Endocrinology Flashcards
1
Q
Hormone
A
A substance secreted directly into the blood by specialised cells
Present in only minute concentrations in the blood and bind specific receptors in target cells to influence cellular reactions
2
Q
Endocrine organs
A
Heart
Liver
Fat
Kidney
Skin
Intestines
3
Q
Endocrine glands
A
Hypothalamus
Pituitary
Thyroid
Parathyroid
Adrenals
Pancreas
Ovary/testes
4
Q
Endocrine glands
A
Hypothalamus
Pituitary
Thyroid
Parathyroids
Adrenals
Pancreas
Ovary/testes
5
Q
3 hormone structures
A
Steroid
Peptide
Thyroid hormones
6
Q
What are all steroid hormones synthesised from
A
Cholesterol
7
Q
What are Catecholamines synthesised from
A
Tyrosine
8
Q
Storage of peptide hormones
A
Day
9
Q
Storage of steroid hormones
A
Min-hour
10
Q
What is important for the production of thyroid hormone
A
Iodine
11
Q
Substrates for thyroid hormone
A
Thyroglobulin
Tyrosine
12
Q
Storage of thyroid hormones
A
Weeks
13
Q
Storage of Catecholamines hormones
A
Day
14
Q
Secretion of peptide hormones
A
Exocytosis
15
Q
Secretion of steroid hormones
A
Diffusion
16
Q
Secretion of thyroid hormones
A
Proteolysis
17
Q
Secretion of Catecholamines hormones
A
Exocytosis
18
Q
Binding protein required for peptide hormones?
A
Some
19
Q
Binding protein required for steroid hormones?
A
All
20
Q
Binding protein required for thyroid hormones?
A
Yes
21
Q
Binding protein required for Catecholamines hormones?
A
No
22
Q
Time to action of peptide hormones
A
Min-hour
23
Q
Time to action of steroid hormones
A
Hour-day
24
Q
Time to action of thyroid hormones
A
Day
25
Time to action of Catecholamines hormones
Seconds
26
Half life of peptide hormones
Min-hour
27
Half life of steroid hormones
Hours
28
Half life of thyroid hormones
Days
29
Half life of Catecholamines hormones
Sec-min
30
How do hormones exert their effect
Cell surface receptors
Intracellular receptors
31
Cell surface receptors
G protein coupling
32
Basic actions of thyroid hormone
Basal metabolic rate
Growth
33
Basic actions of parathyroid
Ca2+ regulation
34
Basic actions of cortisol
Glucose regulation
Inflammation
35
Basic actions of aldosterone
Blood pressure
Na_ regulation
36
Basic actions of Catecholamines
Blood pressure
Stress
37
Basic actions of oestradiol
Menstruation
Femininity
38
Basic actions of testosterone
Sexual function
Masculinity
39
Basic actions of insulin
Glucose regulation
40
Basic actions of ANP
Na+ regulation
41
Basic actions of vitamin D
Ca2+ regulation
42
How to measure hormone concentrations
Bioassays
Immunoassays
Mass spectrometry
43
Anterior pituitary hormone
ACTH
TSH
GH
LH/FSH
PRL
44
Basic actions of ACTH
Regulation of adrenal cortex
45
Basic actions of TSH
Thyroid hormone regulation
46
Basic actions of GH
Growth
Metabolism
47
Basic actions of LH/FSH
Reproductive control
48
Basic actions of PRL
Breast milk production
49
Posterior pituitary hormones
ADH
Oxytocin
50
Basic actions of ADH
Water regulation
51
Basic actions of oxytocin
Breast milk expression
52
Available treatment for thyrotoxicosis
Destruction of thyroid tissue using radioiodine (131I)
Antithyroid drugs to block hormone synthesis
Partial surgical ablation of thyroid
53
Drugs used to treat functioning pituitary tumours
Somatostatin analogues
Dopamine agonists
GH receptor antagonists
54
How to treat under active glands
Hormone replacement therapy
55
Location of adrenal gland
Sit on supramedial aspect of kidneys
56
Are the adrenal glands Intraperitoneal or retroperitoneal
Retroperitoneal
57
Blood supply to adrenal glands
Superior, middle and inferior adrenal arteries
58
What is the superior adrenal artery a branch of
Inferior phrenic
59
What is the middle adrenal artery a branch of
Abdominal aorta
60
What is the inferior adrenal artery a branch of
Renal artery
61
What does the right adrenal gland drain into
Directly into IVC
62
What does the left adrenal gland drain into
Left renal vein and then IVC
63
Which nerve innervates the adrenal gland
Splanchnic nerve
64
Which type of hormones are produced in the adrenal medulla
Catecholamines
65
Which hormones are produced in the adrenal medulla
Adrenaline - 80%
Noradrenaline- 20%
66
What is Catecholamines synthesis dependent on
Cortisol levels
67
What system is the adrenal medulla part of
Autonomic nervous system
- specialised ganglia used ACh s a neurotransmitter
68
Noradrenaline receptors
Alpha
69
Adrenaline receptors
Beta
70
Effects of hormones released by adrenal medulla
Gluconeogenesis
Lipolysis
Tachycardia
Redistribution of circulatory volume
71
Which type of hormone is produced in the Zona glomerulosa of adrenal gland
Mineralocorticoids
72
Which hormone does the zona glomerulosa of the adrenal gland
Aldosterone
73
What triggers secretion of aldosterone
Renin
74
Cortisol can act on,,,…..
Mineralcorticoid receptors
75
Pre-receptor regulation of cortisol is by
11B-HSD2
76
Effects of hormones released by zona glomerulosa of adrenal gland
Salt balance in the kidneys, colon, pancreas, salivary glands and sweat glands
- in DCT increases ENaC expression apically and Na/K ATPase expression basolaterally
77
Which type of hormones does the zona fasciculata of the adrenal gland produce
Cortisol
Corticosterone
78
What does the hypothalamus release - cortisol
Corticotropin releasing hormone CRH
79
Action of corticotropin releasing hormone
Acts on anterior pituitary to stimulate ACTH release
80
Action of ACTH
Binds to GPCRs (Gs subunits) in zona fasciculata of the adrenal gland
Protein kinase A stimulates synthesis of cholesterol
Cholesterol converted to pregnenolone in mitochondria
Further processing in endoplasmic reticulum
Conversion to cortisol in mitochondria
81
Precursors of cortisol
Cholesterol
Pregnenolone
Cortisol
82
Cortisol in blood
90% bound to corticosteroid-binding globulin
5% bound to albumin
5% free
83
Stress and corticosteroid-binding globulin
Stress promotes the release from CBG which means more is free and can be utilised
84
Effects of cortisol
Increased energy mobilisation
Increased amino acid generation - muscle catabolism
Vascular tone- promotes shunt to periphery
Salt and water balance
Immune suppression
Inhibits growth and reproduction
85
Permissive effect
Allows another action to take place eg vasoconstriction via Catecholamines
86
Diurnal rhythm of cortisol
High levels in morning and early afternoon
87
Negative feedback and cortisol
Cortisol acts on hypothalamus and pituitary
88
Which type of hormones are produced in the zona reticularis of adrenal gland
Androgens
89
Most abundant androgen produced by zona reticularis of adrenal gland
DHEA
90
Most potent androgen produced by the zona reticularis of adrenal gland
Testosterone
91
Androgens produced by the zona reticularis of adrenal gland
DHEA
Testosterone
Androstenedione
92
What regulates androgen release from zona reticularis of adrenal gland
ACTH
93
Androstenedione in women
Converted to testosterone in peripheral tissues
94
3 glands involved in cortisol release
Hypothalamus
Pituitary
Adrenal gland
95
3 hormones involved in cortisol release
CRH
ACTH
Cortisol
96
What can trigger release of CRH from hypothalamus (eventually cortisol)
Stress
Cytokines
Diurnal rhythm
97
Location of thyroid gland
Anterior neck between C5 and T1
98
Structure of thyroid gland
2 lobes connected by isthmus
99
Arterial supply to thyroid gland
Superior and inferior thyroid glands
100
What is the superior thyroid artery a branch of
1st branch of external carotid artery
101
What is the inferior thyroid artery a branch of
Subclavian artery
102
What does the superior thyroid artery supply
Superior and anterior portions
103
What does the inferior thyroid artery supply
Posterior and inferior portions
104
What drains the thyroid gland
Middle and inferior thyroid veins
105
Size and weight of pituitary gland
Pea-sized
Weighs 0.5g
106
What does the pituitary gland respond to
Hypothalamus
107
Blood supply to anterior pituitary gland
No arterial blood supply
Receives blood through portal venous circulation from hypothalamus
108
Which hormones released from the anterior pituitary are glycoproteins
TSH
FSH
LH
109
Which hormones released from the anterior pituitary are polypeptides
ACTH
GH
Prolactin
110
Name of portal system between hypothalamus and pituitary gland
Hypothalamic-hypophyseal portal system
111
Which hormone released by the hypothalamus stimulates the release of TSH
TRH -thyrotopin releasing hormine
112
Which hormone released by the hypothalamus stimulates the release of ACTH
Corticotropin releasing hormone
113
Which hormone released by the hypothalamus stimulates the release of FSH
GnRH
114
Which hormone released by the hypothalamus stimulates the release of LH
GnRH
115
Which hormone released by the hypothalamus stimulates the release of growth hormone
GH releasing hormone
116
What inhibits the release of prolactin
Dopamine
117
What inhibits the release of growth hormone
Somatostatin
118
What stimulates growth hormone
Low glucose
Exercise
Sleep
119
What suppresses growth hormone
Hyperglycaemia
120
What mediates the effects of growth hormone
GH and IGF1
121
Actions of growth hormone
Linear growth in children
Acquisition of bone mass
Stimulates - protein synthesis, lipolysis, glucose metabolism
Regulation of body composition
Psychological well-being
122
What regulated thyroid hormone levels
Negative feedback loop between TSH and thyroxine
123
Where is prolactin synthesised
Lactotrophs
124
Prolactin function
Levels increase during pregnancy and breast feeding as important for lactation
Inhibits gonadal activity through central suppression of GnRH
125
Physiological hyperprolactaemia
Physical or psychological stress
Post seizure
Greater in women
Rarely exceeds 850-1000 mU/L
PRL has circadian rhythm with peak during sleep
126
Embryology of pituitary gland
Anterior and posterior glands develop from different tissues before joining together
127
Embryology of anterior pituitary
Protrusion of ectoderm from Rathke’s pouch grows upwards to form anterior pituitary (adenohypophysis)
128
Embryology of posterior pituitary
Neuronal (neurohyophysis)
Extension of neural components of hypothalamus
129
What causes the secretion of hormone of hypophysiotropic hormones
Generation of AP in neurons of hypothalamus
130
What do all pituitary and hypothalamic hormones act on
G-protein coupled receptors (GPCRs)
131
Long-looped negative feedback
Hormone secreted by 3rd endocrine gland exerts negative feedback
132
In which cells is FSH/LH produced
Gonadotrophs
133
Function of FSH
Stimulates germ cell development and release of hormones
134
In which cells is ACTH produced
Corticotrophs
135
In which cells is TSH produced
Thyrotrophs
136
Function of TSH
Stimulates thyroid to secrete T3 and T4– increases metabolism
137
Main hormone involved in negative feedback of HPG axis
Inhibin (and progesterone/ oestrogen or testosterone)
138
In which cells is prolactin produced
Lactotrophs
139
In which cells is GH produced
Somatotrophs
140
What nerves innervate the thyroid gland
Sympathetic trunk
141
T4
Thyroxine (4 iodine)
142
T3
Triiodothronine (3 iodine)
143
What converts T4 to T3
Deiodinase enzymes
144
What 2 iodine-containing molecules does the thyroid gland produce
T4- thyroxine
T3 - triiodothronine
145
Synthesis of thyroid hormone
TSH binds to TSH receptors
Iodide actively co-transported across basolateral membrane via NIS (Na/I symporter)
Iodide then diffuses to apical membrane and transported into colloid
Colloid contains thyroglobulin which binds to the oxidised iodide (iodine) via thyroid peroxidase
Tyrosine bind to 1 or 2 iodine molecules resulting in monoiodotyrosine and diiodotyrosine
When thyroid stimulates T1 and T2 are cleaved and joined to create T3 or T4
Proteolysis of thyroglobulin released T3 and T4
146
Which form of thyroid hormone is biologically active
T3
147
Is T4 or T3 more abundant
T4
148
Where is thyroglobulin stored
Colloid - protein-rich material in follicles
149
What catalyses reaction between iodine and thyroglobulin
Thyroid peroxidase
150
How is iodide actively transported across basolateral membrane
Na/I symporter
151
Function of TSH
Acts on thyroid gland to secrete T3 and T4
Increased protein synthesis in follicular cells
Increased DNA replication and cell division
Increases quantity of rough ER
152
How is T4 converted to T3
Mono-deiodination catalysed by deiodinase enzymes
153
When does the thyroid gland begin to develop
Weeks 3-4
154
Embryology of thyroid gland
At weeks 3-4 , glands appear as an epithelial proliferation at base of pharynx
Glands then migrate down the thyroglossal duct to below larynx
155
When do the thyroid glands begin to produce thyroxine
18-20 weeks
156
Actions of thyroid hormone
Increases metabolic rate
Brain maturation
157
How does T3 increase metabolic rate
Stimulates carbohydrate absorption from small intestine and increases fatty acid release from adipocytes
- energy supports activity of Na/K ATPases , increasing heart production—> temperature homeostasis
158
How is T3 involved in temperature homeostasis
Increasing metabolic rate
159
T3 and growth and development
Required for normal production of growth hormone
Involved in nervous system development
160
How is T3 involved in nervous system development
Formation of axon terminals
Production of synapses
Growth of dendrites and dendritic extensions
Formation of myelin
161
Location of parathyroid glands
Posterior aspect of lateral lobes of thyroid
162
Number of parathyroid glands
2 superior
2 inferior
163
Arterial supply to parathyroid glands
Inferior thyroid artery- from subclavian artery
164
Drainage of parathyroid glands
Into thyroid plexus
165
Innervation of parathyroid gland
Sympathetic trunk- only vasomotor
166
Function of parathyroid gland
Regulates calcium and phosphate levels
167
Function of parathyroid hormone
Increase calcium reabsorption in DCT
increases intestinal calcium absorption (via activation of vitamin D)- duodenum and Jejunum
Increases calcium release from bone (stimulates osteoclast activity)
Decreases phosphate reabsorption
Bind to GPCRs
168
What inhibits PTH transcription
1,25D3
169
What inhibits PTH translation
Increased serum calcium
170
What stimulates secretion of parathyroid hormone
Low calcium
High phosphate
171
How does PTH increase instestinak calcium absorption
Activation of vitamin D
172
Where does PTH increase intestinal calcium absorption
Duodenum
Jejunum
173
How does PTH increase calcium release from bone
Stimulates osteoclasts actiivty
174
Hyperparathyroidism
Raised serum PTH
175
Primary hyperparathyroidism
Parathyroid tumour
Causes hypercalcaemia and low serum phosphate
Loss of negative feedback from hypercalcaemia
Treatment is surgery
176
Secondary hyperparathyroidism
Renal disease
Increased phosphate and decreased activation of vitamin D
Treat with phosphate binders or vitamin D analogues
177
Tertiary hyperparathyroidism
Long-standing secondary hyperparathyroidism leads to irreversible parathyroid hyperplasia
Usually seen when renal disease is corrected, transplantation
Treatment is surgery
178
Parathyroid hormone response to hypercalcaemia
Decreases PTH secretion
179
Decrease PTH secretion in response to hypercalcaemia
Increases calcitonin —> Decreases bone resorption
Decrease urinary phosphate and 1,25D3 production
Increase urinary calcium
Decrease calcium and phosphate absorption
Decreases serum calcium
180
Parathyroid hormone response to hypocalcaemia
Increases PTH secretion
181
Increased PTH secretion in response to hypocalcaemia
Increases bone resorption
Increases urinary phosphate
Increases 1,25D3 production
Decreases urinary calcium
Increases calcium and phosphate absorption
Increases serum calcium
182
1,25D3
Affects absorption of calcium and phosphate in small intestine
183
Where is ADH synthesised in posterior pituitary
Supraoptic nucleus
184
What causes release of ADH
Increased osmotic pressure in blood
Decreased blood volume
Trauma/stress
Increased PCO2
Decreased PO2
185
Effects of ADH
Increased AQP2 expression in cortical collecting duct cells
Vasoconstriction of smooth muscle cells around blood vessels
186
Where is oxytocin synthesised in posterior pituitary
Paraventricular nucleus
187
What stimulates release of oxytocin
Nipple stimukation
188
Effects of oxytocin
Constriction of muscles of breast to promote milk ejection
Uterine smooth muscle contractions
Promotion of labour
189
What type of hormone does the posterior pituitary produce
Peptide
190
How are the hypothalamus and posterior pituitary connected
Via neurons through the infundibulum- hypophyseal system
191
Exocytosis from posterior pituitary is via…
Herring bodies
192
What inhibits ADH release
Caffeine
Alcohol
193
What stimulates ADH response
High osmolality
Low blood volume
Nausea
Vomiting
Stress
Exercise
194
ADH V1a receptors location
Vascular smooth muscle
Platelets
Hepatocytes
Myometrium
195
ADH V1a receptors function
Vasoconstriction, myocardial hypertrophy
Platelet aggregation
Glycogenolysis
Uterine contraction
196
ADH V1b receptors location
Anterior pituitary
197
ADH V1b receptors function
ACTH release
198
ADH V2 receptors location
Basolateral membrane collecting tubule
199
ADH V2 receptors function
Insertion of AQP2 water channels into apical membrane
Induction of AQP2 synthesis
200
Types of ADH receptors
V1a
V1b
V2
201
Osmolality
Concentration of particles per kilo of fluid
202
What molecules affect osmolality
Sodium, potassium, chloride, bicarbonate, urea and glucose
Alcohol , methanol, polyethylene glycol or mannitol
203
Normal osmolality
282-295 mOsmol/kg
204
When calculating plasma osmolality why do you x2 Na+
Accounts for anions associated with Na+
205
Why is there a 0-10 mOsmol/kg gap between measures and calculated plasma osmolality
Higher usually due to alcohol
206
Osmotic threshold for ADH release and pregnancy
Decreased
Thirst also decreased
207
What causes plasma ADH concentrations to increase
Age
Thirst blunting
Decreased renal concentrating ability
Decreased fluid intake
208
Polyuria
Large volumes of urine
209
Polydypsia
Large volumes of drinking water
210
Causes of ADH deficiency
Destruction of hypothalamus
Interruption of connection of hypothalamus to pituitary
211
What is the precursor for all adrenal steriodogenesis
Cholesterol
212
Corticosteroids structure
Cyclopentanoperhydrophenanthrene structure
3 cyclohexane rings
Single cyclopentane ring
213
Mechanism of corticosteroids
Lipid soluble
Bind to specific intracellular receptors
Alter gene transcription directly or indirectly
214
Classification of steroids
Pregnane derivatives - 21 carbons, progesterone and corticoids
Androstane derivatives- 19 carbons, androgens
Estrane derivatives - 18 carbons , oestrogens
215
What stimulates corticosteroid synthesis
ACTH
216
What can cortisol bind to
Mineralcorticoid receptor and glucocorticoid receptors
- excess binding to MR = Cushing disease
217
Actions of glucocorticoids
Increase glucose mobilisation - gluconeogenesis, increased lipolysis
Maintenance of circulation- vascular tone, salt and water balance
Immunomodulation- dampen immune response
218
Transport of glucocorticoids
90% bound to corticosteroid-binding globulin CBG
5% bound to albumin 5% free
219
What regulates glucocorticoid synthesis
ACTH (and CRH) action
Diurnal rhythm
Stress
Illness
220
How does adenocorticotropic hormone regulate glucocorticoid synthesis
Acutely stimulates cortisol release
Stimulates corticosteroid synthesis (and capacity)
CRH stimulates ACTH release
Negative feedback of cortisol on CRH and ACTH production
221
What type of glucocorticoid is bioavaible
‘Free’
222
Action of Mineralcorticoids
Effect on pancreas, sweat glands, salivary glands, colon and kidney to increase sodium resorption
Myocardial collagen production
Role in cardiac fibrosis/remodelling
223
What is production of adrenal androgens regulated
ACTH
224
What is the main source of androgens in women
Adrenal glands
225
Main androgens produced by adrenal androgens
Dehydroepiandrosterone (DHEA)
Androstenedione
226
What is normal Catecholamines synthesis dependent on
High local cortisol levels - permissive effect
227
Stress
Sum of the bodies responses to adverse stimuli
I.e.
infection
Trauma
Haemorrhage
Medical illness
Psychological
Exercise/exhaustion
228
What is the neurotransmitter in the adrenal medulla
ACh
229
Thyroid hormone synthesis
TSH binds to TSHR on basolateral membrane
I- uptake by Na/I symporter
Iodisation of thyroglobulin tyrosyl residues by thyroperoxidase
Coupling of iodotyrosyl residues by thyroperoxidase
Export of mature thyroglobulin to colloid where it is stored
230
Which enzyme binds iodine to tyrosine residues in thyroglobulin molecules to form MIT + DIT
Thyroperoxidase
231
Function of thyroperoxidase
binds iodine to tyrosine residues in thyroglobulin molecules to form MIT + DIT
MIT + DIT = T3
DIT + DIT =T4
232
Hyperthyroidism
Low Serum TSH
High Serum free T4
High Serum free T3
233
Hypothyroidism
High Serum TSH
Low Serum free T4
Low Serum free T3
234
Actions of parathyroid hormone
Increases calcium reabsorption in renal distal tubule
Increases intestinal calcium absorption (via activation of vitamin D)
Increases calcium release from bone (stimulates osteoclast activity)
Decrease phosphate reabsorption
235
Endocrine control of extracellular calcium homeostasis
Parathyroid hormone
Vitamin D
Calcitonin, FGF23
236
Bone and control of bone homeostasis
Mineral phase (calcium/phosphate)
Protein phase (collagen and non-collagenous proteins)
Bone cells bone ‘turnover’ and remodelling units
237
How is calcium in the blood
50% of serum calcium ‘free’ (ionised)
50% bound to albumin
238
Amount of serum calcium
2.1-2.6 mM
239
Structure of parathyroid hormone
84 amino acid peptide but biological activity in first 34 amino acids (PTH 1-34), half-life 8 mins
Cleaved to smaller peptides
Assayed by two site assay (to avoid detecting fragments)
Still detects some inactive fragments e.g. in renal failure
240
Normal adult reference range of parathyroid hormone
1.6 - 6.9 pmol/L
241
Mechanism of parathyroid hormone activation
Binds to G protein coupled receptors mainly in kidneys and osteoblasts
242
Action of parathyroid hormone in kidney
PTH increases distal tubular reabsorption of calcium
(+ inhibition of PO4 reabsorption)
PTH also stimulates production of the active form of vitamin D, 1,25(OH)2D
243
Action of parathyroid hormone in bone
Enhances bone resorption by stimulating osteoclasts
244
What inhibits parathyroid hormone transcription
1,25D3
245
What inhibits parathyroid translation
Increased serum calcium
246
Where is calcitonin produced
Thyroid C-cells (parafollicular)
247
What causes the release of calcitonin
Hyoercalcaemia
248
Action of calcitonin
Inhibits bone resorption by direct effect on osteoclasts
249
3 factors inhibit insulin release
alpha-adrenergic drugs, beta-blockers, sympathetic stimulation.
