endo Flashcards
define endocrinology
study of hormones (and their gland of origin), their receptors, the intracellular signalling pathways, and their associated disease
what do hormones do?
excite
what’s the diff btwn endocrine and exocrine?
endocrine (within glands - pour secretion into blood stream)
exocrine (outside glands - pour secretions through a duct to site of action)
name some examples of endocrine glands (2)
thyroid
adrenal
where are peptides/monoamines stored?
in vesicles
how are steroids synthesised?
on demand
list the hormone classes
peptides
amines
iodothyronines
cholesterol derivatives and steroids
what are the 3 stages of hormone production
preprohormone
prohormone
hormone
what response do amines stimulate?
sympathetic NS - fight or flight
where are peptide hormones stored
in secretory granules
what % of T3 in the circulation is secreted directly by the thyroid?
20%
what are T4/T3 cleaved from
thryoglobulin
are thyroid hormones water soluble?
no, 99% protein-bound
what does vitD stimulate the production of?
mRNA
what type of basal secretion involves hormones?
continuously or pulsatile
define synergism
combined effects of 2 hormones amplified (eg glucagon with epinephrine)
define antagonism
when 1 hormone opposes another (eg glucagon antagonises insulin)
what is hormone receptor down regulation?
hormone secreted in large quantities cause down regulation of its targets receptors
what do hypothalamic neurone synthesise?
oxytocin
ADH
where’s oxytocin/ADH transported to from the hypothalamus?
the posterior pituitary
via the hypothalamic-hypophyseal tract
what is somatostatin aka
(GHIH) growth hormone inhibiting hormone
what are the direct actions of GH?
metabolic
anti-insulin
(fat/carb metabolism)
what are the indirect actions of GH?
growth-promoting (skeletal and extraskeletal)
what kinda effect does thyroid hormone overall have?
increases!
food metabolism protein synthesis carbohydrate metabolism fat metabolism ventilation rate CO and HR growth rate brain development
where are mineralocorticoids produced?
zona glomerulosa
where are glucocorticoids produced?
zona fasciculata
where are androgens produced?
zona reticularis
name a mineralocorticoid
aldosterone
name a glucocorticoid
cortisol androgens
which cell is FSH produced in?
granulosa cell
which cell is LH produced in?
theca cell
which hormone is produced in the heart?
ANP (atrial natriuretic peptide)
which hormone is produced in the liver?
IGF-I (insulin-like growth factor I)
which hormone is produced in the kidney?
erythropoetin
which hormones are produced in the GI tract? (2)
gastrin
incretin
which hormones are produced in blood vessels?
prostanoids
NO
endothelin
how do alcohol and caffeine impact ADH release?
inhibits
how does a lack of ADH influence urine
u urinate more
what are the 3 diff presentations of pituitary dysfunctions?
tumour mass effects
hormone excess
hormone deficiency
what are the investigations for hormone abnormalities? (2)
hormonal tests
if hormonal tests abnormal or tumour mass effects, perform MRI pituitary!
define appetite
desire to eat food
define hunger
need to eat
define anorexia
lack/loss of appetite
define satiety
feeling of fullness (disappearance of appetite after a meal)
define BMI
weight (kg)
_________
height (metre squared)
what is a bmi of under 18.5?
underweight
what is a bmi btwn 18.5 - 24.9
normal weight
what is a bmi btwn 25.0 - 29.9?
overweight
what is a bmi of 30.0 - 39.9?
obese
what is a bmi of >40?
morbidly obese
list 7 risks of obesity
t2 diabetes hypertension coronary artery disease stroke osteoarthritis obstructive sleep apnoea carcinoma (breast, endometrium, prostate, colon)
what type of fat is obesity?
abdominal (visceral) rather than subcutaneous
how does sleeping out of phase contribute to obesity?
sleeping out of phase
- -> lower leptin levels
- -> eat more
- -> cortisol levels higher than they should be
- -> high cortisol levels at night
- -> metabolic issues
what are the opposing forces in appetite regulation?
energy expenditure vs energy intake
why do we eat? (3)
internal physiological drive
feelings that prompt thoughts of food
external psychological drive
what does highly refined sugar lead to?
quick and short satiety
what kinda foods are better?
low glycemic index food
also high protein - prolonged satiety
where is the hunger centre?
lateral hypothalamus
where is the satiety centre?
ventromedial hypothalamic nucleus
which part of the brain plays a central role in appetite regulation?
hypothalamus
what are the main players in appetite regulation?
peripheral factors (leptin, insulin) gut peptides (ghrelin, GLP1, CKK) centra areas, hypothalamus (NPY, POMC, serotonin)
where is leptin expressed?
white fat
what does leptin do?
switches off appetite
immunostimulatory
after a meal, how do leptin levels change?
increase
where are CCK (cholecystokinin) receptors?
pyloric sphincter
what does CCK do? (4ish)
delays gastric emptying
initiates gall bladder contraction
stim insulin release
via vagus - satiety
where is ghrelin expressed?
stomach
how do blood levels of ghrelin change after meal?
high
what are the net effects of leptin and insulin?
increased satiety and decreased appetite
what is the net effect of ghrelin?
increased appetite
what do stretch receptors in the stomach do?
increase satiety
define obesity (WHO definition)
abnormal or excessive fat accumulation that may impair health
what are the 4 tiers of obesity care pathway at an individual level?
tier 1 - universal prevention
tier 2 - lifestyle intervention
tier 3 - specialist services
tier 4 - surgery
why is diabetes a PH issue? (4)
mortality
disability
co-morbidity
reduces QOL
what does the obesogenic environment involve?
physical env (car culture) economic env (expensive fruit n veg) sociocultural env (family eating patterns)
what is a physical mechanism that maintains being overweight?
more weight = more difficult to exercise (arthritis, stress incontinence) and dieting –> metabolic response
what is a psychological mechanism that maintains being overweight?
low self-esteem and guilt, comfort eating
what is a socioeconomic mechanism that maintains being overweight?
reduced opportunities, employment, relationships, social mobility
what are risk factors for obesity?
age, sex, ethnicity, FH, weight, BMI, waist circumference, hypertension, vascular disease, impaired glucose tolerance (IGT) or impaired fasting glucose
what is IGT
impaired glucose tolerance
what is IFG
impaired fasting glucose
list 5 screening tests for obesity
HbA1c random capillary blood glucose random venous blood glucose fasting venous blood glucose oral glucose tolerance test (OGTT)
what does OGTT involve
venous blood glucose 2 hrs after oral glucose load
what is the diagnostic range for IGT?
7.8 - 11.0 mmol/l
what is the diagnostic range for IFG?
6.1 - 6.9 mmol/l
how can society reduce the impact of t2 diabetes? (4)
identifying ppl at risk
early prevention in those at risk
diagnosing diabetes earlier
effective management and supporting self-management
what does the pituitary gland regulate?
growth and development
fertility
metabolism
body composition
does the anterior pituitary gland have a blood supply?
no but receives blood through a portal venous circulation from the hypothalamus
where is prolactin released from?
the anterior pituitary gland
what is prolactin under neg control by?
dopamine
if anything damages the pituitary stalk and thus delivery of dopamine, WHAT levels increase?
prolactin
what hormone can tumours secrete?
prolactin!
what is the most common disease of the pituitary gland?
benign pituitary adenoma
which disease of the pituitary tends to be in younger ppl?
craniopharyngioma
what do a lot of endocrine organs get?
adenomas
what are most adenomas like?
benign
define adenoma
benign tumour formed from glandular structures in epithelial tissue
what are the 3 VITAL points of tumour presentation?
can cause:
pressure on local structures (eg optic nerves)
pressure on normal pituitary (hypopituitarism)
functioning tumour
what is prolactinoma?
too much prolactin
what is acromegaly?
too much GH
what is Cushing’s disease?
too much ACTH
what can pituitary adenoma pressure cause?
headaches
which vision do u lose first?
colour!
what is the field defect u get with a pituitary tumour?
bitemporal hemianopia starting upper quadrantic
pituitary tumours can go through the bottom of the pituitary fossa and drain the nose …. what is a clue to an important diagnosis to make?
CSF has sugar
snot doesn’t
what is the most common prolactinoma?
prolactin microadenoma
prolactin causes suppression of what?
gonadotrophins
as prolactin causes suppression of gonadotrophin, what tends to happen to females? (2)
lose periods
get milk into breasts
how do prolactin levels change during pregnancy?
increase
if somebody checks with period loss/infertility issues… check what?
prolactin (ngl this always seems to be the answer, but maybe bc I’ve only covered this lecture LOL @ future me, come back to this)
how difficult is it to treat hyperprolactin?
87% ppl respond to dopamine agonist!
80% women got pregnant within 3m of starting this
prolactinomas are more common in who?
women
what can be a symptom of prolactinoma?
libido loss, infertility, amenorrhoea
how can a tumour result in gigantism?
tumour presses on pituitary gland, increases GH - don’t go through puberty as bones don’t fuse
what are signs of acromegaly?
thick skin
greasy
sweating
frontal bossing
too much steroid/cortisol can result in which syndrome?
cushing’s
what is the commonest cause of too much steroid?
anti inflammatory drugs
if u have a patient with a pituitary tumour, what are the 3 questions to ask?
is it pressing on the optic chasm?
are they hypopituitary?
do they have a functioning tumour?
cortisol deficiency can result in death - why?
due to an adrenal crisis
what is the HPA axis a classic example of?
negative feedback loop
what does HPA (axis) stand for
hypothalamic-pituitary-adrenal
if deficient with cortisol, what to replace it with?
hydrocortisone
what is hydrocortisone?
the pharmacological name for cortisol
what is the distinct circadian rhythm of cortisol?
rises in the early hours of morning (3am, peaks shortly after waking, declines during the day)
what do cortisol levels parallel?
energy levels
what is the primary zeitgeber?
light
what is a primary disease of adrenal insufficiency?
addison’s disease
what is a secondary disease of adrenal insufficiency?
hypopituitarism
if u ever see low Na and high K - think of what?
addison’s
what is cortisol important for retaining/getting rid of?
retaining Na
getting rid of K
when looking at circadian rhythm & deficiency - look when it’s at its…… ?
highest
when looking at circadian rhythm & excess - look when it’s at its…… ?
lowest
how to treat cortisol deficiency?
2/3x daily hydrocortisone 15-25mg
in primary adrenal insufficiency, replace aldosterone with what?
fludrocortisone
what is a common presentation of adrenal insufficiency?
adrenal crisis
what does an adrenal crisis involve?
hypotension and CV collapse fatigue fever hypoglycaemia hyponatraemia and hyperkalaemia
how would u manage an adrenal crisis?
take bloods (for cortisol and ACTH)
immediate hydrocortisone 100mg IV, IM
fluid resuscitation (1L saline 1 hr)
hydrocortisone 50-100mg IV/IM 6 hourly
what does TDS stand for in pharmacology
3x a day
for adrenal insufficiency, always consider what?
recent steroid use
check cortisol and ACTH
describe the regulation of HPA axis
circadian rhythm controlled by central clock
describe causes of adrenal insufficiency
primary (Addison’s and CAH)
secondary (pituitary)
what is the diff btwn gigantism and acromegaly?
gigantism = before puberty
what are the commonest endocrine disorders?
thyroid diseases
FHx of t1 diabetes is a strong association w what?
thyroid disease ;/
what is found in almost all patients with autoimmune hypothyroidism
thyroglobulin and thyroid peroxidase (TPO) antibodies
what is the mechanism of thyroid cell destruction?
cytotoxic (CD8+) T cell mediated
thryglobulin and TPO antibodies may cause 2ndary damage, but alone have no effect
what are some symptoms of Graves’ disease?
retracted eyelids
bulging eyes
redness
what does Graves’ disease cause
hyperthyroidism
often an enlarged thyroid
what is the cause of Graves’ disease?
thyroid stimulating antibodies
what is Graves’ disease aka
hyperthyroidism
what is myxoedema aka
hypothyroidism
what is the biggest risk factor to thyroid disease?
being female
what are some autoimmune diseases associated w thyroid autoimmunity?
t1 DM
addison’s disease
pernicious anaemia
vitiligo
what is swelling in extra ocular muscles?
thyroid associated opthalmopathy
how can graves disease occur in pregnancy
caused by thyroid stimulating antibodies that may cross the placenta
what is goitre?
palpable and visible thyroid enlargement
endemic in iodine deficient areas
what is sporadic non-toxic goitre?
commonest endocrine disorder
define hyperthyroidism
excess of thyroid hormones in blood
what are 3 mechanisms for increased levels of thyroid hormone?
overproduction of thyroid hormone
leakage of preformed hormone from thyroid
ingestion of excess thyroid hormone
what is pituitary adenoma aka
TSHoma
list some clinical features of hyperthyroidism
weight loss tachycardia hyperphagia anxiety heat intolerance sweating diarrhoea menstrual disturbance
what are thionamides?
anti thyroid drugs
what is essential for thyroid hormone production?
iodine
how is iodine actively transported into thyroid follicular cells?
via Na/I symporter
what are some causes of hypothyroidism
Hashimoto's thyroiditis thyroidectomy iodine deficiency thyroid hormone deficiency pituitary/hypothalamic disease
list some clinical features of hypothyroidism
fatigue weight gain cold intolerance constipation dry, rough skin delayed muscle reflexes
what can u see in the investigation of primary hypothyroidism
increased TSH (most sensitive marker) usually decreased free T4/T3
what is the most sensitive marker of hypothyroidism
TSH
amiodarone (iodine rich) often used to treat what?
atrial fibrillation
many drugs can affect the thyroid, particularly what?
amiodarone
what are the 2 most important hormones in calcium homeostasis?
PTH and calcitriol
what is calcitriol aka
1,25 dihydroxy vit D
what is 1,25 dihydroxy vitD aka?
calcitriol
PTH release is increased in response to what?
low serum ionised calcium
what are the 3 ways in which PTH works to increase serum calcium?
-CONFUSED-
decreasing renal calcium excretion
increasing bone resorption
enhancing dietary calcium absorption (by stimulating prod of calcitriol in kidney)
? increased calcium absorption increased one resorption increased calcium reabsorption ?
what can abnormal circulating calcium levels result in?
impaired muscle and nerve function
cardiac dysrhymias
abnormalities of which hormone levels can be an appropriate response to calcium imbalance OR can be the primary cause of calcium imbalance?
PTH
In secondary hyperparathyroidism, how do PTH levels change?
increase
In secondary hyperparathyroidism, how do calcium levels change?
decrease
In secondary hyperparathyroidism, how do phosphate levels change?
decrease
is PTH appropriate or inappropriate in secondary hyperparathyroidism?
appropriate
In hypoparathyroidism, how do PTH levels change?
decrease
In hypoparathyroidism, how do calcium levels change?
decrease
In hypoparathyroidism, how do phosphate levels change?
increase
what is pseudohypoparathyroidism aka?
PTH resistance
what is another way to say a disorder of PTH resistance?
pseudohypoparathyroidism
in pseudohypoparathyroidism, how do PTH levels change?
increase
in pseudohypoparathyroidism, how do calcium levels change?
decrease
in pseudohypoparathyroidism, how do phosphate levels change?
increase
what kind of feedback is calcium homeostasis?
negative
what is the set point of serum ionised calcium?
1.1 mol/l ish
If Ca decreased by 10%, how much does PTH increase by?
200%
if Ca increases by 10%, how much does PTH decrease by?
70%
what is the equation for corrected calcium?
total serum calcium + 0.02(40 - serum albumin)
if serum calcium = 2.08 mmol/L
and
serum album = 30 g/L
what is the corrected calcium? (mmol/L)
2.28
list 6 consequences of hypocalcaemia
parasthesia (burning/prickling sensation in limbs) muscle spasm seizures basal ganglia calcification cataracts ECG abnormalities (long QT interval)
what is a fairly common cause of hypocalcaemia?
osteomalacia
how to test chvostek’s sign?
tap over facial nerve
look for spasm of facial nerves
how to test trousseau’s sign?
inflate BP cuff to 20mmHg above systolic for 5 mins - clawing dinosaury thing
name some syndromes of hypoparathyroidism
di george
HDR
kenney-caffey
list 4 consequences of hypoparathyroidism
decreased renal Ca reasborption
incresed renal phosphate reabsorption
decreased bone resorption
decreased formation of calcitriol
what are some symptoms of pseudohypoparathyroidism?
short stature
obesity
mild learning difficulties
normal calcium metabolism!
list 6 symptoms of hypercalcaemia
thirst, polyuria nausea constipation confusion (--> coma) renal stones ECG abnormalties (short QT)
define parasthesia
burning/prickling sensation in limbs, consequence of hypocalcaemia
define polyuria
excessive urine prod/passage
above 2.5/3L in 24hrs
what are 2 main causes of hypercalcaemia?
malignancy (bone mets, myeloma, lymphoma etc)
primary hyperparathyroidism
primary hyperparathyroidism can cause what?
hypercalcaemia
what are consequences of primary hyperparathyroidism?
bones, stones, grones, and moans lol
osteoporosis
kidney stones
confusion
constipation/acute pancreatitis
what’s the main cause of primary hyperparathyroidism?
80% due to single benign adenoma :/
what happens in tertiary hyperparathyroidism?
renal failure
cant activate vit D§
hypercalcaemia
define puberty !
physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms
what is the definitive sign of puberty in boys?
1st ejaculation, often nocturnal
what is the definitive sign of puberty in girls?
menarch - 1st menstrual bleeding
when do secondary sexual characteristics occur
at puberty
how does ovarian oestrogen contribute to secondary sexual characteristics?
regulate growth of breast and female genitalia
how do ovarian and adrenal androgens impact secondary sexual characteristics?
pubic and axillary hair
how do testicular androgens contribute to secondary sexual characteristics?
external genitalia and pubic hair growth
enlargement of larynx/laryngeal muscles (voice deepening)
what is a good marker of puberty in boys
testicular growth
how do tanner stages differ?
1 - no pubic hear, testicular vol less than 3ml/elevation of papilla only
5 - adult-type hair spread to medial surface of thighs
- genitalia adult size n shape / classic inverse triangle hair type in females, adult contour breast
what is significant about testicular volume in klinefelters?!
they hardly ever get testicular vol above 5ml
what is testicular size mainly dependant on?
number of germ cells
what is the diff btwn s1 and s2 of tanner stages in girls
s1 - breast bud
s2 - no breast bud
what is a good marker of puberty in girls?
presence of breast bud - can’t grow without oestrogen
define thelarche
breast development
what is thelarche (breast development) induced by?
oestrogen
how long does it take for breasts to develop?
3 years ish
what are the effects of oestrogen on the breast? (3)
ductal proliferation
site specific adipose deposition
enlargement of areola and nipple
other than oestrogen, what other hormones are involved in breast development?
prolactin
glucocorticoids
insulin
can both breasts be in diff stages of tanners?
yuh
what is the (basic) diff btwn prepubertal and postpubertal uterus?
pre - tubular shaped, 2-3cm length
post - pear shaped, 5-8cm length
what are 3 questiosn to ask during a pelvic ultrasound in girls?
- are mullerian structures present?
- is there morphology of the uterus?
is there morphology of ovaries?
what are the 5 ways in which the external genitalia in females changes under the effect of oestrogens?
labia majora/minora increase in size n thickness
rogation/?rotation and change in colour of labia majora
hymen thickens
clitoris slightly enlarges
vestibular glands begin secretion
define adrenarche
the onset of androgen-dependent body changes eg axillary/pubic hair, body odour and acne!
define pubarche
1st appearance of pubic hair at puberty
what is the most pronounced clinical result of adrenarche
pubic hair
what is the hpg axis?
hypothalamus (tertiary)
pituitary (secondary)
gonads (primary)
where is GnRH released
hypothalamus
what does GnRH result in the formation of
LH, FSH from pit gland
for males with early puberty, what is it important to rule out?
brain tumour
“true” precocious puberty - 90% of patients are what?
female
in true precocious puberty, what is the rise in LH:FSH?
above 1
which type of puberty is GnRH dependent?
true precocious puberty
which type of puberty is GnRH independent?
precocious pseudo-puberty
CNS tumours/disorders can result in what?
true precocious puberty
increased andorgen secretion and gonadotropin secreting tumours can reuslt in what?
precocious pseudopuberty
congenital adrenal hyperplasia can result in what?
increased androgen secretion
3 resaons why puberty may be delayed? (they loooong)
idiopathic (constitutional) delay in growth and puberty
hypogonadotropic hypogonadism
hypergonadotropic hypogonadism
what is idiopathic (constitutional) delay in growth and puberty?
delayed activation of the hypothalamic pulse generator
what is hypogonadotropic hypogonadism
sexual infantilsm related to gonadotropin deficiency
lwhat is sexual infantilism?
lack of sexual development after expected puberty or delayed puberty
is delayed puberty more common in boys or girls?
boys
how does delayed puberty impact bone mass?
reduces it
what are some indications of investigation for delayed puberty in girls?
lack of breast development by 13
5+ yrs btwn breast development n period
lack of pubic hair by 14
no period by 15-16
what are some indications of investigation for delayed puberty in boys?
lack of testicular enlargement by 14
lack of pubic hair by 15
5+ yrs for complete genital enlargement
what does CDGP stand for
constitutional delay of growth and puberty
what are some signs of constitutional delay of growth n puberty (cdgp)
shorter for age
delay in bone maturation, adrenarche
FH of late menarche
what are lab investigations for puberty? (low conc of any of these)
complete RBC count
U&E, renal, LFT, coeliac ab
LH,FSH
testosterone, oestradiol
thyroid function, prolactin
DHEA-S, ACTH, cortisol
in ALL girls w short stature and delayed puberty: rule out whAT?
turner’s (X0)
is skeletal or chronological age more closely correlated with pubertal development?
skeletal
what are some functional causes of delayed puberty?
chronic renal disease sickle cell anorexia psychological/stress extreme exercise drugs cushing's hypothyroidism
which type of hypogonadism is it if ovary/testis fails?
primary
what happens in primary hypogonadism
ovary/testis fails:
oestrogen/tesotsterone decrease
slack of feedback
LH n FSH increase
which type of gonadism is it if hypothalamus/pituitary gland fails?
secondary
what happens in secondary hypogonadism
hypothalamus/pituitary fails:
LH n FSH low
no response to feedback
so oestrogen/testosterone decreases
define hyposmia/microsmia
reduced ability to smell and detect odours
define anosmia
when no odours can be detected
what is kallman syndrome
hypogonadotrophic hypogonadism
what is the key symptom of kallman syndrome (hypogonadotrophic hypogonadism)
inability to detect odours
what is hypergonadotropihc gonaidsm?
ripmary gonadal failure (males - klinefelters, females - turners)
list some signs of klinefelter
primary hypogonadism
reduced 2ndary sexual hair
osteoprosis
tallstature
define azoospermia
medical cond of a man whose semen contains no sperm
define gynaecomastia
enlargement of a man’s breast
what are 3 diff presentations of klinefelters
dont go into puberty
go into puberty but stopped, don’t develop fully
infertile (germ cell failure)
list some signs of turners, bitch
at birth - oedema of dorsa of hands/feet
webbing of neck
CV malformations
short stature
what is a horseshoe kidney
fusion of kidney at upper poles
can happen in turner’s
what does female replacement therapy involve?
ethinyl estadirol (Tablet) or oestrogen (tablets, transdermal)
what does male replacement therapy involve?
testosteronen enthane (IM injection)
what is the diff btwn precocious and delayed puberty?
precocious - onset of 2ndary sexual characteristics before 8/9yrs
delayed - absence of 2ndary sexual characteristics by 14/16 yrs
what is the hypothalamic regulation of GnRH secretion
increased stim factors (mostly glutamate and kisspeptin)
what % of the human body is fluid?
60%
what is the distribution of ECF vs ICF?
ECF - 1/3 total body water (14L)
ICF - 2/3 total body water (28L)
what can ECF be split into?
intravascular fluid - 1/4 ECF (3.5L)
interstitial fluid - 3/4 ECF (10.5L)
how does osmotic pressure of fluid compartments differ?
it doesnt, its approx equal
what kinda ions does ECF contain
Na, Cl and bicarb
what kinda ions does ICF contain?
K, Mg and phosphate
ECF/plasma osmolarity and what conc should be considered together n why?
Na conc - bc Na+ comprise majority of solute in ECF
how does the body respond to changes in ECF osmolarity, BP or blood vol?
by altering water reabsorbed by kidneys and fluid ingested
what happens in conditions of water excess?
there’s a fall in plasma osmolality and an influx of water into the cells, increasing the intracellular water content. this reduces thirst, suppresses ADH release thus decreasing water intake and increasing water excretion
what does ADH bind to?
g-protein coupled 7 transmembrane domain receptors
what are the diff g-protein coupled 7 transmembrane domain receptors adh binds to?
V1a (vasculature)
V2 (renal collecting tubules)
V1b (pituitary gland)
what 2 things is ADH release controlled by?
osmoreceptors in thalamus (day to day)
baroreceptors in brainstem/great vessels (emergency)
in a day to day situation, what controls ADH release?
osmoreceptors in the thalamus
in an emergency situation, what controls ADH release?
baroreceptors in the brainstem/great vessels
which receptor does ADH bind to in the renal collecting duct principle cells?
V2 receptors
which receptor does ADH bind to in vasculature?
V1a
which receptor does ADP bind to in the pituitary gland?
V1b
what is the main driver for fluid intake?
thirst
what are 2 main drivers of variable water excretion by urine output?
GFR
ADH
what is omolality
concentration per kilo
list some exogenous solutes that may affect osmolality
alcohol, methanol or mannitol etc
urine osmolality should be _______ serum osmolality
double
what is a normol osmolality?
282-295 mOsmol/kg
how do u approx calculate plasma osmolality?
2xNa+ + glucose + urea
where does rine conc by kidney occur
along theneprhon
vasopressin activates V2 receptors in renal collecting ducts, leading to what?
increased reabsorption of water via the kidneys
(aquaporin2 proteins synthesised and inserted into apical membrane, increasing permeability of renal collecting duct - water is reabsorbed and returned to blood)
when the stimulus for water reabsorption ends, how is aquaporin 2 removed from apical membrane?
endocytosis
what is the cause of cranial diabetes insipidus
lack of ADH
acquired (idiopathic - tumours, infections, inflammatory. primary - genetics, developmental)
how do u manage cranial DI?
treat any underlying cond
desmopressin
(tablets 100-1200 mg/day, nasal spray 10-40mg/day, injection 1-2mg/day)
what is desmopressin used to treat?
cranial DI (or in v high dose, nephrogenic CI)
what is nephrogenic DI?
resistance to ADH action
what are some causes of nephrogenic DI?
acquired (osmotic diuresis / DM), drugs eg lithium, chronic renal failure)
familiar (x linked - v2 receptor defect, autosomal recessive(AQP2 defect)
how can u manage nephrogenic DI?
try and avoid precipitating drugs
define hyponatraemia
serum sodium < 135 mmol/l
what is severe hyponatraemia
serum sodium < 125 mmol/l
what is normal serum sodium range?
137-144 mmol/l
what are some causes of hyponatraemia? (4)
SIADH
drip arm
sodium deficiency
renal failure
what do the signs/symptoms of hyponatraemia depend on?
speed of onset!
quicker onset = greater symptoms
what are some signs of hyponatraemia (less to more severe)
asymptomatic headache lethargy weakness confusion decreased concious level coma
what happens in ECF hypo-osmolality?
water moves into the brain
brain oedema
brain expels electrolytes and osmolytes
water loss accompanies loss of solutes, reducing swelling
what is the diff btwn acute n chronic hyponatraemia?
acute - 48H (rapid correction safer n may be necessary)
chronic - CNS adapts (correction must be slow)
what are the tests to do when hyponatrameia presents? (this is important )
plasma osmolality urine osmolality plasma glucose urine sodium urine diptestfor protein TSH cortisol
what are 3 causes of hyponatraemia
flui doverloaded
normovolaemic
dehydrated
what is SIADH
syndrome of inappropriate ADH secretion
what happens in SIADH
too much ADH when it should not be being secreted low osmolality plasma sodium low urine inappropriately concentrated water retention normal thyroid and adrenal function
what are some causes of SIADH?
CNS disorders (head injury, meningitis, brain tumour)
tumours (carcinoma, lymphoma, leukaemia)
resp causes (pneumonia, tuberculosis, severe asthma)
drugs (carbamazipine, thiazides, MAO inhibitors, vasopressin, desmopressin, SSRIs)
what is the treatment of SIADH? (acute and chronic)
fluid restriction!
acute - daily U+E in hosp
chronic - weekly-monthly U+E
what should be the fluid restriction if SIADH?
<1L/24hr
what is hypertonic saline for?
symptomatic hyponatraemia
what are vaptans?
selective v2 receptor oral antagonist
competitive to ADH
so what can cause DI?
lack of ADH
resistance to ADH
what kind of tissue is the anterior lobe of the pituitary gland?
glandular tissue (75% of total weight)
what kind of tissue is the posterior lobe of the pituitary gland?
nerve tissue (contains axons that originate in the hypothalamus)
what kind of tumours are there in the pituitary gland?
non-functioning pituitary adenomas endocrine active pituitary adenomas malignant pituitary tumours metastases in the pituitary pituitary cysts
where do craniopharyngiomas arise from?
squamous epithelial remnants of Rathke’s pouch
what happens w craniopharyngioma?
remnants of rathe's pouchraised ICP visual disturbances growth failure PH deficiency weight increase
what do rathke’s cysts derive from?
derived from remnants of rathke’s pouch
what does rathke’s cyst present with?
headache and amenorrhoea, hypopituitarism and hydrocephalus
after a pituitary adenoma, what is the commonest tumour there?
meningioma
what is a meningioma associated with
visual disturbance and endocrine dysfunction
what is lymphocytic hypophysitis
inflammation of the pituitary gland due to an autoimmune reaction
what are 3 types of pituitary dysfunction?
tumour mass effects
hormone excess
hormone deficiency
what are investigations for pituitary dysfunction?
hormone tests
if hormone tests abnormal or tumour mass effects, perform MRI pituitary
what are local mass effects of the pituitary? (4)
cranial nerve palsy and temporal lobe epilepsy
visual field defects
headaches
CSH rhinorrhoea (nasal cavity filled w mucus fluid)
a chiasmal compression from the pituitary tumour results in what?
bitemporal hemianopia
what are the 6 hormones the pituitary gland secretes?
gonadotrophins growth hormone prolactin adrenocorticotropin hormone (ACTH) melanocyte-stimulating hormone (MSH) thyroid stimulating hormone (TSH)
what should u measure in pituitary disease
ft4
what does Ft4 stand for?
free thyroxine
what does Ft3 stand for?
free tri-iodothyronine
in primary hypothyroidism, what are the hormone levels?
raised TSH
low ft4
in hypopituitary, what are hormone levels?
normal/low TSH
low ft4
in graves disease, what are hormone levels?
suppressed TSH
high ft4
in TSHoma, what are hormone levels?
normal/high TSH
high ft4
how can u test primary hypogonadism in men
low/raised LH/FSH
how can u test gonadal diseases in women?
before puberty - estradiol low with low LH/FSH
puberty - pulsatile LH and oestradiol ncreases
what happens in primary ovarian failure
high FSH (with high but slightly lower) LH and low oestradiol
how is GH secreted
in pulses with greatest at night
GH levels fall w age ad low in obesity
why might prolactin be raised?
stress
drugs - antipsychotics
stalk pressure
prolactinoma
oral glucose GH suppression test can be used for what?
acromegaly
glucagon test can measure what?
GH deficiency
GnRH stimulation test measures what?
gonadotrophindeficiency
what is the preferred imaging for the pituitary?
MRI
what are symptoms of low GH?
short stature
abnormal body composition
reduced muscle mass
what do u prescribe someone w low GH?
GH
what are the symptoms of low LH/FSH?
hypogonadism
reduced sperm count
infertility
menstruation issues
what do u prescribe someone w low LH/FSH?
tester one in males
oestradiol +/- progesterone in females
what is the symptom of low TSH ?
hypothyroidsim
what is the prescription for someone w low TSH (hypothyroidism)?
levothyroxine
what are the symptoms of low ACTH?
adrenal failure
decreased pigment
what is the treatment for low ACTH?
hydrocortisone
what are the symptoms of low ADH?
DI (ADH deficiency - polyuria)
oestrogen replacement can reduce the risk of what?
cardiovascular disease and osteoporosis
what is the definition of diabetes (measurementS)?
fasting plasma glucose ≥7mmol/l
OGTT fasting ≥7
HbA1c >48mmol/mol
HbA1c measurement >? indicates diabetes?
48 mmol/mol
what are suggestive features of T1 diabetes?
big 3 symptoms:
constant thirst
frequent urination
rapid weight loss
what are T1 diabetics prone to?
ketoacidosis
what are suggestive features of t2 diabetes?
gradual onset
FH positive
T1 or T2?
can be difficult
T1 in younger patients
T2 can be obese
if in doubt: treat w insulin
what happens if t1 diabetes diagnosis is missed?
formation of ketone bodies
reduced insulin leads to fat breakdowna nd formation of glycerol and FFA
what do FFAs do
impair glucose uptake
transported to liver, providing energy for gluconeogenesis
oxidised to form ketone bodies
define ketoacidosis
absence of insulin and rising counter-regulatory hormones which leads to increasing hyperglycaemia and rising ketones
what can ketones cause
anorexia and vomiting- vicious circle of increased dehydration
define hyperglycaemia
plasma glucose above 50 mmol/l
define raised plasma ketones
urine ketones >2+
define metabolic acidosis
plasma bicarb <15mmol/l
what are the causes of DKA?
unknown in half
intercurrent illness
what is DKA a triad of?
hyperglycaemia
ketones
acidosis
what are symptoms of DKA
develops over days polyuria/polydipsia nausea n vomiting weiht loss weakness abdominal pain drowsiness confusion
define polydipsia
excessive thirst
what are some signs of DKA
hyperventilation dehydration hypotension tachycardia coma
what is the biochemical diagnosis of DKA?
hyperglycaemia (<50mmol/l)
K+ high on press despite total K+ deficit
urea and creatinine raised due to pre-rena failure
urinary ketones dipstick >2+ ketones
blood ketones >3
what do u do to manage DKA?
rehydration (3L in first 3hrs)
insulin
electrolyte (K+) replacement
treat underlying cause
what are some complications of DKA?
cerebral oedema
adult resp distress syndrome
thromboembolism
death:/
what are the aims of treatment in t1 diabetes
relieve symptoms
prevent ketoacidosis
prevent vascular complications
what are some microvascular complications of t1 diabetes
diabetic nephropathy (tend to develop retinopathy)
what does the treatment of t1 diabetes aim to achieve
restoration of beta cell physiology
inappropriately high insulin levels confer a high risk of what?
hypoglycaemia
what are some physiological defences of hypoglycaemia
symptoms of sweating, tremor, palpitations
loss of conc, hunger
what is the dilemma for t1 diabetics?
setting higher glucose targets reduces risk of hypoglycaemia but increases risk of diabetic complications
n vice versa
what is HbA1c?
avg blood glucose levels for the last 2-3m
what is the commonest type of monogenic diabetes
MODY (maturity onset disease of the young)
it’s non insulin dependant
what are some endocrine causes of diabetes?
acromegaly
cushing’s syndrome
how is acromegaly an endocrine cause of diabetes
excessive GH secretion
similar to T2
insulin resistance rises, impairing insulin action in liver n peripheral tissues
how is Cushing’s syndrome an endocrine cause of diabetes
increased insulin resistance, reduced glucose uptake into peripheral tissues
hepatic glucose prod incr through stimulating of gluconeogenesis via increased substrates
do glucocorticoids increase or decrease insulin resistance
increase
what are the 3 main microvascular diabetes complications
neuropathy
retinopathy
nephropathy
how can DM cause mortality
acute hyperglycaemia - if untreated leads to a cute met emergencies, DKA
chronic hyperglycaemia - leads to tissue complications
what are some clinical consequences of diabetic neuropathy
pain (burning, paraesthesia)
autonomic (cardiac AN, diarrhoea)
insensitivity (foot ulceration, amputation)
what are some risk factors for diabetic neuropathy
hypertension smoking hba1c change diabetes duration BMI total cholesterol
what involves the treatment of diabetic neuropathy
good glycaemic control
TCAs/SSRIs
anticonvulsants
opioids
what are some consequences of peripheral neuropathy in diabetes
diabetic foot ulceration
peripheral vascular disease
what are some symptoms of PVD
intermittent claudication
rest pain
what is claudication
limping lol
what are some signs of PVD?
diminished/absent pedal pulses
coolness of feet n toes
poor skin n nails
what is the treatment of PVD?
quit smoking
walk through the pain
surgical intervention
what is the journey to diabetic amputation?
neuropathy or vascular trauma ulcer failure to heal infection amputation
what is the hallmark for diabetic nephropathy
development of proteinuria
followed by progressive decline in renal function
major risk factor for CVD
what is the pathophysiology journey of diabetic nephropathy
glomerulus changes
increase of glomerular injury
filtration of proteins
diabetic nephropathy
what does treatment for diabetic nephropathy involve
BP control
glycemic control
ARB/ACEi
proteinuria and cholesterol control
what is the most common cause of kidney failure/end stage renal disease?
diabetic nephropathy
in the fasting state, where does most glucose come from?
liver (a bit from the kidney)
in the fasting state, where does glucose come from?
gluconeogenesis (utilises 3 C precursors to synthesise glucose inc lactate, alanine n glycerol)
in the fasting state, where is glucose delivered to?
insulin independent tissues, brain and RBC
what are insulin levels like in the fasting state?
low
what do the muscles use for fuel in the fasting state?
FFA
post prandial is aka?
?post prandial
what happens after feeding?
physiological need to dispose of nutrient load
what stimulates insulin secretion and suppresses glucagon after eating, and when?
rising glucose levels
5-10min after eating
after feeding, where does glucose ingested go?
40% - liver
60% - periphery, mostly muscle
what suppresses lipolysis after feeding
high insulin and glucose levels
levels of FFA fall
ingested glucose helps to replenish what?
glycogen stores both in liver n in muscle
what is the site of insulin and glucagon secretion in the endocrine pancreas?
islet of langerhans
which cells in the islet of langerhans secrete insulin?
beta cells
which cells in the islet of langerhans secrete glucagon?
alpha cells
which effect (paracrine ‘crosstalk’) is lost in diabetes?
paracrine ‘crosstalk’ btwn alpha n beta cells is physiological
ie local insulin release inhibits glucagon. an effect lost in diabetes
what is the transporter for glucose to enter beta cell?
GLUT2 glucose transporter
???how does glucose go to insulin in muscle n fat cells
??confused?glucose enters cell via GLUT4 (glucose transporter 4)
GLUT4 vesicle mobilisation to plasma membrane
intracellular GLUT4 vesicles
intracellular signalling cascades
insulin receptor
insulin
how does insulin impact hepatic glucose output
suppresses
decreases glycogenolysis and gluconeogenesis
how does glucagon impact hepatic glucose output
increases glucogeolysis n gluconeogenesis
how do insulin n glucagon differ in peripheral glucose uptake
insulin - increases into insulin sensitive tissues eg muscle, fat
glucagon reduces
does insulin suppress or stimulate lipolysis n muscle breakdown?
suppresses
does glucagon suppress or stimulate lipolysis n muscle breakdown?
stimulates
counterregulatory hormones such as adrenaline, cortisol and GH have similar effects to what???
glucagon
they become relevant inc certain disease states inc diabetes
what does insipid mean?
dilute n odourless
hence in DI, kidneys pass abnormally large amt of insipid urine
what is the diff btwn diabetes insipid n mellitus
insipidus - normal blood glucose levels; kidneys cannot balance fluid in the body
mellitus - high blood glucose
how would u describe t1 diabetes?
an insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction
what does failure of insulin secretion lead to?
continued breakdown of liver glycogen
unrestrained lipolysis n skeletal muscle breakdown providing gluconeogeneic precursors
inappropriate increase in hepatic glucose output n suppression of peripheral glucose uptake
rising glucose conc results in increased urinary glucose _____?
losses …as renal threshold (10mM) is exceeded
failure to treat with insulin leads to WHAT?(3)
increase in circulating glucagon, further increasing glucose
perceived ‘stress’ leads to increased cortisol and adrenaline
progressive catabolic state and increasing levels of ketones
how does ketoacidosis happen?
absence of insulin and rising counter regulatory hormones leads to increasing hyperglycaemia and rising ketones
what do ketones cause?
anorexia n vomiting
what is IGT?
impaired glucose tolerance
pre-diabetic state of hyperglycaemia (associated with insulin resistance an increased risk of CV pathology)
impaired insulin action leads to what?
reduced muscle/fat uptake after eating
failure to suppress lipolysis n high circulating FFAs
abnormally high glucose output after a meal
what’s the diff btwn t1/t2 diabetes????
t1 - severe insulin deficiency due to autoimmune destruction of beta cell, initiated by genetic susceptibility n env triggers
t2 - insulin resistance n impaired insulin secretion due to a combo of genetic predisposition and env factors
why doesn’t DKA happening t2 diabetes?
low insulin levels r sufficient to suppress catabolism and prevent ketogenesis
can happen if hormones such as adrenaline rise to high levels
why does obesity cause t2 diabetes?
obesity impairs insulin action. in those already insulin resistant/predisposed, this brings out diabetes at an early stage
in t1d, what should basal insulin control?
blood glucose in btwn meals n particularly during night
basal insulin is adjusted to maintain fasting glucose btwn what?
5-7 mmol/L
how does insulin differ in t1dm vs t2dm?
t1 - insulin deficiency
t2 - insulin resistance
what’s the diff btwn basal n prandial insulin?
basal - long-acting
prandial - rapid-acting/meal time
prandial insulins mimic meal-time insulin secretion and their faster action allows for what?
greater flexibility at meal times
what are the adv of basal insulin in t2 diabetes?
simple for patient, adjust insulin themselves, based on fasting glucose measurements
carries on w oral therapy
less risk of hypoglycaemia at night
what are the disadvantages of basal insulin in t2 diabetes?
doesn’t cover meals
best used with long-acting insulin analogues which are considered exp
what are the adv of pre-mixed insulin?
both basal n prandial components in a single insulin prep
can cover insulin requirements through most of the day
what are the disadvantages of pre-mixed insulin today?
not physiological
requires consistent meal n exercise pattern
increased risk for nocturnal hypoglycaemia
what is the definition of hypoglycaemia
low plasma glucose causing impaired brain function neuroglycopenia 3mmol/l
what is mild hypoglycaemia vs severe
mild - self-treated (many epodes asymptomatic)
severe - requiring help for recovery (excepting children)
what are the 3 types of hypoglycaemia symptoms n some examples of each?
autonomic: trembling, palpitations, sweating, anxiety, hunger
neuroglycopenic: difficult concentration, confusion, weakness, dizziness, vision changes, difficulty speaking
non-specific: nausea, headache
what is neuroglycopenia?
shortage of glucose (glycopenia) in the brain, usually due to hypoglycemia.
glycopenia affects the function of neurons, and alters brain function and behaviour
in most patients, what prevents severe hypoglycaemia/
counter regulatory n symptomatic defences
in t1dm, what are some risk factors for severe hypoglycaemia
history of severe episodes HbA1c < 6.5% (48mmol/mol) long duration of diabetes renal impairment extremities of age
in t2dm, what are some risk factors for severe hypoglycaemia
advancing age cog impairment depression aggressive glycaemia treatment duration of MDI insulin therapy renal impairment n other comorbidities
what are some consequences of hypoglycaemia?
accidents fear QOL prevents desirable glucose targets CV risk seizures coma cog dysfunction
what are glucose targets like in t1dm/t2dm?
aim for lowest hba1c not associated w freq hypoglycaemia
it may sometimes be appropriate to relax targets in patients w advanced disease, complications or limited life expectancy
a target of hba1c < 7.5% (58 mmol/mol) is good 4 what?
few comorbidities
good physical function
preserved cog function
a target of hba1c < 8% (64 mmol/mol) is good 4 what?
multiple chronic illnesses
mild cog impairment
risk of falls n hypoglycaemia
a target of hba1c < 8.5% (69 mmol/mol) is good 4 what?
end-stage chronic illness
moderate-to-severe cog impairment
in long-term care
what are some strategies to prevent hypoglycaemia?
discuss risk factors w patients on insulin
educate patients n caregivers on how to recognise n treat it
instruct patients to report episodes to doctor
what are the 5 steps to treating hypoglycaemia?
- recognise symptoms so they can be treated asap
- confirm need for treatment (blood glucose <3.9mmol/mol is the alert value)
- treat w 15g fast-acting carb to relieve symptoms
- retest in 15mins to ensure blood glucose >4.0 mmol/mol n retreat if needed
- eat long-acting carb to prevent recurrence
what is the alert value for hypoglycaemia in treatment?
<3.9mmol/mol
what is an inevitable side effect of diabetes treatment
hypolycaemia
why does hypoglycaemia occur?
due to inability of insulin therapy to mimic physiology of beta cell
what does metformin help?
liver
inhibition of glucose prod and increase in hepatic insulin sensitivity
nocturia
excessive nighttime urination
what does NAD stand for? (2)
no abnormality detected
OR
no apparent distress
what are incretins
hormones secreted by intestinal endocrine cells in response to nutrient uptake
how do incretins influence glucose homeostasis
via multiple actions including: glucose-dependant insulin secretion postprandial glucagon suppression slowing of gastric emptying
when are incretins secreted
by the gut, into circulation in response to food
name 3 antihyperglycaemics
metformin
SUs (sulfonylureas)
TZDs (thiazolidinediones)
what are SUs
sulfonylureas, antihyperglycaemics
what are TZDs
thiazolidinediones, antihyperglycaemics
what are the benefits of using metformin as an anti hyperglycaemic?
low risk of hypoglycaemia
BP reduction
cardioprotective benefits
what are the drawbacks of using metformin as an anti hyperglycaemic?
lactic acidosis (rare) caution indicated in older patients w CHF
how does metformin affect weight?
weight neutral or slight weight loss
what are the benefits of using SUs (sulfonylureas) as an anti hyperglycaemic?
newer class entrants may have reduced CV risk
what are the drawbacks of using SUs (sulfonylureas) as an anti hyperglycaemic?
may increase risk of CV events
hypoglycaemia
how do SUs affect weight?
weight gain
what are the benefits of using TZDs (thiazolodinediones) as an anti hyperglycaemic?
low risk of hypoglycaemia
positive effects on biomarkers
what are the drawbacks of TZDs as an antihyperglycaemic?
increased CV risk
lipid abnormalities
how do TZDs affect weight?
weight gain
