1
Q
What are glands?
A
A specialized cell, group of cells, or organs that secretes substances to be used by or eliminated from the body.
2
Q
What are the six main functions of the endocrine system?
A
- Maintain constant internal environment via regulation of metabolism and H2O/electrolyte balance
- Adaptive stress response
- Growth and development
- Reproduction
- Red blood cell production
- Integrating with the autonomic nervous system in regulating both the circulation and digestive functions
3
Q
What are hormones?
A
Chemical substances that are secreted directly into the blood at low quantities and exert a physiological effect at a distant target tissue.
4
Q
What are the two major categories of hormones?
A
- Hydrophilic: can be found unbound to carrier molecules within the plasma. Can be peptide hormones (peptides or proteins) + amines (hormones based on single amino acid residues; e.g., catecholamines and thyroid hormones).
- Lipophilic: Generally require carrier molecules for transport throughout the body. They include the amine thyroid hormones and the steroid hormones.
5
Q
What are the two types of amine hormones?
A
Catecholamines (norepinephrine and epinephrine) + thyroid hormones
6
Q
Describe the synthesis of peptide hormones.
A
Peptide hormones are synthesized and secreted by the same cellular machinery that makes proteins within cells.
1. Synthesis – Large precursor proteins called preprohormones are synthesized by ER ribosomes.
2. Packaging – As they travel through the ER and Golgi complex, these preprohormones are processed into active hormones and packaged into secretory vesicles.
3. Storage – These hormone-containing secretory vesicles can be stored until the cell receives the appropriate signal.
4. Secretion – The appropriate signal initiates exocytosis of the vesicles and the hormones are released into the blood.
7
Q
What’s special about thyroid hormones and catecholamines?
A
They are amine hormones, but thyroid hormones are not hydrophilic (they are lipophilic). Catecholamines are also unique in that they are found both free (50%) and bound to carrier molecules (50% albumin).
8
Q
Describe the synthesis of steroid hormones.
A
They are all synthesized from cholesterol. Which steroid hormone is produced by a particular tissue depends on the specific enzymes within the cells of that tissue. Because they are so lipophilic, they are not stored but rather they are released as they are synthesized. Consequently, to regulate the amount of steroid hormone released, you need to regulate its synthesis.
9
Q
True or False: Steroid hormones are stored until they are released upon signals.
A
False. Steroid hormones are lipophilic, they are not stored. They are released as they are synthesized.
10
Q
How hormones interact with their target cells?
A
Only free, unbound hormone can interact with a receptor at its target cell (not an issue for hydrophilic hormones and catecholamines). For lipophilic hormones, they are dynamically unbinding and rebinding, which results in a small fraction of hormone that is unbound at any given time. It’s this unbound hormone is active and able to act on target cells.
11
Q
Where the receptors of peptide hormones, steroid hormones, catecholamines, and thyroid hormones are located in the cell?
A
Peptide hormones and catecholamines => receptors on the outer surface of the plasma membrane of their target cells; unable to freely cross the lipid bilayer.
Steroids and thyroid hormones => can easily slip through the plasma membrane and bind to receptors inside their target cells
12
Q
What happens after peptide hormones and catecholamines bind their receptors?
A
Bind to surface receptor => activate second messenger systems => amplify the initial signal
E.g., cyclic AMP (cAMP), calcium (Ca2+)
13
Q
What happens after steroid and thyroid hormones bind their receptors?
A
They are able to pass through both the plasma membrane and the nuclear membranes. Binding of these hormones to their receptors inside target cells produces effects by regulating gene transcription and protein synthesis. The hormone-receptor complex (H-R) binds to the hormone response element (HRE) within the DNA. DNA binding activates specific genes and produces mRNA, which then leaves the nucleus and binds to a ribosome and proteins are synthesized. These newly synthesized proteins ultimately lead to the cellular response of the hormone.
14
Q
cAMP as a secondary messenger.
A
Begins when an extracellular messenger binds to a receptor, activating a G protein. The G protein then stimulates multiple adenylyl cyclase enzymes, which convert ATP into cAMP. The cAMP molecules activate protein kinase A, which phosphorylates specific target proteins to produce the desired cellular response.
15
Q
Calcium as a second messenger.
A
First, an extracellular messenger binds to a receptor, activating a G protein, which shuttles to activate several phospholipase C enzymes. These proteins convert PIP2 to IP3 and DAG. IP3 mobilizes intracellular Ca2+, which activates calmodulin. The Ca2+-calmodulin complexes then activate Ca2+- calmodulin-dependent protein kinase (CaMkinase), which phosphorylate and activate target protein, bringing about the desired response.
16
Q
Where are lipophilic hormones found?
A
Within the cytoplasm or the nucleus
17
Q
What are the key differences between hormones and neurotransmitters?
A
Neurotransmitters:
- Belong to the nervous system
- Transmitted across a synaptic cleft
- Produced by neurons
- Must travel a short distance to their target
Hormones:
- Belong to the endocrine system
- Transported by the blood
- Produced by endocrine glands
- May travel a great distance
18
Q
Compare and contrast nervous and endocrine control in terms of response time, duration of effects, and number of targets.
A
Nervous control:
- Rapid responses (milliseconds)
- Brief in duration (ends when stimulus stops)
- Hard-wired to one specific target (muscle or gland)
Endocrine control:
- Slow responses (minutes to hours)
- Long in duration (effects persist after stimulus stops)
- Many different targets in the body (blood circulates)
19
Q
Describe the anatomical features of the pituitary gland.
A
- Very small gland located in a bony cavity at the base of the skull.
- Two anatomically and functionally distinct lobes (they don’t communicate with each other).
- Posterior pituitary gland: comprised of neural-like tissues. AKA neurohypophysis.
- Anterior pituitary gland: comprised of glandular epithelial tissues. AKA adenohypophysis.
20
Q
Which organ controls the hormone release from the pituitary gland and how so?
A
Hypothalamus.
For posterior pituitary lobe: Connected to the hypothalamus by neural pathways. Within the hypothalamus, there are two well-defined clusters of neurons, the supraoptic nucleus and paraventricular nucleus. Axons from these nuclei project down the pituitary stalk and terminate on blood vessels in the posterior pituitary.
For anterior pituitary lobe: Connected to the hypothalamus by the hypothalamic-hypophyseal portal system. The hypothalamus secretes hormones into this portal system and they are carried directly to the anterior pituitary where they either inhibit or promote the release of anterior pituitary hormones.
21
Q
What is pituitary stalk?
A
The narrow region connecting the hypothalamus and the pituitary
22
Q
What is the hypothalamic-hypophyseal portal system?
A
Arteries and capillaries that carry blood and regulatory hormones (called releasing hormones) from the hypothalamus to the adenohypophysis, where the target cells of the releasing hormones are located.
23
Q
Where are posterior pituitary hormones synthesized, and how are they released into the bloodstream?
A
Hormones are not produced in the posterior pituitary itself. They are synthesized in the neuron cell bodies located within the hypothalamus. Once synthesized, they are packaged into vesicles which are transported down the axons to the nerve endings in the posterior pituitary. When an appropriate stimulus reaches the hypothalamus, these neurons transmit an action potential that causes the release of these hormone-containing vesicles into the blood.
24
Q
What are the hormones associated with the posterior pituitary gland?
A
Vasopressin (ADH) and oxytocin
25
What are the two major actions of vasopressin?
1. Enhancing the retention of water by the kidneys => most physiologically important
2. Causing contraction of arteriolar smooth muscle
26
What are the two major roles of oxytocin?
1. Stimulate contraction of uterine smooth muscle cells during childbirth
2. Promote milk ejection during breastfeeding
27
True or False: Both posterior and anterior pituitary glands synthesize hormones.
False. Only anterior pituitary synthesize hormones.
28
What are tropic hormones?
Once released, these hormones stimulate other endocrine glands to release their hormones.
29
What kind of hormones does anterior pituitary gland synthesize and release? What is the only exception?
Peptide & tropic. Prolactin (PRL) is the only anterior pituitary hormone that is not tropic.
30
What are the hormones synthesized by the anterior pituitary gland?
1. Thyroid-stimulating hormone (TSH or Thyrotropin): Stimulates the release of thyroid hormones from the thyroid gland.
2. Luteinizing hormone (LH): In females, LH is responsible for ovulation and formation of the corpus luteum. It also stimulates the secretion of estrogen and progesterone from the ovaries. In males, LH stimulates the release of testosterone from the interstitial cells of Leydig.
3. Prolactin (PRL): In females, it enhances breast development and milk production. It's also present in males (function not clear).
4. Follicle-stimulating hormone (FSH): In females, FSH stimulates the growth and development of ovarian follicles and promotes secretion of estrogen by the ovaries. In males, FSH is required for sperm production.
5. Growth hormone (GH or Somatotropin): Primary hormone regulating overall body growth and is also involved in metabolism.
6. Adrenocorticotropic hormone (ACTH): Stimulates secretion of cortisol by the adrenal cortex.
31
How hormones travel through the hypothalamic-hypophyseal portal system?
1. Hypophysiotropic hormones produced by neurosecretory neurons in the hypothalamus enter the hypothalamic capillaries.
2. These hypothalamic capillaries rejoin to form the hypothalamic-hypophyseal portal system, a vascular link to the anterior pituitary.
3. The portal system branches into the capillaries of the anterior pituitary.
4. The hypophysiotropic hormones, which leave the blood across the anterior pituitary capillaries, control the release of anterior pituitary hormones.
5. When stimulated by the appropriate hypothalamic releasing hormone, the anterior pituitary secretes a given hormone into these capillaries.
6. The anterior pituitary capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for ultimate distribution throughout the body by the systemic circulation.
32
Release of anterior pituitary hormones is primarily controlled by?
Hormones produced in the hypothalamus.
33
Which releasing and inhibiting hormones are produced in the hypothalamus that influence the release of anterior pituitary hormones?
These releasing and inhibiting hormones are produced by the neurosecretory neurons in the hypothalamus and are released into the hypothalamic-hypophyseal portal system.
1. Growth hormone inhibiting hormone (GHIH): Inhibits the release of GH and TSH.
2. Prolactin-inhibiting hormone (PIH)
3. Prolactin-releasing hormone (PRH)
4. Thyrotropin-releasing hormone (TRH): Stimulates the release of TSH and prolactin.
5. Growth hormone releasing hormone (GHRH)
6. Gonadotropin-releasing hormone (GnRH): Stimulates the release of FSH and LH.
7. Corticotropin-releasing hormone (CRH): Stimulates the release of ACTH.
34
What is blood-brain barrier?
A highly selective semi-permeable membrane surrounding the brain and spinal cord that separates the circulating blood from the central nervous system.
35
Which two brain influences are particularly important in stimulating hypothalamic hormone secretion?
Stress and emotion
36
What types of inputs do hypothalamic neurons receive to regulate hormone secretion?
Both neuronal and hormonal
37
How does the absence of a blood–brain barrier in some hypothalamic regions affect hormone regulation?
The absence of a blood–brain barrier in some hypothalamic regions allows the hypothalamus to directly sample and monitor the blood. This enables it to detect circulating chemicals and changes in plasma composition, such as osmolarity, and adjust hormone release accordingly.
38
Describe the three-hormone hierarchic chain of command that hypothalamic hormones are involved in.
The hypothalamus releases a hormone into the portal system to regulate pituitary secretion of a tropic hormone. This tropic hormone acts on a target endocrine gland to stimulate release of a third hormone, which produces the physiological effect and exerts negative feedback on both the pituitary and hypothalamus.
39
Describe the anatomical features of the thyroid gland.
It is located over the trachea just below the larynx. It consists of two lobes connected by the isthmus (a thinner section of the gland). There is no difference between the lobes. The entire gland serves the same function, that is to produce and secrete thyroid hormones.
40
Describe the cellular structure of thyroid gland.
Cell type: Follicular cells are arranged to form hollow spheres throughout the gland (appears ring-like structures) + C cells (secrete calcitonin)
Colloid: Primarily made up of a large protein molecule called thyroglobulin, which is where the thyroid hormones are synthesized and stored.
41
What are follicular cells?
The secretory cells of the thyroid gland.
42
What is colloid?
The substance that fills the inside or lumen of the follicles.
43
What is the main function of the C cells of the thyroid gland?
To secrete calcitonin.
44
Where are the thyroid hormones synthesized and stored in the thyroid gland?
Thyroglobulin
45
What are the thyroid hormones? What is unique about them?
The thyroid gland produces tetraiodothyronine (T4 or thyroxine) and triiodothyronine (T3) from tyrosine. A unique feature of both is that they contain iodine.
46
Which is the more active thyroid hormone, T3 or T4?
T3 is considered to be the more active thyroid hormone, as T4 is converted to T3 in target tissues. Both hormones exert the same physiological effects, only with differences in their speed and intensity of action.
47
Which thyroid hormone is secreted more, T3 or T4?
T4 (90%). Only 10% represents T3.
48
The body requires how much iodine a week to ensure sufficient levels of thyroid hormone?
1 mg
49
True or False: Since thyroid hormones are lipophilic, they are not stored in the body but are released upon their synthesis.
False. Thyroid hormones are an exception, as the fully formed hormones can be protected from secretion while they are stored, bound to thyroglobulin in the colloid of the thyroid gland.
50
How thyroid hormones are synthesized?
1. Tyrosine-containing thyroglobulin is produced within the follicular cells by the ER-Golgi complex and is transported to the colloid by exocytosis.
2. Iodide is taken up by follicular cells through iodide trapping. Iodide is driven against its concentration gradient by using a Na+ co-transporter that moves Na+ down its concentration gradient.
3. Iodide is then transferred into the colloid of the follicular lumen.
4. Almost simultaneous to the iodide moving into the colloid, thyroperoxidase converts iodide into a highly reactive state, iodine, which immediately attaches to a tyrosine residue on a thyroglobulin molecule. This process is called iodide organification. The attachment of one iodine to a tyrosine produces monoiodotyrosine (MIT), while the attachment of a second iodine produces diiodotyrosine (DIT).
5. A coupling process occurs that combines MITs and DITs to form the thyroid hormones. The coupling of one MIT and one DIT forms T3 while the coupling of two DITs forms T4. There is no coupling of two MITs. Both T3 and T4 remain bound to the thyroglobulin after the chemical reactions.
51
For thyroid hormone synthesis, how are T3 and T4 formed through coupling?
T3 = MIT + DIT
T4 = DIT x2
There is no coupling of two MITs.
52
What is iodide organification?
The enzyme thyroperoxidase converts iodide into a highly reactive state, iodine (I0), which immediately attaches to a tyrosine residue on a thyroglobulin molecule.
53
How are thyroid hormones released?
1. The follicular cells engulf a portion of the thyroglobulin-containing colloid by phagocytosis and create hormone-filled vesicles.
2. Once inside the follicular cell, lysosomes fuse with the vesicles and digestive enzymes release all of the MIT, DIT, T3 and T4 from the thyroglobulin.
3. Because T3 and T4 are very lipophilic, they immediately cross the plasma membrane to the blood where they bind to plasma proteins, mainly thyroid-binding globulin.
54
How do the timing and duration of thyroid hormone actions compare to those of other hormones?
Slower and the duration of the response can last for days, even after plasma concentrations of thyroid hormone have returned to normal.
55
How does thyroid hormone affect basal metabolic rate and heat production?
It increases the overall basal metabolic rate by increasing O2 consumption and energy expenditure. Increased metabolic rate leads to increased heat production.
56
How does thyroid hormone affect intermediary metabolism at low versus high hormone concentrations?
At low concentrations, thyroid hormone favours glucose storage as glycogen and promotes protein synthesis, whereas at high concentrations it stimulates glycogen breakdown to glucose and increases protein degradation.
57
How does thyroid hormone exert sympathomimetic effects on target cells?
It can increase a target cell's response to catecholamines. This is accomplished by increasing the number of catecholamine receptors.
58
What are the effects of thyroid hormone on the cardiovascular system?
Due to its sympathomimetic effect on the heart, it can increase both heart rate and strength of contraction to increase cardiac output. Other cardiovascular effects include an increase in blood volume and flow but does not impact blood pressure.
59
Do thyroid hormones impact blood pressure?
No, they can increase blood volume and flow.
60
How does thyroid hormone contribute to normal growth and skeletal development?
It stimulates the release of both GH and insulin-like growth factor and also promotes their actions to stimulate the synthesis of new structural proteins and skeletal growth.
61
Which hormone is the most important regulator of thyroid hormone secretion and influences most of the stages of thyroid hormone synthesis and release?
Thyroid stimulating hormone (TSH)
62
What's the direct effect of TSH on the thyroid gland?
In the absence of TSH, the thyroid gland shrinks in size. With excess TSH, thyroid gland follicles get larger and increase in number.
63
How do hypothalamic and anterior pituitary hormones regulate the thyroid gland?
The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH). TSH then acts on the thyroid gland to regulate the production and release of thyroid hormones.
64
The release of both TSH and TRH are under what type of control?
Negative feedback control
65
What are the three main causes of hypothyroidism?
1. Primary failure of the thyroid gland (e.g., Hashimoto's thyroiditis) - typically low levels of T3 and T4 but elevated levels of TSH. This is because there is no T3 and T4 being produced to provide negative feedback and decrease the production of TRH and TSH (goiter present)
2. Secondary failure: occurs when the hypothalamus and/or the pituitary fail to secrete adequate TRH and/or TSH. Hypothyroidism due to secondary failure is characterized by low levels of T3 or T4 (or both) + TRH and/or TSH, depending on the location of dysfunction.
3. Inadequate dietary supply of iodine. This is the most common cause. It is characterized by low T3 and T4 and elevated TSH (goiter present)
66
What is the most common cause of hypothyroidism?
Inadequate dietary supply of iodine
67
Define primary failure and secondary failure of hypothyroidism.
Primary failure = A dysfunction originating in the endocrine gland itself.
Secondary failure = Caused by over- or under-stimulation by the pituitary gland.
68
What are the common symptoms of hypothyroidism?
Cold intolerance, slower reflexes, reduced mental alertness, easy to fatigue, slow/weak heart rate, weight gain due to decreased basal metabolic rate
69
Congenital hypothyroidism is called?
Cretinism. Because thyroid hormone is required for growth and development, cretinism is characterized by dwarfism and intellectual disability.
70
What are the main causes of hyperthyroidism?
1. Secondary failure of the thyroid gland: Generally observed when there is a tumour in either the hypothalamus (that secretes excess TRH) or in the anterior pituitary (that secretes excess TSH). Such tumours generally ignore negative feedback, leading to elevated T3 and T4, with elevated TRH and/or TSH (goiter present)
2. Thyroid tumour: A tumour in the thyroid gland itself results in an increased secretion of thyroid hormones. Elevated T3 and T4, decreased TSH.
3. Grave's disease: The most common cause. The body produces long-acting thyroid stimulator (LATS), an antibody that targets and activates TSH receptors on follicular cells. LATS has the same effects as excessive TSH in that it causes the follicles to grow larger and increase in number. However, because LATS is not under negative feedback control, the hyperthyroid stimulus persists. High T3 and T4, low TSH (goiter present).
71
What is the most common cause of hyperthyroidism? It is also the most common cause of what?
Grave's disease. Also the most common cause of exophthalmos (bulging of the eyes; this is caused by a buildup of water-retaining carbohydrates behind the eyes that retain fluid and push the eyeballs forward)
72
What are the common symptoms of hyperthyroidism?
- Increased heart rate
- Excessive heat production
- Muscle weakness due to skeletal muscle protein degradation
- Mood swings due to increased CNS mental alertness
- Elevated basal metabolic rate that causes weight loss even with increased caloric intake
73
What is one symptom that can arise from both hypothyroidism and hyperthyroidism?
Goiter. It is an enlarged thyroid gland; results from any condition that leads to increased TSH. TSH stimulation of the thyroid gland, to increase the number and size of follicles.
74
What are the anatomical features of the adrenal glands?
They are small and located at the top of the kidneys. Cortex (the outer layer; secrete several steroid hormones) + Medulla (inner layer; secretes catecholamines
75
Which organ secretes catecholamines?
Medulla (inner layer) of the adrenal glands.
76
What are the anatomical features of the adrenal cortex?
The adrenal cortex can be divided into: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Each zone can produce different hormones.
77
What are the characteristics of hormones produced in the adrenal cortex? What are the three main categories?
They are all steroid hormones and are based on cholesterol as a precursor.
1. Mineralocorticoids: Influence mineral (electrolyte) balance. Produced mainly in the zona glomerulosa.
2. Glucocorticoids: Important in glucose, lipid, and protein metabolism. Produced mainly in the zona fasciculata and zona reticularis.
3. Sex hormones: Produced in lower quantities in the zona fasciculata and zona reticularis.
78
Define circulatory shock.
A condition in which blood pressure decreases to the point that adequate blood flow to tissues is compromised.
79
What are aldosterones?
The main mineralocorticoid hormone produced by the adrenal cortex. It is essential for sodium conservation in the kidney, salivary glands, sweat glands and colon.
80
What would happen in the absence of mineralocorticoids?
A person would die as quickly as in a matter of days due to circulatory shock.
81
What is the major mineralocorticoid produced in the adrenal cortex? The absence of it would lead to what?
Aldosterone. In its absence, extracellular fluid volumes drop, causing a decrease in blood pressure that leads to circulatory shock.
82
How is aldosterone secretion regulated, and how does it relate to anterior pituitary control?
Aldosterone secretion is regulated by electrolyte concentrations (especially sodium and potassium), blood volume, and blood pressure, and it is independent of anterior pituitary control.
83
What are the two primary stimuli for aldosterone secretion?
1. Activation of the renin-angiotensin-aldosterone system in response to reduced Na+ and a fall in blood pressure.
2. Direct stimulation of the adrenal cortex by increased K+ concentration.
84
What is the primary glucocorticoid?
Cortisol
85
What are the metabolic effects of cortisol?
Cortisol stimulates gluconeogenesis in the liver using non-carbohydrate precursors like amino acids, promotes protein breakdown in muscle to provide these amino acids, inhibits glucose uptake by most tissues except the brain, and stimulates lipolysis to mobilize free fatty acids for energy.
86
How does cortisol help the body adapt to stress and support energy needs during fasting or injury?
Cortisol shifts metabolism to increase carbohydrate availability for the brain, mobilizes amino acids and free fatty acids from protein and fat stores, and provides building blocks for wound repair, helping the body cope with stress and periods of fasting.
87
Define diurnal rhythm.
Think of it like a constantly changing set point rather than the body trying to maintain steady plasma concentrations 24 hours a day. The diurnal pattern follows the sleep-wake cycle so cortisol secretion in persons who work night shifts adapts to their sleep-wake cycle and not light-dark cycles.
88
How is cortisol secreted?
Cortisol secretion is under negative feedback. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release ACTH. This ACTH stimulates the adrenal glands to release cortisol. Plasma cortisol feeds back to the hypothalamus and anterior pituitary to reduce CRH and ACTH release.
89
What is the diurnal secretion pattern of cortisol, and how can stress affect it?
Cortisol levels are highest in the morning and lowest at night, a rhythm controlled by the hypothalamus and anterior pituitary. Mental or physical stress can override this pattern by increasing CRH release, leading to higher cortisol levels regardless of the time of day.
90
What's dehydroepiandrosterone (DHEA)?
A weaker version of testosterone. DHEA secretion begins at puberty and peaks around 30 years of age, after which there is a steady decline.
91
Where are androgens and estrogens produced?
Androgens (male hormones) are produced in the testes, while estrogens (female hormones) are produced in the ovaries.
92
What is the most important adrenal cortex sex hormone?
Dehydroepiandrosterone (DHEA). It plays little role in males (due to testosterone) but in females, it is important for growth of pubic and armpit hair, enhancement of the growth spurt at puberty, and maintenance of the female sex drive.
93
Where are epinephrine and norepinephrine synthesized and stored?
They are synthesized by the adrenomedullary secretory cells and stored in chromaffin granules. Upon appropriate stimulation, the chromaffin granules undergo exocytosis to release epinephrine and norepinephrine into the bloodstream.
94
What are the alpha and beta adrenergic receptors? For each, indicate whether the general action is excitatory or inhibitory.
Alpha 1: Excitatory (found post-synaptically)
Alpha 2: Inhibitory (found pre-synaptically)
Beta 1: Excitatory
Beta 2: Inhibitory
Beta 3: Excitatory
95
How do norepinephrine and epinephrine differ in their receptor targets and effects on blood vessels?
Norepinephrine, released from nerve endings, mainly binds α and β1 receptors near postganglionic sympathetic terminals. Epinephrine, released from the adrenal medulla, can reach all α and β1 receptors and exclusively activates β2 receptors, causing vasodilation in skeletal muscle, while norepinephrine-mediated sympathetic activation generally constricts vasculature in areas like the GI tract and urinary bladder.
96
Beta 2 receptors are exclusively activated by?
Epinephrine
97
What are the effects of epinephrine on organ systems?
In an emergency or stressful situation, the sympathetic nervous system mobilizes adrenomedullary epinephrine system. This causes an increased heart rate and strength of contraction to increase cardiac output and a generalized vasoconstriction to increase total peripheral resistance and thus blood pressure. As well, there is a vasodilation in skeletal muscle blood vessels and a dilation of the respiratory airways to increase oxygen intake. Both epinephrine and norepinephrine decrease digestive activities.
98
What are the effects of epinephrine on metabolism?
Epinephrine increases blood glucose by enhancing liver gluconeogenesis (synthesis of new glucose) and glycogenolysis (breakdown of glycogen to release glucose). Glycogenolysis is also stimulated in skeletal muscles. Epinephrine also promotes lipolysis to increase circulating free fatty acids that can be used as an energy source by the heart and skeletal muscles.
99
How does the sympathetic stress response, together with the endocrine system, prepare the body to handle stress?
The sympathetic nervous system, working with the endocrine system by releasing epinephrine from the adrenal medulla, prepares the body for stress by increasing muscle strength, mental activity, blood pressure, and cellular metabolism, and by redirecting blood flow to essential organs while reducing it to non-essential organs.
100
What are the systems involved in stress response?
Sympathetic nervous system, renin-angiotensin-aldosterone system, insulin and glucagon, and CRH-ACTH-Cortisol system
101
What is the role of the renin-angiotensin-aldosterone system in stress response?
During stress, there is an increase in vasopressin and angiotensin II, both of which are vasoconstrictors that can help to increase blood pressure in an emergency.
102
What is the role of insulin and glucagon in stress response?
They increase blood glucose. Increased glucagon secretion will break down glycogen stores to produce glucose and decreasing insulin secretion will reduce the rate at which glucose is removed from the circulation.
103
What is the role of the CRH-ACTH-Cortisol system in stress response?
This is the main system involved in the integrated stress response. Cortisol increases blood levels of glucose, free fatty acids, and amino acids to provide energy substrate to the brain and to facilitate repair of any damaged tissues. However, it is also recognized that ACTH may play a role in resisting stress. During the formation of ACTH from a larger precursor molecule, β-endorphin, a natural morphine-like substance, is also produced and released along with ACTH. In the case of stress, β-endorphin could act like analgesia in the case of physical injury.
104
Describe the general pathway of the integrated stress response.
Once the hypothalamus receives input concerning physical and emotional stressors, it activates the sympathetic nervous system, secretes CRH to stimulate ACTH and cortisol release, and triggers the release of vasopressin. Activation of the sympathetic nervous system brings about the secretion of epinephrine, which influences pancreatic secretion of insulin and glucagon.
Also, vasoconstriction due to catecholamine release means less blood flow through kidneys, setting the renin-angiotensin-aldosterone system in motion.
105
What is hyperadrenalism?
Conditions in which the adrenal glands secrete excessive amounts of the hormones they produce.
106
What are the three main patterns of symptoms caused by hyperadrenalism?
1. Cortisol hypersecretion (aka Cushing's syndrome): It can occur due to overstimulation of the adrenal cortex by CRH and/or ACTH, adrenal tumours hypersecreting cortisol independent of ACTH, and ACTH-secreting tumours located somewhere other than the pituitary. Increased circulating cortisol + subsequent increased plasma glucose.
2. Adrenal androgen hypersecretion: Symptoms depend upon the age and sex of the individual.
3. Hyperaldosteronism: Excessive mineralocorticoid secretion can be caused either by an aldosterone-secreting tumour (primary hyperaldosteronism) or by abnormally high activity of the renin-angiotensin-aldosterone system (secondary hyperaldosteronism). The symptoms are based on the activity of aldosterone and include excessive Na+ retention (hypernatremia), K+ depletion (hypokalemia), and high blood pressure.
107
What are the characteristic physical features of Cushing's Syndrome?
Buffalo hump (redistribution of fat causes increased depositions on the back between the shoulder blades) and moon face (excessive oedema in the cheeks)
108
What are the symptoms of adrenal androgen hypersecretion depending on age and sex?
Adult females: Masculine-like body hair (hirsutism). Usually an increase in male secondary sex characteristics (deepening of the voice, more muscular). Breast size decreases and menstruation may cease.
Adult males: Little to no effects
Newborn females: Exhibit male-type external genitalia. During development, the clitoris enlarges and takes on a penile-type appearance.
Prepubertal males: Early development of male secondary sex characteristics called precocious pseudo-puberty.
109
What are the symptoms of hyperaldosteronism?
The symptoms are based on the activity of aldosterone and include excessive Na+ retention (hypernatremia), K+ depletion (hypokalemia), and high blood pressure.
110
Primary vs. Secondary hyperaldosteronism
Primary hyperaldosteronism = aldosterone-secreting tumour
Secondary hyperaldosteronism = abnormally high activity of the renin-angiotensin-aldosterone system
111
What would happen if you were to lose one adrenal gland?
The remaining gland would undergo hypertrophy and hyperplasia to increase its hormone secreting capacity. Because of this, it takes dysfunction of both adrenal glands to occur before any type of adrenocortical insufficiency manifests.
112
What are the two types of adrenocortical insufficiency?
Primary Adrenocortical Insufficiency (Addison’s disease): Caused by underactive adrenal cortex, often due to autoimmune destruction, leading to deficiencies in cortisol and aldosterone. This results in hyperkalemia, hyponatremia, hypotension, hypoglycemia, poor stress response, and skin hyperpigmentation from elevated ACTH. It can be life-threatening if untreated.
Secondary adrenocortical insuffiency: Results from hypothalamic or anterior pituitary dysfunction causing low ACTH, leading to cortisol deficiency while aldosterone remains normal. Symptoms vary with severity and include fatigue, appetite loss, weight loss, nausea, vomiting, diarrhea, muscle weakness, irritability, and depression, but hypotension and muscle spasms are less common than in primary adrenal insufficiency.
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What is metabolism?
The sum of all chemical reactions that occur in all organisms, including the synthesis, degradation, transport of substances into and between different cells, and transformation of proteins, carbohydrates, and fats. These reactions within the cell are called intermediary metabolism or fuel metabolism.
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What are anabolic reactions?
Anabolic reactions lead to the synthesis of larger organic macromolecules from smaller organic molecular subunits and are used for repair, growth, and the storage of excess ingested nutrients.
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What are catabolic reactions?
Catabolic reactions is the breakdown of larger organic macromolecules either through the process of hydrolysis into smaller molecules, or oxidation of smaller molecules, such as glucose, to yield ATP.
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What happens to excess glucose in our body?
Excess glucose is stored in the liver and skeletal muscle as glycogen. Once these glycogen stores are full, any additional glucose is converted into free fatty acids and glycerol for the synthesis of triglycerides, which occurs mainly in adipose tissue.
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What happens to the excess fatty acids in our body?
They are stored as triglycerides.
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What happens to the excess amino acids in our body?
Excess amino acids not needed for protein synthesis are not stored but rather either used for structural proteins or converted to glucose and fatty acids for eventual storage as triglycerides.
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What are the two functional metabolic states of the body?
Absorptive state and post-absorptive state
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What is lipolysis?
The breakdown of lipids and involves hydrolysis of triglycerides into glycerol and free fatty acids
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What happens during the absorptive state?
Anabolism dominates as ingested food is digested and absorbed into the circulation. Ingested simple carbohydrates are converted in the liver to glucose, which is then released to be available as fuel, or it is stored as glycogen. Ingested fats and proteins are also immediately used or stored.
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What happens during the post-absorptive state?
Several hours after ingesting food, catabolism dominates. Glycogen stores in the liver and skeletal muscle becomes the primary energy source. However, if the post-absorptive state persists, glycogen alone cannot meet the body's energy needs, so lipolysis occurs to break down triglycerides.
123
Which organic intermediates can serve as energy sources?
1. Glycerol: It comes from the backbone of triglycerides when they are broken down and can be converted to glucose by the liver.
2. Lactic acid: Can be formed by glycolysis; can also be converted to glucose by the liver.
3. Ketone bodies: Produced in the liver in times of glucose shortages. When the liver uses free fatty acids as an energy source, they are oxidized to acetyl CoA, which does not produce any additional energy through the citric acid cycle. Instead, this acetyl CoA is converted to ketone bodies and released into the blood. In times of starvation, the brain can use ketone bodies as an energy source.
124
The endocrine functions of the pancreas are localized to?
The islets of Langerhans, which are clusters of cells found throughout the pancreas.
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What are the endocrine cells within the islets of Langerhans?
1. Alpha cells: Produce and secrete glucagon.
2. PP cells: Secrete pancreatic polypeptide, which may play a role in reducing appetite.
3. Beta cells: Produce and secrete insulin.
4. Delta cells: Produce and secrete somatostatin.
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What stimulates somatostatin release, and what are its main effects and sources in the body?
Somatostatin is released from pancreatic δ cells in response to circulating glucose and amino acids after a meal. It slows digestion by inhibiting digestion and nutrient absorption, preventing excessive nutrient uptake through negative feedback. Somatostatin is also produced by cells lining the digestive tract, where it acts as a paracrine hormone, and by the hypothalamus, where it inhibits growth hormone and TSH secretion.
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True or False: Somatostatin is only produced by the pancreas.
False. It is also produced in cells lining the digestive tract and hypothalamus.
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What is a peptide hormone?
A hormone whose molecules are short chains of amino acids monomers linked by amide bonds.
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What is the dominant hormone in the absorptive state? What are its effects? What type of hormone is it?
Insulin. It regulates blood sugar and also has effects on fats and proteins. It's a small peptide hormone.
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What are the factors that increase blood glucose?
1. Glucose absorption from the digestive tract
2. Hepatic glucose production through glycogenolysis of stored glycogen and through gluconeogenesis
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What are the factors that decrease blood glucose?
1. Transport of glucose into cells for utilization for energy production, for storage as glycogen through glycogenesis, and for storage as triglycerides.
2. Urinary excretion of glucose (occurs only abnormally, when blood glucose level becomes so high it exceeds the reabsorptive capacity of kidney tubules during urine formation)
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What are the four main effects of insulin on carbohydrate metabolism to maintain blood glucose homeostasis?
1. Stimulate glycogenesis in skeletal muscle and the liver: This promotes the storage of glucose as glycogen.
2. Increase glucose uptake into most cells. Insulin causes the movement of GLUT-4 glucose transporters from an intracellular pool to the plasma membrane where they begin to transport glucose into the cells.
3. Inhibit gluconeogenesis in the liver: This prevents the formation of glucose from amino acids.
4. Inhibit glycogenolysis in the liver: This prevents the catabolism of glycogen and further promotes glucose storage.
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Does brain require insulin for glucose uptake?
No, because the brain always has GLUT-1 and GLUT-3 glucose transporters in the plasma membrane.
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Do exercising skeletal muscles and live require insulin for glucose uptake?
No. Liver uptake of glucose is by GLUT-2 and is also insulin-independent.
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What are the four actions of insulin that lower blood free fatty acids and promote their storage as triglycerides?
1. Enhances the entry of fatty acids into adipose tissue cells
2. Increases GLUT-4 recruitment in adipose cells to increase glucose uptake for the synthesis of triglycerides
3. Enhances the activity of the enzymes involved in synthesizing triglycerides
4. Inhibits lipolysis
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What are the three main actions of insulin on proteins?
1. Promotes the uptake of amino acids into all tissues.
2. Enhances the activity of the enzymes involves in protein synthesis.
3. Inhibits the degradation of proteins.
All three favour protein synthesis.
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How is insulin secretion regulated by blood glucose levels, feedforward mechanisms, and the autonomic nervous system?
Insulin secretion is regulated by negative feedback, where elevated blood glucose stimulates pancreatic β cells to release insulin, lowering blood glucose and reducing further insulin secretion. Insulin is also regulated by feedforward mechanisms, in which gastrointestinal hormones released during digestion stimulate insulin secretion in anticipation of rising blood glucose. In addition, the autonomic nervous system influences insulin release: parasympathetic activity increases insulin secretion in response to food intake, while sympathetic activity decreases insulin secretion, allowing blood glucose to rise during stress or exercise.
138
What is the major pancreatic hormone involved during the post-absorptive state? What triggers its direct secretion? What is its major site of action
Glucagon. Triggered directly by the decrease in blood glucose levels. Liver (has direct opposite effects of insulin).
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What are the effects of glucagon on carbohydrates?
It increases hepatic glucose production by decreasing glycogen synthesis, enhancing both glycogenolysis and gluconeogenesis.
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What are the effects of glucagon on fats?
It promotes lipolysis while inhibiting fat storage. It also enhances the formation of ketone bodies in the liver.
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What are the effects of glucagon on proteins?
It promotes protein catabolism but only in the liver.
142
How do fluctuations in blood fatty acid concentration affect insulin and glucagon secretion?
Changes in blood fatty acid levels produce the same pattern of insulin and glucagon release as changes in blood glucose, with insulin increasing when fuels are abundant and glucagon increasing when they are low.
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Why does a rise in blood amino acid concentration stimulate both insulin and glucagon release, and how does this maintain normal blood glucose after a high-protein, low-carbohydrate meal?
Elevated amino acids stimulate release of both hormones; insulin promotes amino acid uptake and protein synthesis, while glucagon’s hyperglycaemic effects counteract insulin’s glucose-lowering actions, resulting in maintenance of normal blood glucose levels.
144
What is the largest calcium store in the body?
Bones
145
What are the two main periods of rapid growth?
1. First two years of life.
2. Puberty. Prior to puberty, no difference in male and female. During puberty, large acceleration in the lengthening of long bones, more so in males.
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In both males and females, pubertal growth is supported by? What's the difference?
Growth hormone and androgens. The primary androgen responsible for stimulating growth in females is DHEA (released from the adrenal cortex), whereas in males it's testosterone.
147
What is the most abundant hormone produced by the anterior pituitary?
Growth hormone
148
What are the three primary actions of growth hormone on intermediary metabolism?
1. Increased rate of protein synthesis
2. Increased fatty acid mobilization and use
3. Decreased rate of glucose use by body tissues
Overall, this pattern of effects shifts the body to primarily use fat stores for metabolism while sparing glucose. Particularly important during prolonged fasting as it preserves glucose for the brain.
149
What are the actions of growth hormones on soft tissues?
1. Increase the number of cells (hyperplasia) through stimulating cell division
2. Stimulate cells to grow larger (hypertrophy) by promoting protein synthesis
150
How is bone remodelled, and what cell types are responsible for changes in bone thickness and length?
Bone is highly vascularized and constantly remodelled through the activity of osteoblasts, which deposit new bone, and osteoclasts, which dissolve bone. Bone growth can result in increases in thickness or length.
151
What is marrow cavity?
The central cavity of bone shafts where red bone marrow and/or yellow bone marrow (adipose tissue) is stored. It's also called the medullary cavity.
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How bone growth in thickness is achieved?
By adding new bone to the outer layer of existing bone. As osteoblasts are depositing new bone on the outer surface of a bone, osteoclasts on the inside of the bone are removing bone. In this way, both the diameter of bone and the marrow cavity will increase.
153
Where does lengthening of bones occur?
It only occurs at its ends between the epiphysis (the knob at the end) and the diaphysis (the shaft of the bone) in the epiphyseal plate.
154
How does bone lengthening occur?
Long bone growth occurs at the epiphyseal plate between the epiphysis and diaphysis. Chondrocytes divide and stack in columns, causing the bone to elongate; as they mature, they hypertrophy and the surrounding matrix calcifies. Because cartilage is poorly vascularized, older chondrocytes die and are removed by osteoclasts, allowing osteoblasts and capillaries to invade and replace cartilage with bone through ossification. New chondrocyte formation balances removal so the plate remains relatively constant in width. At the end of adolescence, sex hormones cause epiphyseal plates to ossify, ending linear growth, while bone thickening can continue throughout life.
155
How does growth hormone influence bone growth, and what mediates its effects on chondrocytes?
Growth hormone promotes both bone thickness and length, but its effects on chondrocytes are indirect. In the body, growth hormone stimulates the production of somatomedins (insulin-like growth factors, IGF-I and IGF-II), which mediate its effects on chondrocytes and bone growth.
156
How does growth hormone stimulate IGF-I production, and what role does IGF-I play in growth?
Growth hormone stimulates IGF-I production in the liver and locally in other tissues (paracrine action). IGF-I mediates most of growth hormone’s growth-promoting effects.
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Does growth hormone stimulate IGF-II production, and what is the role of IGF-II in development and adulthood?
No. IGF-II is important during fetal development. It's produced in adults but its role is not clear.
158
What hypothalamic hormones regulate growth hormone secretion, and what factors influence its release and diurnal pattern?
Growth hormone is regulated by two hypothalamic hormones: GHRH (stimulates release) and GHIH/somatostatin (inhibits release). Its secretion follows a diurnal pattern, peaking about an hour after deep sleep, and can be increased by exercise, stress, low blood glucose, and high blood amino acids. Its regulation is on negative feedback.
159
What are the causes and consequences of growth hormone deficiency in children and adults, and how do treatments differ?
Growth hormone deficiency can result from dysfunction at the hypothalamus, pituitary, or tissue level. In children, deficiency leads to dwarfism, which can be treated with growth hormone if diagnosed early. Laron dwarfism, caused by tissue insensitivity to GH, responds instead to IGF-I treatment. In adults, GH deficiency causes reduced muscle mass and strength, decreased bone density, and higher risk of heart failure.
160
What causes growth hormone excess, and how do its effects differ between childhood and adulthood?
Growth hormone excess is usually caused by a tumour in the anterior pituitary. In children, it affects the epiphyseal plates, causing rapid growth and gigantism. In adults, after epiphyseal plate closure, height is unaffected, but bones thicken, leading to acromegaly, which is characterized by coarsening of the jaw and cheekbones, enlargement of hands and feet, and thickened fingers and toes.
161
What is the most abundant mineral in the human body?
Calcium. Most are stored in the bone (99%). Intracellular calcium (0.9%) and extracellular calcium (0.1%).
162
Why is calcium important in the human body, and how is it distributed?
It functions as an electrolyte, supports muscular, circulatory, and digestive system health, is essential for bone formation, and aids in blood cell synthesis and function. In the body, calcium is divided into three pools.
163
How is plasma calcium (Ca²⁺) regulated, and which hormones are involved?
Unlike Na⁺ and K⁺, Ca²⁺ is regulated hormonally rather than mainly by the kidneys. Dietary calcium enters the plasma, and excess is stored in bones; during high intake, absorption decreases, and when plasma calcium is low, calcium is mobilized from bones. The three key hormones regulating calcium are parathyroid hormone (PTH), calcitonin, and vitamin D. Phosphate (PO₄³⁻) regulation is also important because it affects calcium storage in bone.
164
What are the examples of important physiological process involving calcium?
o Neuromuscular excitability
o Secretion of vesicles
o Excitation-contraction coupling in cardiac and smooth muscles
o Release of neurotransmitters
o Role as a second messenger
165
Where are the parathyroid glands located, and what is the primary function of parathyroid hormone (PTH)?
The four parathyroid glands are located on the back of the thyroid gland. PTH is essential for life, as removal of the glands causes death from hypocalcemia within days. Its primary function is to raise plasma Ca²⁺ levels by acting on bone, kidneys, and intestines.
166
How does parathyroid hormone (PTH) regulate calcium levels through bone remodelling, and what is the effect on phosphate?
Calcium is primarily stored in bones as hydroxyapatite crystals (Ca₃(PO₄)₂). Bone remodeling by osteoclasts (breakdown) and osteoblasts (formation) allows rapid changes in plasma Ca²⁺. PTH slightly enhances osteoclast activity and inhibits osteoblasts, leading to net bone breakdown, which releases Ca²⁺ and PO₄³⁻ into the plasma. The increase in Ca²⁺ is the intended effect, while the rise in phosphate is a secondary consequence.
167
How does parathyroid hormone (PTH) regulate calcium and phosphate in the kidneys, and what is its effect on vitamin D?
In the kidneys, PTH stimulates Ca²⁺ reabsorption, preventing excessive bone breakdown to maintain plasma calcium. It also promotes phosphate (PO₄³⁻) excretion, preventing high phosphate from promoting hydroxyapatite formation that would lower plasma Ca²⁺. Additionally, PTH stimulates activation of vitamin D, which further helps regulate calcium.
168
How is PTH secretion regulated by plasma calcium levels?
PTH secretion is inversely related to plasma Ca²⁺: it increases when Ca²⁺ levels drop and decreases when Ca²⁺ levels rise.
169
What is calcitonin, where is it secreted from, and how does it affect calcium levels in the body?
Calcitonin is secreted by the C cells of the thyroid gland. It is released in response to high plasma Ca²⁺ levels and acts oppositely to PTH by inhibiting osteoclast activity, which prevents the release of Ca²⁺ and PO₄³⁻ from bone.
170
What is vitamin D (cholecalciferol), how is it activated, and what are its main functions in calcium regulation?
Vitamin D is produced in the skin from 7-dehydrocholesterol via UV light or obtained from the diet. It is hydroxylated by the kidneys to form calcitriol, the active hormone. Its main functions are to increase intestinal Ca²⁺ absorption and enhance bone cell responsiveness to PTH, ensuring proper calcium balance. Dietary calcium is not freely absorbed and without vitamin D, dietary calcium is excreted in the feces.
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How is vitamin D activated, and what role does PTH play in this process?
Vitamin D is activated through two hydroxylation steps: first in the liver, then in the kidneys, producing 1,25-(OH)₂-vitamin D₃ (calcitriol), the active form. PTH stimulates the kidney enzymes for this activation. Together, PTH and vitamin D regulate Ca²⁺ homeostasis, with PTH playing the primary role.
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What is the main effect of activated vitamin D on calcium absorption, and how does it interact with PTH?
Activated vitamin D greatly increases intestinal Ca²⁺ absorption, allowing more dietary calcium to enter the plasma rather than being lost in feces. It also enhances bone responsiveness to PTH, making vitamin D and PTH closely interdependent in calcium regulation.
PHGY 216
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