Endocrine Flashcards
(200 cards)
1
Q
neurosecretory cells
A
above the pituitary
secrete hormones that control the anterior pituitary
2
Q
hypothalamic/hypophyseal portal circulation
A
hypothalamic hormones released to special capillaries that feed the anterior pituitary inferiorly
3
Q
anterior pituitary
A
derived from epithelial lining from mouth
3/4 of adult pituitary size
doubles during pregnancy –> pituitary infarctions
4
Q
thyrotrophs
A
stimulated by TRH
secrete thyrotropin (TSH)
5
Q
gonadotrophs
A
stimulated by GnRH
secrete gonadotropins (LH, FSH)
6
Q
corticotrophs
A
stimulated by CRH
secrete ACTH
7
Q
somatotrophs
A
stimulated by GHRH; inhibited by somatostatin
secrete GH
8
Q
what are hormones released from the hypothalamus?
A
releasing hormones - can be stimulating or inhibitory
small peptides with pulsatile secretion & short half-lives
travel to the anterior pituitary for regulation
9
Q
what are hormones released from the anterior pituitary?
A
tropic hormones
10
Q
pulsatile secretion
A
critical for hypothalamic releasing hormone function
constant stimulation can shut down the response (ex. constant secretion of GnRH can shut down release of LH & FSH
11
Q
circadian rhythm
A
regulation of hypothalamic releasing hormones
12
Q
Corticotropin releasing hormone (CRH)
A
stimulates ACTH release
production of glucocorticoids by and androgens by adrenal cortex
13
Q
Thyrotropin releasing hormone (TRH)
A
stimulates TSH release and prolactin (PRL)
production of thyroid hormones (T3,T4)
14
Q
Growth hormone releasing hormone (GHRH)
A
stimulates GH release
postnatal body growth
15
Q
Luteinizing hormone releasing hormone (LHRH) aka GnRH
A
stimulates FSH and LH release
ovulation, progesterone & estrogen production, testosterone production
16
Q
Somatostatin, somatotropin release inhibiting factor (SRIF)
A
inhibits GH (&GHRH) and TSH release
17
Q
Prolactin (PRL)
A
milk production by mammary glands
inhibited by dopamine; stimulated by TRH
18
Q
Dopamine
A
inhibits prolactin secretion
can have leaking milk from breasts with antagonists
19
Q
lactotrophs
A
stimulated by TRH; inhibited by dopamine
release prolactin (PRL)
20
Q
What hormone is released in direct response to hypothalamic TRH?
A
prolactin
21
Q
role of ACTH
A
increases synthesis of glucocorticoids and androgens in adrenal cortex
proliferation, maintenance of adrenal cortex
cAMP as 2nd messenger
synthesized from POMC (alpha-MSH & CLIP) in corticotrophs
released in response to stress
22
Q
What is a negative feedback of ACTH and CRH release?
A
cortisol
excessive glucocorticoids over time - shut down ACTH and CRH –> adrenal cortex will atrophy
23
Q
What happens if you have too much ACTH?
A
hyperpigmentation - stimulating melanocyte synthesis from alpha-MSH in the POMC
Addison’s disease
24
Q
What is the enzyme used to cleave POMC?
A
pro hormone convertase I –> cleaves to ACTH and beta-lipoprotein
25
role of ADH (AVP) in ACTH release
stimulates production of ACTH by thirst response stress
increases BP indirectly by the production of cortisol
26
role of CRH
comes from the paraventricular nucleus in the hypothalamus - stimulate release of ACTH in anterior pituitary
binds to receptors on corticotrophs --> increase cAMP --> activate PKA --> POMC production/cleavage
27
role of glucocorticoids
negative feedback on ACTH and CRH
excessive ACTH w/o cortisol
dexamethasone suppression of ACTH
28
congenital adrenal hyperplasia
elevated ACTH due to lack of glucocorticoid synthesis --> adrenal hypertrophy and hyperplasia
29
what is the response to stress?
increased CRH secretion - stress signals override
-released during starvation
chronic stress - increases threshold for negative feedback...brain does not respond to cortisol & keeps making ACTH
30
TSH aka thyrotropin
share the same alpha chain with LH & FSH
regulates T3, T4 production and proliferation of thyroid follicular cells
stimulated by TRH; inhibited by thyroid hormones & somatostatin
31
what leads to an enlarged thyroid (goiter)?
no production of thyroid hormone to produce the negative feedback --> release too much TSH
prevented by iodine supplements
32
growth hormone (GH) aka somatotropin
most abundant in anterior pituitary
stimulated by GHRH; inhibited by somatostatin
filtered & eradicated quickly - short half life
JAK/STAT signaling
pulsatility higher at night & in adolescence
also acts on IGF (somatomiden)
33
somatostatin
inhibits GH and GHRH
34
What stimulates the release of GH?
- GHRH
- starvation, low glucose
- gherlin
- exercise & stress
- thyroid hormones
- high levels of amino acids
increases glucose levels, shuts down insulin, releases energy
35
what are the direct actions of growth hormones?
breaks fats (lipolysis) & glycogen --> liberates energy
oxidation of FA
ketogenic
prevents sugar uptake
inhibits insulin - diabetes
increase thyroid secretion
does not break proteins - increases synthesis & transport
36
Anabolic actions of growth hormone
mediated through IGF-1 (somatomedin)
increases muscle mass (protein synthesis), growth, & bone density
37
somatomedin C
longer half life than GH - more accurate measurement when testing to see if someone is deficient
-last longer in blood
bone and cartilage growth when stimulated by GH
38
Gigantism
overproduction of GH before the epiphyseal plates close
39
Acromegaly
overproduction of GH after the epiphyseal plates have closed --> thicker bones
40
Laron syndrome
GH deficiency
- pituitary dwarfism
- IGF deficiency
- GH receptor mutation
will have low sugar, obesity, low muscle mass, high LDL and cholesterol, premature aging
41
role of Prolactin
made in lactotrophs
- JAK/STAT signaling
- stimulated by TRH; inhibited by dopamine
- increase breast development & milk production
- decrease release of LH and FSH - suppress pulses
- absence or excess can cause infertility or cancer (breast or prostate)
- suppress kisspeptin
- regulation of steroid genesis
- immune - associated w/ autoimmune diseases
42
Kisspeptin
peptide in hypothalamus that produces GnRH
inhibited by prolactin
43
treatment for excess prolactin secretion?
dopamine agonist - natural inhibitor of prolactin
44
posterior pituitary
- neuroendocrine system
- does not produce hormones
- stores & releases oxytocin & ADH
45
oxytocin role
uterine contraction, milk ejection
- levels and receptors increased during pregnancy
- stop postpartum hemorrhage
- linked to limbic system (emotions)
- similar structure to ADH - water retention, [] urine, decrease urine output, increase Na+ loss
46
ADH (vasopressin) role
conserve water, concentrate urine
47
where are the neuron bodies located?
paraventricular and supraoptic nucleus in hypothalamus - secrete oxytocin & ADH - stored in posterior pituitary
48
mechanism of oxytocin
activates G coupled receptor --> activate PI3K
PKC and PLC increase intracellular contraction causing contraction
49
other functions of oxytocin
- limbic system - maternal and social bonding
- methylation in receptor - autism
- role in cardiomyocytes & neural development
- anti-depressants
- inhibit fear
- decreases cortisol levels
50
release of oxytocin
- sucking on nipple
- site & sound of infant
- downward movement of fetus through birth canal
51
ADH role
- water, salt, urea retention --> prevent dehydration
- constriction of blood vessels
- increase ACTH secretion
- increase urine osmolarity
- upregulate AQPA2 through cAMP/PKA signaling
- increase Na+/K+ pump, NKCC, ROMK, NCC, ENaC, UTA-1,3
52
release of ADH
- increased plasma osmolality
- drop in blood volume
- angiotensin II
- thirst reflex
53
diabetes insipidus
- lack of functioning ADH receptors or AQP2
- chronic lithium ingestion
- amyloid degeneration, polycystic kidney disease
effects: thirsty, dilute urine, hyperosmolarity blood, excess urine, hypokalemia
54
central vs. nephrogenic diabetes insipidus
central - no production of ADH; giving ADH helps the functioning
nephrogenic - receptors are hindered; giving more ADH does not help
55
SIADH
excess ADH secretion --> hyponatremia, [] urine
- ectopic expression of ADH from tumor
- not much change in volume due to ANP effects
56
why do you not give salt to SIADH patients?
will demyelinate neurons & destroy CNS
57
Another name for Anterior Pituitary
adenohypophysis
58
another name for Posterior Pituitary
neurohypophysis
59
anterior pituitary parts
1. pars tuberalis - wraps around infundibulum
2. pars intermedia - divides anterior/posterior; adjacent to pars nervosa
3. pars distalis - largest; anterior lobe
60
posterior pituitary parts
1. pars nervosa - largest
| 2. pars infundibulum - connecting stalk to hypothalamus
61
hormones released from posterior pituitary
oxytocin, ADH
62
hormones released from anterior pituitary
LH, FSH, ACTH, TSH
63
Hypophyseal (rathke) pouch
formed from oral ectoderm
| forms the anterior pituitary
64
Neurohyphyseal pouch/bud
formed from neuroectoderm
| forms the posterior pituitary
65
Hypothalamic-Hypophyseal Tract
- communication b/w hypothalamus & posterior pituitary (nerves)
- supraoptic nuclei --> synthesize ADH
- paraventricular nuclei --> synthesize oxytocin
66
Hypothalamic-Hypophyseal Portal System
- communication b/w hypothalamus & anterior pituitary (blood vessels)
- superior hypophyseal arteries --> hypophyseal portal veins
- 2 plexuses
67
what does the superior hypophyseal artery supply?
infundibulum & median eminence
68
what does the inferior hypophyseal artery supply?
posterior hypothalamus
69
Pars Distalis
1. chromophils --> acidophils (acidic), basophils (basic)
| 2. chromophobes - no stain; little cytoplasm
70
acidophils - pars distalis
1. somatotrophs (most) - secrete GH (somatostatin)
2. mammotrophs (lactotrophs) - secrete PRL
polypeptide hormones
71
basophils - pars distalis
1. gonadotrophs - secrete FSH, LH, & ICSH (in males)
2. thyrotrophs - secrete TSH
3. corticotrophs - secrete ACTH & LPH
glycoprotein hormones
72
Pars Tuberalis
mostly gonadotrophs (FSH, LH)
73
Pars Intermedius
```
mostly corticotrophs (ACTH) & chromophores
cleave POTC (MSH)
colloid filled cysts (remnants of rathke)
infiltration of basophils into pars nervosa
```
74
Pars nervosa
no synthesis of hormones
PVN & SON --> neurosecretory bodies (NB)
Pituicytes - supporting glial cells for neurons
75
Pituitary Adenomas
- growth in pituitary - overproduction of certain cell types (acidophils or basophils)
- release hormone in high amounts
- hormone producing (PRL, ACTH, GH)
- nonfunctioning - can compress on hypothalamus & optic chiasm
76
Thyroid
- produces T3,T4, & calcitonin
- hormone stored outside of cells (lumen of follicle) & can be held for a long time
- follicular (thyroytes) & parafollicular (C cells)
77
Follicular Cells aka thyrocytes
- squamous or columnar - depending on activity
- produce thyroglobulin stored in colloid lumen
- rich in RER for protein synthesis
78
Parafollicular (C) cells
- larger, lighter staining
- produce calcitonin
- upregulated Golgi apparatus for calcitonin synthesis
79
Parathyroid gland
- PTH release - Ca++ regulation
- supplied by inferior thyroid arteries
1. Principle cells - secrete PTH; replaced w/ adipocytes during aging
2. Oxyphil cells - nonfunctional; less PTH synthesis; more cytoplasm staining
80
Adrenal Glands
- supplied by superior, middle, inferior suprarenal arteries
- drained by suprarenal vein
- cortex and medulla
81
Adrenal Cortex
no granules - secrete steroids (lipid soluble) instead of proteins - large amount of smooth ER
3 zones: zona glomerulosa, fasciculata, reticularis
82
zona glomerulosa
secrete mineralocorticoids - ex. aldosterone
| -ion regulation
83
zona fasciculata
secrete glucocorticoids - ex. cortisol
| -glucose metabolism, immune response
84
zona reticularis
secrete androgens - ex. DHEA
| -precursor for testosterone
85
Addison's disease
autoimmune - adrenal cortical insufficiency
| -degeneration of adrenal cortex --> loss of hormone synthesis
86
Adrenal Medulla
Chromaffin cells (arise from neural crest) --> produces Epi and NE (catecholamines)
```
NE = more e- dense; chromagranin proteins
Epi = less e- dense
```
87
Pineal Gland aka epiphysis cerebri
- regulates daily rhythms
- pinealocytes - produce melatonin
- corpus arenaceum "Brain Sand"
88
beginning molecule for steroidogenesis
cholesterol
- cleaved by cholesterol esterase
- transported across mitochondria membrane by StAR
- no StAR --> no steroidogensis
89
What enzyme is used for the 1st step of side chain cleavage of cholesterol?
CYP11A1
| -cleaves to pregnenolone
90
the precursor for aldosterone
corticosterone
91
the limiting step in aldosterone synthesis
aldosterone synthase (CYP11B2)
- need ACTH, but also 2nd stimulus (K+, SNS, or angII)
- won't have hyperaldosteronemia w/ excess ACTH
92
17-alpha hydroxylase enzyme (CYP17A1)
- convertes pregnenolone and progesterone
- not found in zona glomerulosa
- mutation --> entire kidney would be glomerulosa and produce only aldosterone
- needed to make cortisol & DHEA
93
17, 20-lyase enzyme (CYP17A1)
converts from 21 C to 19 C androgens (DHEA & androstenedione)
94
role of DHEA
- main androgen produced by adrenal cortex
- water soluble, sulfated --> weak steroid/androgen
- organ must have sulfatase to use it or be able to convert to stronger Androstenedione
95
mutation in 3beta-hydroxysteroid dehydrogenase (HSD3B2)
adrenals will only make androgens (DHEA)
96
enzyme 11beta-hydroxylase (CYP11B2)
deoxycorticosterone --> corticosterone
| deoxycycortisol --> cortisol
97
how are androgens removed from the body?
secreted as ketones in the urine
| -measure ketone [] in urine to estimate DHEA levels in blood
98
CYP17 - 17alpha-hydroxylase mutation
low cortisol & DHEA
| -no negative feedback of cortisol --> high ACTH --> hyper pigmentation
99
CYP21A2 - 21 hydroxylase mutation
- low deoxycortisol and cortisol
- don't need much aldosterone (won't have hypoaldosteronemia)
- high ACTH and DHEA
100
CYP11B1 - 11beta-hydroxylase mutation
- high deoxycortisol
| - low cortisol --> continued stimulation from ACTH
101
enzyme HSD11B2
converts active cortisol to inactive cortisone
- cortisol - same actions as aldosterone & same affinity to MR
- HSD1 = gives you active form
- HSD2 = gives you inactive form
102
deficiency in HSD11B2
renal tubules cannot convert to inactive cortisone --> apparent hyperaldosteronemia but aldosterone levels are normal
103
aldosterone role
-carried by albumin & CBG (lower affinity & can be displaced by excessive cortisol) --> high aldosterone in blood (Na+ retention, HTN, K+/H+ secretion)
104
aldosterone actions on nephron
- increase Na+ reabsorption & K+ secretion
- increase H+ secretion & bicarb reabsorption (metabolic alkalosis)
- HTN, hypokalemia, metabolic alkalosis**
105
aldosterone escape
not always hypernatremia w/ high aldosterone
1. prevent long term Na+ retention by ANP
- released from atrial stretching --> filter more water & inhibit Na+ reabsorption
2. pressure natriuresis in HTN
106
primary hyperaldosteronemia
tumor in glomerulosa
- high aldosterone release
- normal levels of renin
107
secondary hyperaldosteronemia
excess activation of RAAS
| -high renin and aldosterone
108
glucocorticoids - cortisol
- binds to CBG (higher affinity than aldosterone)
- increase CBC & total blood cortisol w/ pregnancy
- released more in morning (circadian)
- synthesis by ACTH
- metabolism - breaks fat & proteins, liberates glucose, insulin resistance
109
result of long term treatment w/ glucocorticoids
negative feedback of cortisol on ACTH --> reticularis and fasciculata atrophy
110
glucocorticoids in metabolism
- glycogenolysis, gluconeogenesis
- insulin resistance
- lipolysis
- ketogenesis (energy for CNS)
- increase receptors for NE, Epi, and glucagon
- increase adipocytes in long term excess (buffalo hump)
- deficiency --> hypoglycemia
111
cortisol vs. GH
- both ketogenic, lead to diabetics, same action on lipids/carbs
- cortisol --> breaks proteins
- GH --> builds proteins
112
glucocorticoids - non metabolic actions
- SNS - increase alpha adrenergic receptors (HTN)
- inhibit keratinocytes & collagen --> stretch marks, striae
- promote osteoclasts --> osteoporosis
- Na+ retention (HTN) --> releasing aldosterone from CBG
- lung maturation, fetal development
- activation of lactation by PRL
- anti-inflammation --> block leukotrienes/prostaglandins and suppress inflammatory mediators
113
Cushing's disease
excess glucocorticoids
- muscle wasting
- striae
- obesity (buffalo hump) - high fats/sugars
- poor wound healing, susceptible to infection
- osteoporosis
- HTN
- mood disturbances
114
glucocorticoid deficiency
long term exogenous treatment --> shrinkage of adrenal cortex due to low ACTH
low levels of cortisol --> excess ACTH --> hyperpigment
-stress intolerance
-hypoglycemia
-low BP
115
DHEA
androgen
- converted to androstenedione then to estriol in placenta (estriol then converted to estrogen)
- pubic/axillary hair, maintains sex drive
116
adrenogenital syndrome - excessive DHEA
-deep voice, excess hair, more muscles, smaller breasts, ambiguous genitalia, precocious pseudo puberty
117
Addison's disease
primary adrenocortical insufficiency
- autoimmune
- aldosterone deficiency (hyperkalemia, hyponatremia etc.)
- cortisol deficiency (hypoglycemia, low BP)
- DHEA deficiency (lack of hair)
- excess ACTH --> hyper pigmentation
118
Adrenal Medulla
chromaffin cells - 20% NE, 80% Epi
- modified post-ganglionic fibers that give catecholamines to blood
- excess --> phaeochromocytoma
119
thyroid gland
- thyroid follicle (functional unit)
- Thyroglobulin in colloid
- SNS --> vasodilation --> increase T4 in blood
- parafollicular cells (secrete calcitonin)
120
T4 (thyroxin)
- inactive, most abundant
- transported in blood
- converted to T3 in tissues
121
T3
- active, found in tissues
| - not in blood
122
rT3 (reverse T3)
antagonist to T3
- prevents conversion from T4 to T3
- produced by D3
123
Thyroglobulin (Tg) synthesis
make Tg from ER and Golgi
- contains a lot of tyrosines & some iodine
- used as biomarker for thyroid cancer (found in blood when normally aren't)
124
1st step in thyroid hormone synthesis
make Tg & exocytose into colloid
125
2nd step in thyroid hormone synthesis
bring Na+ and iodine in through NIS symporter
126
role of thyroperoxidase (TPO)
- removes charge from iodine
- couples iodine with Tg (organification of I-)
- upregulated by TSH & hCG during pregnancy
- inhibitors useful for hyperthyroidism
127
T1 (MIT), T2 (DIT)
not permeable, cannot escape, recycles
- nonfunctional
- failure to recycle (deficiency in iodotyrosine deiodinase) --> lost in urine --> iodine deficiency
128
T3, T4
lipophilic, secreted out of cell
- functional
- T3 - has negative feedback on TRH, TSH
129
role of penderin
move iodine into colloid with the exchange of Cl- to be acted on by TPO
-deficiency --> hypothyroidism
130
TSH effect
- upregulate all processes (NIS, TPO, endocytosis)
- cause follicular cell to phagocytose the Tg in the colloid with the bound iodine
- produces T3,T4,rT3
- production & proliferation of follicular cells
131
NIS
Na+/I- symporter
| -can also transport bromide, thiocyanate, and perchlorate after ingestion of radioactive iodine
132
what can also be transported via NIS for imaging?
Technetium
133
increased demand of Iodine (ex. high TSH)
- won't make as much T4 (Tg/I- not in follicle as long)
- more T3 active is produced instead
- faster turnaround
134
thyroxine binding globulin (TBG) aka Tg
- carries T3, T4 (T4 higher affinity, longer half-life in blood)
- aspirin & other drugs compete for TBG (too much T4 in blood leading to hyperthyroidism)
135
hCG in pregnancy
- mimics TSH on follicular cells
- increase TBG and T3, T4 levels
- amount bound and free is normal (increasing both)
- elevated total thyroid level
136
deionization of thyroid hormones in tissues
Selenodeionidases enzyme (selenium core)
- deficiency (high T4, low T3)
- D1 (all tissue) --> activates T4 to T3
- D2 (CNS) --> activates T4 to T3
- D4 --> inactivates both T4, T3
137
iodine deficiency
-won't make enough T3 (no negative feedback on TRH or TSH) --> excess TSH --> goiter of thyroid
138
TSHR
G protein coupled
| -increase cAMP and PLC in follicular cells
139
role of sympathetic activation on thyroid
increase blood flow --> increase TSH to follicular cells --> more T3,T4 release
140
Thyroid hormone receptor (TR) signaling
1. nuclear receptor activation
- higher affinity for T3 than T4
2. has non-classical activation of membrane receptor as well (immediate actions)
141
T3 effects
1. brain development and growth
- stimulate somatotrophs to release GH & IGF-1 for bone & muscle production
2. increase BMR (thermogenesis)
- increase oxidative respiration and UCP-1 to increase heat
3. Metabolic
- high glucose absorption, liberate glucose, breaks fat (lowers cholesterol), increase protein synthesis & degradation
4. cardiovascular
- increase adrenergic receptors/Beta1 (increase HR) -water hammer pulse
- increase CO, alpha myosin heavy chain, SR Ca++ ATPase
5. glucocorticoid inactivation --> high ACTH
142
hyperthyroidism/thyrotoxicosis
- excess TSRH, TSH, T4 to T3 conversion (D1)
- thyroid tumor
- immunoglobulins (graves disease)
- high hCG during pregnant
143
how anti-TSHR (immunoglobulins) leads to goiter
stimulates production of T3,T4 --> no negative feedback --> excess TSH --> goiter
144
hyperthyroidism effects
- heat intolerance, weight loss, hyperreflexia, palpitations, water hammer pulse
- goiter in graves
145
hypothyroidism effects
- cold sensitivity, weight gain, slow reflexes, bradycardia
- selenium deficiency (can't convert T4 to T3, high TSH w/o negative feedback, goiter)
- wolf chaikoff - NIS overload with iodine
146
3 hormones that regulate plasma Ca2+
- PTH
- Vitamin D
- Calcitonin
147
the precursor for Vitamin D
cholecalciferol (D3)
- inactive
- made from cholesterol in skin & UV light
148
self-limiting step in activation of Vitamin D
25-hydroxycholecalciferol
- conversion in liver; inactive
- negative feedback in excess
- adding more Vit. D3 won't make more
149
activated form of Vitamin D
1,25-dihydroxycholecalciferol
- conversion in kidney; active
- PTH dependent (activated by low Ca2+)
150
24, 25-dihydroxycholecalciferol
- formed during high Ca2+, low PTH
| - antagonist to stop making Ca2++
151
vitamin D actions
- activates nuclear retinoid X receptor
- increase calbindin in intestines (increase Ca2+ absorption)
- increase Ca2+ ATPase, NCX1, TRPV5,6 & phosphatase
- low doses --> bone calcification
- high doses --> bone resorption
- anti-depressant
- metabolites can inhibit lung cancer progression
- increase muscle strength, activate T cells, anti-oxidants
152
function of calbindin
shuttles absorbed Ca2+ into basolateral side from luminal side
153
response to PTH
keep Ca2+, dump the phosphate
154
PTH
lung peptide; main regulator for Ca2+ - increase plasma levels during hypocalcemia
- also activates vitamin D
- activated during low Ca2+ levels, inhibited during high levels
155
effect of damaged or removed parathyroid
hypocalcemia - Ca2+ supplements the rest of life
156
PTH-related peptide
secreted by cancer cells --> more Ca2+ and bone reabsorption --> hypercalcemia
157
rapid effects (1st response) to PTH
osteolytic membrane (fluid b/w osteocytes & matrix)
- contains already dissolved Ca2+
- increase Ca++ pumps
- fast (immediate) release of Ca2+ to blood
158
slow/long term (2nd response) to PTH
activation of osteoclasts
- no receptors on osteoclasts, so activate osteoblasts 1st
- osteoblasts --> secrete RANKL and M-CSF that bind to preosteoclasts --> differentiate and proliferate osteoclasts
- suppress OPG (OPG prevents RANKL binding)
159
role of osteoclasts
destroy bone and release Ca2+
160
other PTH effects
- increase Ca2+ and Mg2+ reabsorption - high levels in blood
- increase Na+ & phosphate loss - high levels in urine
- increase 1,25-dihydroxycholecalciferol (increase intestinal Ca2+ and phosphate absorption)
161
regulation of PTH
- low Ca2+ levels --> increase PTH
- high Ca2+ or vitamin D levels --> decrease PTH
- high Ca2+ --> stimulate Ca2+ sensitive receptors (CaSR) --> shut down PTH due to activation of IP3 and DAG
162
Calcitonin
- produced by C cells of thyroid
- released in response to high Ca2+
- lowers blood Ca2+ by inhibiting activation of osteoclasts
163
PTH hyper secretion (hyperparathyroidism)
- hypercalcemia, hyperphosphaturia, renal stones (Ca2+ in urine after Tm is reached), bone decalcification
- increase osteoblasts activity
- low reflexes, arrhythmia
164
PTH hypo secretion (hypoparathyroidism)
- hypocalcemia and hyperphosphatemia
| - hyperreflexes and tetany
165
Vitamin D deficiency
children - rickets
| adults - osteomalacia (soft bones)
166
causes of osteoporosis
- estrogen deficiency
- malnutrition
- lack of exercise
- lack of Vit. C (builds framework of bones)
- Cushing's (excessive ACTH and cortisol) -cortisol stimulates osteoclasts
167
pancreatic beta cells
secrete amylin and insulin
168
pancreatic alpha cells
secrete glucagon
169
pancreatic delta cells
secrete somatostatin
170
pancreatic F cells
secrete pancreatic polypeptide (PP)
171
pancreatic epsilon cells
secrete gherlin (suppresses insulin & slows down emptying of stomach)
172
pancreatic amylin role
- controls appetite - weight loss
- satiety
- increase emptying time of stomach - fuller longer
- inhibit glucagon secretion
173
pancreatic somatostatin
- inhibits secretion of insulin, glucagon, PP
- more inhibition of beta cells rather than alpha cells
- stimulated by glucose, AA ingestion
- reduces GI motility
174
pancreatic peptide (PP)
- reduce gastric secretion and emptying time
| - marker for pancreatic cancer
175
what is the precursor for insulin?
preproinsulin
176
what enzyme converts proinsulin to insulin?
pro hormone convertase (PC1/3) - cleaves 2 AAs out of C peptide
- get A, B, or C peptide fragment
- separate C peptide from insulin
177
role of C peptide
- indicator for insulin secretion (high levels = insulin resistance)
- protect against neuropathy, renal, and vascular damage
- biomarker in gastric cancer
178
regulation of insulin secretion
-hyperglycemia --> increase insulin --> glucose internalized in beta cells by GLUT2 and used to make ATP
179
mechanism of insulin secretion
excess ATP close K+ leak channel --> partial depolarization to activate voltage gated Ca2+ channels--> release of insulin from storage
180
what can block K+ leak channels allowing insulin release?
- hyperkalemia or sulfonylurea
| - amino acids through ATP production
181
how does ACh lead to insulin release?
PLC activation --> IP3 and DAG --> increase intracellular Ca2+ --> insulin release
-store sugar with PNS
182
what inhibits insulin release?
stimulation of alpha adrenergic receptors (SNS)
| -liberate sugar with SNS
183
incretin effects
- secreted from intestines
- primes beta cells for incoming hyperglycemia - release insulin after ingestion of sugar
- increase insulin sensitivity and release (treat type II diabetics)
184
3 main incretins
GLP-1, GIP, CCK
| -GLP-1 stimulated by metformin and inhibits glucagon
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function of dipeptidyl peptidase IV inhibitors
increase GLP-1 and improve glucose tolerance
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what factors stimulate insulin sensitivity?
adiponectin and visfatin --> fat cells that take up more sugar
metformin --> prevent liver for doing gluconeogenesis
-get rid of sugar in blood
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what factors inhibit insulin sensitivity?
- glucocorticoids
- catecholamines
- GH
- resistin and RBP4
- keep sugar in the blood longer
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insulin receptor (IR) signaling
- insulin activates tyrosine --> activate IRS and many others
- also activation of Ras --> activate MAPK --> cell proliferation and anti-apoptotic
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ways of inhibiting IR signaling
1. PTP (tyrosine phosphatase) - dephosphorylation of tyrosine kinase terminates signal --> insulin resistance
2. serine-threonine phosphorylation of IR --> decreases ability to autophosphorylate terminating signal --> type II diabetics
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insulin functions
- promote glycogen synthesis and glycolysis
- inhibit lipolysis & promote lipogenesis
- promote FA synthase and lipoprotein lipase
- inhibit hormone sensitive lipase
- reduce ketone bodies
- promote protein synthesis and inhibit degradation
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3 ketogenic hormones
- GH
- cortisol
- glucagon
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other insulin functions
- satiety
- increase GLUT 4 expression and localization in fat and muscles
- glucagon suppression
- insulin resistance associated with deficient GLUT4 recruitment
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what else induces GLUT 4 expression?
exercise
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moderate exercise
glucose uptake and production are equal
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intense exercise
can have hyperglycemia
| -more breakdown of glycogen and catecholamines inhibit glucose uptake --> need to liberate energy
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chronic stress
- can lead to diabetes
- no recruitment of GLUT4, but have glycogenolysis and gluconeogensis
- increase cortisol and insulin resistance
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what stimulates glucagon release?
- hypoglycemia
- increased AAs
- catecholamines
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what inhibits glucagon release?
- fatty acids
- somatostatin
- insulin
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why do you increase glucagon when you increase insulin?
- don't want to get into hypoglycemia if you eat a protein rich only meal
- balance each other out
- insulin will tone down glucagon when it needs to hide sugar
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glucagon function
- increase glycogenolysis and gluconeogensis
- increase AA transport to liver and urea formation
- increase lipolysis and ketogenesis
