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Endocrine Physiology Flashcards

1
Q

Classification of hormones and examples

A

Polypeptides - vasopressin, oxytocin, insulin, glucagon, prolactin
Glycoproteins - TSH, FSH, KH
Steroids - corticosteroids, aldosterone, sex hormones
Amines - thyroxine, adrenaline
Fatty acid derivatives - prostaglandins

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2
Q

How are polypeptide and glycoprotein hormones transported in the blood

A

Hydrophilic so unbound in blood stream

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3
Q

How are polypeptide hormones stored and released

A

Stored in granules, released by exocytosis

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4
Q

Where are steroid hormones synthesised? From what?
How are they stored
How are they transported

A

Mitochondria from cholesterol
Produced on demand, not stored
Transported bound to proteins as lipophilic

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5
Q

How are amine hormones produced? How are they stored

A

From amino acid tyrosine
Stored in follicles or granules

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6
Q

How can hormones exert a change on cellular function

A

Changes in membrane permeability
Release of second messenger
Changes in intracellular protein synthesis

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7
Q

How do hormone receptors adapt to hormone concentration

A

Downregulate or upregulate to counter hormone amount

Nb down regulation can be drop in receptor number or in receptor response

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8
Q

Where are hormone receptors located

A

Hydrophilic hormone receptors on cell membrane
Lipiophilic hormone receptor in cytoplasm or nuclear

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9
Q

What is hormone permissiveness

A

When a hormone requires small amounts of another hormone to exert its effect
Eg glucocorticoids are required for catecholamines to have their lipolytic effecet

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10
Q

How do hormones alter membrane permeability?
Examples

A

Via GPCRs
Growth hormone, prolactin, insulin

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11
Q

Examples of second messenger mechanisms involved in hormone signalling

A

GPCR increasing cAMP causing intracellular protein phosphorylation (Gs)
GPCR decreasing cAMP reversing above (Gi)
GPCR activating PIP2 degradation to IP3 and DAG - IP3 causes calcium release DAG activates protein kinase c causing cell division and multiplication

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12
Q

Examples of hormones activating Gi receptors

A

Oxytocin, vasopressin, LH, FSH, TSH, ACTH, adrenaline beta receptors, PTH, glucagon

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13
Q

Examples of hormones activating Gi receptors

A

Somatostatin, alpha 2 adrenaline

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14
Q

Examples of hormones acting via PIP2

A

Alpha 1 adrenaline, vasopressin

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15
Q

What hormones act directly on protein synthesis?
How

A

Thyroixine, steroid hormones
Lipophillic so enter cell, bind to receptor in cytoplasm then cross into nucleus and bind to dna upregulating transcription

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16
Q

What factors can stimulate hormone release

A

Ion levels eg. Sodium dependent release of vasopressin
Organic molecules eg glucose dependent release of insulin
Physical/chemical stimulation eg gut hormones

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17
Q

Example of direct and indirect negative feedback on hormones

A

Direct - low glucose, decreased insulin
Indirect - glucocorticoids inhibit acth-rh, reducing acth, reducing cortisol secretion

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18
Q

Why does gland hypertrophy/atrophy occur

A

Continued low or high levels of hormone despite max or min production in an attempt to compensate

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19
Q

Where is the pituitary gland located

A

Sella turcica

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20
Q

Where do the anterior and posterior pituitary glands develop?

A

Posterior directly from hypothalamus
Anterior from rathkes pouch on roof of mouth.

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21
Q

What are the connections between the hypothalamus and the pituitary

A

Both via the pituitary stalk
Anterior via portal circulation
Posterior direct neuronal connection,

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22
Q

What is the portal circulation of the anterior pituitary
Function

A

Arrises from superior hypophyseal artery, primary capillary plexus on floor of hypothalamus absorbs releasing hormones, drains into portal vein to the secondary capillary plexus in the anterior lobe where the releasing hormones trigger release of trophic hormones into blood stream.

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23
Q

Cell types in anterior pituitary, hormones they release and proportion of total cell number for top 2

A

Somatotropes - growth hormone, 50%
Lactotropes - prolactin 10-30%
Corticotropes - ACTH
Thyrotopes - TSH
Gonadotropes - FSH and LH

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24
Q

Where are posterior lobe pituitary hormones produced? How are they released

A

Produced in median eminance of hypothalamus.
Form granules passed down axons in pituitary stalk into posterior pituitary for storage
Released into the blood stream when stimulation occurs

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25
What hormones are produced for release int he posterior pituitary? Precisely where?
Vasopressin - supraoptic nucleus Oxytocin - paraventricular nucleus
26
Functions of TSH Type of hormone, mechanism
Stimulates production of thyroid hormone from thyroid and stimulates growth of thyroid gland Glycoprotein, Gs
27
Functions of ACTH Type of hormone, mechanism Pattern of release
Increased corticosteroid production from adrenal cortex Stimulates melanocytes to produce melanin Polypeptide, Gs Diurnal highest in mornings, lowest in evenings.
28
Functions of GH Other name Type of hormone, mechanism
Promotes protein synthesis, lipolysis and raised BM promoting growth Indirect effects from increased release of other factors such as IGF-1 and 2 Somatotropin Peptide hormone, affects permeability
29
Effect of high or low growth hormone as child
High - gigantism Low - dwarfism All in proportion!
30
Effect of high growth hormone in adults
High - acromegaly
31
Functions of Prolactin Type of hormone, mechanism
Stimulates development of milk producing breast tissue and milk production, suppresses ovulation. Peptide, increased permeability
32
Functions of FSH Type of hormone, mechanism
Stimulates ovulation and spermatogenesis Glycoprotein, Gs
33
Functions of LH Type of hormone, mechanism
Stimulates ovulation and luteinisation of ovarian follicles Stimulates testosterone secretion Glycoprotein Gs
34
Functions of vasopressin Mechanism of action
Water retention All PIP2 V1 receptor - vasoconstriction V2 receptor - insertion of AQP2 into collecting duct V3 receptor - ACTH-RH release
35
What stimulates vasopressin release
Rise in osmotic pressure Decreases in extracellular volume Increased angiotensin II Pain, stress and exercise Nausea and vomiting Smoking
36
What inhibits vasopressin release
Decreased plasma osmotic pressure Increased extracellular fluid volume Alcohol
37
Effect of vasopressin deficiency
Diabetes insipidus
38
Effect of vasopressin excess
Fluid retention, hyposomolality, hyponatraemia
39
What Type of hormone is vasopressin
Polypeptide
40
Functions of Oxytocin Type of hormone, mechanism
Milk ejection from glands, uterine contractionin labour and post partum, sexual arousal Polypeptide Gs
41
What is sheehans syndrome
Severe bleeding and hypovolaemia in childbirth leading to pituitary necrosis
42
What are the hormones produced by the hypothalamus that control anterior pituitary secretion? Type?
All polypeptides TRH ACTH-RH GH-RH and GH-IH (somatostatin) PRH and PIH (dopamine) Gn-RH
43
Examples of crossover in hypothalamic releasing hormones effect
TRH also stimulates prolactin GRH also inhibits TSH
44
Effects on hypothalamic hormone output
Pos/negative feedback Stress Diurnal variation Emotional factors
45
Lobes of the thyroid
Left and right lobes each with upper and lower pole Sometimes there’s a third pyramidal lobe anterior to isthmus
46
Arterial supply to thyroid Venous drainage
Superior and inferior thyroid arteries Superior middle and inferior thyroid veins
47
Structure of a thyroid acini (follicle)
Central colloid full of thyroglobulin and iodine Surrounding thyroid epithelial cells Parafollicular cells (c or clear cells) that secrete calcitonin
48
How are thyroid hormones produced What enzyme is required to do this
Tyrosine in thyroglobulin (large glycoprotein) combines with iodine in 4-8 residue units (MIT monoiodotyrosine, and DIT diiodotyrosine). MIT combines with DIT to form triiodothyronine (T3) and DIT with DIT to from tetraiodothyronine (T4). Under control of thyroid perisidase
49
How is iodine moved into the thyroid colloid
Dietary iodine converted to iodide (I-) in gut Transported to thyroid where concentrated into the thyroid by sodium iodide pumps Secreted into the colloid and oxidised back to iodine
50
Key functions of a thyroid cell
Absorption and concentration of iodide with secretion into colloid Production of thyroglobulin and thyroid peroxidase and secretion into cokkkid Absorption of thyroid hormone back from colloid and into blood stream
51
How is thyroid hormone secretion controlled What is secreted and what circulates? What exerts most end organ effect?
By TSH levels. 90% of secreted hormone is T4 with rest T3 33% T4 converted to T3 with T3 making up 25% of the circulating amount T3 exerts 5x the effect of T4 on tissues and most T4 is converted to inactive rT3
52
How do thyroid hormones travel in the blood
Bound to protiens including albumin and thyroxine binding prealbumin or thyroxine binding globulin. Albumin has largest capacity but TBG has highest affinity so most is in TBG <1% is unbound.
53
Effects of TSH
Release of t3 and t4 Increase size and number of cells in thyroid gland Increase thyroglobulin synthesis, increased colloid Endocytosis,
54
How do thyroid hormones exert their efffect
Enter cells Bind with receptor in nuclei Hormone receptor complex binds to dna upregulating transcription and protein synthesis.
55
Main effects of thyroid hormone
Increased proteins breakdown and lipolysis Increased carbohydrate absorption Increased beta adrenoceptors in heart, increased sensitivity of heart to catecholamines, thus increased iontrophy and chronotrophy with decreased pvr Increased mitochondria with increased metabolic rate, energy utilisation and heat production.
56
Causes of hypothyroidism (broadly) Effects
Pituitary failure Thyroid failure Iodine deficiency Myxoedema, lethargy, slowness, weight gain, cold intolerance, thick stiff skin (lack of protein breakdown) In children cretinism (mental retardation, dwarfism, pot belly, large protruding tongues)
57
Causes of hyperthyroidism Effects
Pituitary overproduction of TSH Thyroid disease Nervousness, tremor, weight loss, sweating, heat intolerance, af, wide pulse pressure
58
What is Graves’ disease
Thyroid autoantibodies that stimulate TSH receptors In 50% also cause tissue deposition behind eye and exophthalmos
59
Types of cells in parathyroid glands
Chief cells containing secretory granules of pth Oxyphil cells with unknown function
60
What is pth
A polypeptide produced in chief cells of parathyroid Converted from preprohormone to prohormone to pth before release from granules into blood
61
Function of PTH
Mobilisation of ca from bones raising plasma Ca Reabsorption of ca in DCT of kidney Decreased reabsorption of phos in pct of kidney Increase phosphate absorption in gi tract Increase production of 1,25dihydroxycholecalciferol
62
Mechanism of action of pth on cells
Gs receptor activation
63
Stimulus for pth release
Low ca levels
64
Vitamin d pathway
7-dehydroxycholestrol [sunlight] Cholecalciferol [liver] 25 hydroxycholecalciferol [kidney] 1.25 dihydroxycholecalciferol
65
How does Vit d exert its effect
Binding to cell nucleus receptors exposing dna binding site altering transcription
66
Effect of Vit d
Increases gi calcium and phosphate absorbtion Increases ca absorption in kidney Increases osteoblast activity laying down ca in bones
67
Where is calcitonin produced Effect
C cells (clear cells, parafolicular cells) of thyroid Reduces ca and phos levels by reducing bone reabsorption
68
Effect of glucocorticoids on calcium
Inhibit bone breakdown reducing calcium but may cause osteoporosis long term
69
Effect of pth deficiency
Hypocalcaemia Hyperphosphatemia Neuromuscular excitability and tetany
70
What is pseudohypoparathyroidism
Resistance to pth leading to similar clinical picture to primary hypoparathyroidism.
71
Effect of Vit d deficiency
Rickets in kids Osteomalacia in adults
72
Effect of excess pth
Hypercalaciema Hypophosphatemia May be kidney stones or metal symptoms
73
What is secondary hyperparathyroidism
CKD Lack of 1.25 Vit d Chronically low ca Parathyroid hypertrophy
74
Effect of excess Vit d
High calcium and phosphate
75
Regions of the adrenal gland What do they secrete
Cortex: Zona glomerulosa - mineralocorticoids Zona fasciculata - glucocorticoids Zona reticularis - adrogenic hormones Medulla: Catecholamines
76
How do the adrenal steroid hormones work
Bind to cytoplasmic receptors Complex enters nucleus altering dna transcription.
77
What proportion of the mineralocorticoid activity is mediated by aldosterone What does the rest
95% Glucocorticoids
78
What stimulates aldosterone production
High plasma na Decreased plasma k Reduced ECF Trauma, stress, surgery, anxiety
79
Effects of mineralocorticoids
Reabsorption of na in kidneys, stomach, sweat, saliva and intestine. Reabsorption of water from kidneys Excretion of k and h from kidneys
80
Half life of aldosterone
20 minutes
81
Control of aldosterone secretion
Mainly angiotensin II as part of RAAS triggered by low na or reduced perfusion to juxtaglomerular apparatus Minor impact from ACTH
82
What is cortisol known as when given in medication from
Hydrocortisone
83
Main glucocorticoids produced by Zona fasciulata
Cortisol Corticosterone Cortisone
84
Production of aldosterone
Cholesterol [ACTH/angiotensin ii] Pregane derivatives Progesterone/corticosteroids [aldosterone synthase] Aldosterone
85
How is cortisol transported in plasma? Half life
Bound to a globulin, transcortin, albumin Half life 100mins but effects last much longer
86
What would be the effect of increased binding proteins on cortisol?
More bound, less free Less negative feedback More acth-rh, more acth, more cortisol produced until free back to equilibrium
87
Effects of glucocorticoids
Increased catabolism of protein and lipids, increased gluconeogenesis Anti-insulin effect Increased water excretion Increased sensitivity to catecholamines Facilitates na to adrenaline Increased RBC and pot Decreased wbcs Mineralocorticoid effects Anti inflammatory when at very high levels
88
What adrogenic hormones are released from the adrenal cortex Zona reticularis Fate of these
Dehydroepiandrosteone (dhea) Androstenedione - converted to testosterone and oestrogen in peripheral tissues and fat
89
Adrenaline synthesis pathway
Phenylalanine Tyrosine Dopa Dopamine Noradrenaline Adrenaline
90
What proportion of adrenal medulla cells secrete what
90% adrenaline 10% NA Small amounts of dopamine and opioid peptides
91
Where are additional areas of adrenaline synthesis found
Along course of aorta
92
What enzyme converts na to adrenaline
N methyltransferase
93
What breaks down catecholamines
Monoamine oxidase Catechol-o-methyl transferase
94
Effects of adrenaline and noradrenaline on heart rate
Adrenaline increases Na decreases
95
Effects of adrenaline and noradrenaline on cardiac output
A increases Na - decreases at low dose, increases at high dose
96
Effects of adrenaline and noradrenaline on peripheral vascular resistance
A - low levels decrease Na increases
97
Effects of adrenaline and noradrenaline on MAP
A - increase low levels Na - increase
98
Non cardiovascular effects of adrenaline and noradrenaline
Increases glycogenolysis, mobilisation of fatty acids, increased metabolic rate, increased heat production Nervous system stimulation
99
Primary receptor stimulated by noradrenaline Primary effects cardiovascularly Effect at higher doses
Alpha receptors Increased SVR Some beta effects at high doses increasing cardiac output
100
Primary receptor stimulated by adrenaline Primary effects cardiovascularly Effect at higher doses
Beta stimulation Increased heart rate and cardiac output. Vasodilates Some alpha effect at higher doses increasing SVR
101
What stimulates medullary hormone production in the adrenal gland
Sympathetic stimulation Needs glucocorticoids to activate n methlytransferase to convert na to a
102
What happens in congenital glucocorticoid deficiency
Upregulated acth Adrenal gland hypertrophy Excess androgen secretion - virilisation of females and precocious puberty in males Increased pigmentation
103
What causes secondary hyperaldosteronism
High renin production - cirrhosis, heart failure, some renal diseases
104
Features of Cushing syndrome
Muscle waisting, thin hair, poor skin, moon face and bufflo hump Hyperglycaemia Hypertension Hyperlipidaemia Osteoporosis
105
What functional units are there in the pancreas Rough function
Acini - exocrine function secreting digestive enzymes Islets of langerhans - endocrine function secreting hormones
106
Cells in the islets of langerhans and what they produce
B (or beta) cells - insulin A (or alpha) cells - glucagon D (or delta) cells - somatostatin F cells - pancreatic polypeptide
107
Structure of insulin Production
Polypeptide made of 2 aa chains linked by pair of disulphide bridges Produced in ER from prepropinsulin, part splits off, folds in two, and disulphide bridges form creating proinsulin. Then c-peptide part is removed forming insulin.
108
How is insulin the medication made
Either bovine or porcine (very close to human) or human by dna recombinant technology
109
Structure of insulin receptor How do they work
2 alpha (extracellular) and 2 beta subunits (transmembrane) Insulin binds to alpha, beta unit activates second messenger by tyrosine kinase. Main Effect is insertion of glut transporters into cell membrane
110
Main effects of insulin
Increased glucose uptake Increased glycogenesis Increased amino acid uptake Increased protein synthesis Increased fatty acid synthesis Increased k uptake Increased ketone uptake Decreased ketone synthesis
111
Structure and formation of glucagon
Polypeptide hormone Preproglucagon to proglucagon to glucagon
112
Effects of glucagon
Opposite to insulin Main effects glycogenolysis in liver (not muscle), gluconeogenesis, lipolysis, ketogenesis
113
Effects of somatostatin
Inhibition of insulin and glucagon Inhibition of pancreatic polypeptide Slows down the propulsive movement in the gi tract
114
Effect of pancreatic polypeptide
Uncertain Possibly to smooth out blood levels of glucose and amino acids after a meal by slowing food absorption
115
What stimulates insulin secretion
High glucose Glucagon Some beta receptor agonists Acetylcholine Sulphonyluresas
116
What inhibit insulin release
Adrenaline Somatostatin Beta blockers Alpha agonists Thiazides
117
What stimulates glucagon release
Hypoglycaemia Hunger Stress Trauma Infection Selective beta agonists
118
What inhibits glucagon release
Hyperglycaemia Somatostatin Insulin Ketones Free fatty acids Selective alpha agonists
119
Which glut channel is insulin sensitive
Glut 4
120
What is the influence of glucocorticoids on carb metabolism Significance
Needed for glucagon to cause gluconeogenesis Excess causes hyperglycaemia, deficiency hypoglycaemia
121
Effect of growth hormone on glucose metabolism
decreases uptake into cells Increases glycogenolysis Decreases binding of insulin
122
Likely pathology behind t1dm
T lymphocyte attack on beta cells in pancreas
123
Causes of insulin excess
Overtreatment with insulin Sulphonylureas or biguanides Rarely insulinoma

Primary Physiology (15 decks)

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