endocrinology Flashcards
What is a hormone ?
a chemical signal synthesised by specialised target cells and secreted into the blood to act on target cells
What are hormones secreted by ?
endocrine glands
What are peptide hormones ?
they are trascribed from DNA translated form mRNA on ribosomes modfied by the golgi packaged into secretory vesicles hydrophillic
What are steroid hormones ?
hydrophobic
they are synthesised from cholesterol
released by diffusion as they are lipophilic
eg. testosterone
What are biogenic amines ?
derived from tyrosine
they can be lipophilic or hydrophilic so can be released by diffusion or exocytosis
What are neurohormones ?
they are released from neuroendocrine cells directly into the blood
Why do hydrophilic peptide hormones travel freely ?
blood is an aqueous solution
How are hydrophobic steroid and thyroid hormones transported ?
need transport proteins
these can be specific or non specific
How is the steroid hormone cortisol transported ?
80% - transcortin - specific carrier
15%- albumin - non-specific
5% - free
What is free hormone ?
only free hormone is biologically active
binding to a carrier protein lengthens half life as free hormone is usually degraded by the liver
carrier proteins prevent liver degradation
What is the mechanism of hydrophilic hormones such as peptide hormone and biogenic amines ?
they cant pass the lipid bilayer
bind to receptors on the plasma membrane
activate a number of intracellular pathways
What is the mechanism of action of hydrophobic hormones ?
enter the cell s they can cross the lipid bilayer
bind to intracellular receptors in the nucleus
bind to receptors on DNA
hormone-receptor complex acts as a TF
this can alter protein levels
What is an example of a steroid hormone that binds to DNA and becomes a TF ?
cortisol
What are the intracellular pathways activated by hydrophilic hormones ?
cyclic AMP pathway
phosphoinositide pathway
tyrosine kinase pathway
What activates the cyclic AMP pathway ?
ADH and LH
What activates the phosphoinositide pathway ?
adrenaline and ADH
What activates the tyrosine kinase pathway ?
insulin - binds to a receptor tyrosine kinase that results in a phosphorylation cascade
What are the 2 types of endocrine control ?
homeostatic or adaptive
What is homeostatic endocrine control ?
the balance of bodily functions
eg. ADH water balance
What is adaptive endocrine control ?
adapting to specific changes in the environment
eg.insulin is released in response to high blood glucose
What are the 2 types of endocrine responses ?
simple - involving one endocrine gland
comp;ex - involving 2 or more endocrine glands
What is an example of a direct endocrine reflex arc ?
the release of insulin from the pancreas in response to high blood glucose
insulin is not released when the blood glucose level returns back to normal
What is an example of complex control ?
hypothalamus - pituitary - thyroid gland axis
How are complex responses controlled ?
with feedback loops
What is a negative feedback loop ?
the hormone output reverses a particular stimulus
eg. insulin
What is a positive feedback loop ?
the hormone output reinforces and encourages the stimulus
eg. oxytocin in uterine contraction
What is the hypothalamus ?
a link between neural and endocrine systems
it is a collection of neuronal cells in the brain that receives input from the body
Which stimuli is the hypothalamus sensitive to ?
blood-bourne olfactory hear info stomach reproductive tract long term stress infection
What does the hypothalamus control ?
pituitary gland
What connects the pituitary gland and the hypothalamus ?
the pituitary gland is at the bottom of the brain and is connected to the hypothalamus by the pituitary stalk
What are the 2 separate parts of the pituitary gland ?
anterior pituitary
posterior pituitary
they are independent of each other due to their different connections to the hypothalamus
How is the anterior pituitary connected to the hypothalamus ?
by the portal vessels
the hypothalamus releases neurohormones into the portal vessels which travel to stimulate the release or inhibition of anterior pituitary hormones from families of endocrine cells
How is the posterior pituitary connected to the hypothalamus ?
by neurosecretory neurones
the axons of these neurones synapse at blood vessels after travelling down the pituitary stalk
Where are posterior pituitary hormones synthesised ?
hypothalamus
Where are posterior pituitary hormones stored and released ?
posterior pituitary
What are magnocellular neurones ?
they span down the pituitary stalk and make Oxytocin and ADH
How are oxytocin and ADH released into the blood ?
an action potential travels down the magnocellular neurone
triggers exocytosis of a post.pituitary hormone into the blood
What is oxytocin secreted from ?
paraventricular nuclei
What is ADH secreted from ?
supraoptic nuclei
What does oxytocin do ?
it circulates in the blood and acts on the mammary glands and the uterus
in the mammary gland it stimulates milk ejection
in the uterus it stimulates contraction
What is mammary gland ejection known as ?
let down reflex
What is uterine contraction known as ?
ferguson reflex
what stimuli is ADH released under ?
low blood pressure
high blood osmolarity
low blood volume
What are the target cells for ADH ?
cells in the collecting duct of the kidney
smooth muscle around blood vessels
What secretes the anterior pituitary hormones ?
families of endocrine cells
What controls the release of hormones from the families of endocrine cells ?
neurohormones released from the hypothalamus into the portal vessels
What do the gonadotropins do ?
they trigger responses in the gonads
gametogenesis - FSH
steroidogenesis - LH
they are released by the family of endocrine cells known as the gonadotrophs
What does growth hormone do ?
trigger metabolism in organs and tissues - eg carb metabolism or lipid synthesis
they are released from the somatotrophs
What does TSH ?
triggers the release of the iodothyronines from the thyroid gland
released from the thyrotrophs
What does prolactin do ?
triggers milk synthesis in mammary glands
and sodium reabsorption in the kidney
released from the lactotrophs
What does ACTH ?
triggers aldosterone and cortisol release from the adrenal cortex
released from the corticotrophs
What is a tropic hormone ?
a hormone whos target is an endocrine cell
What are the tropic anterior pituitary hormones ?
ACTH
TSH
gonadotropins
What is a trophic hormone ?
stimulates cell growth
eg. GH and prolactin
How is secretion of the anterior pituitary hormones controlled ?
neurosecretory hormones that are released from the hypothalamus they can be release stimulating or release inhibiting
What are the release stimulating hormones ?
Corticotropin releasing hormone
GH-releasing hormone
Gonadotropin releasing hormone
TSH releasing hormone
What are the release inhibiting hormones ?
GH-inhibiting hormone
dopamine/PIH - inhibits prolactin from the lactotrophs
What are the possible types of endocrine pathologies ?
hormone excess
hormone deficiency
abnormal responsiveness of target tissue to the hormone
What is hyperthyroidism ?
excess thyroid hormone release
symptoms are bulging neck and eyes
What is primary hypersecretion due to the thyroid ?
adenoma in the thyroid gland releases excess thyroxine
excess thyroxine works via the direct/indirect pathways to inhibit TSH and TRH
graves disease symptoms present
thyroxine levels are high
TSH/TRH are low
What is secondary hypersecretion due to a problem with the pituitary ?
a tumour in the anterior pituitary means excess TSH is released.
thyroxine will act via the indirect/direct pathways to inhibit TSH and TRH
TSH cannot be inhibited as the negative feedback loop is overidden by the increased activity of the anterior pituitary
TRH is inhibited normally by thyroxine
excess thyroxine is produced leading to symptoms of excess
thyroxine is high
TSH is high
TRH is low
What is secondary hypersecretion due to a problem with the hypothalamus
an adenoma in the hypothalamus can mean that excess TRH is released
this leads to excess TSH and thyroxine
thyroxine will try to act via the indirect/direct negative feedback loops to try to inhibit further release
but it is overidden by the increased hypothalamic drive
so that all hormones are at high levels in the blood
symptoms of excess
What is graves disease ?
an autoimmune disease where the body produces antibodies against the thyroid gland
these antibodies stimulate receptors on thyroid cells to produce thyroxine
thyroid gland enlarges
usually due to primary hypersecretion
Treatment option for graves disease ?
anti-thyroid drugs such as thioamides - reduce thyroid gland function
Radioactive iodine - accumulates in the thyroid gland - radioactivity destroys thyroid gland
thyroidectomy
Which crystals provide the structural integrity of enamel and bone ?
calcium hydroxyapatite (99%)
What is calcium needed for ?
trigger neurotransmitter release
blood coagulation
muscle contraction
What happens to the nervous system if the extracellular calcium levels fall below normal ?
nervous system becomes more excitable because of the increased permeability of neuronal membranes to sodium ions
this leads to hyperexcitability - tetanic contractions - hypocalcaemic tetany - indicated by trousseas sign
What are the 2 types of calcium in the ECF ?
filterable - free and anion bound - 60%
non fliterable - protein bound -40%
What proteins is calcium bound to ?
albumins and globulins
What is the osmolarity of calcium in the plasma ?
2.5 mM
of the intake of calcium how much is absorbed by te GI tract ?
35%
How much calcium is excreted in the urine ?
20% - this is only 2% of the filterbale calcium
What is on the surface of the axial skeleton ?
rapidly exchangeable pool of calcium
When calcium moves from the ECF into the bone to form crystals what is this called ?
bone formation
What is bone resorption ?
when calcium moves out of the bone into the ECF fluid
What is the paracellular pathway ?
calcium ions move between the cells
works by passive simple diffusion
occurs in the ileum
if there is no conc gradient there is no uptake and calcium transport is stopped
What is the transcellular pathway ?
calcium moves through the cells
in the cell it binds to CBP which prevent any unregulated triggering
calcium leaves the cell by being pumped out by ATPases
What is advantageous about the transcellular pathway ?
small amounts can be transported into the blood aganst the conc gradient
Where does the transcellular pathway take place ?
duodenum and the jejunum
What is the rate limiting step in the transcellular pathway ?
the pump is the rate limiting step as it can become saturated and lower the rate of calcium transport
What happens during filtration at the nephron ?
the filterable calcium (free and anion bound) is remived from the blood
How is calcium reabsorped in the kidney ?
60% in the transcellular pathway via the proximal tubule
30% by the paracellular pathway in the loop of henle
9% in the distal tubule via the transcellular pathway
What is bone remodelling ?
the continuous process by which bone is reabsorbed and formed
During growth what happens to bone?
the rate of bone formation exceeds the rate of bone resorption
What happens once adult bone mass has been achieved ?
equal rates of formation and resorption
then resorption exceeds formation and bine mass slowly deccreases
Where does bone resorption and formation happen ?
in the trabecular bone
80% of the bone is which type of bone ?
compact bone
What feature of trabecular bone means it is good for calcium exchange ?
greater surface area
What are the primary cell types involved in formation and resorption ?
osteoclasts
osteoblasts
osteocytes
What are osteoblasts ?
differentiated bone forming cells
they secrete osteoid
What is osteoid ?
organic bone matrix made of collagen secreted by osteoblasts
calcium phosphate precipitates on it prior to full mineralisation
What are osteocytes ?
mature bone cells
enclosed in the bone amtrix
connected to the suraf ecells and each other by canalliculi - allow for ion and nutrient exchange
What are osteoclasts ?
large multi nucleated cells
derived from monocytes
they resorb bone by having hydrolytic enzymes that release calcium into the ECF
How does PTH work ?
by stimulating bone resorption via the hydrolytic enzymes in osteoclasts
Where is parathyroid hormone synthesised and secreted ?
the chief cells of the parathyroid glands
How is PTH initially translated ?
as a pre hormone that is biologically inactive
the prosequences are cleaved off to yield a biologically active peptide of 84 amino acids
this is exocytosed into the blood
What is the job of PTH ?
increase plasma calcium as it is a hypercalcaemic hormone
the stimulus for this is a decrease in plasma calcium
What does PTH do to bone ?
it increases osteoclast number
increases osteoclast activity
decrease collagen synthesis - less osteoid formation so less bone formation therefore net transfer to the plasma
What does PTH do to the kidney ?
stimulates calcium reabsorption in the distal tubule via the transcellular pathway
decreases urinary calcium
also stimulates the activity of 1-alpaha hydroxylase in the kidney
What does 1-alpha hydoroxylase do ?
catalyses the formation of 1,25 DHCC
What does PTH do in the GI tract ?
it has no direct effect it works indirectly to stimulate 1- alpha hydroxylase
What is the natural form of 1,25 DHCC ?
vitamin D3
What is the structure of 1,25 DHCC ?
it is a highly aromatic structure
What are the 2 sources of vitamin D3 ?
diet and skin
How is vitamin D3 made in the skin ?
cholesterol is converted to 7-dehydrocholesterol and then with UV light it is made into vitamin D3
Is vitamin D3 active or inactive ?
it is inactive it must be converted to 1,25 DHCC
How is vitamin D3 converted to 1,25 DHCC to be active?
vitamin d3 enters hepatic circulation
enzyme places a hydroxyl group on C25
this enters renal circulation and 1- alpha hydroxylase puts a hydroxyl group on carbon 1
How is 1,25 DHCC activity stimulated ?
by PTH
What does PTH do to 1-alpha-hydroxylase ?
PTH also stimulates 1-alpha hydroxylase to produce 1,25 DHCC
What type of hormone is 1,25 DHCC ?
it is a hypercalcaemic hormone
How does 1,25 DHCC regulate the transcellular pathway ?
it induces the production of CBPs
What do the CBPs do ?
they buffer high intracellular calcium concentrations that arise during initial absorption - this allow calcium to be uptaken against a high concentration
How does 1.25 DHCC act as a steroid hormone ?
it alters the amount of CBp by promoting its synthesis at the gene expression level
What effec does 1,25 DHCC have in the kidney ?
it increases the absorption in the distal tubule but this is minor
What is the effect of 1,25 DHCC in the bone ?
it promotes the actions of PTH - bone resorption
Why is regulation of the hypercalcaemic hormones needed ?
because they stimulate each other and this can lead to hypercalcaemia
How is the level of PTH regulated ?
1,25 DHCC inhibits PTH gene expression in a form of feedback control
What does calcitonin do ?
it decreases calcium concentrations it is a hypocalcaemic hormone
What is the main target for calcitonin ?
it targets the osteoclasts by inhibiting their motility and cell shape which inactivates them
less bone resorption
What effect does calcitonin have on the intestine ?
no effect on the intestine
What effect does calcitonin have on the kidney ?
decreases tubular reabsorption of calcium - but this is weak
Why does calcitonin only have a small effect on calcium conc ?
excess calcitonin does not result in hypocalcaemia
removal of the parafollicular cells does not cause hypercalcaemia
suggests that 1,25 DHCC and PTH dominate
What is osteoporosis ?
reduced bone density and mass loss of organic matrix equilibrium is disrupted resorption > formation trabecular bone is reduced
What is oestrogen ?
a potent stimulator of bone formation
What is treatment for metabolic bone diseases ?
increased calcium
oestrogen replacement / androgens
anti resorptive drugs
What is osteomalacia / rickets ?
inadequate mineralosation of bone matrix
bones lack mineral phase and structural strength
caused by vit.D deficiency
What is vitamin D dependent rickets type 2?
inability to convert vitamin D3 into 1,25 DHCC due to a mutation in the 1,25 DHCC receptor
impaired intestinal calcium absorption
What are the potential causes of hypercalcaemia ?
primary hyperparathyroidism
Adenoma in parathryroid gland
hyperplastic parathyroid tissue
excessive production of 1,25 DHCC
What are the symptoms of hypercalcaemia ?
neuromuscular supression - neuronal cells less permeable to sodium
kidney stones and blocked arteries
What are the treatment options for hypercalcaemia ?
anti resorptive agents
salmon calcitonin
surgery
other cause sog hypercalcaemia ?
malignant cells - destruction of bone - release calcium
vit . D dependent hypercalcaemia - too much 1,25 DHCC made from too much vitamin D
acromegaly - stimulation of 1-alpha - hydroxylase by GH - excess 1,25 DHCC
What are the causes of hypocalcaemia ?
PTH deficient hypoparathyroidism
PTH ineffective hypoparathyroidism - biologically inactive PTH
PTH resistant hypoparathyroidism - pseudoparathyroidism - cells not responsive to PTH
What is secondary hyperparathyroidism ?
malabsorption of vitamin D in GI tract
cant convert vitamin D to 1,25 DHCC in kidney
decreases plasma calcium
PTH stimulkated
tries to return calcium level to normal via the osteoclasts
expense of significant calcium from the bone
What does the pancreas consist of ?
islets and exocrine cells
What is a festure of islets ?
they are highly vascularised which allows hormones to be moved around the body easily
What proportion of cells in the pancreas are exocrine ?
98%
What types of hormone secreting cells are there in an islet ?
D cells
aloha cells
beta cells
What do alpha cells release ?
glucagon - hyperglycaemic hormone
What do beta cells release ?
secrete insulin - hypoglycaemic hormone
What do D cells release ?
somatostatin
What does somatostatin do ?
regulates glucagon/insulin secretion by inhibiting their secretion
What is somatostatin ?
a GIH
hypothalamic neurohormone
What type of hormones are glucagon , insulin and somatostatin ?
peptide hormones
How are the 3 hormones released form the endocrine secreting cells ?
exocytosis into the blood
Which pathway does insulin trigger ?
tyrosine kinase signal transduction pathway
Which pathway does glucagon trigger ?
cAMP signal transduction pathway
What stimuli lead to increased insulin secretion ?
raised blood glucose
amino acids - trigger insuin so they can be taken up
digestive hormones
How can insulin be secreted by neuronal stimulation ?
alpha receptors stimulate insulin secretion in sympathetic pathways
How can insulin be secreted in parasympathetic pathways ?
at cholinergic synapses
What stimuli decreases insulin secretion ?
low blood glucose
somatostatin
How is insulin secretion decreased ?
insulin secretion can be decreased by beta receptors in reactions to stress , hypoxia and hypothermia
Describe the direct endocrine reflex arc of insulin release post a glucose meal ?
insulin secreted post meal
target cells take up glucose
insulin levels fall as high blood glucose is no longer a stimulus
What happens to glucagon levels post a carb meal ?
they decrease
as blood glucose is being returned to normal
What is a glucose tolerance curve ?
it shows the appearance and disappearance of glucose post meal this can be used to diagnose diabetes
What happens to glucose in anabolic reactions ?
insulin triggered - glucose taken up by muscle
glucose is taken up by the liver - without the need for insulin (dont use GLUT4 which is insulin dependent )
Adipose tissue and the liver take up glucose to make triglycerides
What happens to glucose in catabolic reactions ?
glucagon is released in the fasting state
glycogen in the muscle broken down to glucose 6 phosphate
in the muscle glycogen is fully broken down to release glucose
Can adipose tissue convert triglycerides to glucose ?
no
What happens to amino acids in the muscle ?
they go to the liver and take part in gluconeogenesis to make glucose
What happens to excess fatty acids in the liver ?
made into ketone bodies
What happens when a protein rich meal is taken ?
increase in glucagon and insulin
What do amino acids trigger ?
insukin release so they can be taken up
What happens when the insulin is release and what stops this ?
insulin fully removes any glucose from the blood
this means that subjects can become hypoglycaemic
to stop this glucagon levels are also raised - raise blood glucose
What is diabetes mellitus ?
a family of metabolic diseases
can involve an inadequate production of insulin or an abnormal responsiveness by target tissue to insulin
What are the symptoms of DM ?
chronic hyperglycaemia
nocturia - to remove excess glucose
weight loss - individuals enter the fasting state despite high blood glucose
blurred vision - glucose precipitates in the eye
excessive thirst - glucose is osmotically active in the blood - increases blood osmolarity
What is type 1 diabetes ?
insulin dependent
autoimmune disorder means that beta cells are destroyed - no insulin production
enter a fasted state
What happens during type 1 diabetes ?
muscles break down proteins
adipose tissue breaks down triglycerides
liver also synthesises glucose in gluconeogenesis
ketogenesis - leads to ketoacidosis
leads to hyperglycaemia
What is type 2 diabetes ?
insulin resistant diabetes
abnormal target cells responsiveness
eventually become insulin dependent
why is the hyperglycaemia not as severe in type 2 ?
their is functioning insulin
metabolism not normal
delayed respkjksne to ingested glucose
What is the treatment in type 2 ?
exercise
drugs to prevent hyperglycaemia - bignanides - metmorfin - inhibit gluconeogenesis
What does the adrenal gland consist of ?
adrenal medulla
adrenal cortex
What does the adrenal medulla secrete ?
catecholamines eg. noradrenaline
What are the zones i the adrenal cortex ?
Zona reticularis
zona fasiculata
zona glomerulosa
What does zona reticularis secrete ?
glucocorticoids and sex hormones
What does zona fasiculata secrete ?
glucocoritcoids eg . cortisol
What does zona glomerulosa secrete ?
mineralcorticoids eg aldesterone
What are the corticosteroids ?
mineralcorticoids and glucocorticoids
What are the glucocorticoids ?
steroid hormones secreted from the adrenal coretx - eg.cortisol
What are the mineralcorticoids ?
class of steroid hormones secreted from the adrenal cortex - have a highly aromatic structure
What is an example of a mineralcorticoid ?
aldesterone
What is an example of a glucocorticoid ?
cortisol
How do the mineralcorticoids work ?
they stimulate sodium absorption in the kimndey and this follows with water absoprtion whicb allows an increase in blood pressure and blood volume .
What is aldesterone secretion controlled by ?
renin-angiotensin pathway
What does the renin- angiotensin pathway control ?
blood pressure
Desribe the renin angiotensin pathway ?
decrease in blood pressure and volume
detected by the juxtaglomerular cells in the kidney
the kidney releases renin
the liver releases angiotensinogen
angiotensinogen is converted to angiotensin 1 by renin
this enters the pulmonary circulation
ACE converts angiotensin I to angiotensin II
angiotensin II causes vasoconstriction of the arterioles
angiotensin II travels to the adrenal cortex
this stimulates aldesterone secretion
in the kidneys this causes increased sodium absorption and increased water absorption
leads to increased blood pressure and volume
What is ADH stimulated by ?
angiotensinogen II
What does ADH target ?
collecting duct in the kidney
smooth muscle around vessels - allows the increase in blood pressure
What does angiotensin II in the plasma stimulate ?
arterioles - vasoconstriction
cardiovascular centre in the medulla oblangata - cardiovascular response
hypothalamus - ADH and thirst
Adrenal cortex - aldosterone
How is blood pressure calculated ?
BP= CO X PR
How does angiotensin II increase the blood pressure ?
it increases Bp as angiotensin increases BP through PR rising due to vasoconstriction
Describe the hypothalamic - pituitary - adrenal cortex for cortisol ?
CRH
ACTH
Adrenal cortex - releases cortisol
How is cortisol continuously secreted ?
over a diurnal rhythm
What does cortisol secretion increase with ?
stress anxiety emotion trauma oxygen deprivation
Why do animals die of their adrenal glands are removed ?.
they are exposed to significant environmental stress
What are the actions of cortisol ?
immune system - function suppressed (thymus and lymphatic tissue reduced in effectiveness)
liver -gluconeogenesis
Muscle - protein catabolism and the amino acids can be used for gluconeogenesis
Adipose tissue - lipolysis - triglycerides can be used as an alternative to glucose
What is addisons disease ?
disorder of the adrenal glands
reduced cortisol and aldesterone production
cant cope with stress or dehydration
What effect does cortisol have on glucagon ?
a permissive effect
in the absence of cortisol glucagon is unable to respond effectively to hypoglycaemia
cortisol must be present to ensure full responsiveness to glucagon
Why is cortisol useful as a therapuetic drug ?
immunosuppressant
this can be used in allergic reactions and prevention of transplant rejection
What is the problem with exogenous cortisol ?
the body cannot distinguish between exogenous and indogenous cortisol
exogenous cortisol can activate direct/indirect pathways of negative feedback
this stops the bodily production of cortisol
shut down of hypothalamic - pituitary axis
if exogenous cortisol is to be stoppped - must be gradual to relieve inhibition of the hypothalamic - pituitary- adrenal axis
body can produce exogenous cortisol
What is cushings syndrome ?
hypercortisolism
excess lipolysis - redistribution of fat
hyperglycaemia - excess gluconeogenesis
susceptibility to infection - immunosupressant
muscle thinning - protein breakdown
What are the causes of hypercortisolism ?
latrogenic - cortisol therapy
adrenal tumour - adenoma
pituitary tumour
