Download An Introduction to Endocrinology

An Introduction to Endocrinology
Chapter 18 & 19 Human Physiology by Sherwood
BROWN-SEQUARD
- Bull testicle extracts
-  Rejuvination
-  Organotheraphy
-  Placebo
-  Success in 1891
STARLING & BAYLISS
X
Cannula
X
- pancreatic duct
Pancreatic
secretions
Drops out of pancreas
Addition of an extract of jejunal mucosa (acidic) into the blood
Defined “hormone”……
“THESE CHEMICAL MESSENGERS,
HOWEVER, OR “HORMONES” (FROM THE
GREEK, I EXCITE OR AROUSE), AS WE
MIGHT CALL THEM, HAVE TO BE CARRIED
FROM THE ORGANS WHERE THEY ARE
PRODUCED TO THE ORGAN WHICH THEY
AFFECT BY MEANS OF THE BLOODSTREAM
AND THE CONTINUALLY RECURRING
PHYSIOLOGICAL NEEDS OF THE
ORGANSISM MUST DETERMINE THEIR
REPEATED PRODUCTION AND
CIRCULATION THROUGH THE BODY…”
Endocrine system
- A chemical communication system in body
- Hormone-secreting ductless glands
- Hormones : chemical messenger carried by blood
from endocrine gland to target tissue
Hormones
1. Amines (melatonin, thyroid hormones, catecholamines)
2. Peptides/Proteins (insulin)
3. Steroids (cortisol, androgens, oestrogen)
Endocrine System
Major endocrine glands
Physiological Functions
•  Regulation of salt and water balance
•  Regulation of calcium balance
•  Regulation of energy balance/metabolism
•  Coping with a hostile environment (induce adaptive changes)
•  Co-ordination of growth
•  Reproduction and lactation
•  Regulation of circulation and digestion
Hormone: is a chemical secreted by a cell or group of cells into
the blood for transport to a distant target, where it exerts its
effect at very low concentrations.
Receptors in
target organ
Target organ
- hormone influences function of target
Endocrine gland
- releases hormone into blood
Tropic Hormones
•  Regulates hormone secretion by another
endocrine gland
•  Stimulates and maintains their endocrine target
tissues
•  Example
–  Thyroid-stimulating hormone (TSH) secreted from
anterior pituitary stimulates thyroid hormone
secretion by thyroid gland
Termination of action
•  Allows body to adapt to changes in it’s internal state
MECHANISMS OF CONTROL
- limit secretion
- remove/inactivate (metabolites are excreted)
- terminating activity in target cells
Plasma Concentration of Hormones
is influenced by:
•  1. The hormone rate of secretion
•  2. The rate of Metabolic Activation or Conversion
•  3. Transport
•  4. Inactivation
•  5. Excretion
Endocrine Dysfunction
•  Can arise from a variety of factors
•  Most commonly result from abnormal plasma
concentrations of a hormone caused by
inappropriate rates of secretion
–  Hyposecretion
•  Too little hormone is secreted
–  Hypersecretion
•  Too much hormone is secreted
Hyposecretion
•  Primary hyposecretion
–  Too little hormone is secreted due to abnormality within
gland
–  Causes
•  Genetic
•  Dietary
•  Chemical or toxic
•  Immunologic
•  Other disease processes such as cancer
•  Secondary hyposecretion
–  Gland is normal but too little hormone is secreted due to
deficiency of its tropic hormone
Hypersecretion
•  Causes
–  Tumors that ignore normal regulatory input and
continuously secrete excess hormone
–  Immunologic factors
•  Primary hypersecretion
–  Too much hormone is secreted due to
abnormality within gland
•  Secondary hypersecretion
–  Excessive stimulation from outside the gland
causes oversecretion
1. Pituitary Gland
Anatomy of the Pituitary Gland
epithelial tissue
nervous tissue
Chapter 18 The Central Endocrine Glands
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Pituitary Gland
•  Hypophysis
•  Small gland located in bony cavity just below
hypothalamus
–  Thin stalk connects pituitary gland to hypothalamus
•  Consists of two anatomically and functionally
distinct lobes
–  Posterior pituitary (neurohypophysis)
•  Composed of nervous tissue
–  Anterior pituitary (adenohypophysis)
•  Consists of glandular epithelial tissue
Pituitary Gland
•  Posterior pituitary
–  Along with hypothalamus forms neuroendocrine
system
–  Does not actually produce any hormones
–  Stores and releases two small peptide hormones:
•  Vasopressin - Conserves water during urine formation
•  Oxytocin - Stimulates uterine contraction during
childbirth and milk ejection during breast-feeding
Pituitary Gland
Anterior Pituitary
–  Secretes 6 different peptide hormones
•  Tropic hormones
– Thyroid-stimulating hormone (TSH)
» Stimulates secretion of thyroid hormone
– Adrenocorticotropic hormone (ACTH)
» Stimulates secretion of cortisol by adrenal cortex
– Growth hormone (GH)
» Primary hormone responsible for growth
•  Not a tropic hormone
– Prolactin (PRL)
» Enhances breast development & milk production
2. Hypothalamus
Releasing/inhibiting
Releasing
Gonadotrophin releasing hormone
- stimulates FSH/LH release by A.pituitary
Corticotrophin releasing hormone
- response to stress
Inhibiting
Prolactin inhibiting hormone
Growth hormone inhibiting hormone
Dopamine
Act locally as neurotransmitters
Growth Hormone (P.P.)
•  Primarily promotes growth indirectly by stimulating liver’s
production of somatomedins
–  Primary somatomedin is insulin-like growth factor (IGF-1 -2)
•  Acts directly on bone and soft tissues to bring about most growthpromoting actions
•  Stimulates protein synthesis, cell division, and lengthening and
thickening of bones
- Exerts metabolic effects not related to growth
–  Increases fatty acid levels in blood by enhancing breakdown of triglyceride fat
stored in adipose tissue
–  Increases blood glucose levels by decreasing glucose uptake by muscles
Growth Hormone Abnormalities
•  Growth hormone deficiency
–  Due to pituitary defect or hypothalamic dysfunction
–  Hyposecretion of GH in child is one cause of dwarfism
–  Deficiency in adults produces relatively few symptoms
Growth Hormone Abnormalities
•  Growth hormone excess
–  Most often caused by tumor of GH-producing cells of anterior
pituitary
–  Symptoms depend on age of individual when abnormal
secretion begins
•  Gigantism
– Caused by overproduction of GH in childhood
before epiphyseal plates close
•  Acromegaly
– Occurs when GH hypersecretion occurs after
adolescence
Acromegaly
Giantism
3. Thyroid
Follicular cells
Synthesise Thyroglobulin
- exocytosed into colloid
Iodine
- transferred from blood to colloid
Bind together (Storage)
Reuptake by follicular cells
degraded & secreted
Thyroxine (T4)
Tri-iodothyronine (T3)
Thyroid follicles
Effects of thyroid hormone
–  Main determinant of basal metabolic rate
–  Influences synthesis and degradation of
carbohydrate, fat, and protein
–  Increases target-cell responsiveness to
catecholamines
–  Increases heart rate and force of contraction
–  Essential for normal growth
–  Plays crucial role in normal development of
nervous system
Hypothyroidism
•  Causes
– Primary failure of thyroid gland
– Secondary to a deficiency of TRH, TSH, or both
– Inadequate dietary supply of iodine
•  Cretinism
– Results from hypothyroidism from birth
•  Myxedema
– Term often used for myxedema in adults
•  Treatment
– Replacement therapy
– Dietary iodine
Hyperthyroidism
•  Most common cause is Graves’ disease
– Autoimmune disease
– Body erroneously produces thyroid-stimulating
immunoglobulins (TSI)
– Characterized by exopthalmos
•  Treatment
– Surgical removal of a portion of the over-secreting
thyroid
– Administration of radioactive iodine
– Use of antithyroid drugs
4. Adrenal Glands
Adrenal Glands
•  Embedded above each kidney
in a capsule of fat
•  Composed of two endocrine organs
–  Adrenal cortex
•  Outer portion
•  Secretes steroid hormones (aldostrone, cortisol)
–  Adrenal medulla
•  Inner portion
•  Secretes catecholamines
Cortisol
–  Secretion - Regulated by the pituitary through Adrenocorticotropic
hormone (ACTH)
–  Displays a characteristic diurnal rhythm
–  Stimulates hepatic gluconeogenesis
–  Inhibits glucose use by many tissues (except brain!)
–  Stimulates protein degradation in many tissues, especially
muscle also facilitates lipolysis
–  Plays key role in adaptation to stress
–  At pharmacological levels, can have anti-inflammatory and
immunosuppressive effects
•  Long-term use can result in unwanted side effects
Cortisol Hypersecretion
–  Cushing’s syndrome
Cushing
–  Causes
•  Overstimulation of adrenal cortex by excessive
amounts of CRH and ACTH
•  Adrenal tumors that uncontrollably secrete
cortisol independent of ACTH
•  ACTH-secreting tumors located in places other
than the pituitary
–  Signs and symptoms
•  Hyperglycemia and glucosuria (adrenal
diabetes)
•  Abnormal fat distributions
–  “buffalo hump” and “moon face”
Addison’s Disease
Adrenocortical insufficiency
Autoimmune disease
Aldosterone deficiency
Hyperkalemia and hyponatremia
Cortisol deficiency
Hypoglycemia
Lack of permissive action for
many metabolic activities
Poor response to stress
‘Addisonian crisis’
5. Pancreas
–  Endocrine cells – Islets of Langerhans
•  Β (beta) cells
–  Site of insulin synthesis and secretion
•  Α (alpha) cells
–  Produce glucagon
•  D (delta) cells
–  Pancreatic site of somatostatin
synthesis
•  PP cells
–  Least common islet cells
–  Secrete pancreatic polypeptide
•  Insulin and glucagon
–  Most important in regulating fuel metabolism
Insulin
Important after meal
Secretion is increased during absorptive state
•  Primary stimulus for secretion is increase in blood
glucose concentration
•  Promotes cellular uptake of glucose, fatty acids, and
amino acids and enhances their conversion into
glycogen, triglycerides, and proteins, respectively
Lowers blood concentration of these small organic molecules
Glucagon
–  Mobilizes energy-rich molecules from storage
sites during postabsorptive state
–  Secreted in response to a direct effect of a fall in
blood glucose on pancreatic α cells
–  Generally opposes actions of insulin
Diabetes mellitus
Describes several syndromes of abnormal
carbohydrate metabolism that are characterised
by hyperglycaemia.
Impairment in insulin secretion
Varying degrees of peripheral resistance
to the action of insulin.
Diabetes mellitus
•  Type I (insulin-dependent, juvenile-onset)
–  Lack of insulin secretion by ß-cells in pancreas
–  Require exogenous insulin for survival
•  Type II (non insulin-dependent, adult onset)
–  Normal insulin levels produced
–  Target cells less responsive to insulin
Diabetes insipidus (DI) not related to the above
Diabetes is NOT a mild disease
Stroke
Diabetic
retinopathy
Leading cause
of blindness
in working-age
adults1
2- to 4-fold increase in
cardiovascular
mortality and stroke3,4
Cardiovascular
disease
75% diabetic patients
die from CV events4
Diabetic
nephropathy
Leading cause of
end-stage renal disease2
Diabetic
neuropathy
Leading cause of
non-traumatic lower
extremity amputations5
Worldwide prevalence of
TII diabetes in 2030 (projected)
Number of persons
< 5,000
5,000–74,000
75,000–349,000
350,000–1,499,000
1,500,000–4,999,000
> 5,000,000
No data available
Total cases > 300 million adults
World Health Organization Diabetes Programme Facts and Figures.
www.who.int/diabetes/facts/world_figures/en. Accessed 21/07/2005.
Central obesity contributes to
hyperglycemia
Obesity
Visceral Fat
Liver
Glucose
output
Free fatty acids
Insulin Resistance
Muscle
Glucose
uptake