Transcript Chapter 1 A Perspective on Human Genetics

Chapter 19
The Peripheral Endocrine Glands
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Peripheral Endocrine Glands
• Outline
• Thyroid glands
– Anatomy and hormones
• Adrenal glands
– Anatomy and hormones
– Stress response
• Fuel metabolism
• Calcium metabolism
• Pancreas
Follicular cells
Arranged into hollow spheres
Forms functional unit called a
follicle
Lumen filled with colloid
Serves as extracellular
storage site for thyroid
hormone
Produce two iodine-containing
hormones derived from amino
acid tyrosine
Tetraiodothyronine (T4 or
thyroxine)
Tri-iodothyronine (T3)
C cells
Secrete peptide hormone
calcitonin
Fig. 19-1b, p. 684
Thyroid hormone synthesis and release
• Synthesis
– Tg = thyroglobulin
– Transport of Tg to colloid
– Iodine uptake to colloid
– Iodination of tyrosine
– Coupling
• Release
– Stored as Tg
– Phagocytes “bite” Tg
containing colloid
– Phagocytes cleave T3 and
T4 from Tg in the follicular
cells
– T3 and T4 diffuse to blood
(TBG carrier protein in
blood)
– Iodine is recycled after
metabolism
– Activity
• 90% T4 but T3 is 4X as
potent
Colloid
Blood
Thyroid follicular cell
*Endoplasmic
reticulum/Golgi
complex
Lysosome
DIT = Di-iodotyrosine
T3 = Tri-iodothyronine
T4 = Tetraiodothyronine (thyroxine)
TGB = Thyroglobulin
I = Iodine
MIT = Monoiodotyrosine
Fig. 19-2, p. 685
Thyroid Gland
• Effects of thyroid hormone
– Main determinant of basal metabolic rate and
heat production
– Influences synthesis and degradation of
carbohydrate, fat, and protein (intermediary
metabolism)
– Increases target-cell responsiveness to
catecholamines (sympathomimetic effect)
– Increases heart rate and force of contraction
– Essential for normal growth
– Plays crucial role in normal development of
skeleton and nervous system (stimulates GH and
IGF-1)
Thyroid Gland
• Secretion
– Regulated by negative-feedback system between
hypothalamic TRH, anterior pituitary TSH, and
thyroid gland T3 and T4
– Feedback loop maintains thyroid hormones
relatively constant
Stress
Cold in
infants
Hypothalamus
Thyrotropinreleasing
hormone (TRH)
Anterior pituitary
Thyroid-stimulating
hormone (TSH)
Thyroid gland
Thyroid hormone
(T3 and T4)
Metabolic rate and heat production;
enhancement of growth and CNS
development; enhancement of
sympathetic activity
Fig. 19-3, p. 687
Thyroid Gland Dysfunction
Table 19-1, p. 687
Thyroid Gland
• Abnormalities
– 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
Graves disease
Antibody that binds
TSH receptors
no negative FB
Fig. 19-4, p. 688
Hypothyroidism
Goiter
Hyperthyroidism - exopthalmos
Fig. 19-5, p. 688
Thyroid Gland
• Abnormalities
– 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
Adrenal
cortex
Anatomy
Adrenal
medulla
Zona glomerulosa
Cortex
Zona fasciculata
(See next slide)
Zona reticularis
Medulla
Adrenal gland •
•
Embedded above each kidney in a capsule
of fat
Composed of two endocrine organs
– Adrenal cortex
• Outer portion
• Secretes steroid hormones
– Adrenal medulla
• Inner portion
• Secretes catecholamines
Adrenal Glands
Zona glomerulosa
Zona fasciculata
(See next slide)
Zona reticularis
• Adrenal cortex
– Consists of three layers or zones
• Zona glomerulosa – outermost layer
(Mineralocorticoids)
Medulla
• Zona fasciculata – middle and largest portion
(Glucocorticoids)
• Zona reticularis – innermost zone (Sex hormones)
– Categories of adrenal steroids
• Mineralocorticoids
– Mainly aldosterone
– Influence mineral balance, specifically Na+ and K+
balance
• Glucocorticoids
– Primarily cortisol
– Major role in glucose metabolism as well as in protein and
lipid metabolism
• Sex hormones
– Identical or similar to those produced by gonads
– Most abundant and physiologically important is
dehydroepiandosterone (male “sex” hormone)
Effects of Adrenal Cortical Hormones
• Permissive actions on catecholamines
• Stress adaptation (releases building blocks of new
tissue)
• Anti-inflamatory and immunosuppressive
Diurnal
rhythm
Stress
Hypothalamus
Corticotropin-releasing
hormone (CRH)
Anterior pituitary
POMC
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex
Cortisol
Metabolic fuels
and building blocks
available to help
resist stress
Blood glucose
(by stimulating gluconeogenesis
and inhibiting glucose uptake)
Blood amino acids
(by stimulating protein degradation)
Blood fatty acids
(by stimulating lipolysis)
Fig. 19-8, p. 692
Adrenal Glands
• Cortisol
• Zona fasciculata – middle and largest portion (Glucocorticoids)
– Stimulates hepatic gluconeogenesis
– Inhibits glucose uptake and use by many tissues, but not the
brain
– Stimulates protein degradation in many tissues, especially
muscle
– 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
– Displays a characteristic diurnal rhythm (day hi night low)
– Secretion
• Regulated by negative-feedback loop involving hypothalamic CRH
and pituitary ACTH
Adrenal Glands
•
Secretes both male and female sex hormones in both sexes
– Dehydroepiandrosterone (DHEA)
• Zona reticularis – innermost zone (Sex hormones)
• Only adrenal sex hormone that has any biological importance
• Overpowered by testicular testosterone in males
• Physiologically significant in females where it governs
– Growth of pubic and axillary hair
– Enhancement of pubertal growth spurt
– Development and maintenance of female sex drive
Adrenal Glands
• Aldosterone
• Zona glomerulosa – outermost layer
(Mineralocorticoids)
– Secretion is increased by
• Activation of renin-angiotensin-aldosterone system by
factors related to a reduction in Na+ and a fall in blood
pressure
• Direct stimulation of adrenal cortex by rise in plasma K+
concentration
– Regulation of aldosterone secretion is largely
independent of anterior pituitary control
Adrenal Medulla
• Modified part of sympathetic nervous system
• Primary stimulus for increased adrenomedullary secretion
activation of sympathetic nervous system by stress
• Releases epinephrine and norepinephrine
– Secreted into blood by exocytosis of chromaffin granules
– Vary in their affinities for the different adrenergic receptor
types
• Epinephrine
– Reinforces sympathetic system in mounting general
systemic “fight-or-flight” responses
– Maintenance of arterial blood pressure
– Increases blood glucose and blood fatty acids
Table 19-2, p. 697
CNS
Receptor type
target cells
PNS
Somatic
Preganglionic
Postaganglionic
Autonomic sympathetic
Autonomic sympathetic
Autonomic paraysmpathetic
Brainstem
Autonomic parasympathetic
Nicotinic
Alpha-receptors
Beta receptors
Muscarinic
Norephinephrine
Epinephrine
Acetylcholine
Nicotinic
Somatic alpha-motor neuron
Adrenal gland
Skeletal muscle
NE (15%)
Thoracic
E (85%)
Autonomic
sympathetic
Alpha
Blood stream
Chromaffin cell
Sympathetic ANS
Beta
Autonomic
sympathetic
Sacral
Ganglia
Muscarinic
Autonomic parasympathetic
Parasympathetic ANS
fig 10-6, pg 343
Stress Response
• Pattern of reactions to a situation that threatens
homeostasis
• Stress
– Generalized nonspecific response of body to any
factor that overwhelms or threatens to overwhelm
the body’s ability to maintain homeostasis
• Stressor
– Any noxious stimulus that brings about the stress
response
General Adaptation Syndrome
• Alarm reaction- fight or flight response,muscles
tense, HR and BP increase
• Resistance or adaptation-nervous and endocrine
systems deal with stressor. dangerous if long term.
• Exhaustion-resistance drops, immunity suppression,
depletion of energy reserves, stress related disease.
Stressor
Hypothalamus
CRH
Sympathetic
nervous
system
Posterior
pituitary
Anterior
pituitary
ACTH
Vasopressin
Activation of
sympathetic
nervous system
accompanied by
epinephrine
secretion
Prepares body
for fight-or-flight
response
Adrenal medulla
Adrenal cortex
Epinephrine
Cortisol
Activation of CRHACTH-cortisol system
Helps body cope by
mobilizing metabolic
resources
Glucagon-secreting cells
Insulin-secreting cells
Arteriolar
Endocrine
pancreas
smooth muscle
Vasoconstriction
Glucagon
Insulin
Elevation of blood
glucose and fatty
acids Decreased
insulin and increased
glucagon secretion
Blood flow
through kidneys
Renin
Angiotensin
Increased activity of reninangiotensin-aldosterone system
and increased vasopressin
secretion
Aldosterone
Fig. 19-12, p. 700
Endocrine Control of Fuel Metabolism
•
•
•
Metabolism
– All the chemical reactions that occur within the cells of the body
Intermediary metabolism or fuel metabolism
– Includes reactions involving the degradation, synthesis, and transformation of
proteins, carbohydrates, and fats
Nutrient molecules are broken down through the process of digestion into smaller
absorbable molecules
– Proteins → amino acids
– Carbohydrates → monosaccharides (mainly glucose)
– Dietary fats (triglycerides) → monoglycerides and free fatty acids
Anabolism and Catabolism
• Anabolism
– Buildup or synthesis of larger organic macromolecules
from small organic subunits
– Reactions usually require ATP energy
– Reactions result in
• Manufacture of materials needed by the cell
• Storage of excess ingested nutrients not immediately needed
for energy production or needed as cellular building blocks
• Catabolism
– Breakdown or degradation of large, energy-rich organic
molecules within cells
– Two levels of breakdown
• Hydrolysis of large cellular molecules into smaller subunits
• Oxidation of smaller subunits to yield energy for ATP
production
Food intake
Dietary protein
Dietary
carbohydrate
Dietary triglyceride
fat
D I G E S T I O N
Absorbable units
Amino
acids
Glucose
Fatty
acids
Monoglycerides
A B S O R P T I O N
Metabolic pool
in body
Body proteins
(structural or
secretory
products)
Storage, structural, and
functional
macromolecules in cells
Amino
acids
Glycogen storage
in liver and
muscle
Glucose
Triglycerides
in adipose tissue
stores (fat)
Fatty
acids
Urea
Urinary excretion
(elimination from body)
Oxidation to
CO2 + H2O + ATP (energy)
Expired
(elimination from body)
Use as metabolic fuel
in cells
Fig. 19-13, p. 702
Stored Metabolic Fuel in the Body
Metabolic States
•
•
Liver
Absorptive state
– Fed state
– Glucose is plentiful and serves as
major energy source
Postabsorptive state
– Fasting state
– Endogenous energy stores are
mobilized to provide energy
Primary role in maintaining normal blood glucose
levels
Principal site for metabolic interconversions such
as gluconeogenesis
Adipose tissue
Primary energy storage site
Important in regulating fatty acid levels in the
blood
Muscle
Primary site of amino acid storage
Major energy user
Brain
Normally can only use glucose as an energy
source
Does not store glycogen
Mandatory blood glucose levels be
maintained
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
The function of PP is to self regulate
the pancreas secretion activities
(endocrine and exocrine).
Pancreas
Alpha cell
Insulin and glucagon
Most important in regulating fuel metabolism
Beta cell
Delta cell
Capillaries
Fig 15-3, pg 455
Pancreatic Hormones
•
Somatostatin
– Released from pancreatic D cells in direct response to increase in blood sugar
and blood amino acids during absorption of a meal
– Prevents excessive plasma levels of nutrients
– Local presence of somatostatin decreases secretion of insulin, glucagon, and
somatostatin itself
– Physiologic importance has not been determined
• Insulin
– Anabolic hormone
– 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
– Secretion is increased during absorptive state
• Primary stimulus for secretion is increase in blood glucose concentration
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
– No known clinical abnormalities caused by glucagon deficiency or excess
• Excess of glucose can aggravate hyperglycemia of diabetes mellitus
Diabetes Mellitus
• Most common of all endocrine disorders
• Prominent feature is elevated blood glucose levels
– Urine acquires sweetness from excess blood
glucose that spills into urine
• Two major types
– Type I diabetes
• Characterized by lack of insulin secretion
– Type II diabetes
• Characterized by normal or even increased insulin
secretion but reduced sensitivity of insulin’s target cells
Endocrine Control of Calcium Metabolism
• Plasma Ca2+ must be closely regulated to prevent changes in
neuromuscular excitability
– Also plays vital role in a number of essential activities
•
•
•
•
•
Excitation-contraction coupling in cardiac and smooth muscle
Stimulus-secretion coupling
Maintenance of tight junctions between cells
Clotting of blood
Neurotransmitter release
– Hypercalcemia
• Reduces excitability
– Hypocalcemia
• Brings about overexcitability of nerves and muscles
• Severe overexcitability can cause fatal spastic contractions of
respiratory muscles
Endocrine Control of Calcium Metabolism
Three hormones regulate plasma concentration of Ca2+ (and PO43-)
•
Calcitonin
– Hormone produced
by C cells of thyroid
gland
– Negative-feedback
fashion
• Secreted in
response to
increase in
plasma Ca2+
concentration
– Acts to lower plasma
Ca2+ levels by
inhibiting activity of
bone osteoclasts
– Unimportant except
during hypercalcemia
•
Parathyroid hormone
•
(PTH)
– Secreted by
parathyroid glands
– Primary regulator of
Ca2+
• Raises free
plasma Ca2+
levels by its
effects on bone
kidneys, and
intestines
– Essential for life
• Prevents fatal
consequences of
hypocalcemia
– Facilitates activation
of Vitamin D
Vitamin D
– Stimulates Ca2+
and PO43absorption from
intestine
– Can be
synthesized from
cholesterol
derivative when
exposed to
sunlight
– Amount
supplemented by
dietary intake
– Must be
activated first by
liver and then by
kidneys before it
can exert its
effect on
intestines
Negative-feedback Loops Controlling Parathyroid
Hormone (PTH) and Calcitonin Secretion
Bone remodeling
• Bone deposition
• Bone resorption
• Osteoblasts – secrete matrix for calcium phosphate
• Osteocytes – retired osteoblasts
• Osteoclasts – resorb bone
• Osteoporosis
– Bone thinning
– Increased osteoclast activity
– Reduced osteoblast activity
Relieves
Plasma PO43-
(Because of inverse relationship
between plasma PO43- and Ca2+
concentrations caused by solubility
characteristics of calcium phosphate
salt)
Plasma Ca2+
Kidneys
Parathyroid glands
Activated vitamin D
PTH
PO43- reabsorption
by kidneys
Ca2+ reabsorption
by kidneys
Urinary excretion
of Ca2+
Ca2+ absorption
in intestine
(Counteract each other)
Urinary excretion
of PO43-
No change in plasma Ca2+
PO43- absorption
in intestine
Plasma PO43Fig. 19-25, p. 725