CM 6(1)

VIOLATION OF ENDOCRINE FUNCTION OF PANCREAS. DIABETES MELLITUS.

PATHOPHYSIOLOGY OF HYPOPHYSIS AND SUPRARENAL GLANDS. PATHOPHYSIOLOGY OF THYROID AND PARATHYROID GLANDS.

PATHOPHYSIOLOGY OF NERVOUS SYSTEM

 

ROLE OF ENDOCRINE SYSTEM IN VITAL ACTIVITY OF THE ORGANISM

The endocrine system relates the most important regulatory systems. It carries out regulatory influence with the help of hormones practically on all functions of an organism – metabolism , growth, reproduction, mental activity, adaptation, functional activity of all organs.

Hormones can be synthesized:

·         by epithelial cells (one’s own glandular ephithelium );

·         by neuroendocrine cells (hypothalamic cells);

·         by myoendocrine cells (muscular fibres  of  heart atriums).

According to chemical nature they differentiate:

·         steroid hormones (mineral – and glucocorticoids, female and male sexual hormones);

·         derivatives of aminoacids (thyreoid hormones, catecholamines, melatonine);

·         protein peptide hormones (releasing-hormones, vasopressin, oxytocin, hormones of adenohypophysis, insuline,  glucagone, parathyrin, calcitonine).

According to functional effects hormones can be:

·        affectors (act directly on organs – targets);

·        tropic (regulate synthesis of effecting homones);

·        releasing–hormones (regulate synthesis and secretion of tropic hormones).

 

Etiology of endocrine disorders

Reasons and kinds of endocrine disorders. Among numerous ethiological factors of endocrine disorderss it is possible to select the following main ones: a mental trauma, necrosis, tumour, inflamatory process, bacterial and viral infections, intoxications, local disorders of blood circulation (hemorrhage, thrombosis), alimentary disorders (deficiency of iodine and cobalt in food and drinking water, redundant consumption of carbohydrates), ionising radiation, inherent chromosome and gene defects.

There are three variants of endocrine functions disorders :

1. Hyperfunction of endocrine glands

2.  Hypofunction of endocrine glands

3.  Disfunction of endocrine glands.

Disfunction is characterized by different changes of hormonal production and production physiologic active precursors of their biosynthesis in the same endocrine gland or synthesis and entering  in blood of atypical hormonal products.

 

Pathogenesis of endocrine disorders

The mechanisms of function disorders  of an endocrine gland can be various depending on localization and character of process.

In pathogenesis of endocrine disorders it is possible to select three main mechanisms:

1) Disorders of regulation of endocrine glands – disregulatory disorders;

2) Disorders of biosynthesis of hormones and their secretion – glandular disorders;

3) Disorders of the transport, reception and metabolism of hormones – peripheral disorders.

 

Diabetes mellitus

Major index which describes metabolism of carbohydrates, is a sugar level in blood. In healthy peoples it is 4,4-6,6 mmol/l.

This value is summary result of complicated interaction of many exogenous and endogenous influences. The first it reflects a balance between amount of glucose which arrive in blood and by amount of glucose which is utilized by cells.  The second,  glucose level in blood reflects an effect of simultaneous regulatory influence on carbohydrates metabolism of the nervous system and endocrine glands – front pituitary gland (somatotropic, thyreotropic, adrenocorticotropic hormones), adrenal cortex (adrenalin ,noradrenalin)layer, pancreas (insulin, glucagone, somatostatin), thyroid (thyroxin, triiodthyronine). Among enumerated hormones only insulin lowers glucose concentration in blood the rest of hormones  increase it.

Regulation of glucose metabolism

 

The glucose concentration in blood describes carbohydrates metabolism both of healthy man and sick. Illnesses base of which is disorder of carbohydrates metabolism can flow with rise of glucose concentration in blood and with lowering of it. Rise of glucose concentration is named hyperglicemia lowering hypoglicemia. For example, hyperglicemia is very typical for diabetes mellitus,hypoglycemia-  for glicogenosis.

Diabetes mellitus

Diabetes mellitus is heterogenic diseases group which arise on base of absolute or relative insulin insufficiency and have hyperglicemia as general symptom. Classification of diabetes mellitus up to nows remains clinical. Main types – insulin-dependent diabetes mellitus and insulin-independent diabetes mellitus. These two diabetes types affect the majority of patient.

There are counts six millions of patient with insulin-dependent diabetes mellitus in the world. This is mainly illness of white race. It occur more frequent in highly developed countries (Finland, Italy, Sweden, Denmark, Canada, Norway, USA, England). There are about 100 millions of patient with insulin-dependent diabetes mellitus. They consist 85 % of all diabetics. They belong to mainly native population of USA (american indians), Fiji, South Africa, India, Polynesia.

 

Insulin-dependent diabetes mellitus

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

Insulin-dependent diabetes mellitus has genetic base. Inclination to diabetes of this type is conditioned by some genes of major histocompatibility complex (MHC). The system of HLA genes is situated on small extent of short shoulder of 6 chromosome. Here are identified several locuses – A, B, C and area D which includes three locuses – DP,  DQ and DR. High probability of insulin-depending diabetes mellitus is to area D and nominally  with locuses DR. Genes DR3 and DR4 are diabetogenic. The very high risk of illness is created in those person who have both gene – DR3 and DR4. Inclination to insulin-depending diabetes is associated also with locus DQ (genes DQ2 and DQ8).

Diabetes arises only in part of person with diabetogenic genes. For example, alleles DR3 and DR4 occur in 50-60 % healthy person of european race, and illness develops only in 0,25 %. Inheritance of insulin-depending diabetes is conditioned, presumably, by not one gene, but by group of kindred genes.

Where in essence of genetic defect in peoples with genes DR3, DR4, DQ2, DQ8?  Exact answer on these questions while is not found. Think, that the enumerated genes in lone or in combinations form a low resistibility of β-cells of pancreas to external dominances. β–cells of such faces lightly collapse and very difficult restore. High readiness to destruction combines in them by limited capacity for regeneration. The system of HLA genes are inherited from generation to generation, therefore inclination of β-cells to destruction also is inherited from generation to generation. However general amount of β-cells is attached to birth identically in patients and healthy.

Typical affection of Langergans islets attached to insulin-depending diabetes is infiltration of them by lymphocytes and selective destruction of β-cells. Clinical illness picture develops when 80-95% of β-cells are already destroyed.

In such patients mass of pancreas is less, than in healthy people. Amount and volume of Langergans islets also is less. Thus insulin-depending diabetes is result of equilibrium violation between destruction of β-cells and their regeneration. Both process – increase of destruction and limitation of regeneration – are genetically conditioned.

Depending upon affection mechanism of β-cells there are two forms of insulin-depending diabetes mellitus – autoimmune and virus-inductive.

Autoimmune insulin-dependent diabetes arises in persons with genome DR3. It is associated with other autoimmune endocrinopathies, for example, with illnesses of thyroid gland (autoimmune thyreoiditis, diffuse toxic goiter), adrenal gland (Addison’s disease). This diabetes type develops in any age more frequent in women. Autoimmune is diabetes described by presence in blood of patient autoantibodies against of Langergans islets.

Virus-induced insulin-dependent diabetes mellitus binded with genome DR4 and different from autoimmune on mechanisms of development. In this case there are no autoantibodies against islets of pancreas. They certainly can appear in blood but rapidly (pending of year) disappear. They do not perform essential role in pathogenesis of illness. Development of this diabetes type frequently precede the viral infections   epidemic parotitis, german measles, measles, viral hepatitis.

Pathogenic viruses action is not specific. It consists in development of inflammatory process in Langergans islets. Insulitis arises. Lymptoid infiltration of damaged islets develops at first after then destruction. Sometimes the specific (immune) destruction mechanisms of β-cells are linked. The viruses pervert antigen membranes properties of affected β-cells and are followed with attack of autoimmune mechanisms.

There is one more possibility. Membrane β-cells is lightly damaged by much chemical substances even in insignificant concentrations. Such substances are called β-cytotoxic. They are, for example, alloxane and streptosocine. They create a favourable background for immediate viruses action on membrane of β-cells.

Virus-induced diabetes arises early before 30 years of life. It is identically widespread and among males, both among women.

Pathogenesis of insulin-dependent diabetes mellitus

 

Insulin – independent  diabetes  mellitus

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

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

Genetic factors determine hereditary liability to disease. Specific genetic marker (special diabetogenic gene) is not found. It is known only, that inclination to insulin-independent diabetes is not coupled with major complex of histocompatibility.

Function of β-cells of patient with insulin-independent diabetes is violated. Amount of them is diminished. Attached to loading by glucose they do not multiply insulin secretion in necessary amount. Diabetologist  bind up these violations with amyloidosis of Langergans islets.

Insulin-resistance arises or on genetic base or as result of influence of external factors (risk factors). Biological insulin action is mediated over receptors. They are localized on cells-targets membranes (myocytes, lypocytes). Interaction of insulin and receptor is followed with changes of physical state of cells-targets membrane.  As result of this transport system is activated, which carries glucose over cellular membrane. Transmembrane moving of glucose is provided by proteins-transmitters.

 

Pathogenesis  of  insulin-independent  diabetes  mellitus

Amount of glucose carried in cell depends on closeness of insulin receptors on membrane and on receptor affinity to insulin. These parameters depend on insulin level in blood. Hyperinsulinemia diminishes amount of receptors and their affinity to insulin. Hypoinsulinemia on the contrary multiplies amount of receptors and their affinity to insulin.

Some external factors provoke insulin-resistance and development of insulin-independent diabetes. Among these factors in first place belongs to surfeiting and obesity. Mechanisms of insulin-resistance attached to obesity following: iminution of amount of insulin receptors on cells-targets, slowing down of glucose transport over membrane, disorder of intracellular metabolism of glucose.

Chronic resistance of insulin receptors causes a chronic hyperfunction of β-cells and surplus production of insulin. This in turn raises receptor resistance.  Thus arises a vicious circle. Protracted loading of β-cells conduces to exhaustion of their functions.

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

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

Other types of diabetes mellitus

This is large geterogeneous group of illnesses with hyperglycemia. Mains it’s causes following:

·        illnesses of pancreas   innate lack of Langergans islets, trauma and infections, tumor, kystose fibrosis;

·        illnesses of hormonal nature pheochromocytoma, glucagonoma, acromegaly, Itsenko-Cushing illness, thyretoxicosis;

·        medicines and chemical agents – glucocorticoids, thyreoid hormones, diuretics, analgetics and other remedies;

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

·        hereditary syndromes Down’s, Turner’s, Klinefelter’s.

 

symptoms of diabetes mellitus

Major symptoms are hyperglycemia, glucosuria and polyuria.

Hyperglucemia is connected, foremost with lowering of glucose utilization by muscular and fatty tissues. Lowering of glucose utilization has membranogenic nature. In case of insulinopenia and in case of insulin-resistance nteraction of insulin and receptor is damaged. Therefore protein-transporters of glucose are not included in membranes of cells-targets. This limits glucose penetration in cells. It is use on power needs (in myocytes) diminishes. Lypogenesis is slowed-glucose deposit in fats form (in lypocytes). Glycogenesis slows- synthesis of glycogene (in hepatocytes and myocytes).

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

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

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

Complication of diabetes mellitus

The very frequent diabetes complications are following: ketoacidosis, macroangiopathy, microangiopathy, neuropathy.

Ketoacidosis. In healthy peoples synthesis of ketone bodies in liver is strictly controled. Main regulatory mechanism is access limitation of fat acids in mytochondries of hepatocytes. Over head permissible concentration limit of ketone bodies in blood is approximately 0,1 mmol/l. In case of exceeding this level regulatory mechanisms are stated. Foremost ketone bodies put specific receptors back up on membrane β-cells of Langergan’s islets. Insulin excretion in blood increases. Insulin stimulates resynthesis of fat acids. First stage of resynthesis is derivation if malonil–КоА. Surplus amount of malonil–КоА oppresses penetration of fat acids in mytochondries. Synthesis of ketone bodies slows.

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

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

Macroangiopathy. Macroangiopathy is vessels atherosclerosis of cerebrum, heart, kidneys, legs. Diabetes hastens atherosclerosis development. There are three acceleration way of atherogenesis in patients with diabetes. In conditions of insulin insufficiency growth hormone synthesis increases. Here upon proliferation of smooth myocites accelerates key stage of atherogenesis.

Microangipathy develop in shallow vessels – arterials, venues, capillaries. Two process form their pathogenic base – thicking of basal membrane and reproduction endothelium. Direct cause of microangiopathy is hyperglycemia and synthesis of glycoproteids in basal membrane. There are two main clinical forms microangipathy : diabetic retinopathy and diabetic nephropathy.

Diabetic retinopathy                                    Diabetic nephropathy

 

Neuropathy manifest by violation of nerves function sensible, motor, vegetative. Essence of these violations is demyelinisation of nervous fibres, decreasing of axoplasmatic flow.

 

PATHOPHYSIOLOGY OF  HYPOPHYSIS AND SUPRARENAL GLANDS

Hypofunction of adenohypophysis (hypopituitaritism)

There are  panhypopituitarity and partial hypopituitariti.

Panhypopituitarity – is the decrease of formation of  all adenohypophysis hormones. The following clinical forms of  panhypopituitarity are known:

1) Hypophysar cachecsia of Simonds;

2) Afterbearing necrosis of hypophysis – syndrome of Schegan;

3) Chromophobe hypophysis adenomas, i.e. tumors, which grow from chromophobe cells. For want of it the tumour squeezes and damages glandular cells  of adenohypophysis.

The clinical manifestations of panhypopituitarity are connected with deficiency of adenohypophysis hormones and disorders of activity of peripheral endocrine glands (thyroid gland, cortex of adrenal, sexual glands). The first symptoms of lesion of adenohypophysis occur in damage of 70-75 % of  gland tissue, and for development of complete picture of panhypopituitarity destruction of 90-95 %  of adenohypophysis is necessary. Vessels disorders in hypophysis and hypothalamus (most frequently afterbearing longtime spasm of vessels of brain and hypophysis owing of haemorrhage), trauma of the skull basis, tumour of hypophysis and hypothalamus, inflammatory damage (tuberculosis,sepsis) of hypophysis, inherent aplasia and hypoplasia can lead to development of panhypopituitarity. The most frequently gonadotropic function of hypophysis and secretion of STH is damaged with the consequent connection of nonsufficient secretion of ТТH, ACTH and prolactine.

Partial hypopituitarity is the disorder of formation of separate hormones of  adenohypophysis (not all). The following variants of partial hypopituitarity are described:

1) Hypophysar nanism (dwarfishness) – deficiency of STH;

2) Secondary hypohonadism – deficiency of FSH and LH;

3) Secondary hypothyrosis – deficiency of TTH;

4) Secondary hypocorticism – deficiency of ACTH.

The insufficiency of STH results to development of hypophysar dwarfishness, or nanism and appears by such disorders:

1) decrease of intensity of protein synthesis that leads to delay and stop of growth (more than 30 % from average) and development of bones, internal organs, muscles. The disorders of protein synthesis in connective tissue results in loss of its elasticity;

2) decrease of inhibiting action of STH on an absorption of glucose with predominance of insulinic effect and development of hypoglycemia;

3) fallout of fat mobilizing action and tendency to obesity.

Nanism

 

The insufficiency of ACTH leads to secondary partial insufficiency of adrenal cortex. The glucocorticoid function suffers mainly. Mineralocorticoid function practically does not vary.

Insufficiency of TTH causes secondary decrease function of thyroid gland and development of secondary hypothyrosis symptoms. As against in case of primary hypofunction of thyroid gland the introduction of TTH can restore its function.

Insufficiency of gonadotropic hormones results in decrease of ability of Sertoli cells to accumulate androgens and oppression of spermatogenesis and ability to impregnation in men. In case of defect of LG hormone the function of Leidig’s cells is infringed, the formation of androgens ceases and develops eunuchoidism with preservation of partial ability to impregnation, as the process  of spermatozoids maturing does not stop.

 

Hyperfunction of adenohypophysis (hyperpituitarism)

The main reasons of hyperpituitarism development are the benign tumours – adenomas of endocrine cells.

There are  two groups of adenomas.

1. Eosinofilic adenoma, develops from acidophilic cells of adenohypophysis forming STH. Clinically hyperproduction of STH appears by giantism (if adenoma develops in children and young people before closing of epiphysar cartilages) and acromegalia (in adult).  Giantism is characterized by the proportional increase of all body components.

Acromegalia appears by increased growth of hands, legs, chin, nose, tongue, liver, kyphoscoliosis.

Acromegalia

 

Besides that  increased metabolic activity of STH –hyperglycemia, insulin resistanse, even to development of metahypophysar diabetes, fatty infiltration of  liver develop.

2. Basophilic adenoma, grows from basophilic cells of adenohypophysis which more often produce ACTH. During this the Itsenko-Cushing disease develops. It is characterized by: а) secondary hypercorticism; b) strengthened pigmentation of skin. There are tumors which produce other hormones of adenohypophysis less often: TTH, gonadotropic hormones, prolactin, MSH.

The increased level of ACTH during this disease is combined with increase of  level of other products of proopiomelanocortin.

 

Hyperfunction of neurohypophysis

Leads to redundant production vasopressin and oxytocin.

Their main effects:

Vasopressin (antidiuretic hormone) renders the following influence through V₁ and V₂ receptors:

1) Acting on tubulus contortus distalis and collective tubules of kidneys, strengthens reabsorption of water;

2) Causes contraction of smooth muscles of blood vessels;

3) Strengthens glycogenolysis and gluconeogenesis in liver;              

4) Stimulates consolidation of memory traces and mobilization of  saved information (hormone of memory);

5) Endogenic analgetic (depresses pain).

Oxytocin renders the following functional influences:

1) Stimulates secretion of milk (lactation) causing contraction of myoepithelial cells of small-sized ducts of mammary glands;

2) Initiates and strengthens contractions of uterus of pregnant woman;

3) Worsens storing and mobilization of information (amnestic hormone).

Redundant secretion of vasopressin arises in tumors of different tissues forming vasopressin, and also in disorders of hypothalamic endocrine function regulation. Its main manifestation is hypervolemia leading to development of constant arterial hypertension.

 

Hypofunction of neurohypophysis

Insufficient production of vasopressin results to development of diabetes insipidus. There are two  pathogenetic variants: central (neurogenic) during which will a little quantity of vasopressin, is formed and nephrogenic during which the sensitivity of epithelial cells receptors of distal nephron parts and collective tubules to vasopressin action (absence or a little quantity receptors) is reduced. The decreasing of water reabsorption in kidneys results to poliuria and decreasing of circulatting blood volume  (hypovolemia), falling  of arterial pressure and hypoxia.

The decreasing of oxitocin production appears by disorders of lactation, weakness of labor activity.

 

Disorders of adrenal gland function

The most frequently there are following manifestations:

1) Hypofunction of adrenal cortex – hypocorticism

2) Hyperfunction of fascicular zone – syndrome of Itsenko-Kushing

3) Hyperfunction of glomerulose zone – hyperaldosteronism

4) Dysfunction of adrenal cortex – adrenogenital syndrome

 

Insufficiency of adrenal cortex

According to etiology there are  primary and secondary kinds of adrenal cortex insufficiency. Primary insufficiency arises as a result of adrenals injury, secondary is connected with the defeat of hypotalamus (deficiency of corticoliberin), or with hypofunction of adenohypophysis (deficiency of ACTH). Insufficiency of corticosteroids can be total when the operation of all hormones drops out, and partial fallout of activity of one adrenal hormone. Insufficiency of adrenal cortex can be acute and chronic.

Examples of acute insufficiency are:

а) state after removal of adrenals;                

b) hemorrhage in adrenals which arises during sepsis, meningococci infection (syndrome Waterhouse-Friderixan);

c) syndrome of cancellation of glucocorticoides preparations.

 Fast falling of the adrenals function causes development of collaps and the patients can die during the first day.

The chronic insufficiency of adrenals cortex is characterized for Adison’s disease (bronzed disease). The most often reasons of it are: а) tuberculose destruction of adrenals; b) autoimmune process.

І. Manifestation, connected with the falling of mineralocorticoids functions of adrenal cortex:

1) dehydration develops owing to loss of sodium ions (decreases rearbsortion) with the  loss of water (poliuria);

2) arterial hypotension is stipulated by decrease of circulating blood volume;

3) hemoconcentration (condensation of blood) is connected with liquid loss, results to disorders of microcirculation and hypoxia;

4) decreasing of kidney blood circulation is stipulated by increase of arterial pressure with disturbances of glomerular filtration and development of intoxication (nitrogenemia);

5) hyperpotassiumemia is stipulated by decrease of canales secretion of  potassium ions and their output  from the damaged cells. It causes disorders of  function of arousing tissues;

6) distal canales acidosis. It is connected with disorders of acidogenesis in distal nephron canales;

7) gastro-intestinal disorders (nausea,vomiting, diarrhea).

Loss of sodium (osmotic diarrhea) and intoxication have significant meaning. This disorders without appropriate correction result to death.

ІІ. Manifestations stipulated by disorders of glucocorticoid function of adrenals. To such manifestations concern:

1) hypoglycemia which results to starvation;            

2) arterial hypotension (permissive reaction on catecholamines);

3) decrease reaction of fat tissue on lipotropic stimules;

4) decrease resistance of an organism on action of different pathogenic factors;

5) decrease of ability to remove water during water load (water poisoning);

6) muscular weakness and fast tiredness;

7) emotional disorders (depression);

8) delay of growth and development of children;

 9) sensor disorders – loss of ability to distinguish separate shades gustatory osmetic acoustical sensations;

10) distress-syndrome of a newborn (hyalinic membranosis). It is stipulated by disorders  of surfactant formation in lungs owing to what lungs are not straightened after birth  of a child.

 

Increase of adrenals cortex function

 Hyperaldosteronism. Arises during hyperfunction of glomerular zone  of adrenals cortex, which produce mineralcorticoides.

There are primary and secondary hyperaldosteronism.

 Primary hyperaldosteronism (Conn syndrome) arises in adenoma of  zone glomerular, which secretes high quantity of aldosteron. Main manifestations of this disease:

1) arterial hypertension. It is connected with increase of sodium  contents  in blood and in wall of blood  vessels, after what  the sensitivity of their smooth muscles to action of pressore factors,  particularly cathecholamines increases. 

2) hypopotassiumaemia (result of hypersecretion  of potassium ions in canals of kidneys). It causes  disorders of arousing organs  and tissues (disorders of heart activity, miostenia, pareses);

3) ungas alcalosis. It is connected with amplification of acidogenesis in distall nephron canaliculas;

4) polyuria  arises as a consequence  sensitivity of kineys canales epithelium loss to action of vasopressin. It explains absence of volume increase of circulatting blood and edema.

Secondary hyperaldosteronism is a result of renin-angiotensin  system activation. This state appears by:

a) arterial hypertension;

b) aedemas;                                   

c) hypopotassiumaemia;

d) ungas alcalosis.

 

There are two clinical forms of hypercorticism with hyperproduction of glucocorticoides:

1. Cushing’s disease – basophil adenoma of anterior hypophysis part.

2. Cushing’s syndrome:

·        tumoral – adenoma of zona fasticulata of adrenal cortex;

·        ectopic production of АCТH by some malignant tumors (pulmonar cancer);      

·        iatrogenic – introduction of glucocorticoides in an organism with the medical purpose.

Glucocorticoid hypercorticism appears by:

1) arterial hypertension

2) hyperglycaemia – metasteroid diabetes mellitus

3) obesity

4) development of infectious diseases without signs of an inflammation

5) gastric hypersecretion and formation of ulcers in stomach and duodenum

6) osteoporosis

7) muscular weakness

8) slow  of wounds healing

Cushing’s syndrome

 

Adrenogenital  syndrome results from the hereditary stipulated blockade of cortisole synthesis  and amplified formation of androgens from general intermediate products.

Depending on the  level of blockade of cortisole  synthesis there are   three variants of adrogenital syndrome.

І. Disorders of early stages of synthesis – deficiency of glucocorticoides, mineralcorticoides and androgens hyperproduction. Manifestations: signs of insufficiency of gluco- and mineralocorticoidal functions of adrenal cortex features of early sexual maturing in  males, virilization in women (appearance of man’s sexual features).

ІІ. Disorders of intermediate stages – deficiency of glucocorticoides, surplus of androgens,  formation of mineralocorticoides is not infringed (classical androgenic syndrome). Manifestations are the same, as in the first case, only without signs of insufficiency of mineralocorticoidal function.

ІІІ. Disorders at final stages of cortirol synthesis – deficiency of glucocorticoides, hyperproduction of androgens and mineralocorticoide.  Features of hyperaldosteronism are connected with manifestations of classical androgenital syndrome.

 

Disorders of adrenal medulla function

Hypofunction of adrenal medulla  happens seldom because of the fact that these functions can be accepted  by other chromaphine cell.

Hyperfunction of adrenal medulla  arises during tumors of chromaphine cells – pheochromocytome. Appears by arterial hypertension, tachycardia, extrasystole, flatering of atriums, hyperglycaemia, hyperlipidaemia, hyperthermia.  Development of moderately expressed diabetus, thyreotoxicosis is possible. In time of paroxizm  vertigo, headache, hallucinations, increased excitability of the nervous system, cramps appear.

 

Pathophysiology of thyroid and

parathyroid glands

Regulation of formation, biosynthesis, secretion of thyroid hormones, their disorders

In thyroid gland three thyroid hormones are formed – thyroxin (Т₄), triiodthyronin (Т₃) and pararfollicular C-cells synthesize calcitonin which participates in regulation of phosphor-calcium metabolism. Thyroxin and triiodthyronin make metabolic action. In this case Т₃ is more active than T₄ in five times. During deposition in peripheral tissues Т₄ can turn in Т₃.

Regulation of formation and secretion of thyroid hormones is carried out by the system of hypothalamus–adenohypophysis under the following scheme: hypothalamus → thyroliberin → adenohypophysis → thyrotropic hormon (ТТH) → thyroid gland.

The biosynthesis of thyroid hormones is carried out in four stages: а) inclusion of iodine into thyroid gland. Iodine is absorbed in intestine in the form of iodides, then there is a capture and concentration of it in thyrocytes. The transport of iodides is carried out actively against a gradient of concentration with the help of specific transport protein with an expense of ATP energy; b) the inclusion of iodine into  organic compaunds occurs after oxidation by iodineperoxydase and hydrogen peroxide into the membrane of thyrocyte up to the active form, in which it is fixed in a molecule of tyrosine with derivation of monoiodtyrosine (MIT) and diiodtyrosine (DIT); c) condensation on membranes of apical part of thyrocyte Т₃ and Т₄ by junction of two molecules of iodided tyrosines (MIT + DIT – in the first case and DIT + DIT – in second); d) liberation of thyroid hormones from thyrocytes is carried out in such sequence: TTH → it connects with thyrocytes’ receptors → activation of adenilatcyclase → derivation of cAMP → activation of proteolytic enzymes → proteolysis of thyroglobulin in the thyrocytes → put out of Т₄ and Т₃ in perifollicular space → their penetration through capillary wall into the blood. Monoiodthyronin and diiodthyronin are deponed, and iodides are reused for synthesis of hormones.

 

In blood circulatory system thyroid hormones are transported as complexes with proteins: а) thyroxin–connecting globulin will derivate stable connection with hormon and thus creates a reserve of thyroid hormons; b) thyroxin-connecting prealbumine and thyroxin-connecting albumin will derivate a labil fraction of thyroid hormones.

 

Mechanisms of action and biological effects of the thyroid hormones

Thyroid hormonees are hormones with intracellular type of cytoreception. Three intracellular targets are known for their action: plasmatic membrane, mitochondria, nucleus.

On plasmatic membrane sensitive to thyroid hormonees cells there are sites of binding triiodthyronin (Т₃).

In mitochondria Т₃ contacts with enzymes of internal membrane – translocase of adenil nucleotides – and activates it. The concentration of ADP in this time increases in mitochondria which causes strengthening of biological oxydation intensity.

The nucleus is main intracellular target for Т₃ which determines long-term effects of thyroid hormones. During binding of  T₃ (in smaller measure Т₄) with nuclear receptors there is an induction of transcription and synthesis of many functionally important proteins. Among them are:

а) Na–К–ATPase of plasmatic membranes;

b) Enzymes of lipogenesis (in particular NADP–malatdehydrogenase);

c) Enzymes of mitochondria (α–glycerophosphatedehydrogenase);

d) Protein component of β–adrenoreceptors.

All biological effects of thyroid hormones on cells one can divide into three groups:

1.     Anabolic action – influence on– growth and differentiation of tissues.

2.     Metabolic effects – increase of catabolic processes intensity (oxidation, lipolysis).

3.     Sensibilizing effects – increase of cell sensitivity to action of other hormonees, in particular estrogens and catecholamines.

4.      

 

Disturbances of thyroid functions. Hyperthyrosis

Hyperfunction of thyroid gland is designated by the term “thyrotoxicosis” or “hyperthyrosis”.

The reasons of hyperthyrosis can be the following:

1. Central disturbances – increase of thyroliberin and thyrotropic hormone   (ТТH) secretion.

2. Strictly glandular disturbances (primary hyperthyrosis). The most widespread clinical forms of primary hyperthyrosis are:

а) Diffuse toxic goiter (Bazed’s disease, Graves’ disease, Parri’s disease);

b) Toxic adenoma of thyroid gland;

c) Nodular goiter.

The most often reason of development hyperthyrosis is diffuse toxic goiter.

Consider that diffuse toxic goiter is autoimmune disease, in which occurrence matter are thyroid-stimulating antibodies which like ТТH are capable to contact with receptors on basal membrane of thyrocyte, that results in cell activation.

3. Peripheral disorders :

а) Increase of cell sensitivity to action of Т₃ and Т₄;

b) Decrease of binding of thyroid hormonees by transport proteins;

c) Decrease  of thyroid hormonees’ metabolism in liver in its insufficiency.

 

The starting mechanism of diffuse toxic goiter occurrence  in patients with hereditary defect of immune system can be psychoemotional stress or virus which is forming in thyrocyte membrane complex, on which the antibodies will be derivated.

Main manifestations of diffuse toxic goiter:

а) goiter (increase of thyroid gland);

Goiter

 

b) Tachycardia, arrhythmia, cardiac insufficiency;

c) increase of basic metabolism more than 10 %;

d) increase of temperature;

e) weigth loss;

f) muscular weakness;      

g) exophtalmus;

Exophtalmus

 

h) disorders of nervous system –– irritability, instability of mood, inconsistency of acts, tremor.

 

In pathogenesis of hyperthyrosis manifestations the following mechanisms are important:

1. Anabolic effects. They are high-dose effects of thyroid hormones. They are:

а) delay of growth;

b) atrophy of muscles and weakness;

c) weight loss;

d) negative nitrogen balance;

e) increase of nitrogen  leading out, phosphorum, potassium, ammonia;

f) increase in blood of residual nitrogen and nitrogen-containing aminoacids.

2. Strengthening heat-forming action of thyroid hormonees. It appears:

a) by increase of basic metabolism;    

b) by increase heat formation and increase of body temperature;

c) by good adaptation to cold and bad – to high temperature;

d) hyperphagia – increased consumption of energy.

 

Triiodthyronine separates oxidation and phosphorilation in cell mitochondria, therefore the energy of oxidation of NADPH₂ is not accumulated in ATP. The decrease of ATP synthesis increases concentration of  its precursors – organic phosphate. The carry of ADP in mitochondria is changed also, as Т₃ contacts to a carrier of ADP tarnslocase that in turn strengthens oxidizing processes and by that dispersion of energy, causing increase of basic metabolism.

3. Increase of functional activity of excitable tissues. It is connected with  increase of activity of Na-K–pumps in cell membranes and increase of cell sensitivity to catecholamines.

It stipulates the following manifestations of hyperthyrosis:

a) disorders of activity of central nervous system – acceleration of mental processes, anxiety, excitation, insomnia;

b) constant spontaneous contractive activity of skeletal muscles – fibrillar twitching, tremor. It is connected with muscular weakness, tiredness;

c) Changes of activity the increase of heart minute volume, arterial pressure in cardiovascular system – tachycardia;

d) Increase contractive activity of smooth intestinal muscles – diarrhea;

e) Increase of absorbtive and excretive processes intensity. It is connected with hyperglycemia and hypocholesterinemia.

4.Catecholamine effects are stipulated by increase of cells sensitivity  to action of catecholamins.

In clinic of hyperthyreosis the greatest significance have the functional effects of  catecholamins, in particular, their influence on heart – vassel system and metabolic changes.

In tissue the utilization of glucose is increased. There is activated phosphorylase of  liver and muscles, therefore glucogenolis amplifies and there is no glycogen in  these tissue. Increase  activity of hexokinase and glucose  absorbtion in intestines, is accompanied with alimentary hyperglicaemia.

5. Disturbance with unstablished mechanisms of development – orbitopathy and two-sided exophtalm. It is supposed, that in conditions of hyperthyreosis is allocated special exophtalmic factor, however it is not revealed till now .

Thyreotoxic adenoma of thyroid gland functions autonomously and produces surplus of thyroid hormones irrespective of ТТH. Nodal toxic goiter is characterized by absence of changes on the part of orbits an eye and mixedema.

 

Hypothyrosis

In a basis of  hypofunction of thyroid gland the following reasons can be.

  1. Central disorders: decrease of formation both secretion of thyreoliberine and thyreotropic hormone (ТТH).

         2. Gland disorders , which result in development primary hypothyrosis:

         a) destruction of a gland tissue, for example, radioactive iod;

         b) deficiency  of iod drinking water and food – endemic goiter;

         c) autoimmune damage of gland cells – autoimmune thyroiditis of Chaschimoto;

         d) inherent disorders – hypo- and aplasia of thyroid gland, enzymopathy.

  3. Peripheral disorders:

  а) nonsensitivity of peripheral cells for action of thyroid hormones;

  b) increased binding of thyroid hormones with  plasma proteins of blood;  

  c) strengthened metabolism in  liver.

 

In development of manifestations of hypothyrosis  the following mechanisms.

1. Disturbances of growth and defferenciation of tissue.

Thyroid hormonees a necessary for normal process of  enchondrial ossification on boundary between diaphysis and epiphysis, in conditions of hypothyreosis the growth of bones in length is decreased. For want of it periostal growth of bones is saved, in this connection they become thick. The complex of changes of a skeleton – hyperthyroid dwarfism develops. Along side with it the mental development – gradually is developed also arises cretinism.

2. The decrease heat formation of action thyroid hormones, which appears:         

а) decrease of base metabolism (falling on 20-40 of %);

b) by decrease of  heat production, in this connection temperature falls;

c) bad adaptation to a cold for want of preservation of adaptation to high temperature.

3. Decrease of functional activity of exitated tissues.

This is connected with falling of activity Nа–К–АТPаs and changes of processes of ions active transport. Besides that decrease sensitivity of tissues to catecholamins, has significance that is stipulated by decrease of an amount β-adrenoreceptors on cells. The functional changes of exitated organs and tissues are:

а) disorders  of the central nervous system activity – decrease of mental activity, slackness, lethargy,sleepiness  etc.;

b) decrease of functional activity of skeletal muscles – weakness, decrease tone, fast tiredness;

c) by disorders of  heart activity – vessel system – bradycardia, decrease of  heart minute volume, decrease of arterial pressure;

d) decrease of contraction of the  of smooth muscles function of intestines – constipation;

e) disturbance of processes absorbtion and excretion. The decrease glucose absorbtion in intestin couse hypoglycemia and disorders of excretion of cholesterine in structure of bile to  hypocholesterinemia and hereinafter to atherosclerosis.

4. Disturbances with the unknown mechanisms of development. They are mucous edema – mixedema. This is characterized by increasing tissues the quantity glycosaminglycans, connecting water; by a thickening of a skin, puffy face. It is admited mixedema is consiquence of action thyrotropic hormone on connective tissue, amount it is increased on glandular and peripheral forms of hypothyrosis vitally increase.

 

 

The forms of manifestation of thyroid gland hypofunction  depend on age.

1. Cretinism – arises because of insufficiency of thyroid gland, which arises in embrional or early postnatal period. The main reasons are:

а) inherent athyrosis;       

b) introduction of antithyroid preparations of the pregnant woman;

c) hereditary defects of thyroid hormones synthesis .

Characteristic signs of cretinism are:

a) dwarfism;

b) mental undedevelopment (imbecility);

c) infantilism;

d) a combination of different defects – surdomutism, short neck, low front , thick lips, plane nose, languid muscles, large stomach, rare hair, caries of teeth, clumsy gait, enuresis.

2. Child mixedema. Arises for want of to loss of thyroid gland function in children’s age. The main reasons –thyroiditis , tuberculosis, hypopituitarism.

Characteristic signs of a child mixedema are:

а) delay of growth, natural and mental development;

b) lethargy;

c) bad appetite;

d) pale and yellow skin;                

e) hypercholesteremia;

f) delay occification of bones and cartilages.

Child mixedema you may treat by thyroid hormones.

3. Mixedema of the adults. Characteristic signs:

а) pale, dry and thick skin;         

b) mucous edema;

c) thick nose, thick lips, drooped  cheek;

d) edematic face;               

e) increased language;

f) slow speech, hoarse voice;

g) blunt look,  poor  mimic;           

k) lethargy , sleepiness;

l) mental disturbance – loss of memory, stupidity, absence of alive interests;

m) decrease of metabolism.

Hypothyroidism

 

The goiter is a visible increase of thyroid gland. There are three kinds of goiter.

1. Diffuse toxic goiter – hyperthyroid. It is characterized by signs hyperfunction of thyroid gland.

2. Sporadic goiter – euthyroid. Increase of thyroid gland is not accompanied with expressed changes of its functional activity.

3. Endemic goiter – hypothyroid. Appears by clinic of thyroid gland hypofunction.

The reason of endemic goiter is insufficient content of iodine in drinking water and products of feeding. The deficiency of iodine results in disturbance of derivation of thyroid hormonees content of which in blood decreases. It causes increasing of thyroliberin and thyrotropic hormone production. TTH influences on the tissue of thyroid gland, stimulates processes of hypertrophy and hyperplasia – goiter develops.

 

Disorders of thyrocalcitonin secretion.

Thyrocalcitonin will be derivated in light C-cells of parafollicular epithelium of thyroid gland. It renders effect opposite to parathyrin action:

а) oppresses the function of osteoklasts;

b) strengthens transformation of osteoklasts into osteoblasts;

c) act direct effect on appropriate receptors of osteoklasts and is oppressed resorption of bone by osteoklasts;

d) causes calcium uretic and phosphor uretic effects;

e) increases derivation of 1,25-dihydroxyvitamin D₃ and strengthens reabsorption of calcium in intestine.

 

Disturbances of parathyroid functions. Secretion and effects of action of parathyroid hormone

Parathyroid glands secrete parat hormone or parathyrin. The formation and secretion of parathyrin is regulated by the contents of calcium ions in plasma of blood. Secretion of this hormone increases during decrease of concentration of calcium ions in plasma, and on the contrary, decreases during increase of the contents of these ions. Besides the libaration of parathyrin in blood inhibit  24,25 – (OH)₂ vitamin D, which is formed in kidneys.

Biological effects of parathyrin:

·        Action on bone tissue – activation of the osteoklasts.

·        Oppression of phosphor reabsorption in kidneys.

·        Activation of transformation in kidneys of vitamin D in hormoneally active form – 1,25 (OH)₂ vitamin D. The active form of vitamin D strengthens reabsorption of calcium in intestine.

 

Hypofunction of parathyroid glands

The main reasons hypoparathyrosis are:

1) Accidental damage or deleting of parathyroid glands during operations on thyroid gland

2)  Damage of parathyroid glands during treatment with radioactive iodine of thyroid gland diseases

3) Autoimmune damage of parathyroid glands

4) Inherent hypoplasia of parathyroid glands

5) Nonsensitivity of cells targets to action of parathyrin – pseudohypoparathyrosis.

Main manifestation of hypoparathyrosis is hypocalciemia. It causes development parathyroid tetania which appears by acute increase of nervous – muscular excitability, multiple fibrillar twitching of muscles of all body. Then occur attacks of clonic cramps which transform into tonic. The convulsive twitching can be distributed also to internal bodies (pilorospasm, laryngospasm). During one of such attacks the death can occur.

During chronic hypoparathyrosis in animal the clinical picture of parathyrotropic cachexia develops. It is characterized by weight loss, anorexia, increased nervous –muscular excitability, dyspepsia and diverse trophic disorders.

 

Hyperfunction of parathyroid glands

The main reasons of hyperparathyrosis are:

1) Tumor – adenoma of parathyroid gland;

2) Hyperfunction of parathyroid glands stipulated by decrease of endocrine cells sensitivity  to calcium ions as a result of  regulation  disorders by a principle of negative feedback.

Hyperparathyrosis appears by two groups of the connected among themselves changes.

1. Disturbance of bone tissue – generalized fibrose osteodystrophy. It is known as Reklinhausen’s disease. It is stipulated by increase of osteoklasts activity and suppression of the osteoblasts function. It appears by pain in bones and joints, softening of bones, acute deformation of a skeleton. Develops demineralization of bone tissue (osteomalation) which results in increase of the contents of calcium ions in blood  plasma – hypercalciemia.

The indicated phenomena occur as a result resorption of all bone components, and not just demineralization. Dissolved bone is substituted by fibrous tissue, cartilage.

2. Hypercalciemia. It leads to:

а) Calcification of soft tissues (kidneys, vessels, lungs). In severe cases develops renal insufficiency;

b) Formation of calcium stones in kidneys:

c) Disorder of excitability of the nervous system and muscles – muscular weakness, depression, disturbances of memory;

d) Arterial hypertension;

e) Disturbances of gastric secretion and occurrence of ulcers in stomach.

Secondary hyperthyrosis arises as response on hypocalcaemia during syndrome malabsorption, Fancony’s syndrome, chronic renal insufficiency, during hemodialysis. Hyperplasia of parathyroid glands frequently is transformed in adenoma.

 

DISORDER OF MOTOR AND SENSITIVE FUNCTIONS OF NERVOUS SYSTEM. PAIN. DISORDER OF TROPHIC FUNCTION OF NERVOUS SYSTEM. PATHOPHYSIOLOGY OF EXTREME STATES.

 

 

DISORDER OF MOTOR AND SENSITIVE FUNCTIONS OF NERVOUS SYSTEM

Etiology of nervous  system disorders

         The nervous system coordinates and organizes the functions of all body systems. This intricate network of interlocking receptors and transmitters is a dynamic system that controls and regulates every mental and physical function. It has three main divisions:

·         Central nervous system (CNS): the brain and spinal cord

·         Peripheral nervous system: the motor and sensory nerves, which carry messages between the CNS and remote parts of the body

·         Autonomic nervous system: actually part of the peripheral nervous system, regulates involuntary functions of the internal organs.

The fundamental unit that participates in all nervous system activity is the neuron, a highly specialized cell that receives and transmits electrochemical nerve impulses through delicate, threadlike fibers that extend from the central cell body. Axons carry impulses away from the cell body; dendrites carry impulses to it. Most neurons have several dendrites but only one axon. Sensory (or afferent) neurons transmit impulses from receptors to the spinal cord or the brain. Motor (or efferent) neurons transmit impulses from the CNS to regulate activity of muscles or glands. Interneurons, also known as connecting or associatioeurons, carry signals through complex pathways between sensory and motor neurons. Interneurons account for 99% of all the neurons in the nervous system.

From birth to death, the nervous system efficiently organizes and controls the smallest action, thought, or feeling; monitors communication and instinct for survival; and allows introspection, wonder, abstract thought, and self-awareness. Together, the CNS and peripheral nervous system keep a person alert, awake, oriented, and able to move about freely without discomfort and with all body systems working to maintain homeostasis.

 

Thus, any disorder affecting the nervous system can cause signs and symptoms in any and all body systems. Patients with nervous system disorders commonly have signs and symptoms that are elusive, subtle, and sometimes latent.

Nervous system is sensitive to injury influences. Its activity disorders can be caused with:

·        physical factors (mechanical trauma, electricity, high and low temperature, noise and vibration, changed atmospheric pressure),

·        poisons (narcotics, nicotine, carbon dioxide),

·        infectious disease agents (encephalitis, poliomyelitis, rabies), bacterial toxins (botulinic, titanic, diphtheritic),

·        parasites (Echinococcus, Cysticercus, Toxoplasma gondii),

·        сerebral blood circulation functional and organic disorders (arteriosclerosis, thrombosis, embolism, arterial hyperemia, ischemia, hemorrhagy),

·        tumors, 

·        inflammatory processes, which destroy the neural tissue,

·        endocrinic diseases (thyrotoxicosis, myxedema),

·        metabolism violations (starvation, hypoglycemia, hepatic coma),

·        many neural system diseases are genetically based.

         Such phenomena, as insufficient synthesis of energy ieurons, interneuronal and neuro-muscular synaptic contacts get caused with mediators synthesis increase or specific receptors blocked and are of great  importance iervous disorders pathogenesis.

MOTOR DISORDERS

Motions can be divided into intentional and unintentional. The intentional movements are controlled with pyramidal system, which consists of two motoral neurons – the central and peripheral ones. Central neurons corpuses (pyramidal cells) are fixed at locomotoral parts of cerebral hemispheres cortex – precentral gyrus, upper and medial frontal gyruses, parietal lobe, paracentral lobule. Their axons reach locomotory function disorders the anterior horn of the spinal cord, where peripheral motoral  neurons are located. Their long processes give the muscular innervation.

 

Pyramidal system

 

            In the pyramidal tract, most impulses from the motor cortex travel through the internal capsule to the medulla, where they cross (decussate) to the opposite side and continue down the spinal cord as the lateral corticospinal tract, ending in the anterior horn of the gray matter at a specific spinal cord level. Some fibers do not cross in the medulla but continue down the anterior corticospinal tract and cross near the level of termination in the anterior horn. The fibers of the pyramidal tract are considered upper motor neurons. In the anterior horn of the spinal cord, upper motor neurons relay impulses to the lower motor neurons, which carry them  the spinal and peripheral nerves to the muscles, producing a motor response. Motor impulses that regulate involuntary muscle tone and muscle control travel along the extrapyramidal tract from the premotor area of the frontal lobe to the pons of the brain stem, where they cross to the opposite side. The impulses then travel down the spinal cord to the anterior horn, where they are relayed to lower motor neurons for ultimate delivery to the muscles.

 

The motions are also get regulated with extrapyramidal system. It includes nucleus caudatus, the shell, globus pallidus, substantia nigra, red nucleus, subthalamic nucleus.

 

         The body equilibrium, movements coordination and muscular tonus are provided by cerebellum.

  

 

The central and peripheral paralyses. The total central or peripheral neuron falling out causes the central or peripheral paralyses appearance. The partial violation of these neurons provokes the conforming paresis. The central paralyses differs the peripheral one with many signs. These differenses matter for the topographical diagnostics of nervous system injuries.

Upper motor neuron dysfunction reflects an interruption in the pyramidal tract and consequent decreased activation of the lower motor neurons innervating one or more areas of the body. Upper motor neuron dysfunction usually affects more than one muscle group, and generally affects distal muscle groups more severely than proximal groups. Onset of spastic muscle tone over several days to weeks commonly accompanies upper motor neuron paresis, unless the dysfunction is acute. In acute dysfunction, flaccid tone and loss of deep tendon reflexes indicates spinal shock, caused by a severe, acute lesion below the foramen magnum. Incoordination associated with upper motor neuron paresis manifests as slow coarse movement with abnormal rhythm.

Lower motor neurons are of two basic types: large (alpha) and small (gamma). Dysfunction of the large motor neurons of the anterior horn of the spinal cord, the motor nuclei of the brainstem, and their axons causes impairment of voluntary and involuntary movement. The extent of paresis is directly correlated to the number of large lower motor neurons affected. If only a small portion of the large motor neurons are involved, paresis occurs; if all motor units are affected, the result is paralysis.

The small motor neurons play two necessary roles in movement: maintaining muscle tone and protecting the muscle from injury. Usually when the large motor neurons are affected, dysfunction of the small motor neurons causes reduced or absent muscle tone, flaccid paresis, and paralysis.

The muscles innervated by motor neurons in the anterior horn of the spinal cord may also be affected. Paresis results from a decrease in the number or force of activated muscle fibers in the motor unit. The action potential of each motor unit decreases so that additional motor units are needed more quickly to produce the power necessary to move the muscle. Dysfunction of the neuromuscular junction causes paresis in a similar fashion; however, the functional capability of the motor units to function is lost, not the actual number of units.

         The central (spastic) paralyses appear in case of cerebrum cortex violation, where the first neurons corpuses are located, or eather, internal capsule and the cerebrum column, where pyramidal tracts are passing. The central paralysis is characterized with the intentional motions loss; tendonal and periostal reflexes (hyperreflexia) activation, pathological reflexes appearance, for example, the extension of the first ringer in case of the external foot-side irritation (Babinsky reflex) or the crus frontal surface (Openhame reflex). All these changes follow the absence of cerebrum hemispheres cortex inhibiting influence upon the spinal cord neurons. Atrophic and degenerative changes in muscles are not presented.

         Peripheral (flabby) paralysis is observed in fact of spinal cord column. anterior horns, anterior radicles, plexuses and nerves. For peripheral paralysis the total movements loss characteristic – intentional and reflectory. Muscular tonus is absent (atonia). Tendonal reflexes disappear (areflexia), following ars breaking up. Denervated muscles get atrophia exposed, connective tissue spreads. Degenerative changes are characterized.

 

The next kinds of paralyses are differentiated:

·        monoplegia – one extremity is injured;

·        hemiplegia – one half muscles of the body are violated;

·        paraplegia – the upper or the lower extremities are injured,

·        tetraplegia – all of extremities are violated.

 

Myasthenia. Myasthenia gravis is an unusual disorder affecting muscle function. Normally, when a person decides to move, an impulse is sent down a nerve to the muscle. When the impulse reaches the end of the nerve, the nerve releases a substance called acetylcholine. Acetylcholine theormally binds to the muscle and causes the muscle to contract, which creates movement.

In myasthenia gravis, the body produces antibodies which attack the acetylcholine receptors found on muscles. The purpose of these muscle receptors is to bind the acetylcholine that is released from the nerves, which lets the muscle know when to contract. When the antibodies bind to these muscle receptors, the receptors are then blocked or destroyed, making them unable to bind acetylcholine. This causes muscle weakness, because the signals sent by the nerve cannot get to the muscle. So, while the nerves and muscles both technically are okay in myasthenia gravis, they are blocked from interacting because of the antibodies that are produced.

 

Because the antibodies produced in myasthenia gravis attack the persons own body, myasthenia gravis is known as an autoimmune disease. There are many other autoimmune diseases, such as lupus, rheumatoid arthritis and scleroderma. It is not known why a persons body would produce antibodies that attack their own body, but unfortunately, taken as a group, autoimmune diseases are fairly common.

Myasthenia gravis tends to affect younger women, however older persons and males can also be affected. The primary symptom is muscle weakness and fatigue. Classically, the weakness gets worse as the day progresses. The eye muscles are almost always affected, which can lead to a drooping of the eyelids and double vision because the eyes fail to move in a coordinated fashion. The more a muscle is used, the weaker it becomes. If the muscle becomes very weak, a period of rest will often improve its strength. This disease signs are connected with fast fatiguability and muscles weakness. Sometimes the typical paresis and paralyses may happened. Patholodical weakness meets at all muscles at the same time (generalized form) more often, and the separate muscles groups more seldom. Disorders of speaking, chewing,swallowing appear in fact of bulbar form; vision (diplopia), eyelid lowering (ptosis), strabismus – in case of ophthalmic form.

When suspected, a simple test can be done to make the diagnosis of myasthenia gravis. A short acting medication called an anticholinesterase can be given. This medicine works by increasing the amount of acetylcholine around muscles. If a person has myasthenia, this medication will make their weak muscles stronger. If they dont have myasthenia gravis, their muscles will not get stronger with the medication. A blood test that detects the muscle receptor antibodies is often used to confirm the diagnosis.

         Hyperkineses – are the unintentional forcible motions, pyramidally or extrapyramidally caused.

         Pyramidal hyperkineses get shown with the convulsive state. Long lasting unintentional are called tonic convulsions (cramps). If muscular contractions alternate with relaxations, such cramps are called clonic. The first appear in fact of subcortical nuclei irritation, while the second – in of cortical neurons activation.

            Generalized convulsions attacks are characterized for epilepsy. They include two phases – tonic ant clonic. Tonic phase lasts about one minute and reflects the total muscular spasm – tetanus. Muscles contraction and relaxation in clonic phase lasts longer – up to 2-3 minutes. During this phase biting of tongue and lips, unintentional defecation and uresis are possible. If cramp attacks come one by one in short time periods, that is called epileptic status.In the majority of cases, the cause of epilepsy is unknown.  Known causes of epilepsy include:

·        Head Injury/Trauma

·        Brain Infection, such as meningitis

·        Brain Tumor

·        Stroke

·        Lead Poisoning

·        High Fever

·        Poor Nutrition

·        Maternal Injury (infection or illness during pregnancy which affects fetal brain development)

·        Lack of Oxygen During Birth

·        Heredity

·        For some epileptic individuals, triggers for seizures can include:

§  Stress

§  Sleep Deprivation/Fatigue

§  Not Eating Enough

§  Alcohol

§  Hormone Fluctuations related to menstruation and/or menopause (in women)

Although epilepsy can develop at any age, most cases of epilepsy develop in children or in adults over the age of 65. Epilepsy is not ign of mental illness or low intelligence.

         Extrapyramidal caused hyperkinesis include tremor, myoclonia, chorea, atetosis.

         Tremor can be observed in case of parkinsonism. It usually appear in state of ward and is combined with muscles rigidity, motional limitation and por facial expression. The reason of  parkinsonism is the injury of substantia nigra and globus pallidus.

         Myoclonia – is the fast and short or like a group and are not followed with the motional action. This can be observed in fact of  encephalitis, atherosclerosis, hypertonic disease.

         Chorea – is non-rythmis, fast, wide extremities and the body movements, with the elements of unnaturality. Some patients with hereditary Gentingtone’s chorea are in state of constant motion, ward periods are practically absent. Rheumatic and atherosclerotic chorea etiology is understood out of their names.

         Atetosis – are slow vermicular movements in distal parts of arms and legs, sometimes – of face and neck. Generalized form of atetosis is called the torsional dystonia.

 

 

Types of hyperkinesia

 

Type	Manifestations	Mechanisms
Athetosis	Slow, sinuous, irregular movements in the distal extremities Characteristic hand posture Slow, fluctuating grimaces	Believed to result from injury to the putamen of the basal ganglion
Ballism	Severe, wild, flinging, stereotypical limb movements Present when awake or asleep Usually on one side of the body	Injury to subthalamus nucleus, causing inhibition of the nucleus
Chorea	Random, irregular, involuntary, rapid contractions of muscle groups Nonrepetitive Diminishes with rest, disappears during sleep Increases during emotional stress or attempts at voluntary movement	Excess concentration or heightened sensitivity to dopamine in the basal ganglia
Intentional cerebellar tremor	Tremor secondary to movement Most severe when nearing end of the movement	Errors in the feedback from the periphery and goal-directed movement due to disease of dentate nucleus and superior cerebellar peduncle
Myoclonus	Shock-like contractions Throwing limb movements Random occurrence Triggered by startle Present even during sleep	Irritability of nervous system and spontaneous discharge of neurons in the cerebral cortex, cerebellum, reticular activating system and spinal cord
Parkinsonian tremor	Regular, rhythmic, slow flexion and extension contraction Primarily affects metacarpophalangeal and wrist joints Disappears with voluntary movement	Loss of inhibitory effects of dopamine in basal ganglia

        

In case of cerebellum violations, such motional disorders take place:

·        atonia – muscles tonus lowering,

·        astasia – unability of keeping the position,

·        ataxia – movements coordination disorders,

·        dismetria – motional power and the vector unequilibrium,

·        astenia – the fast fatiguibility.

SENSITIVITY DISORDERS

         The sensitive function of system provides the transmission of four sensitivity kinds form peripheral up to cerebrum – algesic, themperatural, proprioceptive, tactile. Sensitivity disorders are available in case of any sensory tract part violation.

         The peripheral nerve injury (traumatic overcut, inflammatory process) leads to all sensitivity kinds loss at the zone of its innervation. The total loss is called anesthesia, sensitivity increase – hyperesthesia.

         The total spinal cord break out is also followed with all sensitivity kinds disappearing below the injury point. The half-cutting of the spinal cord (Brown-Sekar’s syndrome is characterized with such signs:

·        the total loss of proprioceptive sensitivity on the violated side;

·        the total loss of algesic and temperatural sensitivity on the opposite side;

·        the partial loss of tactile sensitivity on the both sides.

The local injury of cerebrum or spinal cord (neoplasm, traumatic pressing, hemorrhagy) provides the selective disappearing of sensitivity, depending of what’s the upgoing ways are violated. The loss of sensitivity is called anesthesia, the loss of algesic sensitivity – analgesia, the loss of themperatural sensitivity – thermoanesthesia. The loss of proprioceptive (deep located) sensitivity is also available. The sensitivity increase is called hyperesthesia, and the appearance of unusual feelings (tingling, anttickling) – paresthesia.

PAIN

The sensitive function of the nervous system consists of four kinds of sensitivity  realization from periphery to brain – they are painful, temperature, tactile and proprioceptive. This is one of major functions of the nervous system. To the brightest manifestations it the perception of the painful information.

Pain and anaesthetization – ancient a problem of medicine. On data WHO, each day on earth suffers from a pain of 3.5 million persons. The pain acquires from 30 % from them intolerable character. Very acutely there is a problem of removal of  pain in the hopeless patients, for example in the patients with an inoperable cancer. In 50-80 % such sufferers the pain is not possible satisfactory to remove. These and many other facts testify to an extreme urgency of a pain problems.

There isn’t generally accepted definition of notion “pain”. There are many sights on essence of this process. To generalize them it is possible as follows. Pain is the typical process, which was generated during evolution and which arises for want of action on an organism painful irritable or for want of weakening antipainful system. This process consists of the following components:  а) perception, realization and comprehension of  pain; b) creation vegetative, emotional and behavioural of responses; c) mobilization of anti- painful systems.

Classification of  pain

It is selected physiological and pathological pain. The physiological pain arises as adequate response of the nervous system on situations, dangerous to an organism. it is the factor of warning, signal about a potentially dangerous situation. This pain is directed on protection of an organism against damage. The pathological pain arises for want of the nervous system damage  more often. Protective character it has not. On the contrary, it exhausts protective forces of the patient and aggravates current of illness.

It is distinguished also acute and chronic pain. Acute pain short-term. It is subdivided into two varieties – primary and secondary. The primary pain arises at once after effect painful irritant – injection, cut, stroke of current, touch of  hot subject. This pain located, it arises in the center of damage. It is not removed morphine. Significance of a primary acute pain precautionary, signal. The secondary pain occurs later. In reply to damage of tissues the biological active substances – histamine, serotonin, prostaglandins, bradycinin, substance Р, ions K⁺ and Н⁺ are stored. they form smarting the non-located pain, which is removed morphine. Signal significance it has not. The chronic pain lasts longly – hours, days, weeks, sometimes – all life. It appears as chronic painful syndromes.

The nociceptive system

The pain – reflex process, which is carried out for want of availability of three main parts of reflex arc – receptor, conductors and central cerebral of structures.

Perception, realization and comprehension of a pain. The pain is perceived by the nervous terminations. There are two points of view on this process. They are made out as two theories – theory of specificity and theory of intensity.

According to the theory of specificity, the painful irritation is perceived special painful receptors. The most characteristic property these receptors – high threshold of sensitivity. They are excited only in the event that acts painful irritant of the large force, which is capable to damage to a tissues.

 

PAIN

Over the years numerous theories have attempted to explain the sensation of pain and describe how it occurs. No single theory alone provides a complete explanation. This chart highlights some of the major theories about pain.

Painful receptors are distributed in an organism non-uniformly. Most of all them in skin, brain shells, pleura, peritoneum, periosteum, in eye and internal ear, in tissue of outside sexual organs. But they practically are absent in bones and tissue of  brain. It is not enough of them in parenhyma of internal organs. Besides for receptors of internal organs the extremely high threshold of sensitivity is characteristic. It is much higher, than for painful receptors of skin or mucous. Therefore pain in internal organs does not arise for want of injection or cut them. It occurs only for want of expansion them or them capsules, and also for want of narrowing or extension internal organs of vessels.

The supporters of the theory of intensity explain perception of  pain slightly in another way. They consider, that painful the impulse arises for want of irritation anyone receptor – painful, temperature or tactile. It is necessary only, that this irritation was strong, that it has damaged  tissue.

Painful the information from receptors is transmitted to brain. Three are involved in this transfer neuron: first is in cerebrospinal  node, second – dorsal horns  of spinal cord, third – in thalamus.

From receptors up to first neurons in cerebrospinal a node painful impulses are conducted by  somatical nerves. These nerves consist of fibres of two kinds – myelinized and nonmyelinized. Myelinized of  fibre (group A) provide fast realization painful of impulses, nonmyelinized of  fibre (group С) conduct them slowly.

From first neuron through dorsal radices painful impulses act(arrive) in grey substance of dorsal horns of spinal cord (second neuron). Impulses, which enter into  back brain on fibres А, form the acute primary pain. The impulses, which enter on fibres C, form acute secondary pain.

From dorsal horns of spinal cord (second neuron) begins spinothalamic path. The fibres of second neuron are lifted from the same party on 1-2 segments and pass to the opposite side. Then in structure side funiculus they are lifted in medulla oblongata, trunk of  brain and visual tuber. Third neuron  is located here.

Spinothalamic the path terminates in three areas visual tuber – ventropostlateral  nucleus, dorsal group of nucleuses and medial nucleuses. In ventropostlateral  nucleus is neural representation of  trunk. In ventropostmedial  nucleus the fibres terminate which bring painful impulses from  face. Both these nucleuses make so-called ventrobasal  complex.

Spinothalamic the path is divided on two paths – neospinothalamic and paleospinothalamic. Neospinothalamic path phylogenetic younger. It the nervous fibres achieve ventropostlateral of  nucleus thalamus. Here is formed discriminating painful sensitivity, that is the localization of  pain is defined. Paleospinothalamic path older. It is connected to nucleuses thalamus around of the Selvium water-pipe, with back group of nucleuses thalamus, with hypothalamus, limbic by structures, cortex brain. It forms feeling of acute pain including of responses endocrine, cardiovascular also of respiratory systems, emotional and motor responses.

With ventrobasal by a complex closely are connected somatosensory of  zone cortex brain. The part of fibres third neuron goes from visual tuber to dorsal central girus. A sensory zone S1 here is located. Here there is a comprehension of  pain, analysis of its significance for an organism.

 

Creation of vegetative, emotional and behavioural  responses. The fibres spinothalamic of path are connected to many nucleuses subcortex – by vasomotor centre, respiratory centre, centre of satiation. Therefore process of a pain creation  is accompanied expressed by vegetative responses, which has adjust protective character. It is increase of heart beat, increase of output, acceleration bleeding, increase arterial of pressure, increase of breath, increase of  level of sugar in blood etc.

The important significance in formation of  pain belongs to limbic derivations and front department cortex brain. They are responsible for formation emotions and behaviour. Consider, that hypothalamus executes functions of the executive body in formation emotions, and limbic  structure (septum, hypocampus, tonsil) cause modulating influence. The pain is always accompanied emotions – mental excitation, anger, fear, aggression.

Assessment of  biological significance of painful stimulus carry out mainly front department of  brain cortex and hyppocampus. Tonsil defines behaviour on these stimulus. The upper wall side sulcus is involved in this. In it  is located second somatosensory zone S₂.  It regulates the motor  act  on  pain.

All responses accompanying a pain – vegetative, emotional, behavioural – in the beginning have protective significance. In case of  chronic pain these responses become parts pathogenesis chronic painful of syndromes.

In all departments of the nociceptive system the transfer of painful impulses is carried out with the help mediator of  pain. Here belong substation Р, glutaminic acid, cholecystokinin, neurotenzine and other substances. Major mediator of a pain considers substation Р. It is revealed at all stages of transfer painful  impulses – in dorsal horns of  spinal cord, trunk of  brain, hypothalamus, visual tuber, cortex  brain. The action of substation Р is blocked by external (morphine) and internal (encephalins, β–endorphins) opiate.

The following three variables contribute to the wide variety of individual pain experiences:

·         Pain threshold: level of intensity at which a stimulus is perceived as pain

·         Perceptual dominance: existence of pain at another location that is given more attention

·         Pain tolerance: duration or intensity of pain to be endured before a response is initiated.

 

The antinociceptive system

This system includes two levels of painful information  control: central – at  level of brain and segmented – at level of  spinal cord. The control is carried out with the help of biologically  active substances. Depending on the mechanism analgesia is selected four antinociceptive systems.

The neuronal opiate system. In 1973 the important opening – in some structures of brain the investigators detected congestions of substances similar on opium. These substances extracted from brain, have determined their chemical structure and have named encephalins. Except for  brain, them have found in cerebrospinal of  liquid and blood.

enkephalins are distributed in  nervous tissue non-uniformly. Most of all them is in those structures of brain, on which the information is transmitted painful. It is gelatinous substation of dorsal horns of spinal cord, reticular formation, grey substance around of Sylvian aquaduct, hypothalamus, limbic  structure, cortex. on neurons, which are included into composition of these structures, are located specific receptors. They are capable to bind endogenous opiate of a type encephalins and exogenous opiates of type morphine and it synthetic analogues. These receptors were called opiate. The binding endogenous or exogenous opiates with specific receptors causes antipainful effect. The mechanism of anti-painful action opiates is connected to the large sizes of their molecules. Opiates competitive bind receptors and do not allow mediators of pain (for example substance Р) to contact with same receptors. The stream of painful impulses from periphery in brain weakens. The pain decreases.

The neuronal neoopiate system. Antipainful action of this system will be realized through noradrenaline, serotonin, dofaminum.

noradrenaline oppresses realization painful of impulses at level of spinal cord and at level of trunk brain. Noradrenergic of structure are concentrated in lateral departments of brain trunk and intermediate brain. Especially it is a lot of them in reticular structure. Stimulation of central adrenergic structures causes analgesia. First of all, are oppressed behavioural and hemodynamical  response.

Serotonin causes antipainful action only for want of significant excess. Manu  of serotoninergic neurons is found in gelatinous  substance of dorsal horns of  spinal cord, medulla oblongata, Varolii pons, medial thalamus.  To serotonin the exclusive role in genesis of  headache belongs. before painful attack the contents serotonin sharply increases and develops vasoconstriction. Then there is  increased serotonin by monoaminooxydase, and also excretion it with urine in the not changed kind. Thus, after hyperserotoninemia the falling it monoamine in blood and antinociceptive structures of  brain occurs. At this particular time appeares headache.

The hormonal opiate system. It is represented by products of anterior hypophysis. adenohypophysis synthesizes difficult substance proopiomelanocortin. Farther with  removal peptide of fragments from it will be derivated adrenocorticotropic, melanocytostimulating and β-lipotropic hormones. All these hormones cause anaesthetic action. Besides from β-lipotropic hormone content substance – β-endorphine. In the structure it contains encephalin and has extremely powerful antipainful effect. Farther from other tissues the new substances containing encephalins were selected. All of them were united in one group and have received the name “large endorphines”. To them belong kytorphine, in – kosomorphine, dinorphine.

The hormones of neopiate system. It is represented vasopressin. This hormone is formed in supraoptic and paraventricular nucleuses hypothalamus and is secreted in blood by dorsal part of  hypophysis. The appearance of a pain quite often is combined with of bloodloss. Vasopressin in these cases influence double action – it detains  liquid and reduces  pain.

Consider that antinociceptive  system influences, mainly, realization of painful  impulses on spinal cord. These submissions base on the theory Melzack and Wall, which  received the name of portal   control  theory.

In opinion of the supporters of this theory, the realization painful of impulses in  spinal cord depends, mainly, on activity neurons gelatinous of substation of spinal cord dorsal horns (substantia gelatinosa). These neurons execute the function of  gate, which pass in brain greater or smaller volume of painful information.

Afferent impulsation come in  spinal cord for two types of nervous fibres – thick and thin. Impulses going on thick fibres, arise for want of operation of the not damaging factors (grinding, electrostriction, acupuncture). The impulses, which go on thin fibres, arise for want of the damaging factors action. They purely also are painful. The balance between these two impulse streams determines how many painful information reaches brain. If the stream of impulses on thick fibres dominates, neurons gelatinous of substation are activated. Arises presynaptic braking nervous terminals, which contact with inserted Т-neurons. The transfer painful of impulses on Т-neurons is braked, and the source gate for painful information is closed. If prevails impulsation on fibres of small-sized calibre, neurons gelatinous substation are oppressed. Painful impulsation breaks on Т-neurons and is transmitted above to brain.

Chronic pain

The chronic pain arises for want of durablis damage of  fabric (fracture, inflammation, tumour). The constant pain impulsation causes extraordinary activation hypothalamus, hypophysis, sympaticoadrenal, limbic  structures. Therefore chronic pain is accompanied by complex and long changes of behaviour of  person, it of mentality, emotions, attitude to the serounding world.  For want of chronic pains nociceptive system always dominate above antinociceptive systems. the sensitivity painful receptors is increased. In this connection even unpainful  influence (touch, easy pressing, movement) can cause painful sensation. The chronic pain appears as painful syndromes.

The phantom pain is a pain in amputated extremeties. The majority of the patients approves, that feels phantom extremety almost at once after amputation. The pain in phantom extremeties has a definite form, it reminds present extremety. The phantom pain lasts very longly, sometimes years and decades.

Causalgia is strong poignant pain connected to strong deformation of nerve for want of wound by high-speed shell (by  bullet, splinter). Causalgia is characterized by unabating intensive pain, which amplifies for want of operation even weak irritable, which in healthy person of pain do not cause (touch, unexpected noise, sharp light, emotional effect).

Neuralgia is characterized by a strong pain also connected to damage of peripheral nerve. On the manifestations it is similar to causalgia. The reasons it is a virus infection (herpes zoster), degeneration of nerves for want of  diabetes mellitus, ischemia extremities, beri–beri, poisoning arsenic or lead.

Especially severe it happens neuralgia trigemnius nerve. Paroxysms of pain arise for want of talk, the use of food or spontaneously.

Eccentric pain is a pain in the certain sites of a skin for want of internal organs defeat. Occurrence it explain as follows. Afferent impulsation from internal organs and from appropriate dermatom acts in same neuron of dorsal horns of spinal cord, which give beginning to spinothalamic path. If the internal organ is injured, from it is going extremely powerful streams of painful  impulses. They increase sensitivity skin receptors appropriate dermatom. In the total the pain going from an internal organ, is perceived simultaneously and as  pain in the certain site of skin.

The projectional pain arises for want of compression and damage of nerve or spinal cord horns of counterfoils. It is territorial  limited to a site innervation of  sensitive nerve. Occurrence it explain to  that the excitation from  place of nerve damage is distributed not only in the central nervous system, but also in a zone innervation.

Methods of anaesthetization

In modern medical practice the following methods of decrease or complete removal of  pain are used: psychological, physical, pharmacological, surgical, neurosurgical.

The psychological methods are directed on removal of general nervous tension, suppression of fear  feeling and concern by the state. It achieve by conversations, autotraining, relaxation.

Physical methods is acupuncture, electropuncture, transcutaneous electrostimulation, ultrasound, electrophoresis.

Acupuncture

For want of it at the expense of a durablis and weak irritation and realization impulses on thick fibres the formation encephalins amplifies. They block realization of painful  impulses at  level of dorsal horns of  spinal cord.

The pharmacological preparations are capable to oppress formation, transfer and perception painful impulses at different levels of the nervous system – receptor, conducting and central (back horns of  spinal cord, trunk of  brain, cortex of  large hemispheres).

The surgical methods are reduced to removal of the pain reason: opening abscess, reposition of parts, splinting extremities, excision scars, desympathization, ganglioectomia.

Neuro-surgical anaesthization is achieved by two methods – by the termination of transfer painful information to highter departments of  brain and stimulation descending antinociceptive of systems through electrodes, which implant in grey substance around Sylvian aqueduct and iucleuses of  seam.

 

DISORDER OF  TROPHIC FUNCTION OF NERVOUS SYSTEM

Nerve cells are the functional units of the nervous system. The nervous system is believed to have ten thousand million of such cells, called neurons and glia, the glia being present in greater numbers thaeurons.Figure is an idealized diagram of a neuron with its three most important structural features: the cell body, the dendrites and the axon terminal.

The anatomy of the neuron

 

The dendrites are finely branched processes arising near the cell body of a neuron. The dendrites receive excitatory or inhibitory effects via chemical messengers called neurotransmitters. The cytoplasm is the material of the cell body in which the organelles-including the cell nucleus-and other inclusions are found. The nucleus contains the cell’s chromatin, or genetic material.
      

The organelles

The nucleus of the nerve cell is atypical compared with that of other living cells in that, although it contains the genetic material deoxyribonucleic acid (DNA), the DNA is not involved in the process of cell division; that is, after reaching maturity, nerve cells do not divide. (An exception to this rule are the neurons in the nose lining (olfactory epithelium).) The nucleus is rich in ribonucleic acid (RNA), which is necessary for the synthesis of protein. Three types of proteins have been identified: cytosolic proteins, which form the fibrillar elements of the nerve cell; intracondrial proteins, which generate energy for cell activity; and proteins that form membranes and secretory products. Neurons are now conceived of as modified secretory cells. Secretory granules are formed, stored in synaptic vesicles and later released as neurotransmitter substances, the chemical messengers betweeerve cells. The fibrillar elements, which form the skeleton of the neuron, participate in the trophic function of the neuron, acting as vehicles of transmission. Axonal transport can be anterograde (cell body to axon terminal) and retrograde (axon terminal to cell body). From the thickest to the thinnest, three types of fibrillar elements are recognized: microtubules, neurofilaments and microfilaments.

In contrast to neurons, glial cells do not, by themselves, carry electrical messages. There are two types of glial cells: the macroglia and the microglia. The macroglia is a name given to at least three types of cells: astrocytes, oligodendrocytes and ependymal cells. Microglial cells are primarily scavenger cells for removing debris after neural damage or infection has occurred.The glial cells also have distinctive microscopic and ultramicroscopic features. Glial cells physically support neurons, but a number of physiological properties are also now beginning to be understood. Among the most important neuron-glial interactions are the glial cell’s role in providing the neurons with nutrients, removing fragments of neurons after their death and, most importantly, contributing to the process of chemical communication. Glial cells, in sharp contrast to neurons, can divide and thus can reproduce themselves. Tumours of the nervous system, for example, result from an abnormal reproduction of glial cells.

What appears in the macroscopic observation of neural tissue as “grey matter” and “white matter” has a microscopic and biochemical basis. Microscopically, the grey matter contains the neuronal cell bodies, whereas the white matter is where neural fibres or axons are found. The “white” appearance is due to a sheath-composed of a fatty substance called myelin-covering these fibres. Myelin of the peripheral nerves originates from the membrane of the Schwann cell which wraps around the axon. The myelin of fibres in the central nervous system is provided by the membranes of the oligodendrocytes (a variety of glial cells). Oligodendrocytes usually myelinate several axons, whereas the Schwann cell is associated with only one axon. A discontinuity of the myelin sheath-designated as nodes of Ranvier-exists between continuous Schwann cells or oligodendrocytes. It is estimated that in the longest central motor pathway, up to 2,000 Schwann cells form the myelin cover. Myelin, whose role is to facilitate the propagation of the action potential, may be a specific target of neurotoxic agents. A morphological classification of neurotoxic substances describes characteristic neuropathological changes of the myelin as myelinopathies.

Trophic function of the neuron

The normal functions of the neuron include protein synthesis, axonal transport, generation and conduction of the action potential, synaptic transmission, and formation and maintenance of the myelin. Some of the basic trophic functions of the neuron were described as early as the 19th century by sectioning the axons (axotomy). Among the processes uncovered, one of the most important was the Wallerian degeneration-after Waller, the English physiologist who described it.Wallerian degeneration provides a good opportunity to describe well-known changes in organelles as a result of either traumatic or toxic damage. Parenthetically, the terms used to describe Wallerian degeneration produced by traumatic axotomy are the same ones used to describe changes resulting from neurotoxic agents. At the cellular level, neuropathological changes resulting from toxic damage to neural tissue are far more complex than those occurring as a result of traumatic damage. It is only recently that changes ieurons affected by neurotoxic agents have been observed.

Twenty-four hours after cutting of the axon, the most distinctive feature is swelling of both sides of the mechanical trauma. Swelling results from accumulation of fluids and membranous elements on both sides of the site of injury. These changes are not unlike those observed in a rain-flooded two-way road with vehicles stopped on both sides of the flooded area. In this analogy, stalled vehicles are the swelling. After a few days, regeneration of the ensheathed axons-i.e., those covered with myelin-occurs. Sprouts grow from the proximal stump moving at the rate of 1 to 3 mm per day. Under favourable conditions, sprouts reach the distal (farther from the cell body) stump. When renervation-joining of the stumps-is completed, the basic features of normal transmission have been re-established. The cell body of the injured neuron undergoes profound structural changes in protein synthesis and axonal transport.

If molecular neurobiology is said to be a young discipline, the neurobiology of the neurotoxic processes is even younger, and still in its infancy. True, the molecular basis of action of many neurotoxins and pharmacological agents is now well understood. But with some notable exceptions (e.g., lead, methyl mercury, acrylamide) the molecular basis of toxicity of the vast majority of environmental and neurotoxic agents is unknown. That is why, instead of describing the molecular neurobiology of a select group of occupational and environmental neurotoxic agents, we still are forced to refer to the comparatively abundant strategies and examples from classical neuropharmacology or from work in modern drug manufacture.

Cytokines and trophic factors (TF) are involved into the nervous system activity regulation that confirms by their secretion and receptors identification withiervous system. Cytokines and TF production increases tremendously in response to CNS alterations or other CNS pathologic events where they are modulated both alterative and protective effects.

Neurotrophins provide trophic and tropic support for different neuronal subpopulations in the developing and adult nervous systems. Expression of the neurotrophins and their receptors can be altered in several different disease or injury states that impact upon the functions in the central and peripheral nervous systems. The intracellular signals used by the neurotrophins are triggered by ligand binding to the cell surface Trk and p75NTR receptors. In general, signals emanating from Trk receptors support survival, growth and synaptic strengthening, while those emanating from p75NTR induce apoptosis, attenuate growth and weaken synaptic signaling. Mature neurotrophins are the preferred ligand for Trk proteins while p75NTR binds preferentially to the proneurotrophins and serves as a signaling component of the receptor complex for growth inhibitory molecules of central nervous system myelin [ie, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgP) and Nogo]. The functional antagonism between Trk and p75NTR signaling may significantly impact the pathogenesis of humaeurodevelopmental and neurodegenerative diseases and further complicate therapeutic uses of exogenous neurotrophins.

Trophic function disorders

The notion of a trophic ulcer is nosologically indefinite at present. These disorders involve hemocoagulation, angiopathic, and chronic inflammatory processes in the derma, that lead to necrosis and sclerosis of dermal connective tissue. Contribution of the body reactivity characteristics to the formation of trophic ulcers is discussed, as are the role of skin morphofunctional features and of exogenous factors. Diabetic ulcers are one example of neuropathic ulcers. They always occur on the foot. They occur either as perforating ulcers on the sole of the foot beneath the heads of the metatarsals or at other bony prominences (e.g. the toes, the ball of the great toe, the malleoli).Typically a diabetic ulcer is deep, painless, and infected and has a ‘punched out’ appearance. These ulcers are known as ‘perforating ulcers’. Tissue surrounding the ulcer is generally well perfused. Peripheral pulses are often palpable. In the case of neuropathic ulcers, there is generalised sensory impairment. There is often a history of minor trauma that precedes the development of the ulcer. Note that infection may spread quickly and may lead to extensive limb-threatening necrosis and septicaemia.

Skin trophic ulcer

 

EXTREME STATES. SHOCK. COLLAPSE. COMA

Definition of concept. General characteristic. Reasons and mechanisms of development

Extreme states are the conditions of organism described by an excessive straining or an exhaustion of adaptive mechanisms. Extreme conditions may develop primarily by action on an organism of various extreme irritators (for example, traumas, endogenic intoxications, severe fluctuations of air temperature and concentration of oxygen) or to become a result of adverse course of disease (for example, insufficiency of blood circulation, respiratory, renal or hepatic insufficiency, anemia etc.).

When pathogenicity of extreme irritator exceeds maximum possibilities of adaptation of an organism, heavy disorders of the vital functions and direct threat of life appear. In such cases preterminal and terminal conditions may occur. Many forms of extreme conditions are convertible, while terminal conditions without special emergency help lead to death of  an organism. In these cases life of the patient depends directly on condition of breath and blood circulation, and also from time which has passed after their stop. The most important and frequently occuring extreme conditions are collapse, shock and coma.

In development of extreme conditions important meaning belongs to activation of sympathoadrenal and pituitary-adrenal systems typical for stress. In the process of deepening of condition heaviness there are narrowing of adaptive reactions, disintegration of functional systems which provide complex adaptive behavioural acts and delicate regulation of locomotor and vegetative functions. One of mechanisms of organism transition on extreme forms of adaptation is progressing switching-off of  central neurons from various afferentation which provide formation of complex functional systems. The minimum afferent signals necessary for realization of breath, blood circulation and other vital functions are reminded only. Regulation of life processes basicly passes to a metabolic level. In this stage, as a rule, there are expressed infringements of all physiological functions. For pathogenesis of extreme conditions development of chain of pathological reactions which aggravate organism disturbance is characteristic.

At all extreme conditions similar disturbances of metabolism and physiological functions, first of all hypoxia, are observed. In some cases hypoxia is initial ethiologic factor which results in development of extreme condition. However, more often hypoxia appears secondary during development of extreme condition caused by any other influence.

Extreme conditions are usually accompanied by the strengthened liberation and formation of histamine, serotonin, kinins, lysosomal enzymes and other biologically active substances. Therefore to extreme conditions disturbances of microcirculation are peculiar: infringement of perfusion of microvessels, dilatation and decrease of their sensitivity to vasopressing influences, increase of permeability of vascular walls and their structural infringements even to necrobiosis. Pathological aggregation of erythrocytes, ‘sludg-syndrome’, hypercoagulation of blood, disseminated intravascular coagulation of blood and microthrombosis of vessels. Disturbance of microcirculation in lungs (so-called ‘shock lung’) may result in their severe infringements of gas change functions, similar changes in kidneys (‘shock kidney’) may lead to renal insufficiency. Infringements of microcirculation system in liver and brain may cause hepatic insufficiency and severe disturbances of nervous system.

At all extreme conditions infringements of hemodynamic system is observed, described by decrease of volume of circulating blood and speed of blood flow, increase of blood deposition, decrease of venous return of blood to heart, fall of tone of arterioles and veins even to their paresis and decrease of general peripheral resistance of vascular system are observed also. As to the heart, the tachycardia, various forms of arrhythmias, insufficiency of coronary circulation, decrease of cardiac output and other attributes, characteristic for heart insufficiency are frequently observed.

Infringements of external breath during the extreme conditions are shown by various changes of its depth and frequency, rhythm of respiratory movements, periodic breath.

Infringements of functions of nervous system at early stages of development of an extreme condition are various. So, at the majority kinds of shock after the period of the general excitation in erectile phase original combination of the kept consciousness with the general deep block in torpid phase is typical. Consciousness is lost only at the end of this phase at transition to a terminal condition.

Shock.  Classification. Ethiology, pathogenesis, consequences

Shock is grave pathological process accompanying with an exhaustion of the vital functions of an organism and resulting it on a side of life and death because of critical decrease of capillary blood circulation in lesion organs.

Depending on the reasons of occurrence there are following kinds of shock:

·        traumatic;

·        hemorrhagic;

·        burn;

·        turnicate (develops after removal of jute after four hours and more after imposing);

·        anhydremic (dehydrative);

·        cardiogenic;

·        pancreatic;

·        septic;

·        infectional-toxic;

·        anaphylactic.  

 

Depending on the initial mechanisms underlying in pathogenesis of shock there are:

·        hypovolemic shock (hemorrhagic, anhydremic);

·        shock connected with disturbances of pump function of heart (cardiogenic);

·        vascular forms of shock (anaphylactic, pancreatic);

·        pain shock at which the central regulation of blood circulation (traumatic, after burning) is damaged.

 

Mechanisms of general hemodynamics infringements and microcirculation during shock

Irrespective of the reasons of occurrence the shock is shown by a complex of infringements of hemodynamics for which are characteristic:

·        reduction of arterial pressure;

·        reduction of circulating blood volume ;

·        decrease of volumetric speed of organ circulation;

·        infringement of reologic properties of blood (aggregation of form elements, increase of blood viscosity).

The complex of the specified infringements is designated as acute insufficiency of blood circulation. Initial infringement of its parameters at any version of shock leads again to infringements of all others. In basis of development of blood circulation disorders  at shock the following mechanisms may lay.

I. Reduction of volume of circulating blood:

1) blood loss (hemorrhagic shock);

2) loss of blood plasma at massive exudative inflammation (burn shock);

3) an exit of fluid from blood vessels (anaphylactic shock);

4) dehydration (anhydremic shock);

5) redistribution of blood in vascular system (thrombosis and embolism of main veins).

II. Reduction of minute volume of heart:

1) infringement of contractive functions of heart (heart attack of myocardium);

2) tamponade of heart (heart break, exudative pericarditis);

3) arrhythmias (fibrillation of ventricles).

III. Reduction of the general peripheral resistance in result of generalized dilation of vessels:

1) fall of neurogenic tone of arterioles (pain forms of shock);        

2) reduction of basal tone of vessels under action of biologicaly active substances (anaphylactic, pancreatic shock) or toxic products (traumatic, turnicate, infection-toxic shock).

IV. Infringements of reologic properties of blood:

1) syndrome of intravascular disseminated coagulation of blood (pancreatic shock);

2) aggregation of form elements of blood (septic, infection-toxic shock);

3) concentration of blood – hemoconcentration (anhydremic shock).

Correlation and expressiveness of pathogenetic mechanisms of each kind of shock are various. At the same time in mechanisms of development of all kinds of shock it is possible to allocate the common part. It is submitted by consecutive inclusion of two types of compensatory-adaptive mechanisms.

The first (vasocontractive) type – activation of sympathoadrenal and pituitary-adrenal systems. They are activated by main pathogenetic parts. Absolute hypovolemia (loss of blood) or relative (decrease of minute volume of blood and venous return to heart) results in decrease of arterial pressure of blood and decrease of baroreceptors  activity , which through the central nervous system activates some adaptive mechanism. The pain irritation, sepsis stimulate its switching. As a result of activation sympathoadrenal and pituitary-adrenal systems there is an emission adrenaline and corticosteroids. Epinephrines would cause consrtiction  of vessels through a-adrenoreceptors of skin, kidneys, organs of abdominal cavity). Circulation in these organs is sharply limited. Coronary and brain vessels do not have  a-adrenoreceptors and do not constrict. Centralization of blood circulation, that is presented by remaining of blood circulation in vital organs and pressure in large arterial vessels takes place.

However, acute restriction of blood circulation in skin, kidneys, organs of abdominal cavity causes their ischemia. Hypoxia appears. It switches the second (vasodilating) type of the mechanisms directed on elimination of ischemia. Vasoactive amines are formed, causing dilation of vessels, increase of their permeability and infringement of reologic properties of blood. Besides there is a disintegration of corpulent cells, activation of proteolytic enzymes, output from cells potassium ions. There is an inadequate dilatation of vessels, change of microcirculation in tissues, decrease of capillary and strengthening of shunt blood flow, change of reaction of precapillary sphincters on epinephrines and increase of permeability of capillary vessels. Thus, the fluid goes out from the vessels into tissues and venous return decreases. Vice circle appears at level of cardiovascular system, leading to reduction of cardiac output and decrease of arterial pressure. There are disorders of lungs’ function (shock lung), kidneys, coagulation of blood. Development of shock depends also on condition of an organism. All factors causing its weakening, promote development of shock.

Pathogenesis of shock

 

Heaviness of consequences of shock depends first all on infringement of blood circulation of: a) brain, b) coronary vessels, c) kidneys. As a result of these disorders the central regulation of vital functions is damaged, even to development of coma, acute cardiovascular and renal insufficiency. Occurrence of hypoxia, acidosis and intoxication leads to generalized and irreversible damage of cells.

Each kind of  shock has its features of development.

Traumatic shock develops owing to large damages of tissues.

In its clinic two stages are distinguished: 1) excitation (erectile); 2) inhibition (torpid). The stage of excitation is short-term, is characterized by excitation of the central nervous system owing to reception of pain impulses from the injured tissues. Thus, pain stress which is shown by strengthening of functions of blood circulation  system , breath, some endocrine glands (adenohypophysis, brain and cortex substances of adrenal glands, neurosecretory nucleus of hypothalamus) with liberation in blood of superfluous quantity of corticotropin, adrenaline, noradrenaline, vasopressin develops.

The stage of inhibition is more  long (from several hours to about day) and is characterized by development inhibition processes in the central nervous system. General inhibition seizes also the centres of the vital functions (blood circulation, breath), they are broken, owing to what oxygen starvation develops. Hypoxia, in turn, aggravates infringements in cardiovascular and respiratory centres. Disorders  of haemodynamic and external breath progress vice circle becomes isolated.

Except nervous – reflex mechanisms in occurrence and development of  traumatic shock the certain role plays also toxaemia, caused by absorbcion in blood of products of impractical tissues disintegration. Recently special value is  given to so-called ischemic toxin. Participation of toxic products in pathogenesis  traumatic shock is proved by experiments with crossed  blood circulation.

       Hemorrhagic shock appears during external (knife, bullet wound, erosion bleedings of stomach at stomach ulcer, tumors, from lung at  tuberculosis etc.) or internal (hemothorax, hemoperitonium) bleedings in conditions of tissues traumation.

Anhydremic shock appears owing to significant dehydratation at  loss of  liquid and electrolytes. During the exudative pleurities, intestinal obturation, peritonitis liquid comes from  vascular system into cavities. During the unrestrained vomitting and strong diarrhea the liquid is lost outside. Develops hypovolemia which plays a role of main pathogenetic link.

Burn shock appears at extensive and deep burns. Thus in the first day permeability of capillaries is sharply increased, especially in  zone of  burn that leads to  significant exit of  liquid from vessels into tissues. A large amount of edematic liquid, mainly in  place of damage, evaporates. Main pathogenetic factors are hypovolemia, pain irritation, expressed increase  of vessels permeability .

Septic (endotoxin) shock appears as complication of sepsis. Main damaging (injuring) factor are endotoxins of microorganisms. The most often reason of  sepsis are grammnegative microorganisms, and also streptococci, staphylococci, pneumococci and many others.

Main pathogenetic parts of  septic shock:

1) Increase of requirement of an organism in oxygen owing to amplification of exchange processes, tachypnoe,  tachycardia,  fever. Then decrease of the general peripheral resistance of vessels is observed;

2) Decrease of  blood oxygenation in lungs and insufficient extraction of oxygen from blood by tissues. Oxygenation  is decreased in connection due to circulation infringements in a small circle, aggregation of trombocytes on walls of vessels;

3) Activation by endotoxins of proteolytic systems in biological liquids (kallikrein-kinin’s, complement, fibrinolytic).

Cardiogenic shock is observed at decrease of pump function of cardiac muscle (heart infarction, myocarditis), at heard disorders of  heart rhythm (paroxysmal tachycardia), at tamponade heart (thrombosis of cavities, exudation or  bleeding in pericardium), at massive embolia of lungs arteries (tromboembolia of lungs). Main mechanism cardiogenic a shock is reduction of stroke and minute volume of blood, arterial pressure and increase of heart filling pressure. As well as at anhydremic  shock, owing to sympathoadrenergic reactions, the tachycardia, increase of peripheral resistance of vessels is observed.

 

Anaphylactic shock develops owing to increased sensitivity of an organism  to substances of an antigenic nature and accumulation histamine and others vasoactive substances (kinins, serotonin).

Thus there is strong reduction of venous return to heart. The reason of it is dilatation of capillary and capacitor vessels. The congestion of blood in capillary vessels and veins results in reduction of circulating blood  volume. Infringement of contractive activity of heart is observed also. Sympathoadrenergic reaction thus is not expressed because of a vascular tone  infringement.

 

Collapse.  Classification. Ethiology, pathogenesis and consequences.

Collapse is an acute vascular insufficiency  which is characterized by fall of a vascular tone, and also acute reduction of circulating blood  volume .

At the collapse there is a reduction of venous blood  inflow to heart, decrease of heart output, fall of arterial and venous pressure, infringement of tissues perfussion and  metabolism, comes hypoxia of brain appears, the vital functions of an organism are oppressed. It is shown in clinics by short-term loss of consciousness,  general weakness, features of acute vascular insufficiency with infringements hemodynamics practically in all organs and  tissues.

In a basis of development of collapse discrepancy between volume of circulating blood and capacity of a vascular system lays. The reasons may be  sudden reduction of blood volume (blood loss, dehydratation), and sudden  dilatation of vessels. Collapse develops as complication at heard diseases and pathological conditions.

The infectious collapse develops as complication of acute infectious diseases: meningoencephalitis, and typhoid fever typhus fever, acute dysentery,  pneumonia, botulism, the Siberian ulcer,  virus hepatites,  toxic influenza. The reason of such complication is the intoxication by endo- and exotoxins of microorganisms, mainly that influence on central nervous system, or receptors of pre- and postcapillaries.

Hypoxic collapse may appear in conditions of reduced partial pressure of oxygen in air. The direct reason of circulation infringements thus is insufficiency of adaptive reactions of an organism to hypoxia. To development of  collapse in these conditions may promote also hypocapnia owing to hyperventilation which leads to expansion of capillaries and vessels, and from here to deposition and decrease   of circulating blood volume.

Ortostatic collapse appears at fast transition from horizontal position in vertical, and also at long time of standing. Thus there is a redistribution of blood with increase of total amount of a venous system and decrease of inflow to heart. In a basis of this condition insufficiency of a venous tone lays. Ortostatic collapse may be observed at recovers after heard diseases of endocrine and nervous system, in the postoperative period, at fast removal of ascitic liquids or as a result of spinal and peridural anesthesias. Iatrogenic ortostatic collapse sometimes appears during wrong use of neuroleptics, ganglioblockers, adrenoblockers, sympatolytics. Among pilots and cosmonauts ortostatic collapse may be caused by redistribution of blood at action of acceleration when blood from vessels of the upper half of body and a head moves into vessels of organs of  abdominal cavity and inferior extremitus, causing hypoxia of brain. Also it may be observed at practically healthy children and teenagers.

Hemorrhagic collapse develops at massive blood loss as a result of fast reduction of circulating blood.

Collapse also may be observed at acute diseases of internal organs ( peritonitis, acute pancreatitis, duodenitis, erosive gastritis), at diseases of heart which are accompanied by acute and fast reduction of strike volume (heart  infarction, infringements of  heart rhythm, acute myocarditis or pericarditis with accumulation  of exudation in  cavity of  pericardium).

It is  possible to mark  two basic mechanisms in pathogenesis: 1) fall of  veinis and arteriols tone  as a result of action of infectious, toxic, physical, allergic and other factors directly on a vascular wall, vasomotoric  centre and on vascular receptors (sinocarotid zones, arches of an aorta); 2) fast reduction of circulating blood volume (blood loss,plasma loss). Reduction of circulating blood  volume  results in decrease of return of blood to heart by veins of the big circle of blood circulation and heart output. Thus the system of microcirculation is damaged, blood accumulates in capillaries, the blood pressure falls, develops circulatory hypoxia, metabolic acidosis, permeability of vessels increases. It promotes transition of water and elctrolytes from blood in intercellular space, are damaged reologic properties of blood, there is a hypercoagulation of blood and pathological aggregation  of erythrocytes and trombocytes, that creates conditions for formation of microblood clots. At a long lasting collapse as a result of hypoxia and disturbances of  metabolism are released vasoactive substances (histamine, kinins, prostaglandins) and formed tissue metabolites – lactic acid,adenosine and its derivatives which cause  hypotonia.

Progressing changes lead to infringement of functions of a brain,  deepening of regulatory and hemodynamic disorders. The death at a collapse comes owing to an exhaustion of power resources of brain,  intoxication and disturbances of  metabolism.

 

Cоmа. Classification. Ethiology, pathogenesis, consequences

Cоmа is a pathological condition which is characterized by deep oppression of functions of the central nervous system and it is shown by loss of consciousness, absence of reflexes on external irritators and disorders of the vital functions  regulation  of an organism.

By origin distinguish:

1. Cоmas at initial injury and diseases of the central nervous system (insult, craniocerebral trauma).

2. Cоmas during the endocrine diseases which apper as at insufficiency of some glands of internal secretion (diabetic, hypocorticoid, hypopituitary, hypothyreoid), and at their hyperfunction (thyreotoxic, hypoglycemic).

3. Toxic cоmas are observed at endogenic ( uraemia, hepatic insufficiency, toxicoinfections, pancreatitis) and exogenic intoxications (alcoholic poisonings, barbiturate poisoning, phosphororganic poisoning and by other substances).

4. Cоmas, caused by infringements of gas exchange at various kinds of hypoxias.

5. Cоmas, caused by loss of electrolytes, water and energetic substances.

Cоmа is a stage of development of some diseases. Conducting in their pathogenesis is  defeat of the central nervous system with infringement of function of  cortex brain, subcortex formations and  trunk brain that results in loss of consciousness. A special role in development of coma plays infringement of reticular formations function  with loss of its activating influences on  cortex brain and oppression  of subcortex formations function and  centres of vegetative nervous system.

Main pathogenetic parts in development of coma are:

1. Infringement of cellular breath and an exchange of energy in  brain. A basis of them is hypoxia, anemia, disorders of brain blood circulation, blockade of respiratory enzymes by cytotoxic poisons, acidosis (at diabetic and uraemic cоma), deficiency of power substances or blockade of their recycling (starvation hypoglycemis coma). In development of brain  hypoxia disorders of microcirculation play role. Owing to hypoxia it is broken oxidizing phosphorelation, the content and use АТP and creatinphosphate decreases.

2. Infringement of synaptic transmission to the central nervous system. They may be connected with:

·        infringement of synthesis, transport, deposition and secretion of neuromediators;

·        replacement of neuromediators by pseudomediators;

·        excessive activation of inhibition postsynaptic receptors;

·        blockade stimulating postsynaptic receptors. This mechanism has the great value in development of hepatic, uremic and toxic comas.

3. Infringement of electrolyte balance with changes of cellular potentials and process of polarization of neurons membranes, and also infringement of osmotic pressure. Disorders of metabolism of K, Ná, Mg, Са in a combination with infringements of the acid-base balance (diabetic, uraemic, chlorinehydropenie, hepatic etc. comas) have the greatest value.

4. Changes of physical properties and structures of  brain and intracranial formations. Pathogenetic value has swelling and edema of brain and brain membrane, increase of intracranial pressure which strengthen infringement of haemodinamics and liquordynamic, make hypoxia of nervous cells heavier and oppress their physiological activity. Mechanical damage  of brain matters cells  at a craniocerebral trauma, tumours,  hemorrhage in brain. At separate kinds of comas whom each of the listed factors may have leading mean, however they act together more often. At deep coma disorders of regulation of vegetative functions result in addition in heavy infringements of  metabolism in an organism, including brain, and create vise circle in pathogenesis of coma.