1. The Peripheral Endocrine Glands
Chapter 19
The Peripheral Endocrine Glands
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

2. Peripheral Endocrine Glands
Outline
Thyroid glands
Anatomy and hormones
Adrenal glands
Stress response
Fuel metabolism
Calcium metabolism
Pancreas

3. Arranged into hollow spheres Forms functional unit called a follicle
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
Figure 19.1: Anatomy of the thyroid gland.
(b) Light-microscope appearance of the thyroid gland. The thyroid gland is composed primarily of colloid-filled spheres enclosed by a single layer of follicular cells.
Fig. 19-1b, p. 684

4. Thyroid hormone synthesis and release
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

5. *Endoplasmic Colloid Blood Thyroid follicular cell reticulum/Golgi
complex
Lysosome
DIT = Di-iodotyrosine
T3 = Tri-iodothyronine
T4 = Tetraiodothyronine (thyroxine)
TGB = Thyroglobulin
I = Iodine
MIT = Monoiodotyrosine
Fig. 19-2, p. 685

6. 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)

7. 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

8. Stress Cold in infants Hypothalamus Anterior pituitary Thyroid gland
Thyrotropin-
releasing
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

9. Thyroid Gland Dysfunction
Table 19-1, p. 687

10. 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

11. Graves disease Antibody that binds TSH receptors no negative FB
Figure 19.4: Role of long-acting thyroid stimulator in Graves’ disease.
Long-acting thyroid stimulator (LATS), an antibody erroneously produced in the autoimmune condition of Graves’ disease, binds with the TSH receptors on the thyroid gland and continuously stimulates thyroid hormone secretion outside the normal negative-feedback control system.
Fig. 19-4, p. 688

12. Hyperthyroidism - exopthalmos
Hypothyroidism
Goiter
Hyperthyroidism - exopthalmos
Figure 19.5: Patient displaying exophthalmos.
Abnormal fluid retention behind the eyeballs causes them to bulge forward.
Fig. 19-5, p. 688

13. Thyroid Gland Abnormalities Hypothyroidism Causes Cretinism Myxedema
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

14. Anatomy Adrenal cortex 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

15. Adrenal Glands Adrenal cortex Consists of three layers or zones
Zona glomerulosa
Zona fasciculata
(See next slide)
Zona reticularis
Adrenal cortex
Consists of three layers or zones
Zona glomerulosa – outermost layer (Mineralocorticoids)
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)
Medulla

16. Effects of Adrenal Cortical Hormones
Permissive actions on catecholamines
Stress adaptation (releases building blocks of new tissue)
Anti-inflamatory and immunosuppressive

17. POMC Stress Diurnal rhythm Hypothalamus Anterior pituitary
Corticotropin-releasing
hormone (CRH)
Anterior pituitary
Adrenocorticotropic
hormone (ACTH)
POMC
Adrenal cortex
Cortisol
Blood glucose
(by stimulating gluconeogenesis
and inhibiting glucose uptake)
Metabolic fuels
and building blocks
available to help
resist stress
Blood amino acids
(by stimulating protein degradation)
Blood fatty acids
(by stimulating lipolysis)
Fig. 19-8, p. 692

18. Adrenal Glands Cortisol Stimulates hepatic gluconeogenesis
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

19. 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

20. Adrenal Glands Aldosterone Secretion is increased by
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

22. 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

23. Table 19-2, p. 697

24. fig 10-6, pg 343 Receptor type CNS PNS target cells Nicotinic
Alpha-receptors
Beta receptors
Muscarinic
Somatic
Preganglionic
Postaganglionic
Autonomic parasympathetic
Autonomic sympathetic
Norephinephrine
Epinephrine
Acetylcholine
Autonomic sympathetic
Autonomic paraysmpathetic
Brainstem
Nicotinic
Cervical
Somatic alpha-motor neuron
Adrenal gland
Skeletal muscle
NE (15%)
Blood stream
Alpha
E (85%)
Thoracic
Chromaffin cell
Autonomic
sympathetic
Sympathetic ANS
Beta
Autonomic
sympathetic
Ganglia
Lumbar
Muscarinic
Sacral
Autonomic parasympathetic
fig 10-6, pg 343
Parasympathetic ANS

25. 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

26. 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.

27. Stressor Hypothalamus CRH Posterior pituitary Anterior pituitary ACTH
Sympathetic
nervous
system
Anterior
pituitary
ACTH
Vasopressin
Adrenal medulla
Activation of sympathetic nervous system accompanied by epinephrine secretion Prepares body for fight-or-flight response
Adrenal cortex
Epinephrine
Cortisol
Activation of CRH-ACTH-cortisol system Helps body cope by mobilizing metabolic resources
Glucagon-secreting cells
Insulin-secreting cells
Endocrine
pancreas
Arteriolar
smooth muscle
Vasoconstriction
Glucagon
Insulin
Elevation of blood glucose and fatty acids Decreased insulin and increased glucagon secretion
Blood flow
through kidneys
Increased activity of renin-angiotensin-aldosterone system and increased vasopressin secretion
Renin
Angiotensin
Aldosterone
Fig , p. 700

28. Endocrine Control of Fuel 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

29. Anabolism and Catabolism
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

30. Food intake Dietary protein D I G E S T I O N Absorbable units Glucose
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)
Amino
acids
Urea Urinary excretion
(elimination from body)
Oxidation to
CO2 + H2O + ATP (energy)
Expired
(elimination from body)
Storage, structural, and
functional
macromolecules in cells
Glycogen storage
in liver and
muscle
Glucose
Triglycerides
in adipose tissue
stores (fat)
Fatty
acids
Use as metabolic fuel
in cells
Fig , p. 702

31. Stored Metabolic Fuel in the Body

32. Metabolic States 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
Liver
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

33. Pancreas Alpha cell Beta cell Delta cell Capillaries
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).
Insulin and glucagon
Most important in regulating fuel metabolism
Pancreas
Alpha cell
Beta cell
Delta cell
Capillaries
Fig 15-3, pg 455

34. 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

35. 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

36. 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

37. 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 PO43- absorption 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

38. Negative-feedback Loops Controlling Parathyroid Hormone (PTH) and Calcitonin Secretion

39. 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

40. (Because of inverse relationship between plasma PO43- and Ca2+
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-
PO43- absorption
in intestine
No change in plasma Ca2+
Plasma PO43-
Fig , p. 725