Power Point Week #11.pptx

Chapter 18
Mechanisms of
Hormonal Regulation
Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved.

 Functions:
 Differentiation of reproductive system and CNS in
fetus
 Stimulation of growth and development
 Coordination of the male and female reproductive
systems
 Maintenance of internal environment
 Adaptation to emergency demands of body
The Endocrine System
2

The Endocrine System (Cont.)
3
From Applegate, E. (2011). The anatomy and physiology learning system (4th ed.). St Louis, MO:
Saunders.

 General characteristics:
 Specific rates and rhythms of secretion
• Diurnal, pulsatile, and cyclic and patterns that depend on
circulating substances
 Operate within feedback systems
 Affect only target cells with appropriate receptors
 Excreted by kidneys or deactivated by liver or cellular
mechanisms
Hormones
4

 Hormones are released:
 In response to an alteration in the cellular
environment
 To maintain a regulated level of certain substances or
other hormones
 Hormones are regulated by chemical, hormonal,
or neural factors
 Negative feedback
Regulation of Hormone Release
5

Feedback Loops
6

 Hormones are released into the circulatory
system by endocrine glands
 Target cell
 Upregulation
 Downregulation
 Hormone effects:
• Direct effects
• Permissive effects
Hormone Transport and Action
7

 Water-soluble hormones circulate in free,
unbound forms
 Short-acting response
 Bind to surface receptors
 Lipid-soluble hormones are primarily circulating
bound to a carrier
 Rapid and long-lasting response
 Diffuse freely across the plasma and nuclear
membranes and bind with cytosolic or nuclear
receptors
Mechanism of Hormone Action
8

Mechanism of
Hormone Action (Cont.)
9

 Hormone receptors
 Located in the plasma membrane or in the
intracellular compartment of the target cell
Mechanism of
10

Mechanism of
 Water-soluble
hormones
 High molecular weight
 Cannot diffuse across
the plasma membrane
 Lipid-soluble
hormones
 Easily diffuse across
the plasma membrane
and bind to cytosolic
or nuclear receptors
11

 Water-soluble hormones
 First messenger:
• Hormone
• Signal transduction
 Second messenger molecules:
• Calcium
• Cyclic adenosine monophosphate (cAMP)
• Cyclic guanosine monophosphate (cGMP)
• Tyrosine kinase system
• Inositol triphosphate (IP3)
Mechanism of
12

 Lipid-soluble hormones
 Steroid hormones
Mechanism of
13

 Steroid hormone mechanism
Lipid-Soluble Hormones
14
From Patton, K.T., & Thibodeau, G.A. (2016). Anatomy & physiology (9th ed.). St Louis, MO:
Mosby.

 Hypothalamic-pituitary axis
 Hypothalamus
Structure and Function
of the Endocrine Glands
15

Anterior pituitary
 Pars distalis
 Pars tuberalis
 Pars intermedia
 Secretes tropic hormones
Posterior pituitary
 Median eminence
 Pituitary stalk
 Pars nervosa
Pituitary Gland
16

Pituitary Gland (Cont.)
17
From Herlihy, B. (2015). The human body in health and illness (5th ed.). St Louis, MO:
Saunders.

 Adrenocorticotropic hormone (ACTH)
 Melanocyte-stimulating hormone (MSH)
 Somatotropic hormones
 Growth hormone
 Prolactin
 Glycoprotein hormones
 Follicle-stimulating hormone
 Luteinizing hormone
 Thyroid-stimulating hormone
Anterior Pituitary
18

 Luteinizing hormone
 β-lipotropin
 β-endorphins
Anterior Pituitary (Cont.)
19

 Hypophysial portal system
Anterior Pituitary (Cont.)
20
From Hall, J.E. (2016). Guyton and Hall textbook of medical physiology (13th
ed.). Philadelphia, PA: Saunders.

 Synthesized with their binding proteins in the
supraoptic and paraventricular nuclei of the
hypothalamus
 Secreted by the posterior pituitary
 Antidiuretic hormone (ADH)
• Controls plasma osmolality
 Oxytocin
• Uterine contractions and milk ejection in lactating women
Posterior Pituitary Hormones
21

 Located near centre of brain
 Secretes melatonin
 Regulates circadian rhythms and reproductive
systems
 Role in onset of puberty
Pineal Gland
22

 Thyroid gland
 Two lobes lie on either side of the trachea
 Isthmus
 Follicles (follicle cells surrounding colloid)
 Parafollicular cells (C cells)
• Secrete calcitonin
 Regulation of thyroid hormone secretion
• Thyrotropin-releasing hormone and thyroid-stimulating
hormone
Thyroid and Parathyroid Glands
23

 Thyroid hormone
 Secreted in response to TSH
 90% T4 and 10% T3
• Most T4 then converted to T3
 Bound to thyroxine-binding globulin, thyroxine-binding
prealbumin, albumin, or lipoproteins
 Affects growth and maturation of tissues, cell
metabolism, heat production, and oxygen
consumption
Thyroid and Parathyroid
Glands (Cont.)
Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 24

 Parathyroid glands
 Small glands located behind the upper and lower
poles of the thyroid gland
 Produce parathyroid hormone (PTH)
• Increases serum calcium and decreases serum phosphate
• Antagonist of calcitonin (thus increases bone resorption and
serum calcium)
• Vitamin D (cofactor) needed for PTH function
Glands (Cont.)
25

Glands (Cont.)
26
From Fehrenbach MJ, et al. (2012). Illustrated anatomy of the head and neck (4th
ed.), St Louis, MO, Saunders.

 Thyroid follicle cells
Glands (Cont.)
27

1. Which is TRUE regarding thyroid hormone and
thyroid-stimulating hormone (TSH)?
A. TSH secretion is controlled by positive feedback.
B. TSH is secreted in excess when stimulated by T4.
C. TSH secretion is regulated by thyrotropin-releasing
hormone.
D. Decreased anterior pituitary release of TSH
stimulates thyroid hormone secretion.
28

 Pancreas is both an endocrine and an exocrine
gland
 Houses the islets of Langerhans
 Secretion of glucagon and insulin
 Cells:
• Alpha—glucagon
• Beta—insulin and amylin
• Delta—somatostatin and gastrin
• F cells—pancreatic polypeptide
Endocrine Pancreas
29

Endocrine Pancreas (Cont.)
30
From Patton, K.T., & Thibodeau, G.A. (2016). Structure & function of the body (15th ed.). St Louis, MO:
Mosby.

 Insulin
 Synthesized from proinsulin
 Secretion is promoted by increased blood levels of glucose,
amino acids, GI hormones
 Facilitates the rate of glucose uptake into the cells of the body
 Anabolic hormone
• Synthesis of proteins, lipids, and nucleic acids
 Amylin
 Peptide hormone cosecreted with insulin
 Delays nutrient uptake
 Suppresses glucagon secretion
31

 Insulin action on cells
32
Redrawn from Levy, M.N., et al. (Eds.). (2006). Berne & Levy principles of physiology (4th ed.). St Louis, MO:
Mosby.

 Glucagon
 Secretion is promoted by decreased blood glucose
levels
 Stimulates glycogenolysis, gluconeogenesis, and
lipolysis
 Pancreatic somatostatin
 Possible involvement in regulating alpha-cell and
beta-cell secretions
 Gastrin, ghrelin, and pancreatic polypeptides
33

2. Insulin is secreted by the pancreas from which
type of cell?
A. F
B. Beta
C. Delta
D. Alpha
34

 Located close to upper pole of each kidney
 Adrenal cortex
 80% of an adrenal gland’s total weight
 Zona glomerulosa
 Zona fasciculata
 Zona reticularis
 Adrenal medulla
 Innervated by the sympathetic nervous systems
Adrenal Glands
35

Adrenal Glands (Cont.)
36
From Damjanov, I. (2008). Pathophysiology. Philadelphia, PA:
Saunders. From Kierszenbaum, A. (2002). Histology and cell biology. St Louis,
MO: Mosby.

 Adrenal cortex
 Stimulated by adrenocorticotropic hormone (ACTH)
 Glucocorticoid hormones
• Direct effects on carbohydrate metabolism
• Anti-inflammatory and growth-suppressing effects
• Most potent naturally occurring glucocorticoid is cortisol
37

 Mineralocorticoid hormones
• Affect ion transport by epithelial cells
 Increase the activity of the sodium pump of the epithelial cells
 Cause sodium retention and potassium and hydrogen loss
• Most potent naturally occurring mineralocorticoid is
aldosterone
 Regulated by the renin-angiotensin system
38

 Adrenal estrogens and androgens
• Estrogen secretion by the adrenal cortex is minimal
• Adrenal cortex secretes weak androgens
 Androgens are converted by peripheral tissues to stronger
androgens such as testosterone
39

 Adrenal medulla
 Chromaffin cells (pheochromocytes)
• Secrete the catecholamines epinephrine (majority) and
norepinephrine
 Release of catecholamines has been characterized
as a “fight or flight” response
 Catecholamines promote hyperglycemia
40

Aldosterone
41

 Organ atrophy and weight loss with vascular
changes
 Decreased secretion and clearance of hormones
 Variable change in receptor binding and
intracellular responses
Aging and the Endocrine System
42

A 24-year-old mother visits her obstetrician’s office 1 week
after delivering her baby. She is having trouble with
breastfeeding and milk expression. The obstetrician
prescribes a nasal spray that will stimulate the posterior
pituitary to release which hormone?
A. Oxytocin
B. Prolactin
C. Calcitonin
D. Incretin
Case Study:
Discussion Questions
43

As the young mother is walking to her car, she
becomes aware that someone is following her. Her
body responds with a “fight or flight” response,
which is regulated by the adrenal medulla’s
secretion of which hormone?
A. Cortisol
B. Catecholamines
C. Glucocorticoids
D. Androgens
Case Study:
Discussion Questions (Cont.)
44

45

Chapter 19
Alterations of Hormonal Regulation

 Failure of feedback systems
 Dysfunction of an endocrine gland
 Secretory cells are unable to produce, obtain, or
convert hormone precursors
 Endocrine gland synthesizes or releases
excessive amounts of hormone
Mechanisms of
Hormonal Alterations
47

 Endocrine gland fails to produce adequate
amounts of hormone
 Increased hormone degradation or inactivation
 Ectopic hormone release
Mechanisms of
Hormonal Alterations (Cont.)
48

 Cell surface receptor–associated disorders:
 Decrease in number of receptors
 Impaired receptor function
 Presence of antibodies against specific receptors
 Antibodies that mimic hormone action
 Unusual expression of receptor function
 Intracellular disorders:
 Defects in postreceptor signaling cascades
 Inadequate synthesis of second messenger
Target Cell Failure
49

Alterations of the
Hypothalamic-Pituitary System
50

 Syndrome of inappropriate antidiuretic hormone
secretion (SIADH)
 Hypersecretion of ADH
 For diagnosis, normal adrenal and thyroid function
must exist
 Clinical manifestations are related to enhanced renal
water retention, hyponatremia, and serum hypo-
osmolality
Diseases of the
Posterior Pituitary
51

 Diabetes insipidus
 Insufficiency of ADH
 Polyuria and polydipsia
 Partial or total inability to concentrate the urine
 Neurogenic
• Insufficient amounts of ADH
 Nephrogenic
• Inadequate response to ADH
 Psychogenic
 Manifestations are related to enhanced water excretion,
hypernatremia, and serum hyperosmolality
Diseases of the
Posterior Pituitary (Cont.)
52

 Hypopituitarism
 Pituitary infarction
• Sheehan’s syndrome
• Hemorrhage
• Shock
 Others:
• Head trauma
• Infections
• Tumours
Diseases of the Anterior Pituitary
53

 Panhypopituitarism
• ACTH deficiency
• TSH deficiency
• FSH and LH deficiency
• GH deficiency
Diseases of the Anterior
Pituitary (Cont.)
54

 Hyperpituitarism
 Commonly caused by a benign, slow-growing pituitary
adenoma
 Manifestations:
• Headache and fatigue
• Visual changes
• Hyposecretion of neighbouring anterior pituitary hormones
Pituitary (Cont.)
55

 Hypersecretion of growth hormone (GH)
 Acromegaly
• Hypersecretion of GH during adulthood
 Giantism
• Hypersecretion of GH in children and adolescents
Pituitary (Cont.)
56

 Hypopituitary dwarfism and pituitary giantism
Pituitary (Cont.)
57
From Patton, K.T., & Thibodeau, G.A. (2013). Anatomy & physiology (8th ed.). St Louis, MO:
Mosby.

 Hypersecretion of prolactin
 Caused by prolactinomas
• In females, increased levels of prolactin cause amenorrhea,
galactorrhea, hirsutism, and osteopenia
• In males, increased levels of prolactin cause hypogonadism,
erectile dysfunction
Pituitary (Cont.)
58

 Hyperthyroidism
 Thyrotoxicosis
 Graves’ disease
• Pretibial myxedema
 Hyperthyroidism resulting from nodular thyroid
disease
• Goitre
 Thyrotoxic crisis (thyroid storm)
Alterations of Thyroid Function
59

Alterations of Thyroid
Function (Cont.)
60

Thyrotoxicosis (Graves’ Disease)
61
From Belchetz, P., & Hammond, P. (2003). Mosby’s color atlas and text of
diabetes and endocrinology. Edinburgh: Mosby.

 Hypothyroidism
 Primary hypothyroidism
• Autoimmune thyroiditis (Hashimoto’s disease)
• Subacute thyroiditis
• Painless thyroiditis
• Postpartum thyroiditis
• Myxedema coma
 Congenital hypothyroidism
Alterations of Thyroid Function
62

Manifestations of
Thyroid Alterations
63
From Damjanov, I. (2012). Pathology for the health professions (4th ed.). St Louis, MO:
Saunders.

 Most common endocrine malignancy
 Ionizing radiation most common cause
 Treated with thyroidectomy, suppression
therapy, radiation, and chemotherapy
Thyroid Carcinoma
64

 Hyperparathyroidism
 Primary hyperparathyroidism
• Excess secretion of PTH from one or more parathyroid
glands
 Secondary hyperparathyroidism
• Increase in PTH secondary to chronic hypocalcemia
 Manifestations:
• Hypercalcemia
• Hypophosphatemia
• Hypercalciuria: kidney stones
• Pathological fractures
Alterations of
Parathyroid Function
65

 Hypoparathyroidism
 Abnormally low PTH levels
 Usually caused by parathyroid damage in thyroid
surgery
 Manifestations:
• Hypocalcemia
 Chvostek’s and Trousseau’s signs
• Hyperphosphatemia
Alterations of
Parathyroid Function (Cont.)
66

1. Which condition is associated with polyuria and
polydipsia?
A. Diabetes insipidus
B. Hypoparathyroidism
C. Hyperthyroidism
D. Graves’ disease
67

 Types:
 Idiopathic type 1
 Autoimmune type 1
 Pancreatic atrophy and specific loss of beta
cells; hyperglycemia when 80 to 90% cells lost
 Macrophages, T-cytotoxic cells, antibodies
 Alterations in insulin, amylin, glucagon
Type 1 Diabetes Mellitus
68

 Genetic susceptibility
 Environmental factors
 Immunologically mediated destruction of beta cells
 Manifestations:
 Hyperglycemia
 Polydipsia
 Polyuria
 Polyphagia
 Weight loss
 Fatigue
Type 1 Diabetes Mellitus (Cont.)
69

 Ranges from insulin resistance with relative
insulin deficiency to insulin secretory defect with
insulin resistance
 Caused by genetic-environmental interaction
 Risk factors are age, obesity, hypertension,
physical activity, and family history
 Metabolic syndrome
Type 2 Diabetes Mellitus
70

 Initial insulin resistance
 Later loss of beta cells
 Manifestations (nonspecific): fatigue, pruritus,
recurrent infections, visual changes, or symptoms of
neuropathy; often overweight, dyslipidemic,
hyperinsulinemic, and hypertensive
Type 2 Diabetes Mellitus (Cont.)
71

 Maturity onset diabetes of youth (MODY)
 Beta-cell function or insulin action affected by
autosomal dominant mutations
 Gestational diabetes mellitus (GDM)
 Any degree of glucose intolerance with onset or first
recognition during pregnancy
Other Types of Diabetes Mellitus
72

 Hypoglycemia
 Diabetic ketoacidosis (DKA)
 Hyperosmolar hyperglycemic syndrome (HHS)
Acute Complications
of Diabetes Mellitus
73

Diabetic Ketoacidosis
74

 Microvascular disease
 Diabetic retinopathy
 Diabetic nephropathy
 Diabetic neuropathies
 Macrovascular disease
 Cardiovascular disease
 Stroke
 Peripheral vascular disease
 Infection
Chronic Complications
of Diabetes Mellitus
75

2. A 12-year-old patient develops pancreatic
atrophy with loss of beta cells. Which condition
does this patient most likely have?
A. Diabetes type 1
B. Diabetes type 2
C. Hypothyroidism
D. Diabetes insipidus
76

 Disorders of the adrenal cortex:
 Cushing’s disease
• Excessive anterior pituitary secretion of ACTH
 Cushing’s syndrome
• Manifestations resulting from chronic excess cortisol
Alterations of Adrenal Function
77

Cushing’s Disease
78
From Zitelli, B.J., et al. (2012). Zitelli and Davis’ atlas of pediatric physical diagnosis (6th ed.). London: Saunders.

 Disorders of the adrenal cortex
 Congenital adrenal hyperplasia
 Hyperaldosteronism
• Primary hyperaldosteronism (Conn’s syndrome)
• Secondary hyperaldosteronism
Alterations of Adrenal Function
79

 Hypersecretion of adrenal androgens and estrogens
• Feminization
• Virilization
Alterations of Adrenal
Function (Cont.)
80

Virilization
81
From Thibodeau, G.A., & Patton, K.T. (2010). The human body in health &
disease (4th ed.). St Louis, MO: Mosby.

 Disorders of the adrenal cortex
 Adrenocortical hypofunction
• Addison’s disease (primary adrenal insufficiency)
 Addisonian crisis
• Secondary hypocortisolism
Function (Cont.)
82

 Disorders of the adrenal medulla
 Adrenal medulla hyperfunction
• Caused by tumours derived from the chromaffin cells of the
adrenal medulla
 Pheochromocytomas
• Secrete catecholamines on a continuous or episodic basis
Function (Cont.)
83

A 12-year-old boy is brought to the emergency
department by his mother. She informs the staff
that he is breathing heavily and smells funny.
Laboratory tests confirm that the child is in DKA.
During DKA, insulin counter-regulatory hormones,
such as catecholamines and cortisol, increase.
Case Study
84

What is the result of profound insulin deficiency?
A. Decreased fat mobilization
B. Activation of glucose-forming pathways in
the liver
C. Increased glucose uptake
D. Activation of bicarbonate buffering
Case Study: Discussion Question
85

While her son is in the hospital, the mother has been
drinking coffee in an attempt to stay awake at the bedside.
She begins to complain of a severe headache. She informs
the staff that the headache is usually related to an increase
in her blood pressure. Although she has been prescribed a
medication and has been taking it regularly, she continues
to have issues. She is sweating and feels her heart racing.
She is transported to the emergency department. She
undergoes a barrage of tests and, 2 days later, her
physician is ready to discuss her diagnosis of
pheochromocytoma.
Case Study
86

Her symptoms are caused by an excessive
production of what substance?
A. Norepinephrine
B. Cortisol
C. Thyroid-stimulating immunoglobulins (TSIs)
D. Growth hormone
Case Study: Discussion Question
87

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