Acute complications of diabetes mellitus : etiology, pathogenesis, diagnostic criteria, treatment

One of the most important tasks for a practice doctor is diagnosis and treatment of urgent states. The large diseases group, which might complicated with acute painful state and require urgent medical treatment, are diseases of endocrine system, and first of all – the diabetes mellitus, which is one of the leader in spreading of diseases structure. Therefore, only the knowledge of clinic symptomatology, diagnostic questions, differential diagnosis and treatment of an urgent state allows the doctor to render the appropriate and qualified treatment for patient.

Diabetes mellitus (DM) is a systemic disease that effects essentially every organ of the body. The fatal outcome is related to the development of acute or chronic complications.

Classification of acute complications of DM.1. Diabetic coma:1) diabetic ketoacidisis (DKA);2) nonketonic hyperglycemic-hyperosmolar coma (NKHHC);3) lactoacidosis (LA).2. Hypoglycemic coma (HC).

At present there are three kinds of diabetic comas: ketoacidic, hyperosmic and lactacidemic. The medical tactics depends on the pathogenic of diabetic coma, therefore a pathogenic disease diagnosis has a special meaning. Yet to take into account that a diabetic ketoacidosis, hyperosmotic and hyperlactacidemical syndromes are rarer as a pure form. Usually two or even three pathogenic varieties in different combinations (including over the expressiveness degree of any syndrome) are appearing from the expressive diabetes decompensation beginning moment.

Diabetic ketoacidisis (DKA).Before the area of insulin therapy, ketosis was the leading cause of death of patients with DM.

Since insulin deficiency worsens the clinical picture and leads to metabolic abnormalities, the complication is more common in young diabetics. Despite insulin usage, mortality remains high (6 - 10 %).

DKA results from grossly deficient insulin modulation of glucose and lipid metabolism. A diabetes ketoacidic coma is one of the most dangerous complications and appears as a result of the growing insulin deficiency. The diabetic ketoacidosis development (DKA) is the more typical for IDDM. But it must be remembered that patient with IDDM may have DKA in cause of the present of stress situations and intercurrent diseases which lead to decompensation of diabetes mellitus.

Precipitating factors:1) newly diagnosed diabetes (presenting manifestation);2) inadequate administration of exogenous insulin;3) increased requirements for insulin caused by the presence of an underlying stressful condition:- an intercurrent infection (pneumonia, cholecyctitis);- a vascular disorder (myocardial infarction, stroke);- an endocrine disorder(hyperthyroidism, pheochromocytoma);- trauma;- pregnancy;- surgery.Predisposing factors of DKA development.1. Unrecognized diabetes mellitus.2. Treatment regime violation (an absence of accurate insulin doses correction).3. Infections and intoxication’s.4. Physical, psychological trauma.5. Surgical operations.6. Acute cardiovascular insufficiency, myocardial infarction, cerebral hemorrhage.7. Pregnancy.8. Prolonged starvation.9. The considerable change of diet, using of alcohol.

10. Insulinresistance (antibodies formation or isolation and destruction of insulin during subcutaneous injection).

11. Physical exercises (loading) during a chronic insulin deficiency.Physical exercises may lead to the early and delayed hypoglycemia’s, increasing the glucose

utilization and causing the more faster insulin absorption, which isn’t balanced with the liver increasing glucose production and supplementary food. There is less known the ability of physical exercises to cause ketoacidosis of those patients, who do not fully chronically receive insulin. Physical load stimulates a production of contrinsular hormones: adrenaline, STH, glucagon. These hormones mobilize glucose and fat and direct a metabolism in liver to the formation of ketones that may rapidly lead to the ketoacidosis during considerable insulin deficiency.

In the base of diabetic ketoacidosis and coma pathogenesis is the increasing insulin deficiency and as a consequence:

1. The infringement of glucose utilization with tissues, cytolemme hypopermeability for glucose, decreasing of processes of its oxidation and energetic using by cell.

2. The infringement of glycogen synthesis, at first of all in liver, that with combination with lipocain deficiency, leads to the fatty infiltration of liver.

3. Increasing of the glycogen dissociation, the compensative formation of glucose of proteins and fats (gluconeogenesis).

4. Hyperproduction of contrinsular hormones which having fatty - mobilized property: somatotrophin, catecholamines, and corticotrophin.

5. Hyperproduction of the basic hormonal antagonist – glucagon which promotes to the glucose production increasing.

6. Lipolysis increasing.At present a ketoacidic coma is very severe complication of diabetes mellitus which is life –

threatening for patient. During DKA mortality is 5-17%.DKA develops then when insulin deficiency is combined with increasing activity of contrinsular

hormones. Their effect (except STH) is showed very rapidly.Glucagon increases hepatic glycogenosis and gluconeogenesis, during DKA its level increases

on 400-500%. At increases the hepatic ketogenesis on 300%, independently on level of free fatty acids and also increases the lipolysis.

The catecholamines excretion is stimulated with activation of the sympathic nerval system, stress, acidosis, fever. The adrenaline level increasing stimulated glycogenolysis in liver and muscules, increases gluconeogenesis in liver, activates the lipase of fatty acids and secondary ketogenesis in liver. During insulin deficiency the increasing of blood CA leads to increasing of the glucose level in 5-7 ones higher then in normal.

The long increased STH level (acromegalia) leads to increasing production of glucose in liver, increases the lipolysis and ketogenesis.

Hyperglycemia causes osmotic diuresis and leads to dehydration, decreasing of electrolytes level and serum hypertony.

Patients, who are using the according to thirst liquid volume and having normal function of kidneys, have a moderately increasing of glycemia level during ketoacidosis, as in normal the kidneys may excreate glucose with the speed which is adequative to the increasing of glucose production.

Patients with vomiting or are in unconscious state can’t use enough liquid to level continuous osmotic diuresis which leads to dehydration and hypovolemia with decreasing of renal function.

It explains that fact only rehydration with solutions without insulin introducing, may to decrease the glucose level in half. The hospitalized patients with DKA have the loss of free water which is usually 10-15% (100-150 ml/kg of body weight) and depends on expressiveness and duration of disease. The hyperglycemia value presents about a dehydration and hypovolemia degree.

Hypovolemia makes more hardly the metabolic acidosis owing to two ways: the decreasing of tissue circulation and development of lactacidical acidosis, which may be 25% of acidemia during DKA. Also hypovolemia decreases the renal function and excreation of organic acids.

The osmotic diuresis during DKA leads to the passive electrolytes and water loss: Na – 5-13 m eq/kg, K – 4-10 m eq/kg, P – 0,5-4 m eq/l.

Every 100mg% (5,5 mmole/l) of the glycemia increasing decreases the sodium level in blood serum on 1,6 m eq/l.

Na = Na (measured) + 1,6 (glucose – 100)/100 Acidosis and catabolism of proteins stimulates the potassium excretion from cells. With urine

the potassium is lossed because of increasing activity of aldosterone, stimulated with dehydration. During rehydration and insulin treatment may appears the hypokalemia (decreasing of serum hypertony, increasing of SHT, acidosis decreasing and potassium entering into a cell).

Clinical presentation.Diabetic ketosis.It is status which is characterized by increased level of ketones in blood, without clinical signs of dehydration and can be corrected by diet (fat restriction) and regular insulin injection.DKA develops over a period of days or weeks.

Signs and symptoms.

1. Polydipsia, polyuria and weakness are the most common presenting complaints.2. Anorexia, nausea, vomiting, and abdominal pain may be present and mimic an abdominal

emergency.3. Ileus and gastric dilatation may occur and predispose to aspiration.4. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the

metabolic acidosis and is obvious when the pH is less than 7.2.5. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude,

stupor and coma (only 10 % patients are unconscious).Physical examination.1. Hypothermia is common in DKA. A fever should be taken as strong evidence of infection.2. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis, acetone may

be detected on the breath (musty (fruity) odor to the breath).3. Tachycardia frequently is present, but blood pressure is usually normal unless profound

dehydration is present.4. Poor skin tugor may be prominent depending on the degree of hydration.5. Hyporeflexia (associated with low serum potassium) can be elicited.6. Signs consistent with a “surgical abdomen” but which follow severe ketonemia can confuse the

clinical picture.7. In extreme cases of DKA one can see hypotonia, stupor, coma, incoordination of ocular

movements, fied dilated pupils, and finally death.8. Other signs from a precipitating illness can be present.

Laboratory findings.1. The hallmark of DKA is the finding of:- hyperglycemia;- ketonemia;- metabolic acidosis (plasma pH and bicarbonates are decreased.

2. A presumptive bedside diagnosis is justified if the urine is strongly positive for both glucose and ketones.

3.4. Different changes of electrolyte levels in the blood can be observed and does not reflect the

actual total body deficits.5. Serum amylase and transaminases can be elevated.6. Leucocytosis occurs frequently in DKA and therefore cannot be used as a sole indication of

infectious process.Types of DKA:- abdominal;- vascular collapse;- cerebral (encephalopathic);- renal;- mixed.

Differential diagnosis.DKA must be distinguished from a variety of clinical conditions, particularly those in which central-nervous system function is altered and also associated with metabolic acidosis. The patients history and physical examination often are adequate diagnostic techniques.

Cardiac arrhythmia is the severest complication of the potassium homeostasis infringement. The DKA development in according with the modern data may be represented with following stages:

I stage of ketoacidosis ( DKAI ).Pathogenesis. This stage is characterized with growing hyperglycemia, which is a result of

insulin deficiency. At that time on the base increasing of sugar level in blood, cells face energetic starvation, as a deficiency doesn’t give possibility for cells to utilize the glucose. The energetic cellular starvation of organism leads to activation of the endogenic glucose formation owing to the gluconeogenesis and glycogenes dissociation. These processes are stimulated with glucagon, catecholamines, glucocorticoids. But the glucose utilization by cells in this situation isn’t arranged of insulin deficiency, and a result of this the hyperglycemia is increased some more. Hyperglycemia is accompanied with the increasing of osmotic pressure of blood serum, cellular dehydration, polyuria, glucosuria (glucose begins to exreat in urine of the glycemia level is 10-11 mmole/l). Glucosuria causes the increasing of osmotic pressure of primary urine, that prevent it from reabsorbtion and intenities polyuria. The compulsory factor of DKA pathogenesis is an activation of the ketonal bodies formation. The insulin deficiency and surplus of contrinsular hormones (in first of all – the somatotrophic having lipolytic effect) lead to the lipolysis activation and free fatty acids (FFA) contains increasing, which are the ketogenic substrate. Exept these, the synthesis of ketonic bodies – beta-oximalar and acetoacetic is owing to “ketogenic” aminoacids (isoleucine, leucine, valine), which are accumulated as a result of proteins catabolism in causes of insulin deficiency. The ketonical bodies accumulation leads to exhaustion of alkaline blood reserves and development of metabolitic acidosis. In first stage of DKA there is appearing the moderate acetonuria which may be inconstant.

Clinics. DKA, as a rule, develops slowly, during some days, on the diabetes mellitus decompensation base. During this stage there is the decreasing or loss of efficiency, muscular debility, appetite disappearance. There is appearing of headache, dispeptic effects (nausea, diarrhea). The polyuria and polydipsia grow. During an examination there are revealed dryness of

skin, tongue and mucousal membrane of oral cavity, feeble oral smell of acetone, muscular hypotony, tachycardia, some dull cardiac tones, possibly the arrhythmia. Sometimes there is pain in abdomen, it may be palpated the painful and increasing liver.

Laboratory data. Hyperglycemia until 18-20 mmole/l, glucosuria, ketonemia (untill 5,2 mmole/l) and ketonuria (ketonic bodies in urine – some positive). The aqueous electrolitic balance on this stage of DKA development is characterized with some hyperkaliemia (owing to the potassium excreation from cell) – until – 5 mmole/l. The potassium deficiency in cell is confirmed with ECG data (asymmetric decreasing of ST interval, the double – phasic T-wave, which may be negative). The acidic-alkaline state (AAS) doesn’t essentially change, but there is decreased the hydrocarbonaties contains until 19-20 mmole/l.

Treatment. Patients with diabetes mellitus on the first stage of DKA must be hospitalized into the endocrinal hospital department. There is important measure on this stage to change the diet regime. It is necessary to recommend easy-digested carbohydrates, fruit saps, honey. The common carbohydrates volume is increased until 70-75% for ketogenesis suppression. The hyperglycemia correction is because of the insulin of early effect, with small doses, not rarer than 6 ones per day (intramuscular). The insulin day doses is counted up owing to the 0,7-1,0 UN/kg of the factic body weight. For acidosis removal are prescribed the alkaline mineral waters (“Borzhomy”), dimephosphone, regidron. Are necessary also a cleansing enemas with 3% solution of sodium hydrocarbonate. As a rule, these measures are sufficiently for treatment of patients with DKA I stage. In case of the dehydration expressive signs to prescribe the intravenous solutions injection.

It must be noted that carly diagnosis and opportune treatment promote to prevention of the ketoacidosis beginning stage passing to the precoma which is vitally dangerous for patient.

Precomatous state (DKA II nd)Pathogenesis. Following are the pathogenetic mechanisms: energetic cellular incompetence

in causes of insulin deficiency is accompanied with activation of protein destruction which is leading to infringement of the nitrogen balance and promotes the azotemia development. It causes the increasing of endogenic glucose production from glycogene, fat and protein, is growing the glucosuria and polyuria owing to the osmotic diuresis. At first a glucosuria and hyperglycemia lead to cellular dehydration and then to general dehydration with decreasing of tissue and renal circulation and mineral deficiency (Na,K,Cl). The renal blood circulation infringement promotes to the ketoacidosis growing, because of kidney stopping the hydrocarbonic ion production (HCO3). Activation of ketoacidosis is increased with the metabolitic acidosis, which is accompanied with decreasing of the blood alkalinity and pH shifting. Stimulation of the respiratory center with hydrogen ions leads to the appearance of characteristic harsh infrequent breathing. Besides, as a result of the lipolysis activation in blood are accumulated FFA, non-etherificated fatty acids, tryglycerides, which increase blood viscosity and promote to infringement of hemorrhological blood properties and microcirculation insufficiency.

Clinics. On the DKA-II the general condition of patient is acute, deteriorated, rapidly grow thirst and polyuria. Patient is suffering of the progressive muscular debility and can’t individually move. It appears the pernicious vomiting and increased abdominal pain. There are often heart pains. During examination there are expressive xerodermia and xeromucous, rubeosis of face (as a result of capillary paresis). Tongue is dry, crimson or coated with brown fur, there is sharp fowl smell of acetone. Muscular tonus is decreased, the eyeboll tonus is decreased, too. Breathing begins infrequent, deep, harsh (Kussmaul respiration). From the side of cardiovascular system there are the following changes: rapid and soft pulse, tachycardia, dull heart sounds, may be the arterial hypertony. Hypokaliemia leads to the intestine motopity decreasing. As a result of intestine atony beginning it is strained off with its contents which is leading to appearance of painful syndrome. Except these, there is the tension of anterior abdominal wall. These changes may be a cause for false diagnosis of the “acute abdomen”. We must take into account that DKA is accompanied with leukocytosis with neutrophilia and formula shifting to the left (owing to hydrovolemia). Therefore the clinics of “acute abdomen”, that is confirmed with laboratory data, is seemed highly convincing. The result of this may be inexcusive laparatomy which making DKA tendency worse.

A peculiarities of the preceding diabetes mellitus tendency, patient age, accompanied diseases, Also as a causes character, which directly cause the acidosis, define the rapidness of its tendency, expressiveness and preclaiming in clinics that or other manifestations.

Due to these there are several forms of the precomatous state tendency. Gastrointestinal (abdominal): there are spasmodic pains in epigastral and iliac regions acquiring then spilling character and seem on peritonitis, the defending tension of abdominal muscles, the restricting of this region during breathing (“acute abdominal” syndrome). Moreover, There are characterized by uncontrollable vomiting and vomitory reflexes with exceation of mucousal or mucous – bilious contents, which often acquiring the “coffee-ground” color (manifestations of the erosive toxic gastritis). Stools disturbances have enough steady and permanent character: persistent constipation’s are interchanged with profuse fetorical diarrheas with painful tenesmuses.

The causes of the hardlest abdomenalgia and pseudoperitonitis until present aren’t standed finally. One supposes that they are connected with stimulation of nodes of celiac plexus owing to the peritoneum vessels spasm. Others investigators assume those in causes of ketoacidic dehydration is developing the aseptic peritonitis. Some authors explain that pain is caused with spastical state of pylorus and intestine.

In some causes the painful sensations are connected with stretching of stomach owing to the toxic gastritis and transudation into its cavity of many liquid.

Abdominal pain caused with ketoacidosis lasts during 4-5 hours from the beginning of treatment. Often this form is found in young age.

Cardiovascular form: More oftenly it manifestetes in older age. The mean clinic manifestation is heavy collapse with considerable decreasing of arterial and venous pressure, tachycardia, weak pulse, different disturbances of cardiac rhythm, cyanosis and cold extremities. The cardiac asthma manifestations and sometimes the acute edema of lungs remind the clinic of acute myocardium infarction meeting during prolonged and hard tendency of diabetes mellitus.

In this form pathogenesis the cause is hypovolemia with considerable decreasing of blood circulated volume, decreasing of the contractive myocardial function in connection with atherosclerosis of coronal arteries and acute metabolic cardiomyopathy (hypokaliemia, acidosis, failure of miocardial energetic guarantee and soon), and also the peripheric vascular paresis. During this coma form the most frequent are developing thrombosises of pulmonary vessles, vessles of lower extremities and coronal vessles (with formation of transmural myocardial infarction).

Cardiovascular disturbances which accompanied with diabetic ketoacidotic coma may be called as a syndrome of acute circular insufficiency, of combined nature (cardiogenic, hypovolemic and metabolic hypocirculatory syndromes). For ketoacidotic coma is characteric a easy hypothermy, therefore the body temperature increasing in this condition on present of the infectional – inflammatory process.

Hypothermy promotes to development of the insulin-resistance, therefore during uncomplicated with infection coma it is necessary to use measures for patient warming.

Renal (nephrotic) ketoacidosis form is developing, as a rule, when the diabetes mellitus exists 20-30 years and during this period was more of less an expressive permanent urinary syndrome (albuminuria, microhematuria, constantly lower urinous concentration). In some causes manifestations of the Kimmelstiel-Wilson syndrome acquire a threatening character with progressively increasing uremia, anuria and general edema.

We can point out on a renal ketoacidosis variety, then decreasing of arterial systemic pressure and renal circulation lead to anuria and all of following clinical disease tendency is defended with acute renal insufficiency.

Encephalopathic (pseudocerebral) form is found in old people who suffer of the cerebral atherosclerosis. During ketoacidosis due to the hypovolemia, cellular dehydration, acidosis, microcirculation infringement is falling decompensation of chronic cerebrovascular insufficiency. It showes with symptoms of local lesions of brain: hemiparesis, assymmetry of reflexes, appearance of one-sided pyramidal signs. In this situation often is difficult to defind – either coma cause this focal symptomatology or insult be comes an cause of ketoacidosis.

The treatment that is beginning in time as ketoacidosis is removed leads to improvement of cerebral circulation and decreased of cerebral symptomatology.

Dehydrative form is observed in the middle and old age. Often a people with asthmatic constitution are suffering of this form, for them for the diabetes mellitus compensation in necessary many insulin (a day dose is about 100 units). Skin is coarse, rough, locally cracking, with grey-mat colour, skin fold doesn’t fall flat, an features are acute, ocular cavities are deep, eyelids are closed on half (mummification of face).

Even patient still in conciousness dosn’t co not contact with surrounded people owing to significant dryness of mucous membranes of mouth, throat, tongue and expressive asthemia. Chest is flat, intercostal spaces are deep and intensivly take part during breathing, abdomen is drawing in with very expressive the upper flaring portions of the iliums.

Laboratory data: on the precoma stuge the glycemia achieves 20-30 mmole/l and is accompanied with expressive polyuria and increasing plasma osmatic pressure untill 320 mo sm/l, it is significantly infringes the water-mineral balance which is showed with hyponatremia (loss 130 mmole/l), hypokaliemia (loss 4 mmole/l). For this stage of DKA are characteric evident infringements of AAS (the blood alkulinity is decreased 40 volume % and loss, HCO3 untill 10-12 mmole/l, pH from 7,35 to 7,10). The protein catabolism (owing to gluconeogenesis) is accompanied with increasing of the urea and creatinine levers in blood, proteinuria. It must be remembered that the urinary syndrome and nitrical compounds accumulation patients who have an diabetic nephropahty.

If on precomatous state to patient isn’t rendered any treatment then during 2-3 hours is developing the ketoacidic coma (DKA III rd).

DKA – III rd. Pathogenesis. The progressive dehydration leads to hypovolemia which is accompaning with blood circulation decreasing in kidneys and brain. An ketoacidosis progress intensifies hypoxia. It is increasing deficiency of the sodium, chlorides and espesially potassium.

Hypovolemia, hypoxia and potassium deficiency in principal define the comatous condition tendency. One of the hypoxia pathogenesis factors is an intestive increasing of concentration of glycosylated hemoglobin (Hb A1 and Hb A1C) which doesn’t transport an oxygen. Hypovolemia leads to development of the circulatory hypoxia. The infringanment of mineral balance is accompanied with myopathy, also with respiratory muscules debility that leads to applying of alveolar hypoxia compound. For hypoxia progress is assisting the activation of an anaerobic glycolysis and lactic acid accumulation in tissues.

These factors (hypovolemia, hypokaliemia, hypoxia and increasing of lactic acid level) promote to development (on the ketoacidosis base) cardiovascular insufficiency and metabolic coagulopathy.

Coagulopathy is showed as a disseminated intravascular coagulatis (DIC-syndrome), peripheric thrombosis and thromboembolisms. As a rule, hypovolemia is accompanied with renal perfusion infringement.

During incorrect and mistaked therapy, as already was mentioned, the ketoacidosis manifestations transfer into precoma and then into ketoacidotic coma.

There a 4 stades:I. Stunning (patient is inhabited, consciousness in confused).II. Somnolentia (patient sleeping, but cann’t independently answer the question).III. Sopor (patient is in condition of deep sleep and may to wake up only under the powerful

stimulations action).IV. Coma (complete loss of consciousness).

Clinic. Patient face is pale, without cyanosis signs, sometimes there is a facial rubeosis. Skin is dry, cold, its turgor is decreased. Breathing begins deep and harsh, the inhalation phase is longed than exhalation (a large Kussmaul respiration). There is an acute smell of acetone from oral cowity, which may be noticed on enter of premises, where a patient is lying. During palpation eyeballs are soft owing to decreasing of the ocular muscles tonus.

Muscular tonus of extremities is decreased. Enough oftenly there are different changes of cardiovascular system (rapid and weak pulse, extrasystoles and ciliary arrhythmia), there is the expressive arterial hypotony.

Tongue is dry, with mal fur, abdomen is some distended. During palpation there is increased liver. Body temperature is decreased (except if there aren’t accompanied infectional – inflammatory processes).

Uresis is intentional, may be oligo- or anuria.Pathogenesis of consciousness derangements and other psychoneurological symptoms of the

ketoacidic coma isn’t understanded complete. During different time these derangements were connected by authors with following factors:

1) toxic affection on brain with ketonic bodies surplus;2) cerebrospinal fluid acidosis (and possibly owing to intracellular acidosis of CNS);3) cerebral cellular dehydration;4) hyperosmotic pressure of intracellular space in CNS.The most confirmed are two last factors. A sufficient proof of this is circumstance that the

consciousness derangement and neurologic symptoms are expressive during hyperosmotic coma and considerably less during ketoacidosis.

Laboratory data. As a rule, glycemia on the ketoacidic coma stage is more than 30 mmole/l which is accompanied with increasing of plasma osmolarity untill 350 mosm/l and more other. Besides, on this stage of DKA is increasing the potassium sodium and chlorids deficiency and hyperazotemia. AAS is characterized with progressived acidosis (pH a decreases untill 7,1 and lower), abruptly decreases the reserve alklinity (30 %) and hydrocarbonatis level of blood. The lactic acid level is increasing untill 1,6 mmole/l and more other.

Treatment of the precomatous condition and ketoacidic coma.

If a patient has diabetes mellitus with precomatous condition development, it is necessary special hospitalization into the emergency department where immediately begins the intensive therapy which consists of following compounds:

a) insulintherapy;b) rehydration;c) mineral balance correction;d) acidic-alkaline state recovery;e) correction of cardiovascular derangements;f) elimination of factors which causing ketoacidosis.

The goals of therapy include:1. Rehydratation.2. Reduction of hyperglycemia.3. Correction of: a) acid-base and b) electrolyte imbalance.4. Investigation of precipitating factors, treatment of complications.

The most important factor to emphasize is the frequent monitoring of the patient both clinically and chemically. Initially, laboratory data should be obtained every 1 – 3 hours and less frequently once clinical improvement is noted. If the patient is in shock, stupor or coma, a nasogastric tube, especially if vomiting, and urinary catheter are recommended.

Frequent assessment of potassium status is vital. A lead II electrocardiogram (ECG) can be provide a rapid assessment of hyperkalemia (peaked T waves) and hypokalemia (flat T waves and presence of U waves). Hyporeflexia and ileus are clinical indications of potassium deficiency.

Careful observation of neurological status is vital to detect the infrequent but devastating presence of cerebral edema.Rehydration.

The average fluid deficit in adults with DKA is 3 to 5 l. A rapid infusion of 0,9 % sodium chloride (e.g., 1 l/h for the first 1 to 2 hours) is given and then reduced to about 0,5 – 0,3 l/h if the blood pressure is stable and the urine follow is adequate. After the initial infusion, intravenous fluid therapy must be adjusted individually on the basis of urine output, clinical assessments of hydration and circulation, determination of plasma electrolytes and glucose. When serum glucose level is about 11 – 13 mmoll/l administration of 5 % glucose with insulin can be performed (1 to 2 unites of insulin on each 100 ml of 5 % glucose solution). The addition of glucose to the intravenous solution is necessary for correction of tissue lipolysis and acidosis.Insulin treatment.

DKA can be treated with low dose insulin regimens; e.g., initial intravenous administration of 10 to 20 units of regular insulin followed by continuous intravenous infusion of 0,1 unit/kg/hour in 0,9 % sodium chloride infusion. (50 units of insulin can be added to a 500 ml bottle of 0,9 % sodium chloride solution to give 1 insulin unite/10 ml of solution.)

If the glucose level does not improve after an hour of infusion, the rate of insulin is doubled until a response is noted. But if there is a tendency for decreasing the level of glucemia we have to decrease the dose of insulin in two times.

When the serum glucose concentration reaches 11-13 mmoll/l, insulin can be given subcutaneously (if plasma and urine persistently negative for ketones). Blood glucose level should be maintained at about 11 mmoll/l during intravenous therapy.

Improvement usually is noted in 8 – 24 hours. Following stabilization of the clinical condition, patients are placed in insulin regimen consisting of five injections of regular insulin.Treatment of electrolyte disorders.

As a rule, potassium should never be given until the state of renal function is known and until the serum potassium concentration is available. In most patients the initial serum potassium is high-normal or elevated, and the initiation of K replacement (20 to 40 mmoll/h) usually can be deferred for 2 hours, using hourly serum measurements as a guide.

Potassium would be to infuse at a rate of ml of 1,5 g/h during 3 – 5 hours.Correction of metabolic acidosis.

The metabolic acidosis occurs due to insulin deficiency and dehydration. So ketone bodies are themselves metabolized to bicarbonate once proper therapy is begun (fluids, electrolytes, insulin) and exogenous administration of bicarbonate can overcorrect to alkalosis.

The use of bicarbonate can be recommended only in the following cases:- if life-threatening hyperkalemia;- when severe lactic acidosis complicates DKA;- with severe acidosis (pH<7), especially when complicated by shock that is not responsive to

appropriate fluid resuscitative measures in an attempt to improve cardiac output.Bicarbonate would be to infuse at a rate of 100 to 300 ml of 2,5 % solution.

Other therapeutic consideration:

- since infection is one of the leading precipitating events of DKA, it should be looked for and, if found, treated appropriately;

- vascular thrombosis (it is secondary to severe dehydration, high serum viscosity, and low cardiac output) – heparin (5000 unites 4 times a day);

- vascular collapse can be treated by mesatone (1 – 2 ml); glucocorticoides (dexametasone 4 mg two times a day). You must remember that development of vascular collapse after initiation of therapy should suggest the presence of gram-negative sepsis or silent myocardial infarction;

- cerebral edema (It is a rare and frequently fatal complication. Some physicians believe that rapid osmotic reduction of plasma glucose should be avoided to minimize rapid osmotic changes. Some patients have premonitory symptoms (e.g., sudden headache, rapid decrease in the level of consciousness), but in others acute respiratory arrest is the initial manifestation. If cerebral edema is diagnosed, therapeutic maneuvers might include the use of : mannitol (1 – 2 g/kg intravenous over 20 min), dexametasone (0,25 – 0,50 mg/kg/day divided q 4 – 6 h). But they are usually ineffective after the onset of respiratory arrest.

Insulintherapy is conducted owing to using of preparations of short-life action insulin (actrapid, rapidad insulrap). At present there is passed the methodics of insulintherapy which is called the “small doses methodics”. It is based on the constant intravenous insulin infusion.

Insulin concentration in blood is 10-20 mc UN/ml suppresses lipolysis, gluconeogenesis and glycogenolysis; it 120-200 mc UN/ml concentration into cell and suppresses ketogenesis that corresponds to insulin infusion rate of 1 UN/hour and 6-10 UN/hour. 500-3000 mc UN/ml insulin concentration (during big doses infusion) stimulates the adrenaline lipolytic effect that decreases the biologic effect of insulin.

It isn’t advisable to rapidly correct the metabolitic desarangement during ketoacidosis. The optimally slowly softly decreasing of glycemia on 5,5-6,6 mmole/l/hour (100-120 mg %) is provided with had indicated insulin blood concentration.

The decreasing of sensitivity to insulin during ketoacidosis is temporary and after 2-4 hours from its first infusion is recovering of normal sensitivity to it.

Insulin dose is defined in depend on initial glycemia level: if glycemia is less than 20 mmole/l then it is infused with 8-12 UN/hour rate; if glycemia is 20-30 mmole/l, then 12-12 UN/hour; during more than 30 mmole/l glykemia to infuse with 14-16 UN/hour rate.Approximately the initial dose of insulin may be defined thanks to the following circulation.On the first 13,8 mmole/l of glucose in blood is infused 40 UN of insulin, on the each next

2,7 mmole/l to apply some more over 4 UN of insulin (sometimes 8 UN).Rehydration may be initiated with infusion of isotonic saline solutions (0,85 % solution of

sodium chlorid, Ringers’s solution), plasma, lowermolecular dextrans. The rehydration rate is: the first liquid litre during the first hour; the second – during two hours; the third – during three hours (in average – 12-15 ml/min), that is 50 % of the necessary infusion solution is used during 6 hours. After this into the transfusional system is introduces insulin.

The intravenous insulin infusion initially provids its entering into the blood channel in the dehydration causes, the small doses protect from the abrupt decreasing of glycemia level which stimulating hypokaliemia and leading to cerebral edema development.

If the glycemia level decreases untill 200-300 mg % (13,3-16,6 mmole/l) also as a acidosis, then the insulin dose is decreased on half and is added the glucose 5 % solution infusion to avert the acidosis returning.

The rate of supplementary glucous infusion may be accounted owing to the next formula: if patient has an 60 kg weight and blood glucosis decreasing during hour is 100 mg % (5,5 mmole/l) then consequenthy he during this period losses approximately 18,0 g of slucose.

60 x 0,3 = 18 l 1 g/l (100 mg %) x = 18 gInfusion of glucose 5 % solution 360 ml during hour provides the such quantity and averts

the following glycemia level decreasing.After the blood vascular volume recovering to add to infusional solution potassium – 40

mmole/l (a half as a chloride, another half – as a phosphate).

1 g KCl = 13,5 mmole/lInitial dose of KCl may be 20 mmole/hour (1,5 g/hour) during 4-5 hours, then 0,5 g/hour.If during therapy process the potassium level doesn’t exceed 3,0 mmole/l, then, the infusion

potassium dose is increasing untill 40 mmole/l/hour (3,0 g/hour). If the KCl concentration is 3-4 mmole/l, then to infuse owing to calculation 27 mmole/hour (2 g/hour), if concentration is 5-6 mole/l – 13,5 mmole/hour (1,0 g/hour of KCl).

During the sodium bicarbonate infusion on every its 100 mmole it is necessary to introduce 13-20 mmole (10-15 ml of 10 % solution) KCL, the rapid acidosis correction causes the increasing of rate of potassium tranfer into a cells and leads to hypokaliemia.

Indications for using of sodium bicarbonate are the decreasing of blood pH lower 7,0 and if its blood concentration is not more than 10 m eq/l. The Kussmaul respiration appears if the arterial blood pH is lower 6,8. It is necessary to infuse the 2,5 fresh preparated solution to infuse the blood pH controle. To infuse bicarbonate if pH is still 7,0.

During surplus its infusion may be observed the following compliocations: cerebral edema; abrupt hypokaliemia; abrupt hypernatriemia; decreasing of cerebrospinal liquid pH; infringement of the oxihemoglobin dissociation.

Approximate dose is: NaHCO3 = NaHCO3 mmole/l = body weight (kg) x 0,3 x BE (deficiency of alkalines).

For avoiding of alkalosis to infuse at once not more than a half of the doses.For infuse over the calculation – 100 mmole/hour (336 ml of 2,5 % solution during hour).A use of sodium bicarbonate infusion during DKA isn’t at present confessed by all doctors.

Arguments against of its using are three positions: The first – rapid infusion of bicarbonate and acidosis correction will change the curved of graphic of the hemoglobin – oxygen dissociation to the left and as a deficiency of 2,3 DPH will infringe an supply of tissues with oxygen. During infusion of big doses of bicarbonate to adults there was observed the fourfold increasing of cardiac activity for compensation of hypoxia. The second and more based argument is that infusion of bicarbonate causes the paradoxal acidosis of the central nervous system and decreasing of CNS oxigenation. Although a brain is very prevented from the changes of acidic-alkalin state, but the hydrocarbon easy passes through the hematoencephalic barrier and decreases pH of the central nervous system. Because of the bicarbonate infusion will increase the peripheric pH, respiratory reaction on the metobolic acidosis will decrease and the parietal blood CO2 pressur will grouth. This increasing will transfer into the brain, leading to pH decreasing and infringement of the central nervous system function. This phenomenon was affirmed on animals and people. The third argument against the bicarbonate using is that the rapid correction of acidosis leads to the passage of potasium into the cells with developing of hypokaliemia. An regime of the bicarbonate infusion may be different (at once or as a prolonged infusion) and it doesn’t influence on the hypokaliemia appearance rate. The cupping period is practically identical in causes when bicarbonete has been infused and hasn’t been infused, but the hypokaliemia is meeting in 6 ones more oftenly in the patients group who has received bicarbonate.

For acidosis correction and ammonia decontamination is prescribed the glutaminic acid (1,5-3,0 g per day). Also it is possible to use the cocarboxylase, ascorbic acid, vitamins B6 and B12.

During the uncontrollable vomiting for renewal of proteins and prevention from starvation after 4-5 hours from the beggining of treatment it is necessaryto infuse 200-300 ml of plasma. For avertion of hypochloremic state to infuse intravenous 10-20 ml of 10 % solution of sodium chloride.

It is better to conduct rehydration using of the Ringer’s solution with lactate – 10-20 ml on 1 kg of patient body weight during first hour. The Ringer’s solution with lactate is isotonic with less chlorides level that decreases risk of the hyperchloremic acidosis development, which sometimes complicates recovery. Moreover, lactate in this solution (28 m eq/l)slowly transfers into bicarbonate. The contained in solution potassium (4 m eq/l) isn’t contrindication for its using, except cause of oliguria.

Therefore patients in the comatous condition must have the catheter of urinary bladder for the exact measuring of diuresis.

Also it is necessary the constant ECG registration for discovering both hypokaliemia and hyperkaliemia.

Success in therapy of precomatous and comatous condition is defined with opportunity of initial intensive therapy, conditious of cardiovascular system, kidneys, patient age and the factor causing ketoacidosis.

Prognosticy unfavorable signs in the ketoacidic coma tendency may be: an arterial hypotension, which isn’t corrected during rehydration and infusion of hypotonical preparations, decreasing of diuresis untill 30 ml/hour and lower, acute insufficiency of left ventricle, the hemorrhagic syndrome (often as a gastrointestinal bleeding), hypokaliemia and increasing of lactic acid level in blood.

During recovery period, approximately during a week after the diabetic coma acute phase cupping (ketoacidic and hyperosmotic), often are developing the expressive total edemas which connecting with infringement of the water-mineral metabolism regulation. This syndrome almost always is accompanied with the lens accomodative function derangement (hypermetropia or myopia) which connects with its hydropical edema. These complications, as a rule, disappear rapidly, independently, but for their more quickly removal it may be using verospiron in usual tharapeuticc dosages.

More hardly and often with enough steady complication of thr ketoacidic coma is the insulin resistance retained sometimes untill several weeks (months).

The most permanent and dangerous complication of diabetic coma passes for the postcomatous neuropathy with injuring of both somatic and vegetative nervous system. Its develop, evidently, connect with preceding expressive or latent diabetic polyneuropathy. The postcomatous neuropathy may advantagly injuries the motor function (atony of stomach, intestine, biliferous tracts, urinal bladder, limbs paresis) or may have tendency to the sensory derangements (infringements of sensibility over the truncal type).

The most dangerous DKA complication is the cerebral edema. It is accidental, unforeseen, lethal. There aren’t discovered any warning signs or indicators which may distinguish a patient with its complication risk. The cerebral edema clinicaly showes in some hours after the treatment beginning, during when is recoveried adequate circulation and heavy acidosis is cupped partically off and the blood glucose falls down.

The brain edema begins with abrupt consciousness derangement, vomiting as a “fountain”, pathological neurologic symptoms, mydriatic pupils. It develops a deep coma with cerebral death, it is possible a respiratory standstill with combination with the truncal infringements.

The diabetic ketoacidic coma in clinical practice must be differented with other similar syndromes of critical states, first of all with – apoplectic, apoplexiformic (during myocardial infarction), uremic, chlorohydropenic, adrenal comas and other comas (during diabetes mellitus): hyperosmotic and lactacidemical.

For example, these are proposed the following criterions of differental diagnosis of the ketoacidic and apoplectic comas: 1) ketoacidic develops more slowly (some days) and has a diabetic history; 2) during ketoacidic coma the hyperglycemia is higher and very expressive glucosuria, acetonuria; 3) arterial pressure always is lower, pulse is rapid and weak; 4) neurogic cymptomatology is not more expressive, and in principal, it isn’t permanent.

The differental-diagnostic criterions of comatous states are in the tableComa

Symptoms Ketoacidic hyperketonemic

Hyperosmotic Hypoglycemia Hyperlactacidemic

Diabetes type Often type 1 DM Often type 2 DM Often type 1 DM Often type 2 DM

Age Any Often older Any Older

Preliminary signs

Weakness, vomit, dryness of month, polyuria

Weakness, labbiness, apathy

Starvation sene, tremor, sweating

Nausea, vomit, muscle pain

Coma Gradually Gradually Quickly Quickly

developingThe precomatous state characters

Graasually loss of consciousness

Flabbiness,Consciousness is kept long

Excitement tranfering into sopor and coma

Sleeeping

Breathing Kussmaul’s Often weak normal

Normal, sometimas weak

Kussmaul’s

Pulse Rapid Rapid Rapid,normal or slow

Rapid

Arterial pressure

Decreased Abrupt decreased,collapse

Normal, decreased or increased

Abrupt decreased, collapse

Temperature Normal Increased or normal

Normal Decreased

Skin Dry, turgor Dry, turgor Humid Dry, turgor

Tongue Dry with fur Dry Humid Dry

Eyeballs tonics Is decreased Decreased Normal or increased

Decreased

Diuresis Polyuria, then oliguria

Polyuria, oligyria and anuria

Normal Oligyria, anuria

Glycemia Higher Higher No No

Natremia Normal Higher Normal Normal

Azotemia Increased or normal

Increased Normal Increased

Alkaline reserve

Lowered Normal Normal Lowered

Ketonemia Higher Normal Normal Normal

Ketonuria Yes No No No

Other symptoms

- Hyperosmotic plasma

Insulintherapy in history

Hyperlactaacidemia, hyperpiruvatemia. In history there is bigyanids therapy

Ketoacidic coma therapy algorithm.Coma diagnosis is stood in:0-1 hour:

1. Usual insulin – 20 UN i/m or i/v in boluce on the 250-300 ml of sodium chloride physiologic solution (for children – 0,1-0,1 UN/kg of body weight). Sodium chloride physiologic solution – 1 litre in dropper owing to – 150 dropes/min (for children – 20 ml/kg of body weight), then the usual insulin 6-8 UN (0,1 UN/kg of body weight/hour), cocarboxilase – 100 mg, 5 ml of 5 % ascorbic acid solution; 0,06 % corglucon solution 0,5 ml.During collapse – 0,5 ml of 1 % phenylephrine hydrochloride introovenous using of dropper and hydrocortisone 75-100 mg i/v in boluces.

2. Unithyole 5 % solution – 10-15 ml i/v in bolues (for children – 2 ml/kg of weight).3. If a blood pH is lower 7,0, then t use 2,5 % sodium hydrocarbonate i/v using of dropper over 100

mmole/hour (for children – 2,5 ml/kg). The sodium hydrocarbonate infusion is stopped if pH is higher than 7,0.

4. Penicillin 500 000-1 000 000 Un i/m per 4 hours (or often antibiotic therapy).5. The moist oxygen inhalation, gastric lavage using of warm solution of sode, mucus aspiration,

aspiration of vomitive mass, cleansing enema, catheterization of urinary bladder (permanent) for a diuresis controlliny.

2-hour:1. Physiologic solution of sodium chloride 500 ml i/v in dropper (150 drops during 1 minute), for

children – 50-150 ml/kg during day (nevertheless, during second hour is using 10-15 % of all doses for a day).

2. Usual insulin 4-6 UN i/v in dropper or 6-8 UN i/m (for children – 0,1 UN/kg).3. Of blood pH is lower 7,0, then to continue a droping infusion of the sodium bicarbonate

solution.4. Of these is an expressive vomiting, then it is necessary to i/v infuse in boluces 10-3 ml of 10 %

solution of sodium chloride, cerrucal – 2,0 ml i/m.5. Contrical 15 000-20 000 UN i/v dropping (over the indications).6. Oxygenal inhalations.

3-hour:1. Sodium chloride physiologic solution 300-500 ml (for children – 10 % of the had counted on

dose during a day), haemodesum 150-200 ml i/v dropping infusion (120 drops per 1 minute).2. Usual insulin 4-6 UN in dropper or 6-8 UN i/m (for children 0,1-0,2 UN/kg of body weight). Of

during first 2-3 hours of treatment the glycemia quotients and patient condition aren’t becomining better, then the insulin doses, which is infused, is doubled. At the same time the rapid decreasing of the blood sugar level (more than 5,5-6,0 mmole/l/hour) may be accompanied with hypoglycemic syndrome.

3. 5 % solution of potassium chloride – 20 mmole/l/hour (1,5 g) i/v using of dropping method under the checking of the blood plasma potassium level and ECG 9for children- 3-6 ml/kg dose, but no more 40 mmole). If there was initially lower potassium level in blood plasma, then the potassium chloride infusion begins at once.

4. Oxygenal inhalaations.4-hour:

1. Sodium chloride physiologic solution 500 ml, haemodesum 100-200 ml i/v in dropper (80-100 drops per minute, for children – 5 % of the had counted on liquid dose a day).

2. Usual insulin 4-6 UN i/v using of dropping method or i/m )for children 0,1 UN/kg of body weight).

3. 5 % solution of potassium chloride – 10-15 mmole/hour i/v in dropper (for children no more 40 mmole in 1 litre of the physiologic solution of sodium chloride).

4. Unithyole 5 % solution – 1-1,5 ml/10 kg of body weight in boluces.5. 2 ml of 25 % solution of cordiamine (over the indications).6. Penicillin 500 000-1 000 000 UN i/m.7. Oxygenal inhalations.

5-hour:1. Physiologic solution of sodium chloride 250-300 ml i/v using of dropping method (80 drops per

minute), for children 50-10 % of the had counted on liquid day doses.2. Usual insulin 4-6 UN i/v using of dropping method or 4-6 UN i/m (0,1 UN/kg of body weight).

6-hour and then every hour untill a glycemia decreasinguntill 11,1-13,9 mmole/l:1. Physiologic solution of sodium chloride 250 ml i/v using of dropping method (60-100 drops per

minute), for children during first 6 hours of treatment of comatous patient to infuse summary 50 % had on liguid day doses, and the next 6 hour – 25 % and the next 12 hours – 25 %.

2. Usual insulin 4-6 UN i/v using of dropping method or i/m (0,1 UN/kg per hour).3. 5 % solution of potassium chloride – 10-15 mmole/hour i/v using of droppeng method under the

blood plasma pottassium level checking.After the recovery from the comatous state and the glycemia lower 13,9-11,1 mmole/l to

begin to insule i/v using of dropping method 5 % solution of glucose – 300-500 ml per 4 hours with supplement of the pottassium chloride 13 mmole (1 gramm), usual insulin 6 UN per 2 hours or 10-12 UN per 4 hours (for children – 0,1-0,25 UN/kg of body weight in dependence on the clycemia level) i/v in dropper or i/m. The infusion of insulin with non = prolonged effet (705 ones per a day) is continuing untill the complete compensation of diabetes mellitus.

After the consciousness recovery to prescribe to patient the sufficient liquid volume-alkaline mineral waters, sodium solution, juices (tomat, apricot, cherry, apple, wild hedge rosal), stewed fruits, thin jelly, millet gruel, potatoes gruel, gratted vegetable soups, meat sufle.

From the diet are excepted fats.Comment. Owing to the hypercoagulation present and for preventing of the DIC-syndrome

develop, during first 6 hours of the ketoacidic coma therapy is infused heparin over 5 000 UN i/m per 6 hours (for children – 150 UN/kg of body weight per 12 hours), then i/m under the blood coagulation system cheching.

It is possible to supplemently infuse splenin over 2 ml i/m 2-3 ones per day, pyridoxine hydrochloride 2 ml 5 % solution.

Moreover, for decreasing of insulin absorbtion with system to wash its using of insulin solution )1 bottle of insulin with the 200-300 ml of sodium chloride physiologic solution) or to add 7 ml of 25 % albumin solution, or 1-2 ml of patient blood plasma with 500 ml of physiologic solution.

Hypoglycemic states and hypoglycemic coma during DM.Hypoglycemia is one of the organism states which is coused with abrupt decreasing of blood

sugar level and uncompletely supplying of the central nervous system cells with glucose. The most dangerous manifestation of hypoglycemic state is – hypoglycemic coma.

During diabetes mellitus hypoglycemic states may appear owing to: a) overdoses of infused insulin or sulfanilamidic hypoglycemical preparations;b) infringement of the diet regime during unopporhune eating after insulin injection or after the eating food with insufficient carbohydrates quantity;c) hypersensitivity to insulin (especially in young and youth age);d) decreasing of the insulin inactivated ability of liver and kidneys (insufficient production of insulinase or activation of its inhibitors);e) alhogolic intoxication (glycogen dissociation lowering);chronic renal insufficiency (prolonged period of circulation of hypoglycemic preparations as a result of their slowering excreting in urine);f) compensatory insulinism on the early stages of diabetes mellitus;g) using of salicylates, sulfanilamidic preparations, adrenolytics during their prescription with combination with insulin or tabletic hypoglycemic preparations.Precipitating factors.- irregular ingestion of food;- extreme activity;- alcohol ingestion;- drug interaction;- liver or renal disease;- hypopituitarism and adrenal insufficiency.

Pathogenesis. The pathogenesis base of hypoglycemia is the decresing of the glucose utilization by CNS cells. It is known that free glucose is the basic energetical substrate for brain cells. An insufficiency of brain supply with glucose leads to developing on hypoxia with following progress of carbohydrates and proteins metabolisms infringement is cells of CNS. The different parts of cerebrum are injuried in special successiveness that determinates a characteristic changes of symptomatology as hypoglycemical state progressing. First of all owing to hypoglycemia is suffered the cerebral cortex, then the subcortical structures, cerebellum, at last are injuried function of the medulla oblongata.

Cerebrum receives its nutrition owing to carbohydrates, but simultaneously it is not many glucose is deposited in it. The energetic requirements of CNS cells are great. The cerebral tissue consumes oxygen in 30 ones more than muscular. Glucose insufficiency is accompanied with decreasing of oxygen using by cells of CNS even if blood is completely saturated with oxygen. Because of these, the hypoglycemia symptoms are analogous to the signs of hypoxia.

In hypoglycemia pathogenesis the principal factors is an ability to glucose utilization, therefore a hypoglycemic states may be even in normal blood glucose level, but during suppression of the glucose entering processes into a cell. Owing to glucose insufficiency in cells of the more

differential cerebral parts (cortex and diencephalic structures), there are appearing a erethism, anxiety, vertigo, sleepiness, apathy, inadequate speech or actions. In case of injuring of the more phylogenetically ancient cerebral parts (the medulla oblongata, upper parts of spinal cord) develop the tonic and clonic convulsions, hyperkinesises, decreasing of tendon and abdominal reflexes, anisocoria, nystagmus.

Hypoclycemia is adequate stimulator of sympathoadrenal system which leads to the blood catecholamins level increasing. This is showed with characteric vegetative symptomatologyweakness, sweating, tremor, tachicardia. At the same time hypoglycemia causes the stimulation of hypothalamus with following activation of contrinsular neurohormonal systems (corticotropin-glucocorticoids-somatotropin). An increasing of the contrinsular systems activity is a compensatory reaction of organism sending to the hypoglycemia liquidation. The considerable part in removing of hypoglycemia over the self-regulation has a glucagon which activates the glycogen dissociation (first of all – in liver).

Prolonged hydrocarbonative starvation and hypoxia of brain is accompanied not only with functional, but and morphological changes, until necrosis or edema of different parts of cerebrum. A catecholamins excess during hypoglycemia leads to infringement of cerebral vessels tonus and vascular blood stasis. Blood flow slowing down leads to increasing thrombogenesis with following complications. There are expressed an opinion that one of the cause of neurological derangements during hypoglycemia may be due to decreasing of amino acids and peptides formation, which are necessary for normal neuronal activity. It must be remembered that the hypoglycemic state leads to ketogenesis. It has such mechanism as: if blood glucose level is decreasing and energetic insufficiency begins to develop, then increases secretion of catecholamins and somatotropin, lipolysis is stimulated which creating a causes for accumulation in blood beta-oxybutyric and acetoacetic acids, the basis substrates of ketosis.

In dependence on individual sensibility of central nervous system to the glucose insufficiency, the hypoglycemic state appears during different levels of glycemia – from 4,0 until 2,0 mmole/l and lower. Sometimes a hypoglycemic states may develop during abrupt decreasing from the very higher level, for example, from 20 and more over mmole/l until normal or even some increased level of glucose in blood (5,0-7,0 mmole/l).

Clinical picture. To develop of hypoglycemic coma are preceding the next clinic stages of hypoglycemia:

First-stage. It is caused with hypoxia of the higher parts of the nerval system cells, advantagly the cerebral cortex.

Clinical signs are very varieties. They are characterized with excitement or inhibition, sense of anxiety, mood lability, haidache. Daring objective examination it may be noted the skin moistness, tacicardia.it’s pity, but not all patient during this stage suffer from starvation sense and owing to these they don’t define their state as a hypoglycemic reaction manifestation.

Second stage. Its pahtogenesis base is consisted of the injuring of the subcortical-diencephalic regimen.

Clinic symptomatology is characterized with inadequate behaviour, mannerism, motor excitement, tremor, excessive sweating, excessive tachicardia and arterial hypertension, headache, uncontrollable starvation , but consciousness on this stage isn’t altered.

Third stage. Hypoglycemia is caused with infringement of functional activity of the midbrain and characterized with abrupt increasing of muscular tonus, develop of tonico-clonical convulsions (like as a epeleptic fit), appearance of the Babinski’s sign, pupils dilatation. Are preserved an excessive skin moistness, tachicardia and increased arterial pressure. Sometimes are joined a delirium and hallucinations.]

This stage tendency may be accompanied with develop of depression or aggression in the patient behavior.

Fourth stage. In connects with injuring of upper parts of the medulla oblongata (it’s directly a coma) and is characterized with develop of spastic syndrome and consciousness loss.

A tendon and periostal reflexes are increased. The eyeballs tonus is increased, too, pupils are dilated. Skin is moinst, body temperature is normal or some increased. Breathing is normal, aceton

smell, as a rule, is abcent. Cardiac sounds may be accent, pulse may be rapid, arterial pressure is increased or normal.

Fifth stage. Injuring of lower parts of the medulla oblongata – is characterized with deep coma, hypotony, tachicardia. May be affected into a process the respiratory and vasomotor centres and in such cause will be fatal outcome.

Clinics of this stage reflects a progress of comatous stage. There is areflexia, decreasing of muscular tonus. An excessive moinstness is stopped, may be a disarrangement of respiration infringement.

It must be noted, that sometimes are atypical hypoglycemic reactions of which pathogenetic bases are a injury of the limbic-reticular region. In such causes the clinical signs of hypoglycemia are characterized with a nausea, vomiting, bradycardia, euphoria.

The dangerous for life with accompaning hypoglycemia is the cerebral edema. It develop is caused with some factors: late diagnosis of coma, erroneous infusion of insulin or overdosage of hypertonic glucose (40 %) solution.

The cerebral edema clinics is characterized with meningeal signs, vomiting, higher temperature and derangement of respiratory and cardiac rhythm.

A consequences of hypoglycemic states may be early and later. The first develop in several hours after hypoglycemical state. They are a hemiparesis, hemiplegias, aphasia, myocardial infarction and infringement of cerebral circulation.

The later consequences are in some days, weeks or months after the hypoglycemic condition develop. They manifest as a encephalopathy, progressive during repeating hypoglycemics – epilepsy, parkinsonism.

A special danger has a hypoglycemical state on the alcoholic intoxication phone, because it is unfavorable for consequences.

The essential diagnostic criterion of hypoglycemic state is a positive reaction on the intravenous glucose infusion.Clinical presentation.Signs and symptoms.

Two distinct patterns are distinguished:1) adrenergic symptoms (they are attributed to increased sympathetic activity and epinephrine

release): sweating, nervousness, tremulousness, faintness, palpitation, and sometimes hunger;2) cerebral nervous system manifestations: confusion, inappropriate behavior (which can be

mistaken for inebriation); visual disturbances, stupor, coma or seizures. (Improvement in the cerebral nervous system manifestations will be with a rise in blood glucose.)

A common symptom of hypoglycemia is the early morning headache, which is usually present when the patient awakes.

Patients should be familiar with the symptoms of the hypoglycemia but some of them are not heralded by symptoms.Physical examination.1. The skin is cold, moist.2. Hyperreflexia can be elicited.3. Hypoglycemic coma is commonly associated with abnormally low body temperature

4. Patient may be unconsciousness.Laboratory findings.1. Low level of blood glucose

Common symptoms of hypoglycemia in different age groupsChildren Young adults Elderly

Tremor Tremor TremorHunger HungerPallor Pounding heart Pounding heart

Sweating SweatingAnxiety

Drowsiness Drowsiness DrowsinessPoor concentration Odd behaviour Poor concentration

Confusion ConfusionWeakness Incoordination WeaknessDizziness Speech diffculty DizzinessBehavioral Nonspecifc NeurologicalTearful Nausea UnsteadinessConfusion Headache Poor concentrationTiredness Double visionIrritable Blurred visionAggressive Slurred speech

Treatment.On the pre-hospital stage. For cupping of the hypoglycemic state first stage it is

sufficiently an eating food consists of carbohydrates which are in normal diet ration of the patient (loaf, boiled cereals, potatoes, thin jelly).

On the second stage of hypoglycemic stage are necessary completely the easy assimilated carbohydrates (sugar, jam). As a rule, the rapid eating of food consisting saccharose and fructose allows to prevent from the progressive hypoglycemical state and normalize the glycemia lewel and patient state. If there are not special indications, these patient don’t need in hospitalization.

For the effective urgent treatment on the third stage of hypoglycemic state in aguiring the immediate infusion of 40 % solution of glucose in such volume that is necessary for complete removal of clinic symptoms of hypoglycemic condition, but no more than 80 ml, because of avoiding of the brain edema. The patient must be hospitalized for prevention of early consequences of hypoglycemia and correction of the dose of hypoglycemical therapy.

The treatment of 4 and 5 stages (hypoglycemic coma) is conducted in resuscitative department.

Algorithm of treatment of patient in hypoglycemic coma.Coma diagnosis was defined in:0-5 minutes:

1. Intravenous in boluces to infuse 40-80 ml of 40 % glucose solution. If it is impossible to make venipuncture, then – i/m 1 mg of glucagon or 0,5-1,0 ml of adrenalin 0,1 % solution. The immediate hospitalization for the venesection and following therapy. If the consciousness is lossed and ther are convulsions, then it is necessary a prophylaxis of traumata, asphyxia, aspiration; i/m infusion of 5-10 ml of magnesium sulfate 25 % solution (for children 0,2 ml/kg).

5-15 minutes:1. If consciousness is lossed, then i/v in boluces 40-80 ml of glucose 40 % solution.2. I/v using of dropper – 300-500 ml of glucose 10 % solution, 5 ml of ascorbic acid 5 % solution,

75-100 mg of hydrocortisone hemisuccinate (Solu-Cortef) or prednisolone 30 mg. If

consciousness returns, but there is a great headache, then – i/m infusion of analgine 50 % solution 2 ml or other analgetics; if there is nausea or vomit – then 2 ml of Reglan (Metaclopramide).

15-30 minutes:If consciousness is absent and glycemia level is 3 mmole/l and higher, there is present of

neurogical or ophthalmologic symptoms of the cerebral edema, then – i/v infusion using of dropping method – 10-20 % solution of mannitol (1 g/kg of body weight) with following i/v infusion of basix 3-5 ml (for children – 1-3 mg/kg of body weight), i/v 10 ml of 2,4 % solution of euphylline, 50-75 mg of hydrocortisone. Oxygenotherapy.

If effect of therapy is abcest, then in 4 hours to repeat the mannitol and hydrocortisone infusion.

If there is lower arterial pressure then complementary to cortisone (prednisolone) it’s possible to infuse 1 ml of phenylephrine hydrochloride or 1 ml s/c of 0,25 % solution of cortiron.

Simultaneously with oxigenotherapy it’s possible to infuse 5 % solution of unihiole (1-2 ml/10 kg of body weight).

After recovery of patient condition and absence of the hypoglycemic coma signs it is recommended infusion during 2-3 weeks, drugs, which improve microcirculation and stimulating the cardohydrates and proteins metabolism in cells of central nervous system: 10 ml of 20 % solution of pyracetam i/v or nootropil over 0,04-3 ones per day, glutamin acid over 1 mg-3 ones per day or 5 % solution of cerebrolysin over 5 ml i/v, stugeron (cinnarizine) over 2 tablet x 3 ones per day, cavinton over 2 ml i/v in dropper on physiologic solution.Hyperosmolar coma (Nonketonic hyperglycemic-hyperosmolar coma (NKHHC or HNC)) – is acute complication of diabetes mellitus, pathogenetic base which is dehydration, hyperglycemia, hyperosmolarity, hypernatremia and azotemia.

Etiology. For develop of hyperosmolar coma are promoted with the following factors:1. Prolonged using of diuretic drugs, immunodepressants, glucocorticoids;2. Acute gastrointestinal diseases accompaning with vomit and diarrhea (gastroenteritis,

pancreatitis, food poisoning);3. large burns;4. massive bleedings;5. hemodialysis or peritoneal dialysis;6. cabohydrates using surplus7. infusion of hypertonic solutions of glucose and sodium chloride;8. infections, traumata;9. acute derangement of cerebral circulation.Any states which accompanied with liquid loss may to lead to the hyperosmolar coma.The hyperosmolar coma usually develops during an insulin independant type of diabetes

mellitus on the base of insufficient treatment or unfound disease.Predisposing factors.1. HNC seems to occur spontaneously in about 5 – 7 % of patients.2. In 90 % of patients some degree of renal insufficiency seems to coexist.3. Infection (e.g., pneumonia, urinary tract infection, gram-negative sepsis) is underlying frequent

precipitating cause.4. Use of certain drugs has been associated with this condition:- steroids increase glucogenesis and antagonize the action of insulin;- potassium-wasting diuretics (hypokalemia decreases insulin secretion), e.g., thiazides,

furosemide;- other drugs, e.g., propranolol, azathioprine, diazoxide.5. Other medical conditions such as cerebrovascular accident, subdural hematoma, acute

pancreatitis, and severe burns have been associated with HNC.6. Use of concentrated glucose solutions, such as used in peripheral hyperalimentation or renal

dialysis, has been associated with HNC.7. HNC can be induced by peritoneal or hemodialysis, tube feeding.

8. Endocrine disorders such as acromegaly, Cushing disease, and thyrotoxicosis have also been associated with HNC.

Pathogenesis. The pathophysiology of HNC is similar to that of ketoacidosis, except that ketoacids do not accumulate in the blood. The reason of this phenomenon is unclear. Initially it was thought that patients with HNC produced enough insulin to prevent lipolysis and ketogenesis but not enough to prevent hyperglycemia. The concept was invalidated by finding similar inappropriately low plasma insulin concentrations in patients with the two syndromes. The finding of lower plasma free fatty acids, as well as cortisol and growth-hormone concentrations, in patients with ketoacidosis has raised the possibility that the absence of ketosis may be the result of decreased cortisol and growth-hormone effects on lipolysis. Suppression of lipolysis by hyperosmolality also has been proposed.

HNC usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration from the hyperglycemia-induced osmotic diuresis.

An acute mechanism in coma develop is the dehydration and hyperglycemia. At first hyperglycemia is accompanied with glucosuria and polyuria, and also promotes to passing of liquid from cells into intercellular space. The osmotic diuresis increases dehydration. A liquid loss is not only owing to osmotic diuresis, but as a result of decreasing of tubular reabsorption and decreasing of antidiuretic hormone secretion. The increasing diuresis causes an intracellular and intercellular dehydration and decreasing of blood flow in organs, including in kidneys. There is develop of dehydrative hypovolemia. Dehydration is accompanied with stasis of blood cells, thrombocytes and erythrocytes agregation, hypercoagulation. To reply on dehydrative hypovolemia it is increased seretion of aldosterone and sodium ions detain in blood. Owing to decreasing of renal blood frow – the sodium excretion is troubled. Hypernatremia promotes to formation of small hemorrhages in brain. In the hyperglycemia and dehydration causes it abruptly increases the blood osmolarity. The osmolarity increasing is accompanied with intracerebral annd subdural hemorrhages.

A characteric specility of the hyperosmolar coma pathogenesis is abcent of ketoacidosis. A ketoacidosis absent in caused with some causes:

1. dehydration causes a decreasing of circulation of pancreas and liver, a inhibition of lyposis in fatty tissue;

2. great infringement of liver function and its hypoxia block the using of fats and ketogenesis;

3. even presence of some endogenic insulin (if there is a older patient with nonserious diabetes) during hyperosmolar coma period, that is proved owing to IRE, prevents from lipolysis and ketogenesis.

Hyperosmolar coma develops gradually, the complete symptomocomplex is appeared only in 10-12 days from the beginning of first signs.

Blood osmolarity achieves extreme higher level untill 400-500 m osm/l (norma is 300-330 m osm/l).

Osm.= 2(K++Na+) +Y+AClinical picture is characterized with derangement of consciousness in different degree

(from the sleepness and sopor untill deep coma), absence of aceton smell in expiratory air, symptoms of organical injuring of CNS (absence of tendom rexlexes, the Babinski’s, Rossolimo’s symptoms – possitive, double nystagmus, muscular hypertonus). There are very excessive the symptoms of dehydration (dry skin and dry mucous membranes, lower tonus of eyeballs). It appeares and dyspnea, tachicardia, rhythm disorders.The most characteric distinction of hyperosmolar coma from ketoacidosis and lactacidosis is the more early and deeper psychoneurological disturbances. There are permanently different over the form and degree a consciousness derangerment (hallucinations, delirium, sopor, deep coma), which accompaning an expressive neurologic signs (aphasia, muscular fasciculations, hemiparesis, pahtologic reflexes, symptoms of derangements of cranial nerves, hemianopsia, hystagmus andd many others). Clinical presentation.Signs and symptoms.

1. Polyuria, polydipsia, weight loss, weakness and progressive changes in state of consciousness from mental cloudiness to coma (present in 50 % of patients) occur over a number of days to weeks.

2. Because other underlying conditions (such as cerebrovascular accident and subdural hematoma) can coexist, other causes of coma should be kept in mind, especially in the elderly.

3. Seizures occur in 5 % of patients and may be either focal or generalized.Physical examination.1. Severe dehydration is invariably present.2. Various neurologic deficits (such as coma, transient hemiparesis, hyperreflexia, and generalized

areflexia) are commonly present. Altered states of consciousness from lethargy to coma are observed.

3. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular disease) may be evident.

Laboratory findings.1. Extreme hyperglycemia (blood glucose levels from 30 mmoll/l and over are common.2. A markedly elevated serum osmolality is present, usually in excess of 350 mOsm/l. (Normal =

290 mOsm/l). The osmolality can be calculated by the following formula: mOsm/l = 2(Na + K) = blood glucose/18 + BUN/2.8.

3. The initial plasma bicarbonate averaged.4. Serum ketones are usually not detectable, and patients are not acidic.5. Serum sodium may be high (if severe degree of dehydration is present), normal, or high (when

the marked shift of water from the intracellular to the extracellular space due to the marked hyperglycemia is present).

6. Serum potassium levels may be high (secondary to the effects of hyperosmolality as it draws potassium from the cells), normal, or low (from marked urinary losses from the osmotic diuresis). But potassium deficiency exists.

A laboratory diagnosis criterions:a) hyperglycemia is 45-50 mmole/l and higher;b) blood hyperosmolarity is 350 m osm/l and higher;c) hypernatremia is 150 mmole/l and higher;d) increasing of blood urea level;e) pachyemia signs.

HNC is a syndrome characterized by impaired consciousness, sometimes accompanied by seizures, extreme dehydration, , and extreme hyperglycemia that is not accompanied by ketoacidosis.

The syndrome usually occurs in patients with type II DM, who are treated with a diet or oral hypoglycemic agents, sometimes it is a complication of previously undiagnosed or medically neglected DM (type II).

In contrast to ketoacidosis, mortality in patients with HNC has been very high (50 %) in most series. Mortality has been associated with convulsions, deep vein thrombosis, pulmonary embolus, pancreatitis and renal failure. Death is usually due to an associated severe medical condition and not to the hyperosmolality.

Treatment.

Treatment. On the pre-hospital stage is required an urgent correction of hemodynamics for supply of transitor of patient into resuscitation department.

Therapy consists of the following compounds: a rehydration, aninsulin therapy, an electrolitic dysbalance correction (hypokaliemia and hypernatremia), removal of hypercoagulotion a brain edema develop prevention.

This condition is a medical emergency and the patient should be placed in an intensive care unit.

Many of the management techniques recommended for a patient with DKA are applicable here as well.The goals of therapy include:- rehydration;- reduction of hyperglycemia;- electrolytes replacement;- investigation of precipitating factors, treatment of complications.Rehydration.

The average fluid deficit is 10 liters, and acute circulatory collapse is a common terminal event in HNC. The immediate aims of treatment are to rapidly expand the contracted intravascular volume in order to stabilize the blood pressure, improve the circulation, and improve the rate of urine production. It is important to remember that it is the severe hyperglycemia and the concomitant obligatory shift of water from the intracellular to the intravascular compartment that prevents this latter space from collapsing at the time of severe fluid depletion. With too rapid a correction of hyperglycemia, potential hypovolimic shock (as fluid moves from the extracellular space back into the intracellular space) may occur.

Treatment is starting by infusion 1 to 3 liters of 0,9 % sodium chloride over 1 to 2 hours; if this suffices to stabilize the blood pressure, circulation and restore good urine flow, the intravenous fluid can be changed to 0,45 % sodium chloride to provide some free water. 0,45 % sodium chloride is used at a rate of 150 to 500 ml/hour depending on the state of hydration, previous clinical response and the balance between fluid input and output. The aim of this phase of intravenous fluid therapy is not to attempt to rapidly correct the total fluid deficit or the hyperosmolality, but rather to maintain stable circulation and renal function and to progressively replenish water and sodium at rates that do not threaten or cause acute fluid overload.

Generally, half of the loss is replaced in the first 12 hours and the rest in the subsequent 24 hours.Insulin therapy.

Insulin treatment in HNC is started by 10 to 20 unites of regular insulin intravenously as a bolus dose prior to starting the insulin infusion and then giving intravenously regular insulin in a dose of 0,05 – 0,10 unites/kg/hour (many authorities routinely use the same insulin treatment regimens as for treating DKA, other authorities recommend smaller doses of insulin, because they believe that patients with type II DM are offer very sensitive to insulin, but this view is not universally accepted, and many obese type II diabetics with NHC require larger insulin doses to induce a progressive decrease in their marked hyperglycemia. It is important to remember that because of insulin therapy causes blood glucose levels to fall, water shifts into the cells and existing hypotension and oliguria can further aggravated. Thus, initially some advocate delaying insulin therapy while infusion normal saline until vital signs have improved.

When the plasma glucose reaches the range 11 to 13 mmoll/l, 5 % glucose should be added to the intravenous fluids to avoid the risk of hypoglycemia. Following recovery the acute episode, patients are usually switched to adjusted doses of subcutaneous regular insulin at 4 to 6-hour intervals. When they are able to eat, this is changed to a 1 or 2 injection regimen.Treatment of electrolyte disorders.

Once urine flow has been reestablished, potassium should be added to begin repletion of the total body deficits.

Potassium replacement is usually started by adding 20 mmoll/l to the initial liter of the intravenously-infused 0,45 % sodium chloride with careful serum potassium and ECG monitoring.

Alhorhythm of treatment of patient in hyperosmolar coma.Coma diagnosis was defined in:

1-hour:1. Usual insulin 8-10 UN i/v in boluce (0,1-0,2 UN/kg) and 8-10 UN i/v;2. Hypotonic (0,45 %) solution of sodium chloride – 1000 ml, usual insulin 6-8 UN i/v in dropper.

The first 400-500 ml i/v in boluce, then using of dropping method (150 drop per minute), cocarboxylase – 100 mg; 5 % solution of ascorbic acid – 3-5 ml; 0,5 ml of o,06 % solution of

corglycon; during collapse – 0,5 ml of 1 % solution of phenylephrine hydrochloride i/v using of dropper; 10% pottassium chloride solution 15 ml (20 mmole/l per hour or 1,5 g) i/v using of dropping method;

3. Heparin 5 000 UN i/v using of dropping infusion method (if there isn’t a collapse, then – i/m);4. Inhalation of humid oxygen, aspiration of mucus and vomiting mass, gastric lavage, cleansing

enema, catheterization of urinary bladder/2-hour:

1. Hypotonic (0,45 %) solution of sodium chloride – 1000 ml, usual insulin 6-8 UN (0,1-0,2 UN/kg), 1 % solution of glutaminic acid 25 ml i/v;

2. During lower arterial pressure – hydrocortisone 75-100 mg or prednisolone 30-60 mg i/v in boluce; 0,5 % solution of cortizon 2 ml i/m;

3. 10 solution of pottassium chloride – 10 ml (13,5 mmole/hour, intravenous using of dropping infusion method);

4. Inhalation of humid oxygen.3-hour:

1. Hypotonic (0,45 %) solution of sodium chloride – 750 ml, usual insulin 6-8 UN (0,1 UN/kg), 10 % solution of pottassium chloride 5 ml (6-7 mmole/hour or 0,5 g) i/v using of dropper.4-hour.

Still recovery of patient with comatous state to continue intravenous dropping infusion of hypotonic (0,45 %) solution of sodium chloride; but if the blood osmolarity is fallen untill 300 m osm/l – then physiologic solution – 500 ml/hour, usual insulin 6-8 UN/hour, 10 % solution of pottassium chloride 5-7,5 ml/hour. During decreasing of glycemia untill 12 mmole/l to pass to the i/m infusion of usual insulin 4-6 UN per 2 hour, if glycemia level is lower 10 mmole/l – then 4-6 UN per 4 hour i/m.

If the blood glucose level is lower 13,8 mmole/l and at the some time there is a blood hyperosmolarity – then to use (i/v dropping) hypotonic (2,5 %) solution of glucose (untill 1000 ml). It is continuing an oxygentherapy, i/v dropping infusion of potassium chloride, heparin, cardiac an d vascular preparations (over indications).

During all therapy there is necessary care of oral cavity, stomach, intestine; examination of arterial and venous blood pressure, ESY; every hour is examined a blood glucose, pottassium and sodium level, plasma osmolarity, if there is oliguria – then the blood urea.

A fatal outcome during hyperosmolary coma on therapy base may be caused with a cerebral edema, which develops as a result of rapid change of the osmotic gradient between blood and cerebrospinal liquid and usually it appears during fast falling of glucose level in blood owing to the maximal unsulin doses with simultaneous surplus infusion of the sodium chloride hypotonic solution. For a brain edema prevention and for correction of metabolism in CNS cells are using a 30-50 ml of 1 % solution of glutaminic acid i/v, pyracetam 20 % solution 5-10 ml, oxygentherapy.

Lactatacidemic acidosis and lactatacidemic coma.Hyperlactacidemia is an unspecifical syndrome with very variety causes. It, first of all, the

diseases which are accompanied with hypoxia of tissues (hypoxia stimulates anaerobic glycolysis which the final metabolitic product is a lactic acid). If may be shock of any genesis, cardiac and respiratory insufficiency, leukosises, chronic alcoholism. A dysbalance between production and utilization of lactaqte is observed during poisoning with salicylates, during parenteral infusion of fructose, biguanids using.

Owing to speciality of the lactacidosis pathogenesis pahtogenesis (including diabetic) is defined its therapy pecualiarity. Because of an expession and prognosi of lactacidosis is precisionly correlated with the blood semur lactate level, the success of therapy is determinated with measures efficacy which are directed on elimination of the acidosis a causal and symptomatic therapy must be directed on the struggle with shock, anemia, hypoxia.

Just therefore is especially actual problem of early diagnosis of lactacidosis, as in developing stage this syndrome is practically incurable. This is caused, on the one hand, with that lactacidosis decreases tissues ability to metabolisate (or excrete) lactate, on the other, it is developed the characteric reversional effect, that in organs which are usually utilizate lactate (for example – in

liver), is a lactic acide synthesis. It is appeared a characteric vicious circle and in such causes the possibility of acidosis compensation owing to use of soda solutions infusion has became complicated (alkaline resistancy). A vicious circle may be broken only with measures directed on the cause of lactacidosis develop.

DM is one of the major causes of LA, a serious condition characterized by excessive accumulation of lactic acid and metabolic acidosis.

The hallmark of LA is the presence of tissue hypoxemia, which leads to enhanced anaerobic glycolysis and to increased lactic acid formation.

Pyruvic acid Lactic acidNADH NADAcetoacetic Beta-hydroxybutyric Piruvic acid is converted into lactic acid by lactic dehydrogenase (LDH) in the presence of

reduced nicotinamide adenine dinucleotide (NADH), which, in turn, is converted into NAD. The reaction is reversible and involves LDH in both directions. The conversion of acetoacetic acid into beta-hydroxybutyric acid also requires the oxydation of NADH. LA results from decreased availability of NAD caused by lack of oxygen. Likewise, the deficiency of NAD impairs the conversion of beta-hydroxybutyric into acetoacetic acid. Thus, LA predisposes to accumulation of beta-hydroxybutyric acid, which does not react with acetest tablet, so, the reaction for ketone bodies may be negative or slightly positive. The normal blood lactic acid concentration is 1mmol/l, and the pyruvic to lactic ratio is 10:1. An increase in lactic acid without concomitant rise in pyruvate leads to LA of clinical importance.Predisposing factors.1. Heart and pulmonary failure (which leads to hypoxia).2. Usage of bigyanids, pheformin therapy.3. Alcohol intoxication.4. Ketoacidosis (it is important to have a very high index of suspection with respect to presence of

LA).Pathogenesis. In a lactacidosis pathogenesis base is hypoxia. In causes of hypoxia are

activated an anaerobic way of glycolysis that is accompanied with accumulation of surplus of lactate. As a result of insulin deficiency is decresed an activity of pyrivate dehyrogenase, enzyme which promotes to the transformation of pyruvic acid into lactate, that intensifies the lactacidosis state. Simultaneously hypoxia causes is hindered resyntesis of lactate into glycogen.

During biguanids therapy a pathogenesis of hyperlactacidemia connects with disorder of passing of purivic acid through membranes of mitochondrions and acceleration of transformation of pyrivate into lactate.

As a result of anaerobic glycolysis in tissues is formed a many lactic acid which passes into blood. From blood a lactic acid passes into liver, where it is used for the glycogen formation, but a lactate formation exceeds possibilities for its using by liver for glycogen syntesis.Clinical picture of lactacidosis is characterized with appetite loss, vomit, muscular debility and pains during phisial load; sometimea with retrosternal pain and hurried breathing. In neurological status it must be noted an apathy, sleepness or excitation with insomnia. The leads syndrome is a progressive cardiovascular insufficiency. It connect with acidosis, but not with hydration. But the more oftenest a lactatacidemic coma develops very fast, during some hours. An excessive metabolic lactacidosis acidosis showes as a syndrome, which accompaning with sleeping, delurium, dehydration, hypotermia, hypotony, the Kussmaul respirastion, oligo- and then anuria with following consciousness loss (owing to hypotony and hypoxia of brain). Clinical presentation.Signs and symptoms.1. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the

metabolic acidosis and is obvious when the pH is less than 7.2.2. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude.3. Anorexia, nausea, vomiting, and abdominal pain may be present.4. Myalgia is common. Physical examination.

1. Acrocyanosis is common.2. Tachycardia frequently is present, blood pressure is decreased.3. Poor skin tugor and dry skin may be prominent.4. Hypothermia is common in LA.5. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis.4. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular

disease) may be evident.Laboratory findings.1. Blood glucose level is not high2. Glucosurea is absent.3. Blood lactic acid is high.For a laboratory criterions of diagnosis are concerned:

1. Increasing of the blood lactic acid level (higher of 1,5 mmole/l);2. Decreasing of the blood bicarbonates (index is lower 50 %);3. Moderative hyperglycemia (12-14 mmole/l) or normal glycemia during general hurd

condition of the patient;4. Acetonuria absence;5. Glucosuria rate depends on the functional renal state.

Algorhythm of treatment of patient in lactacidic coma. Diagnosis was defined in:1-hour:1. 2,5-4 % solution hydrocarbonate 400 ml, 1% solution of methylene blue (2,5 mg/kg of

body weight) i/v using of dropping infusion method;2. 5 % solution of glucose – 300 ml, usual insulin 6-8 UN (during normoglycemia,

hyperglycemia the insulin dose is increased – 0,5 UN per every 0,5 mmole/l which are higher 8 mmole/l), cocarboxylase – 100 mg, 5 solution of corglycon 0,5 ml or 0,025 % solution of strofantine 0,5 ml intravenous lyusing of dropper. Cordiamine 25 % solution – 1-2 ml intramusculare;

3. Hydrocortisone 250 mg or 100 mg of prednisolone i/v in boluces;4. Rheopolyglucinum – 20 ml i/v using of dropping method;5. Plasma – i/v using of dropper – 150-200 ml;6. 5 % solution of unithyile – 10 ml i/v (1-2 ml/kg of body weight);7. Oxygenotherapy, care for oral cavity, gastric lavage, catheterization of urinary bladder

antibiotic therapy.2-hour:1. 4 % solution of sodium hydrocarbonate 250 ml, 1 % solution of methylene blue (2,5-5

mg/kg of body weight) i/v dropping;2. 5 % solution of glucose 250 ml, usual insulininsulin 4-6 UN i/v dropping method;3. Hydrocortisone 75-100 mg (i/v, during lower arterial pressure – i/v).4. Oxygenotherapy.3-hour and further still recovery from the comatous state.It is continuing i/v dropping infusion of sodium hydrocarbonate, usual insulin over 4-6 UN

i/m per 2-3 hours or i/v dropping with 5 % solution of glucose – 250-300 ml, cardiotonic, vascular preparations, glucocorticoids (over indications), unithyole, oxygenotherapy.

During infusion of sodium hydrocarbonate it is necessary to fulfil monitoring of ECG, CVP, blood pottassium level. The sodium hydrocarbonate infusion is contindicated during myocardial infarction, cardiovascular insufficiency (owing to the sodium ions presence in solution which increase the liquid retention). In such causes is using a trisaminol. It is infused i/v as a 3,66 % solution 500 ml/hour (120 drops per minute); the maximal dose of preparation doesn’t exceed 1,5 g/kg per day. There are data about successful treatment of lactacidosis using of dichloracetanum which activates the pyrivate dehydrogenase, owing to this is increasing the lactate transformation into pyrivate.

For stimulation aerobic glycolysis it is advisable to infuse with glucose as usual insulin (8 UN per 500 ml of 5 % glucose solution).

As expelled prescription of preparations, which make the tissues respiration worse: barbiturates, salicylates, sulfanilamids, antihistaminic preparations, tetracycline and lithium.

References:Main literature

1. Endocrinology. Textbook/Study Guide for the Practical Classes. Ed. By Petro M. Bodnar: - Vinnytsya: Nova Knyha Publishers, 2008.-496 p.

2. Basіc & Clіnіcal Endocrіnology. Seventh edіtіon. Edіted by Francіs S. Greenspan, Davіd G. Gardner. – Mc Grew – Hіll Companіes, USA, 2004. – 976p.

3. Harrison‘s Endocrinology. Edited J.Larry Jameson. Mc Grew – Hill, USA,2006. – 563p.4. Endocrinology. 6th edition by Mac Hadley, Jon E. Levine Benjamin Cummings.2006. –

608p.5. Oxford Handbook of Endocrinology and Diabetes. Edited by Helen E. Turner, John A. H.

Wass. Oxford, University press,2006. – 1005p.Additional literature

6. Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC Graw-Hill Book, 1985. - P. 232-236.

7. Іnternatіonal Textbook of Dіabetes Mellіtus (Ed by R.A. Defronzo, E. Ferrannіnі, H. Keen, P. Zіmmet. John Wіley & Sons, Ltd. England, 2004. – Vol. 1 – 1100p., Vol. 2 – 1913p.

8. Joslіn’s Dіabetes Mellіtus. Selected Chapters from the 14-th ed. Edіted by C. Ronald Kahn, et al. Lіppіncott Wіllіams & Wіlkіns, USA, 2006. – 328p. Manual of Endocrinology and Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.- Boston-New York-Toronto-London, 1994. - P. 519-527, 561-574.

9. The diabetic foot. 2nd edition. Edited by A.Veves, J.M.Giurini, F.W. LoGerfo (ebs), Humana Press, Totowa, New Jersey,2006. – 224p.

Lecture prepared assistant, c.m.s. Chernobrova O.I. It is discussed and confirm on endocrinology department meeting " 31 " august 2012 y. Protocol № 1.