Endo MedEd BRS tutorial Flashcards
1
Q
What is the anterior pituitary derived from?
A
epithelial tissue
2
Q
What is the anterior pituitary controlled by?
A
hypothalamic parvocellular neurons
3
Q
How does the anterior pituitary work? eg thryoid hormone
A
1) hypothalamus releases TRH to the median eminence
2) TRH travels to anterior pituitary via portal circulation
3) TRH stimulates thyrotrophs
4) thyrotrophs make TSH that travel to thyroid gland to make thyroxine
4
Q
What are the 5 cells of the anterior pituitary?
A
1) somatotrophs
2) lactrotrophs
3) thyrotrophs
4) gonadotrophs
5) corticotrophs
5
Q
somatotrophs: hormone produced/releasing and inhibiting factor/ target organ and function?
A
growth hormone
growth hormone releasing hormone AND somatostatin inhibits
body tissues - GH works directly on tissues
6
Q
lactotrophs: hormone produced/releasing and inhibiting factor/ target organ and function?
A
prolactin
dopamine INHIBITS
lactation on breasts
7
Q
thyrotrophs: hormone produced/releasing and inhibiting factor/ target organ and function?
A
thyroid stimulating hormone (TSH)
thyrotrophin releasing hormone (TRH)
thyroxine from thryoid
8
Q
gonadotrophs: hormone produced/releasing and inhibiting factor/ target organ and function?
A
LH and FSH
gonadotrophin releasing hormones
testes in men
ovaries in females
9
Q
corticotrophs: hormone produced/releasing and inhibiting factor/ target organ and function?
A
ACTH
corticotrophin releasing hormone
adrenal cortex to make cortisol and aldosterone
10
Q
What hormone is in excess in acromegaly?
A
growth hormone AFTER puberty
11
Q
Symptoms of acromegaly?
A
macroglossia
large jaw
increased hand and feet size
sweatiness
headache
12
Q
What is the posterior pituitary dervied from?
A
neural tissue
13
Q
How is the posterior pituitary different to the anterior pituitary?
A
posterior is continuous w hypothalamus
14
Q
What 2 hormones does the posterior pituitary release?
A
arginine vasopressin
oxytocin
15
Q
What are the two-nucleus associated with posterior pituitary and what hormones do they make?
A
supraoptic (AVP)
paraventricular (oxytocin)
16
Q
How does the posterior pituitary work?
A
1) hypothalmic magnocellular neurons get excited
2) they release AVP or oxytocin
3) hormones diffuse out of posterior pituitary into the blood
17
Q
What does increases ADH do?
A
increases water reabsorption in kidney
AVP binds to V2 receptor
activates adenylate cyclase -> cAMP -> protein kinase A
causes aquaporin-2 to be inserted into apical membrane
water moves into cell then out through aquaporin-3 into the blood through basal membrane
water reabsorbed
causes vasoconstriction by acting on V1 receptor
less urine produced
18
Q
What are the 2 functions of oxytocin?
A
delivery of baby
milk ejection
19
Q
How does oxytocin cause delivery of baby?
A
uterus at parturition
myometrial cells contract
delivery of baby
20
Q
How does lactation work?
A
USES BOTH ANTERIOR AND POSTERIOR PITUITARY
Anterior pituitary makes prolactin that increases milk production from mammary gland.
Posterior pituitary makes oxytocin which causes contraction of myoepithelial cells -> milk ejection.
21
Q
What stimulates lactation?
A
mechanical stimulation of the nipple which leads to…
less dopamine for anterior
more oxytocin for posterior
22
Q
Where is the parathryoid gland found?
A
embedded in the thyroid gland
23
Q
What do the follicular cells contain?
A
nucleus
TSH receptors
24
Q
What occurs at the colloid?
A
iodination
T3/T4 made
25
Why during thyroid surgery hoarseness of patient voice a complication?
left recurrent laryngeal nerve runs close (near aortic arch asw) and can be damaged
26
How is thyroxine produced? (8 steps)
1) TSH binds to TSH receptor on thyroid follicular cells.
2) TSH receptor acts on nucleus of follicular cells to produce thyroglobulin and causes production of thyroid peroxidase.
3) Iodide is pumped from the follicular cell to the colloid.
4) TPO and hydrogen peroxide cause the iodination of thyroglobulin to creaate moniodtyrosine (MIT) and diiodotyrosine (DIT) bounded to thyroglobulin.
5) Coupling reaction occurs in colloid to form triiodothyronine (T3) and thyroxine (T4) bonded to thyroglobulin.
6) Thyroglobulin bonded to T3/T4 enters follicular cell.
7) Thyroglobulin is separated from T3/T4 by lysosomes.
8) T3 and T4 diffuse into the blood from follicular cells.
27
What enzyme converts T4 (thyroxine) into T3?
peripheral deiodinase enzyme
28
Is T3 active/inactive and what does it bind to?
active hormone
binds to TRE nucleus receptors to alter gene expression and create its effect
29
What are the 3 main plasma proteins that transport thyroxine?
thyroid binding globulin (TBG)
albumin
prealbumin
30
What are the 3 functions fo the thyroid hormone?
growth and bone formation
CNS maturation
raises glucose production, lipolysis, protein synthesis, cardiac output
31
What is hypothyroidism?
failure of thyroid gland to make thyroxine
32
What are the most common causes of hypothyrodism?
Hashimoto thyroiditis
thyroidectomy
33
What are the symptoms of hypothyrodism?
WHOLE BODY SLOWING DOWN AND BECOMING TIRED AND COLD
fatigue
goitre
weight gain
slowed heart rate, weakness
low libido
hair loss
34
What are the TSH and T3/T4 levels in primary hypothyroidism?
high TSH
low T3/T4
35
What are the most common causes of hyperthyroidism?
Graves disease
toxic nodule
multinodular goitre (bumpy)
36
What are the symptoms of hyperthyrodism?
WHOLE BODY SPEEDING UP AND BECOMING EXCITED SWEATY AND HOT
nervousness/irritability
weight loss
shaking hands
increased heart rate, high bp
goitre
37
What are the TSH and T3/T4 levels in primary hyperthyroidism?
high T3/T4
low TSH
38
What are the triad of high yield symptoms in Graves' disease?
smooth goitre
exophthalmos
pretibial myxedema (swelling of shins)
39
What is the arterial and venous supply of both adrenal glands?a
R and L adrenal glands supplied by R and L adrenal arteries from ABDOMINAL AORTA.
R adrenal gland vein drains into IVC.
L adrenal gland vein drains into L renal vein.
40
What is the adrenal gland made up of?
adrenal cortex
adrenal medulla
41
What does the adrenal cortex make?
corticosteroids
42
What does the adrenal medulla make?
catecholamines (adrenaline and noradrenaline)
43
What is the adrenal cortex made up of?
zona glomerulosa (aldosterone)
zona fasciculata (cortisol)
zona reticularis (cortisol)
44
How does aldosterone increase bp and blood volume?
stimulates Na+ reabsorption
stimulates K+ and H+ secretion
leads to the reabsorption of water
raising blood volume and bp
45
How does the renin angiotensin work?
1) Decreased renal perfusion pressure due to low bp and decreased sodium in the blood detected by macula densa cells.
2) Leads to increased renal SNS stimulating JGA (juxtaglomerular apparatus) cells.
3) JGA cells stimulate extraglomerular cells to make renin.
4) Renin cleaves angiotensinogen made from the liver to angiotensin I.
5) Angiotensin I is converted to angiotensin II but ACE receptors in lungs.
6) Angiotensin II stimulates zona glomerulus to create aldosterone.
46
What is Conn's syndrome?
tumour of zona glomerulosa making TOO MUCH ALDOSTERONE
metabolic alkalosis
hypertension and hypokalemia
47
How would you diagnose Conn's syndrome?
low renin to aldosterone ratio
(XS aldosterone -> high BP -> less renin made)
48
What is used for the management of Conn's syndrome?
spironolactone and eplerenone both MR receptor antagonists
spironolactone prevents Na+ reabsorption and K+ excretion in kidney -> reduced bp
49
What are the side effects of spirnolactone?
menstrual disturbances (+ progesterone receptor)
gynecomastia (- androgen receptor)
50
What is cortisol regulated by?
ACTH
51
What is cortisol involved in?
glucose production
fat metabolism
protein breakdown
boost glucagon and catecholamines
52
What kind of rhythm does cortisol have?
circadian (high in morning, low when you sleep)
53
What is Addison's diease?
primary adrenal failure
54
What are causes of adrenal failure?
surgery (removal of adrenal gland)
autoimmune
TB
congenital adrenal hyperplasia
55
What are the symptoms of Addison's disease?
increased pigmentation
autoimmune vitiligo
low bp (due to low aldosterone)
low blood glucose (due to low cortisol)
salt loss
56
Why do patients with Addison's disease have a good tan?
Pro-opio-melanocortin (POMC) is precursor of ACTH and MSH.
We need more ACTH, so more POMC is broken down into ACTH and MSH.
MSH causes the tan.
57
What is Cushing's syndrome?
excess cortisol
58
What are the 4 main causes of Cushing's syndrome?
too much oral steroid medication
cushing's disease (pituitary adenoma)
ectopic ACTH (lung cancer)
adrenal adenoma
59
What are the symptoms of Cushing syndrome?
thin skin
myopathy
obesity
diabetes
hypertension
immunosuppression
moon face
striae
60
How can you diagnose Cushing syndrome?
low dexamethasone suppression test: no suppression of cortisol
high 24h urine and blood diurnal cortisol levels
61
What is used to manage Cushing syndrome?
metyrapone (11 beta hydroxylase inhibitor)
side effects of hypertension and hiurtisim
ketoconazole (17 alpha hydroxylase inhibitor)
can cause liver damage so monitor LFTS
used to control symptoms prior to surgery/after radiotherapy
62
What is the surgical management of Cushing syndrome?
removal of organ causing raised cortisol (eg adrenal gland, pituitary, lung cancer)
63
What are phaeochromocytomas?
tumour arising from adrenal medulla secreting adrenaline and noradrenaline
64
What is used as the mangement for phaeochromocytomas?
alpha blocker
then beta blocker (to reduce heart rate)
then surgery
65
When do you suspect a phaeo?
young patient hypertension resistant to treatment
episodic hypertenion on abdominal palpitation
66
What 3 hormones are involved in the regulation of calcium?
vit D
parathyroid hormone (PTH)
calcitonin
67
Which hormones increase plasma calcium concentration? And where do they act on? (3)
vit D and PTH
act on bone, kidney and gut
68
Which hormone decreases plasma calcium concentration?
calcitonin secreted by thyroid parafollicular cells
ACUTE effect only
69
Where is 99% of calcium found in the body? And in what form?
skeleton and teeth
calcium hydroxyapatite crystals
70
What is bound calcium bound to? Is it biologically active or inactive?
INACTIVE makes up 55% of extracellular calcium
bound to plasma proteins
or anions (bicarbonate, phosphate, lactate)
71
Is unbound calcium biologically active or inactive?
ACTIVE makes up 45% of extracellular calcium
72
What are the 2 types of vit D?
ergocalciferol (vit D2) -> comes from plant consumption
cholecalciferol (vit D3) -> comes from animal consumption and yolks/oily fish
73
How is vit D produced in the skin?
1) UV radiation gets through the skin.
2) Changes 7-dehydroxycholesterol to pre-vitamin D3 which becomes vit D3.
3) Vit D3 enters circulation and travels to the liver.
4) 25-hydroylase converts vit D3 into 25(OH)cholecalciferol (INACTIVE)
5) Travels to kidneys
6) 1-alpha-hydroxylase converts 25(OH)cholecalciferol to 1,25(OH)cholecalciferol (aka CALCITROL which is ACTIVE).
74
What is the active form of vit D?
calcitriol
75
How does calcitriol regulate its own synthesis?
by decreasing transcription of 1-alpha-hydroylase in a negative feedback loop to avoid hypercalcaemia
76
Where is PTH made?
chief cells in the 4 parathyroid glands
77
When is PTH secreted?
in response to changes in serum calcium concentrations
78
What are the changes in serum calcium concentration detected by?
G-protein coupled calcium receptors on chief cells (CaSR - calcium sensing receptor)
79
Where are the 4 parathyroid glands embedded?
posterior side of each of the two lobes of thyroid gland
80
What happens when there is an increased calcium conc in plasma?
sensed by CaSR on chief cells
LESS PTH secretion
81
What type of calcium is hormonally regulated?
only extracellular calcium
82
What is the major role of calcitriol?
GUT increase of calcium and phosphate absorption
BONES increases calcium reabsorption
KIDNEYS increases calcium and phosphate reabsorption
83
What does PTH act on? Directly/indirectly?
Bones directly - increases calcium reabsorption
Kidneys directly
Gut indirectly
84
What are the effects of PTH on kidneys?
increases calcium reabsorption
increases phosphate excretion
increases 1-alpha-hydroxylase activity
85
What are the effects of PTH on gut?
PTH having upregulated renal 1-alpha-hydroxylase, there is more calcitriol which directly acts on the gut to
increase calcium absorption
increase phosphate absorption
86
Does phosphate loss from kidney outweigh increase absorption and reabsorption from gut and kidney?
yes due to calcitriol
87
Overall, what are the effects of PTH on serum calcium and phosphate concentration?
increases serum calcium conc
decreases serum phosphate
88
What does PTH do to bones?
1) PTH binds to PTHR on osteoblasts.
2) Osteoblasts then express osteoclast activating factors (Eg RANKL).
3) Osteoblasts become osteoclasts.
4) Osteoclasts perform bone resorption -> mobilising calcium and increasing serum calcium conc.
Not good for long term bone health -> weakness and osteoporosis
89
What does calcitriol do to bone?
1) Calcitriol binds to calcitriol receptor on osteoblasts.
2) Upregulates OAFs (eg RANKL).
3) Osteoblasts converted to osteoclasts.
4) Osteoclasts perform bone resorption -> mobilising calcium and increasing serum calcium conc.
90
Does PTH and calcitriol effects depend on calcium?
PTH no
Calcitriol yes
91
What happens in normal/high calcium conc with calcitriol?
calcitriol promotes bone formation and deposition of calcium
osteoblast action predominates
92
How is PTH production regulated?
PTH increases serum calcium but that is not wanted indefinitely.
Negative feedback:
1) CaSR on chief cells of parathyroid glands stop the production of PTH with increasing calcium conc in serum.
2) Calcitriol receptors on chief cells of parathyroid glands stop production of PTH with increasing calcitriol conc.
93
What is calcitonin secreted by?
thyroid parafollicular cells upon detection of increased calcium conc
94
What is the function of calcitonin? How does it do it? (2)
reduce serum calcium conc
increases renal calcium excretion
decreases osteoclast activity
95
What 3 hormones regulates phosphate?
1) calcitriol - increases phosphate absorption in gut and reabsorption in kidney
2) FGF23
3) PTH
96
How does FGF23 regulate phosphate?
blocks Na/PO4 co-transporter on apical membrane of cells of proximal convoluted tubule of nephron
blocks actions of calcitriol -> increases phosphate excretion
97
How does PTH regulate phosphate?
blocks Na/PO4 co-transporter on apical membrane of cells of proximal convoluted tubule
reduced phosphate reabsorption and increases phosphate excretion
98
What are the signs and symptoms of hypocalcaemia?
CATS go numb
Convulsions
Arrhythmias
Tetany - muscle contracts and cannot relax properly
Paraesthesia in hands, mouth, feet and lips
99
What are the 2 tests for hypocalcemia and tissue over-excitability?
CHVOSTEK'S SIGN
tap facial nerve just below zygomatic arch
+ve response = twitching of facial muscles
indicated neuromuscular irritability due to membrane over-excitability due to hypocalcaemia
TROUSSEAU'S SIGN
evident carpopedal spasm upon inflation of BP cuff for several minutes
100
What are the 5 causes of Vit D deficiency?
1) malabsorption/ dietary insuficiency (less vit D2 and D3 from diet)
2) inadequate sun exposure
3) liver disease
4) renal disease
5) vit D receptor defects (rare)
101
What are the causes of hypocalcaemia?
low PTH levels
vit D deficiency
102
What are the causes of low PTH levels (hypoparathyroidism)?
surgical - thyroidectomy
autoimmune
Mg deficiency
congenital (very rare)
103
What are the consequences of vit D deficiency?
rickets - lack of bone mineralisation by calcium in children due to vit D deficiency. soft bendy bones.
osteomalacia - increased fractures and proximal myopathies
104
What happens to membrane excitability in hypercalcaemia?
slows everything down
decreased membrane excitability
105
What are the symptoms of hypercalcaemia?
STONES, MOANS AND PSYCHIC GROANS
stones - calcium excreted through kidneets. results in nephrocalcinosis (kidney stones).
moans - atonal muscles decrease peristalsis = constipation, dyspepsia and pancreatitis
psychic groans - CNS effects of fatigue, depression, impaired concentration
106
What are the 3 types of diabetes mellitus?
T1DM
T2DM
MODY maturity onset diabetes of the young
107
What do delta-cells of islets of langerhans make?
somatostatin and pancreatic polypeptide
108
What is the function of somatostain?
inhibits/blocks both insulin and glucagon production
109
What are other ways in which insulin production is stimulated? other than beta cells
amino acids and some GI hormones after a meal stimulate insulin
PNS activity (rest and digest) stimulates insulin
110
What ways is too much insulin being released prevented?
glucagon prevents overshoot
SNS (fight or flight that needs glucose) inhibits insulin release via alpha adrenergic pathways
somatostatin inhibits insulin release
111
How does the insulin get into cells?
1) Insulin binds to alpha-subunit of insulin receptor located on extracellular domain.
2) Induces a conformational change in tyrosine kinase domains of beta-subunits.
3) Mobilisation of GLUT4 receptors on the cell surface membrane.
112
Where are insulin receptors located?
skeletal muscle
adipocytes
113
How do beta cells release insulin?
1) Beta cells detect glucose with GLUT2 receptors.
2) Allows glucose to pass freely into cell.
3) Glucose converted to G6P by hexokinase IV which is then metabolised to ATP.
4) Increasing blood glucose = increased beta-cell ATP.
5) Blocks K+ channels with K+ accumulating in cell.
6) Opens up voltage-gated Ca2+ channels, massive influx of Ca.
7) Increased insulin vesicle exocytosis.
114
In what form is insulin formed in beta cells?
pro-insulin
115
How does pro-insulin become insulin?
proteolytic cleavage to form insulin and C-peptide
116
How is insulin levels measured in blood?
measure C-peptide instead of insulin due to instability of assay while measuring insulin
= direct reflection since it is a twin product of cleavage of pro-insulin
117
Why is measuring C-peptide levels better esp for people with diabetes?
people w diabetes undergo progressive loss of pancreatic beta cells
lose more and more endogenous insulin production
impossible to distinguish between analogue and endogenous insulin
C-peptide entirely unaffected by analogue insulin - gives a direct measurement of degree of endogenous insulin production
118
Why is insulin release after oral glucose intake much higher than after intravenous glucose intake? INCRETIN EFFECT
GI hormones (GLP-1 and GIP) stimulate insulin release from beta cells
119
What is GLP-1?
Glucagon like peptide-1
gut hormone secreted in response to nutrients in gut by L-cells
stimulates insulin release
suppresses glucagon
120
What are the effects of GLP-1?
increases satiety
suppresses appetite
121
What is GLP-1 used for treating?
T2DM
short half-life due to breakdown of dipeptidyl peptidase-4
found in injection medicine ozempic
