Biochem 1

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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].

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