biochemistry Flashcards
what are the 3 main different types of secretion?
endocrines
- ie hormones
paracrine
- stuff acts locally
autocrine
- affects the cell secreting the protein
where is the pituatory gland situated?
pituatory gland aka?
what are the two parts of the pituatory gland?
- aka?
how are each controlled?
situateed in the sella turcica, a depression in the sphenoid bone
hypophysis
anterior lobe
- makes up 75% of gland
- aka adenohypophysis
- controlled by hormones released by hypothalamus (ends in RH - releasing hormone)
posterior lobe
- makes up 25% of gland
- aka neurohypophysis
- controlled by neuronal control from hypothalamus
what hormones are:
- produced in anterior pituatory lobe? 6
- stored in posterior pituatory lobe? 2
anterior pituatory
- growth hormone
- prolactin
- ACTH (adrenocorticotrophic hormone)
- TSH (thyroid stimulating hormone)
- FSH (follicle stimulating hormone)
- LH (lutenising hormone)
posterior pituatory
- ADH
- oxytocin
nb hypothalamus INHIBITS secretion of prolactin
- it stimulates everything else
what are the causes of anterior pituatory hypofunction? 5
- tumours (non-secretory adenoma or metastatic carcinoma)
- trauma
- infarction
- inflammation (granulomatous, autoimmune, other infection)
- iatrogenic
what are the two types of clinical effects caused by primary pituatory tumours?
functional clinical effect
- secondary to hormone being over-produced
local effects:
- due to pressure on optic chiasma or adjacent pituatory
what are three most common types of anterior pituatory adenomas?
- which is most common?
- what syndromes do they cause?
prolactinoma
- commonest
- galactorrhoea + menstural disturbance
growth hormone secreting
- gigantism in children
- acromegaly in adults
ACTH secreting
- cushings syndrome
thyroid:
- 3 parts?
- what is anterior to it?
- what is posterior to it?
- right lobe
- isthmus
- left lobe
- strap neck muscles are anterior to it
- it surrounds the thyroid cartilage around the trachea
- recurrent laryngeal nerve located in the tracheo-oesophageal groove close to posterior aspects of lateral lobes
why can thyroid enlargement (or botched thyroidectomy) cause horseness of voice?
due to damage to recurrent laryngeal nerve
what are the two types of cell in the thyroid gland?
what does each produce/secrete?
follicular cells
- secretes T3 + T4
parafollicular cells (aka C cells) - secretes calcitonin
what is the function of calcitonin?
lowers blood calcium (opposite of parathyroid hormone) by stimulate reabsorbtion by bone
chronic lymphocytic thyroiditis
- aka?
- what does it cause?
- pathogenesis?
- who does it normally affect?
- what does it increase your risk of?
aka hasimotos thyroiditis
hypothyroidism
the autoimmune production of anti-thyroid antibodies -> chronic inflammation (painless goitre)
- thyroid cancer
mainly older women
graves disease:
- what gender/age most at risk?
- pathogenesis?
- females
- 20s + 30s
autoimmune process leading to production of thyroid-stimulating autoantibodies
T3 + T4 elevated, TSH markedly suppressed
what is pretibial myxoedema?
what causes it?
hyperpigmentation and non-pitting oedema on the anterior lower limb (pre-tibial)
graves disease
nb only about 5% of people with graves disease have it
multinodular goitre:
- what is it?
- does it cause hyper or hypothyroidism?
- potential complications?
enlargement of thyroid with varying degrees of nodularity
- one or more palpable nodules
can be either but most patients are euthyroid (ie neither hypo or hyper)
tracheal compression or dysphagia may develop with large nodules
nb dominant nodule may be mistaken clinically for thyroid carcinoma
follicullar adenoma
- what is it?
- gender/age mainly affected?
- how differentiated from multinodular goitre?
- clinical presentation?
benign encapsulated tumour of follicular cells
- female
- middle/old aged
normally solitary nodule (as opposed to many)
often asymptomatic, painless neck mass
most don’t produce any T3 or T4 but if they do then called TOXIC follicular adenoma
what are the two types of carcinomas arising from follicular cells of the thyroid?
what % of thyroid cancers does each make up?
who does each tend to affect?
likelihood of lymph node spread at presentation?
papillary carcinoma:
- > 70% (commonest)
- females
- wide age range, mean 45years (tends to be younger women)
- 50% have lymph node involvement at presentation
follicular carcinoma:
- about 15%
- females
- middle/old aged
- only 5-10% have involvement at presentation
what histological findings may be seen in papillary carcinoma of the thyroid? 3
- can be ill defined/infiltrative or some may be encapsulated (better prognosis)
- may by cystic (better prognosis)
- psammoma bodies are common (calcifications, can be seen on USS)
what oncogene mutation is seen in many patients with follicular carcinoma of the thyroid?
Ras mutations
symptoms of thyroid cancer? 7
- lump in the thyroid
- swollen glands (lymph nodes)
- unexplained hoarse voice
- dysphagia
- sore throat
- fatigue
- weight loss
nb symptoms are often not present/very mild
what is the difference between primary, secondary and tertiary hyperparathyroidism:
- calcium levels?
- PTH?
- causes?
primary:
- calcium usually high
- PTH inappropropriately high
- cause: sporadic or familial
secondary:
- hyperplasia of glands with elevated PTH in response to prolonged hypocalcaemia
- calcium normal or low
- PTH appropriately high
- causes: mainly CKD or vit D deficiency
tertiary:
- in associated with longstanding secondary hyperparathyroidism, parathyroid glands loose ability to switch off, though calcium is within normal ranges
- calcium usually high
- PTH inappropiately high
- causes: after prolonged secondary HPT, usually in CKD
nb chemically, tertiary looks very similar to primary but different causes
causes of hyperparathyroidism:
- primary? 3
- secondary? 3
primary:
- 85% are due to single adenomas
- 10-15% diffuse chief or clear cell hyperplasia
- 1% carcinoma
secondary:
- chronic kidney disease (failure to convert vit D)
- vit D deficiency
- malabsorption
what are the risk factors fordeveloping primary hyperparathyroidism? 4
- female
- old
- ionising radiation
- MEN 2a syndrome
(MEN = multiple endocrine neoplasm)
symptoms of primary hyperparathyroidism? 15
- what are the symptoms due to?
what % are asymptomatic?
70-80% are asymptomatic
excessive calcium reabsorption from bone:
- osteopenia + osteoporosis -> BONE PAIN + PATHOLOGICAL FRACTURES
excessive renal calcium excretion:
- RENAL CALCULI (most common presentation)
hypercalcaemia:
- muscle WEAKNESS, FATIGUE
- neuropsychiatric manifestations: DEPRESSION, DEMENTIA, CONFUSION, MEMORY PROBLEMS
- POLYURIA, POLYDIPSIA, DEHYDRATION
- HYPERTENSION
- ABDO PAIN, NAUSEA, VOMITTING
- CONSTIPATION
“bones, stones, abdominal groans, and psychic moans”.
what actions does the release of parathyroid hormone trigger? 4
what stimulate the parathyroid glands?
- Increases the release of calcium from bone matrix
- Increases calcium reabsorption by the kidney
- Increases renal production of 1,25-dihydroxyvitamin D3, which increases intestinal absorption of calcium
- Increases phosphate excretion by kidney
LOW blood Ca stimulate glands
what are the three familial neoplastic syndromes which parathyroid adenomas can form part of?
what is the inheritence pattern?
- MEN 1
- MEN 2
- hyperparathyroidism + jaw tumour syndrome
autosomal dominant inheritence
nb there are quite a few overlapping MEN syndromes, with varying patterns, don’t need to know details of each just be aware they exist
what is the difference in morphology/histology of the glands in primary hyperparathyroidism when compared to secondary/tertiary?
primary:
- one enlarged gland
- others smaller than normal (due to neg feedback)
secondary/tertiary:
- all glands show hyperplasia as they are all responding to low blood calcium
histology is the same for all three!!
adrenal glands:
- what’s produced in the medulla? 3
- what’s produced in the cortex? 3
MEDULLA:
- adrenaline
- noradrenaliine
- dopamine
CORTEX:
- androgens (eg testosterone)
- glucocorticoids (eg cortisol)
- mineralcorticoids (eg aldosterone)
“basically stuff that’s also used as neurotransmitters are in the MIDdle (ie MEDulla) because brain is inside the skull, think of cortex like the skull”
what type of hormones are adrenaline, noradrenaline and dopamine?
(ie what group of hormones is produced by the adrenal medulla?)
catecholamines
which part of the adrenal gland is under the control of the hypothalamus/pituatory?
cortex
“medulla is in the middle so more hidden away from blood stream etc”
main three types of causes of cushing’s syndrome?
what hormone is it an excess of?
exogenous causes
- excessive glucocorticoid medication (ie iatrogenic)
endogenous causes
- adrenal cortical tumours
- adrenal cortical hyperplasia
- ACTH secreting pituitary adenoma
paraneoplastic syndrome
- from small cell lung cancer
- very rare though
cortisol (glucocorticoids)
symptoms of cushings syndrome? 17
hint: cortisol is stress hormone! - think about what body would do if chronically stressed!
- truncal obesity
- ‘buffalo hump’ (fat deposits on back of neck + shoulders)
- ‘moon face’ (round, red, puffy)
- weak muscles
- weak bones (osteoporosis)
- mood swings/depression
- headaches
- chronic fatigue
- increased hair growth (hisuitism)
- prominent stretch marks (abdo striae)
- excessive sweating
- acne
- erectile dysfunction
- irregular/aabsent periods
- thin skin
- cuts/bruises heal slowly
- high blood pressure
conn’s syndrome:
- aka?
- gender/age affected?
- causes? 2
- pathogenesis?
primary hyperaldosteronism
- females more
- middle aged (30-50)
- adrenal cortical hyperplasia/adenoma
- familial hyperaldosteronism
excess production of the hormone aldosterone -> salt + water retention and low potassium (due to increased kidney secretion of it)
signs/symptoms of conn’s syndrome? 5
- high BP
- headaches
- muscle weakness
- muscle spasms
- excessive urination
bottom 3 symptoms are due to low blood potassium
- however over half of people with conns will have blood potassium within normal range
nb this is almost always asymptomatic
- only sign is nor high BP which is often mistaken for essential hypertension
addisons disease:
- what is it?
- most common cause?
- treatment?
- prognosis?
primary adrenal cortical insufficiency (mainly lack of cortisol, but also low aldosterone)
- caused by adrenal dysgenesis or dysfunction
autoimmune cause is most common
- though condition is very rare!
treatment = long term steroid replacement
if undiagnosed can prove fatal!
symptoms/signs of addisons disease? 7
- hyperpigmentation
- postural hypotension
- hyponatraemia
- hypoglycaemia
- weight loss
- tiredness
- abdo pain
nb need a high index of suspision, very non-specific signs
phaeochromocytoma:
- what is it?
- cause?
- test?
- benign or malignant?
catecholamine-secreting (noradrenaline + adrenaline) tumour arising from adrenal medulla
most are sporadic
- can be part of familial cancer syndromes though (eg MEN 2a+b, von hippel-lindau etc)
- urine test for catecholamines (will be elevated)
90% benign, 10% malignant
excellent prognosis for benign when surgically removed
- malignant tumours may be aggressive
nb can get extra-adrenal ones too!!!
nb 10% are in kids, can happen at any age
signs/symptoms of phaeochromocytoma?
- hypertension
- palpitations
- excessive sweating
- headaches
- anxiety
“basically constant ‘fight or flight’ response due to too much adrenaline”
peptide hormones vs steroid hormones:
- 3 examples of each?
- where act on target cell?
- how produced/stored?
peptide hormones:
- eg PTH, ACTH, TSH
- tend to act on cell-membrane recptors -> intracellular cascade -> mRNA transcription
- stored in granules then released
steroid hormones:
- eg testosterone, oestradiol, cortisol
- tend to act on INTRA-cellular receptors -> mRNA transcription
- made when they are needed
nb steroid hormones can also act on cell-surface receptors but, as they are lipophillic, can get through cell membranes without need for receptors
how are steroid hormones transported in the blood?
circulate bound to serum proteins
what hormone is produced by the thymus gland to stimulate T-cell production?
thymosin
what hormone is produced by the heart?
what is this in response to?
what effect does it have?
BNP (brain naturitic peptide - weirdly named!)
in response to excessive myocyte stretch
trigger naturesis (sodium excretion) in the kidney to lower blood pressure + so reduce strain on heart
“the policies of the BNP parties strain my heart!”
what peptide is produced as a side effect of endogenous insulin production?
c-peptide
nb thought to just be a waste product but now thought to have endocrine actions of its own
what brain structure is responsible for circadian/diurnal rhythms?
what hormone does it secrete?
pineal gland (main mart of the epithalamus, a part of the diencephalon)
melatonin
melatonin triggers you to fall asleep (natural light inhibits melatonin production)
nb melanin is produced by melanocytes in the skin and is pigmented - don’t get them confused!!
TSH and T3/T4 levels in:
- primary hypothyroidism?
- secondary hypothyroidism?
- primary hypothyroidism, not taking thyroxine consistently?
- primary hyperthyroidism?
- secondary hyperthyroidism?
primary hypothyroidism:
- low T3/T4
- high TSH
secondary hypothyroidism:
- low T3/T4
- low TSH
primary hypothyroidism, not taking thyroxine consistently:
- high T3/T4
- high TSH
primary hyperthyroidism
- high T3/T4
- low TSH
secondary hyperthyroidism:
- high T3/T4
- high TSH
what 5 types of cancers can cause ectopic ACTH secretion -> high cortisol? (a type of paraneoplastic syndrome) 5
- benign carcinoid tumours of the lung
- small cell lung cancers
- islet cell tumours of pancreas
- medullary carcinoma of the thyroid
- tumours of the thymus gland
what is the name for primary adrenal insufficiency?
addisons disease
aka primary hypocortisolism
what principles of testing are used to test for hormone overor under production?
hormone levels vary through out the day so random tests are of little help
need to do dynamic testing
if you suspect excess production, try to suppress production
if you suspect insufficient production, try to stiumulate production
describe the normal distribution of blood cortisol levels throughout the day
there is a peak in cortisol at about 9am then steadily lowers throughout the day (but peaks after eating and exercise)
then low during the night
what is the difference between cushing’s disease and cushing’s syndrome?
cushing disease is primary adrenal overproduction of cortisol
cushing’s syndrome is another cause of excess cortisol, eg exogenous steroid use, ACTH secreting tumour etc
if you have over production of cortisol do you get amenorrhoea/oligomenorrhea (very light periods) or menorhagia (very heavy periods)?
if high cortisol (cushings):
- amenorrhoea/oligomenorrhoea
if very low cortisol (addisons):
- menorhhagia
“think of it like, if your body is under a lot of stress, cortisol is stress hormone, then body’s priority is NOT to become pregnant and thus put extra strain on body”
nb men with cushings can often be impotent
what may back pain in cushing’s syndrome be a sign of?
what psychiatric disturbances can be seen in cushings?
osteoporosis
depression, psychosis (+ others)
nb can also get high BP, muscle weakness, headaches, nausea + visual disturbances
what test is used to test for cushing’s disease? how does it work?
overnight dexamethasone suppression test
tests patient’s cortisol level during day
then patient takes a dexamethasone (steroid) pill at midnight, this should suppress endogenous steroid production
then retest blood cortisol at 9am in morning and it should be lower than the previous day, if not, then high likelihood of cushings
what is the test for addisons disease/primary adrenal failure? how does it work?
measure blood cortisol at 9am
then give SYNACTHEN (an ACTH analogue)
then measure blood cortisol 30 mins later, if not significantly increased then high likelihood of adrenal insufficiency
which thyroid hormone is the active form?
which is in higher abundance?
T4 is in higher abundance and is converted into T3 (the active form
“normally things like proteins are activated by having something removed, so going from T4->T3, you are removing one T”
what is ‘sick euthyroid syndrome’?
what is the mechanism that causes it?
what does this mean in clinical practise?
when a patient is very unwell (with whatever condition), lots of cytokines are produced as part of the inflammatory response
the cytokines act systemically and, as well as many other actions, they decrease the circulating T3 + T4
therefore if you test someones blood T3/T4 levels when they are very sick, they are likely to have low T3/T4 levels, even if there is no thyroid pathology
so you shouldn’t test people’s thyroid function when they are unwell
nb euthyroid means normal thyroid (ie not hypo or hyper)
what is the enzyme responsible for converting T4 -> T3?
when is it inhibited?
deiodinase
in sick euthyroid syndrome -> low T3 levels
nb there are also other mechanisms that lower T3/T4 in sick euthyroid syndrome
what test can you do to work out if a woman is going throught the menopause?
what is the mechanism behind this?
why should you be cautious in doing this?
test their levels of FSH
when ovaries stop producing oestrogen (menopause) then the hypothalamus/pituatory doesn’t get negative feedback and so produces a lot MORE FSH
so a women going throught the menopause will have high blood FSH
HOWEVER a women who is still ovulating (pre-menopausal) will physiologically have high FSH in the middle of her cycle
therefore this test is not very relaible and so is not done often in clinical practise
what are the three main peaks of testosterone production in a male’s life?
a peak in foetus, then drops before birth
a peak around 2-4 months of age (get spotty) then drops
low during childhood
massive peak during puberty/low 20s then slowly decreases throughout adulthood
what is the test for a phaeochromocytoma?
what two things are being tested for?
24hr urine collection
measure levels of catecholamine metabolites
nb do this because the actual catecholamines are very unstable and present at low concentrations in blood + vary wildly throughout day so hard to reliably measure however metabolites are excreted in urine
nb phaeochromocytoma is a tumour of the adrenal medulla
what is whipple’s triad?
what is it a test for?
the clinical presentation of pancreatic insulinomas, 3 criteria:
- FASTING hypoglycaemia
- symptoms of hypoglycaemia
- immediate relief of symptoms after the administration of IV glucose
insulinomas
nb this is in no way related to whipple’s disease but IS named after the same surgeon who invented the whipple’s procedure for surgical resection of cancers of the head of the pancreas
what is the current gold standard test for insulinomas?
what would indicate a positive result?
in adults who fit the whipple’s criteria (low blood glucose, symptoms of hypoglycaemia), the patient has to undertake a 72-hour fast (in hospital) - they are allowed water!
then blood glucose and insulin are tested
results in a normal person:
- low blood glucose
- LOW blood insulin
results in someone with an insulinoma:
- low blood glucose
- HIGH blood insulin
nb before doing this fast you would check other medical and drug history to see if there was any other cause for the hypoglycaemia
nb in addition c-peptide levels are measured (which should be as high as the insulin levels), if they are low then it indicates the excess insulin is exogenous (has been injected)
what are the two groups of symptoms seen in hypoglycaemia/insulinomas?
pathophysiology?
give some examples
neuroglycopenia:
- double/blurred vision
- confusion/abnormal behaviour
- amnesia
- seizures
- loss of consiousness
- coma
adrenergic
- weakness, warmth
- sweating
- hunger
- tremor
- palpitations/tachycardia
- anxiety
brain has a high demand for glucose so is the first thing to suffer is the brain -> neuroglycopenic symptoms
when the blood glucose drops it triggers a release of adrenaline by the adrenal glands (in ordewr to try to raise blood glucose) -> adrenergic symptoms
nb while adrenaline may raise the glucose levels in normal patients with moderately low glucose levels, it is insufficient to overcome the effect of the continuously secreted insulin by insulinomas
what are two other names for:
- type 1 diabetes mellitus?
- type 2 diabetes mellitus?
type 1 DM:
- insulin dependent DM (IDDM)
- ketotic DM
type 2 DM:
- non-insulin dependent DM (NIDDM)
- non-ketotic DM
