PATHOPHYSIOLOGY OF ENDOCRINE SYSTEM DM.Prof.Yu.I.Bondarenko

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PATHOPHYSIOLOGY OF ENDOCRINE
SYSTEMDM.Prof.Yu.I.Bondarenko

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Role of endocrine system in vital activity of the
organism

• The endocrine system is the most important
  regulatory system. It carries out regulatory
  influence by means 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 (ones own glandular ephithelium ) b) by
  neuroendocrine cells (hypothalamic cells) c) by
  myoendocrine cells (muscular fibres of heart
  atriums).

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Role of endocrine system in vital activity of the
organism

• According to chemical nature they differentiate
  ?) steroid hormones (mineral and
  glucocorticoids, female and male sexual
  hormones) b) derivatives of aminoacids (thyreoid
  hormones, catecholamines, melatonine) c) protein
  and 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)
  b) tropic (regulate synthesis of effecting
  homones) c) releasing-hormones (regulate
  synthesis and secretion of tropic hormones).

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Etiology of endocrine disorders

• Reasons of disorders
• mental trauma, necrosis, tumor, 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.

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Types of endocrine 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 entrance in blood of atypical
  hormonal products.

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Pathogenesis of endocrine disorders

• 1. Disorders of endocrine glands regulation
  disregulatory disorders
• 2. Disorders of hormones biosynthesis and
  their secretion glandular disorders
• 3. Disorders of the transport, reception and
  metabolism of hormones peripheral disorders.

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Disorders of endocrine gland regulation

• 1. Nervous (impulse-mediators) or parahypophysis
  regulation. By means 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.Releasing-hormones are
  synthesized, which regulate activity of
  adenohypophysis.

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Disorders of endocrine gland regulation

• 3. Endocrine regulation. One hormones influence
  on synthesis and 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.

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Disorders of endocrine gland regulation

• Pathological processes which primary are
  developed in hypothalamus lead to disorders of
  transhypophysar and parahypophysar regulation of
  endocrine glands function.
• The activity of hypothalamic centres can be
  disturbed also secondary in connection with
  disorders in limbic system (hypocampus, tonsil,
  olfactory brain) and upper parts of central
  nervous system which are closely connected with
  hypothalamus.
• The large role belongs to mental trauma and other
  stress influences.

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Disorders of endocrine gland regulation

• Transhypophysar regulation includes synthesis of
  peptides, which are moving in axons and reach
  adenohypophysis in neurosecretory cells of
  mediobasal part of hypothalamus. Here they either
  stimulate or inhibit formation of tropic
  hormones. Stimulating peptides are called
  liberines or releasing-factors thyroliberin,
  gonadoliberin, somatoliberin etc. Inhibiting
  peptides are named statines thyrostatin,
  somatostatin etc. Their ratio among themselves is
  determined formation of appropriate tropic
  hormone. 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.

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Disorders of endocrine gland regulation

• By means of parahypophysar mechanism
  secretion, 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.

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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.

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Disorders of hormones biosynthesis and their
secretion

• 1. Changes of amount of functionally active
  endocrine cells
• a) decrease of their amount (removal
  of gland or its part,
  damage, necrosis), that results to endocrine
  hypofunction
  
  b) 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) disorders of biosynthesis of
  hormones
• b) disorders of processes of their
  secretion.
• The main 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.

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Disorders of transport, reception and hormones
metabolism

• 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 associated with proteins in
  blood and circulate in two forms connected and
  free.
• Connected hormone is biologically inactive.
• Free form of hormone is active.
• 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.

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Disorders of endocrine functions, connected with
disturbances of interaction of hormones with
peripheral cells

• The influence of hormones on cells - targets is
  carried out throug their action on specific
  proteins receptors and is performed in three
  ways
• 1) influences on permeability of biological
  membranes
• 2) stimulation or inhibition of enzymes
  activity
• 3) influences on the genetic apparatus of a
  cell.
• Types of hormones cytoreception.
• 1. Membrane type of cytoreception. It is the main
  mechanism of action of protein- peptide hormones
  and catecholamines. Nowadays we known secondary
  messengers which are represented by the following
  substances a) cyclic nucleotides - cAMP, cG?P
  b) ions of ?? c) phospholipide messengers-
  diacilglycerol (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.

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Disorders of endocrine functions, connected with
disturbances of interaction of hormones with
peripheral cells

• 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.

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Disorder of endocrine functions, connected with
disturbances of hormones metabolis

• The destruction of protein-peptide hormones is
  realized in liver by means of peptidase enzymes.
• The disturbances of hormone metabolism
  transformations can stimulate development of
  peripheral disorders of endocrine function. So,
  in case of decrease 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 liver cirrhosis hormone
  metabolism is oppressed.

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Disturbances of hypophysis functions.
Hypofunction of adenohypophysis
(hypopituitaritism)

• There are panhypopituitarity and partial
  hypopituitarity.
• Panhypopituitarity is decrease of formation of
  all adenohypophysis hormones.
• Clinical forms of panhypopituitarity
  
• 1. Hypophysar Simonds cachexia
• 2. Postpartal necrosis of hypophysis syndrome
  of Schegan
• 3. Chromophobe hypophysis adenomas, i.e. tumors,
  which grow from chromophobe cells.
• Clinical manifestations of
  panhypopituitarity are connected with deficiency
  of adenohypophysis hormones and disorders of
  peripheral endocrine glands activity (thyroid
  gland, cortex of adrenal, sexual glands).

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• 
  Hypophyseal Simonds
  cachexia

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Disturbances of functions of hypophysis.Hypofunct
ion of adenohypophysis (hypopituitaritism)

• The first symptoms of lesion of adenohypophysis
  occur in damage of 70-75 glandular tissue, and
  for development of complete picture of
  panhypopituitarity necessary destruction of
  90-95 adenohypophysis.
• Vascular disorders in hypophysis and
  hypothalamus (most frequently postpartal longtime
  spasm of brain vessels and hypophysis owing to
  hemorrhage), trauma of the skull basis, tumor of
  hypophysis and hypothalamus,inflammatory damage
  (tuberculosis,sepsis) of hypophysis, inherent
  aplasia and hypoplasia can lead to development of
  panhypopituitarity. The most frequently is
  disordered gonadotropic function of hypophysis
  and secretion of STH with following development
  of insufficient secretion of ??H, ACTH and
  prolactine.

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Disturbances of functions of hypophysis.Hypofunct
ion of adenohypophysis (hypopituitaritism)

• 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 hypogonadism - 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.
• 3) fallout of fat mobilizing action with tendency
  to obesity.

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Disturbances of functions of hypophysis.Hypofunct
ion of adenohypophysis (hypopituitaritism)

• 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. 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 Leidigs 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.

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Hyperfunction of adenohypophysis
(hyperpituitarism)

• The main reason of hyperpituitarism is
  development of benign tumor adenoma of
  endocrine cells.
• There are two groups of adenomas.
• 1. Eosinophilic 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. Besides that
  increased metabolic activity of STH
  -hyperglycemia, insulin resistanse, even to
  development of metahypophysar diabetes, fatty
  infiltration of liver develop.

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• The tallest man in the world Sultan Kosen (2 m
  47 sm)
• The lowest man in the world He Pingping (74,61
  sm) died in the last year in Italy

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Khagendra Thapa Mager world smallest man
(64 sm growgh, 10 kg
weight). Nepal.
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Thapa Mager with
your
parents
He is18 years ago
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Thapa Mager
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Hyperfunction of adenohypophysis
(hyperpituitarism)

• 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
• ?) 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.

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BASOPHILIC ADENOMA OF HYPOPHYSIS
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Hyperfunction of neurohypophysis

• Their main effects
• Vasopressine (antidiuretic hormone) renders the
  following influence through V1 and V2 receptors
• 1. Act 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).

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Hyperfunction of
neurohypophysis

• Oxytocin realizes the next functions
• 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 stable
  arterial hypertension.

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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 vasopressine is formed
• Nephrogenic during which the sensitivity of
  epithelial cells receptors of distal nephron to
  vasopressin 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 decrease of oxytocin production appears by
  disorders of lactation, weakness of labor
  activity.

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Disorders of adrenal gland function

• 1. Hypofunction of adrenal cortex -
  hypocorticism
• 2. Hyperfunction of fascicular zone -
  Itsenko-Cushings syndrome
• 3. Hyperfunction of glomerulose zone -
  hyperaldosteronism
• 4. Dysfunction of adrenal cortex - adrenogenital
  syndrome.

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Insufficiency of adrenal cortex

• 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?) state
  after removal of adrenals b) hemorrhage in
  adrenals which arises during sepsis, meningococci
  infection (syndrome Waterhouse-Friderixan) c)
  syndrome of cancellation of glucocorticoides
  after prolonged use their in large dose.

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Insufficiency of adrenal cortex

• 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 Adisons disease (bronzed
  disease). The most often reasons of it are ?)
  tuberculose destruction of adrenals b)
  autoimmune process.
• ?. Manifestation, connected with the isufficient
  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

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Insufficiency of adrenal cortex

• 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.

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Insufficiency of adrenal cortex

• ??. Manifestations stipulated by disorders of
  glucocorticoid function of adrenals.
• 1) hypoglycemia
• 2) arterial hypotension (permissive reaction on
  catecholamines)
• 3) decrease of response 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.

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President of USA J.Kennedy suffered Addisons
desease
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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 pressor factors,
  particularly catecholamines increases. 2)
  hypopotassiumaemia (result of hypersecretion of
  potassium ions in canaliculas 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.

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Increase of adrenals cortex function

• Secondary hyperaldosteronism is a result of
  renin-angiotensin system activation. This state
  appears by a) arterial hypertension b) edema
  c) hypopotassiumaemia d) ungas alcalosis.
• Hypercorticism with hyperproduction of
  glucocorticoides
• 1. Cushings disease basophil adenoma of
  anterior part of hypophysis.
• 2. Cushings syndrome ?) tumor adenoma of zona
  fasticulata of adrenal cortex b) ectopic
  production of ?C?H by some malignant tumors
  (pulmonar cancer) c) iatrogenic
  introduction of glucocorticoides in an organism
  with the medical purpose.

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Increase of adrenals cortex function

• Depending on the level of blockade of cortisole
  synthesis there are three variants of
  androgenital syndrome.
• ?. 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).
• ??. Disorders of intermediate stages deficiency
  of glucocorticoides, surplus of androgens,
  formation of mineralocorticoides is not
  disordered (classical androgenic syndrome).
  Manifestations are the same, as in the first
  case, only without signs of insufficiency of
  mineralocorticoidal function.
• ???. Disorders at final stages of cortizol
  synthesis deficiency of glucocorticoides,
  hyperproduction of androgens and
  mineralocorticoides. Features of
  hyperaldosteronism are connected with
  manifestations of classical androgenital syndrome.

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Disorders of adrenal medulla function

• Hyperfunction of adrenal medulla arises in
  tumors of chromaphine cells pheochromocytome.
• It appears by arterial hypertension, tachycardia,
  extrasystole, flatering of atriums,
  hyperglycaemia, hyperlipidemia, hyperthermia. In
  time of paroxizm vertigo, headache,
  hallucinations, increased excitability of the
  nervous system, cramps appear.

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TO YOU !!!