Disorders of Carbohydrate Metabolism

Normal glucose level in the blood 65 -110 mg/% 65 -110 mg/% 3.50 - 6.05 mmol/L3.50 - 6.05 mmol/L

(5.5 (5.5 mmol/L)mmol/L)

Impairments of glucose balance

• Hypoglycemia (less than 2.5 mmol/L results in Hypoglycemia (less than 2.5 mmol/L results in coma)coma)

• HyperglycemiaHyperglycemia

GLUCOSEGLUCOSE

3.50 6.05NORM HyperglycemiaHyperglycemiaHypoglycemiaHypoglycemia

Blood Glucose & Blood Glucose & HormonesHormones

HormoneHormone InsulinInsulin GlucortocoidsGlucortocoids GlucagonGlucagon Growth HormoneGrowth Hormone EpinephrineEpinephrine

ActionAction GlucoseGlucose GlucoseGlucose GlucoseGlucose GlucoseGlucose GlucoseGlucose

Regulation of glucose metabolismRegulation of glucose metabolism The glucose concentration in The glucose concentration in

blood describes blood describes carbohydrates metabolism carbohydrates metabolism both of healthy man and sick. both of healthy man and sick. Illnesses base of which is Illnesses base of which is disorder of carbohydrates disorder of carbohydrates metabolism can flow with rise metabolism can flow with rise of glucose concentration in of glucose concentration in blood and with lowering of it. blood and with lowering of it.

Rise of glucoseRise of glucose concentration is named concentration is named hyperglicemiahyperglicemia lowering lowering hypoglicemiahypoglicemia. .

For exampleFor example, , hyperglicemiahyperglicemia is is very typical for very typical for diabetes diabetes mellitusmellitus, , hypoglycemiahypoglycemia – for – for glycogenosisglycogenosis.  . 

Regulation of carbohydrate metabolism

Counter-insulin hormones

ACTH, growth hormone, cortisol, thyroid

hormone, glucagon, adrenaline

1.Stimulate absorption of carbohydrates (cortisol, thyroid

hormone)

2. Increase glycogenolysis in liver and muscles, inhibit

glycogenesis (adrenaline, cortisol, thyroid)

3. Inhibit hexokinase activity and therefore its utilization

(cortisol, growth hormone)

4. Stimulate gluconeogenesis (cortisol, thyroid, glucagon)

5. Activate insulinase (growth hormone, thyroid)

Blood glucose balance Blood glucose balance regulationregulation

Insulin

• Permeability Permeability of cellular of cellular membranesmembranes

• glucokinase glucokinase reaction ratereaction rate• synthesis of synthesis of glycolytic glycolytic enzymesenzymes• gluconeogenesisgluconeogenesis

• glucose-6-glucose-6-phosphate phosphate productionproduction

Counter-insulin

hormones(glucagon, adrenaline, thyroids,

glucocorticoids sgrowth

hormone, ACTH)

inhibition

activation

Below is a summary of the way insulin influences the Below is a summary of the way insulin influences the physiological processes within the cells of each of these physiological processes within the cells of each of these

tissues.tissues.       Liver   Muscle   Adipose

        Stimulation of glucose uptake                                

           Stimulation of cellular respiration                                          

           Stimulation of glycogenesis                                

  Inhibition of glycogenolysis                                

  Stimulation of amino acid uptake                      

  Stimulation of protein synthesis                                          

  Inhibition of protein degradation                                          

 Stimulation of fatty acid and triglyceride synthesis

                               

  Inhibition of lipolysis                                

  Stimulation of lipoproteins uptake                      

The most important ones are emphasised by the pointing fingers.

A       indicates that the process stated is stimulated within the cells of that tissue by the hormone.

The Metabolic Effects of The Metabolic Effects of GlucagonGlucagon

     The Liver   Muscle   Adipose

        Stimulation of glycogenolysis                      

  Inhibition of glycogenesis                      

        Stimulation of gluconeogenesis                      

        Stimulation of lipolysis                      

  Stimulation of ketone formation                      

  Stimulation of amino acid uptake                      

 

Like insulin, glucagon is a polypeptide hormone. However, in contrast to insulin, receptors for glucagon are not as abundant in cells

throughout the body. The action of glucagon to increase blood glucose concentrations is largely as a result of the effects it has on cells of the

liver after binding to membrane receptors.

Hypoglycemia

Exogenous

EndogenousEndogenousFunctionalFunctional

Exogenous hypoglycemia

• Insulin injection

• Alcohol (develops 6-36 hours

after heavy consumption)

• Some drugs (e.g. salicylates)

• Long term physical exercise

Endogenous hypoglycemiaEndogenous hypoglycemia

insulinoma (hyperplasia of insulinoma (hyperplasia of -cells)-cells) glycogenosisglycogenosis hereditary fructose intolerancehereditary fructose intolerance insufficiency in insufficiency in

phosphoenolpyruvate carboxykinasephosphoenolpyruvate carboxykinase Hepatocellular insufficiencyHepatocellular insufficiency Impaired absorptionImpaired absorption

1.Alimentary (after gastrectomy, demping syndrome)

2.Spontaneous reactive (cause is not known diarrhea, tachycardy, tremor, headache, weakness)

3.Alcohol (consumption in hungry state)4.Endocrine insufficiency (decrease in counter-

insulin hormone )5. Hepatic failure6. Malnutrition 7. Heavy physical load (without carbohydrate

uptake)8. Transient functional hypoglycemia of children• Neonatal (10%)• Maternal diabetes• Erythroblastosis• Ketogenic

Functional HypoglycemiaFunctional Hypoglycemia

Manifestations of hyperglycemiaManifestations of hyperglycemia GlucosuriaGlucosuria PolyuriaPolyuria PolydypsiaPolydypsia Hypohydration of the organismHypohydration of the organism Arterial hypotensionArterial hypotension

Manifestations of hypoglycemiaManifestations of hypoglycemia StarvationStarvation TremorTremor Excessive sweatingExcessive sweating TachycardiaTachycardia Headache, dizzinessHeadache, dizziness Impaired visionImpaired vision Anxiety, fearAnxiety, fear Impaired cognitionImpaired cognition

mellitus

• Diabetes mellitus is heterogenic diseases group which arise on base of absolute or relative insulin insufficiency and have hyperglycemia as general symptom. 

• Impairment in carbohydrate, lipid, protein metabolism

• Hyperglycemia

• Non-enzymatic glycosylation

ClassificationClassificationPrimary DMPrimary DM – – (primary - no other disease)(primary - no other disease)

Type I – IDDM / Juvenile – 10%.Type I – IDDM / Juvenile – 10%. Type II – NIDDM /Adult onset – 80%.Type II – NIDDM /Adult onset – 80%. MODY – 5% maturity onset - GeneticMODY – 5% maturity onset - Genetic Gestational DiabetesGestational Diabetes

Secondary DMSecondary DM – (secondary to other dis.) – (secondary to other dis.) Pancreatitis, tumors, hemochromatosis.Pancreatitis, tumors, hemochromatosis. Infectious – congenital rubella, CMV.Infectious – congenital rubella, CMV. Endocrinopathy.Endocrinopathy. Drugs – Corticosteroids.Drugs – Corticosteroids.

There are counts six millions of patient with insulin-dependent diabetes mellitus in the world. This is mainly illness of white race. It occur more frequent in highly developed countries (Finland, Italy, Sweden, Denmark, Canada, Norway, USA, England).

There are about 100

millions of patient with insulin-dependent diabetes mellitus. They consist 85 % of all diabetics. They belong to mainly native population of USA (american indians), Fiji, South Africa, India, Polynesia.

Normal Pancreatic Islet:Normal Pancreatic Islet:

ß cells ß cells (Insulin) αα cells cells (Glucagon)

δδ cells cells (Somatostatin) pp Cells pp Cells (pan prot)

ßß αα

Type-I Type-I Type-IIType-II Less commonLess common Age < 25 YearsAge < 25 Years Insulin- Dependent Insulin- Dependent Onset: WeeksOnset: Weeks Acute Metabolic Acute Metabolic

complicationscomplications Autoantibody: YesAutoantibody: Yes Family History: NoFamily History: No Insulin levels: very Insulin levels: very

lowlow Islets: InsulitisIslets: Insulitis 50% in twins50% in twins

More commonMore common Adult >25 YearsAdult >25 Years Insulin Independent Insulin Independent

* * Months to yearsMonths to years Chronic Vascular Chronic Vascular

complications.complications. NoNo YesYes Normal or high *Normal or high * Normal / ExhaustionNormal / Exhaustion 60-80% in twins60-80% in twins

Insulin-dependent diabetes mellitusInsulin-dependent diabetes mellitus

Insulin-dependent diabetes Insulin-dependent diabetes mellitus arises as result of mellitus arises as result of absolute insulin insufficiency. It absolute insulin insufficiency. It is described by is described by insulinopenia insulinopenia and by inclination to and by inclination to ketoacidosis.ketoacidosis. This diabetes This diabetes occur more frequently is in occur more frequently is in children and young peoples (till children and young peoples (till 30 years). Insulin is needed for 30 years). Insulin is needed for sustentation of patient life. sustentation of patient life. Attached to it’s absence Attached to it’s absence ketoacidic coma develops. ketoacidic coma develops.

Carbohydrate metabolism in normal conditions and diabetes mellitus

INSULININSULINIMPAIRMENTIMPAIRMENT

1. Increase in permeability of myocyte and adipocyte membranes for glucose (Glut-4)

2. Increase in activity of glucokinase, glycogen-sythetase, aerobic glycolysis, pentose-phosphate shunt and Krebs cycle enzymes

3. Increased rate of glycogen synthesis in liver

4. Increase in synthesis of lipids from glucose

5. Inhibition of gluconeogenesis

HYPERGLYCEMIAHYPERGLYCEMIA

PATHOGENESIS OF DIABETES MELLITUSPATHOGENESIS OF DIABETES MELLITUS

Insulin insufficiency

Fatty acids

Ketone bodies

- hydroxybutirate, acetoacetate accumulation in

blood

Metabolic acidosis

Ketonuria

Kussmaul's respiration

CNS depression

Blood glucose level

glucosuria

polyuria

dehydration thirst

HypovolemiaSHOCK

Poly-dipsia

Insulin-independent diabetes Insulin-independent diabetes mellitusmellitus

This diabetes type principle differs from the first. This diabetes type principle differs from the first. Patients, as a rule don’t need to exogenic insulin. Patients, as a rule don’t need to exogenic insulin. Metabolic disorders attached to this diabetes are Metabolic disorders attached to this diabetes are minimal. Diet therapy and per oral glucose minimal. Diet therapy and per oral glucose decreasing medicines are sufficiently for their decreasing medicines are sufficiently for their compensation. Only in stress (trauma action, compensation. Only in stress (trauma action, sharp infection) conditions patient use insulin. sharp infection) conditions patient use insulin. Illness can course for years without Illness can course for years without hyperglycemia. Sometimes it is disclosed in age hyperglycemia. Sometimes it is disclosed in age more 40 years.more 40 years.

There are three factors group, which play a There are three factors group, which play a decisive role in forming of this diabetes type.  decisive role in forming of this diabetes type.  Here are the genetic factors, functional Here are the genetic factors, functional disturbance of disturbance of ββ-cells and insulin -cells and insulin resistanceresistance..

Pathogenesis of insulin-Pathogenesis of insulin-independent diabetes mellitusindependent diabetes mellitus

Diabetogenic action has diet is Diabetogenic action has diet is result of diet, which contains a result of diet, which contains a surplus of high-calorie products. surplus of high-calorie products. They are fats and purified simple They are fats and purified simple carbohydrates. Such action is carbohydrates. Such action is result of diet, which contains a result of diet, which contains a small amount of complex small amount of complex carbohydrates (food fibres).carbohydrates (food fibres).

Inhibiting influence of obesity on Inhibiting influence of obesity on insulin receptors very clearly insulin receptors very clearly displays in conditions of low displays in conditions of low physical activity. Regular physical physical activity. Regular physical exercises on the contrary raise exercises on the contrary raise receptor affinity to insulin and raise receptor affinity to insulin and raise tolerance to glucose. tolerance to glucose.

The other types of diabetes mellitus• This is large geterogeneous group of illnesses with

hyperglycemia. Mains it’s causes following: • а) illnesses of pancreas innate lack of Langergans

islets, trauma and infections, tumor, kystose fibrosis; • b) illnesses of hormonal nature pheochromocytoma,

glucagonoma, acromegaly, Itsenko-Cushing illness, thyreotoxicosis;

• c) medicines and chemical agents – glucocorticoids, thyreoid hormones, diuretics, analgetics and other remedies;

• d) change of insulin receptors diminution or lack of them (gene mutation in 19 chromosome), antibodies to receptors (mutations of 2 and 14 chromosomes);

•  e) hereditary syndromes Down’s, Turner’s, Klinefelter’s.

IMPAIRMENT OF LIPID METABOLISM IN DIABETES MELLITUS

Decreased glucose utilization

Decreased lipogenesis

Mobilization of fats to depoes

Hyperlipidemia

Metabolic acidosis Increased ketogenesis and cholesterol productoin

Ketonemia and hypercholesterolem

ia

Ketonuria

Loss of Na+

Keto-acidotic coma

Insulin deficiency

Decreased glucose utilization

Increase in proteolysis

Aminacidemia, increased uptake of aminoacids by the liver

1. Activation of gluconeogenesis

2. Increased removal of nitrogen via urea

Loss of potassium and other ions by the cells

Dehydration of the cells

Potassium loss by the organism

Insulin deficiency

IMPAIRMENT OF PROTEIN METABOLISM IN DIABETES MELLITUS

Symptoms of diabetes mellitusMajor symptoms are:• hyperglycemia, • glucosuria and • polyuria.

Pathogenesis of diabetes mellitus symptoms

HyperglycemiaHyperglycemia HyperglycemiaHyperglycemia is connected, foremost with lowering of is connected, foremost with lowering of

glucose utilization by muscular and fatty tissues. glucose utilization by muscular and fatty tissues. Lowering of glucose utilization has membranogenic Lowering of glucose utilization has membranogenic nature. In case of insulinopenia and in case of insulin-nature. In case of insulinopenia and in case of insulin-resistance nteraction of insulin and receptor is damaged. resistance nteraction of insulin and receptor is damaged. Therefore protein-transporters of glucose are not Therefore protein-transporters of glucose are not included in membranes of cells-targets. This limits included in membranes of cells-targets. This limits glucose penetration in cells. It is use on power needs (in glucose penetration in cells. It is use on power needs (in myocytes) diminishes. myocytes) diminishes.

Lypogenesis is slowed-glucose deposit in fats form (in Lypogenesis is slowed-glucose deposit in fats form (in lypocytes). lypocytes).

Glycogenesis slows- synthesis of glycogene (in Glycogenesis slows- synthesis of glycogene (in hepatocytes and myocytes). On other hand, attached to hepatocytes and myocytes). On other hand, attached to diabetes a supplementary amount of glucose is secreted diabetes a supplementary amount of glucose is secreted in blood. In liver and muscles of diabetics glycogenolysis in blood. In liver and muscles of diabetics glycogenolysis is a  very active. Definite endowment in hyperglycemia is a  very active. Definite endowment in hyperglycemia belongs to gluconeogenesis. Here with glucose will is belongs to gluconeogenesis. Here with glucose will is derivated in liver from amino acids (mainly from alanine). derivated in liver from amino acids (mainly from alanine).

GlucosuriaGlucosuria

In healthy man practically has not glucose in urine. It In healthy man practically has not glucose in urine. It is excreated in amount not more 1 g. Attached to sugar is excreated in amount not more 1 g. Attached to sugar diabetes amount of exreted glucose increases diabetes amount of exreted glucose increases repeatedly. It is explainet by next wayrepeatedly. It is explainet by next way. . If glucose If glucose concentration in blood and primary urine does not concentration in blood and primary urine does not exceed 9 mmol/l, epithelium of canaliculi reabsorbed exceed 9 mmol/l, epithelium of canaliculi reabsorbed it. This maximum concentration is called it. This maximum concentration is called nephritic nephritic threshold.threshold. If a glucose concentration exceeds a If a glucose concentration exceeds a nephritic threshold (9 mmol/l), part of glucose goes in nephritic threshold (9 mmol/l), part of glucose goes in secondary urine (glucosuria).secondary urine (glucosuria).

Polyuria

• Glucose is osmotic active substance. Increasing of it’s concentration in primary urine raises osmotic pressure. Water is exuded from organism together with glucose (osmotic diuresis). Patient excretes 3-4 l of urine per day, sometimes till 10 l.

Decreased glucose utilization

Increased glucose production

Hyperglycemia

Glucosuria

Osmotic diuresis

Hyperosmolarity and dehydration

PATHOGENESIS OF HYPERGLYCEMIC PATHOGENESIS OF HYPERGLYCEMIC COMACOMA

C O M A SHOCKDEATH

DIC syndrome

Insulin deficiency

 Complication of diabetes mellitus

The very frequent

diabetes complications

are following: ketoacidosis, macroangiopathy, microangiopathy, neuropathy.

angiopathy

Ketoacidosis.Ketoacidosis. In healthy peoples  synthesis of ketone bodies In healthy peoples  synthesis of ketone bodies in liver is strictly controled. Main regulatory mechanism is in liver is strictly controled. Main regulatory mechanism is access limitation of fat acids in mytochondries of access limitation of fat acids in mytochondries of hepatocytes. Over head permissible concentration limit of hepatocytes. Over head permissible concentration limit of ketone bodies in blood is approximately 0,1 mmol/l. ketone bodies in blood is approximately 0,1 mmol/l.

In case of exceedingIn case of exceeding this level regulatory mechanisms are this level regulatory mechanisms are stated. Foremost ketone bodies put specific receptors back stated. Foremost ketone bodies put specific receptors back up on membrane β-cells of Langergan’s islets. Insulin up on membrane β-cells of Langergan’s islets. Insulin excretion in blood increases. Insulin stimulates resynthesis of excretion in blood increases. Insulin stimulates resynthesis of fat acids. First stage of resynthesis is derivation if malonil-fat acids. First stage of resynthesis is derivation if malonil-КоА. Surplus amount of malonil-КоА oppresses penetration of КоА. Surplus amount of malonil-КоА oppresses penetration of fat acids in mytochondries.  Synthesis of ketone bodies slows.fat acids in mytochondries.  Synthesis of ketone bodies slows.

Attached to diabetes mellitus disturb mechanism of both Attached to diabetes mellitus disturb mechanism of both synthesis regulation of ketone bodies – both on level of β-synthesis regulation of ketone bodies – both on level of β-cells, and on level of hepatocytes. Receptor stimulation of β-cells, and on level of hepatocytes. Receptor stimulation of β-cells by ketone bodies does not cause increased excretion cells by ketone bodies does not cause increased excretion insulin in blood. In conditions of insulinopenia fat acids insulin in blood. In conditions of insulinopenia fat acids penetrate in hepatocytes in unrestricted amount. Liver penetrate in hepatocytes in unrestricted amount. Liver synthesizes many ketone bodies. Extrahepatic tissues can synthesizes many ketone bodies. Extrahepatic tissues can not utilize them. Amount of ketone bodies in blood increases. not utilize them. Amount of ketone bodies in blood increases. Metabolic acidosis occur. It can complete by ketoacid  coma.Metabolic acidosis occur. It can complete by ketoacid  coma.

Seldom attached to  diabetes mellitus lactoacidosis occur. It Seldom attached to  diabetes mellitus lactoacidosis occur. It is attached to insulin-independent diabetes mellitus, is attached to insulin-independent diabetes mellitus, attached to combination of diabetes with hypoxia,  sepsis, attached to combination of diabetes with hypoxia,  sepsis, shock. shock.

MacroangiopathyMacroangiopathy  is vessels atherosclerosis of cerebrum, heart, kidneys, legs. Diabetes lead to atherosclerosis development.  There are three acceleration way of atherogenesis in patients with diabetes. In conditions of insulin insufficiency growth hormone synthesis increases. Here upon proliferation of smooth myocites accelerates key stage of atherogenesis. Attached to diabetes vessels endothelium damages. Synthesis of thromboxane increase, and this helps to adhesion of thrombocytes. Thrombocytes excret mitogene (thrombocytic growth factor). It also stimulates proliferation of smooth myocytes. Attached to diabetes concentration of  lipoproteids low density, increase concentration of lipoproteids of high density.

Microangiopathy

• Microangiopathy develop in shallow vessels – arterials, venues, capillaries. Two process form their pathogenic base – thicking of basal membrane and reproduction endothelium. Direct cause of microangiopathy is hyperglycemia and synthesis of glycoproteids in basal membrane.

• There are two main clinical forms microangiopathy: diabetic retinopathy and diabetic nephropathy.

A composite photograph showing a pretreatment fundus photograph (A), and a photograph demonstrating radiation retinopathy at 24 months (B). A fluorescein angiogram demonstrates intraretinal microangiopathy next to the tumour (C), and regression to chorioretinal scar after laser photocoagulation (D).

Galactosemia

• This is hereditary illness. In it’s base lies an blockade of galactose metabolism. In organism intermediate metabolits accumulate. There are two the main forms of galactosemia on base of transferase insufficiency and on base of galactokinase insufficiency.

GLYCOGENOSISGLYCOGENOSIS TypeType І – І –Girke diseaseGirke disease. . Deficit ofDeficit of glucosoglucoso-6--6-

phosphatasephosphatase TypeType ІІ – ІІ –Pompe diseasePompe disease.. Deficit ofDeficit of acidic maltaseacidic maltase

(α-1,4- (α-1,4-glucosidaseglucosidase)) TypeType ІІІ – ІІІ –Cori diseaseCori disease, , ForbsForbs diseasedisease.. Deficit ofDeficit of

amyloamylo-1,6- -1,6- glucosidaseglucosidase TypeType ІV – ІV –Anderson diseaseAnderson disease.. Deficit ofDeficit of amyloamylo- -

1,4,1,6-1,4,1,6-transglucosidasetransglucosidase TypeType V – V –McArdel diseaseMcArdel disease Deficit ofDeficit of phosphorilase of phosphorilase of

myocytesmyocytes ТТypeype VІ – VІ –Hers diseaseHers disease.. Deficit ofDeficit of phosphorilasic phosphorilasic

complex in complex in liverliver ТТypeype VІІ. VІІ. Deficit ofDeficit of musclemuscle phosphofrutphosphofrutккinaseinase

Glycogenoses•  Simple carbohydrates deposit in organism as polysaccharides. In

muscles and liver accumulates glycogen. It consist of 4 % of liver weight and 2 % of  muscles  weight. Muscles glycogen is used as of ready fuel source for immediate guaranteeing by energy. Liver without interruption provides cerebrum and erythrocytes with glucose .

• Synthesis and splitting of glycogen are exactly adjusted and coordinated processes. Attached to immediate need in glucose α–cells of pancreas secret glucagone. It activates adenylatcyclase of hepatic cells. Adenilatcyclase stimulates derivation of cAMP. Under action of cAMP takes place activation of proteinkinase and this enzyme raises activity glycogenphosphorilase and oppresses activity of glucogensynthase. Here upon starts intensive glycogenolysis. Supplementary amount of glucose is secreted in blood.

• In other situation after consuming of carbohydrates in blood accumulates surplus of glucose. β-cells of pancreas multiply insulin synthesis.  Insulin raises activity of glycogensyntase. Active glucogenesis starts too. Surplus of glucose reserves in appearance of glucogen in liver and muscles.

• There are illnesses in base of which is accumulation of glycogen in organs. They are called glycogenoses. All of them are hereditary enzymopathy. There are seven main types of glycogenoses.

Glycogenosis type I – Girke’s disease.• Girke’s disease cause deficit of

glucose-6-phosphatase. This enzyme provides 90 % of glucose which disengages in liver from glycogen. It play central role in normal glucose homeostasis. Glucose which disengages attached to disintegration of glycogen or is derivated in process of gluconeogenesis obligatory goes over stage of glucose-6-phosphate. Enzyme glucose-6-phosphatase tears away a phosphate group from glucose. There free glucose is formed it  goes out in blood. Attached to Girke’s disease stage of tearing phosphate group is blocked. There are no free glucose hypoglycemia occur. Hypoglycemia arises. Attached to Girke’s disease glycogen is deponed in liver and kidneys.

Glycogen Storage Disorders:

• Type 1= Von Gierke’s:– Shortly after birth: Severe lifethreatening Hypoglycemia– Lactic acidosis –due to isolated glycolysis of G6Po– Hyper-uricemia, hyper lipidemia– Increased association with epistaxis – *Hepatomegaly– **Adverse response to Glucagon with worsening Lactic acidosis

• Management requires IV glucose, and then as outpt, close NG corn-starch or glucose solution administration to achieve close to nl glucose homeostasis.

• Frequent snacks and meals. Continuous nighttime glucose infusions up to the age of 2.

Type ІІ glycogenosis – Pompe’s disease.• Illness is related to

deficit of lysosomal enzyme – sour maltase, or α-1,4-glucosidase. This enzyme slits glycogene to glucose in digestive vacuoles. Attached to it’s deficit glycogen accumulates at first in lysosomes and then   in cytosole of hepatocytes and myocytes.

Glycogen Storage Disorders:

• Type 2- Pompe’s disease:• Normal Glucose• Do to an accumulation of glycogen in lysosomes. • **Ancient city of Pompeii was destroyed by Mt. Vesuvius- 79 AD**

• Manifested by massive Cardiomegaly, Hepatomegaly, Macroglossia.

• Fatal If results in CHF. • Limited therapies in Neonatal Variant.

– Attempts at enzyme replacement ongoing.

Type ІІІ glycogenosis – Cori’s disease,  Forbs’ disease

This illness is named limited ecstrinosis. In it’s base lies a deficit of amylo-1,6-glucosidase. Degradation of glycogen pauses in sites of  branching. Glycogen accumulates in liver and muscles. Cure is diet with big proteins maintenance.

Glycogen in the Liver (left stained to show glycogen, right normal)

Glycogen in Muscle Cells

Type ІV glycogenosis – Anderson’s disease.

• It is called by deficit of amilo-1,4,1,6-transglucosidase (branching enzyme). As result of this there is derivated anomalous glycogen with very long branches and rare points of branching. It is not exposed to degradation and accumulates in liver, heart, kidneys, spleen, lymphatic nods, skeletal muscles.

Type V glycogenosis – McArdel’s disease.

• It’s cause is deficit of phosphorilase of myocytes. Typical pain displays   in muscles after physical loading. Glycogene does not slit only in muscles. Here it accumulates. In liver mobilization of glycogen comes normal.

Type VІ  glycogenosis – Hers’ disease.

• Illness arises as result of insufficiency of hepatic phosphorilase complex. Glycogen accumulates in liver. Typical sign is hepatomegalia.

Type VІІ glycogenosis.Type VІІ glycogenosis. Illness Illness essence is in oppression of muscle essence is in oppression of muscle phosphofrutkinase. Symptoms are phosphofrutkinase. Symptoms are similar to McArdles disease. similar to McArdles disease.