endocrine system Flashcards
What is the overall ‘goal’ of the endocrine system
secrete chemicals that affect different parts of the body to maintain bodily functions and homeostasis
what are the 3 types of signalling in the endocrine system
autocrine = self
paracrine = neighbouring cell (close)
endocrine = target cell through blood stream (distant)
what are some major functions of the endocrine system
growth and dev
pregnancy
sleep and wake cycles
temp regulation
muscle and strength dev
what are the two diff types of glands in the endocrine system
endocrine (ductless > secretes into surrounding fluids)
exocrine (ducted > travel through these)
what are the two types of endocrine glands
classical and nonclassical
give examples of non classical glands and one eg of their chemicals
heart - ANP
skin - vitamin D
stomach - gastrin
kidney - renin
placenta - oestrogens
liver - thrombopoietin
give examples of classical glands (MAJOR GLANDS)
pineal gland, hypothalamus, pituitary gland > CENTRAL
thyroid gland
parathyroid glands
adrenal glands
pancreas
ovary
testes
thymus > PERIPHERAL
what are the three types of hormones
peptide, steroid, amine
describe peptide based hormones
amino acids, varying lengths, hydrophilic, short life span, stored in secretory vesicles, released via exocytosis
describe steroid based hormones
derived from cholesterol, extended life span due to being bound to carrier proteins, synthesised when needed, activate genes for protein synthesis
describe amine hormones
from tyrosine (catecholamines, thyroid hormones) + tryptophan (melatonin)
what are the two types of tyrosine derived amine hormones
catecholamines - tyrosine derived, hydrophilic, extracellular receptors, e.g noradrenaline, adrenaline and dopamine > MORE LIKE PEPTIDES
thyroid hormones - iodinated tyrosine derived, hydrophobic, intracellular receptors > MORE LIKE STEROIDS
what are the two types of receptors
intracellular (for steroid hormones) and cell surface (for peptide hormones)
what are the two cell surface receptors
g coupled protein (ligand bind > ion channel open)
receptor enzyme (ligand bind >enzyme activate)
what are intracellular receptors
found in nucleus and cytoplasm
what is signal transduction
receptor enzyme > amplifying enzymes activated > many secondary messengers > series of reactions > SIGNAL TRANSDUCTION
what determines the extent of hormone activity
number of receptors (down regulation/up regulation)
amount of hormone circulating
bond affinity
what is up regulation
target cells form more receptor cells usually in response to increased hormone
what is down regulation
target cells lose receptor cells usually in response to decreased hormone
what are the 4 factors of timing of hormones
onset
duration
clearance
half life
what are the types of hormonal stimulation
humoral = level of substance in the blood
neural = nerve fibres
hormonal (TROPIC) = stimulated by another hormone
what are the three types of hormone combinations
permissiveness = one hormone permits the action of another
antagonist = one hormone reduces the effect of another
synergism = ‘summation’ of action of multiple hormones
negative feedback eg of endocrine system
TRH from hypothalamus > TSH from pituitary gland > T4 and T3 from thyroid gland > system metabolic effects > homeostasis
factors which affect hormone concentration
rate of secretion (most commonly regulated)
rate of binding (to carrier proteins)
rate of metabolism (activation/degradation)
what is a primary disorder
abnormality in the gland
what is a secondary disorder
normal gland, but too much/little stimulation
what is hyposecretion and what disease can it lead to
too little hormone secreted e.g diabetes
what is hypersecretion and what disease can it lead to
too much hormone secreted e.g tumour/cancer
causes of endocrine dysfunction
problems in the signal transduction pathways
down regulation
loss of stimulus
autoimmune destruction of gland
how can endocrine dysfunction be treated
hormone supplements
drugs to promote/decrease release of hormones
what are the structures in the pancreas
pancreatic islets
exocrine cells
endocrine cells (beta cells, alpha cells, D cells, pp cells)
bile duct
pancreatic duct
explain how glucose stimulates insulin secretion
glucose enters cell
oxidative metabolism occurs
increased ATP
closed potassium ATP channels
depolarisation
opening of voltage gated Ca2+ channels
increase Ca2+
insulin secretion
explain how insulin promotes glucose entry into skeletal muscles and adipose tissue
insulin binds to receptor
signal transduction cascade occurs
exocytosis of GLUT 4
increase glucose entry into cells
explain how insulin promotes glucose utilisation
insulin binds to receptor
activates secondary messengers
secondary messenger pathways are initiated
increase in transcription factors and enzymes
changes in metabolism
what cells release insulin
beta
what cells release glucagon
alpha
explain how liver and skeletal muscles store excess glucose as glycogen
high insulin
GLUT 2 helps move glucose into liver cell
signal cascade occurs
ATP used in the process of converting glucose into glycogen via glycogen synthase
explain the regulation of insulin secretion in the case of low plasma glucose
sympathetic stimulation (adrenaline)
low free fatty acids
somatostatin
> inhibits insulin secretion
explain the regulation of insulin secretion in the case of high plasma glucose
GI hormones
high free amino acids
parasympathetic stimulation
> stimulates insulin secretion
what is GLUT 4
glucose transporter into skeletal muscle and adipose cells
explain glucagon regulation in the case of high plasma glucose
insulin
high free fatty acids and ketoacids
> inhibits glucagon secretion
explain glucagon regulation in the case of low plasma glucose
sympathetic stimulation (catecholamines)
high free amino acids
low free fatty acids
> stimulates glucagon secretion
what are the actions of glucagon
decrease glycogen synthesis/increase breakdown of stored glycogen
stimulate gluconeogenesis
promotes fat breakdown and inhibits triglyceride synthesis and increases ketogenesis > increase in blood levels of fatty acids and ketones
what is type 1 diabetes mellitus
no insulin secretion (autoimmune destruction of beta cells)
ketoacidosis, polyuria, glucosuria, polydipsia
coma + death
what is type 2 diabetes mellitus
not as much insulin produced post feeding
genetic component
down regulation > progressive development of insulin resistance
what are micro- macrovascular complications of diabetes
increased risk of heart attack, stroke, blindness and ischemia
hypetension
atherosclerosis
what are peripheral/ANS complications of diabetes
impaired bladder control
impaired CV reflexes
distal sensory neuropathy
where is the hypothalamus located
in the diencephalon, surrounded by the limbic lobe
what systems does the hypthalamus link
endocrine + nervous
‘post office’ > receive info, sort info, relay info
what tissue is the anterior pituitary gland made of
glandular epithelial
what tissue is the posterior pituitary gland made of
nervous tissue
how are the two parts of the pituitary gland developed
anterior pituitary = up growth from oral cavity > vascular connection with hypothalamus
posterior pituitary = down growth from brain > neural connection with hypothalamus
what does the posterior pituitary gland do
stores + secretes hormones that were formed in the hypothalamic neurons (ADH and oxytocin)
where are ADH and oxytocin synthesised
cell bodies of neurons located in hypothalamic paraventricular and supraoptic nuclei
what stimulates the release of ADH
increase osmolarity
decrease BP
increase stressors
how does ADH work
V2 receptors on kidney tubules > increase in cAMP > increase insertion of aqua-poring in collecting ducts > INCREASE H2O REABSORPTION
V1 receptors on blood vessels > INCREASE VASOCONSTRICTION
V1b receptors on anterior pituitary corticotrophs > increase ACTH > increase aldosterone > INCREASE NA2+ AND H2O REABSORPTION
what is the positive feedback loop associated with oxytocin
childbirth
fetus drops lower in uterus > cervical stretch > oxytocin from posterior pituitary / prostalglandins from uterine wall > uterine contractions > cervical stretch > repeat
what does oxytocin do
promotes ejection of milk in mammary glands
oxytocin vs ADH chemically
very similar chemically (both peptides that are 9 amino acids long) but DIFF FUNCTIONS
what are the pituitary cells, hormones, targets and functions
thyrotrophs - THS - thyroid - t3 and t4 secretion
corticotrophs - ACTH - adrenal cortex - cortisol secretion
gonadotrophs - FSH and LH - ovaries and testes - reproduction
lactotrophs - prolactin - mammary glands - milk production
somatotrophs - GH - bone, tissues, liver - growth
how does hormone release in the anterior pituitary work
short axon neurones synthesise hypophysiotropic hormones >
release into capillary bed of hypothalamic-hypophyseal portal system >
portal vessels carry hormones to anterior pituitary >
endocrine cells of anterior pituitary controlled by hypophysiotropic hormones >
secrete anterior pituitary hormones into blood
what are hypophysiotropic hormones
peptide neurohormones
releasing hormones/inhibiting hormones
neuroendocrine system (fast + specific)
what are the hypophysiotropic hormones associated w anterior pituitary
thyrotropin releasing hormone (TRH) > release of TSH
corticotropin releasing hormone (CRH) > release of ACTH
gonadotropin releasing hormone (GnRH) > release of FSH and LH
growth hormone releasing (GHRH) > release of growth hormone
growth hormone inhibiting hormone (GHIH) > inhibits release of GH and TSH
prolactin releasing hormone (PRH) > release of prolactin
prolactin inhibiting hormone (PIH) > inhibits release of prolactin
what is growth
progressive increase in size of an organism
elongation of bone
increase in size and number of cells in soft tissue
requires net synthesis of protein
what factors influence growth
genetics
growth influencing hormones
nutrition
stress/disease
what factors affect fetal growth
uterine environment
genetics
placental hormones
what factors affect post natal growth
growth hormones
increase GH during puberty
increase androgens (sex steroids)
what hormones influence growth
excess insulin > excess growth
androgens > pubertal growth spurt and protein synthesis
hypothyroidism can stunt growth, BUT this doesn’t mean that excess thyroid hormones lead to excess growth
what is a growth hormone
peptide hormonem, synthesised by somatotrophs in anterior pituitary (secretion regulated by GHRH and GHIH)
stimulates growth
what is the overall purpose of a growth hormone
protein synthesis, increase use of fat storage, increase hyperglycaemia
what are the GH secretion patterns
larger bursts during sleep
irregular pulses
during puberty then declines
what are the positive stimuli that release GH
major:
exercise
circadian rhythm
stress
hypoglycaemia
fasting
minor:
increase amino acids
decrease fatty acids
what decreases GH and through what mechanism does this occur
IGF inhibits somatotrophs > decrease GH
IGF stimulates GHIH
GH inhibits GHRH > increases GHIH
these occur through a negative feedback loop
what does GH stimulate in liver
somatomedins
what are somatomedins
peptide hormone w strong mitogenic properties
produced mainly in the liver
two types (IGF1 and IGF2)
what does IGF1 do
it is in most cells of the body > increase cell growth, multiplication and decrease apoptosis
what does IGF2 do
growth promoting hormone during gestation
what growth hormone receptor is GH associated w
JAK/STAT signal transduction > surface membrane receptors > turns on transcription to synthesise protein > increase GH
what are the GH influences on metabolism
increase protein synthesis
increase lipolysis
increase glucose output from liver (hepatic gluconeogenesis)
decrease insulin sensitivity in muscle (decrease glucose uptake by muscles so they use free fatty acids which increase blood glucose)
what are GH influences on growth
increased protein synthesis
decreased protein degradation
increase hyperplasia
increase hypertrophy
stimulates proliferation of epiphyseal cartilage
increase proliferation of periosteal osteoblasts
what are gonadotropins
luteinising hormones (LH) and follicle-stimulating hormone (FSH)
acts on gonads by activating cAMP
increase in GnRH activity > puberty
what does FSH and LH stimulate in males
FSH = spermatogenesis
LH = testosterone secretion
what does FSH stimulate in females
follicle dev
induces LH receptors on dominant follicle
stimulates estrogen secretion from follicles
what does LH stimulate in females
ovulation
maintains corpus luteum
what happens during the early to mid follicular phase
FSH stimulates growth of ovarian follicles + oocyte maturation > follicles secrete more oestrogen
rising levels of oestrogen > selectively inhibits FSH sections from gonadotrophs / inhibits GnRH secretion / promotes proliferation of endometrium
what happens during follicle development
granulosa cells proliferate > surrounding CT differentiates into thecal cells > thecal cells produce androgens which are converted into estrogen in granulosa cells > oocyte in each follicle enlarges
follicles grow + secrete increasing amounts of estrogen > single dominant follicle develops
follicle ruptures > ova released
how are FSH and LH linked
LH stimulates thecal cells which convert cholesterol into androgen which diffuses from thecal cells into granulosa cells
FSH stimulates granulosa cells which convert androgen into estrogen
estrogen from LH stimulation and estrogen from FSH stimulation is then secreted into blood, remains in the follicle, or stimulates proliferation of granulosa cells
what happens during late follicular phase
inhibin inhibits FSH secretion from pituitary
high levels of estrogen trigger LH surge > reinitiation of oocyte meiosis / luteinisation of follicular cells to luteal cells
what happens during early to mid luteal phase
LH causes differential of both thecal and granulosa cells into luteal cells of the corpus luteum > corpus luteum secretes progesterone, estrogen and inhibin
what does progesterone do
-ve feedback on hypothalamus and anterior pituitary
secretory changes in endometrium
thickens cervical mucus
exerts thermogenic activity
what happens during late luteal phase
no pregnancy > corpus luteum deteriorates > decrease in progesterone > endometrial necrosis > progesterone decrease means FSH can increase again to start new cycle
pregnancy > maintain increased progesterone, estrogen and inhibin
what are the phases of the uterine cycle
proliferative phase (endometrium repair + proliferation under influence of estrogen)
secretory phase (endometrial glands secrete glycogen and mucus)
menstrual phase (uterine prostaglandins > vasoconstriction, contractions and cramping, discharge of blood
what does hyper secretion of GH lead to
children (body stays in proportion) = gigantism
adults (bone doesn’t length) = acromegaly
what are the cause, effect and treatments of gigantism
causes = pituitary adenoma / pituitary hyperplasia
effects = rapid growth of all tissues / hyperglycaemia
treatment = surgery / somatostatin analogs
what are the cause, effect and treatments of acromegaly
causes = pituitary tumour
effect = increase width of bone > enlargement of hands and feet, ribs and tongue
treatment = surgery / somatostatin analogs
how does reduced growth occur
social/psychological factors > decreased stimulation of hypothalamus > lack of GHRH/increased GHIH > no growth hormone > down regulation > decreased IGF
where is the thyroid gland located
directly below the larynx
on either side of and anterior to the trachea
what are the two lobes of the thyroid gland connected by
isthmus
what does the thyroid gland consist of
follicular cells > secrete thyroid hormones
c cells > secrete calcitonin
capillaries
thyroid follicles > functional units
colloid (lumen within follicular cells) > contain thyroglobulin
what are thyroid hormones
amine based hormones that affect almost all cell types
what are the two pathways that thyroid hormones have to impact the body
effects on metabolic pathways
effects on cellular development and differentiation
elaborate on the impact of thyroid hormones on metabolic pathways
they boost energy metabolism in mitochondria which increase basal metabolic rate and influences body temp
elaborate on the impact of thyroid hormones on the cellular development and differentiation pathways
they promote development and differentiation of many cells
how is secretion from the thyroid gland regulated
TRH > TSH > T3 and T4 (free and unbound ones are biologically active)
-ve feedback loop = maintains relatively constant supply of thyroid hormones
what are the two types of impacts that TSH has
genomic and non genomic
what are genomic impacts of TSH
iodide pump, thyroglobulin, T3/T4 synthesis
increase blood flow through vasodilation
hyperplasia and hypertrophy of gland
what nongenomic impacts does TSH have
increased iodide trapping
increased T3 and T4 synthesis
increased pleased of T3 and T4
what effects do thyroid hormones have
oxygen delivery (up regulates beta adrenergic receptors > increase HR, SV and RBC mass)
metabolism (increase mito number and size, increase lipolysis and glycogenesis)
neural activity (increase alertness, memory, learning)
reproduction and growth (required for reproductive capabilities / enhances effect of GH)
what mechanism causes thyroid disorder
hypothyroidism (iodine deficiency):
decrease iodine > no t3 and t4 > no negative feedback
hyperthyroidism (graves disease):
autoantibodies (TSI) > too much negative feedback
what three factors can lead to hyperthyroidism
grave’s disease
excess hypothalamic/anterior pituitary secretion
hyper secreting thyroid tumour
what three factors can lead to hypothyroidism
iodine deficiency
failure of anterior pituitary or hypothalamus
failure of thyroid gland
how is thyroid functions assessed
use radio iodide > scans or urinary excretion
what are some pathological causes of hypothyroidism
primary = antibodies against thyroimmunoglobulins and TSH receptors (hasimoto’s disease)
secondary = pituitary deficit
tertiary = hypothalamic deficit
latrogenic = treatments for hyperthyroidism
what are signs and symptoms of hypothyroidism
fatigue, decreased HR, decreased Q, weight gain, decreased growth
what are pathological causes of hyperthyroidism
grave’s disease > TSI > overstimulates thyroid
what are signs and symptoms of hyperthyroidism
protrusion of eyeballs (exophthalmos)
tachycardia
decreased weight despite no loss of appetite
fatigue due to muscular atrophy
why must Ca2+ be tightly regulated
free Ca2+ in ECf is biologically active
> NT release
> Hormone secretion
> blood clotting
> muscle contractility
what hormones are involved in the endocrine regulation of Ca2+
parathyroid hormone (PTH)
activated vitamin D
calcitonin
where are the parathyroid glands located
posterior surface of thyroid
what are the 3 main actions PTH has
increase PTH in kidneys > increase renal Ca2+ reabsorption > less urinary excretion of Ca2+ > increase plasma Ca2+
increase PTH in kidneys > increase activation of vitamin D > increase absorption of Ca2+ in intestine > increase plasma Ca2+
increase PTH in bone > mobilisation of Ca2+ from bone > increase plasma Ca2+
what is vitamin D
synthesised from cholesterol
must be activated into calcitriol by liver and kidneys before having effect on intestines
what does vitamin D do
activation increased by PTH > increases Ca2+ absorption from intestine
how does vitamin D increase Ca2+ absorption in intestines
increase expression of calcium channels
increase expression of calbindin
increases expression of Ca-ATPase pumps
what is calcitonin
produced by c-cells of thyroid
what does calcitonin do
protective against hypercalcemia
protecting skeletal integrity
how does calcitonin maintain homeostasis
decreases the mvmt of Ca2+ from labile pool and inhibits osteoclast activity
decreases reabsorption of Ca2+ from kidney tubules
increase plasma Ca2+ > thyroid C cells stimulated > increase calcitonin > decrease plasma Ca2+
where are the adrenal glands (suprarenal glands) located
on top of each kidney
what is the structure of adrenal glands
outer = adrenal cortex (release steroids)
inner = adrenal medulla (release catecholamines)
what are the 3 layers of the adrenal cortex
zona reticularis
zona fasciculata
zona glomerulosa
outline the release of hormones from the zona reticularis
releases androgens in the form of DHEA
secretion is increased by ACTH
main function is ‘male’ sex hormone
outline the release of hormones from the zona fasciculata
release glucocorticoids in the form of cortisol
secretion is increased by ACTH
main function is to help resist stress / metabolism
outline the release of hormones from the zona glomerulosa
release mineralocorticoids in the form of Aldosterone
secretion is increased by plasma K+ and angiotensin II
main function is to maintain electrolyte balance and blood pressure
outline the release of hormones from the adrenal medulla
release catecholamines in the form of adrenaline
secretion is increased by sympathetic NS
main function is to resist stress
what are the adrenal sex hormones
estrogen and androgens, which are regulated by ACTH
DHEA = only sex hormone of biological importance (in males, it is overpowered by testosterone and in females, it promotes pubic and axillary hair growth and maintains sex drive)
what is stress
body’s non specific response to any demand made on it
what are examples of stressors
physical e.g trauma
psychological e.g fear
physiological e.g pain
social e.g change in lifestyle
chemical e.g toxins
what type of reactions can stressors have
specific and non specific
what comprises the General Adaptation Syndrome (non specific response)
alarm reaction - fight or flight/acute/varies bases on sex and severity of stressor
resistance stage - adaptation and defence
allostatic overload - protective and damaging effects > long term damage due to prolonged impact of stressors e.g depression
what happens during the alarm reaction
hypothalamic activation of the sympathetic NS
> release of noradrenaline from nerve terminals
> secretion of noradrenaline and adrenaline from adrenal medulla
how does the adrenal medulla release catecholamines
sympathetic stimulation of post ganglionic neurons (chromaffin cells) using ACTH > chromaffin cells release NA and A (in a 1:5 ratio) into the bloodstream
how are catecholamines made
L tyrosine > L dopa > dopamine > NA > using PNMT (only in adrenal medulla) > A
what do catecholamines do
heart > increase HR and contraction (beta 1 receptors
kidney > vasoconstriction (alpha receptors) and increase renin release (beta receptors)
liver > glycogenolysis (beta receptors) and gluconeogenesis (alpha receptors)
pancreas > increase glucagon and decrease insulin (alpha and beta cells)
what are acute response to stress
increased HR
increased metabolic rate
change in blood flow pattern
dilation of bronchioles
increase BP
increase glycogenolysis
what are the impacts of aldosterone in longer term stress response
increase retention of sodium and water
increase blood volume and BP
what are the impacts of cortisol in longer term stress response
increase gluconeogenesis
increase proteolysis
increase lipolysis
decrease immune system
how is release of mineralocorticoids and glucocorticoids regulated
CRH from hypothalamus > ACTH from anterior pituitary > acts of zona fasciculata > cortisol release
what is the HPA axis
hypothalamic-pituitary-adrenal axis
what is the cortisol secretion pattern
high during early morning and lower during night to prevent hypoglycaemia over overnight fast»_space;» circadian diurnal rhythm
what are the actions of cortisol on metabolism
increase BG
stimulate hepatic gluconeogenesis
inhibit glucose uptake
inhibit protein synthesis/promote protein degradation
facilitates lipolysis
cortisol acts in…to actions of insulin
opposition
why does cortisol act in opposition to insulin
life threatening situation > protect brain from malnutrition during extended fasting period
what are the actions of cortisol on CV function
increases sensitivity of heart to adrenaline, noradrenaline and angiotensin II > maintains cardiac contractility, vascular tone and BP
how does cortisol affect CV function
increases synthesis of hormone receptors
increases synthesis of catecholamines and Na/K ATPase pumps
decreases synthesis of nitric oxide
what are the actions of cortisol on immune responses
decreases formation of prostaglandins and leukotrienes > decrease vasodilation, decrease capillary permeability
inhibit accumulation of macrophages
decreases production of T cells and B cell proliferation
reduces fever
what are the actions of cortisol on bones, blood, memory
inhibits bone formation
alters mood and behaviour
affects memory and learning
stimulates RBC production
stimulates gastric acid secretion
what does aldosterone do
increases reabsorption of sodium while increasing excretion of potassium
how does aldosterone have its impact
renin-angiotensin-aldosterone system (RAAS)
> decrease Na+ > increase renin > increase angiotensin I > increase angiotensin II > combine with impact of increase plasma K+ and increase ACTH > increase aldosterone > increase tubular Na+ reabsorption and K+ secretion > increase urinary K+ excretion and decrease urinary Na+ excretion
what are diseases linked to adrenal hyper secretion
phaeochromocytoma (adrenal medulla tumour)
conn’s syndrome
cushing’s syndrome
what results from phaeochromocytoma
catecholamine excess > increase HR, systemic hypertension, anxiety, pallor, sweating, hyperglycaemia
what are primary causes of conn’s syndrome
small, aldosterone secreting tumour of zona glomerulosa
what are secondary causes of conn’s syndrome
RAAS too active due to low renal blood flow
what does conn’s syndrome lead to
mineralocorticoid excess > hypokalaemia, hypertension due to hypervolaemia, ANP secretion from heart
what are primary causes of cushing’s syndrome
adrenal cortex adenomas
what are secondary causes of cushing’s syndrome
increase ACTH from pituitary tumour
what does cushing’s syndrome lead to
glucocorticoid excess
> increase gluconeogenesis > increase hyperglycaemia > decrease sensitivity to insulin > adrenal diabetes
increase fat mobilisation from lower body to thorax and abdomen
facial oedema
protein loss
DHEA excess
acne, excess growth of facial hair
results from tumour within z.reticularis or congenital adrenal hyperplasia
what are primary causes of adrenal insufficiency
anatomic destruction of adrenal glands due to autoimmune attack (addisons disease)
what are secondary causes of adrenal insufficiency
negative feedback suppression of HPA axis due to steroid medications
what does adrenal insufficiency lead to
glucocorticoid deficiency
> decrease gluconeogenesis > hypoglycaemia, weight loss, weakness
> decrease normal feedback by cortisol > increase melanocyte stimulating hormone > hyperpigmentation
mineralocorticoid deficiency
> increase K+ and H+ > tachycardia, chills, sweating, mild acidosis, hyperkalaemia
