Endocrine Diseases Endocrine Diseases Endocrine Diseases Endocrine Diseases Th P th l i l B i f Di Qiao Qiao Li MD PhD Li MD PhD The Pathological Basis of Disease - Graduate Course CMM5001 Graduate Course CMM5001 Qiao Qiao Li, MD, PhD Li, MD, PhD Faculty of Medicine Faculty of Medicine University of Ottawa University of Ottawa Qi Li@ Qi Li@ Qiao.Li@uottawa.ca Qiao.Li@uottawa.ca Q L
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Parathyroid glands(on dorsal aspect of thyroid gland)
• Pituitary • Thyroid • Parathyroid
Thymus
Adrenal glands
• Adrenal Neuroendocrine organ
HypothalamusPancreas
Gonads
Hypothalamus Exocrine & endocrine
Pancreas, gonads, placenta Other
• Testis (male)• Ovary (female) Other
Thymus, heart, kidney etc.
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Characteristics
Originll l d i f th ith li ( ll th l )all glands arise from the epithelium (all three germ layers)
Microscopic Structure d l h ll f lli l & b d t ill icords, clumps, hollow follicles & abundant capillaries
Merocrine Secretion
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Endocrine Function
Controls & IntegratesG th d d l tGrowth and developmentMaintenance of electrolyte, water & nutrient balance of bloodRegulation of cellular metabolism & energy balanceMobilization of body defensesReproduction
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Homeostasis
Hypothalamus connectsi h d i i i inervous with endocrine via pituitary
Hypothalamic is controlled by neural connections negative feedback from hormones
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Homeostatic ImbalanceHomeostatic Imbalance
Increases risk of diseaseCauses changes associated with agingCauses changes associated with aging
control systems less efficient
most disease seen as a disturbance of homeostasis (homeostatic imbalance)
aging associated with progressiveaging associated with progressive decrease in our ability to maintain
homeostasis (greater risk for illness)
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The Summary
Hypothalamic Hormone Anterior Pituitary Hormone Target Organ
Described as “accessory renal tissue”, “loose flesh” (left gland) by Claudius Galen (130-201) Depicted in 1552 by Bartholomeaus Eustachius on copper plateR d d b i i 1563
Three layers of cortex produce three corticosteroids Zona glomerulosa - mineralocorticoids Zona glomerulosa mineralocorticoids Zona fasciculata - glucocorticoids Zona reticularis - gonadocorticoids
CapsuleZona
glomerulosa
Hormonessecreted
Aldosterone
g
Cor
tex
Zonafasciculata
Adrenal gland• Medulla• Cortex
Kid
Cortisolandandrogens
Med
ulla
Zonareticularis
Adrenalmedulla
Kidneyandrogens
Epinephrineandnorepinephrine
Photomicrograph (115x)Drawing of the histology of theadrenal cortex and a portion ofthe adrenal medulla
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Adrenal Gland – Low Power
Capsule
Periadrenal fatZona glomerulosa
Zona fasciculata
Zona reticularis
Medulla
The Internet Pathology Laboratory
for Medical Education
Adrenal Gland – Low & High Power
HP
sinusoid
HP-zrHP-zf
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Adrenal Cortex Steroids
Zone Class Representative Physiologic Effects
glomerulosa mineralocorticoids aldosterone salt and water homeostasis
reticularis sex steroids androgens & estrogen minimal effects
O CH2OH O
CH2OH O
O CH
O O O
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Adrenal Steroidogenesis
Glucocorticoids & the Receptor
CortisolCortisol (hydrocortisone) (hydrocortisone) the majority of the majority of glucocorticoidglucocorticoid activity in most mammalsactivity in most mammals
90% f i l ti90% f i l ti ti lti l bi d tbi d t ti lti l bi dibi di 90% of circulating 90% of circulating cortisolcortisol binds to binds to cortisolcortisol binding binding globulin (CBG), for transportation, also limiting the rate globulin (CBG), for transportation, also limiting the rate of metabolic clearance & the concentration fluctuationof metabolic clearance & the concentration fluctuation
E t ll b i diff iE t ll b i diff i Enter cells by passive diffusionEnter cells by passive diffusion
Histone acetylationp300/CBP
TAFII250
RNA Pol IITBP
RNA Pol II
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Effects & Usage of Effects & Usage of Glucocorticoids
Carbohydrate, proteins and fat metabolismCarbohydrate, proteins and fat metabolismgluconeogenesisgluconeogenesisg gg gmuscle breakdownmuscle breakdownlipolysislipolysis
AntiAnti--inflammatory and immunosuppressiveinflammatory and immunosuppressive
Medical Application:Medical Application:arthritis, dermatitisarthritis, dermatitisautoimmune diseases autoimmune diseases fear phobicfear phobicfear phobicfear phobic
* 1656: * 1656: Thomas Wharton Thomas Wharton - Adrenals took something from the nerves and secreted it into the circulation
* 1936: * 1936: Edward Kendall and Edward Kendall and TadeusTadeus ReichsteinReichstein- Isolation and synthesis of cortisone
* 1949:* 1949: Edward Kendall and Philip HenchEdward Kendall and Philip Hench 1949: 1949: Edward Kendall and Philip HenchEdward Kendall and Philip Hench-- Effects of cortisone and ACTH on rheumatoid arthritisEffects of cortisone and ACTH on rheumatoid arthritis
* 1950: Nobel Prize to * 1950: Nobel Prize to Kendall, Reichstein & HenchKendall, Reichstein & Hench"for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects"
* General languor and debility* Remarkable feebleness of the heart's action* P li h i th l f th ki* Peculiar change in the color of the skinChronic adrenocortical insufficiency
progressive destruction of 90%of cortexprogressive destruction of 90%of cortex extreme weakness and fatigue extreme weakness and fatigue unintentional weight lossunintentional weight lossloss of appetiteloss of appetiteloss of appetite loss of appetite darkening of the skindarkening of the skinlow blood pressure, low blood pressure, dizziness or faintingdizziness or faintingcraving for saltcraving for salt
Thomas Addison 1855
craving for saltcraving for saltnausea, diarrhea, vomitingnausea, diarrhea, vomitingirritability, depression irritability, depression
For people with Addison’s Disease i t 1930 90% di d ithi 5 prior to 1930, 90% died within 5 years from 1930, much better prognosis since 1950, normal life span