REB Endocrine Flashcards
1
Q
what are the types of hormones?
A
- steroid
- amine
- peptide
- protein
2
Q
what are steroid hormones derived from?
A
cholesterol
3
Q
what are amine hormones derived from?
A
from amino acid modification of tryptophan and tyrosine
4
Q
what are peptide hormones derived from?
A
multiple amino acids linked together
5
Q
what type of hormones need transport proteins?
A
steroid hormones
6
Q
steroid hormones arrive at the nucleus with the help of transport proteins. what does the activated receptor bind to?
A
HREs (hormone response elements) of DNA
7
Q
what are HREs?
A
regions of DNA that contain a consensus sequence located upstream to the initiation site and associated with transcription factors
8
Q
hormone signalling duration is _____ but effect duration is _____
A
short
long
9
Q
how is cAMP signalling controlled
A
negative feedback by pKA
10
Q
what does pKA activate?
A
phosphodiesterases
11
Q
what do phosphodiesterases do?
A
deactivate cAMP
12
Q
what substance is activated by G-proteins and cleaves membrane-bound phospholipids
A
phospholipase C
13
Q
phospholipase C cleaves membrane-bound proteins into
A
IP3 and DAG
14
Q
what causes the phosphorylation cascade?
A
protein kinases activated by DAG
15
Q
IP3 increases release of
A
Ca2+
16
Q
Ca 2+ acts as a second messenger by binding tp
A
calmodulin
17
Q
what does calmodulin do
A
modulates protein kinase activity within the cells
18
Q
what is the second messenger of a GPCR dependent reaction?
A
calcium
19
Q
what is the second messenger of a GPCR independent reaction?
A
cGMP
20
Q
explain a GPCR independent reaction
give an example
A
involves the conversion of GTP to GMP when ligand binds by membrane-bound receptor guanylate cyclase
eg. ANP –> increase Na excretion –> decrease ECF
21
Q
explain the binding of insulin
A
insulin binds
tetramer dimerises and autophosphorylation occurs
the insulin response element is then phosphorylated and hence activates
22
Q
describe a sandwich elisa
A
monoclonal antibodies plates –> antigen binds –> sandwiched by second monoclonal antibody modified with enzyme –> colour produced
23
Q
in a sandwich elisa what is the relationship between colour produced and amount of antigen
A
colour produced directly proportional to amount of antigen
24
Q
describe a competitive elisa
A
antibody incubated with sample –> mixture added to wells coated with the same antigen –> bound to antibodies in mixture washed away ; free antibodies will bind to antigen (2nd antibody is added for colour)
25
in a competitive elisa what is the relationship between colour produced and amount of antigen
colour produced inversely proportional to amount of antigen
26
where does the anterior pituitary gland arise from
Rathke's pouch - epithelioid nature
27
where does the posterior pituitary gland arise from
neural tissue outgrowth from hypothalamus - glial type
28
what types of neurons are in the posterior pituitary. where are their cells?
neurosecretory neurons in the hypothalamus
29
what are the main nuclei in the posterior pit
supraoptic
| paraventricular
30
what hormones are produced by the posterior pit
vasopressin/ADH
| oxytocin
31
what nuclei produces vasopressin
supraoptic mostly
| 1/6 by the paraventricular
32
what nuclei produces oxytocin
paraventricular mostly
| 1/6 by the supraoptic
33
vasopressin and oxytocin are produced as
prohormones
34
vasopressin and oxytocin are bound to carrier proteins called
neurophysins
35
how long does it take to transport vasopressin and oxytocin to go to the posterior pituitary
several days
36
nervous impulses cause the release of both neurophysins and hormones into the
capillaries (they separate immediately)
37
Unlike the post pit gland, the anterior pituitary gland synthesises its own hormones. What are these hormones?
1. somatotrophs (GH)
2. corticotrophs (ACTH)
3. Gonadotrophs (FSH and LH)
4. Lactotrophs (prolactin)
5. Thyrotropes (TSH)
38
all hormones are trophic except
prolactin
39
what hormones control the release of anterior pituitary hormones
hypothalamic releasing and inhibitory hormones
40
the hypothalamus releases hormones which control secretions of the anterior pituitary by the
hypothalamic hypophyseal portal system
41
where does the hypothalamic hypophyseal portal system begin?
median eminence (base of hypothalamus)
42
the hypothalamic hormones act on the ________ of the anterior pituitary
glandular cells
43
anterior pituitary hormones are regulated by
1. hypothalamic hypophysiotropic hormones
| 2. negative feedback
44
what are the types of feedback loops
1. ultrashort
2. short
3. long
45
how are ultrashort feedback loops regulated
hypothalamic hormones self-inhibit
46
how are short feedback loops regulated
pituitary hormones inhibit hypothalamic hormones and other pituitary hormones
47
how are long feedback loops regulated
hormones from peripheral endocrine glands
48
PIH is identical to
dopamine (has more than 1 effect)
49
a hormone may be regulated by more than one hormone. example....
GH by GHRH and GHIH
50
what is primary hypo/hyper secretion
hypo/hyper secretion of the anterior pit cells
51
what is secondary hypo/hyper secretion
hypo/hyper secretion of the hypophysiotropic hormones
52
what is tertiary hypo/hyper secretion
hypo/hyper secretion of endocrine gland
53
what is panhypopituitarism
decrease in secretion in all anterior pituitary hormones
54
effect of panhypopituitarism on children
rate of development is decreased and they never go through puberty
55
effect of panhypopituitarism in adults
become sterile but can be treated with thyroid/ adrenocortical hormones
56
what illness is characterized by:
- decrease in secretion in all anterior pituitary hormones
- rate of development is decreased and they never go through puberty
panhypopituitarism in children
57
what illness is characterized by:
- decrease in secretion in all anterior pituitary hormones
- person becomes sterile but can be treated with thyroid/ adrenocortical hormones
panhypopituitarism in adults
58
what cells produce growth hormone
somatotropes
59
treatment of panhypopituitarism in adults
thyroid/ adrenocortical hormones
60
which hormones are closely related to GH and its function
thyroid hormone
| sex hormones
61
what i sthe most abundantly produced ant pit hormone
GH
62
secretion of GH _____ with age
decreases
63
is GH secreted after growth has seized
YEP
64
metabolic effects of GH are triggered by
direct binding to the target hormone
65
what are the metabolic effects of GH
1. metabolization of FA in adipose tissue for energy. this increases FA in the blood and conserves glucose for the brain
2. decreased rate of glucose utilization throughout the body (decreases uptake) --> GH induced insulin resistance eg Muscles uptake of glucose decreases
3. increased rate of protein synthesis
66
growth- promoting effects are done by stimulating
somatomedins
67
somatomedins are structurally and functionally similar to
insulin called insulin-like growth factor (IGF1 or somatomedin C)
68
where is IGF 1 produced
liver
69
what is the purpose of IGF?
promotes growth upon stimulation (bone growth and protein synthesis)
70
bone growth occurs through
thickening of the epiphyseal plate and increase in bine length
71
regulation of GH
1. negative feedback on GHRH and GHIH secretions (short loop)
2. diurnal rhythm - GH secretion increases 1hr into sleep
3. other factors - low blood glucose (GH conserves glucose), exercise (fat usage instead), high protein (protein synthesis) and decrease in plasma FA (mobilisation)
72
GH deficiency in children can lead to what conditions/ illnesses?
dwarfism
laron dwarfism
african pygmies
73
symptoms of Dwarfism
short stature
decrease in development of muscles
increase in subcutaneous fat
74
cause of laron dwarfism
blood GH normal but GH receptor is abnormal
75
cause of african pygmies
blood GH normal, receptor normal, lack of IGF 1
76
symptoms of african pygmies
no growth function but normal metabolism
77
symptoms of GH deficiency in adults
reduced skeletal muscle mass
increased bone density
increased risk of heart failure
78
excess GH in children can lead to what conditions/ illnesses?
gigantism
| hyperglycemia (GH conserves glucose)
79
symptoms of GH excess in adults
bones and tissue thicken and proliferate
hyperglycemia
** shows mostly in face
80
explain the change in glucose level if there is a GH deficiency
normally after a meal, insulin should decrease glucose levels which should trigger GH secretion, allowing glucose to rise again.
if deficient, glucose levels cannot rise again
81
what test can be done to determine if a person has excess GH secretions
glucose loading test
82
explain the glucose loading test and its result if GH is excessively secreted
patient given glucose --> increase in glucose --> increased GHIH --> decrease glucose normally
if excess, decrease would not be as significant either due to not enough GHIH or too much GH acting
83
what does prolactin normally stimulate
proliferation and branching of ducts in the breasts
84
what does prolactin stimulate in pregnancy
development of lobules of alveoli for milk production
85
what does prolactin stimulate post partum
milk production and secretion
86
what effect does prolactin have on immunity
decreases immune responses to accept foetal tissue
87
prolactin increases during pregnancy until
mother stops breastfeeding
88
deficiency in prolactin leads to
inability to lactate
89
how is prolactin regulated
short-loop negative feedback by PRH and PIH or dopamine
90
how does excess prolactin specifically affect women
infertility, loss of menstruation, inappropriate lactation
91
how does excess prolactin specifically affect men
decreased testosterone levels, sperm production, breast development
92
how does excess prolactin generally affect both genders
decreased libido
93
treatment of excess prolactin
dopaminergic drugs (perform PIH functions)
94
what stimulates oxytocin secretion
positive feedback when suckling or birth canal stretch
95
what are the functions of oxytocin
milk ejection
| contraction of uterus
96
what are the functions of vasopressin
enhances retention of water by kidneys
| constriction of arterial smooth muscle
97
what stimulates the release of vasopressin
1. osmotic: osmoreceptors increased osmolality and increased firing rate --> ADH secretion
2. volume: decreased volume of BP causes release detected by baroreceptors or stretch receptors located in the walls of the left atrium and pulmonary veins
3. age: older --> more ADH
4. ethanol: suppresses ADH release (this is why you get thirsty)
98
explain ADH levels after hemorrhage
during low volume
| ADH is secreted 50 times more to bring back blood volume
99
what is a deficiency in vasopressin caused by
diabetes (hyperglycemia --> increased blood osmolarity)
100
symptoms of vasopressin deficiency
same as the symptoms of diabetes (hyperglycemia, polyuria, polydipsia, nocturia)
101
symptoms of excess vasopressin
electrolyte disturbance
| CNS symptoms from too low osmolarity
102
source of thyroglobulin
epithelial cells surrounding the colloid space or lumen
103
where is thyroglobulin stored
lumen
104
where is parathyroid hormone released from
parathyroid gland
105
what is the effect of parathyroid hormone of Ca
increases calcium levels
106
where is calcitonin released from
parafollicular (C) cells
107
what is the effect of calcitonin of Ca
decreases calcium levels
108
where are parafollicular (C) cells located?
between follicles in the thyroid gland
109
what regulates thyroglobulin synthesis
TSH through active transport of Iodine (iodinating tyrosine residues)
110
steps of thyroid hormone synthesis
1. thyroglobulin is synthesised by epithelial cells and transported into the colloid space
2. TSH causes cells to actively transport iodine into the cytosol. once inside, they are trapped to prevent escape and oxidised into the active form by peroxide.
3. iodine enters the lumen through NIS (sodium, iodide symporter). thyroperoxidase iodinates tyrosine molecule on thyroglobulin forming either 2MITs or 1DIT (# of iodine attacks)
4. MIT and DIT --> T3 and 2DIT --> T4
5. epithelial cells ingest the colloid by endocytosis and fuses the vesicle with lysosomes where thyroglobulin is cleared releasing 90% T4 and 10% T3.
6. since the thyroid hormones, T3 and T4, are lipid soluble, they diffuse across the membrane and into the bloodstream.
111
what hormone causes cells to actively transport iodine into the cytosol?
TSH
112
what oxidises iodine in the cytosol?
peroxide
113
iodine enters the lumen through
NIS
114
what iodinates tyrosine molecules on thyroglobulin
thyroperoxidase
115
thyroperoxidase iodinates tyrosine molecule on thyroglobulin forming
either 2MITs or 1DIT
116
1MIT and 1DIT forms
T3
117
2DIT forms
T4
118
of the total TH made, how much is T4 and how much is T3
90% T4 and 10% T3
119
T4 is a ____ of T3
prohormone
120
which TH is more biologically active
T3
121
deiodination of T4 forms
```
T3
reverse T3 (metabolization of T4)
```
122
iodine is converted to ____ by bacteria in the gut
iodide
123
how is iodide transported in the blood
bound to serum proteins
124
how does the NIS work in transporting iodine
transfers both iodine and sodium in one direction using gradient of sodium
125
how is TH regulated
1. TRH secretion - stimulated by exposure to cold; inhibited by T3 and T4 levels
2. TSH secretion from anterior pituitary by thyrotropes - stimulated by TRH during the day and inhibited by T3 (beta subunit) during the night
126
what part of the T3 inhibits TSH
Beta subunit
127
what is the significance of the binding of TH to a transport protein
to prevent free diffusion into random cells
128
Active TH are _____ and can hence freely diffuse into cells to elicit an action.
unbound
129
what transport proteins are TH bound to and describe their affinity and capacity
1. thyroxine-binding globulins (TBG) - high affinity, low capacity
2. albumin - low affinity, high capacity
3. thyroxine binding prealbumin (TBPA) - low affinity, high capacity
130
describe the genomic action of TH
TH are steroid hormones (hydrophobic). they diffuse into the cell and T4-->T3 in the cytoplasm. T3 binds to the thyroid receptor activating it. the receptor then complexes with TRE and Retinoid X receptor).
131
what stimulates and inhibits TRH secretion
stimulated by exposure to cold; inhibited by T3 and T4 levels
132
what stimulates and inhibits TSH secretion
stimulated by TRH during the day and inhibited by T3 (beta subunit) during the night
133
TH increases the body's sensitivity to
catecholamines (adrenaline and noradrenaline)
134
temporal effects of TH levels
Daytime - low - anabolic - low metabolic rate - protein and glycogen synthesis
night time - high - catabolic - high metabolic rate - protein and glycogen breakdown
135
Explain the effects of TH on metabolism
```
presence of TH --> catabolism
increased glucose absorption
glycogenolysis
gluconeogenesis
increased fat mobilization --> increased FA
```
136
what is the metabolic function of TH
increases overall BMR
most important regulator of oxygen consumption and energy expenditure
it degrades fats and glycogen but doesn't affect proteins
137
what is the calorigenic effect of TH
increases metabolic activity --> increases heat production
138
what is the effect of TH on the nervous system of children
TH is essential for myelination and CNS development
139
what is the effect of excess TH on the nervous system of adults
restlessness and hypersensitivity
140
what is the effect of a TH deficiency on the nervous system
lethargy and mental deficit
141
what the effect of TH on growth
stimulates GH secretion and increases synthesis of IGF-1 and promotes GH and IGF effects on growth and development
142
what the effect of TH deficiency on growth in children
stunts growth --> dwarfism (african pygmies)
143
what is the effect of TH on the cardioresp system
TH increases blood flow and increases sensitivity to catecholamines which increase HR, SV and BP
144
what is the primary cause of hypothyroidism
Gland tissue
145
what is the secondary cause of hypothyroidism
anterior pituitary/ hypothalamus
146
symptoms of hypothyroidism
```
reduces BMR
poor tolerance to cold
slow mental response
weight gain
weak pulse
lethargy
husky voice
dry scalp/skin
```
147
what is myxedema
severe hypothyroidism
increased H2O retention of carbs
increases interstitial fluid
148
clinical presentation of myxedema
edemic appearance (puffy) with bagginess under eyes and face swelling
149
clinical presentation cretinism
congenital --> since birth
they experience dwarfism (no IGF-1) and mental retardation
**effects may not show before birth as the mother supplies the embryo
150
cretinism can be caused by hypothyroidism or
can also be due to iodine deficiency
151
treatment of cretinism
T4 supplements few weeks after birth or permanently
152
diagnostics of hypothyroidism (test and results)
done by measuring TSH and T4 levels in blood
people with hypothyroidism should have high TSH and low T4 (low negative feedback)
if issue is secondary, then low TSH and TRH
153
most common cause of hyperthyroidism
grave's disease
154
what is grave's disease
autoimmune disease characterised by the production of LATS that also target TSH receptors (not TH)
growth and secretion continue unchecked
155
what does grave's disease stimulate
growth and secretion of thyroid gland
156
grave's disease has a similar function to
TSH
| ** but it is not inhibited by TH
157
symptoms of grave's disease
elevated BMR
increased appetite and weight loss
intolerance to heat
degradation of fat, protein and carb stores at an abnormal rate
HR and SV increase significantly --> palpitations
excessive degree of mental awareness --> anxiety
158
clinical signs of grave's disease
inflammation and swelling of eye muscles --> eye bulge out and lids cannot close --> irritation
159
diagnostics of grave's disease
done by measuring TSH and Thyroxine (TH) in plasma
| TSH should be very low (inhibited) but TH levels very high.
160
what is a goitre
an enlarged thyroid thyroid gland
161
when are goitres present (in relation to TH release)
they are present in hypo and hyperthyroidism or none
162
when in hypothyroidism is a goitre present?
issue with thyroid gland or lack of iodine
| where there is excessive stimulation of the gland by TSH but no TH is being secreted
163
when in hyperthyroidism is a goitre present?
1. Grave's disease (PRIMARY) - hypersecretion due to LATS which acts like TSH but has no inhibition (continuous stimulation)
2. Secondary defect - excessive TSH secretion due to tumor leads to excessive stimulation --> goitre
164
when in hypothyroidism is a goitre not present?
when the issue is with hypothalamus or anterior pituitary since there is no TSH secretion --> no stimulation --> no goitre
165
when in hyperthyroidism is a goitre not present?
when there is excessive secretion without extra stimulation --> thyroid tumor
166
where is calcium stored
bone reservoir, ECF and cells
167
disorders of Ca are closely related to disorders of
magnesium
| phosphates
168
what are the functions of calcium
1. muscle contraction and nerve excitability. Ca2+ deficit causes hyperexcitability of neurons and excess Ca2+ causes increased contractility
2. NT and hormone release into synaptic cleft
3. Blood coagulation (essential cofactor for clotting factors)
169
regulation of calcium is done by
parathyroid hormone released from parathyroid glands --> increases Ca2+
calcitonin released from thyroid gland --> decreases Ca2+
170
effect of parathyroid hormone on Ca
increases Ca2+
171
effect of calcitonin on Ca
decreases Ca2+
172
calcium is absorbed in the ____ but requires ____
small intestine
| vitamin D
173
how is plasma Ca2+ levels controlled by the kidney
regulation of excretion of extra calcium and reabsorption if levels are low
174
if there is impairment of intestines, parathyroid glands and kidneys, how is plasma Ca2+ maintained
at the expense of bone calcification
175
what are the functions of PTH
1. increases Ca2+ and Mg2+ reabsorption in the kidneys
2. increases Ca2+, Mg2+ AND HPO4- uptake from GI tract into blood
3. increases activity of osteoclasts --> bone breakdown --> increased Ca2+ levels
4. promotes vitamin D formation by increasing Ca2+ absorption in small intestine
176
PTHrP is structurally similar to
PTH
177
what are some additional functions of PTHrP (beside those similar to PTH)
mammary gland development
lactation
placental transfer of Ca2+
178
where is PTHrP secreted from
breast and lung tumors
179
unlike PTH, PTHrP does not stimulate
vitamin D synthesis
| nor calcium absorption (bone decalcification only)
180
what are the PTH receptors
type 1 - high affinity for both PTH and PTHrP and is a G-protein receptor located in the bone and kidney
type 2 - binds to PTH but low affinity for PTHrP
181
which PTH receptor has a low affinity for PTHrP
type 2
182
which PTH receptor has a high affinity for both PTH and PTHrP
type 1
183
calcitonin is produced by
parafollicular (C) cells
184
calcitonin binds to a ____ receptor
Calcitonin
185
where is the calcitonin receptor located
on osteoclasts (inhibiting fxn)
osteoblasts ( promotes fxn)
kidneys
186
what type of receptor is the calcitonin receptor
GPCR
187
effect of calcitonin receptor on osteoclasts
inhibits fxn
188
effect of calcitonin receptor on osteoblasts
stimulates fxn
189
mRNA in C-cells contain _____ exons which code for _______
4 of 6 exons
| pre procalcitonin
190
calcitonin opposes the fxn of §
PTH
191
mRNA in CNS contain _____ exons which code for _______
5 of 6 exons
| calcitonin-gene related peptide (CGRP)
192
what is the function of CGRP
potent vasodilator
193
vitamin d can be obtained through the diet as __ in vegetables and __ in meat
D2
| D3
194
how can vitamin D be obtained other than through the diet
endogenously through UV action on the skin producing Calcitriol
195
formation of vitamin D
7 dehydrocholesterol --> vitamin D3 -- liver (hydroxylation) --> 25 hydroxyvitamin D3 -- kidney (hydroxylation) ---> Calcitriol (1,25 dihydroxyvitamin D3)
enzyme of last step - 25 hydroxyvitamin 1 alpha hydroxylase
196
where does 1 alpha hydroxylase work
kidney
197
____ stimulates 1 alpha hydroxylase
PTH
198
____ inhibits 1 alpha hydroxylase
vitamin D (calcitriol)
199
____ inhibits PTH
calcitriol
200
vitamin D is transported in the blood bound to
vitamin D-binding protein
201
inactive form of vitamin D is
25-hydroxyvitamin D
202
active form of vitamin D is
1,25-hydroxyvitamin D (calcitriol)
203
25-hydroxyvitamin D is from the
liver
204
1,25-hydroxyvitamin D is from the
kidney
205
vitamin D has a lower affinity for which form of vitamin D
25-hydroxyvitamin D (inactive)
206
which form of vitamin D has a longer half life
25-hydroxyvitamin D (inactive)
207
when vitamin D binds to its receptor, it forms a complex with
RXR (like TH) which then goes onto the vitamin D response element
208
functions of vitamin D
1. increases calcium uptake
2. mineralises excretion of Ca2+ from kidney by increasing Ca2+ reabsorption
3. stimulates osteoclast activity
** same as PTH
209
calcium is mostly reabsorbed in the
PCT but some in the loop of henle
210
the functions of vitamin D are similar to that of
PTH
211
does vitamin D increase or decrease calcium uptake
increases calcium uptake
212
____% of Ca2+ in the body is found in the blood
____% is bound to albumin or an anion (inactive)
____% is found in it's free form (Ca2+ ionised form) (active)
0.1
45
55
213
changes in albumin alters the ________ of calcium but NOT the ________
total amount
| fraction of free ionized Ca+
214
does changes in H+ alter fraction of free ionized Ca+?
YEP
215
How does changes in H+ alter fraction of free ionized Ca+?
H+ competes with Ca2+ to bind to anions --> increase H+ --> increase acidity --> increase free ionised Ca2+
216
describe the effect of alkalosis and acidosis on the fraction of free ionised Ca2+
Alkalosis --> less H+ --> decreased free ionized Ca2+
| Acidosis --> more H+ --> increased free ionized Ca2+
217
what are the different types of cells involved in bone turnover and what is the purpose of each
1. osteoclasts - bone forming
2. osteoblasts - bone-resorbing cells
3. osteocytes - embedded osteoblasts - they regulate concentration if osteoblasts and osteoclasts
218
what is hyperparathyroidism
excess PTH --> increased bone resorption (break down)
219
what is osteomalacia and rickets
vitamin D deficiency
osteomalacia - demineralizing of pre-existing bones
rickets - in the children version where there is continued collagen formation but incomplete mineralization
220
In rickets, there is continued ______ formation but incomplete mineralization.
collagen
221
what is osteoporosis
disorder of reduced bone matrix
| ** not a disorder of Ca+ metabolism
222
osteoporosis resembles _______ but normal plasma Ca2+
osteomalacia
223
treatment of osteoporosis
treated with calcitonin to increase mineralisation
224
what is paget's disease
increased osteoclast activity
there is new bone formation but osteoclasts make it weaker
(easy to fracture)
225
diagnosis of paget's disease
increased serum alkaline phosphatase (ALP)
226
symptoms of hypocalcemia
constipation and arrhythmia
227
clinical presentation of hypercalcemia
trousseau's sign (wait sign)
| chvostek's sign (twitch of lip or facial spasm)
228
symptoms of hypercalcemia
muscle cramps
| excess Ca2+ --> increase muscle contraction
229
insulin is secreted by
B cells of Langerhan in the pancreas
230
when is insulin released in the blood
when glucose levels in the rise after parasympathetic stimulation
231
insulin facilitates the uptake of
glucose into the cell
232
what are the cell types in the islets of langerhans and what do they produce
1. alpha cells (20%) - glucagon
2. beta cells (75%) - insulin
3. delta cells (5%) - somatostatin
233
somatostatin is inhibits
GH secretion
| release of pancreatic and GI hormones
234
somatostatin is released by
Hypothalamus and delta cells
235
insulin inhibits
somatostatin and glucagon
236
somatostatin inhibits
insulin and glucagon
237
glucagon promotes
insulin and somatostatin
238
why does glucagon promote insulin production
it is needed for glucose transport
239
insulin synthesis
1. synthesised initially as pre proinsulin with 4 domains (in beta cells)
2. removal of N-terminus signal peptide becoming proinsulin with 3 domains. Amino B, Middle C and Carboxyl A.
3. removal of C peptide forms mature insulin with only 2 domains linked by alpha sulfide bonds --> mature --> amino B and carboxyl A
240
what domain is removed from insulin first
N-terminus
241
what domain is removed from inulin second
C peptide
242
mature insulin and C-peptide are packaged into secretory vesicles by
Golgi
243
insulin release is triggered by the
influx of glucose
244
describe the steps in insulin release
1. glucose enters beta cells via facilitated diffusion through the GLUT 2 transporter
2. Glucose metabolised by glucokinase into G-6-P trapping it in the cell
3. ATP generated via glycolysis for K+ channels
4. closure of ATP-sensitive K+ channels --> no K+ influx --> depolarises cell leading to opening of Ca+ channel --> Ca2+ influx
5. increased intracellular Ca2+ triggers the release of insulin - containing vesicles/ granules.
245
the 2 domains left on the mature insulin molecule is linked by
alpha sulfide bonds
246
insulin release - glucose enters beta cells via facilitated diffusion through the
GLUT 2 transporter
247
insulin release - Glucose metabolised by _____ into G-6-P trapping it in the cell
glucokinase
248
insulin release - ATP generated via glycolysis for
K+ channels
249
insulin release - closure of ATP-sensitive _____ --> depolarises cell leading to opening of _____-->
K+ channels
| Ca+ channel
250
insulin release - increased intracellular Ca2+ triggers the release of _____
insulin - containing vesicles/ granules
251
hyperinsulinism can be induced by
tumors or by excessive insulin intake
252
hyperinsulinism can lead to
hypoglycemia which can cause brain damage
253
regulation of insulin release
1. nutrients - glucose and amino acids leucine, isoleucine, alanine, arginine
2. pancrine via somatostatin and glucagon (inhibition)
3. GI hormones - GIP, glucagon-like peptide (GLP) and catecholamines (noradrenaline and adrenaline)
254
glycogen is synthesised by
aloha cells
| interstitial neuroendocrine L cells (gut) and brain
255
glucagon is secreted is stimulated by
low glucose
high protein
catecholamine stimulation
256
glucagon is first synthesized as _____ before undergoing post-translational processing
proglucagon
257
proglucagon in pancreatic alpha cells is converted to (3)
1. glucagon
2. GRPP (glicentin related pancreatic peptides)
3. major proglucagon fragment (MPF)
258
proglucagon in pancreatic alpha cells is converted by what hormone
prohormone convertase 2 (PC2)
259
proglucagon in neuroendocrine or enteroendocrine L cells is converted to
1. glicentin
2. GLP 1 (glucagon-like peptides) - stimulator of insulin secretion and somatostatin secretion but inhibit glucagon secretion
3. GLP 2 - useless
260
function of glicentin
stimulator of insulin secretion, inhibits secretions of gastric acid, and reduces gut motility
(increases beta secretions)
261
effect of glicinten on pancreatic cells
increases secretion of B cells
262
effect of GLP 1 on pancreatic cells
decreases secretion of alpha cells
| increased secretion of B and D cells
263
proglucagon in neuroendocrine or enteroendocrine L cells is converted by
prohormone convertase 1 and 3
264
what are the immediate effects of insulin
increased transport of glucose, amino acids and K+ into cells
265
what are the intermediate effects of insulin (4)
increased entry of AA
increases glycolysis and glycogen synthesis
decreased gluconeogenesis and glycogenolysis
decreased protein degredation
266
what are the delayed effects of insulin
Increase in mRNA for lipogenic enzymes to store glucose in the form of lipids in adipose tissue
267
the insulin receptor is an RTK receptor which has an ____ subunit extracellularly and a ____ subunit intracellularly
alpha
| beta
268
when insulin binds to its receptor, it causes
auto-phosphorylation of tyrosines in the beta subunit
269
auto-phosphorylation of tyrosines in the beta subunit allows the receptor to phosphorylate
IRS-1
270
when insulin binds, the whole receptor moves intracellularly allowing
lysosomes degrade insulin
271
what glucose transporter is found on muscle and adipose?
| do they require insulin?
GLUT 4
| YUP
272
what glucose transporter is found on brain and kidneys? do they require insulin?
GLUT 3
| NOPE
273
what glucose transporter is found on liver and pancreas?
| do they require insulin?
GLUT 2
| NOPE
274
what glucose transporter requires insulin
GLUT 4
275
hypoglycemia is due to
insulinomas or congenital
276
type 1 diabetes is caused by
immune-mediated B cell destruction --> hyperglycemia
277
describe the onset of type 1 diabetes
fast
278
type 1 diabetes may cause
ketoacidosis
279
type 2 diabetes is caused by
B cell dysfunctional insulin resistance and associated with obesity and sedentary lifestyle
280
describe the onset of type 2 diabetes
slow
281
type 2 diabetes may cause
blurred vision
| slow healing
282
diagnosis of type 2 diabetes
hyperglycemia but with normal insulin levels
283
diabetic ketoacidosis is a symptom of
uncontrolled diabetes
284
without insulin, the body cannot break down glucose.
| what is the new fuel source
break down of fat instead
285
the break down of fat produces
ketone bodies
286
a buildup of ketone bodies in the liver after beta oxidation can lead to
keto acidosis
287
keto acidosis is caused by
a buildup of ketone bodies in the liver after beta oxidation
288
where does beta oxidation occur
liver
289
explain the cause of glycosuria
too much glucose --> kidney cannot reabsorb 100% of glucose --> its in piss
therefore, with a high glucose concentration in urine, volume increases and there is more piss
290
normal glycogen levels in the body is
70-120 mg/dL (3.9-7.1 mmol/L)
291
glucagon regulates blood glucose levels by
stimulating glycogen breakdown
292
process of glucagon secretion
1. hypoglycemia causes intracellular glucose concentration to fall
2. reduction in glycolysis ATP --> K+ channels close
3. intracellular K+ concentration rises --> depolarises cell --> Ca2+ channels open --> influx of Ca2+
4. influx of Ca2+ causes secretion of glucagon through exocytosis
293
in glucagon secretion, there is a reduction in glycolysis ATP which causes the closure of the
K+ channels
294
in glucagon secretion, the influx of ____ causes secretion of glucagon through endocytosis
Ca2+
295
what factors stimulate glucagon release (3)
1. low blood glucose
2. protein rich meal (secreted with insulin)
3. catecholamines (glucagon levels increase in anticipation for increased glucose use)
296
what factors inhibit glucagon release (2)
1. high blood glucose
| 2. insulin
297
metabolic effects promoted by glucagon (3)
glycogenolysis
gluconeogenesis
ketogenesis (liver and adipose tissue)
298
metabolic effects inhibited by glucagon (2)
glycogenesis
| glycolysis
299
what type of receptor is the glucagon receptor
GPCR
300
what type of reaction is catalysed by enzymes which are active when phosphorylated
catabolism
301
what type of reaction is catalysed by enzymes which are active when dephosphorylated
anabolism
302
what is whipple's triad
1. hypoglycemic symptoms - motor impairment, NSB problems
2. blood glucose levels < 50 mg/dL (normal 70-120)
3. symptoms resolve after glucose administration
303
types of hypoglycemia (4)
1. insulin-induced
2. post-prandial
3. fasting
4. alcohol-induced
304
cause of insulin-induced hypoglycemia
self-injection
305
what is postprandial hypoglycemia
exaggerated insulin release after a meal
306
how is postprandial hypoglycemia treated
eating less
| more frequently
307
cause of fasting hypoglycemia
insulinoma, adrenal insufficiency (catecholamines stimulate glucagon), liver damage
308
risk group for alcohol-induced hypoglycemia
alcoholics that take irregular meals
309
how does alcohol consumption increase the risk of hypoglycemia
metabolism of alcohol --> excess NADH --
| > diverts oxaloacetate away from gluconeogenesis --> increased the risk of hypoglycemia
310
prediabetes is also known as
intermediate hyperglycemia
311
plasma glucose concentration of prediabetes
6.1-6.4 mmol/L
312
plasma glucose concentration of diabetes
>= 7 mmol/L
| > 125 mg/dL
313
plasma glucose concentration of acute hyperglycemia
| at what glucose concentration is the person symptomatic
>= 8 mmol/L
| symptomatic at >= 15 mmol/L
314
symptoms of hyperglycemia (6)
1. decreases glucose entry into tissues and increased hepatic output
2. glycosuria
3. osmotic diuresis - polyuria and polydipsia (increased thirst)
4. polyphagia - (increased appetite since body thinks its hypoglycemic)
5. weight loss - excess metabolism of proteins and fats
6. increase HbA1C - especially following an episode as diagnostic trace. it is glycated hemoglobin
315
how does osmotic diuresis affect electrolyte composition
excess loss of Na+ and K+ --> dehydration
316
diabetic ketoacidosis is caused by
alteration of carb, protein and lipid metabolism
317
DKA is a hallmark of what type of diabetes
type 1
318
what causes the increases ketosis in DKA
severe insulin deficiency and/or elevated levels of counter-regulatory hormones
319
what the counter-regulatory hormones of insulin secretion
glucagon
catecholamines
cortisol
320
the excess ketone production in DKA is from the breakdown of
fat and protein
321
excess ketone production by the breakdown of fats and proteins can lead to
metabolic acidosis
322
what hormone is responsible for the shift of K+ into cells
insulin
323
explain the effect of insulin deficiency on K+ levels of patients
they can be normal or elevated due to extracellular migration
however, cells are being depleted of K+ --> hypokalemia
324
what is ketogenesis
it is the enhanced lipolysis of lipids in adipose tissue
325
ketogenesis leads to the release of ____ into the bloodstream
FA
326
FA are taken up from the blood by the liver where ______ of FA occurs
B oxidation
327
the B oxidation of FA occurs in the
liver
328
the B oxidation of FA results in the production of _____ from acetyl coA
ketone bodies
329
the B oxidation of FA results in the production of ketone bodies from
acetyl coA
330
how is acetone produced
spontaneous decarboxylation of acetoacetate
331
how is acetone eliminated from the body
slowly through urine
332
what is ketonemia
presence of abnormally high concentrations of ketones in blood
333
what is ketonuria
excretion of abnormally large amounts of ketone in urine
334
symptoms of DKA (3)
1. dehydration
2. fruity breath
3. CNS shit
335
DKA can eventually lead to
coma
shock
death
336
```
Diagnosis of DKA
give the corresponding values for
hyperglycemia
ketonemia
acidemia
anion gap
```
hyperglycemia >11 mM
ketonemia >3mM
acidemia pH<7.3
anion gap >12 mmol/L
337
what is an anion gap
difference between measured cations and anions
338
how is DKA treated
IV fluid replacement
IV insulin
potassium replacement
339
in the treatment of DKA, what IV fluids are used
isotonic initially
| hypotonic when Na concentration is fixed
340
in the treatment of DKA, when should insulin therapy be started
after fluid replacement
| only if K>3.3 mmol/L
341
if DKA is resolved through treatment, the patient starts to take
subcutaneous insulin
342
chronic hyperglycemia can be caused by
microvascular and macrovascular complications
343
microvascular complications involve the formation of ______ caused by prolonged (chronic) hyperglycemia and protein glycation
advanced glycation end-products (AGE)
344
microvascular complications involves the nonenzymatic binding of
glucose with amino groups ( m- terminal) of proteins
345
what causes the accumulation of AGEs
binding to structural and functional proteins causes permanent changes (resembles protein denaturation) --> alters fxn of protein
346
what is the receptor for AGEs
RAGE
347
effect of binding of AGE to its receptor on endothelial cells
altering intracellular signalling and gene expression which leads to the release of proinflammatory molecules and free radicals --> extracellular matrix degradation
348
effect of binding of AGE to its receptor on platelets
causing aggregation --> vascular proliferation
349
effect of binding of AGE to its receptor on vascular smooth muscle cells
uncontrolled proliferation
350
where in the body are RAGE located
epithelial cells
platelets
vascular smooth muscle
351
binding of AGE to its receptor on _____ leads to extracellular matrix degradation
epithelial cells
352
binding of AGE to its receptor on _____ leads to uncontrolled proliferation
vascular smooth muscle
353
binding of AGE to its receptor on _____ leads to vascular proliferation
platelets
354
what is the most common cause of chronic kidney failure
diabetic nephropathy
355
cause of diabetic nephropathy
causes kidney failure --> leads to unhealthy glomerulus where protein spills into urine due to damage at the capillary wall
356
what is the predictor of diabetic nephropathy
microalbuminuria (albumin in urine)
357
cause of diabetic retinopathy
changes in vessels of the eye
358
complication of diabetic retinopathy
exudates (lipoprotein leaks)
microaneurysms
hemorrhage
359
complications of diabetic retinopathy contribute to ischemia which leads to the activation of
hypoxia-induced factor (HIF)
360
The activation of HIF in diabetic retinopathy is due to
ischemia by complications of diabetic retinopathy which are:
exudates (lipoprotein leaks)
microaneurysms
hemorrhage
361
The activation of HIF in diabetic retinopathy leads to the formation of ___
new vessels
362
how will the new vessels formed by activation of HIF in diabetic retinopathy be affected by AGE
AGE makes them leaky again
363
symptoms of diabetic retinopathy
sudden and complete loss of vision
discoloured spots
blurred vision
364
diabetic neuropathy develops as a result of
AGEs leading to ischemia and nerve cell injury (stroke)
365
what are the 2 types of neuropathy
1. peripheral
| 2. autonomic
366
what does peripheral neuropathy affect
limbs (numbness, burning, pain)
367
what complication can arise from peripheral neuropathy
minor skin injuries may lead to serious infections because of the loss of sensation
368
what is autonomic neuropathy
damage of nerves including myelin degeneration
| it affects autonomic function
369
autonomic neuropathy is the damage to nerves involved in autonomic regulation of
autonomic regulation of BP, cardiac function, respiratory, urinary and GI systems
370
what does autonomic neuropathy affect
weight loss, erectile dysfunction, no sensations of heart attacks
** it affects autonomic function
371
how do macrovascular complications contribute to hyperglycemia
damages vascular endothelium, increases platelet aggregation, decreases thrombolysis, making it difficult to restore blood as well as promoting pro-inflammatory responses
372
how do macrovascular complications affect platelet aggregation
increases platelet aggregation,
373
how do macrovascular complications affect thrombolysis
decreases thrombolysis
374
macrovascular complications lead to
heart disease
stroke
peripheral vascular disease
375
what are the 3 main types of microvascular complications
1. diabetic nephropathy
2. diabetic retinopathy
3. diabetic neuropathy
376
what are the regions of the adrenal gland
1. zona glomerulosa
2. zona fasciculata
3. zona reticularis
4. medulla
377
what hormone is produced in the zona glomerulosa
mineralocorticoids --> aldosterone
378
what hormone is produced in the zona fasciculata
glucocorticoids --> cortisol
379
what hormone is produced in the zona reticularis
androgens --> DHEA
380
what hormone is produced in the medulla
catecholamines --> adrenaline and noradrenaline
381
cortisol can be made in the zona fasciculata and the
zona reticularis
382
androgens can be made in the zona reticularis and the
zona fasciculata
383
what hormones are produced by the ovaries
estrogens and progesterone
384
what hormones are produced by the testes
large amounts of androgens
385
in what part of the cell does steroid hormone synthesis occur
mitochondria
| ER
386
are steroid hormones lipid soluble?
yes
387
can steroid hormones be stored?
nope
388
adrenocorticoids are bound to _______ to prevent reentry into the cell
plasma proteins
389
where is cholesterol synthesised
liver
390
cholesterol is synthesised in the liver as an _____ molecule
amphiphatic
391
all steroids are synthesised from
cholesterol
392
all steroid are synthesised from cholesterol via what process
hydroxylation of steroid nucleus
393
what is the RLS of steroid synthesis
conversion of cholesterol to pregnenolone catalysed by cytochrome P450
this step requires NADPH and oxygen
394
what protein controls the uptake of cholesterol into the mitochondria
Star
395
what enzymes involved in steroid synthesis are found in the ER
3B-OH
delta 5,4 isomerase
17-OH
21-OH
396
what enzymes involved in steroid synthesis are found in the mitochondria
11B-OH
| 18-OH
397
conversion of cholesterol to pregnenolone catalysed by ______ . it also requires ______ and _____
cytochrome P450
| this step requires NADPH and oxygen
398
in steroid synthesis, pregnanalone is converted to
progesterone
399
conversion of pregnenolone to progesterone is catalysed bv
3B-OH
| delta 5,4 isomerase
400
3B-OH and delta 5,4 isomerase catalyses the conversion of
pregnenolone to progesterone
401
cytochrome P450 catalyses the conversion of
cholesterol to pregnenolone
402
describe aldosterone synthesis from progesterone
progesterone --> 11-deoxycorticosterone (21-OH)
11-deoxycorticosterone --> corticosterone (11B-OH)
corticosterone --> aldosterone (18-OH, aldosterone synthase)
403
describe cortisol synthesis from progesterone
progesterone --> 17 hydroxyprogesterone (alpha 17-OH)
17 hydroxyprogesterone --> 11-deoxycortisol (21-OH)
11-deoxycortisol --> cortisol (11B-OH)
404
which hormones are used in aldosterone synthesis
21-OH
11B-OH
18-OH, aldosterone synthase
405
which hormones are used in cortisol synthesis
alpha 17-OH
21-OH
11B-OH
406
how does hypersecretion of mineralocorticoids affect electrolytes
increases Na in ECF
K depletion
--> hypokalemia and hypertension
407
mineralocorticoids are released in response to
decreased ECF volume
| high K+ concentration
408
the secretion of mineralocorticoids stimulate the transcription of the Na/K pump by
increasing numbers of sodium pumps on the basolateral membrane of epithelial cells
** facilitates uptake of sodium and water from the tubular lumen
409
Na+ is reabsorbed in the kidney at the expense of K+ and H+. how does this affect ECF volume and electrolyte concentration
increase in ECF volume (dec BP)
decreased K+
INCREASED Na+
410
what parts of the nephron does aldosterone act
DCT
| collecting ducts
411
aldosterone is secreted by activation of
RAAS
412
RAAS activation promotes secretion of
aldosterone
413
what is the main function of glucocorticoids
inhibit anabolism and stimulate catabolism
414
how do glucocorticoids inhibit anabolism and stimulate catabolism
reverses insulin functions
| breakdown of muscle and aa uptake into liver for gluconeogenesis and lipolysis of adipose tissue
415
what is congenital adrenal hyperplasia (CAH)
autosomal recessive disorders of cortisol biosynthesis
416
CAH is caused by deficiency in which hormones
3B-OH
17 alpha-OH
21 alpha-OH
11B-OH
417
explain the effect of a deficiency of 3B-OH
no conversion of pregnenolone to progesterone and hence the pathway to all steroid hormones are affected --> salt excretion in urine and female-like genitalia
418
explain the effect of a deficiency of 17 alpha-OH
no conversion of progesterone to 17-hydroxyprogesterone
no androgens or cortisol can be produced but there will be high amounts of aldosterone secretion --> increased fluid retention --> hypertension and hypokalemia
female-like genitalia
419
explain the effect of a deficiency of 21 alpha-OH
no conversion of progesterone to 11-deoxycorticosterone and 11-deoxycortisol
no mineralocorticoids and no glucocorticoids but there is an increase in androgens --> masculinization of external genitalia in females and early sterilization in men
420
explain the effect of a deficiency of 11B-OH
no conversion of 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol
no mineralocorticoids and no glucocorticoids but there is an increase in androgens --> masculinization of external genitalia in females and early sterilization in men
increased production of deoxycorticosterone --> fluid retention (hypertension)
421
a protein shortage leads to
muscle wasting
poor healing
weakened skeleton
422
effects of an increase and a decrease of aldosterone
i - hypokalemia; hypertension
| d - hyperkalemia; salty urine; decreased BP and volume
423
effects of an increase and a decrease of cortisol
i - adrenal diabetes; fat digestion; decrease in protein
| d - hypoglycemia, increased ACTH, dark skin
424
effects of an increase and a decrease of androgens
i - male-like genitalia
| d - female like genitalia
425
In CAH, a deficiency in which enzymes cause female-like genitalia
deficiency of 3B-OH
| deficiency of 17 alpha-OH
426
In CAH, a deficiency in which enzymes cause masculinization
deficiency of 11B-OH
| deficiency of 21 alpha-OH
427
In CAH, a deficiency in which enzymes cause hypertension
deficiency of 11B-OH
| deficiency of 17 alpha-OH
428
what is the metabolic function of glucocorticoids
increases glucose concentration at the expense of proteins and lipids
- catabolism
429
what is the permissive function of glucocorticoids
enhances glucagon and catecholamines
430
what is the immune function of glucocorticoids
anti-inflammatory, decreases stress, and boosts immune response following tissue injury
- important of transplants
431
what are the factors which control glucocorticoid secretions (3)
1. CRH --> ACTH from corticotropin --> zona fasciculata --> cortisol --> CRH and ACTH (by negative feedback)
2. diurnal rhythm which acts on the hypothalamus to vary CRH secretion
- highest in morning, lowest at night
3. dramatic increases in stress increases CRH release
432
what is cushing's syndrome
cortisol hypersecretion
433
adrenal diabetes is caused by
excessive glucose (hyperglycemia)
434
clinical features of cushing's syndrome
extra glucose deposited as fat in face, abdomen and shoulder but thin otherwise
435
what is the significance of DHEA in males and in females
males - overpowered by testosterone
| female - governs androgen-dependent processes (pubic hair, growth spurts, sex drive)
436
in both sexes, the zona reticularis produces
estrogens
| androgens
437
what controls secretions of the adrenal cortex
ACTH
438
DHEA inhibits
GRH
439
the inhibition of GRH by DHEA inhibits
FSH and LH
440
do adrenal hormones feedback to the axis?
NOPE
441
hypersecretion of androgens may be caused by
tumour or defect in part of the cortisol pathway.
442
what is the effect of hypersecretion of androgens in newborn females
male type external genitalia
443
what is the effect of hypersecretion of androgens in adult females
secondary male characteristics
444
what is the effect of hypersecretion of androgens in prepubescent boys
early puberty but no sperm production
445
what is the effect of hypersecretion of androgens in adult males
overpowered by testosterone
446
If one adrenal gland is non-functional, will there be renal insufficiency? why?
nope
| the second one can take over
447
What is Addison's disease?
Primary adrenocortical insufficiency where all layers of the adrenal cortex are undersecreting due to an autoimmune disease that destroys cells of the adrenal cortex
There is a decrease in aldosterone and the cortisol
448
Explain the resultant aldosterone deficiency of Addison's disease
K retention --> hyperkalaemia --> disturbs cardiac rhythm (smooth muscle contraction)
Na depletion --> excessive urinary loss of sodium --> salty urine
Reduced ECF volume --> reduce in pressure --> hypotension, shock
449
Explain the resultant cortisol deficiency of Addison's disease
Poor response to stress
decrease in gluconeogenesis
hyperglycaemia
no ACTH negative feedback therefore increased ACTH release and darkening of skin
450
What is a secondary adrenocortical insufficiency?
Pituitary or hypothalamic abnormality only cortisol is affected.
451
What is hormones or affected by a primary adrenocortical insufficiency?
Aldosterone and cortisol
452
What is hormones or affected by a secondary adrenocortical insufficiency?
Cortisol only
453
What are chromaffin cells and where are they located?§
Modified sympathetic neurons which are part of the adrenal medulla (modified part of SNS)
454
What do chromaffin cells produce and how much (%)?
Adrenaline 80% and noradrenaline 20%
455
Do the axonal fibres of chromaffin cells terminate at the effector organ?
nope
456
the axonal fibres of chromaffin cells do not terminate at the effector organ. Release of Catecholamines is stimulated by....
Released directly into circulation upon stimulation by preganglionic fibres
457
Secretions of chemicals by preganglionic fibre is by the __NS
ANS
458
Adrenaline is produced exclusively by the
Adrenal Medulla
459
Noradrenaline is produced in far greater quantities by
SNS postganglionic fibers
460
What is the function of catecholamines?
Involved in the flight or fight response
461
Effects of catecholamines on heart, GI system and skeletal muscle
Increases stroke volume, heart rate, blood pressure and shifting blood to heart and skeletal muscles (vasodilation) and includes respiration
reduces digestive activity
inhibits insulin and stimulates glucagon secretion
462
Catecholamines inhibit
Insulin
463
Catecholamines stimulate
Glucagon
464
Secretions of the adrenal Medulla are controlled by
Sympathetic input into gland
465
Now you have to do REB endocrine 2
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