endocrine physiology p138 Flashcards
3 modes of communication in the body
cell -> cell (neural synapse)
cell -> several cells (paracrine)
several cells -> many cells (endocrine)
process of synapse
impulse arrievs at terminal presynaptic cell
transmitter released from storage vesicles
transmitter diffuses in synaptic cleft
transmitter binds to receptor on posynaptic cell
alters postsynaptic cell:
- excitatory e..g impulse generated, muscle contracts, glnf secretes
- inhibitory e.g. postsynaptic cell is switched off
transmitter action is terminated
drug actions on synapses
enhance or block
paracrine communication
one cell to several
immune cells often
often part of cascade reactions
autocrine commuication
chemcial acts on a cell releasing it (self-feedback)
can also be regulated by drugs
endocrine transmission
secreted by a gland
hormone sent to all parts of the body via blood stream
acts only on cells with correct membrane protein corresponding to it
nerves
actions very specific and often localised
rapid transmission
sutiable for rapid responses e.g.:
- vol. muslce contractions
- thinking
- salivary secretions
- oral/pharyngeal and oesphageal functions
hormones
can affect many cells (different body parts)
co-ordinated body wide actions
slow to act but effect persists
suitable for prolonged controls e.g.
- small intestine gland response
- control of metabolism/growth
- regulation of blood calcium and glucose
can nerves and hormones work together
some body functions involve both types of communication
- regulation of blood pressure
- stress reactions
- thermal regulation
2nd messengers
peptide transmitters (1st messengers) can’t cross cell membrane so instead act on a receptor protein on the cell membrane
intracellular effects are therefore regulated by second messengers
- G proteins and cAMP
- calcium ions (G proteins/ Ca2+)
steroid hormones
properties
can pass through target cell membrane and act on receptors inside the target cell
anterior pituitary hormones
- adrenocorticotropic hormone (ACTH)
- follicle stimulating hormone (FSH)
- luteinsing hormone (LH)
- thyroid stimulating hormone (TSH)
- growth hormone (GH)
- prolactin (PL)
hypothalmic anterior pituitary hormones
hypothalamus secretes ‘releasing’ hormones
passed to the anterior pituitary via blood vessels - hypothalamic pituitary portal vessels
trigger hormone secretion from ant pituitary
hypothalmic AP hormones
- corticotropin releasing hormone (CRH)
- gonadotropin releasing hormone (GRH)
- thryotropin releasing hormone (TRH)
- growth hormon releasing hormone (GHRH)
- somatostatin (SS; GH inhibiting hormone)
- prolactin releasing hormone (PLRH)
- dopamine (DA; also PLIH)
posterior pituitary
signalled by
hormones relased
hormones made in hypothalamus go to posterior pituitary along nerve axons
hormones relased by PP
- ADH (vasopressin)
- oxytocin
cortex hormones from adrenal glands
mineralcorticoids e.g. aldosterone
glucocorticoids e.g. cortisol
sex hormones e.g. androgens, oestrogens
medulla of adrenal glands releases
adrenaline
modified sympathetic ganglion
pancreatic islets relaseases
glucagon - α cells
insulin - β cells
somatostatin - δ cells
pancreatic δ cells release
somatostatin
pancreatic β cells release
insulin
pancreastic α cells release
glucagon
glucagon
released in response to low blood sugar
acts to raise blood glucose
actions:
- when glucose is gone you need glucagon
- glycohenesis in the liver
- gluconeogenesis in the liver
- lipolysis and ketone synthesis
insulin
released in response to raised blood glucose concentrations
acts to lower blood glucose
facilitates glucose entry into - muscle cells, adipocytes
gluocse uptake to liver is not insulin dependent
promotes formation of m acromolecules
somatostatin
functions as a local hormone, inhibits secretion of both insulin and glucagon
seperate from the action of inhibiting growth hormone release from anterior pituitary
diabetes melliyus
abnormality of glucose regulation (lots of sweet pee)
diabetes insipidus
abnormality of renal function - watery pee
reduced ADH
type 1 diabetes mellitus
insulin defcicient
type 2 diabetes mellitus
insulin resistant
type 1 diabetes mellitus
is
immune mediated pancreatic β cell destruction
ciculating antibodies present:
- glutanic acid decarbozylase
- islet cell antibodies
- insulin cell antibodies
causes hyperglyceamia (inc blood glucose)
results in ketoacidosis
ketoacidosis
type 1 diabetes mellitus
body breaks fdown fats - produce ketone bodies
build up in insulin def and lower blood pH
blood glucose is raised concurrent to this
due to these phenomena there is osmotic diuresis and resultant dehydration
sodium and potassium loss due to leaking out of cells and into urine
signs of ketoacidosis
polyuria
polydipsia
tiredness
acute presentation of ketoacidosis
hyperglyceamia
type 2 diabetes mellitus is
insulin resistance and relative insulin deficiency
metabolic disorder
- elevataed basal insulin (defect in insulin resistance)
- decreased overal insulin (β cell response to hyperglycaemia inadequate)
- basal hepatic glucose increased (insulin fails to supress glucose)
- insulin stimulated muscle glucose uptake reduced
sigsn of type 2 diabetes
glucose intolerance in body
hyperinsulinaemia
hypertension
abdominal obesity
dyslipidaemia (abnormal lipid levels in blood)
procoagulant epithelial markers (causes early platelet adhesions, sticky endothelium)
early and acclerated athersclerosis
typical characteristics of type 1 diabetes
younger
thin
family Hx of autoimmune disease
diabetic symptoms
easily get ketosis
typical characteristics of type 2 diabetic
older
obese
strong family Hx
present with secondary complications (cardiac etc)
rarley get ketosis
drugs for diabetes
oral hypoglucaemic drugs (reduce blood glucose Hyper>Drug=Hypo)
bisguianides
sulfonylureas
carbohydrate absorptiono delayers
bisguanides
good drug, lowers blood glucose, reduce gluconeogenesis but doesn’t lead to hypo
e.g. metformin
- taste distubance
- lactic acid build up due to taking it - can be fatal
- insulin sensitisers
sulfonylureas
stimulate insulin secretion
risk of causing hypo and weight gain (due to increase macromolecules)
insulin scretagogues
e.g. gliclazide
carbohydrate absorption delayers
does what it says
e.g. A-carbose
type 2 diabetes specific management
weight loss
diet restriction
diet pills (orlistat, sibutramine)
gastric bypass
type 1 diabetes specific management
insulin sub cutaneously
different preparations/regimes - indivualised
ideal sugar 4<7
HbA1C (6<10%) measure of glucose bound to haemoglobin
macrovascular complications of diabetes
PVD lower limbs
neuropathy (autonomic - impacts small vessels, causes ischaemia and diabetic foot)
cerbrovascular (stroke, TIA)
microvascular diabetic complications
retinopathy - blindness
nephropathy (backflow from bladder)
types of multiple endocrine neoplasia
1
2a
2b
MEN1
multiple endocrine neoplasia
- parathyroid
- pancreaitc islets
- anterior pituitary
MEN2a
multiple endocrine neoplasia
- parathyroid
- medullary thryoid
- phaechromocytoma
MEN2b
multiple endocrine neoplasia
- medullary thyroid
- pahechormocytoma
- mucosal neuromas
- marfanoid appearance
pituitary tumours are called
adenomas
functional adenomas can cause
amenorrhea-galactorrhea syndrome
Cushing’s disease
Acromegaly
amenorrhea-galactorrhea syndrome
hyperprolactinaemia - infertilty, poor breast milk production
Cushing’s disease
caused by excess of gluocorticoids secodary to adreanl hyperplasia
excess ACTH production
signs
- moon face
- buffalo hump
- central obesity + proximal muscle wasting
- hirsutism in females
systmic effects
- cortisol = insulin resistance = impaired glucose tolerance/diabetes
- mineralcortcoids = salt and water resistance- oedema and HT
Cushing’s syndrome
non-pitutary
caused by primary adrenal disease
decreased GH
- growth failure in children
- metabolic changes in adults - inc fat, reduced vitality
non functional adenomas
acromegaly
growth hormone excess after epiphyseal plates have fused
if in children known as Gigantism - Test for IGF-1 (insuliln like growth factor 1)
signs
- coarse facial features
- visual field defects - bitemporal hemianopia (optic nerve crossover)
- enlarged tongue
- denture no longer fitting
- inc diastema and reverse overbite
- ankylosis of TMJ
- hypertension
- large hands and feet
- type 2 diabetes
- nerve pathology - III, IV and VI palsies
- CVD - ischaemic heart disease, acromegalic cardiomyopathy
non-functional adenomas
space occupying tumours
visual field defects
hormone deficiencies due to destruction of paraenchyma of pituitary (replaced with tumour)
can be reduced with trans-spehnoidal surgery
thryoid hormones
T3: tri-iodothyronine (deiodinated form of T4 works once in target cells)
T4 -thyroxine (more numerous than the former)
hyperthyroidsim
excess T3 and T4
hyperthyroidism can cause
graves disease
toxic multi-nodular goitre
toxic adenoma
graves disease
due to hyperthyroidism
- auto-antibodies stimulate the TSH receptor = more hormone produced in pituitary
- exopthalmos
- finger clubbing
- opthalmopathy
toxic multinodular goitre
goitre is swelling of thyoid resulting in excess bound hormone (thryotoxicosis)
toxic adenoma
takes control of hormone release
signs
- tachycardia
- atrial fibrilation
- tremor
- exopthalmos
- goitre
- diffuse multi-nodular? iodine?
- solitary? caner risk!
symptoms
- weight loss
- heat intolerance
- tremor/irritability
- emotional
tx for toxic adenoma
carbimazole > methimazole (anti-thyroid drug), block and replace w T4 as needed
partial thyroidectomy
radioactive iodine
can both lead to hypothyroidsm
hypothyroidism aka
myxoedema
priamry cause of hypothyroidism
hashimoti’s thyroiditis
Hashimoti’s thyroiditis
gradual autoimmune destruction of thyroid gland
- goitre and hypothyroid features
- vitiligo
- type 1 diabetes
- pernicious anaemia (B12/Folate)
- Addison’s disease
- Down’s syndrome
idiopathic atrophy (10x more in female, lymphocyte infiltrate into organs cause organ specific autoimmune disease)
radiodine treatment/thyroidectomy surgery
iodine deficiency (goitre)
caused by drugs used for hyperthryoidism - carbimazole, amiodarone, lithium
congenital
secondary cause of hypothyroidism
hypothalmic/pituitary disease - don’t release the hormones that act on the thyroid gland
decreased TRH (hypothalamus)
decreased TSH (ant.pit)
sigsn of hypothyoidism
- dry coarse skin
- bradycardia
- hyperlipidaemia
- confused state/memory loss
- goitre (hashimoto’s and iodine def)
- delayed reflexes
symptoms of hypothyroidism
- lethary
- cold intolerance
- depression
- weight gain
- hoaeseness, puffed face adn extremitis
- angina
- hair loss
hyperthyroidism tx
Carbimazole *TASTE DISTURBANCES
- Titration
- block and replace w/ T4
β- blockers
Radioiodine
- Hypothyroid risk w/time
Partial Thyroidectomy (w/ drug therapy to stabilise)
Graves Opthalmopathy- simple treatments
hypothyroidism tx
thyroxine
monitor TSH levels
dental aspects of thyroid issues
Hyperthyroid- Pain, Anxiety problems, don’t treat until controlled
Hypothyroid- if severe avoid sedation!!!
If controlled treat patient as if normal
Goitre is detectable to the dentist
thryoid cancer
Papillary - good prognosis
Folicular- poor prognosis
Undifferentiated in Elderly
Cold Nodules on radioisotope scan
Can affect TSH- give T4 post op
Addison’s disease basic
destruction of adrenal tissue
Cushing disease/syndrome basic
excess adrenal action
therapeutic corticosteroids basic issue
suppress adrenal action and their adverses affects
adrenal gland is
op top of kidneys
made of 3 main zones
produces hormones thanks to cholesterol made in the liver
3 main zones of adrenal gland
zona glomerulosa
zona fasicularis
zona reticularis
zona glomerulosa makes
aldosterone - mineralcotocoid
RAAS system - BP + Salt/H2O
- dec BP detected
- Angiotensin II causes secretion of aldosterone
- Aldosterone causes increased reabsorption of Sodium and increases water retention to increase blood pressure
- Increases Pottasium loss
ACE inhibtors affect this hormone but have side effects
- cough
- angio-oedema
- oral lichenoid reaction
AT2 blockers
zona fasicularis makes
cortisol - glucoroticoid - ACTS ON ANGIOTENSIN
aka “The Stress Hormone”
Breakdown of fat and protein
Reduces osteogenesis
Counteracts Insulin= Higher blood sugar
Decreases amino acid uptake by muscles
lowers immune reactivity
raises blood pressure
Circadian release- Nocturnal peak
zona reticularis makes
adrenal androgens
DHEA
testosterone precursor
involved in adrenarche a.k.a early maturation puberty etc
therapeutic steroids
given ‘point values’ based on their potency against naturally occuring Cortisol
cortisol has value of 1
e.g 5mg Prednisalone = 20mg of Hydrocortisone
Hydrocortisone = 1
Prednisalone = 4
Triamcinolone = 5
Dexamethasone = 25
Bethamethasone = 30
Enhance glucorticoid effect- think of what cortisol does normally (x multiplied by factor of steroid potency)
Enhanced mineralcorticoid effect- salt and water retention w/ aldosterone action in RAAS = Hypertension
side effects of steroids
- hypertension - aldosterone
- osteoporosis - cortisol
- type 2 diabetes - cortisol
- increased infection risk - cortisol
- increased cancer risk
adrenal disorders
hyperfunction
glucoticoids (cortisol) - Cushing’s syndrom
Mineralcorticoids (aldosterone) - Conn’s syndrome
Cushing’s syndrome
hyperfunction of adrenal (cortisol)
- arenal tumour (primary)
- pituitary tumour (secondary) = inc ACTH level
- ectopic ACTH production from lung tumour (weird)
Conn’s syndrome
hyperfucntion of adrenal gland - mineralcorticoid (aldosterone)
- caused by adrenal tunour
- either hyperplasia/malignancy
- excess sodium retention - hypertension
- excessive potassium loss - polyuria and muscle weakness
adrenal disorders
hypofunction
addison’s disease (primary) - gland destruction
pituitary failure (secondary)
Addison’s disease
hypofunction of adrenal gland - primary
GLAND DESTRUCTION
surgical/TB/ cancer can cause, but main one is Autoimmune adrenalitis
- thyroid
- diabetes mellitus
- pernicious anaemia (B12 and folate
signs
- postural hypotension (BP drops upon standing - head rush) - due to salt and water loss
- weight loss and lethargy
- hyperpigmentation - scars, mouth, skin creases
- vitiligo
symptoms
- weakness
- anorexia
- loss of body hair (females)
Addison’s disease test will have
high ACTH
low cortisol
synacthen - negative
addisonian crisis
- hypotension
- vomitting
- eventual coma
- hyponatraemia (low sodium) hence the hypotension
- hypovolaemic shock (>20% of blood volume lost)
cortisol and fludrocortisone
managing addisonian crisis
treat the problem
fluid reuscitation
- saline infusions
- corticosteroids IV
- correct hypoglycaemia
- treat precipitating event (infection)
pitituary disease (secondary)
causes reduction in secretion of adren-corticotropic releasing hormone
low ACTH
low cortisol
synacthen - positive
synacthen
tests ACTH stimulation
if ACTH normal = negative result
if ACTH low = positive result
adrenal hyperfunction tx
Detect Cause
- pituitary
- Renal
- Ectopic (lung)
Surgery follows
- pituitary
- Adrenalotomy
- Adrenalectomy
adrenal hypofuntion tx
Hydrocortisone- replace cortisol
Fludrocortisone- replace aldosterone
steroids in dentistry
If someone has stopped prolonged systemic steroids in last 3 months
- High risk
- Cover with 100mg IM dose of steroid to cover patient
ALWAYS ASK ABOUT STEROID USE PAST 6 MONTHS
Diabetes and CV disease in Addison’s
Candidiasis in Cushing’s
Oral Pigmentation in Addison’s and Cushing’s
Can be other causes
- Melanotic Macule
- Drugs- Minocycline (antibiotic), Azidothymidine (HIV/AIDs), Oral Contraceptive
- Naevus
- Pregnancy
