endocrine physiology lectures 10-20 lol Flashcards
To learn the very basics
5 roles of calcium in the body
1) important part of the blood clotting cascade
2) important part of cell signalling
3) role in apoptosis
4) skeletal strength- 99% of calcium in the body is wrapped up in bone, to give strength to the skeleton
5) membrane excitability
Is there a role of calcium in muscle contraction?
yes
Calcium distribution throughout the body?
99% in the body
Intracellular 0.9%
only 0.1% is in the extracellular fluid.
Out of the 0.1% of calcium in the extracellular fluid, how much is actually free vs bound to protein?
0.05% is bound to protein, and then 0.05% physiologically active.
Where is calcium stored intracelluarly?
mitochondria and sarcoplasmic reticulum
What are the three hormones involved in endocrine control of calcium homeostasis?
1) Parathyroid hormone
2) Calcitriol (from inactive Vit D, now turned steroid hormone by liver and kidneys)
3) calcitonin- peptide hormone
Which two hormones act to increase calcium levels in the blood/serum?
PTH
Calcitriol (from inactive vit D, made into steroid hormone by liver and kidneys).
What type of a hormone is calcitonin, and where is it released from
peptide hormones, released from parafollicular (clear) cells of the thyroid gland
When is PTH released?
in response to decrease in free calcium plasma
How does PTH act to increase calcium in the plasma?
1) Bind to osteoclasts to increase release of calcium and phosphate in bones
2) Inhibit osteoblasts from reabsorbing calcium
3) Increasing reabsorption of calcium from kidney tubules, to therefore decreasing its excretion in the urine
4) Increasing renal excretion of phosphate.
5) Stimulate kidney to synthesise calcitriol from Vit D
so basically: control calcium at bone level, stop it from leaving the body, (controlling phosphate will stop bones level) and bring in another helper
Why does PTH, increasing renal excretion of phosphate, help elevate calcium serum levels?
In order to put calcium back into bone, phosphate is required.
What does hypocalcaemia lead to?
Increases hyperexcitation of neurons (imagine calcium controls the neurons)
Increases permeability of sodium
So more calcium = less sodium
What symptoms of hypocalcaemia in extreme?
tetany, and if spreads to larynx and respiratory muscles, asphyxiation
What does hypercalcaemia lead to?
reduces exciteability of neurons, so reduce neuromuscular activity
Extreme cases of hyper-calcaemic can lead to what symptom?
cardiac arrhythmias
Plasma proteins have a high or low affinity for calcium?
high
Calcium in bones is stored in the form of what?
hydroxyapatite (in the extra-cellular matrix).
Why is phosphate homeostasis important?
Phosphate needed for packing calcium into hydroxyapatite
No phosphate has what affect on bones
weak
How much of the 0.1% of plasma calcium, being bound to proteins like albumin, or being free, is determined by what?
pH
If body more alkaline, what does this so to Ca plasma levels? and why
lowers because binding is increased
What happens to calcium levels if you hyperventilate?
pH rises because you blow off more CO2, therefore decrease H ions, so up pH (less acidic)
so more binding
therefore hypo calcaemic tetany
acidosis affect on calcium levels
decrease in binding capacity, therefore plasma calcium rises
Why does pH affect calcium levels?
Because H ions compete with calcium for the binding sites on the plasma proteins.
Total body calcium equation
= calcium in - calcium out
What happens to your bones when it’s put under a sustained amount of stress?
The denser your bone becomes (bone ends up be constantly remodelled)
Osteoblasts become what in established bone?
osteocytes
How to osteoclasts work? (2)
Secrete H+ ions to dissolve calcium salts
Provide enzymes to digest ECM
Why would PTH ever stop being secreted?
It’s a negative feedback mechanism
Part of the ways that PTH increases the level of calcium in the serum, is to stimulate production of calcitriol at kidney level. What is calcitriol?
An active form of vitamin D
What does calcitriol do?
Increase absorption of calcitriol from the gut
Where is calcitriol derived from?
cholesterol. but also like vitamin D3 so i don’t even know
The formation of which hormone is enhanced by prolactin in lactating women? (That help’s with calcium levels in serum).
calitriol
What level of vitamin D is deficient at ng/ml
20
When vitamin D deficient, and the body makes up for lack of calcitriol (getting calcium from diet), PTH starts removing Ca from bone. What does this mean for the bones?
You can get easily fractured bones
What happens to calcium absorbency from the gut with age?
Decreases with age
Vitamin D deficiency affects bone development in children. What disease could this lead to?
Rickets
Thyroid cancer could lead to the release of lots of calcitonin (which decreases levels of calcium in the blood). What happens to the levels of calcium in the blood?
Normal
What is calcitonin produced by? And what type of hormone is it
It’s produced by the thyroid gland, and it’s a peptide hormone.
What are the main actions of calcitonin? Like actual actions
Bind to osteoclasts, and inhibit bone resorption, and increase renal excretion of phosphate
State the hormones produced by the adrenal gland, in order from outside in
aldosterone,
cortisol,
testosterone,
norepinephrine and epinephrine (of medulla)
what’s that rhyme to remember hormones produced by different layers of adrenal gland
salt sugar sex stress
How does cortisol affect glucose levels
releases stored glucose
If all steroid hormones are derived from cholesterol, how are different hormones produced from different zones?
different enzymes are found in different adrenal zones, resulting in different end products
How does insulin alter Ca balance
increases bone formation, and antagonises action of cortisol.
Oestrogen does what to Ca levels
Promotes bone formation via oestrogen receptors on osteoblasts. Post-menopausal osteoporosis is major problem
Growth hormone affects Ca levels how?
constant stimulus for bone formation
Prolactin affects Ca levels in the blood how
Promotes calcium absorption from the gut by stimulating synthesis of calcitriol.
Most common reason for adrenal gland hypofunction?
where adrenal gland has been destroyed by some pathological process
meaning of adrenal insufficiency, and how serious is it
where adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.
Addison’s disease vs adrenal insufficiency
Addison’s disease is specifically when the adrenal glands have been damaged
Hyposecretion of which two hormones in Addison’s disease?
Cortisol and aldosterone
Most common cause of Addison’s disease
autoimmune
Secondary adrenal insufficiency results from what?
Lack of adrenocorticotropic hormone (ACTH), therefore adrenal glands aren’t stimulated, so no cortisol.
Because of damage to pituitary gland.
Describe the process of being stressed, leading to release of cortisol i.e the hypothalamo-hypopituitary adrenal axis…..
stress
brain sends stimulus to hypothalamus (acts as neural integrator)
hypothalamus releases CRH,
which acts on the anterior pituitary,
which then secretes ACTH
which acts on the adrenal gland
therefore cortisol is released.
Symptoms of adrenal insufficiency?
Fatigue, dizziness, and fainting
Muscle weakness and muscle cramps
Thirst and craving salt
Weight loss
Abdominal pain
Depression
Reduced libido
Rhyme for remembering adrenal insufficiency
Feeling tired, dizzy, and faint,
Muscles weak, cramps like a complaint.
Thirsty for salt, weight on a slide,
Abdominal pain, in yourself you hide.
Depression looms, libido takes flight,
These are the signs, don’t let them alight.
Two important signs of adrenal insufficiency? remembering that its a drop in aldosterone (and cortisol) and rise in ACTH
bronze hyperpigmentation of the skin
hypotension especially when standing up
What causes the bronze hyperpigmentation of the skin in hypo/ insufficiency of the adrenal glands/ addison’s?
ACTH builds up, which starts to interact with melanocytes, which then produce melatonin
Most important investigation for adrenal insufficiency? that could be only one
hyponatraemia (low sodium)
Biochemical findings of calcium, potassium and glucose in adrenal insufficiency
High potassium
Low glucose
High calcium
What is the test of choice for diagnosing adrenal insufficiency?
The short Synacthen test
When do you perform the short synacthen test?
early in the morning
What does the short synacthen test involve?
The test involves giving a dose of Synacthen, which is synthetic ACTH. The blood cortisol is checked before and 30 and 60 minutes after the dose. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol. The cortisol level should at least double
What is synacthen?
Synthetic ACTH, given for the short synacthen test IM or IV
How to manage adrenal insufficiency?
Replacement steroids
How to replace cortisol
hydrocortisone (a glucocorticoid)
How to replace aldosterone
fludrocortisone
What’s a steroid card?
Card, given alongside ID tag and emergency letter, to alert emergency services that they depend on steroids for life.
In adrenal crises, patients present with: (4)
Reduced consciousness
Hypotension
Hypoglycaemia
Hyponatraemia and hyperkalaemia
Management of adrenal crises?
ABCDE
Hydrocortisone IM or IV
Intravenous fluids
Correct hypoglycaemia (IV dextrose)
Careful monitoring of electrolytes and fluid balance
Plasma ACTH: meaning of if it’s suppressed vs elevated in adrenal insufficiency?
Elevated = primary
Suppressed = secondary
Meaning of secondary adrenal insufficiency? (Knowing primary = damage to actual adrenal gland).
damage to pituitary gland, because the pituitary gland releases the ACTH
Why does the pituitary gland release ACTH?
Because it acted upon by CRH, which was released by the hypothalamus
What glucocorticoid replacement when you have addisons
hydrocortisone 20-30mg daily, given in two separate doses to mimic normal bodily functions.
What synthetic hormone to replace aldosterone?
Fludrocortisone
People with adrenal gland insufficiency, what do you do to steroid dose during periods of illness like the flu?
double the dose
Commonest symptom of hyperfunction of the adrenal gland?
hypertension
Why hypertension with hyperfunction of the adrenal gland?
Hypersecretion of aldosterone
Definition of Cushing’s
excess of corticosteroids produced by adrenal gland. So prolonged level of glucocorticoids in the body.
What are the two groups of corticosteroid hormones?
Glucocorticoids: like cortisol
Mineralocorticoids: like aldosterone
The biggest glucocorticoid that the adrenal gland produces?
cortisol
What’s cushings disease in particular
pituitary adenoma = excessive ACTH release, therefore excessive cortisol release from adrenal glands.
All causes of cushing’s with CAPE mnemonic:
Cushing disease: so like, pituitary adenoma releasing lots ogexcessive ACTH
Adrenal adenoma releasing excess cortisol
Paraneoplastic syndrome (ACTH released from tumour somewhere other than adenal gland or pituitary)
Exogenous steroids- like taking too much synthetic ones
In which of the 4 CAPE causes of cushing’s, which two has golden skin due to excess ATCH causing melanocytes to secrete melanin?
Cushing’s disease- pituitary tumour
or
paraneoplastic
Cuz it’s excess ACTH,
for adrenal adenoma, it’s excess cortisol, and obvs not exogenous steroids.
How to diagnose cushings?
dexamethasone suppression tests. It should reduce ACTH, and reduce cortisol. If cortisol isn’t suppressed, then hypersecretion clearly!
How long does the dexamethasone test in Cushing’s last?
Low-dose overnight test (used as a screening test to exclude Cushing’s syndrome)
Low-dose 48-hour test (used in suspected Cushing’s syndrome)
What imaging for cushings disease?
MRI for pituitary adenoma
What imaging for potential adrenal tumours?
CT abdomen
Treatment of cushings?
Removal of tumour
biggest cause of cushings
pituitary tumour, i.e. pituitary disease
Does cushing’s affect the cortex or the medulla of the adrenal gland?
cortex
Does cushing’s cause hypertension, or hypotension
hypertension
Because the adrenal medulla is an extension of the sympathetic nervous system, what are these tumours called
paragangliomas.
But the biggest subtype is the phaeochromocytoma
Biggest symptoms of a phaeochromocytoma- tumour of adrenal medulla
Hypertension
But also
paroxysmal attacks when bending, coughing, pooping > headache, sweating, palpitations.
also sense of impending doom and pale
PALE AND PANIC
Why
paroxysmal attacks when bending, coughing, pooping > headache, sweating, palpitations for phaeochromocytoma- tumour of adrenal medulla
Because it’s an increase in extra=abdominal pressure, leading to release of catecholamines, which causes those symptoms.
What to do if you have clinical suspicion of a phaeochromocytoma?
If you have a clinical suspicion,
you do 24 hour urine collection for metanephrines or you
measure plasma metanephrines.
repeat tests to make sure
What are Metanephrines
Metanephrines are chemical compounds that are part of the catecholamine group, which includes neurotransmitters and hormones like epinephrine (adrenaline), norepinephrine, and dopamine. Metanephrines are metabolites, meaning they are products of the breakdown (metabolism) of these catecholamines.
After diagnosis of phaeochromocytoma, what do you do
genetic testing
Why is removing a tumour of the adrenal medulla so difficult?
If you touch it, it’ll release loads of catecholamines, which will increase hypertension etc and cause cardiac arrest.
so you need to pharmacologically block the tumour first with alpha adrenergic blockers
In adrenal cortex, cholesterol goes to progesterone, goes to 21- hydroxylase. This is a key step in which two hormones
aldosterone and cortisol
Does a deficit in 21-hydroxylase cause
adrenal hyperplasia?
yes bc increase in ACTH production, causing enlargement of the glands
When you measure someone’s head, (e.g. a child with an endocrine disorder), where do you put the tape?
Around forehead and occipital prominence (maximal circumference).
How do you calculate mid parental height?
correct for sex- take away 15 cm for dad, add 15 cm for mum and then find the middle.
then ten up and down from the midpoint, are your standard deviations
What’s the bone age test?
we use tanner white house test, for 20 bones (long and short) and compare then against standardised maturity for that age.
What’s being measured in tanner’s method of measuring puberty? (1-5, with 1 being pre puberty, 5 being post puberty)
pubic hair
breasts in girls
genital growth
axillary hair growth
What testicular volume suggests the child has started to go into puberty?
Systematic enquiry for growth of a child is important because seemingly unimportant things like celiac disease and inflammatory bowel disease could cause pubertal delay. True or false?
true
When is LH and FSH dormant?
pre-puberty
then release during puberty especially during sleep
LH and FSH comes from where
The pituitary (FSH and LH then stimulate the gonads)
How is final height affected by obesity?
obese children always grow tall, so if they haven’t, there is a problem possibly endocrine.
Common treatment of teenage boys with constitutional delay of growth and puberty
short course of testosterone
Common treatment of a child born small for gestational age
growth hormone treatment if not caught up by 3 or 4 years.
How quickly do children, having been given growth hormone replacement for their deficiency, catch up?
remarkably quickly usually
First sign of puberty in boy vs girl?
breast budding
testicular volume of 3-4 mls
When do girls/boys go into puberty exactly?
8-13 girls
9-14 boys
What’s infantile thelarche?
girls less than 2 years of age already have a bit of a breast bud, stays a little, up and down, usually goes by the time they’re 2
Signs of precocious puberty in children
breast development progressing fairly rapidly and really quick height growth and advanced bone age
Why advanced bone maturity when precocious puberty
because oestrogen and testosterone
Initial imaging of what if precocious puberty
pituitary espc in girls
How to treat precocious puberty?
GnRH agonist
What’s GnRH?
Gonadotropin releasing hormone for releasing LH and FSH
Why might you have early sexual characteristics that doesn’t appear to be progressing to full puberty?
pathological source of sex hormones
What’s the life threatening condition that results in ambiguous genitalia?
congenital adrenal hyperplasia- child could go into adrenal crises within a matter of a week or so and die
For what condition, resulting in ambiguous genitalia, do we have screening for?
congenital adrenal hyperplasia
4 drugs that make you put on weight?
insulin
steroids
antithyroid drugs
sodium valproate
General appearance of children with endocrine disorders?
short and chubby
When calcium levels rise, what happens to PTH levels?
decrease.
But if PTH rises, calcium decreases
What is trousseau’s sign?
It’s a specific type of muscle spasm, that occurs in the hand and wrist due to neuromuscular irritability, which tends to be a definitive sign of hypocalcaemia
As well as hypocalcaemia, when else can trousseau’s sign occur?
when low magnesium
How to see trousseau’s sign?
Flexion of hand, wrist, pronation of hand, flexion of thumb but digits remain extended.
when blood pressure cuff been put on arm, and inflated above systolic blood pressure.
Why does trousseau’s sign occur?
We’re occluding brachial artery, which supplies nerves and muscles that are already irritable and excited (because of lack of calcium). Ischaemia causes spasm therefore
What would both dementia and MS look like on MRI?
hyper-pigmented white matter
If you have hypocalcaemia, you automatically check levels of what other hormone?
PTH
In type 1 diabetes, the liver will continue to raise glucose because why
body thinks it’s starviing
Why abdominal pain in acute Type 1 diabetes?
ketones
Diabetes. But there are no ketones, and no symptoms. Almost full chance it is what type of diabetes?
2
How do corticosteroids cause diabetes?
Auto-immune diseases can be in two different categories:
organ specific (usually endocrine gland)
or
non organ specific
Are auto-immune diseases more common in males or females
Males
is tolerance to self antigens good or bad
good, failure of self tolerance = immune reaction against self
What do dendritic cells of the immune system do
pick up antigens, and track down b and t cells in order to deliver said antigens to them, in order to activate specific immune system.
what happens during the breakdown of central and/or peripheral tolerance
auto-immune disease
purpose of central tolerance
eliminate/inactivate self-reactive lymphocytes (T and B cells) whilst they mature in the primary lymphoid organs
T and B cells, which are lymphocytes, mature in primary lymphoid organs: what are these?
Thymus for T cells
and
Bone marrow for B cells
What is the purpose of peripheral tolerance?
To eliminate B and T cells.
As well as elimination in peripheral tolerance, what is induction of anergy?
Just making the T cells in particular less responsive to stimulation.
What are ‘Tregs’ in peripheral self tolerance?
regulatory T cells that suppress the activation and action of other T cells.
Where can antigens not go (due to anatomy)?
Brain due to blood brain barrier
Testes
Eyes
What are the three mechanisms of peripheral tolerance
Anergy- functional unresponsiveness- they recognise but not full blown response
Treg suppression- block activation (may help promote cancer suppression
Apoptosis when they recognise the antigens
What are the three main factors that lead to breakdown of tolerance and therefore cause auto-immune diseases?
Genes
Infections
Environmental factors
What is the autoimmune exception that is more common in men than women?
ankylosing spondylitis
If lymphocytes attack the self antigen- TSH receptor- what does that lead to?
hyperthyroidism or hypothyroidism
f lymphocytes attack the self antigen- acetylcholine receptor- what does that lead to?
myasthenia gravis
What’s molecular mimicry (leads to auto-immune disease)?
Viruses can produce proteins that look a lot like self proteins
Drugs can also cause molecular mimicry!
Most common microbial antigen that causes molecular mimicry?
Strep A
Strep A antigens are very similar to the antigens found where, thus causing what?
In cardiac muscle, thus causing rheumatic fever
Autoimmune disease caused by infection due to molecular mimicry: how quickly do they go (usually)?
Within a few weeks, they’re not usually long-term.
3 things we try and do with treatment of autoimmune disease
attack self reactive lymphocytes
corticosteroids for tissue damage
replacement therapy e.g. of hormones for organ dysfunction
Problem with corticosteroids
Side effects, can’t give for too long.
What does somatostatin do
Inhibit glucagon and insulin secretion
Microalbuminurua =
Leak of protein (albumin)
What happens in nephropathy? (Remembering that the kidneys have loads of tiny little blood vessels).
“Hypertension” of the renal blood vessels (glomerulus)
Early marker of diabetic nephropathy?
Protein leak
How to treat end stage renal dysfunction?
Dialysis
We screen urine for nephropathy in diabetes. What are we looking for?
Albumin
Way does neuropathy happen?
There’s a contribution of glucose levels, and osmotic effects etc directly on these long axons… (onto tiny blood vessels that supply the long nerves that run all the way from our brain or spine to our extremities
What happens in autonomic neuropathy? What symptoms might occur?
Autonomic neuropathy can cause GI effects on stomach and intestines like irregular vomiting, gastric emptying etc
So food intake
Why would you do an x-ray in the case of a foot ulcer?
To see the extent of infection
How much of a risk is retinopathy with diabetes?
Very high risk
What happens with specifically ‘prolific’ retinopathy?
When there is ischaemia, there is also new blood vessel formation, vitreous haemorrhage, and retinal tears.
Basically actual blockage in capillaries, so new ones form, these may haemorrhage, that may cause blindness
How to treat retinopathy?
Laser photocoagulation
Laser eye treatment in diabetes works how?
Burn little holes in retina to seal it off, prevent spreading of the ischaemic area therefore vision is preserved.
Requirements for bariatric surgery?
BMI of 35 with obesity related comorbidity
Diabetes has what percentage remission following bariatric surgery?
Like 40%
Name three bariatric surgeries?
Gastric band
Gastric sleeve
Gastric bypass
How much weight do you lose with a gastric bypass?
Maybe 30% on average, of total body mass
Men (not women) have central adiposity. What is this type of fat?
Visceral fat
Men (not women) have central adiposity. What does this mean?
Metabolic syndrome
So like:
Heart disease
Dementia
Cancer
Basically fat affects the visceral organs, in woman fat is in the thighs/ peritoneal
Is bariatric surgery cost effective?
Yes in the long run
M or f have greater risk reduction for cancer?
Female, risk reduces significantly
Why do you inject fluid into a gastric band?
To tighten it
Why might you put on weight when you’ve got a gastric band? Real simply
Because too tight = eat liquid food, which is high in calories
With a gastric bypass, you bypass the Fundus. What does this mean hormonally?
Well Fundus releases ghrelin, which triggers feelings of hunger
With a gastric bypass, you bypass the Fundus and go to the jejunum. What does this mean hormonally?
Body doesn’t understand why so much food there. So it secretes GLP-1 which is an incretin hormone. So this switches off your feelings of hunger, and increases insulin sensitivity instead.
Why use GLP-1 analogue for obesity?
Because that’s an incretin. It’ll switch off feelings of hunger
What happens to your weight when you start insulin, and you’re type 2?
Your weight goes up
How quickly can you go home after a gastric bypass
Like even maybe the same day
How often suicide after bariatric surgery and why
Very often because you take away their source of comfort- which is food
Which type of bariatric surgery can lead to reflux?
Sleeve
Why might you be thirsty and constipated after bariatric surgery?
Because you struggle to eat and drink at the same time, so one or the other really (stomach too small)
What supplements might you give when you have bariatric surgery?
Vitamin D, calcium, iron, B12 injection
HbA1C is what
Average blood sugar level
Diabetic neuropathy affect on cardiovascular system:
Tachycardia, blood pressure fluctuations
What do I mean by ‘silent MI’s’ for diabetes?
No chest pain
So might come in with heart failure, breathlessness or whatever
What do we call it when the foot in diabetes gets like soft and weirdly bulgy
Charcot foot
What is Charcot’s foot?
It is a problem which can affect the foot in people with neuropathy (nerve damage with numbness). The bones of the foot become very fragile and can start to break or dislocate in response to very minor forces – even in response to the forces which occur with standing or walking.
What sexual dysfunction might occur with diabetes?
Erectile dysfunction
How is ADH secreted?
Anti diuretic hormone. It’s made in hypothalamus, travels to posterior pituitary gland, and is released into the blood stream that way.
