved in signal transmission across membrane. 14. UREA CLEARENCE TEST. ● It is the end product of protein metabolism. After being filtered by the glomeruli, it is partially reabsorbed by the renal tubules. ● Urea clearance is less than the GFR and further, it is influenced by the protein content of the diet. For these reasons, urea clearance is not as sensitive as creatinine clearance for assessing renal function. ● It is defined as the volume [ml] of plasma that would be completely cleared of urea per minute.
● It is applicable if the output of urine is more than
2ml/min. This is referred as “maximum urea clearance” and the normal value is around 75ml/min. ● Standard urea clearance [Cs] - It is observed that the urea clearance drastically changes when the volume of urine is less than 2ml/min. ● Normal value is around 54ml/min. It is calculated by a modified formula. ● Diagnostic importance: below 75% of the normal is viewed seriously, it is an indicator of renal damage. ● Blood urea level as such is found to increase only when the clearance falls below 50% normal. It is better indicator for renal function. 15. ACUTE INTERMITTENT PORPHYRIA. ● It occurs due to the deficiency of the enzyme uroporphyrinogen 1 synthase. It is characterized by increased excretion of porphobilinogen and delta- aminolevulinate. ● The urine gets darkened on exposure to air due to the conversion of porphobilinogen to porphobilin and porphyrin. Features:- ● It is usually expressed after puberty in humans. ● The symptoms include abdominal pain, vomiting and cardiovascular abnormalities, neuropsychiatric disturbances. ● The symptoms are more severe after administration of drugs [barbiturates] that induce the synthesis of cytochrome P450. ● Patients are not photosensitive since the enzyme defect occurs prior to the formation of uroporphyrinogen. ● It is treated by administration of hematin which inhibits the enzyme ALA synthase and accumulation of porphobilinogen. ● The disease- acute intermittent porphyria- has historical importance. King George3 ruled England during the period of American Revolution. He was a victim of this disease and possessed by chatacteristric manifestations [red colour urine] and was considered mad. 16. THYROID HORMONE. ● Thyroid gland is located on either side of the trachea below the larynx. It produces two principal hormones- thyroxine [T4] and triiodothyronine [T3] - which regulate the metabolic rate of the body. ● Synthesis of thyroid hormone: refer qns.no-1 ● Storage and release: thyroglobulin containing T4 and T3 can be stored for several months in the thyroid gland. Stored hormones can meet the body requirement for 1-3months. ● The FT4 [90%] and T3 [10%] are released into the blood, a process stimulated by TSH. MIT and DIT produced in the thyroid gland undergo de-iodination by the enzyme deiodinase and the iodine thus liberated can be reutilized. ● Transport of T4 and T3- Two specific binding proteins- thyroxine binding globulin [TBG] and thyroxine binding pre-albumin [TBPA]- are responsible for the transport of thyroid hormones. ● Regulation of T3 and T4 synthesis:
Abnormalities of the thyroid function:
● Goiter ● Goitrogenic substances [goitrogens] ● Simple endemic goiter ● Hyperthyroidism ● Hypothyroidism- children- cretinism and adult- myxoedema. 17. FLUID AND ELECTROLYTE BALANCE IN PYLORIC STENOSIS. ✔ Hyponatremia ✔ Hypokalemia ✔ Hypomagnesaemia ✔ Hypochloraemia ✔ Metabolic alkalosis ✔ Paradoxical aciduria ● Because of severe vomiting which contains acid as well as undigested retained food, sodium, chloride, potassium, magnisum levels drop, causing metabolic alkalosis. ● Alkalosis can lead to hypocalcaemia causing tetany. It is called as GASTRIC TETANY. ● To control alkalosis, kidney secretes excess bicarbonate [in alkalosis without hyponatraemia, bicarbonate is secreted along with sodium]. ● Here, due to hyponatraemia, body conserves sodium and so bicarbonate is secreted along with hydrogen ion. So urine becomes acidic. It is called PARADOXICAL ACIDURIA. 18. METABOLIC ALKALOSIS. ● The primary abnormality in metabolic alkalosis is an increase in HCO3 concentration. ● This may occur due to excessive vomiting [resulting in loss of H+] or an excessive intake of sodium bicarbonate for the therapeutic purpose [eg- control of gastric acidity], cushing’s syndrome [hypersecretion of aldosterone] causes increased retention of Na+ and loss of K+ from the body. ● It is commonly associated with low K+ concentration. In severe K+ deficiency, H+ ions are retained inside the cells to replace K+ ions. ● In the renal tubular cells, H+ ions are exchanged with the reabsorbed Na+. Paradoxically, the patient excretes acid urine despite alkalosis. ● The respiratory mechanism initiates the compensation by hypoventilation to retain CO2. This is slowly taken over by renal mechanism which excretes more HCO3 and retains H+. 19. INSULIN METABOLISM. ● Insulin plays a key role in the regulation of carbohydrate, lipid and protein metabolisms. Insulin exerts anabolic and anti-catabolic influences on the body metabolism. 20. HYPOKALEMIA. ● Potassium is the intracellular cation. It is equally important in the extracellular fluid for specific functions. Dietary requirements- 3 to 4 g/day. ● Plasma conc. Of potassium is 3.4 to 5.0 mEq/l. ● Disease states: serum potassium conc. Is maintained within a narrow range. ● Hypokalemia- decrease in the concentration of serum potassium is observed due to:- - Overactivity of adrenal cortex [Cushing’s syndrome], - Prolonged cortisone therapy, - Intravenous administration of K+ free fluids, - Treatment of diabetic coma with insulin, - Prolonged diarrhea and vomiting. ● Symptoms- irritability, muscular weakness, tachycardia, cardiomegaly and cardiac arrest. ● Changes in the ECG are observed [flattened waves with inverted T wave]. 21. GLUCOSE TOLERANCE TEST [GTT]. ● The diagnosis of diabetes can be made on the basis of individual’s response to the oral glucose load, referred to OGTT. Preparation of the subject for GTT: ● The person should have been taking carbohydrate-rich diet for at least 3days prior to the test. All drugs known to influence carbohydrate metabolism should be discontinued. The subject should avoid strenuous exercise on the previous day of the test. ● He/she should be overnight [at least 10hrs] fasting state. During the course of GTT, the person should be comfortably seated and should refrain from smoking and exercise. ● Procedure: In the morning [ideal 9 to 11am]. A fasting blood sample is drawn and urine collected. The subject is given 75g glucose orally dissolved in about 300ml of water, to be drunk in about 5 minutes. Blood and urine samples are collected at 30 minute intervals for at least 2 hours. ● Interpretation of GTT- 23. SERUM 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 the liver to form bilirubin and excreted in bile. Degradation of heme to bile pigment- Metab olism: Serum bilirubin- ● The normal concentration of serum bilirubin is in the range of 0.2 to 1.0 mg/dl. ● Of this, the conjugated bilirubin [diglucuronide 75%, monoglucuronide 25%] is about 0.2- 0.4mg/dl, while the unconjugated bilirubin is 0.2- 0.6 mg/dl. Conjugated bilirubin- ● In the liver bilirubin is conjugated with two molecules of glucoronate supplied by UDP-glucuronate. This reaction catalyzed by bilirubin glucuronyltransferase resulting in the formation of water soluble bilirubin diglucuronide. Excretion of bilirubin into bile- ● It is excreted into the bile canaliculi against a concentration gradient which then enters the bile. ● Normally there is a good coordination between the bilirubin conjugation and excretion into bile. 24. SERUM CREATININE. The normal concentration of creatine and creatinine in human serum and urine- Serum – Creatine– 0.2 – 0.6 mg/dl Creatinine- 0.6 – 1 mg/dl Urine- Creatine- 0 – 50 mg/dl Creatinine- 1 – 2 g/dl ● Estimation of serum creatinine [along with blood urea] is used as a diagnostic test to assess kidney function. ● Sr. concentration is not influenced by endogenous and exogenous factors, as is the case with urea. Serum creatinine as a more reliable indicator of renal function. ● The amount of creatinine excreted is proportional to total creatine phosphate content of the body and in turn the muscle mass. ● The daily excretion of creatinine is usually constant. ● Creatinine coefficient is defined as the mg of creatinine and creatine excreted per kg body weight per day. Normal adult man- 24 – 26mg, woman- 20 -22mg. ● Increased output of creatine in urine is referred to as creatinuria. It is observed in muscular dystrophy, DM, hyperthyroidism, starvation. 25. ACID PHOSPHATASE [ACP] ● It is increased in the cancer of prostate gland [normal 0.5- 4 KA units/dl]. ● The tartarate labile ACP [normal <1 KA units/dl] is useful for the diagnosis and prognosis of prostate cancers. It is a good tumor marker. ● Increase in the serum acid phosphatase is a specific for detection of prostatic carcinoma. PSA, mol wt.32 KD, though not an enzyme is a more reliable marker for detection of prostate cancer. ● Normal serum concentration of PSA is 1-4ng/ml. ● A non-specific increase in certain enzymes like LDH, ALP and transaminase may be associated with malignancy in any part of the body. 27. THYROID FUNCTION TEST. ● Measurement of basal metabolic rate [BMR] was once used to reflect thyroid activity. ● The estimation of serum protein bound iodine [PBI], representing the circulating thyroid hormones was employed for a long time to assess thyroid function. ● The normal serum PBI concentration is 3-8micro g/100ml. ● Hypothyroidism is associated with decreased PBI and hyperthyroidism with increased PBI. ● The concentration of free T3 and T4 and TSH are measured and their serum normal concentrations are Free T3- 80 to 220 ng/dl Free T4- 0.8 to 2.4 ng/dl Total thyroxine [T4]- 5 to 12 micro g/dl TSH - <10 micro U/ml. 28. BLOOD UREA. ● In healthy people the normal blood urea concentration is 10-40mg/dl. ● Higher protein intake marginally increases blood urea level. About 15-30 g of urea is excreted per day. ● It is widely used as a screening test for the elevation of kidney function. Elevation of blood urea classified into 3categories. ● Pre-renal: This is associated with increased protein breakdown leading to a negative nitrogen balance as observed after major surgery, diabetic coma, prolonged fever, thyrotoxicosis etc. In leukemia and bleeding disorders also blood urea is elevated. ● Renal: In renal disorders like AGN, chronic nephritis, nephrosclerosis, polycystic kidney, blood urea is increased. ● Post-renal: There is an obstruction in the urinary tract [eg. Tumors, stones, enlargement of prostate gland] blood urea is elevated. This is due to increased reabsorption of urea from the renal tubules. ● The term uremia is used to indicate increased blood urea levels due to renal failure. ● Azotemia reflects a condition with elevation in blood urea or other nitrogen metabolites which may or may not be associated with renal diseases. 29. ALKALINE PHOSPHATASE [ALP]. ● It is elevated in bone and liver diseases [normal 3-13KA units/dl]. ALP is useful for the diagnosis of rickets, hyperparathyroidism, carcinoma of bone and obstructive jaundice. ● Isoenzymes of ALP: As many as 6 isoenzymes of ALP have been identified. ALP is a monomer the isoenzymes are due to the difference in the carbohydrate content. ● The most important ALP isoenzymes are alpha1-ALP, alpha2- heat ALP, alpha2- heat stable ALP, pre- beta ALP, gama-ALP. ● Increase in alpha2- heat ALP suggest hepatitis, pre- beta ALP indicates bone diseases. ● In rickets ALP activity is elevated. It is concerned with the process of bone formation. There is an overproduction of ALP related to more cellular activity of the bone. ● A rise in serum ALP usually associated with elevated serum bilirubin is an indicator of biliary obstruction [obstructive/post-hepatic jaundice]. ● It also elevated in cirrhosis of liver and hepatic tumors. The liver and bone isoenzymes of ALP can be separated by electrophrosis. 30. HYPONATREMIA. ● This is a condition in which the serum sodium level falls below the normal. In the plasma [serum] the normal concentration of sodium is 135-145 mEq/l. ● It may occur due to diarrhea, vomiting, chronic renal diseases, adrenocortical insufficiency [Addison’s disease]. ● Administration of salt free fluids to patients may also cause hyponatremia. This is due to overhydration. ● Decreased serum sodium concentration is also observed in edema which occurs in cirrhosis or congestive heart failure. ● Manifestations include reduced blood pressure and circulatory failure. 32. MAGNISIUM. ● The adult body contains about 20g Mg, 70% - found in bones in combination with calcium and phosphorus. 30% - soft tissues and body fluids. ● It is required for formation of bones and teeth. Normal serum concentration of Mg is 2-3 mg/dl. ● Dietary requirement- adult man-350mg/day, adult women-300mg/day. ● Sources- cereals, nuts, beans, vegetables, meat, milk, fruits. ● Absorption- it is absorbed by the intestinal cells through a specific carrier system. 50% of the dietary Mg is normally absorbed. Consumption of large amount of Ca, phosphate and alcohol diminishes Mg absorption. PTH increases Mg absorption. ● Disease state- Mg deficiency causes neuromuscular irritation, weakness and convulsions. Malnutrition, cirrhosis of liver may lead to Mg deficiency. ● Low levels of Mg may be observed in uremia, rickets and abnormal pregnancy. 33. LIVER FUNCTION TEST. ● Liver performs several functions. It is the central organ of body’s metabolism. ● Functions of liver- metabolic, excretory, protective functions and detoxification, hematological and storage functions. ● Test to assess the liver function: LFT are the biochemical investigations to assess the capacity of the liver to carry out any functions it performs. It will help to detect the abnormalities and extent of liver damage. ● Major LFT may be classified- Excretory function- measurement of bile pigments, bile salts, bromosulphthlein. ● Serum enzyme derived from liver- determination of transaminases, ALP, 5’-nucleotidase, gama-glutamyl- transpeptidase. ● Metabolic capacity- galactose tolerance, antipyrine clearance. ● Synthetic function- PT, serum albumin. ● Detoxification- hippuric acid dynthesis. Markers of liver function: 34. GASTRIC FUNCTION TEST. ● Fractional test meal [FMT] - this is old and not used these days. ● Alcohol test meal - test meal in the form of 100ml of 7% alcohol is administered. The response to alcohol test meal is more rapid. Clear specimens can be collected by this test and free acidity levels are relatively higher. ● Pentagastrin stimulation test - the stomach contents are aspirated by Ryle’s tube in a fasting condition. This is referred to as residual juice. The gastric juice elaborate for next 1hr is collected and pooled. Pentagastrin is now given to stimulate gastric secretion. The gastric juice is collected at 15 min intervals for 1hr and measured for acidity by titrating the samples with N/10 NaOH to PH- 7.4 -Basal acid output [BAO] - Acid output under the basal conditions [basal secretion]. -Maximum acid output [MAO] - Acid output after the gastric stimulation by pentagastrin [max. secretion]. ● Augmented histamine test meal: Histamine [0.04mg/kg body weight] is administered subcutaneously and the gastric contents are aspirated for the next one hour. ● Insulin test meal: Also known as Hollander’s test mainly done to assess completeness of vagotomy [vagal resection]. Insulin is administered intravenously which causes hypoglycemia [blood glucose- 40mg/dl], within 30mins, in normal persons. If the vagotomy is successful insulin administration does not cause any increase in the acid output compared to basal level. ● Tubeless gastric analysis: Administration of a cation exchange resin that gets quantitatively exchanged with the H+ ions of the gastric juice. It is excreted into urine which can be estimated for an indirect measure of gastric acidity. Diagnex blue containing azure-A-resin is employed in this analysis. ● Abnormalities in gastric function: - Increased gastric HCL secretion is found in Zollinger-Ellison syndrome, chronic duodenal ulcer, gastric cell hyperplasia, excessive histamine production. - Decreased in HCL is observed in gastritis, gastric carcinoma, pernicious anemia.
39. ESSENTIAL FATTY ACIDS.
● The unsaturated fatty acids which the body cannot synthesize and must be consumed in the diet are referred to as EFA. ● Fatty acids- linoleic and linolenic acid cannot be synthesized in humans. Arachidonic acid can be synthesized from linoleic acid in some animal species. ● Functions: these are the structural components of the biological membrane. Participate in the transport and utilization of cholesterol. Required for the synthesis of prostaglandins. Maintain the proper growth and reproduction of the organisms. ● Deficiency of EFA: Impairment of growth and reproduction, increased BMR and high turnover of phospholipids, poor wound healing and hair loss. ● Scaly dermatitis on the posterior and lateral aspect parts of limbs and buttocks. This is known as pyoderma or toad skin. ● Content of foods- frequently called PUFA- vegetable oils, fish oils. Rich vegetable sources- sunflower oil, cotton oil, corn oil, soya bean oil. ● Dietary intake- 30% of the dietary fat should contain PUFA. Very high intake of PUFA may not be advisable. It is injurious to the cells due to the overproduction of free radicals. 43. METABOLIC ACIDOSIS. ● The primary defect is a reduction in bicarbonate concentration which leads to fall in blood PH. It is decreased due to its utilization in buffering H+ ions loss in urine or gastrointestinal tract or failure to be regenerated. ● Most important Cause – Major clinical causes-
● Metabolic acidosis is commonly seen in severe
uncontrolled DM which is associated with excessive production of acetoacetic acid and beta-hydroxybutyric acid. ● Anion gap and metabolic acidosis: increased production and accumulation of organic acids causes an elevation in the anion gap. ● This type of picture seen in metabolic acidosis associated with diabetes [ketoacidosis]. ● Compensation of metabolic acidosis: acute metabolic acidosis is usually compensated by hyperventilation of lung. This leads to an increased elimination of CO2 from the body. ● But respiratory compensation is short lived. Renal compensation sets within 3-4 days and the H+ ions are excreted as NH4 ions. 46. RENAL FUNCTION TEST. ● Vital organ of the body performing major functions: Maintenance of homeostasis, excretion of metabolic waste products, retention of substances vital to body, hormonal functions [erythropoietin, 1,25- dihydroxycholecalciferol, renin]. ● RFT divided into 4 groups- ● Glomerular function test: all the clearance tests- inulin, creatinine, urea. ● Tubular function test: urine concentration/dilution, acidification test. ● Analysis of blood/serum: blood urea, serum creatinine, protein and electrolytes. ● Urine examination: routine examination of urine for volume, PH, specific gravity, osmolality and presence of certain abnormal constituents [blood, proteins, ketone bodies, glucose etc].