Module 1: Endocrine Physiology Flashcards
1
Q
what is the endocrine sys comprised of
A
many different glands
2
Q
what do glands form
A
a coordinated system as they all secrete hormones, and many functional interactions take place between them
3
Q
how is the endocrine system a major regulatory system
A
uses hormones to produce homeostatic adjustments
4
Q
what are the 6 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
- RBC production
- Integrating with autonomic nervous sys in regulating both circulation and digestive functions
5
Q
what are hormones
A
chemical substances that are secreted directly into the blood at low quantities, and exert physiological effect at a distant target tissue
6
Q
what are the 2 major classes of hormones
A
- hydrophilic (water loving)
- lipophilic (lipid loving)
7
Q
what are hydrophilic hormones?
A
- highly H2O soluble
- low lipid solubility
- can be found unbound to carrier molecules within the plasma
- 1st group are mostly peptides or proteins (called peptide hormones), the 2nd are amines (hormones based on amino acid residues)
8
Q
what are peptides
A
short chains of amino acids
9
Q
what are proteins
A
longer chains of amino acids
10
Q
2 types of hydrophilic hormones
A
- peptide hormones
- amines
11
Q
2 types of amine hormones
A
- catecholamines (NE & E)
- thyroid hormones (note these are not hydrophilic)
12
Q
where are catecholamines found
A
unique bc they are found both free and bound to carrier molecules
13
Q
how are peptide hormones synthesized and secreted
A
by the same cellular machinery that makes proteins within cells
- synthesis: large precursor proteins called preprohormones are synthesized by ER ribosomes
- packaging: travel through ER and Golgi complex, then preprohormones are processed into active hormones and packaged into secretory vesicles
- storage: hormone-containing secretory vesicles can be stored until the cell receives the appropriate signal
- secretion: appropriate signal initiates exocytosis of vesicles and the hormones are released into the blood
14
Q
what are lipophilic hormones
A
- highly soluble in lipids
- poorly soluble in H2O
- generally require carrier molecules for transport throughout the body
- include amine thyroid hormones and steroid hormones
15
Q
what single molecule are steroid hormones synthesized from
A
cholesterol
16
Q
how are different steroid hormones produced
A
depends on a particular tissue on the specific enzymes within that tissue
ex: enzyme leading to cortisol synthesis is only found in adrenal cortex which is why only that organ can make cortisol
17
Q
how are steroid hormones stored and released
A
so lipophilic they are not stored, but rather released as they are synthesized
18
Q
how do you regulate the amount of steroid hormone released
A
you need to regulate its synthesis!
19
Q
what do you need for hormones to achieve their desired effect
A
only free, unbound hormone can interact w a receptor at its target cell
(not rly a problem for hydrophilic hormones and catecholamines mainly found in their unbound state, but lipophilic hormones need carrier molecules and the consideration of dynamic equilibrium of hormone binding to its carrier)
hormones are dynamically unbinding and rebinding, resulting in a small fraction of hormone that is unbound at a particular time. it is this unbound hormone that is active and able to act on target cells.
20
Q
what happens when peptide hormones and catecholamines bind to their receptor?
A
produces effects within cells by activating 2nd messenger system. are able to amplify initial signal, as low concentrations of hormones trigger cellular responses.
21
Q
how does cyclic AMP (cAMP) work as a secondary messenger
A
- extracellular messenger binds to receptor
- activates G protein
- shuttles to and activates several adenylyl cyclase
- these activated proteins convert many molecules of ATP to cAMP
- which activate protein kinase A
- the activate protein kinase A enzymes then phosphorylate and activate target proteins
which can bring about the desired result
22
Q
how does Ca2+ work as a secondary messenger
A
- extracellular messenger binds to receptor activating G protein
- shuttles to activate several phospholipase C enzymes
- these proteins convert PIP2 to IP3 and DAG
- IP3 mobilizes intracellular Ca2+
- activating calmodulin
- Ca2+-calmodulin complexes and activates Ca2+-calmodulin complexes then activate Ca2+-calmodulin-dependent protein kinase
- which phosphorylate and activate target proteins bringing the desired response
23
Q
what happens after steroid and thyroid hormones bind to their receptor
A
- are able to pass through plasma membrane and the nuclear membranes of the cell
- binding produces effects by regulating gene transcription and protein synthesis
24
Q
how do lipophilic hormones exert their effects on cells
A
by regulating protein synthesis
*lipophilic hormone receptors can be found within the cytoplasm or the nucleus
25
what are the 6 steps of lipophilic hormones regulating protein synthesis
1. free lipophilic hormone diffuse across the plasma membrane and/or the nuclear membrane to interact with intracellular receptors
2. hormone-receptor complex (H-R) binds to the hormone response element (HRE) within the DNA
3. DNA binding activates specific genes and produces messenger RNA (mRNA)
4. mRNA leaves the nucleus
5. mRNA binds to a ribosome and proteins are synthesized
6. the newly synthesized proteins ultimately lead to the cellular response of the hormone
26
name some differences between neurotransmitters and hormones
- neurotransmitters belong to the nervous system, hormones are endocrine system
- neurotransmitters are transmitted across a synaptic cleft, hormones are transmitted by the blood
- hormones are produced by endocrine glands, neurotransmitters are produced by neurons
- neurotransmitters must travel a short distance to their target, hormones may travel a great distance
27
nervous control vs endocrine control for response time
nervous = rapid responses (milliseconds)
endocrine = slow responses (minutes to hours)
28
nervous control vs endocrine control for duration of effect
nervous = brief in duration (ends when stimulus stops)
endocrine = long in duration (effects persist after stimulus stops)
29
nervous control vs endocrine control for # of targets
nervous = hard-wired to one specific target (muscle or gland)
endocrine = many different targets in the body (blood circulates)
30
what is the pituitary gland
- very small gland located in a bony cavity at the base of the skull
- divided by the posterior and anterior pituitary gland
31
what is the posterior pituitary gland
- comprised of neural-like tissues and is sometimes called neurohypophysis
32
what is the anterior pituitary gland
- comprised of glandular epithelial tissues and is also called the adenohypophysis
33
what does the hypothalamus do
controls hormone release but does so in a different matter for either posterior/anterior lobe
34
What is the relationship between the hypothalamus and the posterior pituitary
- hypothalamus is connected to the posterior pituitary by a neural pathway
- in the hypothalamus there are 2 well-defined clusters of neurons, called supraoptic nucleus and the paraventricular nucleus, axons from these nuclei go down the pituitary stalk and terminate on blood vessels in the posterior pituitary
35
are hormones produced in the posterior pituitary gland itself
no
35
What is the relationship between the hypothalamus and the anterior pituitary
- hypothalamus is connected to the anterior pituitary by a unique vascular link: the hypothalamic-hypophyseal portal system
- hypothalamus secretes hormones into this portal system where they are carried directly to the anterior pituitary where they inhibit/promote the release of anterior pituitary hormones
36
where are hormones synthesized in the neuron cell bodies
the hypothalamus
37
what happens once hormones are synthesized by the hypothalamus
- they are packed into small vesicles which are transported down the axons to the nerve endings in the posterior pituitary
- once an appropriate stim reaches the hypothalamus, these neurons transmit an action potential that cause the release of hormone-containing vesicles into the blood
38
what is vasopressin
- aka antidiuretic hormone (ADH)
- enhances retention of water by the kidneys
- causes contraction of arteriolar smooth muscle (vasoconstriction)
39
what is oxytocin
- stim contraction of uterine smooth muscle cells during childbirth
- promoting milk ejection during breastfeeding
40
1. what 6 hormones does the anterior pituitary gland synthesize and release. 2. what do we call these hormones?
1. GH, ACTH, LH, TSH, FSH, PRL
2. tropic hormones
41
what is GH
growth hormone
- regulates overall body growth and is involved in metabolism
42
what is ACTH
stimulates secretion of cortisol by adrenal cortex (metabolic actions, stress response)
43
what is LH
luteinizing hormone
in females: responsible for ovulation and formation of corpus luteum, stim secretion of estrogen and progesterone in the ovaries
in males: stim release of testosterone from interstitial cells of Leydig
44
what is TSH
thyroid-stimulating hormone
- stim release of thyroid hormones from thyroid gland
45
what is FSH
follicle-stimulating hormone
in females: stim growth and development of ovarian follicles and promotes secretion of estrogen by ovaries
in males: required for sperm production
46
what is PRL
prolactin
- only anterior pituitary hormone that is not tropic!
in females: enhances breast development and milk production
in males: its physiological purpose is unclear
47
what is the hypothalamis-hypophyseal portal system
a vascular link between the hypothalamus and anterior pituitary
48
describe the steps of the hypothalamic-hypophyseal portal system
1. hypophysiotropic hormones produced by neurosecretory neurons in the hypothalamus enter the hypothalamic capillaries
2. the hypothalamic-hypophyseal portal system, a vascular link to the anterior pituitary
3. 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 stim by appropriate hypothalamic releasing hormone, the anterior pituitary secretes a given hormone into these capillaries
6. anterior pituitary capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for ultimate distribution throughout the body by systemic circulation
49
what does TRH release
thyrotropin-releasing hormone simulates the release of TSH and prolactin
50
what does GnRH stimulate
gonadotropin-releasing hormone stimulates the release of FSH and LH
51
what does GHIH stimulate
growth hormone inhibiting hormone inhibits the release of GH and TSH
52
what does CRH stimulate
corticotropin-releasing hormone stimulates the release of ACTH (corticotropin)
53
what does GHRH stimulate
growth hormone releasing hormone stimulates the release of growth hormone
54
what does PRH stimulate
prolactin-releasing hormone stimulates the release of prolactin
55
what does PIH stimulate
prolactin-releasing hormone stimulates the release of prolactin
56
hypothalamic neurons secrete hormones that receive a vast array of inputs, what are the 2 inputs?
neuronal and hormonal
they include both inhibitory and stimulatory inputs
57
do all sections of the hypothalamus have a blood-brain barrier?
no, some sections do not
bc of this the hypothalamus can monitor blood and respond to circulating chemicals o changes in plasma composition (osmolarity)
58
what are the hypothalamic hormones (for the most part) involved in
the 3 hormone hierarchic chain of command
59
what is the 3 hormone hierarchic chain of command
the hypothalamic hormone is released into portal sys, before traveling to pituitary gland to regulate output of a tropic hormone. this tropic hormone is transported by systemic circulation to its target endocrine gland where it regulates secretion of 3rd hormone producing a physiological effect
60
what hormone ultimately acts in negative-feedback fashion to reduce secretion of regulatory hormones higher in chain of command?
the hormone ultimately secreted by the target gland
61
in response to stress, the hypothalamus increases secretion of _______________
corticotropin-releasing hormone
62
corticotropin-releasing hormone then simulates the __________ pituitary to release ___________
anterior, adrenocorticotropic hormone
63
ACTH then acts on the adrenal ____________ to release ____________
cortex, cortisol
64
cortisol acts in a -'ve feedback fashion to reduce secretion of regulatory hormones from the ___________ and _____________
hypothalamus, anterior pituitary
65
what is the thyroid gland?
- located over the trachea just below the larynx
- consists of 2 lobes connected by a thinner section of the gland known as the isthmus
- no diff between lobes, the whole gland serves to produce and secrete thyroid hormones
66
what are the 2 thyroid gland hormones produced from
the amino acid tyrosine
67
what is a unique feature of both thyroid hormones
they contain iodine
68
what is the similarity and difference between the 2 thyroid hormones
- they exert the same physiological effects
- only differences in their speed and intensity of action
- T3 is considered to be the more active thyroid hormone
- T4 is converted to T3 in target tissues
69
what are the 2 thyroid hormones
1. tetraiodothyronine (T4 or thyroxine)
2. triiodothyronine (T3)
70
how many iodine molecules does tetraiodothyronine (T4 or thyroxine) contain
4, represents 90% of thyroid hormones secreted
71
how many iodine molecules does triiodothyronine (T3) contain
contains 3 iodine molecules and represents the remaining 10% of secreted hormones
72
how much iodine a week does the body require to ensure sufficient levels of thyroid hormone
1 mg
73
when ingested what does iodine circulate as
iodide
74
1. what is an example a lipophilic hormone that (unlike others) are fully formed hormones and can be protected from secretion while they are stored?
2. what are they bound too during this?
1. thyroid hormones
2. bound to thyroglobulin in the colloid of the thyroid gland
75
describe the 5 steps of thyroid hormone synthesis
1. tyrosine-containing thyroglobulin is produced within the follicular cells by ER-golgi complex and transported to colloid by exocytosis
2. iodide is taken in by follicular cells through iodide trapping. iodide is driven against its concentration gradient by using Na+-cotransporter that moves Na+ down its concentration gradient
3. iodide is transferred into colloid of follicular lumen
4. simultaneously to iodide moving into colloid, thyroperoxidase converts iodine which attaches to tyrosine residue on thyroglobulin molecule. called iodide organification. attachment of 1 iodine to tyrosine produces monoiodotyrosine (MIT) while the attachment of second iodine produces diiodotyrosine (DIT)
5. coupling process occurs that combines MITs and DITs to form the thyroid hormones. 1 MIT and 1 DIT forms T3, 2 DITs form T4. there is no coupling for 2 MITs, and T3 and T4 remain bound to thyroglobulin molecule after chemical reactions
76
how are thyroid hormones released (3 steps)
1. follicular cells engulf a portion of thyroglobulin-containing colloid by phagocytosis and create hormone-filled vesicles
2. once inside follicular cell, lysosomes fuse with vesicles and digestive enzymes release all the MIT, DIT, T3, T4 from the thyroglobulin
3. bc 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
77
what are the 5 actions of thyroid hormones
1. metabolic rate and heat production
2. intermediary metabolism
3. sympathomimetic
4. cardiovascular system
5. growth
78
what do thyroid actions do on the metabolic rate and heat production
increases overall basal metabolic rate by increasing O2 consumption and energy expenditure. a consequence of increasing metabolic rate is an increased heat production.
79
what do thyroid actions do on the intermediary metabolism
- influences enzymes flueling metabolism. - low concentrations of thyroid hormone = conversion of glucose to glycogen and protein synthesis are favoured
- higher concentrations = causes breakdown of glycogen to glucose and degradation of proteins
80
how do thyroid actions cause sympathomimetic effects
- increase target cell's response to catecholamines
- accomplished by increasing # of catecholamine receptors
81
what do thyroid actions do to the cardiovascular system
bc of sympathomimetic effect on heart, thyroid hormone can increase HR and strength of contraction to increase CO. also increases blood volume + flow
82
what do thyroid actions do to growth
thyroid hormone is essential for normal growth. stim the release of both growth hormone and insulin-like growth factor, and also promotes their actions to stim the synthesis of new structural proteins and skeletal growth
83
the hypothalamus secretes _____________ that acts on the anterior pituitary to secrete ______________
TRH, TSH
84
what is TSH why is it important
- most important regulator of thyroid hormone secretion, influences most of the stages of thyroid hormone synthesis and release
- directly affects thyroid gland bc without it the gland shrinks in size, w too much the gland gets too large
85
the release of both TSH and TRH are +'ve or -'ve feedback control
-'ve
86
what does feeling stressed cause the hypothalamus to do to thyroid gland
1. STRESS
2. hypothalamus
3. TRH release
4. anterior pituitary
5. TSH release
6. thyroid gland
7. T3 and T4 release
8. increased metabolic rate, heat production, growth, CNS development, sympathetic activity
87
what is hypothyroidism
low thyroid or underactive thyroid
- occurs when thyroid does not secrete enough hormone into the blood
88
what is primary failure of thyroid gland
Hashimoto's thyroiditis
- low levels of T3 and T4, but elevated levels of TSH
- no T3 or T4 being produced to provide -'ve feedback and decreased production of TRH and TSH
89
what is secondary failure of thyroid gland
hypothalamus and/or pituitary fail to secrete adequate TRH and/or TSH
- low levels of T3 or T4 (or both), as well as TRH and/or TSH depending on location of dysfunction
90
what is the most common cause of hypothydroidism
inadequate dietary supply of iodine
- characterized by low T3 and T4, and elevated TSH
91
common sympt of hypothyroidism
- cold intolerance
- slower reflexes
- reduced mental alertness
- easy to fatigue
- slow, weak heart rate
- weight gain due to decreased basal metabolic rate
92
what is congenital hypothyroidism
(thyroid hormone deficiency acquired from birth)
called cretinism
- bc thyroid hormone is required for growth and development, this can cause dwarfism and intellectual disability
93
hyperthyroidism due to secondary to excess hypothalamic or anterior pituitary secretions
- when there is usually a tumour in either hypothalamus (secreting excess TRH) or in anterior pituitary (secreting excess TSH)
- tumours generally ignore -'ve feedback, resulting in elevated T3 and T4, w elevated TRH and/or elevated TSH
94
what would you expect to see from a tumour in the thyroid gland itself
- results in an increased secretion of thyroid hormones
- elevated T3 and T4, decreased TSH
95
what is grave's disease
- most common cause of hyperthyroidism
- an autoimmune disease in which body produces long-acting thyroid stimulator (LATS), an antibody that targets and activates TSH receptors
- LATs has same effect as too much TSH (causes follicles to grow larger and increase in number
- LATs are not under -'ve control, the hyperthyroid stim persists
- T3 and T4 are high, while TSH levels are low
96
hyperthyroidism symptoms
- increased HR
- 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
97
what is goiter
- hypothyroidism AND hyperthyroidism (a goiter)
- an enlarged thyroid gland that is quite visible, results from increased TSH
98
what are the adrenal glands
- small and located at the top of the kidneys (2 endocrine organs)
- outer layers are the adrenal glands called the cortex they secrete several steroid hormones
- inner layer of adrenal gland is called medulla and secretes catecholamines
99
what 3 zones can the adrenal cortex be divided into
zona glomerulosa
zona fasciculata
zona reticularis
100
what are the 3 main categories of adrenal cortex hormones
mineralocorticoids
glucocorticoids
sex hormones
101
what are mineralocorticoids
- class of corticosteroids produced in adrenal cortex
- influence salt & water balances in body
- w/o them a person would die in days bc of circulatory shock
- major one: aldosterone!
- secretion is related to: electrolyte concentrations, blood volume, blood pressure, and is independent of anterior pituitary control
102
what are the 2 primary stimuli for mineralocorticoid secretion
- activation of RAAS sys in response to reduced Na+ and fall in blood pressure
- direct stim of adrenal cortex by increased K+ concentration
103
what is the primary glucocorticoid
cortisol
104
what are the metabolic effects of cortisol
in liver, stimulates gluconeogenesis. (produces glucose from non-carbohydrate precursors like amino acids). cortisol stim protein degradation in muscle to get these amino acids. cortisol inhibits glucose uptake in most tissues minus the brain, and also breaks down lipid stores to mobilize free fatty acids that can be used as a fuel source.
105
what is cortisols role in adaptation to stress?
not fully known why
- cortisol causes shift away from protein + fat stores while increasing carb stores
- w increased glucose this ensures good brain activity during times of fasting
- increased levels of amino acids, free fatty acids, and glucose provide building blocks for wound repair
106
cortisol secretion from adrenal cortex is under _______ feedback involving the _________ and _________
-'ve, hypothalamus, anterior pituitary
107
describe cortisol secretion
1. hypothalamus releases CRH, which stim the anterior pituitary to release ACTH
2. ACTH stim adrenal glands to release cortisol
3. plasma cortisol feeds back to hypothalamus and anterior pituitary to reduce CRH and ACTH release to maintain balance
108
what 2 other influences help modulate cortisol secretion
1. cortisol has a diurnal secretion pattern, w highest levels occurring in morning and lowest at night. this diurnal rhythm is intrinsic to hypothalamus and anterior pituitary control systems
2. mental and physical stress can override normal patterns of cortisol secretion. stress leads to large increase in CRH release from hypothalamus
109
what are androgens
male sex hormones (but are important for females too)
110
whats estrogen
female sex hormones (but needed for males too)
111
the adrenal cortex secretes _______ levels of androgens and estrogens
low
112
how does the adrenal cortex release androgens and estrogens
release is stim by ACTH, which regulates cortisol secretion, so sex hormone secretion parallels cortisol secretion. amount of sex hormones secreted is considered insignificant to those secreted by gonads.
113
what is the most important adrenal cortex sex hormone
dehydroepiandrosterone (DHEA)
- in males: plays little role (due to high testosterone
- in females: important for growth of pubic and armpit hair, enhancement of growth spurt at puberty, and maintenance of female sex drive
114
what are catecholamines synthesized by
the adrenomedullary secretory cells
115
what happens once catecholamines are synthesized
chromaffin granules, which are similar to neurotransmitter storage vesicles found in nerve ending. when stimulated they undergo exocytosis to release NE and E into bloodstream
20% if secreted catecholamines are NE, functionally we only consider actions of E
116
general action of a1
excitatory!
117
general action of a2
inhibitory
118
general action of b1
excitatory
119
general action of b2
inhibitory
120
what does NE mainly bind with (what receptors)
a and b1 receptors
bc it is predominantly released from nerve endings, and those receptors are near postganglionic sympathetic nerve terminals
121
what receptors does E bind w
can reach all a and b1 receptors, b2 are exclusively activated by E
122
effects of E on organ systems
- SNS mobilizes adrenomedullary E sys
- increases HR, strength of contraction, increases CO, generalized vasoconstriction to increase total peripheral resistance and bp
123
effects of E on metabolism
fight or flight!
- increases blood glucose
- increases liver gluconeogenesis (synthesis of new glucose) and glycogenolysis (breakdown of glycogen to release glucose)
- promotes lipolysis to increase circulating free fatty acids that can be used as an energy source by heart and skeletal muscles
124
SNS & E
increased: muscle strength, mental activity, bp, cellular metabolism, blood flow to essential organs and decreased blood flow to non-essential organs
125
stress with insulin & glucagon
these work to increase blood glucose
- increased glucagon secretion will break down glycogen stores to produce glucose and decreasing insulin secretion will reduce rate at which glucose is removed from circulation
126
what is the CRH-ACTH-Cortisol sys
main sys involved in integrated stress response
- cortisol increases blood glucose levels, free fatty acids, and amino acids to provide energy to brain and repair damaged tissues
also recognized that ACTH may play a role in resisting stress
- during formation of ACTH from a larger molecule B-endorphin, a natural morphine like substance, is also produced and released w ACTH. B-endorphin can act like analgesia in case of physical injury
127
what is RAAS sys
sympathetic sys increasing bp
- w stress there is an increase in vasopressin and angiotensin 2, both are vasoconstrictors that can help increase bp in an emergency
128
steps of stress response
1. hypothalamus receives input concerning physical and emotional stressors
2. activates SNS
3. secretes CRH to stim ACTH and cortisol release
4. triggers release of vasopressin
129
what is hyperadrenalism
- adrenal glands secrete excessive amounts of hormones they produce
130
what is cortisol hypersecretion
cushing's syndrome
- due to overstim of adrenal cortex by CRh and/or ACTH
- adrenal tumours hypersecreting cortisol independent of ACTH, and ACTH-secreting tumours located somewhere other than pituitary
- causes buffalo hump (redistribution of at between shoulder blades) and moon face (cortisol causes excessive oedema in cheeks)
131
adrenal androgen hypersecretion in adult females
- develop masculine-like body hair, called hirsutism
- usually an increase in male secondary sex characteristics
- breasts shrink, and menstruation may cease
132
adrenal androgen hypersecretion in adult males
little to no effects as the actions of DHEA are minor compared to that of testosterone
133
adrenal androgen hypersecretion in newborn females
- exhibit male-type external genitalia
- during development, clitoris enlarges and takes on a penile-type appearance
134
adrenal androgen hypersecretion in prepubertal males
early development of male secondary sex characteristics called precocious pseudo-puberty
135
what is hyperaldosteronism
excessive mineralocorticoid secretion can be caused by an aldosterone-secreting tumour or by abnormally high activity of RAAS sys
- sympt are based on activity of aldosterone including hypernatremia, hypokalemia, and high bp
136
primary adrenocortical insufficiency (addison's disease)
- occurs when all layers of adrenal cortex are under secreting, often caused by autoimmune destruction of cortex
- typically aldosterone and cortisol deficient *can be fatal
- pt's display hyperkalemia and hyponatremia
137
secondary adrenocortical insufficiency
occurs if there is a problem in hypothalamus or anterior pituitary characterized by reduced ACTH
- there is a cortisol deficiency but aldosterone levels are unaffected
- sympt depend on 3 factors: level of cortisol deficiency, rate of reduction in cortisol levels, underlying health of individual
causes: severe fatigue, loss of appetite, weight loss, nausea, vomiting, diarrhea, muscle weakness, irritability, and depression
aldosterone levels are usually unaffected
low bp and muscle spasms are not as likely as they are in primary insufficiency
138
2 reactions within the cell related to metabolism
1. intermediary metabolism
2. fuel metabolism
139
what are anabolic reactions (in metabolism)
leads to synthesis of larger organic macromolecules from smaller organic molecular subunits and are used for repair, growth, and storage of excess ingested nutrients
140
what are catabolic reactions in metabolism
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
141
where is excess glucose stored?
- in the liver and skeletal muscle as glycogen
- when these are full any additional glucose is converted into free fatty acids and glycerol for synthesis of triglycerides which mainly occur in adipose tissue
142
what are excess fatty acids stored as
triglycerides
143
what are excess amino acids used for
they are not needed for protein synthesis and are not stored, but rather either used for structural proteins or converted to glucose and fatty acids for eventual storage as triglycerides
144
how are most excess nutrients stored and why
most are stored as triglycerides in adipose tissue
when needed, this energy store can undergo catabolism to form free fatty acids and glycerol
145
what is the body's 2 functional metabolic states
1. absorptive state
2. postabsorptive state
146
what is 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 released to be available as fuel or stored as glycogen
- ingested fats and proteins are also immediately used or stored
147
what is the postabsorptive state
- several hrs after ingesting food, catabolism dominates
- glycogen stores in the liver and skeletal muscle become primary energy source
- if postabsorptive state persists, glycogen alone cannot meet the body's energy needs, so lipolysis occurs to break down triglycerides
148
where does glycerol come from
the backbone of triglycerides when they are broken down and it can be converted to glucose by the liver
149
what is lactic acid formed by
glycolysis, can be converted to glucose by the liver
150
what are ketone bodies
- group of compounds produced by liver in times of glucose shortages
- liver uses free fatty acids as an energy source, they are oxidized to acetyl CoA, which does not produce any additional energy through citric acid cycle
- this acetyl CoA is converted to ketone bodies and released into the blood
- in times of starvation, the brain can use ketone bodies, instead of glucose, as an energy source
151
what kind of organ is the pancreas
exocrine and endocrine
- exocrine functions are important for digestion
- endocrine functions are localized to the islets of Langerhans which are clusters of cells found throughout the pancreas
152
alpha cells produce and secrete...
glucagon
153
beta cells produce and secrete...
insulin
154
delta cells produce and secrete...
somatostatin
155
PP cells cells produce and secrete...
pancreatic polypeptide, which may play a role in reducing apettite
156
what is somatostatin
- delta cells secrete this
- slows down digestive system to inhibit digestion and absorption of nutrients
- -'ve feedback manner, prevents too many nutrients being absorbed
- found in pancreas, and is also produced in cells lining the digestive tract where it acts as a paracrine hormone to inhibit digestion
- also released by hypothalamus where it inhibits the secretion of growth hormone and TSH
157
what is insulin
- small peptide hormone produced by beta cells of the pancreatic islets
- dominant hormone in the absorptive state and plays a major role in anabolism
- has been associated primarily w regulation of blood sugar, but has effects on fats and proteins as well
158
factors that increase blood glucose
- glucose absorption from digestive tract
- hepatic glucose production: through glycogenolysis, through glycogenolysis of stored glycogen
159
factors that decrease blood glucose
- transport of glucose into cells: for utilization for energy production, for storage as glycogen through glycogenesis, for storage as triglycerides
- 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)
160
Insulin has 4 main effects on carbohydrate metabolism to maintain blood glucose homeostasis what are they?
1. inhibit the uptake of glucose into most cells
2. inhibit glycogenolysis in the liver
3. stimulate glycogenolysis in skeletal muscle and the liver
4. inhibit gluconeogenesis in the liver
161
4 effects of insulin on fats
- enhances the entry of fatty acids into adipose tissue cells
- increases GLUT-4 recruitment in adipose cells to increase glucose uptake for the synthesis of triglycerides
- enhances the activity of enzymes involved in synthesizing triglycerides
- inhibits lipolysis
162
4 effects of insulin on proteins
- promotes the uptake of amino acids in all tissues
- enhances the activity of the enzymes involved in protein synthesis
- inhibits the degradation of proteins
163
insulin is directly related by the plasma glucose level with a ______ feedback system
-'ve
164
3 steps of regulation of insulin secretion
1. elevation of blood glucose stim the islet b cells to secrete insulin. actions of insulin will lower blood glucose levels and secretion of insulin will stop. insulin promotes anabolism during absorptive state and lack of insulin promotes catabolism during postabsorptive state
2. insulin release is caused by a feedforward state. GI hormones secreted by digestive tract stim insulin release to prepare for rise in blood glucose about to occur
3. cells of the islets of langerhans are innervated by ANS. presence of food in digestive sys activates PSNS. the SNS has opposite effect to decrease insulin secretion. allows blood glucose levels to rise during fight-or-flight or when exercising
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what is glucagon
- major pancreatic hormone involved during postabsorptive state
- secretion is triggered by decrease in blood glucose levels
- major site of action is liver, where its effects are direct opposite of insulin
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effects of glucagon on carbohydrates
increases hepatic glucose production by decreasing glycogen synthesis, enhancing both glycogenolysis and gluconeogenesis
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effects of glucagon on fats
promotes lipolysis while inhibiting fat storage. also enhances formation of ketone bodies in liver.
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effects of glucagon on proteins
promotes protein catabolism but only in liver
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a rise in blood amino acid concentration stimulates the release of both:
insulin and glucagon
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bones are the largest _________ store, and thus play a large role in preserving _____________ homeostasis
calcium
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when are the 2 main periods of rapid growth
1. first 2 yrs of life
2. puberty
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in both males and females pubertal growth is supported by __________ and ____________
GH, and androgens
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what are the 3 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
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what are the soft tissue actions of GH
GH can increase the # of cells (hyperplasia) through stimulating cell division, or stimulate cells to grow larger (hypertrophy) by promoting protein synthesis
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what do osteoblasts do
deposit new bone
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what do osteoclasts do
dissolve bone
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how do bones grow in thickness
achieved by adding new bone to outer layer of existing bone
- osteoblasts deposit new bone on outer surface of a bone
- osteoclasts on inside of bone are removing bone
- both the diameter of bone and marrow cavity will increase
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how do bones grow in length?
- lengthening of long bones only occurs at its ends between the epiphysis and diaphysis in the epiphyseal plate
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what is the epiphysis
the knob at the end
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what is the diaphysis
shaft of the bone
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describe the process of bone growth in length
1. cartilage forming cells called chondrocytes divide and stalk themselves into columns w newer cells towards the epiphysis and older cells near the diaphysis
2. this division and increase in # of chondrocytes are what cause the long bones to elongate. as chondrocytes mature they hypertrophy, which pushes the epiphysis away from the diaphysis and the matrix around them calcifies
3. the older chondrocytes are too far away from nutrient supply so they die. osteoclasts will now remove dead chondrocytes and the calcified matrix, allowing osteoblasts and their capillary supply, to invade this new space and start depositing bone through the process of ossification.
4. formation of new chondrocytes is matched to the removal of dead chondrocytes such that the width of the epiphyseal plate remains fairly constant as the bone lengthens. end of adolescence, sex hormones cause the epiphyseal plate to completely ossify and linear bone growth ceases. thickening of bone can occur throughout life.
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how are the effects of GH mediated
through other peptides known as somatomedins also called insulin-like growth factors (IGFs). there are two IGFs: IGF-1 and IGF-2.
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describe what IGF-1 is
- GH stim the synthesis and release of IGF-1 primarily in liver
- do not get released into the blood, but rather IGF-1 might have paracrine actions
- IGF-1 mediates mots of the growth promoting actions of GH
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describe what IGF-2 does
GH does not stim the production of this. this is important during fetal development. it is produced in adults but the role is not clear.
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what are GH 2 regulatory hormones from the hypothalamus
1. growth hormone-releasing hormone (GHRH) stimulates its release
2. growth hormone-inhibiting hormone (GHIH; aka somatostatin) inhibits its release
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what can deficiency of GH lead to?
- can be a consequence of dysfunction either at level of the hypothalamus, the pituitary, or tissue level
- if during childhood the result is dwarfism (this can be successfully treated w GH if seen early enough)
- laron dwarfism, is caused by lack of response from tissues to GH. this type of dwarfism responds to IGF-1 treatment.
- GH deficiency has less sympt in adults
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what happens with a growth hormone access
- usually caused by a tumour in the anterior pituitary
- to occur in children, GH excess would have a pronounced effect on the epiphyseal plates, causing rapid growth and producing gigantism
- if it occured after epiphyseal plate closure then height is not affected
- bones can thicken and cause the condition acromegaly
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how can calcium be regulated
- under hormonal control to ensure proper concentration is maintained
- Ca can be ingested thru diet to enter plasma and excess Ca is generally stored in bones
- during high dietary intake periods of Ca, excess is avoided by decreasing absorption
- when there is a need for increased Ca in plasma, Ca can be readily removed from the bones
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what 3 hormones regulate Ca2+ concentrations
- parathyroid hormone (PTH)
- calcitonin
- vit D
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how is the parathyroid hormone (PTH) secreted
by parathyroid glands
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why is PTH essential
bc removing the parathyroid glands causes death due to hypocalcemia within a few days. the primary action of PTH is to raise plasma Ca2+ levels by its effects on bone, the kidneys, and intestines
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how is the parathyroid hormone and the bones interconnected
- primary storage f Ca2+ is within bones
- bone is constantly undergoing remodelling
- this remodelling allows for very rapid changes in free Ca2+ just by regulating the activity of these cells
- under the influence of PTH, osteoclast activity if slightly enhanced and osteoblast activity is slightly inhibited, meaning there is more breakdown of bone than build up, the net release is Ca2+ and PO4^3- into plasma
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how is the parathyroid hormone and kidneys interconnected
in kidneys, PTH stim reabsorption of Ca2+
- necessary otherwise the body would be forced to keep degrading bone to maintain plasma Ca2+ levels
- PTH also stim the kidneys to remove PO4^3-
is an important feature as high levels of plasma PO4^3- levels cause bone to increase hydroxyapatite precipitation, which would further remove Ca2+ from plasma
- PTH also stim kidneys to activate vit D
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as Ca2+ levels rise... PTH secretion __________
decreases
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describe the regulation of PTH release
decreased plasma Ca2+ concentration -> parathyroid glands -> increased PTH -> bone or activation of vit D or kidneys
- if kidneys then to activation of vit D increases which moves to intestine, increased absorption of Ca2+ in intestine, increased plasma Ca2+
- if kidneys and not to activation of vit D, then increased renal tubular Ca2+ reabsorption, to decreased urinary excretion of Ca2+, to increased plasma Ca2+
- if bone then to mobilization of Ca2+ from bone which results in increased plasma Ca2+
(all increase plasma Ca2+)
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what is calcitonin secreted from
the thyroid gland
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what are the actions of calcitonin
- opposite to those of parathyroid hormone
- secreted in response to increased plasma Ca2+ levels
- acts on osteoclasts to decrease their activity, which prevents the release of Ca2+ and PO4^3- from the bone
- C cells of the thyroid secrete calcitonin
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plasma Ca2+ concentration decreases what happens next
- decrease in parathyroid glands
- increase in PTH
- increase in plasma Ca2+ concentration
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plasma Ca2+ levels increase what happens next
- increase in thyroid C cells
- increase in calcitonin
- decrease in plasma Ca2+ concentration
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1. what is vitamin D properly called
2. how is vitamin D further hydroxylated
3. how does vitamin D function
1. cholecalciferol
2. by the kidneys to form calcitriol, the biologically active form of vitamin D
3. functions as a hormone as it can be produced by skin. main function is to increase intestinal absorption of Ca2+. vit D increases the responsiveness of bone cells to PTH
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describe the activation of vitamin D
1st - occurs in liver
2nd - occurs in kidneys
each step adds a hydroxyl group to the compound
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how does PTH play a role in the formation of vitamin D
by stim the enzymes in the kidney. end result is the formation of 1,25-(OH)2-vitamin D3 (calcitriol), which is the active form. PTH and vit D work together in Ca2+ homeostasis, although it is PTH that plays the primary role
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what is the most dramatic effect of activated vitamin D
to increase Ca2+ absorption in the intestine
- majority of ingested Ca2+ is typically not absorbed but is lost in feces
- vit D increases the responsiveness of bone to PTH
- vit D and PTH are closely independent
