Endocrinology Flashcards
1
Q
what is endocrinology?
A
study of hormones, their receptors, intracellular signalling pathways, and diseases/conditions associated w/ them
2
Q
what’s the difference btwn an endocrine vs exocrine gland?
A
endocrine: does not have a duct system (thyroid)
exocrine: has a duct system (salivary)
3
Q
what is an ex of a gland that is endocrine and exocrine?
A
pancreas
4
Q
what is a hormone?
A
compound that are secreted into bodily fluids, particularly the blood stream, by a specific group of cells and regulate activity of other cells (greek: “setting in motion”)
5
Q
what are the 3 kinds of hormones based on structure?
A
proteins, lipids, monomamines
6
Q
what are 3 kinds of protein hormones?
A
small peptides, polypeptides, glycoproteins
7
Q
what is a characteristic of protein hormones?
A
are water-soluble (plasma)
8
Q
what are 2 kinds of lipid hormones?
A
steroids (from cholesterol), eicosanoids (from arachidonic acid)
9
Q
what is a characteristic of lipid hormones?
A
water-insoluble (lipid-soluble)
10
Q
what are 2 categories of monoamine hormones?
A
catecholamines and thyroid hormones (both from tyrosine)
11
Q
what steroid hormones can cholesterol be converted into? (6)
A
cholesterol->pregnenolone->progesterone or testosterone, progesterone->aldosterone or cortisol or testosterone, testosterone->estrogen
12
Q
what’s the difference btwn endocrine, neuronendocrine, paracrine and autocrine signalling?
A
endocrine: cell-cell through blood
neuroendo: neuron-cell in blood
para: cell-cell through ECF
auto: cell-self through ECF
13
Q
what are 2 kinds of hormone receptors and their ligands?
A
cell-surface: proteins and catecholamines (lipid-insoluble, water-soluble)
intracellular: steroid and thyroid (lipid-soluble-pass through memb)
14
Q
what are 2 kinds of cell surface receptors?
A
GPCRs and catalytic receptors (tyrosine kinases)
15
Q
what are 3 locations for intracellular receptors?
A
in cytoplasm, in nucleus, bound to DNA
16
Q
what is similar btwn all intracellular receptors?
A
all end up in nucleus and act as transcription factors
17
Q
what are 4 factors that affect hormone activity?
A
synthesis/secretion, binding to plasma proteins, metabolism, #/location of receptors
18
Q
where are most protein hormones secreted from?
A
hypothalamus, pituitary, pancreas, parathyroid, GI
19
Q
where are catecholamines (monoamines) secreted from?
A
adrenal medulla
20
Q
what are 7 similarities btwn protein and catecholamine hormones?
A
water-soluble, from aa (catecholamines from tyrosine), in granules/exocytosed, don’t need solubilization in blood, cell-surface receptors, change intracellular pathways, effects within mins/hours
21
Q
what are 7 similarities btwn steroids and thyroid hormones?
A
lipid-soluble, from cholesterol (thyroid Hs from tyrosine), not stored/diffusion, bound to plasma proteins, intracellular receptors, regulate genes, effects in days/weeks
22
Q
where are most steroid hormones released from? (3)
A
adrenal cortex, ovaries, testes
23
Q
where are thyroid hormones released from?
A
thyroid gland
24
Q
What supplies the anterior and posterior pituitary with neurons?
A
Hypothalamus
25
What joins the hypothalamus and the anterior and posterior pituitary?
Pituitary stalk
26
What is the region right above the pituitary stalk?
Median eminence
27
What is the anterior pituitary a.k.a.?
Adenohypophysis
28
The posterior pituitary a.k.a.?
Neurohypophysis
29
What is the posterior vs anterior pituitary a growth of?
Posterior: down growth of brain
Anterior: up growth of mouth region
30
How are NTs supplied to the anterior pituitary? (4)
hypothalamic neurons synapse onto the primary plexus (supplied by an artery directly in the hypothalamus), portal blood vessels bring hypothalamic NTs to second plexus in anterior pituitary where veins carry ant. pit. NTs
31
what is the NT system btwn the hypothalamus and ant. and post. pit.?
neuroendocrine
32
how are NTs supplied to the post. pit.? (3)
neurons in supraoptic and paraventricular nuclei (SON, PVN) travel from hypothalamus to post. pit., hypothalamic NTs transfer into post pit. plexus (supplied by an artery directly in post. pit.), veins export NTs
33
compare the hypothalamus innervation of the ant vs post pit.
ant: neurons in hypo terminate at median eminence in primary plexus, portal blood vessels bring hypo NTs to ant pit. where veins export ant pit. NTs
post: SON and PVN supply neurons from hypo that terminate in post pit., veins export hypothalamic NTs (are stored in post pit.)
34
what are 6 ant pit hormones?
follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone
35
what does FSH stand for?
follicle-stimulating hormone
36
what does LH stand for?
luteinizing hormone
37
what does ACTH stand for?
adrenocorticotropic hormone
38
what does TSH stand for?
thyroid-stimulating hormone
39
what does PRL stand for?
prolactin
40
what does GH stand for?
growth hormone
41
what is the mnemonic to remember ant pit hormones?
FLAT P(I)G
42
what are all ant pit hormones?
proteins
43
t/f: ant pit hormones come from diff cell types
true, EXCEPT for FSH and LH which come from same cells
44
what is the main target of FSH and LH?
Ovaries and testes
45
What is the main target of adrenocorticotropic hormone?
Adrenal cortex
46
What is the main target of thyroid-stimulating hormone?
Thyroid gland
47
What is the main target of prolactin?
Mammary glands
48
What is the main target of growth hormone?
Most tissues (bone)
49
What is the hypothalamus-pituitary-target gland axis?
higher brain centers control hypothalamus which releases hypothalamic hormones that stim/inh ant pit to release ant. pit hormones that mediate target gland, target gland hormones can work in +/- feedback mech to adjust hypo or ant pit.
50
what is the mnemonic to remember hypothalamus hormones?
The Drunk Girl Got Some Courage
51
what are the 6 hypothalamic hormones?
thyrotropin-releasing hormone, prolactin inhibiting hormone (dopamine), growth hormone-releasing hormone, gonadotropin-releasing hormone, growth hormone inhibiting hormone (somatostatin), corticotropin releasing hormone
52
what does GnRH stand for?
gonadotropin-releasing hormone
53
What does CRH stand for?
Corticotropin-releasing hormone
54
What does TRH stand for?
Thyrotropin-releasing hormone
55
What does PIH (DA) stand for?
Prolactin inhibiting hormone/dopamine
56
What does GHRH stand for?
Growth hormone-releasing hormone
57
What does SS/GHIH stand for?
somatostatin/growth hormone inhibiting hormone
58
what are all hypothalamic hormones? exception?
peptides, except PIH/DA (monoamine)
59
what is the most abundant ant pit hormone?
growth hormone
60
t/f: growth hormone shows species specificity
true
61
what are 2 features of GH secretion?
pulsatile (in bursts) and circadian rhythm (cyclical pattern)
62
what are 2 targets of GH?
bone (for growth) and metabolism
63
what kind of receptors does GH act on?
cell-surface (protein kinase)
64
what are the epiphysis, epiphyseal plate, and diaphysis of a bone?
epiphysis: end of bone
epiphyseal plate: cartilage that separates epiphysis and diaphysis
diaphysis: shaft of bone
65
what is the epiphyseal plate being open vs closed mean?
open: responsive to GH
closed: bone can't grow (puberty)
66
what cells and processes cause bone growth?
progenitor cells/fibroblasts differentiate into cartilage cells/chondrocytes which proliferate into more cartilage cells, ossification of cartilage cells makes bone
67
what does GH only causing growth in vivo but not in vitro suggest?
it causes the release of another hormone (IGF) that causes growth (can be direct too)
68
what are the effects of GH on fats? (2)
incr lipolysis, incr free fa (for E)
69
how does GH effect carbohydrates?
decr glucose uptake by cells so incr [glucose] in blood (hyperglycemia) - "diabetogenic"
70
what are the effects of GH on proteins? (3)
incr aa uptake into cells, incr protein synthesis, incr cell size (hypertrophy)
71
what 2 hormones incr GH secretion?
GHRH, ghrelin
72
what 3 hormones decr GH secretion?
GHIH/somatostatin, GH and IGF (- feedback)
73
what 2 metabolic signals incr GH secretion?
hypoglycemia (GH incr blood glucose), incr aa/arginine (GH incr aa cellular uptake)
74
what 2 metabolic signals decr GH secretion?
hyperglycemia and incr fa (- feedback)
75
what 2 other factors incr GH secretion?
deep sleep, "stress" (exercise)
76
what other factor decr GH secretion?
ageing
77
what 2 abnormalities can too much GH cause?
gigantism (bone lengthening), acromegaly (bone thickening, enlargement of extremities)
78
what 2 abnormalities can too little GH cause?
dwarfism (decr GHRH, GH, IGF or receptors), metabolic effects
79
what are the 2 post pit hormones?
antidiuretic hormone/vasopressin, oxytocin
80
what does ADH stand for?
antidiuretic hormone
81
what does OXY stand for?
oxytocin
82
where are post pit hormones from?
SON and PVN in hypothalamus (neurons extends from hypo and terminal ends in post pit where NTs are stored)
83
what is the source of ADH vs OXY?
ADH: SON
OXY: PVN
84
what are the 2 main targets of ADH?
kidneys (antidiuretic), blood vessels
85
what are the 2 main targets of OXY?
uterus, mammary glands
86
what kinds of hormones are ADH and OXY?
peptides
87
what is the mechanism of action of ADH in the kidney? (3)
ADH in blood acts on ADH receptors (V2) on basal side on principle cells (in collecting duct), incr cAMP which transports vesicles w/ inactive aquaporins (AQ2) onto apical memb, incr renal H20 reabsorption from filtrate
88
what 2 factors affect ADH secretion?
incr osmotic P/osmolarity (dehydration), decr ECF/blood V (hemorrhage)
89
what receptors detect incr osmotic P for ADH secretion?
osmoreceptors in hypothalamus
90
what receptors detect decr ECF/blood V for ADH secretion?
baroreceptors in cardiovasc. system
91
what do incr osmotic P and decr ECF/blood V both do to incr ADH secretion?
cause release of ADH from neurons in post pit which acts on kidneys for antidiuresis
92
what are 3 effects of ADH on kidneys?
incr renal H2O reabsorption, decr osmotic P of ECF, incr ECF/blood V
93
what abnormality does too much ADH cause?
syndrome of inappropriate ADH secretion (SIADH) - incr BV
94
what 2 abnormalities does too little ADH cause? diff?
central or neurogenic diabetes insipidus (decr ADH, incr dilute urine), nephrogenic diabetes insipidus (abnormal ADH receptors in kidneys, incr dilute urine)
95
what 2 factors affect and are the effects of oxytocin?
affect: cervical stretch during parturition and suckling causes +FB (incr OXY) effects: uterine contractions during parturition (incr cervical stretch), and lactation (milk ejection reflex)
96
what are the 3 zones of the adrenal cortex? (outside to in)
zona glomerulosa, zona fasciculata, zona reticularis
97
what are all hormones of the adrenal cortex?
corticosteroids (cortex-steroids)
98
what is the hormone family, ex, and function of the zona glomerulosa?
mineralocorticoids, aldosterone, salt
99
what is the hormone family, ex, and function of the zona fasciculata?
glucocorticoids, cortisol, sugar
100
what is the hormone family, ex, and function of the zona reticularis?
androgens, DHEA and androstenedione, sex
101
what is a trick to remember the functions of the zona glomerulosa, fasciculata, and reticularis? (out to in)
functions get sweeter (salt, sugar, sex)
102
how are corticosteroids made? (4)
cholesterol -> pregnenolone -> progesterone -> cortisol, aldosterone, adrenal androgens (DHEA, androstenedione) - pregnenolone can make products
103
what kind of steroid is cortisol?
glucocorticoid
104
what kind of steroid is aldosterone?
mineralocorticoid
105
what kind of steroids are DHEA and androstenedione?
adrenal androgens
106
what are 4 major actions of aldosterone?
in kidney: incr Na and H2O (2nd) reabsorption (to blood), incr K and H secretion (loss in urine)
107
what does aldosterone do in the principal vs intercalated cells of the collecting duct? (5)
incr gene transcription of 5 proteins:
principal cells: apical Na channels (Na reabsorption), apical K channels (K secretion), apical NHE (Na reabsorption, H secretion), basolateral Na/K ATPase (Na reabsorption, H secretion)
intercalated cells: apical H pump (H secretion)
108
how does aldosterone cause incr H2O reabsorption?
H2O follows Na back into bloodstream by osmosis
109
what 4 factors affect and are the effects of aldosterone?
affect: decr ECF V, BP, [Na], incr [K] in ECF
effects: incr ECF V, BP, [Na], decr [K] in ECF
110
what is the RAAS mechanism regulated to return ECF, BP, and Na levels back to normal? (6)
decr ECF V, BP, or [Na] causes kidneys to release renin (enzyme from juxtaglomerular cells), converts angiotensinogen (substrate in plasma) to AT1 (inactive peptide), ACE (lung enzyme) converts AT1 to AT2 (active peptide), AT2 causes vasoconstriction and adrenal cortex to release aldosterone, incr Na and H2O reabsorption, incr ECF V, BP and [Na]
111
what is the homeostatic mechanism regulated by aldosterone to return K levels back to normal? (3)
incr K in ECF acts on adrenal cortex to incr aldosterone, K secretion incr, and K in ECF decr (diff from ECF V/BP/Na which act on kidney)
112
What are effects of cortisol on metabolism in muscles (2), adipose (2), liver (2), vasculature (1), CNS (1)?
Muscles: incr protein breakdown, decr glucose uptake
Adipose tissue: incr fat breakdown, decr glucose uptake
Liver: incr glucose formation (gluconeogenesis), incr glycogen formation
Vascular: incr blood glucose (hyperglycemia)
CNS: incr glucose uptake
113
What are 5 effects of cortisol on immune system?
Decr lymph node size, decr lymphocyte #, decr humoral/cellular immunity, decr production of inflammatory substances (anti-inflammatory), incr infections
114
What 5 other systems (and their effects/1 ea) are impacted by cortisol?
```
GIT: incr acid secretion
CVS: incr CO
Bones: decr growth
Kidneys: incr GFR
CNS: depression/irritability
```
115
What is the general difference btwn stress hormones released from the adrenal medulla vs cortex?
Cortex: hormones for chronic stress
Medulla: hormones for acute stress
116
What is the hypothalamus-pituitary axis for cortisol? (Including initiator: 8)
Stress +> hypo +> CRH (corticosteroid releasing hormone) +> ant pit +> ACTH (adrenocorticotropic releasing hormone) +> adrenal cortex +> cortisol -> hypo/ant pit (neg feedback)
117
What is the 5 step process for catecholamine synth?
Tyrosine -> Dihydroxyphenylalanine (DOPA) -> dopamine -> NA/NE -> A/E
118
Where does catecholamine synthesis occur?
Chromaffin cells of adrenal medulla
119
What hormones are primarily made in catecholamine synth (and %)?
NA/NE: 20%
| A/E: 80%
120
What disorder results from too much aldosterone (4 effects)?
Conn’s syndrome: incr ECF V, incr BP, hypokalemia, metabolic alkalosis
121
What disorder results from too little aldosterone (3 effects)?
Addison’s disease: hypotension (decr BP), metabolic acidosis, hyperkalemia
122
What disorder results from too much cortisol (4 effects)?
Cushing’s disease/syndrome: incr blood glucose, muscle wasting (incr protein breakdown), “moon face”/“buffalo hump” (incr fat in ventral area, decr in extremeties), decr resistance to infection (decr inflammatory response)
123
What disorder results from too little cortisol (1 effect)?
Addison’s disease (same as too little aldosterone): decr blood glucose
124
What results from too much (1) vs too little (2) adrenal androgens?
Too much: masculinization of females (vs males proportionally)
Too little: decr sexual hair growth, decr female libido
125
What 3 systems do catecholamines affect (majorly)?
Cardiovascular system, smooth muscle, metabolism
126
What are 5 effects of catecholamines (NA/A) on the cardiovascular system?
Incr HR, contractility, CO, and BP, also blood redistribution (skin, gut, etc. -> heart, brain, skeletal muscle)
127
What are 3 effects of catecholamines (NA/A) on smooth muscle?
Dilation of pupils, bronchodilation, decr GIT motility
128
What are 3 effects of catecholamines (NA/A) on macromolecule metabolism?
Incr glycogenolysis (glycogen breakdown in liver and skeletal muscle), incr lipolysis (fa for E), incr gluconeogenesis (glucose synth)
129
How is catecholamine secretion controlled? (3)
Splanchnic nerve (symp pregang) stimulates adrenal medulla by releasing ACh, chromaffin cells (~postgang) release NA/A, catecholamines move into blood vessels for export (act as hormones - are also NTs)
130
What is the external structure of the thyroid gland?
Butterfly shape around trachea (lobes wrap around to back)
131
What is the internal structure of the thyroid gland?
Epithelial/follicular cells form globules filled with colloid, parafollicular/c cells are btwn follicular cells
132
What do parafollicular/c cells secrete?
Calcitonin
133
What is the diff btwn active vs resting thyroid follicles?
Active: decr colloid due to incr thyroid hormone secretion
Resting: incr colloid due to thyroid hormone build up (flattens epi cells)
134
What is the process of thyroid hormone synthesis -> storage? (6)
I- (iodide) uptake from blood (active transport by I-/Na pump) into follicular cells, pendrin exports I- into colloid, thyroglobulin (tyrosine-containing glycoprotein) synthesis (in cell), iodination of Tyr (MIT or DIT) on thyroglobulin by thyroid peroxidase (in colloid), coupling of iodotyrosines (T3 or T4), storage in colloid
135
What controls PTH secretion?
blood Ca levels (inverse relationship, low Ca = high PTH, high Ca = low PTH)
136
T/f: the hypo-pit axis controls PTH secretion
False, controlled by blood Ca levels
137
What detects Ca levels to control PTH secretion?
Chief cells in parathyroid gland have “Ca sensors” that are GPCRS (Gi and Gq)
138
What are 2 sources of vitamin D?
Sunlight (UV-B) and from diet (fish, eggs)
139
What form of vitamin D does sunlight provide?
7-dehydrocholesterol
140
What is the process of active vitamin d synthesis?
Cholecalciferol (vit D) is converted to 25-OH cholecalciferol in the liver, and converted to 1.25(OH)2-cholecalciferol by 1a-hydroxylase in the kidneys
141
What is 1.25(OH)2-cholecalciferol aka?
Calcitriol or active vitamin D
142
What major form of vitamin d is stored?
25-OH cholecalciferol
143
How does PTH incr active vit D3? Process?
incr 1a-hydroxylase; incr conversion of 25-OH cholecalciferol to active vit D (in kidneys)
144
Where in the GIT is Ca absorbed?
Duodenum of sm intes
145
What is the process of Ca absorption in an enterocyte (duodenal cell)? (5)
Ca in lumen (from diet) passes through apical Ca channels, binds to calbindin, transverses to basolateral side of cell, dissociates, Ca exits through basal Ca ATPases
146
What incr Ca absorption in the gut?
Vitamin D (incr transcription of proteins for entire process-Ca channels, calbindin, etc.)
147
What is the structure of PTH, active vit D3, and calcitonin?
PTH: peptide
Vit D3: steroid-like
Calcitonin: peptide
148
What is PTH, active vit D3, and calcitonin secreted from?
PTH: parathyroid gland (chief cells)
Vit D3: kidney (prox tubule cells)
Calcitonin: thyroid gland (parafollicular/c-cells)
149
How does PTH, active vit D3, and calcitonin effect blood Ca?
PTH: incr blood Ca
Vit D3: incr blood Ca
Calcitonin: decr blood Ca
150
How does PTH, active vit D3, and calcitonin effect blood phosphate?
PTH: decr blood phosphate
Vit D3: incr blood phosphate
Calcitonin: decr blood phosphate
151
How does PTH (3), active vit D3 (3), and calcitonin (1) effect Ca and phosphate levels?
PTH: incr bone resorption, incr Ca and decr P reabsorption in kidneys, indirectly incr Ca and P absorption in GIT by incr vit D3/1a-hyroxylase
Vit D3: *incr Ca and P absorption in GIT*, incr bone resorption (w/ PTH), incr reabsorption of Ca and P in kidneys
Calcitonin: decr bone resorption
152
What incr secretion of PTH, active vit D3, and calcitonin?
PTH: decr blood Ca
Vit D3: PTH
Calcitonin: incr blood Ca
153
What is MIT vs DIT?
MIT: mono-iodotyrosine (1 I2 + Tyr)
DIT: di-iodotyrosine (2 I2 + Tyr)
154
What is T3 vs T4?
T3: tri-iodothryonin (MIT + DIT)
T4: tetra-iodothryonine or thyroxine (2 DIT)
155
Is more T3 or T4 stored in the colloid?
T4
156
What is the process of thyroid hormone release -> binding?
Endocytosis of colloid into follicular cell, breakdown and recycling of I- and Tyr by lysosomal enzymes, secretion of T3 and T4 into blood, transport in bound form (plasma proteins), T4 converted to T3 in tissues, hormone binding to nuclear receptor
157
Is more T3 or T4 secreted into blood from thyroid gland?
T4
158
Is majority of T3 and T4 transported in bound or free form?
Bound (free T3 = 0.4% and free T4 = 0.03%)
159
What makes T3 the major thyroid hormone not T4 if more T4 is stored and secreted?
T4 acts as a prohormone (most converted to T3 in tissues)
160
Does T3 or T4 bind more strongly to receptor in nucleus?
T3
161
What is the half life of T3 vs T4?
T3: 1 day
T4: 7 days (relatively long)
162
What are 3 general physiological actions of thyroid hormones?
Act on most tissues to change transcription/translation, incr “metabolism” (sum of all chem rxns), necessary for growth and development
163
What are 6 specific actions of thyroid hormones on metabolism?
incr BMR (incr O2 consumption and heat production), incr carb absorption/utilization, incr protein (muscle) breakdown, incr fat breakdown, incr cholesterol metabolism (excretion in bile), decr blood cholesterol levels (catabolism > anabolism, both incr)
164
What are 4 specific actions of thyroid hormones on growth/development?
Act as “tissue growth factors”, incr protein synthesis (small amounts), incr GH/IGF production, proper CNS maturation in fetus/newborn
165
How can thyroid hormone cause incr protein breakdown but also protein synthesis?
Dose-dependent (small amounts incr synthesis)
166
What are 4 other specific actions of thyroid hormones?
Incr HR/F, potentiation of symp system (B-adrenergic Rs), proper function and fertility of reproductive system, incr bone turnover
167
What is the hypothalamus-pit axis for thyroid hormones? (7)
(Cold?) +> hypo +> TRH (thyrotropin-releasing hormone) +> ant pit +> TSH (thyroid stimulating hormone) +> thyroid gland +> thyroid hormones (T3 and T4) -> hypo and anti pit (TRH and TSH)
168
What disease is caused by over activity of the thyroid gland? Cause? 3 symptoms?
Grave’s disease; autoimmune rxn (Ab) stimulates thyroid gland receptors; incr BMR, exophthalmos (protrusion of eyeballs), goitre
169
What is goitre?
Enlargements of thyroid gland
170
What disease is caused by under activity of the thyroid gland (hypothyroidism)? 2 causes? 3 symptoms?
Hashimoto’s disease; autoimmune rxn destroys thyroid gland/blocks hormone release or iodine deficiency (TH synthesis); myxedema (skin puffiness), goitre, cretinism in children (abnormal brain development)
171
What is total body Ca (1kg) stored in body? Maj?
Bone (1kg) > other tissues (11g)
172
Where is Ca (11g) in tissues stored? Maj?
ICF (10g) > ECF (1g)
173
What form is Ca stored in ECF (1g)? Maj?
Free Ca (500mg) = bound Ca (500mg)
174
What form is Ca stored in ICF (10g)? Maj?
Free Ca (0.1mg) < bound Ca (10g)
175
Is there more free Ca in ICF or ECF?
ECF (500mg vs 0.1mg in ICF)
176
Where is Ca obtained from?
Diet
177
What are the processes of Ca in blood plasma -> bones vs bones -> blood plasma?
Ca in plasma -> bone: ossification/mineralization
| Ca in bone -> plasma: resorption/demineralization
178
What organs control Ca filtration/excretion?
Kidneys
179
What are 4 reasons Ca is important?
Structural role (bones, teeth, etc.), blood coagulation, intracellular messenger, regulates neuromuscular excitability
180
What are 3 reasons phosphate (P) is important?
Structural role (w/ Ca), “metabolism” (phosphorylation: ATP, nucleus acids, etc.), buffer
181
What 3 hormones regulate Ca and P levels? Source?
PTH (parathyroid hormone) from parathyroid gland, vitamin D from kidneys, calcitonin from thyroid gland (parafollicular/c cells)
182
What are 3 targets for PTH, vit D, and calcitonin?
Bone (Ca and P storage), GI tract (Ca and P absorption/secretion), kidneys (Ca and P retention/excretion)
183
What comprises the calcified matrix of bone?
Protein framework (Osteoid) and Ca and phosphate salts
184
What protein mainly comprises osteoid?
Collagen
185
What salt mainly comprises salts embedded in osteoid?
Hydroxyapatite
186
What are 3 bone cells and diff functions?
Osteoblasts: bone building
Osteoclasts: bone destroying
Osteocytes: respond to stress?
187
What is the most common bone cell?
Osteocytes
188
Where are the parathyroid glands located? Usual #?
Embedded in back lobes of thyroid gland; 4
189
What are the effects of PTH on Ca and phosphate levels in plasma?
Incr Ca and decr P
190
What cells in the parathyroid gland release PTH?
Chief cells
191
What is the process of osteocytic osteolysis? 3 steps?
Breakdown of bone by osteocytes; osteocytes (centre of bone) take up Ca via Ca channels, Ca transported from osteocytes to osteoblasts (surface), osteoblasts export Ca via Ca pumps (to ECF)
192
What is the process of osteoclastic resorption? General process?
Resorption of bone by osteoclasts; osteoclasts form a ruffled border (closed spaces) and secrete proteolytic enzymes and H+ (acidic) to break down collagen and Ca/P resp.
193
How is bone repaired following osteoclastic resorption? (4)
Osteoblasts (on surface of bone) fill hole made by osteoclasts, secrete osteoid (mainly collagen), osteoblasts trapped in colloid become osteocytes (in centre of bone), Ca and P deposited on surface
194
How does PTH incr Ca and decr phosphate in blood plasma? (Bone, GIT, kidneys)
Bone: incr bone resorption (Ca and P to blood)
GIT: incr absorption (Ca and P to blood)
Kidneys: incr Ca retention and P excretion
195
What causes NET phosphate decr w/ PTH if it is absorbed from bone and GIT?
PTH incr P excretion in kidneys (not Ca, therefore accumulates in blood plasma)
196
How do Ca sensors in parathyroid chief cells alter PTH secretion? (3)
Incr Ca binding to Ca sensors, decr cAMP (Gi) and incr IP3/intracellular Ca (Gq), PTH decr
197
What disorders occur w/ too much vs too little PTH?
Too much: “bones, stones, and groans” (incr resorption, Ca -> kidney stones, pain)
Too little: tetany (muscle spasms)
198
What disorders occur with too little active vitamin D3?
Rickets in children and osteomalacia in adults
199
What’s the difference btwn rickets in children and osteomalacia in adults?
Rickets: decr vit D causes decr Ca absorption, causes decr mineralization on growth plate/cartilage of bone, remains closed and decr growth/bone softening
Osteomalacia: decr vit D causes decr Ca absorption, causes decr mineralization on osteoid of bone, causes bone softening
200
What disorders occur with decr calcitonin?
None discovered yet (physiological significance still uncertain)
201
What is a possible explanation for inverse relationship btwn Ca and excitability? (Decr PTH causing tetany)
Low PTH = low EC Ca which favours opening of Na channels = incr excitability
202
What are 2 cell types in the pancreas? Secretions?
Exocrine: acinar cells secrete pancreatic juice/enzymes (has ducts-duct cells)
Endocrine: islets of langerhans secrete pancreatic hormones into nearby blood vessels
203
What are islets of langerhans? 2 cell types?
Clusters of cells in endocrine pancreas; alpha and beta (maj.) cells
204
What are the 5 hormones of the pancreas?
Glucagon*, insulin*, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide
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What cells secrete glucagon vs insulin?
Glucagon: alpha cells of islets of langerhans
Insulin: beta cells of islets of langerhans
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What % of islet cells are alpha (secretes glucagon) vs beta (secretes insulin)?
Alpha: 15-20%
Beta: 65-90%
207
What are 5 highlights in the discovery of pancreatic hormones (insulin)?
1889: Minkowski and con Mering removed dog pancreas which caused diabetes mellitus (sweet urine)
1921: Frederick Banting, Charles Best, James Collin and John Macleod found pancreatic extract (crude insulin) treated diabetes in dogs
1922: insulin use in humans
1923: Banting and Macleod awarded Nobel prize for insulin discovery
1922/23: Kimball and Merlin discovered glucagon in pancreatic extract
208
What are overall actions of glucagon vs insulin?
Insulin: incr glucose absorption, decr breakdown of storage
Glucagon: decr glucose absorption, incr breakdown of storage
209
What is a way to remember functions of insulin vs glucagon?
Insulin: “feasting” (absorb glucose from blood)
Glucagon: “fasting” (release glucose from storage)
210
what is the effect of insulin in the liver? (2 glycogen, 5 glucose, 2 protein)
glycogen: incr glycogenesis, decr glycogenolysis
glucose: incr glycolysis, decr gluconeogenesis, incr fat synthesis (FA, TriG), decr fat breakdown, decr ketogenesis,
proteins: incr synthesis, decr breakdown
211
what is the effect of insulin in muscle? (1 glucose, 2 glycogen, 3 protein)
glucose: incr glucose uptake
glycogen: incr glycogenesis, decr glycogenolysis
protein: incr aa uptake, incr protein synthesis, decr protein breakdown
212
what is the effect of insulin on adipose tissue? (2 glucose, 3 FA)
glucose: incr glucose uptake, incr glycolysis
FA: incr FA uptake, incr fat (TriG) synthesis, decr fat breakdown
213
what is the structure of the insulin receptor? 4 subunits?
tyrosine kinase; 2 a extracellular, 2 B transmembrane subunits
214
how/what does the insulin receptor exhibit its intracellular effects on?
tyrosine kinase activity phosphorylates insulin receptor substrates (IRS)
215
what are 3 effects of insulin receptor substrates (IRS)?
affects: transport systems, enzyme activity, gene expression
216
what are 2 mechanisms for glucose transport?
2ndary active transport (uphill, Na-dependent) and facilitated transport (downhill, Na-independent)
217
what 2 major proteins enable 2ndary active transport of glucose?
SGLT 1 and 2
218
what 2 major proteins enable facilitated transport of glucose?
GLUT 1 and 2
219
what glucose transporter is insulin-dependent?
GLUT 4 (facilitated transport)
220
what is the process of glucose uptake w/ vs wo/ insulin in muscle/adipose tissue?
wo/ insulin: vesicle w/ GLUT4 don't merge w/ pmemb
| w/ insulin: GLUT4 vesicles translocate to pmemb (via IRS)
221
which tissues exhibit insulin dependant vs independent glucose transport?
insulin-dependent: muscle and adipose
| insulin-independent: liver
222
where is the main site of action of glucagon?
liver
223
where does glucose come from in ST, LT and longer LT?
ST: bloodstream after a meal
LT: liver glycogen stores (glycogenolysis)
longer LT: glucose made from aa (non-carb gluconeogensis)
224
what are the actions of glycogen? (7)
decr glycogenesis, incr glycogenolysis, decr glycolysis, incr gluconeogenesis, decr lipogenesis, incr lipolysis, incr ketogenesis
225
how does insulin vs glucagon affect blood sugar levels?
insulin: hypoglycemia
glucagon: hyperglycemia
226
what does amylin do? (pancreatic H)
may decr food intake, decr rate of gastric emptying, and decr glucagon secretion (secreted w/ insulin)
227
what does somatostatin do? (pancreatic H)
may inhibit insulin and glucagon secretion from pancreas (paracrine)
228
what does pancreatic polypeptide do?
may decr pancratic enzyme secretion and inhibit gallbladder contraction
229
what does vasoactive intestinal polypeptide do? (pancreatic H)
may decr pancreatic water secretion, diarrhea in excess
230
how does glucose cause insulin secretion in the pancreas? (7)
glucose enters B islet cells via GLUT 2 (insulin-dep), incr intracellular ATP, closes ATP-sensitive K channels, intracell K incr (cant exit through channel), depol, Ca channels open, Ca causes release of storage vesicles w/ insulin
231
what effect does incr glucose have on insulin and glucagon secretion?
insulin: incr
glucagon: decr
232
what effect does incr aa have on insulin and glucagon secretion?
insulin: incr
glucagon: incr
233
what effect does incr GIT Hs (CCK, secretin, etc) have on insulin and glucagon secretion?
insuline: incr
glucagon: depends on incretin
234
what effect does incr SS have on insulin and glucagon secretion?
insulin: decr
glucagon: decr
235
what effect does incr insulin have on insulin and glucagon secretion?
insulin: none
glucagon: decr
236
what effect does incr glucagon have on insulin and glucagon secretion?
insulin: incr
glucagon: none
237
what effect does incr parasympathetic activity (ACh) have on insulin and glucagon secretion?
insulin: incr
glucagon: none
238
what effect does incr sympathetic activity (NA) have on insulin and glucagon secretion?
insulin: depends on receptor
glucagon: incr
239
how do insulin and glucagon restore blood glucose levels after a meal?
incr blood glucose, incr insulin, decr blood glucose (incr storage), and decr glucagon, decr blood glucose (decr breakdown)
240
why is glucagon incr by aa?
protein-rich meal causes no initial change in blood glucose, aa cause incr insulin (to store aa) which decr glucose, so glucagon must be released to raise glucose back to normal
241
what are 2 potential causes for incr insulin (too much)?
insulin-secreting tumour, insulin overdose
242
what are 3 consequences of having too much insulin?
decr blood glucose (hypoglycemia), ANS and endocrine responses (incr symp activity, incr "counter Hs"), hunger/confusion/drowsiness
243
what is type 1 diabetes mellitus?
type 1: autoimmune disease, B islet cells destroyed, insulin deficiency, younger ppl (5-10% cases)
244
what is type 2 diabetes mellitus?
type 2: insulin resistance, initial incr insulin secretion, decr insulin effects, adults but incr in younger ppl (obesity, 90-95% cases)
245
what is the most common issue with diabetes mellitus?
hyperglycemia
246
where/how is glucose uptake affected w/ diabetes mellitus?
decr uptake into insulin-dependent tissues (muscle, adipose), incr uptake into insulin independent tissues (liver)
247
metabolism of what macromolecules is affected w/ diabetes mellitus?
carbs, proteins, and fats
248
what are 5 current/future treatments for type 1 diabetes mellitus?
insulin administration, pancreatic transplant, islet cell transplant (Edmonton protocol), gene therapy, incr islet cell growth
249
what are 3 current/future treatments for type 2 diabetes mellitus?
dietary control and exercise, drugs to incr insulin secretion/response to insulin, insulin administration
250
how does decr insulin cause polyphagia?
decr glucose uptake, decr intracell glucose, hunger, polyphagia
251
how does decr insulin cause polydipsia?
incr glucose release, incr blood glucose, glucosuria, osmotic diuresis, dehydration, thirst, polydipsia
252
how does decr insulin cause decr BP/kidney failure?
incr glucose release, incr blood glucose, glucosuria, osmotic diuresis, dehydration, decr blood volume, decr BP and kidney failure
253
how does decr insulin affect aa/proteins?
decr aa uptake and incr protein breakdown, incr blood aa, incr gluconeogenesis in liver (incr blood glucose)
254
how does decr insulin cause metabolic acidosis?
decr fa uptake and incr fat breakdown, incr blood fa, excess acetyl-CoA, incr ketone bodies (acids), metabolic acidosis (incr respiration)
255
how does decr insulin cause tissue wasting?
incr fat and protein breakdown
256
what is ketogenesis?
production of ketone bodies in the metabolism of fats
