endocrine Flashcards
autocrine cell
prods substance that binds to specific receptor on own cell surface/receptors inside cell
local mediator
paracrine cell
prods substance that binds specific receptor on nearby target cell, e.g. NMJ
local mediator
endocrine cell
prods substance transported in blood, bind to specific receptors on distant target cells
sys to circulate hormones
endocrine glands
collection glands that secr hormones directly into circulatory sys to carry to distant target
cell types in islet of langerhans
- alpha secr glucagon
- beta secr insulin
- delta secr somatostatin
- F secr pancreatic polypeptide
production of insulin
beta cells synth pro-hormone proinsulin -> active insulin by removal water soluble polypep
half life 5-8mins
what does insulin bind to
specific tyrosine kinase mem receptor
how do beta cells cause prod insulin
- glucose enters via GLUT2
- raised intracellular gluc = incr ATP
- ATP sensitive potassium channs blocked
- K+ accumulates in cyt => depol cell mem
- causes V-gated Ca2+ channs open
- Ca2+ in => exocytosis vesicles cont insulin
neg feedback mech
further control of insulin
- GI hormones GIP + GLP-1 = anticipatory release to prevent surge in gluc absorp after meal
- parasymp activity incr secr during + after meal
- symp activity inhibit secr
- incr plasma aas after meal incr secr
where is gluc uptake independent of insulin
- brain (GLUT3 transporters)
- mammary gland, GI tract + kidney = 2AT coupled to Na+ transport
overview how insulin cause effects
- binds tyrosine kinase receptor
- receptor phosphorylates insulin-receptor substrates
- 2nd messenger pathways alter prot synth + existing prots
- => cell metab + mem transport changed
insulin in the liver
GLUT2 receptors can work either way
1. fasted = hepatocytes make gluc + transport out -> blood
2. fed = gluc -> hepatocyte + insulin stims hexokinase gluc -> gluc-6-p for low intracellular conc gluc
GLUT2 always present in cell mems
clinical signs insulin deficiency
- hyperglycaemia
- weight loss bc decr prot synth + incr prot breakdown
- PU/PD
- ketoacidosis bc lots B-ox bc needing E from fat metab => krebs = oxaloacetate -> liver for gluconeogenesis = ketone bods => lots
glucose in CNS
metab almost 100% reliant on gluc = steady transport in + can’t incr/decr rate
gluc level in CSF direct proportional to blood sugar
* excess incr osmolarity CSF => water out neurons
* too little = neurons starve
cells not sensitive to insulin
functions of insulin
- incr glucose oxidation
- incr glycogenesis
- incr lipogenesis
- incr prot synth
- inhibit enzs in catabolic processes
- inc cellular uptake of gluc + aas
==> incr stores glycogen, fat + prot
glucagon
- alpha cells secr + store as active
- water soluble polypeptide
- binds specific G-prot coupled mem receptor
half life 4-6 mins
what stims release glucagon
- decr blood gluc
- incr plasma aas after meal = avoid prot induced hyperinsulinemia (=> hypoglycaemia)
- parasymp activity
- symp activity
effects of glucagon
- incr gluconeogenesis
- incr glycogenolysis
- incr ketogenesis
catabolic
somatostatin effects
- decr secr growth hormone
- paracrine inhibition of insulin + glucagon release
diabetes mellitus clinical signs
- hyperglycaemia
- PD + PU
- ketoacidosis
can get a combo of type I + II
type I vs type II diabetes mellitus
1 = due inadequate insulin secr (more common dogs)
2 = due abnormal target cell responsiveness (more common cats)
why does diabetes cause PU/PD
incr gluc in blood => freely filtered into nephron + renal threshold for reabsorp exceeded => glucosuria => incr urine
AND ECF vol decr + plasma osmolarity incr => thirst centre in hypothal stimmed
why does diabetes cause ketoacidosis
‘fasted state’ => adipose tiss broken down => FAs in blood => liver uses beta-ox to break down but not all acetyl CoA can enter citric acid cycle => excess forms ketone bods, e.g. acetone => large amounts cause illness
topographical anatomy pituitary gland
- extends down from brain via thin stalk
- cradled + protected by sphenoid bone
anterior pituitary
made up endocrine cells derived from oral ectoderm of Rathke’s pouch = upgrowth epithel of pharynx towards base brain = endocrine gland
posterior pituitary
extension of hypothal (neural ectoderm) into anterior pit
* cell bods in hypothal
* axons = stalk of post pit
* nerve endings in post lobe
anatomy pituitary
2 fused glands
function post pit
release hormones synthed hypothal cell bods (oxytocin + ADH) -> caps
cap sys pit gland
== hypothalamic-hypophyseal cap portal sys in series
1. neurones synth tropic hormones -> cap sys 1
2. portal vessels carry neurohormones -> ant pit to act on endocrine cells
3. endocrine cells release peptide hormones -> cap sys 2 -> bod
tropic vs trophic hormones
tropic = causes release of another hormone
trophic = regs growth + development target organ
anterior pituitary hormones + their effect/target organ
all trophic hormones, all but prolactin tropic hormones
what kind of feedback do tropic hormones allow
short loop as ant pit hormones feedback to hypothal + long end-organ loop that can feedback to hypothal or ant pit
intermediate lobe of pituitary
- same embryological origin as ant lobe
- secr melanocyte=stimming hormones == MSH
label
thyroid location
2 lobes either side trachea just below larynx
hormone path to stim thyroid gland
neurones secr thyrotropin releasing hormone (TRH) -> portal vessels -> endocrine cells secr thyrotropin/thyroid stimulating hormone (TSH) -> thyroid gland
thyroid gland structure
spherical grps epithelial follicular cells around non-cellular filling
synth thyroid hormone
follicular cells:
1. trap iodide via NaI symporter, ox it to iodine + transport -> colloid
2. synth + transport thyroglobulin, tyrosine, enzs -> colloid
3. T3 + T4 synthed in colloid + bound thyroglobulin
4. droplets colloid reenter follicular cells by pinocytosis + bind lysosomes
5. Ts cleaved from thyroglob - lipophilic = diff into blood
6. Ts prot bound in blood
T(no.) indicates no. iodines it has
what are T3 + T4 bound to in blood
- 70-80% to thyroxine binding globulin (TBG)
- 20-30% to albumin
what are thyroid hormones
T3 = triiodothyronine
T4 = thyroxine
T4 = main hormonal product, T3 more biologically active so T4->T3 in peripheral tiss
metab of tyroid hormones
free T4 -> T3/reverseT3 (inactive, from deiodination)
free T3 in peripheral tiss (mostly from metab T4) - partic liver, musc, kidney
storage thyroid hormones
- colloid = store 2-3mo, bound to thyroglobulin
- prot bound in blood = store few days
as free mols bind target receptors more mols dissociate from TBG
reg thyroid hormones
secr TRH from hypothal driven by CNS
* long-loop + short-loop feedback but dominant reg pathway = TSH (incr thyroid horms in blood inhibit it)
* no TSH = thyroid follicular cells inactive
effect prolonged incr TSH conc
follicular hyperplasia + hypertrophy
goitre = enlarged thyroid gland
role thyroid hormones
- incr metab rate all tiss (except gonad, brain, spleen)
- => incr O2 consumpt + thermogenesis (so more thyroid horms after prolonged cold)
- required normal growth + development - incr prot synth + cell division
- required normal CNS development
- promote target responsiveness to symp NS
- promote axonal conductivity
- required normal gonadal function
all cells but CNS + testes have intracellular receptors for thyroid horm
iodine deficiency
sheep are prone if on sheep deficient pasture
* cabbage reduces iodine uptake
hormone classes
- water soluble bind receptors on cell surface - insulin, glucagon
- lipid soluble mostly bind receptors in cyt/nucleus
water soluble hormones
- freely soluble in plasma
- bind cell surface receptors
- activate 2nd messenger sys w/in cell = amplify signal
- rapid action
- short half-life
- metabed by liver + excreted in kidney
lipid soluble horms
- mostly bind cytosolic/nuclear receptors
- prot bound in plasma (store) + free portion physiologically active
- require carrier prot for transport in blood
- less immediate action
- longer 1/2-life
affected disturbances plasma prot conc
advantages carrier prots for horms
- hormone reservoir - active interacts w receptor, used, new particles detach from transport prot
- hormone buffer - prevent spikes in active hormone conc, e.g. during synth = more stable long-term conc
- reduce hormone loss - prot bound horms no filtered out at kidneys but free lost in urine
disads carrier prots for horms
- affected by disruptions blood levels carrier prot - decr = incr free horm conc
- competition from substances like drugs - esp less specific, e.g. albumin
reg growth hormone (GH) secr
by 2 hypothalamic neurohorms:
1. GHRH
2. GHIH = somatostatin
direct effects + stims liver prod insulin growth factor-1
* mediates growth-stimming effects of growth horm (neg feedb on GH secr cells in pit + stims GHIH in hypothal)
from ant pit
GH vs IGF-1
- prot (191aas) vs peptide (70aas)
- 50 vs 95% prot bound
- both tyrosine kinase receptor
- GH sim struct prolactin vis IGF sim proinsulin
GH-synthing cells = most abundant cells in ant pit
what incr GH secr
- CNS input
- strenuous physical activity
- starvation
- stress
- decr plasma gluc + FFAs
- incr plasma aas
- ghrelin from parietal cells + hypothal
- thyroid horm, androgens + oestrogens
functions GH
- stim growth body mass + elongation bones - essential growth until sk complete)
- bone, cart, soft tiss growth
- lactation
- anabolic: stim prot synth, lipolysis, inhibit tiss uptake + use gluc
what is required for normal growth
- GH
- thyroid hormones
- insulin
- sex horms at puberty
- adequate diet, absence chronic stressors, disease
result of excessive GH prod
before growth plate closure = gigantism
after growth plate closure = acromegaly = grow too fast
how is Ca in bone found
hydroxyapatite = complex of calcium phosphate
calcium homeostasis where
reg Ca2+ + phosphate linked conc free Ca in plasma
* tight reg w/in 2% of limits at 2.5mM/l (50% free, 10% assoc anions, 40% prot bound)
how does Ca homeostasis occur
- intestinal absorp
- renal excr
- release + uptake from bone
vit Ds where proded
D2 proded by plants
D3 proded by action UV light
v lil biological activity until hydroxylated
hydroxylation vit D
- 1st in liver -> stored adipose tiss
- 2nd in kidney -> active form calcitrol
active form inhibits enzs hydroxylase enzs to reg
role calcitrol
transported bound globulin -> bind intracellular receptors incr conc Ca in plasma by:
* incr Ca2+ + PO43- uptake from SI
* incr renal reabsorp Ca
* incr mobilisation Ca from bone
lipid soluble
parathyroid glands
2 pairs glands (cr + cd) at poles 2 lobes thyroid
* chief cells make parathyroid horm (PTH)
release PTH
cells in gland detect v small decr free Ca => release PTH incr Ca conc in plasma:
1. incr absorp Ca from GI tract (indirect via calcitrol)
2. incr mobilisation Ca from bone
3. decr urinary excr Ca
neg feedback loop
PTH related prot (PTHrP)
same struct as N terminal end PTH = activates same receptors w same function
* more diverse actions, e.g. cell proliferation
* proded some cancers = no neg feedback = overprod = hypercalcaemia
proded most tisses
calcitonin
made C-cells (parafollicular cells) of thyroid gland
label
thyroid follicle
role calcitonin
secr in response incr free Ca2+ to decr by affecting transport mechs in bone
* targets osteoclasts = bone remodelling less active = flux Ca/P bone -> plasma decr
not essential in terrestrial vertebrates
oter effects calcitonin
- incr urinary loss
- decr gut absorp Ca
how is phophate in bod
85% in bone as hydroxyapatite
ICF + ECF as:
* inorganic phosphates (H2PO4-) + (HPO42-)
* organic phosphates: phospholipids, nucleotides, ATP…
phosphate homeostasis
normally kept w/in normal limits in Ca2+ metab
* absorbed in intestines, filtered, reabsorb, secr in urine
* calcitrol incr absorp from GI tract
depends on urinary excr as opposed absorp from SI for Ca2+
what does PTH do to phosphate
- decr serum phosphate
- incr urinary excr phosphate
- incr calcitrol secr
result of chronic kidney disease
hyperphosphataemia stims PTH prod + inhibits activation vit D
late preg/partur + Ca homeostasis
- mammary cells extract large amount Ca2+ from ECF
- mineralisation foetal skeleton late preg
homeostatic mechs have supply incr demand Ca
laying hens + Ca homeostasis
- 2wks b4 lay oestrog + progest stim extra bone dep BM cavities
- incr oestrog = incr Ca-binding plasma prots
- shell synth starts = PTH incr…
adrenal gland
== suprarenal gland
* paired beneath peritoneum
* cranio-medial to each kidney
zones adrenal gland
- medulla = symp neuroendocrine cells ((nor)adrenaline)
- zona reticularis secr androgens
- zona fasciculata secr glucocorticoids - cortisol
- zona glomerulosa secr mineralocorticoids - aldosterone
derivation steroid horms
= adrenocortical horms
- all from cholesterol -> prenenalone
- -> glucocorticoids/mineralocorticoids/androgens
proded on demand, not stored locally
1 = rate-limiting step
glucocorticoids
- affect CHO (gluc), lipid + prot metab + help animals resist effects of stress
- bound CBG + albumin in blood
- inactivated liver
1/2 life longer than aldosterone bc more tightly prot bound
what do mineralocorticoids do
homeostasis of Na+ + K+ in blood (affects blood vol/press)
* bound corticosteroid-binding globulin (CBG) + albumin in blood
* inactivated in liver
1/2 life 20mins
what does aldosterone do
- cause rapid incr Na+ reabsorp + K+ secr in principal cells DCT + CD
- incr Na+ reabsorp salivary glands + LI
==> reabsorp water = incr vol ECF + incr art press
methods reg aldosterone
- plasma K+ depolarises cell mem proding cells = prod
- RAAS renin in response decr bp
- ACTH required secr but minor role reg
- decr Na+ in ECF moderately stims secr
glucocorticoids release
- receptors in all nucleated cells
- released response high sustained levels stress (infection, trauma, psychological)
essential for life
variation in secr glucocorticoids
circadian variation strong in humans + in domestics but less pronounced
what do glucocorticoids do relation gluc
reg gluc metab:
* promote gluconeogenesis in liver
* decr gluc uptake by tiss other than brain
== incr blood sugar levels = assist bod cope w stress
Cushing’s syndrome
hyperadrenocorticism = too much glucocorticoids + mineralocorticoids = hyperglycaemia, muscle wastage, hair loss, PU/PD due interference w ADH
Addisons disease
hypoadrenocorticism = not enough glucocorticoids/mineralocorticoids = keep too much K+, lose too much Na+ =
* cardiac arrhythmias (K+) inc bradycardia
* hypovolaemia (bc hyponatraemia)
==> hypovolaemic shock (can’t incr HR) = circulatory collapse
what do glucocorticoids do related fat + prot
- incr lipolysis
- incr breakdown sk musc prots = substrate for gluconeogenesis
==> for ox FAs + aas for E use = preserve gluc
other roles glucocorticoids
- permissive action on other horms, e.g. catecholamines cause vasoconstr
- IS to maintain low-level inflammation - high conc cortisol (e.g. at partur) = immunosuppression (stop inflamm, allergic reactions)
- Ca balance via effects GI tract, bone, kidney
- prot catabolism inhibits DNA synth so growth
reg glucocorticoids
neg feedback as cortisol inhibits ant pit + hypothal + ACTH (stims cortisol) inhibits hypothal
acth
adrenocorticotropic hormone
- required for cholesterol -> pregnenolone (= for all hormones proded adrenal cortex)
- regs androgen + glucocorticoid prod
reg glucocorticoids vs mineralocorticoids
mineralocorticoids = also renin, Na+ conc (external factors)
catecholamine secr
normally low, not essential for low, incr by stress + hypoglycaemia
catecholamines
adrenaline, noradrenaline, dopamine
* proded adrenal medulla
* derived aa tyrosine
* water soluble
reg catecholamine release
controlled preganglionic symp nerve fibres
functions catecholamines
- incr CO (incr HR, contractility, bp)
- redistribute blood -> sk musc
- incr plasma [gluc] (glycogenolysis, gluconeogenesis)
- incr breakdown triglycerides -> FAs
urinary excr adrenaline good measure activity adrenal medulla
horms that influence blood gluc
w origin + effect
- insulin, pancreatic beta, decr
- GLP-1, intestinal L, decr
- somatostatin, pancreatic delta, decr
- glucagon, pancreatic alpha, incr
- adrenaline, adrenal medulla, incr
- cortisol, adrenal cortex, incr
- growth hormone, ant pit, incr
- thyroxine, thyroid gland, incr
prolactin vs GH
v similar struct w similar receptor (tyrosine kinase)
* water soluble
what does prolactin do
- stims growth + diff mammary tiss
- stims milk prod after partur
- important in maternal behaviour
- luteotrophic in bitch
- incr prior to onset brooding in birds
reg prolactin
horms from hypothal:
* TRH stims
* dopamine inhibits
- oestradiol stims secr via direct effect on proding cells in ant pit (causes hyperplasia + hypertrophy)
- suckling reduces dopamine secr = incr prolactin secr
pineal gland
- centre of brain bet 2 hemispheres behind thalamus outside BBB
- tryptophan -> serotonin -> melatonin (secrs m)
in mammals
what affects melatonin secr
light exposure to eyes (photoperiods)
circadian rhythms
body clock
primary clock in suprachiasmic nuclei in hypothal w inputs from cells at back retina
* melatonin causes drowsiness + lowers body temp
leptin is
- peptide horm in grp adipokines
- stored in adipose tiss + secr incr in parallel w body fat stores so plasma level indicated level triglyc stored adipocytes
leptin does
regs E intake + expenditure inc appetite + hunger, metab + behaviour
* binds receptor in hypothal to inhibit food intake
insufficient food = decr leptin = incr appetite
clinical signs milk fever
- sk musc weakness, tremors, recumbency
- head tucked into flank
- hypothermia
- bloat
- constipation
- urine retention
- dystocia = uterine inertia
- dilated pupils
older = slower to mobilise Ca stores = more common
CKD in relation Ca + P
less P excr = retained = hyperphosphataemia => hyperparathyroidism
1. directly
2. P binds ionised Ca = hypocalcaemia => release PTH
3. P decr calcitriol prod + calc decr PTH release normally
label
pituitary gland
label
thyroid + parathyroid glands
* CT capsule around each
* trabeculae to divide each into lobules
label
pancreas
label
mammary gland
