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CLINICAL PATHOPHYSIOLOGY OF THE ENDOCRINE SYSTEM

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.

Disorders of endocrine gland regulation


Regulation of endocrine gland activity can be carried out with the help of four
mechanisms:
1. Nervous (impulse-mediators) or parahypophysis regulation. With the help of
direct nervous influences the activity of following structures is regulated: )
adrenal medulla; b) neuroendocrine structures of hypothalamus; c) epiphysis.

2. Neuroendocrine or transhypophysar regulation. It is carried out by


neuroendocrine cells of hypothalamus, which transform nervous impulses in
specific endocrine process. Along releasing-hormones, which regulate activity of
adenohypophysis are synthesized and get secreted in the system of portal
vessels of hypophysis .
3. Endocrine regulation. It is that some hormones influence on synthesis and
other influence secretion of the others. An example of this mechanism is the
influence of adenohypophysis tropic hormons on activity of adrenal cortex,
thyroid gland, sexual glands.
4. Non-endocrine humoral regulation is carried out by unspecific humoral factors,
in particular by metabolites, ions.
Pathological processes which are primarity developed in hypothalamus lead to
disorders of transhypophysar and parahypophysar regulation of endocrine glands
function. The activity of hypothalamic centres can be disturbed also secondarily
in connection with disorders in limbic system (hypocampus, tonsil, olfactory
brain) and upper parts of central nervous system which are closely connected
with hypothalamus. At that the large role belongs to mental trauma and other
stress influences.
Transhypophysar regulation includes synthesis of peptides which are moving by
axons and reach adenohypophysis in neurosecretory cells of mediobasal part of
hypothalamus. Here they either stimulate or inhibit formation of tropic
hormones. Stimulating peptides have received the name of liberins or releasingfactors, they are: thyroliberin, gonadoliberin, somatoliberin etc. Inhibiting
peptides are named statins thyrostatin, somatostatin etc. Their ratio among
themselves is determined formation of appropriate tropic hormone. Then
formation of tropic hormones begins in adenohypophysis somatotropic (STH),
gonadotropic (GTH) etc. Tropic hormones act on appropriate targets and
stimulate derivation of hormones in appropriate glands, and STH stimulates
formation of somatomedines in tissues polipeptide hormones, through which
they act.
By means of parahypophysar mechanism secretory, vessel and trophic influence
of CNS on the function of endocrine glands is carried out. For adrenal medulla,
Langerhans islets and parathyroid glands it is a major pathway of their
regulation. In realization of the function of other glands both pathways of
regulation take place. So, the function of thyroid gland is determined not only by
TTH, but also by sympathetic impulsation. The direct irritation of sympathetic
nerves increases absorption of iodine by the gland, synthesis of thyroid
hormones and their secretion. Denervation of ovaries causes their atrophy and
weakens response on gonadotropic hormones.
The disorders of trans- and parahypophysar regulation leads to disfunction of
endocrine glands. The disturbanc of one gland function is called monoglandular
process, several glands pluriglandular process. The disorders of the glandular

function can be partial, when production of only one hormone is disturbed, or


total, when secretion of all hormones is changed .

Role of mechanisms feedback bond in endocrine disturbances


The mechanism of feedback bond is obligated link in self regulation of glandular
activity. The essence of negative adverse effects is that formed hormones
oppress activity of structures which carry out the previous stages of regulation.
Therefore the increase of secretion of effectory hormone through certain parts
causes decrease of its formation and entering in blood, and on the contrary, the
decreasing of the hormone contents in blood causes increase of intensity of its
formation and secretion. In this way regulation of cortizol secretion, thyroid and
sexual hromones is carried out.
By the principle of the mechanism of feedback bond inhibition of the function
(even atrophy) of the gland during treatment by their or other hormones can
occur.

Disorders of hormones biosynthesis and their secretion


Strictly glandular disorders of endocrine functions can be conditioned:
1. By changes of functionally active endocrine cells amount :
a) by decrease of their amount (removal of gland or its part, damage, necrosis),
that results to endocrine hypofunction;
b) by increase of their amount (benignt and malignant tumors of glandular
epithelium) that is accompanied by features of endocrine hyperfunction.
2. Qualitative changes in cells:
a) by disorders of biosynthesis of hormones;
b) by disorders of processes of their secretion.
The main possible reasons of protein-peptide hormones synthesis disorders are:
1) disorders of transcription;
2) disorders of translation;
3) deficiency of essential aminoacids;
4) deficiency of ATP;
5) disorders of posttranslatory modification and activation.

Disorders of transport, reception and hormones metabolism.


The peripheral mechanisms determine activity of hormones excreted into blood ,
development of peripheral disorders of endocrine functions occurs due to:
1. Disorders of the hormones transport in organism.
2. Disorder of metabolic inactivation of hormones.
3. Disorders of interaction of hormones with peripheral cells - targets.
All hormones is excreted from gands associate with proteins in blood and
circulate in two forms connected and free. From these two forms connected
hormone is biologically inactive. The activity is peculiar only to free form of
hormone.
The disorders of the hormone transport in an organism can appear in two types
of endocrine function disorders:
) hypofunction increase of hormone binding and decrease of its contents in
the free form;
b) hyperfunction decrease of hormone binding and increase in blood of
concentration of the free form.

Disorders of endocrine functions, connected with disturbances of interaction of


hormones with peripheral cells
The influence of hormones on cells - targets is carried out through their action on
specific proteins receptors and is performed in three ways:
1) influences on permeability of biological membranes;
2) stimulation or oppression of enzymes activity;
3) influences on the genetic apparatus of a cell.
There are two types of cytoreception of hormones.
1. Membrane type of cytoreception. It is the main mechanism of action of
protein- peptide hormones and catecholamines. Nowadays we known secondary
intermediaties which are represented by the following substances: a) cyclic
nucleotides - cAMP, cGP; b) ions of ++; c) phospholipide messangersdiacilglycerol (DAG) and inozitoltriphosphate (ITP). The specificity of the answer
of a cell on this or other hormone is determined by specificity of the receptor,
which is connected only with a certain hormone, and also by nature of specific to
a cell proteinkinase and protein substrats.
2. Intracellular type of cytoreception. It is in the base of mechanism of steroid
and thyroid hormones action.

The blockade of hormonal receptor is the widespread mechanism, which results


to hormonal insufficiency: active hormone does not find receptor on a cell or in it
because of receptor loss or fixing on its surface of antagonist, conformation
changes of the receptor, which interfere connection with the hormone. Usually
concentration of hormone in such cases is normal or increased. The introduction
of the hormones with the medical purpose is not accompanied by appropriate
effect.

Disorder of endocrine functions, connected with disturbances of hormones


metabolism
The destruction of protein-peptide hormones is realized in liver with the help of
peptidase enzymes. The disturbances of metabolic hormones transformations
can stimulate development of peripheral disorders of endocrine function. So, in
case of slowing- down of hormones inactivation their contents in blood is
increased, that appears in glands hyperfunction. And on the contrary, the
accelerated transformation of hormones in their inactive forms is accompanied
by development of endocrine hypofunction. In hepatitis and cyroses of a liver
hormones metabolism is oppressed.

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.
Causes of Diabetes Mellitus
Diabetes mellitus is caused by an absolute or relative lack of insulin that, among
other consequences, leads to an increase in plasma glucose concentration The
disease was given its name because of the glucose excretion in the urine. The
disease can be classified into several types, depending on its cause and course.
This classification is useful, even though it is greatly simplified.
In type I (insulin-dependent diabetes mellitus [IDDM], previously called juvenile
diabetes) there is an absolute lack of insulin, so that the patient needs an

external upply of insulin. The condition is caused by a lesion in the beta cells of
the pancreas, as a rule produced by an autoimmune mechanism that may, in
certain circumstances, have been triggered by a viral infection. The pancreatic
islets are infiltrated by T lymphocytes and autoantibodies against islet tissue
(islet cellantibodies [ICA]) and insulin (insulin autoantibodies [IAA]) can be
detected. ICA may in some cases be detected years before the onset of the
disease. After the death of the beta cells, the ICA again disappear. 80% of
patients form antibodies against glutamatedcarboxylase expressed n the beta
cells. Type I diabetes mellitus occurs more frequently in the carriers of certain
HLA antigens (HLA-DR3 and HLA-DR4), i.e., there is a genetic disposition.
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Type II (non-insulin-dependent diabetes mellitus [NIDDM], formerly called
maturityonset diabetes) is by far the most common form of diabetes. Here, too,
genetic disposition is important. However, there is a relative insulin deficiency:
the patients are not necessarily dependent on an exogenous supply of insulin.
Insulin release can be normal or even increased, but the target organs have a
diminished sensitivity to insulin.
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Most of the patients with type II diabetes are overweight. The obesity is the
result of a genetic disposition, too large an intake of food, and too little physical
activity. The imbalance between energy supply and expenditure increases the
concentration of fatty acids in the blood. This in turn reduces glucose utilization
in muscle and fatty tissues. The result is a resistance to insulin, forcing an
increase of in sulin release. The resulting down-regulation of the receptors
further raises insulin resistance. Obesity is an important trigger, but not the sole
cause of type II diabetes. More important is the already existing genetic
disposition to reduced insulin sensitivity. Frequently, insulin release has always
been abnormal. Several genes have already been defined that promote the
development to obesity and type II diabetes. Among other factors, the genetic
defect of a mitochondrial decoupling protein limits substrate consumption. If
there is a strong genetic disposition, type II diabetes can already occur at a
young age (maturity-onset diabetes of the young [MODY]).
Reduced insulin sensitivity predominantly affects the insulin effect on glucose
metabolism, while the effects on fat and protein metabolism are still well
maintained.

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Glucose rugulation
Thus, type II diabetics tend especially toward massive hyperglycemia without
corresponding impairment of fat metabolism (ketoacidosis). Relative insulin
deficiency can also be caused by autoantibodies against receptors or insulin as

well as by very rare defects in the biosynthesis of insulin, of insulin receptors, or


of intracellular transmission. Even without any genetic disposition, diabetes can
occur in the course of other diseases, such as pancreatitis, with destruction of
the beta cells (pancreas-deprived diabetes), or by toxic damage to these cells.
The development of diabetes mellitus is promoted by an increased release of
antagonistic hormones. Among these are somatotropin (in acromegaly),
glucocorticoids (in Cushings disease or stress [so-called steroid diabetes]),
epinephrine (in stress), progestogens and choriomammotropin (in pregnancy),
ACTH, thyroid hormone, and glucagon. Severe infections increase the release of
several of the above hormones and thus the manifestation of diabetes mellitus. A
somatostatinoma can cause diabetes because the stomatostatin secreted by it
inhibits the release of insulin.
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Pathogenesis of DM

Acute Effects of Insulin Deficiency


Insulin acts to create energy reserves. It promotes the uptake of amino acids and
glucose, especially in the muscle and fat cells. In hepatic, muscle, and fat cells
(among others) insulin stimulates protein synthesis and inhibitis protein
breakdown; in the liver and muscles it promotes glycogen synthesis, inhibits its
breakdown, stimulates glycolysis, and inhibits gluconeogenesis from amino
acids. Also in the liver, insulin promotes the formation of triglycerides and
lipoproteins as well as the hepatic release ofVLDL. At the same time it stimulates
lipoprotein lipase and thus accelerates the splitting of triglycerides into
lipoproteins in blood (especially chylomicrons). The free fatty acids and glycerol
are then taken up by the fat cells and stored again as triglycerides. Insulin
stimulates lipogenesis and inhibits lipolysis in the fat cells. Lastly, it promotes
cell growth, increases renal tubular absorption of Na+, and cardiac contractility.
Part of insulin action is mediated by cell swelling (especially antiproteolysis) and
intracellular alkalosis (stimulation of glycolysis, increased cardiac contractility).
Insulin achieves this effect by activating the Na +/H+exchanger (cell swelling
and alkalinization), the Na+-K+-2 Cl cotransporter (cell swelling), and Na+-K+ATPase. This results in K + uptake by the cell and hypokalemia. As glucose is
coupled to phosphate in the cell, insulin also reduces plasma phosphate
concentration. It further stimulates the cellular uptake of Mg2+. Insulin also
paracrinally in hibits the release of glucagon and thus diminishes its stimulating
action on glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis.
In acute insulin deficiency the absence of its effect on glucose metabolism
results in hyperglycemia. The extracellular accumulation of glucose leads to
hyperosmolarity. The transport maximum of glucose is exceeded in the kidney so

that glucose is excreted in the urine. This results in anosmotic diuresis withrenal
loss of water (polyuria), Na+, and K+, dehydration, and thirst. Despite the renal
loss of K+, there is no hypokalemia because the cells give up K+ as a result of
reduced activity of Na+-K+ -2 Clcotransport and of Na+-K+-ATPase. The
extracellular K+ concentration, which is therefore more likely to be high,
disguises the negative K+balance. Administration of insulin then causes a lifethreatening hypokalemia. Dehydration leads to hypovolemia with corresponding
impairment of the circulation. The resulting release of aldosterone increases the
K+ deficiency, while the release of epinephrine and glucocorticoids exacerbates
the catabolism. The reduced renal blood flow diminishes the renal excretion of
glucose and thus encourages the hyperglycemia.
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The cells further lose phosphate (P) and magnesium that are also excreted by
the kidney. If there is an insulin deficiency, proteins are broken down to amino
acids in muscles and other tissues. This breakdown of muscles will, together with
electrolyte abnormalities, lead to muscular weakness. Prevailing lipolysis leads to
release of fatty acids into blood (hyperlipidacidemia). The liver produces
acetoacetic acid and -hydroxybutyric acid from the fatty acids. Accumulation of
these acids leads to acidosis, which forces the patient to breathe deeply
(Kussmaul breathing). Some of the acids are broken down to acetone (ketone
bodies). In addition, triglycerides are formed in the liver from fatty acids and
incorporated into VLDL. As the insulin deficiency delays the breakdown of
lipoproteins, the hyperlipidemia is further aggravated. Some of the triglycerides
remainin the liver anda fatty liver will develop. The breakdown of proteins and fat
as well as polyuria will result in weight loss. The abnormal metabolism,
electrolyte disorders and the changes in cell volume brought about by changed
osmolarities can impair neuronal function and cause hyperosmolar or
ketoacidotic coma. The main effects of relative insulin deficiency are
hyperglycemia and hyperosmolarity, while in absolute insulin deficiency the
consequences of increased proteolysis and lipolysis (ketoacidosis) are added to
these effects.

Late Complications of Prolonged Hyperglycemia


The metabolic abnormalities of inadequately treated relative or absolute insulin
deficiency will in the course of years or decades lead to extensive irreversible
changes in the organism. Hyperglycemia plays a central role in this.
Glucose is reduced to sorbitol in cells that contain the enzyme aldosereductase.
This hexahydric alcohol cannot pass across the cell membrane, as a result of
which its cellular concentration increases and the cell swells. Due to an
accumulation of sorbitol in the lens of the eye, water is incorporated, impairing
lenticular transparency (clouding of the lens [cataract]). Accumulation of sorbitol
in the Schwann cells and neurons reduces nerve conduction (polyneuropathy),
affecting mainly the autonomic nervous system, reflexes, and sensory functions.

To avoid swelling, the cells compensate by giving off myoinositol which then,
however, will not be available for other functions. Cells that do not take up
glucose in sufficient amounts will shrink as a result of extracellular
hyperosmolarity. The functions of lymphocytes that have shrunk are impaired
(e.g., the formation of superoxides, which are important for immune defense).
Diabetics are thus more prone to infection, for example, of the skin (boils) or
kidney (pyelonephritis). These infections, in turn, increase the demand for
insulin, because they lead to an increased release of insulin-antagonistic
hormones. Hyperglycemia promotes the formation of sugar-containing plasma
proteins such as fibrinogen, haptoglobin, 2-macroglobulin as well as clotting
factors VVIII. In this way clotting tendency and blood viscosity may be increased
and thus the risk of thrombosis raised.
By binding of glucose to free amino-groups of proteins and a subsequent, not
fully understood, irreversible Amadori reaction, advanced glycation end products
AGEs) are formed. They also occur in increasing amounts in the elderly. A protein
network can be formed through the formation of pentosin. AGEs bind to
respective receptors of the cell membrane and can thus promote the deposition
of col lagenin the basement membranes of the blood vessels. The formation of
connective tissue is in part stimulated via transforming growth factor (TGF-).
Additionally, however, the collagen fibers can be changed by glycosylation. Both
changes produce thickening of the basement membranes with reduced
permeability and luminal narrowing (microangiopathy). Changes occur in the
retina, also as a result of microangiopathies, that ultimately may lead to
blindness (retinopathy). In the kidney glomerulosclerosis (KimmelstielWilson)
develops, which can result in proteinuria, reduced glomerular filtration rate due
to a loss of glomeruli, hypertension, and renal failure. Because of the high amino
acid concentration in plasma, hyperfiltration takes place in the remaining intact
glomeruli, which as a result are also damaged. Together with a rise of VLDL in
blood and the raised clotting tendency of the blood (see above), hypertension
promotes the development of a macroangiopathy that can further damage the
kidneys and cause myocardial infarction, cerebral infarction, and peripheral
vascular disease. Lastly, glucose can react with hemoglobin (HbA) to form HbA
1c, whose increased concentration inblood points to a hyperglycemia that has
been present for some time. HbA 1c has a higher oxygen affinity than HbA and
thus releases oxygen in the periphery less readily. The persisting insulin
deficiency further leads to a reduction in the erythrocytic concentration of 2,3bisphosphoglycerate (BPG), which, as allosteric regulator of hemoglobin, reduces
its oxygen affinity. The BPG deficiency also results in an increased oxygen affinity
of HbA. Diabetic mothers have a statistically higher chance of giving birth to a
heavier than normal baby. This may be the result of an increased concentration
of amino acids in blood, producing an increased release of somatotropin.
v

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Pathogenesis of diabetes mellitus symptoms

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q=tbn:ANd9GcQbuzqesBSNnNfvE2nU2MpBnhNQuCH7UjAKsa71kXlh4vTAEKfczQ

Clinical manifestations of DM

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Atherosclerosis due to DM

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Diabetic retinopathy

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Diabetic nephropathy
CLINICAL PATHOPHYSIOLOGY OF THYROID GLAND
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 (H)
secretion.
2. Strictly glandular disturbances (primary hyperthyrosis). The most widespread
clinical forms of primary hyperthyrosis are:
) Diffuse toxic goiter (Bazeds disease, Graves disease, Parris 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 H are capable to contact
with receptors on basal membrane of thyrocyte, that results in cell activation.
3. Peripheral disorders :
) Increase of cell sensitivity to action of 3 and 4;
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:
) goiter (increase of thyroid gland)
http://1.bp.blogspot.com/upAwBhh_Ts4/TeFgBvCK1DI/AAAAAAAAAMw/qmuNwQ9Fryg/s1600/Goiter1.jpg
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
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q=tbn:ANd9GcSSJqOnlPAFA9djDtosrZJoGCyKdsh9WaTEKT6BGTqxUgfdbnYeTA
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:
) 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 hormones. 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 3 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 H. Nodal toxic goiter is
characterized by absence of changes on the part of orbits an eye and mixedema.

Pathogenesis of syndromes of hyperthyroidism

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 (H).
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:
) 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:
) 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 N--Ps 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 adrenoreceptors on cells. The functional changes of exitated organs and tissues
are:
) 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:
) 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:
) 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:
) 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.

Pathogenesis of syndromes of hypothyroidism

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