PHYS - Endocrine Flashcards
(87 cards)
1
Q
endocrine vs exocrine glands
A
- endocrine: secrete chemicals that travel long distances in the blood to their target organ (no ducts)
- exocrine: secrete chemicals that travel short distances to their target organ via ducts
2
Q
hormones produced by the hypothalamus
A
- stimulate anterior pituitary: TRH (thyrotropin-releasing hormone), GHRH, CRH, GnRH (gonadotropin-releasing hormone)
- inhibitory hormones: DA (dopamine), SST (somatostatin)
- released by posterior pituitary: oxytocin, ADH
3
Q
hormone secreted by the pineal gland
A
- melatonin
4
Q
hormones secreted by anterior pituitary
A
- GH
- TSH
- LH
- ACTH
- FHS
- prolactin
5
Q
hormones secreted by posterior pituitary
A
- oxytocin
- ADH
6
Q
hormones secreted by thyroid gland
A
- triiodothyronine (T3)
- thyroxine (T4)
- calcitonin
7
Q
hormone secreted by liver
A
- IGF-1 (insulin-like growth factor > stimulated by GH)
8
Q
hormones secreted by GIT
A
- gastrin
- ghrelin
- secretin
- cholecystokinin (CCK)
- somatostatin (SST)
- GLP1 and GIP
9
Q
hormones secreted by the pancreas
A
- insulin
- glucagon
- SST (somatostatin)
10
Q
hormones secreted by adipose tissue
A
- leptin
- adipokines
11
Q
hormones secreted by the kidneys
A
- renin
- erythropoietin (EPO)
- calcitriol (active form of vitamin D)
12
Q
hormones secreted by adrenal cortex
A
SALT, SUGAR, SEX
- mineralocorticoids (aldosterone)
- glucocorticoids (cortisol, corticosterone)
- weak androgens (DHEA, androstenedione)
13
Q
hormones secreted by adrenal medulla
A
- adrenaline
- noradrenaline
14
Q
hormones produced by ovaries
A
- progesterone
- oestrogens (oestradiol, oestrone)
- androgens (androstenedione, testosterone)
- inhibins
15
Q
hormones produced by testes
A
- androgens e.g. testosterone
- oestrogens (oestradiol, oestrone)
- inhibins
16
Q
hormones produced by placenta (when pregnant)
A
- progesterone
- oesterogen
- human chorionic gonadotropin
- human placental lactogen
17
Q
hormones produced by uterus when pregnant
A
- prolactin
- relaxin
18
Q
3 types of hormones + e.g.s
A
- protein/peptide (most common) e.g. insulin
- steroid e.g. cortisol, aldosterone
- amine hormones (derivatives of tyrosine) e.g. adrenaline, noradrenaline, T3, T4
19
Q
synthesis of a protein/peptide hormone
A
- preprohormone produced @ ribosome
- cleaved into inactive pro hormone @ RER
- pro hormone modified in Golgi
- secretory vesicle cleaves prohormone to make active hormone > exocytosis
20
Q
protein hormone signalling pathway
A
- binds to specific receptor
- activates secondary messenger e.g. cAMP > initiates protein kinase cascade
- protein kinase can directly affect cellular function, OR act as a transcription factor, switching on a gene for a particular protein
- single hormone can have many effects on a cell
21
Q
features of steroid hormones
- what are they derived from?
- are they hydrophilic or hydrophobic?
- what controls their synthesis?
- are they always synthesised?
- how are they released from a cell?
- how are they transported?
A
- derived from cholesterol
- hydrophobic
- synthesis is controlled by protein hormones
- synthesised as needed
- secreted by diffusion b/c lipophilic, not exocytosis
- mostly bound to protein, but small amounts are free
22
Q
compare a protein-producing cell with a steroid-producing cell
A
- protein: lots of RER, Golgi and secretory vesicles
- steroid: lots of mitochondria and lipid droplets (store of cholesterol)
23
Q
steroid hormone signalling pathway
A
- diffuses thru plasma membrane and binds to an INTRACELLULAR receptor
- receptor-hormone complex enters nucleus and binds to specific region of DNA
- this initiates synthesis of a new protein = slower acting than protein hormones
24
Q
two types of amine (tyrosine) hormones
- e.g.
- where are they made
- hydrophilic or lipophilic?
- how are they transported
- where are the receptors
A
- catecholamines (e.g. adrenaline + noradrenaline): made by adrenal medulla or hypothalamus, hydrophilic, transported freely in plasma, receptor ON target cell
- thyroid hormones (T3 + T4): made by thyroid gland, with 2 tyrosines and iodine. lipophilic, bound to transport proteins, receptors IN target cell
25
3 factors which determine the plasma levels of hormones
- rate of synthesis and secretion
- binding proteins in plasma
- rate of removal from blood
26
3 main stimuli for hormone secretion
- plasma concentration of ions/nutrients (negative feedback e.g. decreased Ca2+ stimulates PTH secretion)
- neurotransmitters
- other hormones
27
patterns of hormone secretion
- some released in a circadian pattern e.g. cortisol
- some released in short bursts - up and down plasma concentrations e.g. LH, FSH
- or both: e.g. GH
28
function and e.g.s of free vs protein bound hormones
- free (H2O soluble): has biological activity e.g. protein and amine (catecholamine) hormones
- bound (lipid soluble): provides a reservoir and slows the metabolism of hormones. CANNOT be metabolised e.g. steroid and amine (thyroid) hormones
- free + bound hormones are in equilibrium
29
positive feedback example
- uterine contractions cause baby to push against cervix
- cervical stretch causes oxytocin release from posterior pituitary which further triggers uterine contractions
30
4 main endocrine disorders
- hyposecretion (enzyme deficiency or partial destruction of a gland)
- hypersecretion (usually tumour evades -ve feedback system and continuously produces hormone)
- hyporesponsiveness of a target cell to a hormone
- hyper-responsiveness of a target cell to a hormone
31
synthesis/secretion pathway of oxytocin + ADH
- both synthesised in separate clusters of neurons in PVN and SON (hypothalamus)
- transported down the axon to posterior pituitary
where they are stored in herring bodies (outpouchings of vesicles in nerve terminals)
- neurotransmitters acting on the PVN and SON generate an AP > causes release of stored hormone into blood by exocytosis
32
hypophysiotropic (hypothalamic releasing/inhibiting) hormones
- what are they?
- why are they important?
- e.g.s
- hypophysiotropic hormone triggers secretion of anterior pituitary hormone > triggers secretion of a hormone from another gland, which acts on target cells (EXCEPT dopamine)
- allow amplification of a small number of neurons into a large peripheral response
- e.g. CRH, thyrotropin-releasing hormone (TRH), somatostatin (SST), GHRH, GnRH, dopamine (DA)
33
secretion pathway of hypophysiotropic hormones
- after exocytosis from neurons, they enter median eminence capillaries and are carried by hypothalamo-hypophyseal portal vessels to anterior pituitary
- diffuse into interstitial fluid of anterior pituitary and bind to specific membrane-bound receptors to stimulate or inhibit the release of anterior pituitary hormones
34
function of GnRH, GHRH and SST
- GnRH: stimulates production of LH + FSH by anterior pituitary > act on gonads to control spermatogenesis and folliculogenesis
- GHRH stimulates and SST inhibits secretion of GH by anterior pituitary, which acts on liver + other tissues to control growth + metabolism
35
function of TRH, DA, CRH
- TRH: stimulates release of TSH by anterior pituitary, which acts on thyroid to produce T3 and T4
- DA: inhibits prolactin release by anterior pituitary which acts on breasts
- CRH: stimulates release of ACTH by anterior pituitary which acts on adrenal cortex
36
'long + short loop' negative feedback
- long loop: e.g. in hypophysiotropic hormones, increasing concentrations of the 3rd hormone in sequence can stop production of the 1st/2nd hormones
- short loop: when the 2nd hormone inhibits production of the 1st hormone (less common)
37
growth hormone
- is it mostly free or bound?
- functions
- pathologies
- mostly free, but a significant proportion is bound which increases its 1/2 life
- stimulates bone lengthening, increased muscle mass and growth of all organs except the brain (via IGF-1)
- promotes lipolysis, reduces muscle and fat uptake of glucose, increases gluconeogenesis in liver (independently of IGF-1)
- too much = gigantism (children) or acromegaly (adults), too little = dwarfism
38
factors which increase GH secretion
- sleep
- exercise
- stress
- postprandial decline in BGL
- increase in specific amino acids
39
factors which inhibit GH secretion
- postprandial hyperglycaemia
- elevated free FAs
- elevated IGF-1 (insulin-like growth factor-1)
- aging
40
IGF-1 functions
- GH causes IGF-1 to be secreted by tissues e.g. liver, bone, muscle and mediates the growth effects (if people have low IGF-1 they can have a short stature despite normal GH levels)
- also regulates -ve feedback of GH production
41
which signalling pathways does GH activate?
- JAK2 and Src
42
gigantism vs acromegaly + Tx
- gigantism = increased GH in children = abnormal lengthening of bones
- acromegaly = increased GH in adults = abnormal thickening of bones and loss of circadian pattern of secretion
- Tx: surgery to remove pituitary tumour which is causing excess secretion OR dopamine agonists, somatostatin analogs or GH receptor antagonists
43
two types of dwarfism + Tx
- idiopathic
- laron: reduced sensitivity to GH due to mutations in receptors or binding proteins
- Tx: daily subcut or IM injections of GH for as long as the child is growing
44
features of normal growth
- regulated by 3 factors: endocrine status, nutrition, heredity
- involves hypertrophy, hyperplasia and differentiation of cells
45
other hormones responsible for regulating growth (apart from GH)
- oestrogen and testosterone: stimulate secretion of GH and IGF-1 to induce growth patterns at puberty - hands and feet, limbs and trunk. BUT ALSO promote epiphyseal fusion to terminate growth spurt
- insulin is required for GH to promote growth including in utero
- thyroid hormones are necessary for GH to promote growth (regulate metabolic rate and growth of bones)
- glucocorticoids inhibit bone mineralisation and growth of all tissues except gonads
46
effects of oestrogen vs testosterone in growth
- testosterone: promotes linear increase in muscle mass and body weight
- oestrogen: very low concentrations stimulate growth, high concentrations inhibit growth
47
leprechaunism
- children are born small and stay small due to insulin receptor defects
48
processes which require calcium
- bone formation
- muscle contraction
- normal heart rhythm
- signal transduction
- insulin release
- neurotransmission
- blood clotting
49
calcium
- what proportion is free?
- 3 sites which regulate Ca2+ in the body
- 50% free (active)
- GIT + kidneys control intake/output of Ca2+ and bones control distribution
50
how is bone resorbed and remodelled?
- osteoblasts signal for differentiation of osteoclast precursors into mature osteoclasts
- osteoclasts break down bone by secreting H+ (which dissolves crystals) and hydrolytic enzymes (which digest osteoid) = releases Ca2+ and phosphate into the blood
- osteoclasts also release growth factors such as INF and TGF-B which recruit and mature osteoblasts
- osteoblasts take up Ca2+ and phosphate for formation of bone osteoid
51
hormones which favour bone resorption (decreased bone mass)
- PTH
- cortisol
- thyroid hormones
52
hormones which favour bone formation (increased bone mass)
- GH + IGF-1
- insulin
- oestrogen
- testosterone
- calcitonin
53
how do hormones regulate bone remodelling
- RANKL (ligand) expression is stimulated by PTH, vit D, cortisol
- osteoblasts express RANKL which binds to RANK receptor on the surface of osteoclast precursors = increased osteoclast differentiation + activity
- OPG (decoy receptor) expression stimulated by oestrogen (explains post-menopausal osteoporosis)
- osteoblasts also produce OPG that binds RANKL = inhibits bone resorption
- therefore balance between OPG and RANKL determines level of bone resorption
54
effect of PTH on the GIT
- PTH stimulates formation of vit D, which increases intestinal absorption of Ca2+
- PTH = indirect effect
55
role of bones in STORING calcium
- store 99% of total body calcium
- per day, 500mg of bone gets mineralised and resorbed but more can be resorbed if levels drop in the body
56
3 main hormones which regulate calcium concentration
- PTH
- vit D
- (calcitonin) - limited role in humans
57
what regulates PTH secretion?
- normal/high Ca2+ activates Ca2+ sensing receptor on chief cells of parathyroid glands = signalling cascade inhibits PTH synthesis and release
- low Ca2+ inactivates Ca2+ sensing receptor on chief cells = signalling cascade inhibits PTH synthesis and release = removes inhibition of PTH synthesis
58
MOA of PTH
- directly increases resorption of bone by osteoclasts = increased Ca2+ and phosphate in blood
- also stimulates formation of vit D = increased intestinal absorption of Ca2+ and phosphate
- also stimulates renal Ca2+ reabsorption
59
formation of 1,25-(OH)2 vit D
- we intake dietary vit D3 AND sunlight triggers formation of vit D3 in skin
- transported to liver and OH group added by 25-hydroxylase = 25-OH-D
- transported to kidneys and second OH group added by 1-hydroxylase = 1,25-(OH)2-D - stimulated by PTH
60
function of vit D
- stimulates intestinal absorption of Ca2+ and phosphate
- also stimulates resorption of bone by osteoclasts
- DOES NOT promote renal reabsorption of Ca2+
61
calcitonin
- where is it secreted?
- function
- use in humans
- parafollicular cells of the thyroid gland
- counteracts PTH by inhibiting osteoclasts activity and renal + GIT reabsorption of Ca2+
- debated role in humans
- inhibits osteoclastic bone resorption in so used to treat hypercalcaemia + osteoporosis
62
rickets
- deficient mineralisation in bone matrix due to vit D deficiency > bones are soft and easily fractured
- also causes varus deformity (bowleggedness) due to weight bearing on weakened developing bones
63
osteoporosis + Tx
- loss of bone matrix and minerals due to imbalance between bone formation and resorption = increased fragility of bone and risk of Fx
- greater effect on highly trabecular bones e.g. pelvis, vertebrae
- can be caused by excess hormones that favour bone resorption or too little hormones that favour bone formation
- Tx: bisphosphonates (inhibit osteoclastic activity), calcitonin, selective oestrogen receptor moderators (SERMs)
64
risk factors for osteoporosis
- increased PTH and RANKL
- decreased oestrogen
- decreased Ca2+/vit D
65
hypercalcaemia
- pathophys
- Sx
- caused by hyperparathyroidism (tumour causing excess PTH secretion and therefore vit D secretion by the kidney) = increased bone resorption, intestinal Ca2+ reabsorption, decreased renal Ca2+ excretion
- Sx: fatigue, depression, bone weakening, N&V, muscle weakness
66
hypocalcaemia
- pathophys
- caused by hypoparathyroidism = decreased PTH and vit D from kidney = decreased bone resorption, decreased intestinal Ca2+ absorption and renal reabsorption
- increased excitability of nerves and muscles
67
bone density test interpretation
- given as T score (no. of standard deviations)
- T score of -1 or more = normal
- T score between -1 and -2.5 = osteopenia
- T score lower than -2.5 = osteoporosis
68
catecholamine synthesis pathway + rate limiting step
- tyrosine > L-dopa > dopamine > noradrenaline > adrenaline
- rate-limiting step = conversion of tyrosine to L-dopa via tyrosine hyroxylase
69
difference between adrenaline + noradrenaline
- adrenaline binds to a- and B- receptors (non-specific)
- noradrenaline mostly binds to a-receptors (more specific)
70
adrenaline MOA
- binds to a- or B- receptors > activates G proteins
- adenylyl cyclase generates cAMP = binds and activates protein kinase A (PKA)
- PKA mediates fight/flight response
71
what is the hypothalamic-pituitary-adrenal (HPA) axis and how does it work?
- regulates adrenal cortex hormones
- circadian rhythm + stress stimulate parvocellular neurons in the PVN to secrete CRH into hypophyseal portal vessels
- CRH induces anterior pituitary to produce ACTH (can also be stimulated by ADH)
- ACTH stimulates adrenal cortex to produce steroid hormones (mostly cortisol and aldosterone) by increasing activity of enzymes
- cortisol feeds back to pituitary + hypothalamus to suppress ACTH + CRH production (-ve feedback)
72
cortisol MOA
- transported in blood bound to corticosteroid-binding globulin (CBG)
- released from CBG and binds to cytosolic glucocorticoid receptors in cells (CGR)
- hormone-receptor complex binds to specific sites on DNA (glucocorticoid response elements)
- gene expression altered to produce various proteins based on response
73
functions of cortisol
- during fasting, cortisol promotes gluconeogenesis by promoting breakdown of proteins + lipolysis and upregulating liver enzymes that do so
- increases adrenergic (a/B) expression to regulate BP and CO
- immunosuppressive/anti-inflammatory function
- decreases reproductive and growth function due to high anabolic cost
74
3 phases of stress - general adaptation syndrome (GAS)
- alarm reaction (<48 hrs) - adrenaline + noradrenaline: initial decrease in stress b/c fight/flight is mobilised, then increase
- resistance (>48 hrs) - cortisol: increased adaptation to initial stressor but decreases to additional stressors
- exhaustion (1-3 months - still elevated cortisol): muscle wasting, immune atrophy, hyperglycaemia, vascular damage - decreased ability to cope
75
thyroid hormone trigger pathway
- cold, stress, circadian rhythm triggers hypothalamus to produce TRH into hypothalamo-hypophyseal portal system
- TRH binds to G-protein coupled receptor on thyrotroph cells in anterior pituitary > stimulates production of TSH
- TSH enters general circulation and binds to receptor on surface of thyroid epithelial cells
- thyroid follicles produces T3 (active - 10%) and T4 (pro-hormone - 90%)
76
how is T4 converted to T3
- mostly via type I deiodenase (tissues w/ high blood flow e.g. liver, kidneys) = supplies T3 for uptake by other tissues
- type II deiodenase helps maintain constant levels of T3 even if T4 levels drop = expressed in glial cells of CNS
77
T3/T4 synthesis process
- circulating iodide is co-transported w/ Na+ across basolateral membrane of follicular epithelial cells, through the cell and into the lumen (colloid), where iodide is oxidised to iodine
- follicular cells produce thyroglobulin (which contains tyrosine) and secrete into colloid
- iodine attaches to tyrosine within thyroglobulin, mediated by thyroid peroxidase
- iodine/thyroglobulin complex goes back into epithelial follicular cells, where lysozymes break it up into T3/T4 = go into blood
78
functions of T3/T4
- growth: maturation of bone, tooth, hair, nail
- CNS: development of CNS, emotional tone, enhances alertness/responsiveness
- metabolism: increased glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis = increased fuel sources to maintain metabolism
- BMR: increased activity of Na+/K+ ATPase and therefore metabolic heat production, O2 consumption, BMR
- CVS: increased CO by up-regulating B-receptors
79
which factors trigger insulin secretion
- high BGL
- amino acids
- incretins
- parasympathetic nervous system
80
how is high blood glucose regulated
- low-affinity GLUT2 transporter acts as glucose sensor on B cells
- high BGL = increased respiration and ATP production = closed K+ channels = depolarisation
- triggers opening of Ca2+ channels = release of insulin
- 50% of insulin is degraded in liver and never reaches general circulation
- the other 50% causes GLUT4 transporter (high affinity) to rise to surface of cell and promote glucose uptake in muscle + liver cells, as well as glycogenesis, protein synthesis and lipogenesis
81
relative affinity + expression of GLUT1, 2, 4 transporters
- GLUT1: high affinity, constant expression
- GLUT2: low affinity, constant expression
- GLUT4: high affinity, inducible expression
82
where are GLUT 1, 2 and 4 found?
- GLUT 1: basal glucose uptake in cells
- GLUT 2: found in pancreas
- GLUT 4: adipose tissue
83
how is low blood glucose regulated
- low BGL triggers a-cells of pancreas to produce glucagon
- glucagon triggers lipolysis, glycogenolysis, gluconeogenesis
84
structures of islets of langerhans
- 70% B-cells (insulin)
- 20% a-cells (glucagon)
- <10% delta cells (SST)
- <5% PP cells (pancreatic polypeptide)
85
healthy BMI range
- 20-25
86
causes of proteinuria
- fever, exercise, glomerulonephritis
87
causes of haematuria
- UTI
- contamination from menstruation
- vit C intake = false -ve
