By MD, PhD, Associate ProfessorBy MD, PhD, Associate Professor

Ivano-Frankivsk National Medical Ivano-Frankivsk National Medical UniversityUniversity

By MD, PhD, Associate ProfessorBy MD, PhD, Associate Professor

Ivano-Frankivsk National Medical Ivano-Frankivsk National Medical UniversityUniversity

Pathophysiology of the endocrine Pathophysiology of the endocrine system. General adaptation system. General adaptation

syndrome. Violation of syndrome. Violation of

hypophysis and adrenal glands.hypophysis and adrenal glands.

CONTENTCONTENT1.1. Endocrine regulatory dysfunction. Endocrine regulatory dysfunction. 2.2. The main types of endocrine dysfunctions: hyper-, The main types of endocrine dysfunctions: hyper-,

hypo- and dysfunction. Gland disorders of endocrine hypo- and dysfunction. Gland disorders of endocrine function. function.

3.3. Peripheral disorders of endocrine function. Peripheral disorders of endocrine function. 4.4. Panhypopituitarism: causes, mechanisms of Panhypopituitarism: causes, mechanisms of

development, main manifestations.development, main manifestations.5.5. Partial hypofunction of adenohypophysis.Partial hypofunction of adenohypophysis.6.6. Hyperfunction of adenohypophysis: eosinophilic and Hyperfunction of adenohypophysis: eosinophilic and

basophilic adenoma. Cushing’s disease.basophilic adenoma. Cushing’s disease.7.7. Disorders of hypothalamo-neurohypophyseal Disorders of hypothalamo-neurohypophyseal

system. Disorders of secretion of antidiuretic system. Disorders of secretion of antidiuretic hormone. hormone. Diabetes insipidus.Diabetes insipidus.

8.8. Describe the etiology, pathogenesis, and Describe the etiology, pathogenesis, and manifestations of hyperfunction and hypofunction of manifestations of hyperfunction and hypofunction of the adrenal cortex. the adrenal cortex.

9.9. Characterize aCharacterize adrenal medulla hyperfunction.drenal medulla hyperfunction.10.10. Describe SelyeDescribe Selyes historic general adaptation s historic general adaptation

syndrome; cite its stages. How does stress reactions syndrome; cite its stages. How does stress reactions develop?develop?

Actuality of the lecture.Actuality of the lecture. The endocrine system is involved in all of the integrative The endocrine system is involved in all of the integrative

aspects of life, including growth, sex differentiation, aspects of life, including growth, sex differentiation, metabolism, and adaptation to an ever-changing metabolism, and adaptation to an ever-changing environment. This chapter focuses on general aspects of environment. This chapter focuses on general aspects of endocrine function, organization of the endocrine system, endocrine function, organization of the endocrine system, hormone receptors and hormone actions, and regulation of hormone receptors and hormone actions, and regulation of hormone levels.hormone levels.

The endocrine system uses chemical substances called The endocrine system uses chemical substances called hormones hormones as a means of regulating and integrating body as a means of regulating and integrating body functions. The endocrine system participates in the functions. The endocrine system participates in the regulation of digestion, use, and storage of nutrients; growth regulation of digestion, use, and storage of nutrients; growth and development; electrolyte and water metabolism; and and development; electrolyte and water metabolism; and reproductive functions. Although the endocrine system once reproductive functions. Although the endocrine system once was thought to consist solely of discrete endocrine glands, it was thought to consist solely of discrete endocrine glands, it is now known that a number of other tissues release is now known that a number of other tissues release chemical messengers that modulate body processes.chemical messengers that modulate body processes.

The functions of the endocrine system are closely linked with The functions of the endocrine system are closely linked with those of the nervous system and the immune system.those of the nervous system and the immune system.

Role of endocrine system inRole of endocrine system in vital vital activity of the activity of the organismorganism

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

•The endocrine system, along The endocrine system, along with the nervous system, is with the nervous system, is responsible for responsible for coordinating our coordinating our responsesresponses.. •The endocrine system is a The endocrine system is a slowerslower system and the nervous system and the nervous system is a system is a fasterfaster response. response.

Chemical signalsChemical signals Chemicals found in both systems and also as Chemicals found in both systems and also as

part of other signaling mechanisms bind to part of other signaling mechanisms bind to specific receptor proteins on or in target cells.specific receptor proteins on or in target cells. Hormones Hormones – produced by endocrine glands,– produced by endocrine glands,

travel through the blood stream to target organstravel through the blood stream to target organs

ex – insulin, estrogenex – insulin, estrogen Local regulatorsLocal regulators

(a) paracrine signals – act on neighboring cells, ex. (a) paracrine signals – act on neighboring cells, ex. – cytokines, interferon, prostaglandins– cytokines, interferon, prostaglandins

(b) autocrine signals – act on secreting cells itself, (b) autocrine signals – act on secreting cells itself, ex – cytokines ex – cytokines

HormonesHormones can be synthesized: can be synthesized:

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

• b) by neuroendocrine cells (hypothalamic cells);

• c) by myoendocrine cells (muscular fibres of heart atriums).– Neurotransmitters – secreted by neurons

at synapses ex- serotonin, nitric oxide (NO)– Neurohormones – secreted by

neurosecretory cells, travel through the blood stream to target organs or synapses

ex- epinephrine– Pheromones – released into the

environment; between individuals ex – insects marking trails, mating, etc.

(a) Endocrine signaling

ResponseBloodvessel

(b) Paracrine signaling

Response

Response

Response

Response

(c) Autocrine signaling

Neuron

(d) Synaptic signaling

(e) Neuroendocrine signaling

Neurosecretorycell

Bloodvessel

According to chemical nature they According to chemical nature they differentiatedifferentiate::

аа) ) steroid hormonessteroid hormones ( (mineralmineral – and – and glucocorticoidsglucocorticoids, female and male , female and male sexual hormones); sexual hormones);

bb) ) derivatives derivatives of aminoacidsof aminoacids ((thyreoidthyreoid hormones, hormones, catecholaminescatecholamines, , melatoninemelatonine); );

cc) ) protein peptide protein peptide hormoneshormones ((releasingreleasing-hormones, -hormones, vasopressinvasopressin, , oxytocinoxytocin, hormones, hormones of of adenohypophysis, adenohypophysis, insuline, glucagone, parathyrin, insuline, glucagone, parathyrin, calcitonine).calcitonine).

Somatostatin

Lipid-solubleLipid-soluble hormones (steroid hormones (steroid hormones) hormones) pass easilypass easily through through cell membranes, whilecell membranes, while water- water-solublesoluble hormones (polypeptides hormones (polypeptides and amines) and amines) do notdo notThe solubility of a hormone The solubility of a hormone correlates with the location of correlates with the location of receptors inside or on the receptors inside or on the surface of target cellssurface of target cells

• Water-solubleWater-soluble hormones are secreted hormones are secreted by by exocytosisexocytosis, travel freely in the , travel freely in the bloodstreambloodstream, and bind to cell-surface , and bind to cell-surface receptorsreceptors• Lipid-solubleLipid-soluble hormones diffuse hormones diffuse across across cell membranescell membranes, travel in the , travel in the bloodstream bound to transport bloodstream bound to transport proteins, and diffuse through the proteins, and diffuse through the membrane of target cellsmembrane of target cells

Signalreceptor

TARGETCELL

Signal receptor Transportprotein

Water-solublehormone

Fat-solublehormone

Generegulation

Cytoplasmicresponse

Generegulation

Cytoplasmicresponse

OR

Signal receptor

Water-solublehormone

Fat-solublehormone

TARGETCELL

NUCLEUS(a) (b)

Transportprotein

Signalreceptor

(a) NUCLEUS (b)

According to functional effects According to functional effects hormones can be:hormones can be:

а) affectors (act directly on organs - targets);

b) tropic (regulate synthesis of effecting hormones);

c) releasing-hormones (regulate synthesis and secretion of tropic hormones).

Multiple Effects of HormonesMultiple Effects of Hormones

The same hormone may have different The same hormone may have different effects on target cells that haveeffects on target cells that have• Different receptors for the hormoneDifferent receptors for the hormone• Different signal transduction pathwaysDifferent signal transduction pathways• Different proteins for carrying out the response Different proteins for carrying out the response

due to different transcription factors they due to different transcription factors they activateactivate

A hormone can also have different A hormone can also have different effects in different specieseffects in different species

Glycogendeposits

receptor

Vesseldilates.

Epinephrine

(a) Liver cell

Epinephrine

receptor

Glycogenbreaks downand glucoseis released.

(b) Skeletal muscle blood vessel

Same receptors but differentintracellular proteins (not shown)

Epinephrine

receptor

Different receptors

Epinephrine

receptor

Vesselconstricts.

(c) Intestinal blood vessel

Mechanisms of hormone actionMechanisms of hormone action

1. Target cells [with receptors]1. Target cells [with receptors] a. On cell membranea. On cell membrane b. Inside the cellb. Inside the cell2. Effects on target cells 2. Effects on target cells a. Membrane permeability or potentiala. Membrane permeability or potential b. Protein synthesisb. Protein synthesis c. Enzymesc. Enzymes d. Secretiond. Secretion e. Mitosise. Mitosis3. Plasma membrane receptors and second-messenger systems [all 3. Plasma membrane receptors and second-messenger systems [all

amino acid-based hormones amino acid-based hormones (except thyroid hormone) & (except thyroid hormone) & eicosanoids]eicosanoids]

a. The cyclic AMP signaling mechanism a. The cyclic AMP signaling mechanism 4. Intracellular receptors and direct gene activation [steroid (& thyroid) 4. Intracellular receptors and direct gene activation [steroid (& thyroid)

hormones]hormones]

Target cell specificityTarget cell specificity1. Blood levels of hormone1. Blood levels of hormone2. Number of hormone receptors [receptors are constantly being synthesized and broken down; 2. Number of hormone receptors [receptors are constantly being synthesized and broken down;

generally, a target cell has generally, a target cell has 2000-100,000 receptors for a particular hormone2000-100,000 receptors for a particular hormone]]• a. a. Down-regulationDown-regulation: decrease in number of receptors [i.e., hormone levels are high]: decrease in number of receptors [i.e., hormone levels are high]• b. b. Up-regulationUp-regulation: increase in number of receptors [i.e., hormone levels are low]: increase in number of receptors [i.e., hormone levels are low]3. Affinity of hormone & receptor3. Affinity of hormone & receptor4. Other hormones [see below, "Interaction of hormones at target cells"]4. Other hormones [see below, "Interaction of hormones at target cells"]

• Half-life, onset, and duration Half-life, onset, and duration of hormone activityof hormone activity

1. The concentration of a hormone reflects its rate of release, and the rate of inactivation and 1. The concentration of a hormone reflects its rate of release, and the rate of inactivation and removal from the body. removal from the body.

2. The half-life of a hormone is the duration of time a hormone remains in the blood, and is shortest 2. The half-life of a hormone is the duration of time a hormone remains in the blood, and is shortest for water-soluble hormones. for water-soluble hormones.

3. Target organ response and duration of response vary widely among hormones. 3. Target organ response and duration of response vary widely among hormones.

• Interaction of hormones at Interaction of hormones at target cellstarget cells

1. 1. PermissivenessPermissiveness [one hormone must be present in adequate amounts for the full exertion of [one hormone must be present in adequate amounts for the full exertion of another hormone's effect; e.g., thyroid hormone increases the number of receptors for another hormone's effect; e.g., thyroid hormone increases the number of receptors for epinephrine in cells]epinephrine in cells]

2. 2. SynergismSynergism [actions of several hormones are complementary and their combined effects is grater [actions of several hormones are complementary and their combined effects is grater than the sum of their separate effects; e.g., follicle stimulating hormone (FSH) and testosterone than the sum of their separate effects; e.g., follicle stimulating hormone (FSH) and testosterone on spermatogenesis]on spermatogenesis]

3. 3. AntagonismAntagonism [when one hormone causes the loss of another hormone's receptors; e.g., [when one hormone causes the loss of another hormone's receptors; e.g., progesterone inhibits uterine responsiveness to estrogen]progesterone inhibits uterine responsiveness to estrogen]

Etiology of endocrine disordersEtiology of endocrine disorders Reasons and kinds of endocrine disorders.Reasons and kinds of endocrine disorders. Among numerous Among numerous

ethiological factors of endocrine disorderss it is possible to select ethiological factors of endocrine disorderss it is possible to select the following main ones: the following main ones:

a mental trauma, a mental trauma, necrosis, necrosis, tumour, tumour, inflamatory process, inflamatory process, bacterial and viral infections, bacterial and viral infections, intoxications, intoxications, local disorders of blood circulation (hemorrhage, thrombosis), local disorders of blood circulation (hemorrhage, thrombosis), alimentary disorders (deficiency of iodine and cobalt in food and alimentary disorders (deficiency of iodine and cobalt in food and

drinking water, redundant consumption of carbohydrates),drinking water, redundant consumption of carbohydrates), ionising radiation,ionising radiation, inherent chromosome and gene defects.inherent chromosome and gene defects.

There are three variants of There are three variants of endocrine functions disorders:endocrine functions disorders:

1. HyperfunctionHyperfunction of endocrine glands

2. HypofunctionHypofunction of endocrine glands

3. DisfunctionDisfunction 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 Pathogenesis of endocrine disordersdisorders

Pathogenesis of endocrine Pathogenesis of endocrine disordersdisorders

• 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 mechanismsmechanisms:

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 Disorders of endocrine gland of endocrine gland regulationregulation

Regulation Regulation ofof endocrine gland endocrine gland activity can be carried out with the activity can be carried out with the help of four mechanisms:help of four mechanisms:

1. 1. NervousNervous ( (impulse-mediatorsimpulse-mediators) or) or parahypophysis regulation parahypophysis regulation. With the . With the help of direct nervous influences the activity of following structures is help of direct nervous influences the activity of following structures is regulated: regulated:

аа) ) adrenal medullaadrenal medulla; ; bb) ) neuroendocrineneuroendocrine structures structures of hypothalamus of hypothalamus; ; cc)) epiphysis epiphysis..2. 2. NeuroendocrineNeuroendocrine or or transhypophysartranshypophysar regulation regulation. It is carried out. It is carried out by by

neuroendocrine cells of hypothalamusneuroendocrine cells of hypothalamus, , which transform which transform nervous nervous impulses in specific impulses in specific endocrine endocrine process. Along releasing-hormones, process. Along releasing-hormones, which regulate activity of adenohypophysis are synthesized and get which regulate activity of adenohypophysis are synthesized and get secreted secreted in the system of portal vessels in the system of portal vessels of hypophysisof hypophysis..

3. 3. Endocrine regulationEndocrine regulation. It is that some hormones influence on . It is that some hormones influence on synthesis and other influence secretion of the others. An example of synthesis and other influence secretion of the others. An example of this mechanism is the influence of adenohypophysis tropic hormones this mechanism is the influence of adenohypophysis tropic hormones on activity of adrenal cortex, thyroid gland, sexual glands.on activity of adrenal cortex, thyroid gland, sexual glands.

4. 4. Non-endocrine humoral regulationNon-endocrine humoral regulation is carried out by unspecific is carried out by unspecific humoral factors, in particular by metabolites, ions. humoral factors, in particular by metabolites, ions.

Pathological processes which are

primarity developed in hypothalamusprimarity developed in hypothalamus lead

to disorders of transhypophysartranshypophysar and

parahypophysarparahypophysar regulation of endocrine

glands function. The activity of hypothalamic centers can be

disturbed also secondarilysecondarily in connection with disorders in limbicdisorders in limbic systemsystem (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 traumamental trauma and other stress influencesstress influences.

TranshypophysarTranshypophysar regulation includes regulation includes synthesis of synthesis of peptidespeptides which are which are moving by axonsmoving by axons and reach and reach adenohypophysisadenohypophysis in neurosecretory cells in neurosecretory cells of mediobasal part of hypothalamus. Here they either of mediobasal part of hypothalamus. Here they either stimulate or inhibit formation of tropic hormonesstimulate or inhibit formation of tropic hormones. .

Stimulating peptidesStimulating peptides have received the name of have received the name of liberins or releasing-factorsliberins or releasing-factors, they are: , they are:

thyroliberin, gonadoliberin, somatoliberin etc.thyroliberin, gonadoliberin, somatoliberin etc. Inhibiting peptidesInhibiting peptides are named are named statinsstatins – – thyrostatin, somatostatin etc. thyrostatin, somatostatin etc. Their ratio among themselves is determined formation Their ratio among themselves is determined formation

of of appropriate tropic hormoneappropriate tropic hormone. Then formation of tropic . Then formation of tropic hormones begins  in adenohypophysis – hormones begins  in adenohypophysis – somatotropicsomatotropic (STH), (STH), gonadotropic gonadotropic (GTH) etc. (GTH) etc.

Tropic hormonesTropic hormones act on appropriate targets and act on appropriate targets and stimulate derivation of hormones in appropriate glands, stimulate derivation of hormones in appropriate glands, and and STHSTH stimulates stimulates  formation  of formation  of somatomedines somatomedines in in tissues – polipeptide hormones, tissues – polipeptide hormones, through which they through which they actact..

• By means of parahypophysarparahypophysar 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 gonadotrophic hormones.

The disorders of The disorders of trans- and trans- and parahypophysarparahypophysar regulation regulation leads to disfunction of endocrine leads to disfunction of endocrine glands. glands.

The disturbance of one gland The disturbance of one gland function is called function is called monoglandularmonoglandular process, several glands – process, several glands – pluriglandular pluriglandular process. process.

The disorders of the glandular The disorders of the glandular function can be function can be partialpartial, when , when production of only one production of only one hormone is disturbed, or hormone is disturbed, or totaltotal, , when secretion of all hormones when secretion of all hormones is changed.is changed.

Role of mechanisms feedback bond Role of mechanisms feedback bond in endocrine disturbancesin endocrine disturbances

Role of mechanisms feedback bond Role of mechanisms feedback bond in endocrine disturbancesin endocrine disturbances

• The The mechanism of feedbackmechanism of feedback bond is obligated link in bond is obligated link in self self regulationregulation of glandular activity. The essence of negative of glandular activity. The essence of negative adverse effects is that formed hormones oppress activity of adverse effects is that formed hormones oppress activity of structures which carry out the previous stages of regulation. structures which carry out the previous stages of regulation.

• Therefore the Therefore the increase of secretionincrease of secretion of of effectory hormone through certain parts effectory hormone through certain parts causes causes decrease of its formationdecrease of its formation and and entering in bloodentering in blood, and on the contrary, the , and on the contrary, the decreasing of the hormone contentsdecreasing of the hormone contents in in blood causes blood causes increase of intensity of its increase of intensity of its formation and secretionformation and secretion. In this way . In this way regulation of cortizol secretion, thyroid and regulation of cortizol secretion, thyroid and sexual hormones is carried out.sexual hormones is carried out.

• By the principle of the mechanism of By the principle of the mechanism of feedback bond inhibition of the function feedback bond inhibition of the function (even atrophy) of the gland during (even atrophy) of the gland during treatment by their or other hormones can treatment by their or other hormones can occur. occur.

Pathway Example

StimulusLow pH induodenum

S cells of duodenumsecrete secretin ( )

Endocrinecell

Bloodvessel

PancreasTargetcells

ResponseBicarbonate release

Neg

ativ

e fe

edb

ack

–

• Hormones are assembled into regulatory pathways• A negative feedback loop inhibits a response by reducing the initial stimulus• Negative feedback regulates many hormonal pathways involved in homeostasis

Negative feedback and Negative feedback and antagonistic hormone pairs antagonistic hormone pairs are common features of the are common features of the endocrine systemendocrine system

Control of hormone releaseControl of hormone release1. Negative feedback ["stimulatory-inhibitory"]2. Positive feedback ["stimulatory-stimulatory"]3. Endocrine gland stimuli: humoral stimuli, neural stimuli, hormonal stimuli

Disorders of hormones Disorders of hormones biosynthesis and their biosynthesis and their

secretionsecretion

Disorders of hormones Disorders of hormones biosynthesis and their biosynthesis and their

secretionsecretion• Strictly glandular disorders of endocrine functions can be

conditioned:1. By changes of functionally active endocrine cells amount : • a) by decreasedecrease of their amount (removal of gland or its

part, damage, necrosis), that results to endocrine endocrine hypofunctionhypofunction;

• b) by increaseincrease of their amount (benignt and malignant tumors of glandular epithelium) that is accompanied by features of endocrine hyperfunctionendocrine hyperfunction.

2. Qualitative changes in cells:    • a) by disorders of biosynthesis of hormones; • b) by disorders of processes of their secretion.

• Strictly glandular disorders of endocrine functions can be conditioned:

1. By changes of functionally active endocrine cells amount : • a) by decreasedecrease of their amount (removal of gland or its

part, damage, necrosis), that results to endocrine endocrine hypofunctionhypofunction;

• b) by increaseincrease of their amount (benignt and malignant tumors of glandular epithelium) that is accompanied by features of endocrine hyperfunctionendocrine 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-The main possible reasons of protein-peptide hormones synthesis disorders are: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 glands associate with proteins

in blood  and circulate in two forms – connectedconnected and freefree. 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:

• а) hypofunctionhypofunction –  increase of hormone binding and decrease of its contents in the free form;

• b) hyperfunctionhyperfunction –  decrease of hormone binding and increase in blood of concentration of the free form.

DisorderDisorderss of of endocrine endocrine functions, connected functions, connected with disturbanceswith disturbances of interaction of of interaction of hormones hormones

withwith peripheral peripheral cellscells

• 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.

This gland makes me wake up in the This gland makes me wake up in the morning and ready to go!morning and ready to go!

Pineal Gland

melatonin

"The 3rd Eye""The 3rd Eye"

Coordination of Endocrine and Coordination of Endocrine and Nervous Systems in VertebratesNervous Systems in Vertebrates

The The hypothalamus hypothalamus receives information from receives information from the nervous system and initiates responses the nervous system and initiates responses through the endocrine systemthrough the endocrine system

Attached to the hypothalamus is the Attached to the hypothalamus is the pituitary pituitary gland gland composed of the posterior pituitary and composed of the posterior pituitary and anterior pituitaryanterior pituitary

The The posterior pituitary posterior pituitary stores and secretes stores and secretes hormones that are made in the hypothalamushormones that are made in the hypothalamus

The The anterior pituitary anterior pituitary makes and releases makes and releases hormones under regulation of the hypothalamushormones under regulation of the hypothalamus

This gland This gland is called the is called the “master “master gland” gland” because it because it secretes nine secretes nine hormones hormones many of which many of which control other control other endocrine endocrine glands by glands by feedback feedback control.control.

This gland This gland is called the is called the “master “master gland” gland” because it because it secretes nine secretes nine hormones hormones many of which many of which control other control other endocrine endocrine glands by glands by feedback feedback control.control.

Pituitary GlandPituitary Gland

Tropic effects only:FSHLHTSHACTH

Nontropic effects only:ProlactinMSH

Nontropic and tropic effects:GH

Anterior Pituitary

Posterior pituitary Stimulates milk

ejection and uterine contractions

Ovary and testisOxytocin

Conservation of body water

KidneyAntidiuretic hormone

Control of reproductive function

Ovary and testisFollicle stimulating hormone

Control of reproductive function

Ovary and testisLuteinizing hormone

Milk production Mammary glandProlactin

Stimulates secretion of glucocorticoids

Adrenal gland cortexAdrenocorticotrophic hormone

Stimulates secretion of thyroid hormones

Thyroid glandThyroid stimulating hormone

Promotes growth (indirectly), control of protein, lipid and carbohydrate metabolism

Liver, adipose tissueGrowth hormone

Major physiologic effects

Major target organsHormone

Type of Type of AdenomaAdenoma

SecretionSecretion StainingStaining PathologyPathology

Corticotrophic Corticotrophic adenomasadenomas

Secrete Secrete adrenocotrophic adrenocotrophic hormone (ACTH) and hormone (ACTH) and Proopiomelanocortin Proopiomelanocortin (POCM)(POCM)

BasophilicBasophilic Cushing’s diseaseCushing’s disease

Somatotrophic Somatotrophic adenomasadenomas

Secrete Secrete growth hormonegrowth hormone (GH)(GH)

AcidophilicAcidophilic Acromegaly Acromegaly (Gigantism)(Gigantism)

Thyrotrophic Thyrotrophic adenomas (rare)adenomas (rare)

Secret Secret thyroid stimulating thyroid stimulating hormone (TSH)hormone (TSH)

BasophilicBasophilic Occasionally Occasionally hyperthyroidism hyperthyroidism usually does not cause usually does not cause symptomssymptoms

Gonadotrophic Gonadotrophic adenomasadenomas

Secrete Secrete luteinizing hormone luteinizing hormone (LH), follicle stimulating (LH), follicle stimulating hormone (FSH)hormone (FSH)

BasophilicBasophilic Usually does not Usually does not cause symptomscause symptoms

ProlactinomasProlactinomas Secret Secret prolactinprolactin AcidophilicAcidophilic Galactorrhea, Galactorrhea, hypogonadism, hypogonadism, amenorrhea, amenorrhea, infertility and infertility and impotenceimpotence

Null cells Null cells adenomasadenomas

Do not secrete hormonesDo not secrete hormones May stain positive May stain positive for synaptophysinfor synaptophysin

Disturbances of functions of hypophysis.Hypofunction of adenohypophysis

(hypopituitaritism)

There are panhypopituitarity and partial hypopituitarityThere are panhypopituitarity and partial hypopituitarity

Panhypopituitarity – is the decrease of Panhypopituitarity – is the decrease of formation of  all adenohypophysis hormonesformation of  all adenohypophysis hormones

Panhypopituitarity – is the decrease of Panhypopituitarity – is the decrease of formation of  all adenohypophysis hormonesformation of  all adenohypophysis hormones

• The following clinical forms of  panhypopituitarity are known:  The following clinical forms of  panhypopituitarity are known:     1) Hypophysar cachecsia of SimondsSimonds; 2) Afterbearing necrosis of hypophysis – syndrome of Schegansyndrome 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 manifestationsclinical 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 symptomsfirst 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 disordersVessels 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 functiongonadotropic function of hypophysis and secretion of STH is damaged with the consequent connection of nonsufficient secretion of ТТH, ACTH and prolactine.

Hypophyseal Simond’s cachexia

Causes of HypopituitarismCauses of HypopituitarismTumors and mass lesions — pituitary adenomas, cysts,

metastatic cancer, and other lesionsPituitary surgery or radiationInfiltrative lesions and infections — hemochromatosis,

lymphocytic hypophysitisPituitary infarction — infarction of the pituitary gland after

substantial blood loss during childbirth (Sheehan’s syndrome)Pituitary apoplexy — sudden hemorrhage into the pituitary glandGenetic diseases — rare congenital defects of one or more

pituitary hormonesEmpty sella syndrome — an enlarged sella turcica that is not entirely filled with pituitary tissueHypothalamic disorders — tumors and mass lesions

(e.g., craniopharyngiomas and metastatic malignancies),hypothalamic radiation, infiltrative lesions (e.g., sarcoidosis),trauma, infections

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

Hypophysar Hypophysar nanismnanism

1) Hypophysar nanism (dwarfishnessdwarfishness) - deficiency of STHSTH;2) Secondary hypohonadism - deficiency of FSH and LHFSH and LH;3) Secondary hypothyrosisSecondary hypothyrosis - deficiency of TTHTTH;4) Secondary hypocorticismSecondary hypocorticism - deficiency of ACTHACTH.

• The insufficiency of STHThe insufficiency of STH results to development of hypophysar dwarfishness, or nanism and appears by such disorders:• 1) decrease of intensity of protein synthesisdecrease 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 STHdecrease of inhibiting action of STH on an

absorption of glucose with predominance of insulinic effect and development of hypoglycemia;

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

By producing too much of one or more hormonesBy producing too much of one or more hormones

• Adrenocorticotropic hormoneAdrenocorticotropic hormone::– causes weight gain (particularly in the body’s trunk, not causes weight gain (particularly in the body’s trunk, not

the legs or arms)the legs or arms)– high blood pressurehigh blood pressure– high blood sugarhigh blood sugar– brittle bonesbrittle bones– emotional changesemotional changes– stretch marks on the skinstretch marks on the skin– easy bruising.easy bruising.

The insufficiency of ACTH leads to secondary partial The insufficiency of ACTH leads to secondary partial insufficiency of adrenal cortex. insufficiency of adrenal cortex.

The glucocorticoid function suffers mainly. The glucocorticoid function suffers mainly. Mineralocorticoid function practically does not varyMineralocorticoid function practically does not vary

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

  Insufficiency of gonadotropic hormones Insufficiency of gonadotropic hormones results in results in decrease of ability of Sertoli cellsdecrease of ability of Sertoli cells to to accumulate androgensaccumulate androgens and and oppression of oppression of spermatogenesisspermatogenesis and and ability to impregnation ability to impregnation in menin men. .

In case of In case of defect of LGdefect of LG ( (LuteinizingLuteinizing) ) hormone the function of hormone the function of Leidig’s cells is Leidig’s cells is infringedinfringed, the formation of androgens ceases , the formation of androgens ceases and develops eunuchoidism with and develops eunuchoidism with preservation of partial ability to impregnation, preservation of partial ability to impregnation, as the process  of spermatozoids maturing as the process  of spermatozoids maturing does not stop.does not stop.

Hyperfunction of Hyperfunction of adenohypophysis adenohypophysis (hyperpituitarism)(hyperpituitarism)

The main reasons of The main reasons of

hyperpituitarism development are hyperpituitarism development are

the benign tumours – adenomas of endocrine cells.the benign tumours – adenomas of endocrine cells. There are There are   twotwo groups of adenomas groups of adenomas.. 1. 1. Eosinophilic adenomaEosinophilic adenoma, develops from , develops from

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

GigantismGigantism

Jane Bunford 2.41mJane Bunford 2.41m

Zeng Jinlian 249 smZeng Jinlian 249 smYao Defen 2.34Yao Defen 2.34

• By producing too much of one or more hormones

• Growth hormone: causes ACROMEGALY– a syndrome that includes:

• excessive growth of soft tissues and bones

• high blood sugar• high blood pressure• heart disease• sleep apnea• excess snoring• carpal tunnel syndrome• pain symptoms (including

headache).

• Acromegaly 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.

BITEMPORAL

HEMIANOPSIA

Usually the bitemporal hemianopsia is Usually the bitemporal hemianopsia is NOT perfectly symmeetrical. Why? NOT perfectly symmeetrical. Why?

Because pituitary tumors are under no Because pituitary tumors are under no law to grow perfectly midline.law to grow perfectly midline.

• 2. Basophilic adenomaBasophilic adenoma, grows from basophilic cells of adenohypophysis which more often produce ACTH. During this the Itsenko-Cushing 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.

BASOPHILIC ADENOMA OF HYPOPHYSISBASOPHILIC ADENOMA OF HYPOPHYSIS

Hyperfunction of neurohypophysisHyperfunction of neurohypophysis• Leads to redundant production vasopressin and Leads to redundant production vasopressin and

oxytocin. Their main effects:oxytocin. Their main effects:• VasopressineVasopressine (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 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.

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Hypofunction of neurohypophysisHypofunction of neurohypophysis

Insufficient production of vasopressin results to Insufficient production of vasopressin results to development of development of diabetes insipidusdiabetes insipidus. .

There are two pathogenetic variants: There are two pathogenetic variants: central (neurogenic)central (neurogenic) during which will a little quantity of during which will a little quantity of

vasopressine, is formed and vasopressine, is formed and nephrogenic nephrogenic duringduring which the sensitivity of epithelial which the sensitivity of epithelial

cells receptors of distal nephron parts and collective cells receptors of distal nephron parts and collective tubules to vasopressin action (absence or a little quantity tubules to vasopressin action (absence or a little quantity receptors) is reduced. receptors) is reduced.

The The decreasing of water reabsorptiondecreasing of water reabsorption in kidneys results in kidneys results to to poliuriapoliuria and decreasing of circulatting blood volume  and decreasing of circulatting blood volume  ((hypovolemiahypovolemia), ), falling of arterial pressurefalling of arterial pressure and and hypoxiahypoxia..

The The decreasing of oxytocindecreasing of oxytocin production appears by production appears by disorders of lactation, weakness of labor activitydisorders of lactation, weakness of labor activity..

Adrenal cortex - secretes several classes of steroid hormones (glucocorticoids and mineralocorticoids) - with three concentric zones of cells that differ in the major steroid hormones they secrete.

Adrenal medulla - source of the catecholamines epinephrine and norepinephrine. - chromaffin cell is the principle cell type. - The medulla is richly innervated by preganglionic sympathetic fibers and is, in essence, an extension of the sympathetic nervous system.

Effects ofmineralocorticoids:

Effects ofglucocorticoids:

1. Retention of sodium ions and water by kidneys

2. Increased blood volume and blood pressure

2. Possible suppression of immune system

1. Proteins and fats broken down and converted to glucose, leading to increased blood glucose

Adrenalgland

Kidney

Adrenal cortex

Adrenal cortexGlucocorticoids – glucose from noncarb sources, such as musclesMineralocorticoids (aldosterone) – induces kidneys to reabsorb water and saltsBoth of these deal with long-term stress

Actions of CortisolActions of CortisolMajor InfluenceMajor Influence Effect on BodyEffect on Body

Glucose metabolismGlucose metabolismStimulates gluconeogenesisStimulates gluconeogenesisDecreases glucose use by the tissuesDecreases glucose use by the tissues

Protein metabolismProtein metabolismIncreases breakdown of proteinsIncreases breakdown of proteinsIncreases plasma protein levelsIncreases plasma protein levels

Fat metabolismFat metabolismIncreases mobilization of fatty acidsIncreases mobilization of fatty acidsIncreases use of fatty acidsIncreases use of fatty acids

Anti-inflammatory action Anti-inflammatory action (pharmacologic levels)(pharmacologic levels)

Stabilizes lysosomal membranes of the inflammatory cells, preventing Stabilizes lysosomal membranes of the inflammatory cells, preventing the release of inflammatory mediatorsthe release of inflammatory mediators

Decreases capillary permeability to prevent inflammatory edemaDecreases capillary permeability to prevent inflammatory edemaDepresses phagocytosis by white blood cells to reduce the release of Depresses phagocytosis by white blood cells to reduce the release of

inflammatory mediatorsinflammatory mediatorsSuppresses the immune responseSuppresses the immune response Causes atrophy of lymphoid tissueCauses atrophy of lymphoid tissue Decreases eosinophilsDecreases eosinophils Decreases antibody formationDecreases antibody formation Decreases the development of cell-mediated immunityDecreases the development of cell-mediated immunityReduces feverReduces feverInhibits fibroblast activityInhibits fibroblast activity

Psychic effectPsychic effect May contribute to emotional instabilityMay contribute to emotional instability

Permissive effectPermissive effectFacilitates the response of the tissues to humoral and neural influences, Facilitates the response of the tissues to humoral and neural influences,

such as that of the catecholamines, during trauma and extreme stresssuch as that of the catecholamines, during trauma and extreme stress

Disorders of adrenal gland Disorders of adrenal gland functionfunction

The most frequently there are following The most frequently there are following manifestations:manifestations:

1) 1) HypofunctionHypofunction of adrenal cortex - of adrenal cortex - hypocorticism hypocorticism Addison diseaseAddison disease;;

2) 2) HyperfunctionHyperfunction of fascicular zone - of fascicular zone - syndrome of syndrome of Itsenko-CushingItsenko-Cushing – – Hypersecretion of cortisolHypersecretion of cortisol;;

3) 3) HyperfunctionHyperfunction of glomerulose zone – of glomerulose zone – hyperaldosteronism – hyperaldosteronism – Hyperfunction of Hyperfunction of adrenal cortex resulting in excess secretion adrenal cortex resulting in excess secretion of aldosteroneof aldosterone;;

4) 4) DysfunctionDysfunction of adrenal cortex - of adrenal cortex - adrenogenital syndrome adrenogenital syndrome

Insufficiency of adrenal cortex• According to etiology there are primary and secondary

kinds of adrenal cortex insufficiency. • Primary insufficiencyPrimary insufficiency arises as a result of adrenals injury,• secondarysecondary is connected with the defeat of hypotalamus

(deficiency of corticoliberin), or with hypofunction of adenohypophysis (deficiency of ACTH).

• Insufficiency of corticosteroids can be totaltotal when the operation of all hormones drops out, and partial partial fallout of activity of one adrenal hormone.

• Insufficiency of adrenal cortex can be acuteacute and chronicchronic.• Examples of Examples of acute insufficiencyacute insufficiency are 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 The chronic insufficiencychronic insufficiency of of adrenals cortex is characterized foradrenals cortex is characterized for Adison’s disease Adison’s disease (bronzed disease).(bronzed disease).

• The most often reasons of it are:The most often reasons of it are:

а) tuberculose destruction of adrenals;

b) autoimmune process. Tuberculose of adrenal gland. Adison’s disease

Skin hyperpigmentation at case of Adison’s disease

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

• 1) dehydration develops owing to loss of sodium ionsloss 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 hypoxiadisorders of microcirculation and hypoxia;

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

• 5) hyperpotassiumemia is stipulated by decrease of canales decrease of canales secretion of potassium ionssecretion 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 disorders of acidogenesisacidogenesis 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.

ІІІІ. Manifestations stipulated by disorders of . Manifestations stipulated by disorders of glucocorticoid function of adrenals. To such glucocorticoid function of adrenals. To such

manifestations concern:manifestations concern:

ІІІІ. Manifestations stipulated by disorders of . Manifestations stipulated by disorders of glucocorticoid function of adrenals. To such glucocorticoid function of adrenals. To such

manifestations concern:manifestations concern: • 1) hypoglycemia which results to starvation;             • 2) arterial hypotension (permissive reaction on catecholamines); • 3) decrease reaction of fat tissue on lipotrophic 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 osmotic 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 functionIncrease of adrenals cortex function •  HyperaldosteronismHyperaldosteronism.. Arises during hyperfunction of glomerular zone  of

adrenals cortex, which produce mineralcorticoides.There are primaryprimary and secondary hyperaldosteronismsecondary hyperaldosteronism.•  Primary hyperaldosteronismPrimary hyperaldosteronism (Conn syndromeConn 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 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.

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

a) arterial hypertension; b) edemas;                                   c) hypopotassiumaemia; d) ungas alcalosis.

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

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

2. Cushing’s syndromeCushing’s syndrome: • а) tumoral – adenoma of zona

fasticulata of adrenal cortex; • b) ectopic production of

АCТH by some malignant tumors (pulmonar cancer);        

• c) iatrogenic – introduction of glucocorticoides in an organism with the medical purpose.

MOON FACIES

BUFFALO HUMP

STRIAE

Glucocorticoid Glucocorticoid hypercorticism appears by: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.

• Adrenogenital syndromeAdrenogenital 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.

Adrenogenital  Adrenogenital  syndromesyndrome

Disorders of adrenal medulla functionDisorders of adrenal medulla function Hypofunction of adrenal medullaHypofunction of adrenal medulla happens  happens

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

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

HYPOADRENALISMHYPOADRENALISMCaused by any anatomic or metabolic lesion of the adrenal Caused by any anatomic or metabolic lesion of the adrenal cortex that impairs output of the cortical steroids.cortex that impairs output of the cortical steroids.Primary Acute Adrenal InsufficiencyPrimary Acute Adrenal Insufficiency

-- Waterhouse Friderichsen Syndrome Waterhouse Friderichsen Syndrome due to overwhelming septicemic infection caused by due to overwhelming septicemic infection caused by

meningococci, but occasionally other virulent meningococci, but occasionally other virulent organism such as gonococci,pneumococi and organism such as gonococci,pneumococi and staphylococci.staphylococci.

morphology: massive bilateral adrenal hemorrhagemorphology: massive bilateral adrenal hemorrhage

ADRENAL MEDULLAADRENAL MEDULLA

PHEOCHROMOCYTOMA:PHEOCHROMOCYTOMA:

- associated with catecholamine-

Induced hypertension.

- occassionally, this tumor produces other biogenic steroids or peptides associated with Cushing’s Syndrome.

-morphology: - ave . weight of 100 gms

- Zellballen appearance

This large adrenal neoplasm This large adrenal neoplasm has been sectioned in half. has been sectioned in half. Note the grey-tan color of the Note the grey-tan color of the tumor compared to the yellow tumor compared to the yellow cortex stretched around it and cortex stretched around it and a small remnant of remaining a small remnant of remaining adrenal at the lower right. adrenal at the lower right. This patient had episodic This patient had episodic hypertension. This is a tumor hypertension. This is a tumor arising in the adrenal medulla arising in the adrenal medulla - a - a pheochromocytomapheochromocytoma. .

T

N

Cardiovascular:Cardiovascular: Coronary artery Coronary artery disease, hypertension, stroke, arrhythmia. disease, hypertension, stroke, arrhythmia. Muscles:Muscles: Tension headaches, backache Tension headaches, backache Connective tissues:Connective tissues: Rheumatoid arthritis Rheumatoid arthritis Pulmonary:Pulmonary: Asthma.Asthma. Immune:Immune: Immunosuppression, deficiency, Immunosuppression, deficiency,

autoimmunityautoimmunity Gastrointestinal:Gastrointestinal: Ulcer, irritable bowel Ulcer, irritable bowel

syndrome, diarrhea, nausea and vomiting, syndrome, diarrhea, nausea and vomiting, ulcerative colitisulcerative colitis

Integumetary:Integumetary: Eczema, neurodermatitis, Eczema, neurodermatitis, acneacne

Endocrine:Endocrine: Diabetes mellitus, amenorrhea Diabetes mellitus, amenorrhea Central nervous:Central nervous: Fatigue and lethargy, Fatigue and lethargy,

type A behavior, overeating, depression, type A behavior, overeating, depression, insomnia.insomnia.

Literature: Literature: 1.1. General and clinical pathophysiology / Edited by Anatoliy V. General and clinical pathophysiology / Edited by Anatoliy V.

Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P. Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P. 588588––612612..2.2. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko,

I.P. Gurcalova // Study guide for medical students and practitioners. I.P. Gurcalova // Study guide for medical students and practitioners. Edited by prof.Zaporozan, OSMU. – Odessa. – 2005.– P. 271–282. Edited by prof.Zaporozan, OSMU. – Odessa. – 2005.– P. 271–282.

3.3. Essentials of Pathophysiology: Concepts of Altered Health States Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams & Wilkins), Trade paperback. – 2003 (Lippincott Williams & Wilkins), Trade paperback. – 2003 / / Carol Carol Mattson Porth, Kathryn J. Gaspard. – Chapter 30, 31. – P. 529–545. Mattson Porth, Kathryn J. Gaspard. – Chapter 30, 31. – P. 529–545.

4.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. – 2010. – P. 484–493, 506–512.medicine Publishing. – 2010. – P. 484–493, 506–512.

5.5. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart. New York. – 2000. – P. 256–271. Thieme. Stuttgart. New York. – 2000. – P. 256–271.

6.6. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition. Copyright ВJ. – 3th edition. Copyright В. . – Lippincott Williams & Wilkins – 2008. – – Lippincott Williams & Wilkins – 2008. – Chapter 9. – P. 245– 249, 251–255, 260–264, 267–274, 277–279.Chapter 9. – P. 245– 249, 251–255, 260–264, 267–274, 277–279.

7.7. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. – 2007. – Chapter Abbas, Fauto. – 2007. – Chapter 2020. – P. . – P. 751–757, 789–801751–757, 789–801..

8.8. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 904–914, Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 904–914, 920–926, 931–936.920–926, 931–936.

9.9. Pathophysiology, Concepts of Altered Health States, Carol Mattson Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin. – New York, Milwaukee. – 2009. – P. 1008–1030.Porth, Glenn Matfin. – New York, Milwaukee. – 2009. – P. 1008–1030.