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PHYSIOLOGY ENDOCRINE Flashcards

1
Q

What are the endocrine signalling mechanisms?

A

1) Regulated secretion of hormones into ECF
2) Diffusion into vasculature
3) Binding to specific receptor in target organ

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2
Q

What are the types of message transmission (with examples)?

A

Paracrine (adjacent) –> neurotransmitters

Hormonal (endocrine) –> neurohormone

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3
Q

What does the exocrine pancreas mainly secrete?

A

Adiponectin

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4
Q

What does the endocrine pancreas mainly secrete?

A

Insulin
Glucagon
PP

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5
Q

What does the thyroid gland mainly secrete?

A

T3 & T4

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6
Q

What do the parathyroid glands mainly secrete?

A

PTH

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7
Q

What does the cortex of the adrenal glands secrete?

A

Cortisol
Aldosterone
Sex hormones

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8
Q

What does the medulla of the adrenal glands secrete?

A

Catecholamines (adrenaline, dopamine, noroepinephrin)

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9
Q

What is another name for adrenaline?

A

Epinephrine

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10
Q

Where are the hormones secreted by the hypothalamus directed to?

A

Pituitary gland

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11
Q

What is the main classification of hormones?

A

Peptides
Glycoproteins
Steroids
Amines

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12
Q

Where are peptide hormones produces?

A

Hypothalamus

Hypophysis

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13
Q

5 examples of peptide hormones?

A 
Growth hormone
Vasopressin (ADH)
Insulin/Glucagon
Parathyroid hormone (PTH)
Adrenocorticotropin (ACTH)
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14
Q

How are peptide hormones stored?

A

As INACTIVE polypeptides (pre-hormones) inside of vesicles

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15
Q

What peptide hormone is used as a marker for insulin and why?

A

C-peptide & insulin are released simultaneously (and in similar amounts) from the pancreas

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16
Q

Where are glycoprotein hormones mainly produced?

A

Hypohphysis

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17
Q

What is the common subunit of glycoprotein hormones?

A

a-subunit

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18
Q

What is the specific subunit for glycoprotein hormones?

A

B subunit

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19
Q

What are the 4 glycoprotein hormones?

A

Thyrotropin (TSH)
Follicle stimulating hormone (FSH)
Luteinising hormone (LH)
Chorionic Gonadotropin (HCG)

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20
Q

What is chronic gonadotropin (HCG) used for?

A

Pregnancy indicator

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21
Q

Description of the action of peptide hormones

A

Water-soluble
Fast effect
Short half-life

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22
Q

What are the 5 steroid hormones?

A 
Estradiol
Progesterone
Testosterone
Cortisol
Aldosterone
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23
Q

What is the common precursor of steroid hormones?

A

Cholesterol

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24
Q

Where are steroid hormones produced?

A

Cortex of adrenal gland

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25
Where do steroids act on, on a cell?
Receptor of the nucleus of a cell
26
Water affinity and implications for steroid hormones
Hydrophobic | Require transport proteins to bind in target cells
27
What is the common site for hormonal binding and what is the exception?
Common site: cell membrane | Exception: steroids
28
What are the amine hormones?
Thyroid hormones | Catecholamines
29
Where do thyroid hormones act on, on a cell?
INSIDE the nucleus of a cell
30
Where do catecholamines act on?
Medulla of adrenal gland
31
What is the common structure in amine hormones?
Tyrosine amino acid
32
Which hormone is the only which has a positive feedback mechanism?
Estrogen
33
What is the implication of hormonal binding in membrane of a cell?
Faster effect
34
What is the implication of hormone binding inside the cell/cell nucleus?
Slower effect
35
What part of the hormone is able to interact and penetrate the target organ?
Free-fraction
36
What is the difference between the circadian & ultradian rythms?
Circadian: daily Ultradian: monthly
37
When are cortisol levels highest?
In the morning, after waking up
38
When are growth hormones produced?
During sleep | Peak within 2 hours of sleep onset
39
What is the main determinant of sex hormones?
Pulsatility of hypothalamic GnRH
40
What is ACTH can its rapid degradation be prevented?
Precursor of cortisol | By conserving it in ice
41
Which disease requires the cortisol levels to be measured at night?
Cushing's disease
42
In a patient with polycystic ovary syndrome, when is the most appropriate time to measure sex hormones?
During 1st part of menstrual cycle
43
What transporters do lipophilic hormones (thyroxine and cortisol) require?
Globulin - lipoproteins
44
What is the main lipoprotein transporter for thyroxine?
Thyroxine-binding globulin (TBG)
45
What is the main lipoprotein transporter for cortisol?
Cortisol-binding globulin (CBG)
46
What are the clinical implications of the transport of hormones?
Alterations in binding proteins Free-hormone fractions Therapeutic modulation of transporter proteins
47
What kind of hormonal alteration can occur during pregnancy?
False hypothyroidism | Increased levels of estrogen --> increased levels of TBG
48
What is the therapeutic modulation for the condition of polycystic ovaries?
Increased levels of androgens --> bind androgens (steroid) to transporters so that they are not free and cannot act
49
What is the most relevant membrane receptor family?
G-protein coupled receptors
50
What are the 1st and 2nd messengers, respectively?
1st: hormones 2nd: cAMP
51
What is the mechanism of action of hormones via G-protein coupled receptors?
Hormones bind Dissociation of alpha subunit from beta and gamma subunits Alpha subunit triggers cascade of events to form cAMP cAMP produces mediators (adenylcyclases, phosphorylases, kinases) Mediators activate transcription factors that alter gene expression
52
What are the 5 main characteristics of peptide hormones?
``` Synthesized as pre-hormones Stored in secretory vesicles/granules Regulated at level of secretion Can circulate in blood freely Hydrophilic --> no need for binding proteins ```
53
What are the 5 main characteristics of steroid hormones?
``` Derived from cholesterol Regulated at level of enzymatic pathway Transported in blood bound to binding globulins Signal through intracellular receptors Oral administration ```
54
What are the 5 main characteristics of thyroid hormones?
``` Derived from tyrosine/iodothyronines Lipophilic but stored in thyroid follicular cells Regulated at all levels Transported bound to proteins Signal through intracellular mechanisms ```
55
What do tyrosines couple to form?
Iodothyronines
56
What is the difference between the primary and secondary gene transcription mechanisms?
Primary: thyroid hormones act directly on gene transcription Secondary: steroid hormones act by mediators on gene transcription
57
What is the classification of diseases as primary, secondary and tertiary diseases like?
Primary diseases in target organ Secondary diseases in anterior pituitary gland Tertiary disease in hypothalamus
58
What is the mechanism of feedback regulation for ADH?
Via changes in ion concentration (osmolarity)
59
What allows ovulation?
Positive feedback | LH increased production by pituitary gland triggers ovulation
60
What is another name for pituitary gland?
Hypophysis
61
What is the best indicator of hypothyroidism?
TSH (thyroid stimulating hormone) not T3 nor T4
62
What happens from the days 12-14 of the menstrual cycle?
Hypothalamus releases GnRH --> Adrenal gland releases FSH, LH --> Ovaries (glands) secrete Estradiol --> Estradiol acts on endometrium (target organ) Estradiol ENHANCES release of more FSH & LH by adrenal gland
63
What region gives rise to the adenohypophysis and what is its orientation?
Epithelium | Anterior
64
What region gives rise to the neurohypophysis and what is its orientation?
``` Neural origin (nervous tissue) Posterior ```
65
What bone and structure house the pituitary gland?
Sphenoid bone | Sella Turcica
66
What does the invagination of the oral cavity form?
Rathke's Pouch
67
What forms the pars tuberalis?
The infundibulum (diencephalic prolongation) and the Rathke's Pouch
68
What hormones does the adenohypophysis secrete?
``` TSH ACTH Prolactin GH FSH LH ```
69
How do the hormones secreted by the adenohypophysis reach the anterior pituitary gland?
Via the pituitary portal system
70
What hormones does the neurohypophysis secrete?
ADH | Oxytocin
71
How do the hormones secreted by the neurohypophysis reach their target organs?
Move down axon to axon endings
72
How do hypothalamic hormones affect the anterior pituitary hormones?
By inhibiting or stimulating their production and secretion ("certain situations such as mental stress or mood disturbances have repercussions on pituitary hormonal secretion, and consequently function of the peripheral glands")
73
Via which artery are oxytocin & ADH released into the general circulation?
Inferior hypophyseal artery
74
What regulates the secretion of pituitary hormones?
Hypothalamus (CNS) | Hormones produced by peripheral glands
75
What is/are the main stimulators and inhibitors of GH?
Stimulator: GHRH Inhibitor: Somatostatin
76
What is/are the main stimulators and inhibitors of TSH?
Stimulator: TRH Inhibitor: Somatostatin
77
What is/are the main stimulators and inhibitors of Prolactine?
Stimulator: VIP, SER Inhibitor: Dopamine!!
78
What is/are the main stimulators and inhibitors of ACTH?
Stimulator: CRH, Vasopressin (ADH) Inhibitor: -
79
What is/are the main stimulators and inhibitors of FSH & LH?
Stimulator: LNRH (AKA GNRH) Inhibitor: GnIH (Gonadotropin inhibitory hormone)
80
The levels of which hormone would increase if the infundibular stalk were cut and why?
``` Prolactine Dopamine (its inhibitor) would not be able to inhibit its production (since dopamine is produced in the hypothalamus) therefore prolactine levels would increase ```
81
How can an adenoma (benign tumor) of GH be treated?
By administering an analogue of somatostatin (since it inhibits the action of GH)
82
What is the relation between prolactine and the menstrual cycle?
Prolactine inhibits gonadotropin releasing hormone (gnrH) which results in the abscence of the menstrual cycle
83
What produces inhibin?
Sertolli cells (In men in the testicles & adrenal glands) (In women only in adrenal glands)
84
What is the "feedback-loop" of GH (pituitary hormone) with its corresponding peripheral hormone?
GH stimulates IGF-I | IGF-I inhibits GH
85
What is the "feedback-loop" of TSH (pituitary hormone) with its corresponding peripheral hormone?
TSH stimulates T3 & T4 | T3 & T4 inhibits TSH
86
What is the "feedback-loop" of ACTH (pituitary hormone) with its corresponding peripheral hormone?
ACTH stimulates cortisol | Cortisol inhibits ACTH
87
What is the "feedback-loop" of FSH (pituitary hormone) with their corresponding peripheral hormone?
FSH & LH stimulate Estrogens, Progesterone, Testosterone and Inhibin Estrogens, Progesterone, Testosterone and Inhibin!! inhibit FSH
88
What is the "feedback-loop" of LH (pituitary hormone) with its corresponding peripheral hormone?
LH stimulates release of Estrogens, Progesterone, Testosterone and Inhibin Estrogens, Progesterone and Testosterone inhibit LH Inhibin DOES NOT inhibit LH
89
What are the levels of FSH like in a menopausal woman?
High levels of FSH because inhibin and estrogens are inhibited (inhibitors of FSH inhibited, therefore levels of FSH rise)
90
What factors stimulate GH secretion?
Sleep Stress Exercise
91
What does GH produce in the liver?
IGF-1
92
What is the most important transport protein linked to IGF-1?
IGFBP3
93
What factors inhibit GH secretion?
Starvation Acute hypoglycaemia Aging
94
What condition results from the hyper-secretion of GH?
Acromegaly
95
In a person without acromegaly, what is the effect of glucose overload on GH secretion?
Decrease (inhibition)
96
In a person with acromegaly what is the effect of glucose overload?
No effect on GH release
97
What test is done to confirm diagnosis of acromegaly (GH hyper-secretion)?
Oral glucose overload
98
At what time of the sleep do GH levels increase?
2 hours after sleep is initiated
99
What are the main physiological effects of GH and IGF-1?
Cell growth | Anabolism
100
What is the main difference (in terms of physiological effects) between GH and IGF-1?
GH has lipolytic effect (thereby reducing adiposity) | IGF-1 increases insulin sensitivity
101
What molecules are the main inhibitors of growth plate chondrocytes?
Glucocorticoids
102
What are the main functions of IGF-1?
Development of: - Thymus - Neural - Cardiovascular - Musculoskeletal - Glomerular - Fetus - Ovarian folliculogenesis
103
What is the main controller of the hypothalamic-pituitary-adrenal axis?
Suprachiasmatic nucleus receiving afferences (sensory fibers) from retina
104
What are the hormones responsible for the secretion of ACTH on the pituitary gland?
``` Mainly CRH (corticotropin-releasing hormone) Also ADH ```
104
What are the hypothalamic hormones responsible for the secretion of ACTH on the pituitary gland?
``` Mainly CRH (corticotropin-releasing hormone) Also ADH ```
105
What is the main function of ACTH and where does it carry this function out?
Stimulate synthesis of cortisol | Adrenal cortex
106
What is the effect of cortisol on the pituitary gland and on the hypothalamus?
Negative feedback
107
What are the main molecules secreted by cortisol?
Pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-a) which stimulate the hypothalamic-pituitary-adrenal axis
108
What is the global stimulator of the hypothalamic-pituitary-adrenal axis?
Stress
109
What is the best time of the day to measure cortisol levels?
After waking up (8am)
110
What stimulates the release of prolactin?
``` Sleep Stress Food Exercise Pregnancy ```
111
What drugs (pharmacological) inhibit the release of prolactin?
Antipsychotics | H2-blockers
112
What hormones regulate the release of prolactin from the pituitary gland?
Serotonin stimulates | Dopamine inhibits
113
What effects does prolactin have?
Lactation (postpartum period) Mammary gland development Kidney sodium reabsorption (Electrolytic homeostasis)
114
How do estrogens stimulate the production of prolactin?
Via inhibition of TIDA (tuberoinfundibular dopamine)
115
What is the most common cause of hyperprolactinemia?
Pharmacological hyperprolactinemia (antipsychotics, H2-blockers)
116
When are prolactin levels (ideally) measured?
First thing in the morning (fasting state)
117
When are prolactin levels (ideally) measured in WOMEN?
Follicular phase of menstrual cycle
118
What hormones have a circadian rythm?
GH Prolactin TSH
119
How is T4 converted into T3?
Deiodination (removal of iodine) of T4
120
What is the effect of stress on the hypothalamic-pituitary-gonadal axis?
Inhibition on secretion of gonadotropins
121
What effect does LHRH (leutinising hormone releasing hormone) AKA GnRH (gonadotropin releasing hormone) on the secretion of FSH and LH?
Stimulation | LH > FSH
122
What is the importance of a pulsatile secretion of GnRH?
Every 90 minutes to maintain bioactivity of LH and FSH
123
What hormones inhibit the release of FSH and LH from the pituitary gland?
Testosterone Inhibin Estradiol Progesterone
124
In what part of the menstrual cycle does estradiol have a stimulating effect on the release of FSH and LH?
Follicular (periovulatory) phase
125
What is the effect of inhibin (of gonadal origin) on the hypothalamus-pituitary-gonadotropin axis?
SELECTIVELY inhibit the release of FSH
126
What are FSH levels like in menopausal women or after a gonadectomy? Why?
FSH levels are elevated because inhibin is decreased
127
What is the effect of kisspeptin on GnRH-neurons?
Stimulatory effect --> stimulates secretion of FSH and LH
128
What are the receptors for vasopressin and where are they found?
V1 - blood vessel V2 - kidney V3 - pituitary gland
129
What is the effect of V1 (vasopressin 1) receptor?
Vasoconstriction
130
What is the effect of V2 (vasopressin 2) receptor?
Increased reabsorption of water
131
What is the effect of V3 (vasopressin 3) receptor?
Stimulates ACTH producing cells
132
What is cranial diabetes insipidus due to?
ADH deficiency
133
What is nephrogenic diabetic insipidus due to?
Defects in collecting tubule
134
What is the best imaging test to investigate the causes of pituitary dysfunctions?
MRI
135
What is the campimetry test used for?
Pituitary macroadenoma
136
What is the effect of hypopituitarism on GH?
Growth delay
137
What is the effect of hypopituitarism on PRL?
Postpartum agalactia (reduced lactation)
138
What is the effect of hypopituitarism on ACTH?
Secondary (cortical) adrenal insufficiency
139
What is the effect of hypopituitarism on TSH?
Secondary hypothyroidism
140
What is the effect of hypopituitarism on FSH/LH?
Secondary hypogonadism
141
What is the effect of hypopituitarism on ADH?
Cranial diabetes insipidus
142
What are hyper-functioning syndromes of GH?
Acromegaly (gigantism in children)
143
What are hyper-functioning syndromes of Prolactin?
Hyperprolactinemia
144
What are hyper-functioning syndromes of ACTH?
Cushing's disease | Hypercortisolism
145
What are hyper-functioning syndromes of TSH?
Secondary hyperthyroidisim
146
What are hyper-functioning syndromes of FSH/LH?
Gonadotropinomas
147
What are hyper-functioning syndromes of ADH?
Inadequate secretion of ADH
148
What joins the two lobes to form the thyroid gland?
Isthmus
149
Should thyroid gland be palpable under physiological conditions?
No (palpation must be painless)
150
Where is the thyroid gland located?
In front of the trachea
151
How many parathyroid glands are there?
``` Usually 4 (2 upper and 2 lower) 10% of people have a 5th (variable location) ```
152
What nerve is located posterior to the thyroid gland?
Recurrent laryngeal nerve
153
What can cutting the recurrent laryngeal nerve cause?
Dysphonia
154
What does the hypothalamus pituitary thyroid axis consist of?
Hypothalamus produces TRH Pituitary gland produces TSH Thyroid gland produces T3 (10%) and T4 (90%)
155
How is TRH conducted from the hypothalamus to the anterior pituitary gland?
Via the hypothalamic-pituitary portal system
156
What amount of T4 undergoes deiodination to become T3?
90%
157
What hormone mediates the feedback mechanism of the hypothalamus-pituitary thyroid axis?
T3
158
What hormones inhibit the secretion of TSH?
Dopamine Somatostatin Glucocorticoids Stress (not a hormone, I know)
159
What does a thyroid follicle consist of?
Follicular cells and a colloid
160
What is the colloid of a thyroid follicle?
Reservoir of: - Thyroglobulin - Iodothyrosines - Thyroid hormones
161
What is thyroglobulin?
Protein made of thyroxine and iodine
162
What is the main function of the capillaries surrounding the thyroid follicles?
Iodine transport
163
What supplementation must pregnant women take?
Folic acid | Iodine salt
164
What is the iodine turnover rate?
Iodine intake = iodine excretion (daily)
165
What is TSH's receptor?
G-protein coupled receptor
166
What is the final effect of TSH?
Synthesis of thyroid hormones
167
What does the chronic elevation of TSH promote?
Goiter: growth of thyroid gland
168
What is the most frequent cause of hyperthyroidism?
Grave's disease (TSHR antibody - overstimulates TSH receptor to overproduce thyroid hormones)
169
What is the 1st step in the synthesis and secretion of thyroid hormones?
Iodine (circulation) active transport by NIS (Na+/I- symporter) in basolateral membrane of thyroid epithelial cells
170
What is the 2nd step in the synthesis and secretion of thyroid hormones?
Iodine travels through thyroid epithelial cells to apical membrane Transported to colloid via Pendrin (I-/Cl-) transporter
171
What is the 3rd step in the synthesis and secretion of thyroid hormones?
Iodination Iodine binds to tyrosine residues (in thyroglobulin) Thyroid peroxidase (TPO) catalyses conversion into MIT and DIT
172
What is the 4th step in the synthesis and secretion of thyroid hormones?
Coupling (catalysed also by TPO) MIT + DIT = T3 (10%) DIT + DIT = T4 (90%)
173
What is the 5th step in the synthesis and secretion of thyroid hormones?
Endocytosis of vesicles with TG bound to MIT, DIT, T3, T4 into follicular cells Release of T3 & T4 in circulatory system Recycling of iodine and tyrosine
174
What does TPO stand for?
Thyroid peroxidase
175
What is the effect of excessive iodine intake?
TPO blockage known as Wolff-Chaikoff effect
176
Why is iodine prescribed to patients with hyperthyroidism?
Because it blocks TPO action thereby reducing release of T3 and T4
177
How is thyroid hormone transported in circulation?
99% bound to proteins | 1% free (active)
178
How must thyroid be measured in blood?
In the free form (active)
179
Why can a pregnancy be a false indication of hypothyroidism?
``` Estrogens (elevated in pregnancy) increase TBG (thyroid binding globulin) More TBG = less free thyroid Less free (active) thyroid = hypothyroidism ```
180
What are the "transport" proteins found in the 99% of thyroid protein-bound?
70% TBG 20% Albumin 10% Transthyretin
181
Why is T4 prescribed preferably to T3?
Half life of T4 is longer | T4 is more stable
182
What does the largest proportion of circulating T3 come from?
From T4!!
183
What is the site of conversion of T4 into T3?
Mainly peripheral circulation
184
What enzymes catalyse the conversion of T4 into T3?
Deiodinase (D) - D1, D2, D3
185
What is the function of D1?
Peripheral conversion of T4 into T3
186
What is the function of D2?
Peripheral and HYPOTHALAMIC conversion of T4 into T3
187
What is the function of D3?
Conversion of T4 into REVERSE T3 (inactive) | Found in sick euthyroid syndrome
188
How do T3 and T4 enter the target cells?
Via diffusion
189
What does T3 interact with once inside the target cell?
Thyroid hormone receptor (TR) - nuclear receptor of thyroid hormones
190
What is the main outcome of gene transcription by T3?
Stimulates B-adrenergic receptors
191
What is the main mechanism of metabolism/excretion of thyroid hormones (T3 and T4)?
T4 and T3 metabolised into T2 (inactive) via deiodinases & excreted in urine, feces or bile
192
What are the main actions of thyroid hormones in cardiovascular system (MUST KNOWS)?
Positive inotropic and chronotropic effects
193
What are the main actions of thyroid hormones in metabolic system (MUST KNOWS)?
Increase basal metabolism | Indirectly increasing brown adipose tissue
194
What are the main actions of thyroid hormones in hormonal systems (MUST KNOWS)?
GH modulation Regulation of gonadal function E2/T ratio (estrogen/testosterone)
195
What are the main actions of thyroid hormones in bones (MUST KNOWS)?
Aid in bone maturation | Decrease glycosaminoglycans
196
What are the main actions of thyroid hormones in respiratory system (MUST KNOWS)?
Increase respiratory rate
197
What are the main actions of thyroid hormones in muscular system (MUST KNOWS)?
Muscle trophism
198
What are the main actions of thyroid hormones in autonomous nervous system (MUST KNOWS)?
Synergy with catecholamines
199
What are the main actions of thyroid hormones in nervous system (MUST KNOWS)?
Aid in neuronal development Increase alert, memory, cognition Osteotendinous reflexes Gastrointestinal motility
200
What is the main functional difference between calcium and phosphorus?
Phosphorus is a component of phospholipid membranes (calcium is not)
201
What are the main functions carried out by calcium and phosphorus?
Enzymatic activation Muscle contraction Coagulation Bone mineralization
202
What is the effect of pH on ionic calcium quantities in blood plasma?
Acidosis INCREASES ionic calcium | Alkalosis DECREASES ionic calcium
203
What percentage of calcium is ionised and what percentage is free in plasma?
50% ionised | 50% free
204
What are the key elements of calcium and phosphorus homeostasis?
Intestinal absorption Renal elimination Bone exchange
205
What calciotropic hormones are involved in the regulation of calcium metabolism?
PTH | Vitamin D
206
What are the only 2 regulative elements of Ca2+ and bone metabolism that has an anabolic function?w
``` Growth hormone (GH) Insulin like growth factor (IGF-1) ```
207
What is the effect of thyroid hormones, cortisol and cytokines in the BONES?
Induce catabolism
208
What is the effect of sex steroids and somatotropic axis (growth-hormone axis) in the BONES?
Induce catabolism
209
What 2 things does bone remodelling involve?
1) Bone formation (osteoblasts) | 2) Bone destruction (osteoclasts)
210
What is an osteoid?
Bone matrix that is yet to be mineralised
211
What controls the mineralization of osteoids?
Calcium and Pi (inorganic phosphate)
212
Where is PTH (parathyroid hormone) synthesised and secreted?
Parathyroid glands (4 or 5 - 10% of population-)
213
What is the predominant parenchymal cell type in the parathyroid gland?
Principal or chief cell
214
Where does the biological activity reside in the peptide chain of PTH?
First 34 amino acids
215
How long is the half-life of PTH?
Short (2 min)
216
What stimulates PTH secretion via interaction with CaSR (calcium-sensing receptor) in the principal/chief cells?
Hypocalcemia | Catecholamines
217
What factors suppress PTH release?
Hypercalcemia Hypomagnesemia Vit D administration
218
What effect does activation of beta2-adrenergic receptor have on PTH secretion¿
Stimulates PTH secretion
219
What is the pathway of Vitamin D from the moment of its intake to the moment it carries out its function?
Food & skin "absorb" Vit. D 25-hydroxylase catalyses Vit.D into 25(OH) D 1 a-Hydroxylase catalyses 25(OH)D into 1.25(OH)2D 1.25(OH)2D acts in GI tract to stimulate calcium and phosphorus absorption
220
What is the active form of Vitamin D?
1.25(OH)2D
221
What stage of vitamin D is measured in blood tests?
25(OH)D
222
What is the action of PTH related to calcium, phosphorus and phosphate?
Stimulates calcium and phosphorus resorption Stimulates release of 1 a-hydroxylase Stimulates phopshate excretion
223
What is the main modulator of calcium absorption in small intestine?
1 a-hydroxylase
224
What is the effect of PTH on osteoclasts and on osteoblasts?
DIRECT activation of osteoblasts | INDIRECT activation of osteoclasts
225
How are osteoclasts formed?
Prosteoclasts (osteoclast precursors) have RANK RANK ligand binds to RANK Induces osteoclastogenesis --> osteoclasts
226
What generates RANK ligands?
Osteoblasts
227
What occurs when there is an excess secretion of PTH?
Increase in resorption that translates into osteoporosis
228
What effect does osteoprotegerin have?
Inhibits osteoclastogenesis by acting as a decoy receptor (inhibitor) for RANKL
229
What is the effect of Denosumabe?
Human monoclonal antibody that acts on RANKL to inhibit osteoclastogenesis Administered in situations of osteoporosis
230
What effect does PTH have on the proximal tubule of the kidneys?
Promotes destruction of phosphate co-transporter IIa --> stimulates phosphate excretion (instead of reabsorption) Activates 1 a-hydroxylase --> Vit. D synthesis
231
What effect does PTH have on distal tubule of the kidneys?
Stimulates calcium resorption
232
What receptor senses alterations in calcium levels?
CaSR (calcium-sensing receptor)
233
What is the effect of 1,25 Vitamin D on PTH gene?
Inhibitory effect of PTH gene | Stimulation of synthesis of CaSR
234
What is the most important effect of Vitamin D?
Increase intestinal absorption of calcium
235
Where does Vitamin D come from?
Synthesis of cholecalciferol from provitamin D from UV light
236
Via hydroxylations of which molecule is Vitamin D transformed into its active form?
Successive hydroxylations of Cholecalciferol
237
What is FGF23? Where is it produced? What is its function?
Fibroblast growth factor 23 Produced by mature osteoblasts Phosphate and Vit.D metabolism and regulation
238
Where does FGF23 mainly act on?
Proximal tubules of kidneys via FGFR/Klotho receptor
239
What are the main effects of FGF23?
Decreases active Vit.D and causes phosphaturia (phosphate excretion) by inhibiting 1 a-hydroxylase
240
What occurs with the Klotho receptor (FGFR/Klotho) in kidney diseases?
Decreased expression of klotho receptor
241
Why is PTH not used to measure hypocalcemia?
Because it is very expensive
242
What is the effect of increased PTH levels on cytochrome p450 1a?C
Rapid stimulation (increase)
243
What condition produces PTHrp (PTH related peptide)?
Cancerigenous (malignant) tumors
244
What is the effect of PTHrp (PTH related peptide)?
Hypercalcemia by stimulating renal calcium resorption & bone resorption
245
What is calcitonin used for in medical exams?
Biomarker for medullary thyroid cancer
246
What is the main effect of calcitonin?
Reduces blood calcium levels | Opposes effect of PTH (antagonists)
247
In what condition was calcitonin previously administered and why?
Osteoporosis because it has an antiresorptive effect at bone level
248
What is the most common secondary disease of patients with kidney complications?
Cardiovascular problems
249
What types of hormones are produced by adrenal glands?
Steroids | Catecholamines
250
What is the origin of the cortex and the medulla of the adrenal glands?
Cortex - mesodermal origin (epithelial) | Medulla - ectodermal origin (neural)
251
What is the venous drainage of the right adrenal gland?
Right suprarenal vein drains directly onto vena cava
252
What is the venous drainage of the left adrenal gland?
Left suprarenal vein drains into left renal vein which then drains onto inferior vena cava
253
What are the 3 zones of the adrenal cortex?
Zona glomerulosa Zona fasciculata Zona reticularis
254
What do each of the 3 zones of the adrenal cortex secrete, respectively?
Zona glomerulosa - mineralocorticoids Zona fasciculata - glucocorticoids Zona reticularis - sex hormones
255
Where are 50% of circulating androgens of women produced?
In the adrenal glands
256
How do ACTH and cortisol levels relate?
Parallel
257
What is axis regulates cortisol synthesis?
Hypothalamic-pituitary-adrenal (HPA) axis
258
What does cortisol exert a negative feedback on?
CRH (corticoid releasing hormones) and ACTH (adrenocorticotropic hormone) All hormones of the HPA axis
259
What situations stimulate the release of CRH and ACTH?
Cold Injury Hypoglycemia Pain
260
What is the effect of increased glucocorticoid levels in the menstrual cycle?
Absence of menstrual cycle
261
What is the mechanism via which CRH stimulates ACTH production?
``` CRH reaches pituitary corticotrope cells via portal system Triggers intracellular signalling pathways Activates CREB (protein) & AP-1 (transcription factor) to generate ACTH ```
262
Where is CRH produced?
In the paraventricular nucleus of the hypothalamic nuclei
263
How does calcium affect ACTH release?
Direct stimulation
264
How does ADH (Vasopressin) affect ACTH release?
Indirect stimulation | Stimulates intracellular calcium mobilization therefore ACTH secretion
265
In which part of the adrenal cortex does ACTH interaction cause a greater hormonal response?
Zona fasciculata - secretes cortisol
266
What does the interaction of ACTH with the receptors of the zona fasciculata stimulate?
Entry of LDL-cholesterol | Synthesis of of StAR protein
267
What is the StAR protein responsible for and why?
Transfers cholesterol to inner mitochondria membrane because mitochondria is the site of steroid production
268
What does the interaction of ACTH with receptors in the zona fasciculata of the cortex of the adrenal glands ultimately generate?
Pregnenolone (precursor of most steroid hormones)
269
What condition is related to increased aromatase?
Obesity
270
What component do people with congenital adrenal insufficiency lack?
21-Hydroxylase
271
What is the function of the aromatase enzyme?
Androgens conversion into estrogens
272
What is the function of 21-Hydroxylase?
Catalyses glucocorticoid and mineralocorticoid pathways to produce cortisol and aldosterone, respectively
273
What hormone induces virilizartion (in a girl)?
Androstenedione
274
What is transcortin?
Cortisol binding globulin
275
What is the function of transcortin?
Balancing free fraction of cortisol | Preventing loss of cortisol in urine
276
What hormone increases the concentration of transcortin?
Estrogens
277
What are the main functions of cortisol?
Lipolysis Catabolism Stress reactivity regulation Anti-inflammatory properties
278
What type of intracellular receptors does cortisol interact with?
Glucocorticoids | Mineralocorticoids
279
Why are glucocorticoids prescribed?
Most potent anti-inflammatory
280
How can the metabolic effects of cortisol be increased via pharmacological treatment?
Administration of synthetic glucocorticoids
281
Why is cortisol considered an anti-inflammatory?
Inhibits transcription factor NF kappa beta involved in inflammatory & immune responses exerted on T lymphocytes and macrophages
282
What is the half-life of cortisol in blood?
100 minutes
283
What is the pharmacological treatment used in primary adrenal failure?
Fludrocortisone (oral preparation of mineralocorticoid) | Or cortisol as hydrocortisone
284
What are the main effects of angiotensin II in the RAAS system?
1) Aldosterone secretion 2) ADH secretion 3) Arteriolar vasoconstriction 4) Sympathetic activation
285
What is the main trigger for the secretion of aldosterone?
Elevated potassium levels (hyperkalemia)
286
What are the most important enzymes in the synthesis of aldosterone?
21-Hydroxylase 11-b-hydroxylase 18-hydroxylase
287
What can excess aldosterone cause?
``` Oxidative sterss Cardiac fibrosis Hypertension Dyslipidemiia Obesity ```
288
What does hyperaldosteronism lead to?
Alkalosis
289
What type of innervation does the adrenal medulla receive?
Preganglionic innervation
290
What is a pheochromocytoma and where is it found?
Neuroendocrine tumor in adrenal medulla
291
What are the proportions of the production of hormones by the adrenal gland?
20% - noradrenaline | 80% - adrenaline
292
What is paracrine vs endocrine action?
Endocrine: acts on distant target cells Paracrine: acts on target cells at point of release
293
What is the mechanism of action of adrenaline and that of noradrenaline?
Adrenaline - endocrine action | Noradrenaline - paracrine action
294
What enzyme catalyses the conversion of tyrosine into dihydroxyphenylalanine (DOPA)?
Tyrosine hydroxylase
295
From what amino acid is epinephrine biosynthesized upon?
Tyrosine
296
In what part of the adrenal medulla is noradrenaline converted into adrenaline?
Cytoplas
296
In what part of the adrenal medulla is noradrenaline converted into adrenaline?
Cytoplasm
297
What enzyme catalyses the conversion of norepinephrine into epinephrine?
PNMT (phenylmethanotamine-N-methyltransferase)
298
What is the effect of cortisol on PNMT?
Stimulation
299
Where are the catecholamines stored?
In vesicles in chromaffin cells of adrenal medulla
300
With which other molecules are catecholamines CO-SECRETED?
Chromogranin A (notably), B, C neuropeptide Y....
301
What is the clinical relevance of chromogranin A?
Screening of catecholamine-producing tumors (due to feedback on catecholamine production)
302
On what receptor does adrenaline preferentially act on?
Beta receptors
303
On what receptor does noradrenaline preferentially act on?
Alpha receptors
304
What is the main effect achieved via A1 receptor?
Vasoconstriction
305
What is the main effect achieved via A2 receptor?
Decreased insuline release
306
What ARE the main effectS achieved via B1 receptor?
Cardioacceleration | Increased myocardial strength
307
What ARE the main effectS achieved via B2 receptor?
``` RELAXATION (and vasoconstriction) Intestinal and bladder wall relaxation Uterus relaxation Bronchodilation Calorigenesis Glycogenolysis Lipolysis ```
308
What is the primary mechanism of action of A2 receptor?
Decreased cAMP (inhibition)
309
What is the mechanism of action of ventolin (albuterol) for asthma?
Acts on B2 adrenergic receptors Relaxes bronchial smooth muscle Secondary effect: increased HR
310
What ENZYME (notably) catalyses the metabolism of of epinephrine and norepinephrine?
COMT (catechol-orthomethyl transferase)
311
What are the resultant molecules from the metabolism of epinephrine and norepinephrine?
Metanephrine and normetanephrine
312
What is the clinical relevance of metanephrine and normetanephrine?
Diagnosis of pheocromocytoma and paranganglioma
313
What axis and nervous system does stress activate?
Hypothalamic-pituitary-adrenal axis | SNS
314
Via which nucleus are the HPA axis and SNS activated?
Locus ceruleus
315
What is the effect of the activation of the locus coeruleus nucleus?
Insulin resistance | Hypertension
316
What is the effect of ACUTE physical exercise on adrenergic receptors?
Activation of ALL of them
317
What are the general consequences of stress?
Obesity development Carbohydrate intolerance Dyslipidemia Arterial hypertension
318
Why can stress cause irregular menstrual cycles?
Releases corticotropin releasing hormone which: | Inhibits GnRH --> inhibits LH/FSH --> inhibits gonadrotropins
319
What is the effect of an increase in cortisol?
Inhibitory effect on total secretion of anterior pituitary gland
320
What do the a cells of the islet of langerhans release?
Glucagon
321
What do the b cells of the islet of langerhans secrete?
Insulin
322
What do the delta cells of the islet of langerhans secrete?
Somatostatin
323
What do the F cells of the islet of langerhans secrete?
Pancreatic polypeptide (AKA PP cells)
324
What do the epsilon cells of the islet of langerhans secrete?
Ghrelin
325
What is the most prevalent type of islet of langerhans?
B-cells
326
What molecule is measured to differentiate between type 1 and type 2 diabetes and why?
C peptide because it is produced at the same rate as insulin but has a longer half-life
327
What enzyme breaks down C-peptide?
Proinsulinases by breaking sulfide bridges
328
What is the main mechanism for adjustment of insulin secretion?
Phosphorylation of glucose into glucose-6-phosphate
329
What is the pattern of insulin secretion?
5% is INITIALLY released as PREFORMED - 1st phase 95% is released 2HRS later - 2nd phase (postpandrial = after a meal) Biphasic curve
330
How does the SNS regulate the release of insulin?
Via A2 adrenergic rcp | Inhibitory effect on insulin release
331
What are incretin hormones?
Stimulate internal insulin secretion GLP-1 (glucagon-like-peptide 1) GIP (gastric inhibitory peptide)
332
Where are GLP-1 and GIP cells released from respectively?
GLP-1: L cells of small & large intestine | GIP: duodenal and jejunal K cells
333
What conditions and hormones inhibit insulin secretion?
Fasting, hypoglycemia, glucagon, adrenaline, GH, cortisol,
334
What is the composition of the insulin receptor?
2 alpha subunits + 2 beta subunits held together by disulfide linkages
335
What are the only type of cells that can use glucose without the intermediation of insulin?
Brain cells because they are PERMEABLE to glucose
336
What is the treatment for diabetes type 2?
Blockage of SGLT-2 (sodium-glucose cotransporter)
337
What is the main function of GLUT2 (apart from transporting glucose)?
Stimulate release of insulin in beta cell
338
What is the main function of GLUT4 (apart from transporting glucose)?
Intracellular metabolisation of glucose
339
What is THE MAIN effect of insulin?
Anabolism!!!!
340
What is the product of the conversion of proglucagon by alpha cells (islet of langerhans)?
Glucagon
341
What is the product of the conversion of proglucagon by intestinal L cells?
GLP-1 | GLP-2
342
What are the main actions of glucagon?
``` Thermogenic effects on brown adipose Appetite inhibition Can be used to assess pancreatic reserve of insulin Hepatic glucose production Proteolysis, ketogenesis, contractility ```
343
Why does GLP-1 not cause hypoglycemia?
Because their effect is dependent on glucose levels (irregularity) - they stop acting as soon as glycemia normalises
344
What is the effect of an increase in ghrelin (fasting state)?
``` Appetite stimulation Increases glucagon Reduces insulin Favours lipolysis Favours hepatic glucose production ```
345
What are the consequences of obesity?
Adipocytes hypertrophy Dysfunctional adipocyte (insulin sensitivity, secretory function, lipid storage) Subcutaneous tissue can sometimes not accommodate all of the fat
346
What are the types of adipocytes?
White Beige Brown
347
What confers thermogenic capacity in adipocytes?
Uncoupling protein 1 (UCP 1)
348
Where are the essential and non-essential WHITE adipocytes located?
Essential - subcutaneous | Non-essential - visceral
349
Why is white adipose tissue in the visceral compartment not good?
White adipose tissue in visceral compartment (abdominal location) drains FFA to portal vein of liver --> releases TNF (inflammatory marker) --> insulin resistance
350
What type of adipocyte expresses UCP1?
Brown adipose tissue
351
What are the main differences between white and brown adipocytes?
Brown: highly vascularised and SNS innervation
352
What percentage of the population with normal and overweight BMI meet diagnostic criteria for obesity?
29% of people with normal BMI | 80% of people with overweight BMI
353
What is the total daily energy expenditure based upon from most to least?
Basal metabolic rate Thermic effect of food Non exercise activity Exercise activity
354
What transporter is needed for beta-oxidation?
Carnitine
355
What are the 3 main pathways of lipid metabolism?
Exogenous pathway Endogenous pathway Reverse transport pathway
356
What does the exogenous pathway consist of?
Fat intestinal digestion and absorption --> liver
357
What does the endogneous pathway consist of?
Fat from liver that reaches tissues
358
What does the reverse transport pathway consist of?
HDL collects FA from tissues and takes it to liver
359
Characteristics of chylomicrons (lipoprotein)
Transport triglycerides | Lowest density
360
Which lipoproteins are atherogenic?
Apo B100 and Apoa
361
Which lipoproteins contain the apoprotein ApoB48?
Chylomicrons | Chylomicron remnants
362
Which lipoproteins contain the apoprotein B100?
VLDL IDL LDL LpA
363
What apoproteins does lipoprotein A contain?
Apo B 100 | Apo a
364
Elevated value of which cholesterol value is associated with cardiovascular protection?
HDL
365
What are chylomicrons composed of?
Triglycerides ApoB-48 Cholesterol Phospholipids
366
What is the exogenous pathway of lipid metabolism?
Chylomicron (thoracic duct --> vena cava) --> FA and chylomicron remnant FA to muscle and adipose tissue Chylomicron remnant to liver for cholesterol recycling
367
What is the endogenous pathway of lipid metabolism?
Liver: synthesis of VLDL --> circulation VLDL --> FFA (by lipoprotein lipase) that accumulates in adipose tissue High concentration of chylomicrons --> VLDL remnants that reach liver
368
What happens if LDL receptors in hepatocytes decreases?
LDL particles remain in circulation Increase LDL concentration Oxidation & glycosylation of LDL makes it more atherogenic
369
What is the self-regulatory mechanism in a situation of dyslipidemia?
Statins inhibit HMG-CoA reductase --> cholesterol production is inhibited --> increase in LDL rcp. --> lower LDL in macrophages
370
Why can PCSK9 inhibitors be used in hypercholesterolemia?
PCSK9 degrades LDL receptor
371
What is the function of the SR-BI receptor?
Mediate selective uptake of HDL-derived cholesteryl esters into tissues
372
What is SR-BI receptor?
Type of HDL

SOI2 (9 decks)

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