CARBOHYDRATES Flashcards
explain Classification of carbohydrates ,derivatives , Df of each ,
–Carbohydrates are a class of organic substances whose general
formula can be represented as (CH2O)n. All carbohydrates can be
divided into:
1.monosaccharides (simple sugar)
2.oligosaccharides
3.polysaccharides
1-Monosaccharides : depending on the number of carbon atoms
called tri-, tetra-, pentoses or hexoses (respectively 3, 4, 5 or 6
carbon atoms). The main monosaccharide in humans is glucose. In
addition to it, the composition of food or components of cellular
structures in humans include such hexoses as fructose, mannose and galactose, and the part of nucleic acids (RNA and DNA) – pentose (ribose and deoxyribose).
-monosaccharides’ derivatives, it is necessary to mention :
1.1 sugar acids, which include glucuronic acid. The binding of
various organic substances to it in the liver leads to a decrease in
their toxicity and an increase in solubility in water (for example, the formation of mono- and diglucuronide bilirubin)
1.2 Sialic acids represented by carbohidrates with nine carbon atoms (acetylneuraminic acid, glycolylneuraminic acid) are part of the connective tissue. Sialic acids are determined in the patients’ blood as one of the inflammation markers.
2-Oligosaccharides can contain from 2 to 10 monosaccharides.
Among them, three disaccharides are of great importance – sucrose, lactose and maltose
2.1 Sucrose is composed of glucose and fructose units, it enters the body in the form of cane sugar or beet sugar, as well as in food. Part of sucrose is formed as a result of hydrolysis of carbohydrates in small intestine.
2,2 Lactose includes galactose and glucose units; its main source is
milk. In humans and other mammals, it can be synthesized by the
cells of the secretory epithelium of the mammary glands during
lactation.
2,3 Maltose consists of two glucose units
NB ! In addition to disaccharides, oligosaccharides are also a number of carbohydrates that are part of glycoproteins and glycolipids. These substances are part of cell membranes of various organs.
3-Polysaccharides are the most common group of carbohydrates.
Among them, there are homopolysaccharides, the repeating unit of which is any monosaccharide, and heteropolysaccharides, the basis for the repetition of which is the disaccharide.
The most important
3.1.1 homopolysaccharides for humans are starch,
glycogen and cellulose.
3.1.2 Starch enters the human body with food of plant origin. It is
subjected to the breakdown of enzymes of the gastrointestinal tract and is an important source of glucose.
3,1,3 Glycogen is an analogue of starch in animal tissues. A person
receives glycogen from food of animal origin. In addition, part of the glycogen is resynthesized and deposited in the liver and muscles, serves as a reserve of glucose.
3,1,4 Cellulose is not synthesized or broken down in human body. Its source is a plant food. In the intestine, cellulose increases intestinal motility, adsorbs some toxic substances and participates in the fecal masses formation.
3,2.1 Heteropolysaccharides are a part of proteoglycans and form the basis of the ground substance of human connective tissue.
Proteoglycans contain glucosamine or galactosamine, so this group of substances is also called glycosaminoglycans.
Glycosaminoglycans in aqueous solutions are highly hydrated and
form gels, which is reflected in their former name –
mucopolysaccharides. There are next major classes of
glycosaminoglycans – hyaluronic acid, chondroitinsulfate, dermatan sulfate, and heparin. Most glycosaminoglycans are synthesized by connective tissue fibroblasts, only heparin is synthesized by mast cells
3.2.2 Hyaluronic acid is a part of cell walls, synovial fluid, vitreous,
surrounds the internal organs, is a jelly-like bactericidal lubricant.
3.2.3 Chondroitin sulfates serve as the main structural components of
cartilage, tendons, cornea of the eye; also contained in the bones and skin.
3.2.4 Heparin is one of the main physiological anticoagulants in the human body.
The functions of carbohydrates in the human body
- Energy – up to 67% of the daily energy consumption in the
body is provided by the oxidation of carbohydrates, and 2/3 of this
amount is spent on energy supply to the brain. - Structural: carbohydrates are an essential component of cell
membranes and cellular organelles. - Plastic: carbohydrate breakdown metabolites are used for the
synthesis of polysaccharides, aminoacids and lipids. Pentoses
(ribose, deoxyribose) are part of nucleic acids. - Support: glycosaminoglycans are found in ground substance
of connective tissue, including the musculoskeletal system (cartilage, bones, etc.). - Reserve: glycogen is a source of energy and plastic material.
- Maintaining the liquid state of the blood: heteropolysaccharide heparin is a physiological anticoagulant.
- Detoxication – the glucuronides formation in the liver is
necessary for the neutralization of toxic substances, for example, the conversion of indirect bilirubin into direct. ( ciliose )
source of Carbohydrate , daily requirement , refined and
unrefinde
-Their main source is vegetable products (grains, vegetables,
fruits, pulses, nuts, seeds). Animal food is a source of glycogen, and dairy foods of lactose (milk sugar). Carbohydrate foods are an
important source of fiber and other nutrients
-a daily requirement for carbohydrate of
130 g/day for adults and children aged ≥1 year was established. This value was based on the amount of sugars and starches required to provide the brain with an adequate supply of glucose , carbohydrates of 45–65% of total calories.
-Carbohydrates of food are divided into refined (released from
the accompanying impurities in the purification process) and
unrefined, represented mainly by starch with accompanying fiber.
1- refined : contain no ciliose Ex carbohydrate
2- unrefined : contain ciliose Ex mushroom , fiber food , oatmeal
Carbohydrate metabolism
-Sucrose, fructose and glucose contained in them are rapidly
absorbed into the blood and contribute to fat formation with
excessive content in the diet. The starch of potatoes, cereals,
vegetables and fruits is broken down gradually, the formed
monosaccharides are absorbed slowly, and fiber is partially
processed by the intestinal microflora. Its dietary fibers are also
involved in the fecal masses formation and regulate the intestinal
motor function
1-Digestion of carbohydrates begins in the oral cavity. Under the
action of α-amylase of the salivary glands, part of the starch and
glycogen of the food is broken down to form dextrins (shortened
chains of starch and glycogen) and a small amount of maltose
disaccharide.
2-In the stomach, enzymes that break down complex
carbohydrates are absent. However, inside the bolus the saliva
enzymes continue functioning for some time, until the inactivation of α-amylase hydrochloric acid gastric juice takes place.
3-Further metabolism of polysaccharides is carried out in the
duodenum under the action of amylolytic enzymes of pancreatic
juice: α-amylase, oligo-1,6-glucosidase, amyl-1,6-glucosidase. The
wall enzymes of the small intestine (maltase, sucrose, γ-amylase,
trehalase and lactase) act on oligosaccharides formed during
cleavage, From the small intestine cavity monosaccharides (glucose, fructose, mannose and galactose) are transferred by active transport to enterocytes, where most of them are converted into glucose through a number of reactions
4- From the small intestine cavity monosaccharides (glucose,
fructose, mannose and galactose) are transferred by active transport to enterocytes, where most of them are converted into glucose through a number of reactions
5-Up to 90% of the formed glucose is absorbed into the blood. The
remaining 10% fall into the lymph. Through the portal vein system,
monosaccharides enter the liver and undergo various transformations in it, and are utilized by cells of various organs and tissues. then Intermediate metabolism of carbohydrates
—-Intermediate metabolism of carbohydrates\
nside the cells, glucose is phosphorylated to glucose-6-
phosphate. All subsequent transformations are carried out through this stage
explain Intermediate metabolism of carbohydrates
-Inside the cells, glucose is phosphorylated to glucose-6-
phosphate. All subsequent transformations are carried out through this stage
1-Glycogen synthesis. Neither glucose nor glucose-6-phosphate
can accumulate in cells. The reserve form of carbohydrates in the
human body is glycogen. Its greatest reserves are formed in the liver and skeletal muscles. When the level of glucose in blood is reduced, glycogenolysis (glycogen breakdown) is activated to restore its level. Glycogenolysis is enhanced by the excitation of the central nervous system,the liver contains enzymes glucose-6-phosphatase and glucose-1-phosphatase, converting glucose-6-phosphate and glucose-1-phosphate, respectively, into free glucose and phosphate. Glucose enters the blood and serves as a source of nutrition for various tissues,
2-Glycolysis is the central pathway of glucose catabolism and
many other carbohydrates. It can be carried out in the presence of
oxygen or without it (aerobic or anaerobic glycolysis). Before the
pyruvate formation, these processes occur by the same enzymatic
reactions. Under anaerobic conditions, pyruvate is converted to lactic acid (lactate). This reaction is catalyzed by the enzyme lactate
dehydrogenase (LDH). Lactic acid is absorbed into the blood,
extracted from it by the liver cells and re-converted into glucose.
,LDH is able to catalyze the reverse reaction – the conversion of lactate into pyruvate. This reaction is more active in well-supplied organs: heart, lungs, kidneys, etc. The resulting pyruvate undergoes transformations in a pyruvate dehydrogenase complex consisting of three enzymes and five coenzymes :
-enzymes : Pyruvate dehydrogenase ,Dihydrolipoyl transacetylase ,Dihydrolipoyl dehydrogenase
-Cofactors : TPP (thiamine pyrophosphate) , Lipoate ,
coenzyme A , FAD, NAD
3-Gluconeogenesis :is the synthesis of glucose from noncarbohydrate products: lactate, pyruvate, glycerin and glycogenic amino acids. Activation of gluconeogenesis is observed during fasting, when a person depletes glycogen stores, and the brain and contracting skeletal muscles need a continuous supply of glucose. Most of the reactions of gluconeogenesis are the reverse reactions of glycolysis. The intensity of gluconeogenesis is
significantly increased in diabetes mellitus.
4-The pentose phosphate pathway : is an alternate route of glucose
oxidation, which turns no more than 2% of all carbohydrates.
However, its biological significance is big, because in it NADP·H2
and ribose-5 phosphate are formed. Ribose-5-phosphate is necessary for the synthesis of a number of important biological molecules: RNA and DNA, ATP, COA, NAD and FAD. Therefore, the high demand for ribose-5-phosphate is noted in cells with a high rate of nucleic metabolism. They are embryonic tissues, epithelial cells, testes, stem cells of hematopoietic organs, regenerating tissues. The pathway may continue to the formation of the NADP·H2, which is necessary for the synthesis of fatty acids, steroids, amino acids ,glutathione reducing in red blood cells. Thus, the reactions of pentose phosphate pathway of carbohydrates intensively occur in white adipose tissue, liver, adrenal, breast and thyroid glands. Oxidation of 1 mol of glucose allows obtaining 12 mol NADP·H2. The cycle of transformations takes place in the cytosol of cells
Hormonal regulation of blood glucose
-Due to the interaction of the above described biochemical
processes, a constant level of glucose in blood is maintained.
Hormonal regulation of glucose metabolism mainly occurs when the glucose concentration in blood increases or decreases. At a normal glucose level, its metabolic regulation is used.
After eating, a person has a short-term hyperglycemia (no more
than 1.5-2 hours), stimulating the release of the hormone insulin
from β-cells of the pancreatic islets.
1-Insulin is synthesized as inactive proinsulin, consisting of two
polypeptide chains connected by a pair of disulfide bridges. In the
secretory granules of the Golgi β-cell apparatus, a small fragment (Cpeptide) is cleaved from proinsulin. Both substances, insulin and Cpeptide, are stored in granules in equimolar amounts until releasing from the cell by exocytosis.
Insulin helps to reduce the glucose concentration in the blood
due to the following effects:
- insulin facilitates entry of glucose into muscle, adipose and
several other tissues;
- enhancing glycogen synthesis in the liver and muscle tissue by
activating glycogen synthase and inhibiting glycogenolysis;
- activates enzymes of glucose phosphorylation and its
transformation into glucose-6-phosphate (glucokinase in the liver
and hexokinase in muscle, fat and other tissues). Increasing the
concentration of glucose-6-phosphate leads to the activation of
anaerobic glycolysis, pentosophosphate pathway and tricarboxylic
acid cycle, for which glucose-6-phosphate is the starting product;
- reduces formation of free glucose – gluconeogenesis,
glycogenolysis due to inhibitory effects on individual enzymes;
- inhibits lipolysis.
2-somatotropin enhances gluconeogenesis, reduces the
absorption of glucose in the periphery, as well as increases lipolysis, which increases the concentration of free fatty acids that inhibit the action of insulin on the membrane transport of glucose;
3– glucocorticoids stimulate protein catabolism and
gluconeogenesis, reduce membrane glucose transport and its
utilization in the periphery, increase glycogen content in the liver and to a lesser extent in muscles;
4-ACTH mediates hyperglycemic action mainly through
glucocorticoids;
5- thyroid hormones increase the absorption of glucose in the
intestine, glycogenolysis and lipolysis, increase the activity of Krebs
cycle enzymes.
DISORDERS OF CARBOHYDRATE METABOLISM AND
THEIR LABORATORY DIAGNOSIS
1-Blood glucose level is the main biochemical indicator of
carbohydrate metabolism.
According to recommendations, the normal values of fasting
blood glucose are 3.5-5.7 mmol/l, or 60-100 mg/DL (for people
under the age of 50 years) and 4.4–6.1 mmol/l, or 80-110 mg/DL (for people over 50 years)
-NB! An increase in
glucose concentration above 6.1 mmol/l is called hyperglycemia, and
a decrease below 3.5 mmol/l is called hypoglycemia.
Glucose is a vital energy raw material for the brain, so
hypoglycemia can lead to disruption of brain function, up to death.
Clinical symptoms of hypoglycemia are divided into adrenergic,
due to the release of catecholamines and activation of the
sympathetic nervous system, and neurological, caused by CNS
dysfunction. Adrenergic symptoms in acute hypoglycemia develop
earlier and include irritability, weakness, headache, sweating, tremor of the limbs, tachycardia, fear and hunger. Neurological symptoms include: inhibition of verbal and motor reactions, confusion, impaired motor function, abnormal behavior, impairment or loss of consciousness, convulsions. Hypoglycemia can result in hypoglycemic coma. In most cases, neurological symptoms occur when the blood glucose level is below 2.8 mmol/l. These symptoms appearing depends on the blood glucose lowering rate, on the amount of glycogen stores in the liver and muscles, Patients with type I diabetes may not feel adrenergic symptoms due to impaired secretion of glucagon, adrenaline and dysfunction of the autonomic nervous system.
-The most common reasons for hypoglycemia:
1) alimentary hypoglycemia (prolonged fasting);
2) exhausting physical work, intense physical activity;
3) overdose of insulin or hypoglycemic medications for
diabetes;
4) hormone deficiency in endocrine diseases (Addison’s disease,
hypothyroidism, hypopituitarism, etc.);
5) insulinoma;
6) diseases, accompanied by a decrease in the absorption of
carbohydrates in the intestine (enteritis, the consequences of
gastrectomy, pancreatic diarrhea, etc.);
7) severe arsenic poisoning, chloroform, alcohol intoxication,
etc., occurring with inhibition of liver function, including a violation
of glycogenesis and gluconeogenesis;
8) renal diabetes (impaired reabsorption of glucose in the
tubulopathy);
9) hereditary fermentopathy (glycogenosis, galactosemia, etc.).
-the main reasons for hyperglycemia are:
1) physiological short-term hyperglycemia (food, rich in refined
carbohydrates; significant emotional stress);
2) diabetes mellitus type I or II (insufficient insulin production
or increased tissue tolerance to this hormone);
3) diseases of the pituitary gland, accompanied by increased
secretion of growth hormon and adrenocorticotropic hormone
(ACTH) (Cushing’s disease, acromegaly);
4) diseases of the adrenal glands, combined with enhanced
production of catecholamines or glucocorticosteroids
(pheochromocytoma, Cushing’s syndrome);
5) thyrotoxicosis;
6) pancreatic diseases (acute and chronic pancreatitis, pancreatic
tumor).
2-Random blood glucose Random it means without regard to time since the last meal. Usually this test is done just in case of emergency. It may be useful also in asymptomatic patients. If the level of random glucose is more than 11.1 mmol / l and if it is accompanied by the classic symptoms of diabetes (polyuria, polydipsia, weight loss), it is enough to diagnose diabetes.
3-Glucose tolerance test (GTT)
There are several modifications of GTT: oral GTT, intravenous
GTT and prednisolone-glucose tolerance test:
3.1 Oral glucose test.
You must carry out GTT, when:
1) there are doubtful results of fasting glucose measurement
(possible postabsorption results or accidentally detected
hyperglycemia);
2) there are clinical signs of diabetes with normal blood glucose;
3) glucosuria is accidentally detected.
When fasting glucose in venous blood plasma is above 15 mmol
/ L (or if there are several definitions above 7.8 mmol / L), GTT is
not used to diagnose diabetes.
When carrying out GTT, the patient should receive regular food
(with a carbohydrate content of more than 150 g per day) for 3 days before the study, as well as not to eat in the evening before the examination. During GTT, the fasting glucose level is determined, after which it is allowed to drink 75 g of glucose dissolved in 300 ml of warm water or tea with lemon for 3-5 minutes (for children – 1.75 g / kg, but not more than 75 g ). Re-measure glucose after 2 hours. During the test, the subject is not allowed to smoke. Also the patients should be normally active and not to have any acute illness. Medications that may impair glucose tolerance like diuretics, contraceptive drugs, glucocorticoids and others should be avoided on the day of test.
Evaluation of GTT results (by the venous blood plasma level) table
-Time to take blood: Fasting glucose level (mmol/l)
-Normal level : Less than 5.5
-Impaired glucose tolerance : 5,6 - 6.7
- Diabetes : Over 6.7
—–
-Time to take blood: 2 hours after glucose load (mmol/l)
-Normal level : Till 7, 8
-Impaired glucose tolerance :7, 8 - 11.1
- Diabetes : More than 11.1
NB! In addition, the results of GTT may be doubtful if:
1) at least one of the indicators was above the norm;
2) in the initial examination revealed indicators of impaired
glucose tolerance, and when repeated – normal data.
NB! :There are the following main causes of impaired glucose
tolerance
–Increased tolerance (fasting, no peak blood glucose in
response to the load):
1) decrease in the rate of absorption of glucose from the intestine
on the background of adrenal hypofunction, intestinal diseases
(Whipple’s disease, tropical sprue, celiac disease), hypothyroidism;
2) increased insulin secretion in insulin.
–Decreased tolerance:
1) increase in the rate of absorption from the intestine with
excessive consumption of glucose with food, hyperthyroidism,
conditions after gastroectomy, vagotomy;
2) increased glycogenolysis and gluconeogenesis on the
background of hyperthyroidism, hyperfunction of the adrenal cortex, pheochromacytoma, infections, pregnancy;
3) disturbance of glycogen formation in severe liver disease,
glycogen storage;
4) reduction of glucose utilization by tissues against the
background of CNS lesions (injuries, tumors of the hypothalamus).
3.2 B. Intravenous glucose tolerance test
The intravenous (IV) glucose tolerance test (IGTT) is rarely
used, and is never used to diagnose diabetes. With IGTT, glucose is
injected into a vein for 3 minutes. Blood insulin levels are measured before the injection, and again at 1 and 3 minutes after the injection. The timing may vary.
IGTT helps estimate the time of the diabetes onset among
individuals expressing anti-islet autoantibodies.
3.3 C. Prednisolone glucose tolerance test
The test helps to identify hidden disorders of carbohydrate
metabolism, as prednisolone stimulates the processes of
gluconeogenesis and inhibits the formation of glycogen. In
combination with glucose loading, this leads to more significant
glycaemia in persons with functional insufficiency of pancreatic β-
cells. The indications for the test are:
1) doubtful data of standard glucose tolerance test;
2) the presence of hereditary predisposition to diabetes
4-Glucose in urine
In the urine of a healthy person glucose is not determined.
Glucosuria is detected when blood glucose exceeds a certain level the renal threshold for glucose, which is 8.8-10 mmol/l. In this case,the amount of glucose filtered into the primary urine exceeds the ability of kidneys to reabsorption. With age, the renal threshold for glucose increases, for people over 50 years it is more than 12 mmol/l.
5-Determination of glycosylated hemoglobin (HbA1c)
Hyperglycemia in diabetes leads to non-enzymatic glycosylation
of hemoglobin of red blood cells. This process occurs spontaneously and normally throughout the life of red blood cells, but with an increase in the concentration of glucose in the blood reaction rate increases. In the initial stage, the glucose residue is attached to the Nterminal residue valine in β-chain of hemoglobin, forming an unstable compound – aldimine. With a decrease in blood glucose
aldimine breaks down, and with persistent hyperglycemia isomerized into a stable, stable ketamine and circulates in this form the entire life of the red blood cell, ie, 100-120 days. Thus, the level of glycosylated hemoglobin (HbA1c) is directly dependent on the level of blood glucose. HbA1c reflects average plasma glucose over the previous 2-3 months. It can be performed at any time of the day and does not require any special preparation such as fasting. This method, as compared with the determination of glucose level, does not depend on the time of day, physical activity, food intake, prescribed medications, emotional state.
The level of glycosylated
hemoglobin is increased in the blood cells of persons with poorly
controlled diabetes mellitus. It may be also used as a diagnostic test for diabetes and as a screening test for persons at high risk of
diabetes.
The normal level for glycosylated hemoglobin is less than 5.7%:
Normal: HbA1c below 5.7%
Prediabetes: HbA1c between 5.7% and 6.4
Diabetes: HbA1c of 6.5% or higher.
The test permits to control of treatment at patients with
diabetes. Levels above 9% show poor control, and levels above 12% show very poor control. It is commonly recommended that
glycosylated hemoglobin be measured every 3 to 6 months in
diabetes.
6-. Serum fructosamine
Excess glucose in the blood binds not only to hemoglobin, but
blood protein, mostly albumin. Lysine albumin, binding to glucose,
forms an unstable compound-aldimine, which is subsequently
converted into ketamine – resistant protein-glucose compound, also called fructosamine. Fructosamine in the serum of healthy people contained in the amount of 2-2.8 mmol/l. The period of their half-life is about 3 weeks. Therefore, the level of fructosamines reflects the state of carbohydrate metabolism for 2-3 weeks before the examination. The advantage of fructosamine over HbA1c is that it’s not affected by changes in red blood cells and level of hemoglobin caused by anemia, blood loss. Fructosamine level may be not true in people who have thyroid disease, intestinal disease (protein-losing enteropathy), kidney disorder (nephrotic syndrome) or liver disease ,The test is used to estimate diabetes compensation: 2.8 – 3.2
mmol/l indicates compensated diabetes; and more than 3.2 mmol/l is a sign of diabetes mellitus decompensation.
7-Immunoreactive insulin Safety assessment of insulin production is carried out according to the level of immunoreactive insulin and C-peptide.
In the fasted state the normal level of insulin in blood serum is
6-24, mIU/l (29-181 pmol/l). Normally, the level of hormone in the
blood increases sharply after eating, as carbohydrates are the main regulator of hormone secretion from the pancreas.
This reaction makes it possible to use the test for differential
diagnosis of diabetes mellitus type I and II in parallel with GTT
8-C-peptide
C-peptide is a fragment of the proinsulin molecule, which is
cleaved during the formation of active insulin. It is released into the
bloodstream in almost equal concentrations with insulin. Unlike
insulin, C-peptide is biologically inactive and metabolized in the
liver several times slower. Therefore, the ratio of C-peptide and
insulin in peripheral blood is 5:1. When using the ELISA method,
the C-peptide does not cross-react with insulin and therefore allows evaluating insulin secretion even against the background of
exogenous insulin, as well as in the presence of autoantibodies to
insulin. The sample of blood is taken usually after 8-10 hours of fasting. The normal concentration of C-peptide is 0.5 to 2.0 ng/mL. After orally takig glucose, there is a 5-6 times increasing in C-peptide. Determination of C-peptide is used:
1) to control a function of pancreatic β-cells, especially during
administration of insulin preparations and after surgical removal of a part of pancreas;
2) for differential diagnosis of hypoglycemic states
(insulinomas);
3) for differential diagnosis of type I and type II diabetes (in
type I peptide is reduced, in type II ‒ elevated);
4) for assessment of possible fetal pathology in pregnant women
with diabetes mellitus.
C-peptide level is increased:
after taking meal;
in type II diabetes;
in renal failure.
C-peptide level is reduced in:
type I diabetes;
administration of insulin preparations;
alcoholic hypoglycemia;
stress;
presence of antibodies to insulin
9-The level of reticulocytes
Normally, the level of reticulocytes is 2-10 ‰ (0.2–1.0 %).
The content of reticulocytes in patients with diabetes is often
increased. This is associated with tissue hypoxia, developing on the background of angiopathy in diabetes, as well as due to glycosylation of hemoglobin and erythrocyte membrane proteins. Glycosylated hemoglobin has a great affinity for oxygen and gives it worse to tissues.
With the development of diabetic nephropathy, the level of
reticulocytes can be reduced, which is associated with a decrease in the erythropoietins production by the kidneys.
10- Albuminuria
Albuminuria (formerly microalbuminuria) are a well-established
cardiovascular risk marker, in which increases over time to macroalbuminuria (>300 mg/day) are associated with kidney disease and an increased risk for progression to end-stage renal disease in diabetic patients.
11-Ketonuria :Ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) are insignificant in the blood and urine of normal individuals. However, these ketoacids become important sources of metabolic energy in circumstances in which the availability of glucose is restricted, as during prolonged fasting, or when the ability to use glucose is greatly diminished, as in decompensated diabetes mellitus.
LABORATORY DIAGNOSTICS OF COMATOSE STATES IN DIABETES
—Depending on the cause, the coma of diabetes is divided into:
- hyperglycemic or ketoacidotic coma in combination with
absolute insulin deficiency and ketoacidosis;
- hyperglycemic hyperosmolar coma characteristic for patients
with moderate insulin deficiency;
- hyperglycemic coma with lactic acidosis, proceeding with
severe hypoxia, cardiovascular shock;
- hypoglycemic coma, the development of which is associated
with an overdose of insulin, insufficient intake of carbohydrates or
their excessive consumption due to physical activity
——————————
-Diabetic ketoacidosis, if it progresses and worsens without
treatment, can ultimately cause loss of consciousness due to a
combination of very high blood sugar, dehydration and shock, as
well as exhaustion. Coma occurs only at a late stage, usually 36 or
more hours after the deterioration of vomiting and hyperventilation. In the early and middle stages of ketoacidosis, patients tend to redden and breathe quickly and deeply, but upon reaching a coma, visible dehydration, pale appearance due to reduced perfusion,
shallow breathing and rapid heartbeat are often observed. However,
these functions are variable and not always as described.
If the patient is known to have diabetes, a diagnosis of diabetic
ketoacidosis is usually suspected by the appearance and history of
vomiting within 1-2 days. The diagnosis is confirmed when routine
emergency blood tests show high blood sugar and severe metabolic
acidosis.
The treatment of diabetic ketoacidosis consists of isotonic fluids
for fast stabilization of blood circulation, continued intravenous
administration of physiological saline with potassium and other
electrolytes to fill the deficiency, insulin to eliminate ketoacidosis
and closely monitor complications.
—-Non-ketotic hyperosmolar coma usually develops more
insidiously than diabetic ketoacidosis, because the main symptom is lethargy, progressing to flow, and not vomiting and obvious illness. Extremely high blood sugar levels are accompanied by dehydration due to insufficient fluid intake. Coma is most commonly found in patients with type 2 diabetes or steroid diabetes and with impaired ability to recognize thirst and drink. This is a classic nursing home condition, but can occur at any age.
The diagnosis is usually detected by a chemical examination due
to extremely high blood sugar (often above 1800 mg / dl (100 mM))
and dehydration. Treatment consists of insulin and gradual
rehydration with intravenous fluids.
——Severe hypoglycemia (very low blood glucose levels) can lead
to loss of consciousness and coma if not treated.
In most cases the body will restore blood sugar levels to normal
by releasing glucagon to raise blood sugar levels.
Coma is more likely to occur from low blood glucose levels if:
A large insulin overdose is taken
Alcohol is in the body during hypoglycemia
Exercise has depleted the body’s glycogen supply
Laboratory diagnosis of these conditions, in addition to the
above parameters, also includes the definition of the following
indicators of carbohydrate metabolism :
1. Lactic acid is the final product of anaerobic glycolysis. Its
content is normally significantly different in various biological
fluids: in arterial blood is 0.33-0.78 mmol/l; in venous blood is 0.56- 1.67 mmol/l; in cerebrospinal fluid is 0.84 – 2.36 mmol/l.
Lactic acid is also detected in gastric cancer in gastric juice,
although it is usually not there. Increase in lactic acid in the blood is noted in the following
conditions:
- hypoxia due to the transition of tissues to anaerobic glycolysis;
- heavy physical activity;
- increased muscle contractions (seizures in epilepsy, tetanus,
- childbirth;
- inflamed tissues, with fever;
- cancer tumour;
- heart failure with stagnation;
- cirrhosis;
- chronic alcoholism;
- complications of diabetes mellitus (lactic acid coma).
2. Pyruvic acid (PVA)
Formed during glycolysis, PVA enters the Krebs cycle through
the formation of acetyl-CoA in the pyruvate dehydrogenase complex. The excess of the formed pyruvate in anaerobic conditions is converted to lactic acid.
The content of PVA in the blood is normally 45.6 – 114 µmol/l.
PVA level increases in:
- vitamin B1 deficiency (disorders of PDG-complex), vitamin
B1 deficiency-Beri-Beri disease;
- hepatitis, liver cirrhosis (violations of pyruvate
transformation);
- diabetes (increased production by accelerating the breakdown
of amino acids);
- poisoning by salts of heavy metals;
- polycythemia, erythremia.
3. Sialic acid : As one of the markers of inflammation and destruction of connective tissue, it is used to determine the level of sialic acids in the blood. The content of sialic acids is normally 2.0–2.36 mmol/l and increases in the following cases:
- cytolysis of cells of various organs (myocardial infarction,
hepatitis, etc.), as sialic acids are part of cell membranes;
- destruction of connective tissue (collagenoses, osteomyelitis,
bone fractures);
- defeat of the basement membrane (glomerulonephritis, vasculitis).
GLYCOGENOSES
-This is a group of hereditary diseases that occur due to
deficiency or complete absence of enzymes that catalyze the
processes of glycogen breakdownn, and characterized by excessive accumulation of glycogen in various organs and tissues.
This group includes the following diseases :
1. Von Gierke disease (glycogenosis type I) is glucose-6-
phosphatase deficiency. As a result, glucose-6-phosphate is not converted into glucose, and undergoes transformations along the way of glycolysis. Patients are characterized by low fasting glucose
levels. Activation of glycolysis is accompanied by an increase in the
level of blood lactate Lactic acid inhibits the excretion of urates by
the kidneys, and hyperuricemia occurs. The amount of ATP
produced is not sufficient
-Laboratory diagnostics:
1) hypoglycemia and low insulin levels;
2) hyperlactatemia;
3) type I or V hyperlipoproteidemia;
4) hyperuricemia;
5) bleeding (due to impaired synthesis of coagulation factors in
the liver);
6) the lack of increase in blood glucose with the introduction of
glucagon;
7) acetonemia, acetonuria;
8) the study of liver biopsy – deficiency of glucose-6- phosphatase
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2. Cori-Forbes disease (glycogenosis type III) is a amylo-1,6-
glucosidase deficiency. The disease is characterized by the development of hepatomegaly due to the accumulation of glycogen in the liver and the relative benign course. It can develop liver fibrosis, delayed physical and sexual development. With age, moderate myopathy may occur due to reduced muscle glycogenolysis.
Laboratory diagnostics:
- hypoglycemia;
- moderate increase in triglycerides and cholesterol in the blood;
- normal level of blood lactate.
Glucagon in patients increases glucose levels only after meals,
not on an empty stomach, as is normal
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3. Andersen’s disease (glycogen storage disease type IV) is a
glycogen branching enzyme deficiency or the deficit of
amilo-1,4;1,6-glucosidase.
It manifests itself in early childhood as liver failure, quickly
leading to liver cirrhosis and death. Muscle symptoms (hypotension, weakness) are shaded by hepatic ones.
The diagnosis is based on biochemical findings from a liver
biopsy, revealing an abnormal glycogen content, and on the evidence of enzymatic deficiency in the liver, muscle, erythrocytes, or fibroblasts, and in the trophoblast or cultured amniotic cells. Prenatal diagnosis is possible by enzyme assay and/or DNA analysis.
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4. Hers’ disease (glycogen storage disease type VI) is a
deficiency of liver phosphorylase.
Clinic and symptoms are similar to type I, but less pronounced.
It is manifested by hepatomegaly and growth retardation.
Hypoglycemia may not be severe; the test with glucagon is negative. Decisive in the diagnosis is a decrease in the activity of the enzyme in white blood cells. Also, the diagnosis of Hers’ disease can be based on a test for liver phosphorylase enzyme activity. A small piece of liver tissue is removed surgically (biopsy) and analyzed for enzyme activity. In people with Hers’ disease, this enzyme activity will be reduced
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-Muscle glycogenoses storage is the following :
1. Disease McArdle (glycogen storage disease type V) is a lack
of muscle phosphorylase , After heavy physical activity, patients may experience seizures.
At the same time myoglobinuria is revealed and in blood there is an increased activity in muscle enzymes (myophosphorylase, MM-creatinkinase, LDH4-5, aldolase). The concentration of lactate remains normal, as muscles receive energy not due to glucose, but due to the breakdown of fatty acids.
Diagnostics:
- Blood tests for muscle enzymes such as MM creatine kinase
- DNA blood tests for known mutations of Macardle disease
- electromyography to measure the electrical activity of muscles
- Forearm Workout Test
- A muscle biopsy to examine muscle cells for glycogen
accumulation
- Urine tests to check for myoglobin, which obscures urine
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2. Tarui’s disease (glycogenosis type VII) is a deficiency of the
phosphofructokinase enzyme.
Patients are able to tolerate moderate muscle load. The clinic is
similar to type V, but differs in the presence of moderate hemolytic
anemia.
The diagnosis is based on biological findings, revealing
increased amounts of abnormal glycogen and enzyme deficiency (1 to 33% residual activity) in a muscle biopsy, whereas activity in
erythrocytes is over 50%. Compensated hemolysis (increased
bilirubin and reticulocytes) and hyperuricemia are also associated.
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3.The glycogen storage of mixed type include the disease of
Pompe (glycogen storage disease type II), arising from a defect of
1,4-glucosidase. This is generalized glycogenosis, glycogen accumulates in all glycogen-containing organs: liver, spleen, kidneys, muscles, nervous tissue, red blood cells. In infancy, a large tongue develops, lethargy, slow weight gain,
and cyanosis are noted. An enlarged heart quickly leads to severe
heart failure and death in infancy.
There is a describing of three types of Pompe disease, which
differ in severity and the age at which they appear. These types are
known as classic infantile-onset, non-classic infantile-onset, and late onset.
MUCOPOLYSACCHARIDOSISES
-This is a hereditary pathology associated with the accumulation
of glycosaminoglycans (mucopolysaccharides) in various tissues
caused by a defect of specific lysosomal hydrolases. Products of
incomplete cleavage of glycosaminoglycans accumulate in the
lysosomes of the musculoskeletal system, internal organs, central
nervous system.
-General signs: dwarfism, deformation of the facial skeleton,
joints, hepatosplenomegaly, heart, blood vessels. It is characterized by delay of psychomotor and mental development.
In the most severe cases, death occurs in adolescence from
cardiovascular failure or secondary respiratory infections.
Diagnosis: detection of cases among relatives, detection of
glycosaminoglycans in the urine, reducing the activity of enzymes in leukocytes or skin fibroblast culture.
