case 23: health behaviours, diabetes and endocrine disease Flashcards
by which organ and cells is insulin produced
beta cells in the islets of langerhans of the pancreas
what is C peptide
is by-product of insulin production and is used as a measure of endogenous insulin
which process does glucagon inhibit
glycolysis
process of thyroid hormone being released
hypothalamus realises TRH which stimulates pituitary
pituitary releases TSH which stimulates the thyroid
thyroid releases T3 and T4
Qs for itchy penis
pain
discharge
dysuria
itching/burning
sexual history
testicular swelling
lymph node swelling in groins
history of trauma/previous surgery
proper name for penis thrush
candidal balanitis
rfs for candidal balanitis
diabetes mellitus
oral abx
poor hygiene
immunosuppression
normal blood sugar levels
4-7mmol before meals
less than 9mmol 2hrs after meals
glucose criteria for diagnosing diabetes
in symptomatic:
fasting glucose greater than or equal to 7mmol
random glucose greater than or equal to 11.1
if asymptomatic above criteria must be met on 2 separate occasions
HbA1C criteria for diagnosing diabetes
if asymptotic- 48 or above
if asymptomatic- need 2 separate readings which are 48 or above
under which conditions would you mot use HbA1C to diagnose diabetes
under 18s
pregnant/2 months postpartum
symptoms for less than 2 months
high diabetes risk who are acutely ill
on medication (long-term corticosteroids) which increase hyperglycaemia risk
acute pancreatic damage (including surgery)
end stage renal disease
HIV
hallmark symptoms of T2D
tiredness
polyuria/polydypsia
recurrent infections (thrush)
increased hunger
unintentional weight loss
blurred vision (retinopathy)
foot ulcers/sores (peripheral neuropathy)
areas of dark skin for example in armpits/neck (acanthuses nigricans)
risk factors for T2D
family history
high BMI
high sugar and fat diet
inactivity
afro-caribbean, hispanic, asian
hyperlipidaemia
over 45
history of gestational diabetes
other conditions which cause insulin resistance- PCOS, haemachromatosis
what do alpha cells in the islets of langerhan produce
glucagon
role of insulin
reduces amount of glucose in blood
binds to its receptors on adipose tissue/muscle
this makes glucose transporter fuse with the cell membrane
glucose is then transported into the cell
role of glucagon
increases the amount of glucose in the blood
stimulates the liver to do gluconeogenesis and glycolysis
is T1D or T2D more common
10%= 1
90%= 2
what type of hypersensitivity is T1D
type 4- T cells attack the pancreas
where genetically is the issue in T1D
on chromosome 6, major histocompatibility complex (MHC), human leukocyte antigen (HLA 3 and 4)
other name of hunger
polyphagia
what causes weight loss and hunger in diabetes
lack of glucose in muscle and adipose tissue
adipose tissue undergoes lipolysis
muscle breaks down into proteins
causes weight loss and hunger
what causes polyuria in diabetes
increased glucose in blood means more filtered by kidneys and more in urine
glucose is osmotically active so draws water with it
what causes polydipsia in diabetes
the excess water loss leads to dehydration and therefore thirst
process of DKA
there is lipolysis of adipose tissue meaning increases fatty acids
the liver converts these to ketone bodies
ketones bodies can be used for energy but they also increase the acidity of the blood- ketoacidosis
what type of respiration may be seen in DKA
kussmaul breathing- this is a deep laboured breathing to reduce CO2 and reduce the acidity of the blood
what electrolyte abnormality may be observed in DKA
hyperkalaemia
what happens to the ions in DKA
there is a high anion gap (large difference in unmeasured ions)
this is due to the ketoacid buildup
what causes fruity breath in DKA
acetone
treatment of DKA
fluids for dehydration
insulin to lower blood glucose
electrolytes (K+)
what happens to the beta cells in T2D
there is hyperplasia and hypertrophy
(this is due to the body producing insulin but there being no response as cells don’t reposed, therefore the body increases beta cells to make more insulin)
amyloid deposits and T2D
the beta cells also make islet amyloid polypeptide (amylin)
hyperplasia and hypertrophy of beta cells mean more amylin- leads to amyloid deposits
the maxed out beta cells can then undergo hypotrophy and hypoplasia
pathophysiology of HHS
when glucose is very high in blood (hyperosmolar state) water goes from the bodies cells meaning they shrivel
blood vessels which are full of water lead to increased urination which leads to total body hydration
overlap between HHS and DKA
in HHS there is sometimes mild ketonemia and acidosis
in DKA there may be some hyperosmolarity
is DKA/HHS more common in type 1 or 2 diabetes
DKA= more common in 1
HHS= more common in 2
what trimester is most commonly affected by gestational diabetes
3rd
what is checked at an annual diabetic review
BP
eye tests
foot examination
blood sugars
urine
HbA1c
height and weight
cholesterol
diet and lifestyle management of T2D
initial weight loss target of 5-10%
reduce alcohol
stop smoking
encourage exercise (150-300mins of moderate intensity aerobic exercise per week)
eat carbohydrates from vegetables, pulses, and whole grains
eat low fat dairy products and oily fat
limit foods with saturated fats/trans fatty acids
when do you give medication for T2D
HbA1C is checked every 3-6months until stable
if lifestyle has failed and is 48 or higher, consider medication
how does metformin work
it is a biguanide
leads to activation of AMP-activated protein kinase (AMPK)
this increases insulin sensitivity and decreases hepatic gluconeogenesis
most common side effect of metformin
GI disturbance (taking with meals/metformin MR can reduce this)
2nd line medication for T2D if metformin isn’t reducing HbA1C
SGLT2 inhibitors (flozin)
when would you consider insulin therapy in T2D
if using 3 medications and HbA1C still not controlled
drugs which reduce insulin resistance in T2D
biguanides (metformin)
thiazolidenediones (pioglitazone)
drugs which increase beta cell activity in T2D
sulphonylureas (gliclazide, glipizide)
meglitinides (nateglinide, repaglinide)
drugs which increase GLP1 activity in T2D
DPP4 inhibitors (sitagliptin, vildagliptin)
incretins, GLP1 agonists (exenatide, liraglutide)
drugs which enhance glucose secretion in T2D
SGLT2 inhibitors (dapaflozin, canagliflozin)
drugs for T2D which can cause weight gain
sulphonyureas
meglitinides
insulin
drugs for T2D which can cause hypoglycaemia
sulphonyureas
meglitinides
insulin
drugs for T2D which can cause GI disturbance
metformin
incretins
acarbose
drugs for T2D which can cause weight loss
metformin
SGLT2 antagonists
incretins
which T2D drug can be associated with osteoporosis
pioglitazone
what other side effect can SGLT2 inhibitors be linked to
UTIs
what hypertension drug class is first line for all diabetes
ACE inhibitors
when would you give statins with diabetes
recommended in most T1D
recommended in T2D if QRISK greater than 10%
what is the blood pressure target for diabetes
below 140/80
below 130/80 if there is end organ damage (kidneys, eyes etc)
diagnostic criteria for DKA
capillary blood glucose over 11 (or known diabetes)
capillary ketones over 3 (or urinary over 2)
venous pH less than 7.3 or venous bicarbonate less than 15
(must have all 3 for diagnosis)
at what rate do you give insulin for DKA
IV fixed rate insulin is at 0.1 units/kg/hr
K+ and insulin
giving insulin drips K+ (makes sense as insulin is used to manage hyperkalaemia)
when would you escalate DKA to critical care
venous bicarbonate less than 5
pH less than 7.1
drowsy GCS of less than 12
stats less than 92% on room air
K+ less than 3.5 on admission
pregnant
HF
oliguria/anuria
persistant hypotension
with DKA when would you change fixed rate IV insulin to subcutaneous insulin
when patient is eating and drinking normally
pH over 7.3 or blood ketones less than 0.6
effect of insulin on adipose tissue and skeletal muscle
increases glucose uptake
increases glycolysis
effect of insulin on liver
increases glycolysis
increases glycogenesis
increases protein synthesis
increases lipogenesis
decreases gluconeogenesis
decreases lipolysis
decreases glycogenolysis
decreases protein breakdown
clinical presentation of T2D
asymptomatic
infections
fatigue
blurred vision
4ps:
paraesthesia
polydipsia
polyuria
polyphagia
retinopathy and T2D
may see:
cotton wool spots
haemorrhage
microaneurysm
macular thickening
can cause glaucoma and cataracts
peripheral neuropathy and T2D
can have:
increased or decreased pain
painless injury
decreased reflexes
autonomic neuropathy and T2D
can have:
resting tachycardia
urinary frequency
erectile dysfunction
nephropathy and T2D
can have:
glomerulosclerosis
pyelonephritis
macrovascular complications of T2D
coronary heart- chest pain, CHF, dyspnoea
cerebrovascular- haemorrhage, cerebral infarct, memory problems
peripheral vascular- atherosclerosis, gangrene, ulceration
3 vascular changes in diabetes
atherosclerosis
arteriosclerosis
inflammation
(occurs due to alterations in vascular homeostasis due to endothelial and smooth muscle cell dysfunction)
hyperglycaemia and its effect on cells in T2D
due to hyperglycaemia cells take up lots of glucose
this forms reactive O2 species
this forms advanced glycalated product (AGP) and protein kinase C
protein kinase C causes more reactive O2 species to be made (a cycle)
effects of protein kinase C in T2D
increases VEGF and other growth factors- this causes angiogenesis and cell growth
increases endothelin- causes platelet aggregation
increases NFkappaB- is inflammatory mediator so increases inflammation and vascular permeability
the increased vascular permeability allows LDL and monocytes (which become macrophages) to come into blood
macrophages and LDL (atherosclerosis)
macrophages engulfs the LDL- becomes a foam cell
foam cell releases inflammatory mediators (TNF-alpha and IL-1) which causes inflammation
causes of DKA (the 5 is)
infection
intoxication
inappropriate withdrawal of insulin
intercurrent infection
infarction
what other investigations are important for DKA
ABG (monitor pH)
urinalysis
FBC
ECG
all sound women presenting with abdominal pain must have what
pregnancy test
what is a basal bolus of insulin
long acting insulin is given as a subcutaneous injection to act as endogenous insulin (basal or base)
rapid acting insulin is given to replicate the normal response to food (bolus)
3 boluses a day are given with meals (varies depending on how may meals they’re having)
what is a mixed bi-phasic insulin regime
usually one two or three insulin injections per day
they are premixed insulin preparations which contain insulins of different durations of action (slow and fast)
what is a continuous insulin regime
insulin pumps can be used to deliver rapid acting insulin at a very slow rate as background insulin
mealtime insulin can be delivered by the patient according to what they eat
insulin is delivered subcutaneously via cannula- the two main types are tethered pumps or catch pumps
where do you administer insulin injections
anywhere where there is subcutaneous fat (tummy, thigh, top of arm, buttocks)
what education programme should diabetics be offered
DAFNE (dose adjustment for normal eating programme)
counselling on following- carbohydrate counselling, sick day rules, hypo awareness, diabetic complications and the need for screening
how many times a day should a diabetic on insulin check their glucose levels
at least 4 times per day
when are particularly important times to check your blood glucose if diabetic and on insulin
before each meal and before bed
what are the blood glucose targets for diabetes
5-7mmol/l on waking
4-7mmol/l before meals and at other times of the day
sick day rules for insulin check
blood sugars more frequently
staying hydrated
eat little and often
keep taking medications
is the mortality for DKA or HHS higher
higher for HHS
key features on blood in DKA
hyperglycaemia, hypovolaemia, ketonaemia and anion gap metabolic acidosis
what causes fluid and electrolyte loss in DKA
there is lots of glucose in the blood
this increases the osmotic pressure
fluid shifts from intracellular to extracellular space, pulling fluid into the vasculature
leads to osmotic diuresis- causes the hypovolaemia (can lead to hypovolaemic shock)- this will also decrease the eGFR meaning the kidneys struggle to excrete glucose in the urine, furthering the problem
electrolytes follow the water
the breakdown of what creates ketones
lipids
lactic acid and DKA
the hypovolaemia causes poor tissue perfusion
this causes cells to switch to anaerobic metabolism
creates lactic acid as a result- this further worsens the problem of the metabolic acidosis (increases anion gap)
how do you work out anion gap
Na+ + K+) - (Cl- + HCO3-)
normal anion gap
4-12mmol/L
hypokalaemia and DKA
because of the intracellular acidosis there is lots of K+ inside cells
to combat this, there is a shift of K+ from intracellular to extracellular
this combined with osmotic diuresis leads to low K+
administering insulin furthers this problem
glucose levels in DKA vs HHS
glucose levels in HHS are typically much higher than DKA
onset of DKA vs HHS
DKA= less than 24hrs
HHS= can be weeks-months
main differences between DKA and HHS
no ketosis in HHS
more glucose in HHS
DKA is quicker onset
in HHS no kaussmals breathing, nausea and vomiting, ketone breath and abdominal pain
more diuresis in HHS (severe dehydration 9-10litres)
PH in DKA vs HHS
DKA= acidosis
HHS= normal (if acidosis will be due to lactic acid buildup due to hypoperfusion and anaerobic respiration)
is CNS disturbance more common in DKA or HHS
HHS due to the severe hypovolaemia
management of DKA and HHS
treating underlying cause- could be infection
fluid replacement- 0.9% saline with (rapid bolus in 1st 1hr depending on BP and Na+), continue until fluid volume is restored
treating hyperglycaemia- IV insulin (more in HHS due to higher glucose) until normal pH (need to wean off)
electrolyte replacement- if K+ less than 5.5mmol/L
what nail disorder is associated with graves disease
oncholysis (painless separation of the nail from the nail bed)
antibodies seen in thyroid disease
TSH receptor antibodies- in 90% with graves
TPO antibodies- in 80% hashimotos thyroiditis
thyroglobulin antibodies- in 80% hashimotos thyroiditis
does thyroid move on swallowing
yes
it is attached to thyroid cartilage and upper end of the trachea
what cells make up the thyroid
cuboidal epithelium
how are thyroid hormones made
they are produced by the iodination of tyrosine residues bound to thyroglobulin in thyroid follicles
iodine is taken up by the thyroid gland under the control of TSH
is more T4 or T3 released by the thyroid gland
10x more T4 than T3
3 most common causes of hyperthyroidism in UK
graves disease
toxic multi nodular goitre
solitary toxic adenoma
examination findings which are specific to graves
exophthalmos
opthalamoplegia
thyroid acropachy
pretibial myxoedema
what does sub-clinical hyperthyroidism look like on bloods
T3 and T4 normal (on high side of normal)
TSH decreased (due to negative feedback)
thyroid eye disease symptoms and their causes
retraction of upper and lower lids (sympathetic override)
lid lag
swelling of eyelids/conjunctiva
exposure/dehydration of cornea (dry eye and inadequate blink coverage)
protrusion of eyeballs- exopthalamos/proptosis
double vision/squint (inflammation and fibrosis of muscles)
optic neuropathy (visual failure from optic nerve compression)
treating thyroid eye disease
regular thyroid medications
artificial tears
smoking cessation
selenium
surgical intervention to improve lid closure
prisms in glasses for quint/diplopia (may need surgery eventually)
if severe or a threat to the optic nerve- high dose steroid (prednisone)/immunosupression
surgical orbital decompression
what are the thyroid follicles filled with
colloid
the 2 main cells in the thyroid gland and what they produce
columnar epithelium (thyroid follicular cells)- make thyroglobulin
interspersed C-cells- make calcitonin
can TRH from the hypothalamus be measured
no
what drug can result in strange TFTs
amiodarone (it contains lots of iodine)
is thyroid eye disease more common in men or women
women but typically more severe in men
antibodies against which growth factor receptor can be seen in thyroid eye disease
insulin like growth factor receptor 1
insulin like growth factor receptor 1 antibodies effects
increases collagen production which builds up in tissue around the eyes
this causes fibrosis
can push on nerves, blood vessels and the eye itself
which medication is specific for thyroid eye disease
teprotumumab- human monoclonal antibody which blocks IGF-1R activation (it degrades the receptors)
what is T3 and T4s overall effect
increase metabolic rate
examples:
growth (of muscles)
CNS development
cardiovascular (cardiac output and HR)
what is thyrotoxic crisis/thyroid storm
it is a severe acute complication of hyperthyroidism
role of T3 specifically
majority of T4 is converted to T3 in the blood
T3 role:
speeds up cells basal metabolic rate- cells produce more proteins and burn more energy (fats and sugars)
increases cardiac output
stimulates bone resorption
activates sympathetic nervous system- triggers fight or flight
why can thyrotoxic crisis/thyroid storm happen
more unbound thyroid hormone in the blood
tissues might become more sensitive to thyroid hormone
body might become more sensitive to catecholamines (adrenaline/dopamine)
triggers for thyrotoxic crisis/thyroid storm
stressors- surgery, trauma, infection, childbirth
abruptly stopping treatment (for hyperthyroidism)
taking too much thyroid hormone (for hypothyroidism)
all of which lead to a severe state of hypermetabolism
symptoms thyrotoxic crisis/thyroid storm
weight loss (despite increased appetite as metabolism is increased)
heat intolerance (body is producing more heat)- can lead to fever
tachycardia- can lead to cardiac arrhythmia and high output cardiac failure
sweating, hyperactivity, anxiety, insomnia (effect of thyroid hormone on sympathetic nervous system)- can lead to agitation, confusion seizures and coma
diagnosis of thyrotoxic crisis/thyroid storm
based on severity of symptoms
on ECG can see cardiac arrhythmia
there isn’t much difference in thyroid hormone (it is to do with how the hormone is affecting the body symptoms)
treatment for thyrotoxic crisis/thyroid storm
beta blockers (for symptoms)
thionamides (block thyroid hormone production)
iodine preperations
glucocorticoids
bile acid sequestrants
if the above fails can do plasmapheresis (remove plasma, take thyroid hormone out then put clean plasma back in)
what links the hypothalamus to the anterior pituitary
the hypophyseal portal system
what is the most common cause of hypothyroidism in the developing world
iodine deficiency (iodine is essential for thyroid hormone synthesis)
iodine is added to food such as table salt to reduce deficiency likelihood
medications which can cause hypothyroidism
lithium (it inhibits thyroid hormone)
amiodarone (interfere with thyroid hormone production and metabolism)- but this one can also cause thyrotoxicosis
central causes of hypothyroidism
hypopituitarism which can be due to:
tumours
infection
vascular pathology (sheehans syndrome- massive blood loss during surgery)
radiation
fluid and hypothyroidism
can have oedema, pleural effusion, ascites
what does secondary hypothyroidism look like on bloods
there is a problem with pituitary therefore TSH is low
because of this T3 and T4 is also low
what are the 3 main treatment options for hyperthyroidism
antithyroid medication- carbimazole, methimazole, propylthiouracil
total thyroidectomy
radioactive iodine therapy
(beta blockers can manage symptoms such as anxiety tremor and palpitations)
potential serious side effects of carbimazole
neutropenia (low neutrophils)
agranulocytosis (acute febrile condition marked be severe decrease in granulocytes)
safety netting you need to do when prescribing carbimazole
report signs of infection (especially sore throat)- need urgent FBC
need to stop treatment if white cells are low
smoking and hyperthyroidism
worsens graves disease (especially thyroid eye disease)
pregnancy and hyperthyroid medication
ask if planning to conceive, check sexual history and contraception
needs to be switched to propylthiouracil if trying to conceive as carbimazole is associated with congential abnormalities
propylthiouracil in 1st trimester then switch to carbimazole from 2nd (as propylthiouracil can cause liver failure)
what blood tests would you check before administering carbimazole
FBC TFTs LFTs
monitoring bloods following prescribing mediation for thyroid disease
TFTs very 4-6 weeks whilst the dose is being titrated
TFTs every 3-6 months once patient is euthyroid and maintenance dose achieved
how does radioactive iodine treatment for hyperthyroidism work
radioactive iodine-131 is taken orally and taken up rapidly via the thyroid gland, the release of radiation destroys the tissue over 6-18 week period
complications of radioactive iodine
early complications= neck discomfort and possible precipitation of graves opthalmology (review to check)
longer term= progressive incidence of hypothyroidism, most need thyroxine after several years
is solitary toxic nodule cancerous
no
it is benign
pathological cardiovascular effect of thyrotoxicosis
AF- there is 3x the risk in over 60s
how long are you treated for hyperthyroidism
6-24 months as if it is graves it may go into remission (but it can sill come back after redrawing drug)
management of agranulocytosis
hospitalisation and antibiotics
is there a risk of cancer with radioactive iodine 131
no
does radioactive iodine 131 cause infertility
no, however women are advised to not get pregnant until 6 months after treatment
what are the limitations following giving radioactive iodine-131
no close contact (less than 1m) with children and pregnant people for at least 9 days
after 3 weeks they can have limited contact (less than 15mins)
when using higher doses can have an adult in the same bed for at least 4 days and cant use public transport
in conclusion the limitation is up to 3 weeks after
what is the standard surgery for hyperthyroidism
near-total thyroidectomy (patient takes levothyroxine after and relapse is less than 2%)
potential complications of near-total thyroidectomy
it is dependant on the surgeon (if they have done more than 20 cases it is preferred)
obviously hypothyroidism is inevitable
permeant parathyroid damage (2-4%)
vocal cod paralysis (less than 1%)
bleeding (less than 2%)
keloid scars
what is seen in bloods with sub-clinical hypothyroidism
raised TSH
normal T3 and T4
how to investigate thyroid nodules
US scan
fine needle aspiration
what is euthyroid sick syndrome
systemic illness causing low T3/4 and TSH (rarely can be secondary hypothyroidism)
check if asymptomatic and if euthyroid clinically repeat TFTs one month later
how to work out how many mg to give for levothyroxine
do 1.6 multiplied by their weight in kg
tablets come as 25mg so round to nearest 25
levothyroxine and pregnancy
increase dose by 25-50mg (or 25%)
repeat TFTs every 4-6 weeks and titrate to TSH
refer to endocrinology for close monitoring of her antibodies- if raised need additional growth scans
1st line management of T2D if they already have cardiovascular disease
metformin plus SGLT2 inhibitor
