Endocrinology Flashcards
what embryological layer does the pancreas arise from
endoderm
at what stage in embryological development does the pancreas first appear
week 5
at what stage in embryological development does there start to be an increase in the secretion of pancreatic hormones
week 7
at what week do the pancreatic cells start to differentiate and in what order does this happen
week 10
- alpha cells (glucagon)
- delta cells (somatostatin)
- beta cells (insulin)
at what week in embryological development is glucagon detectable in the fetal plasma
week 15
explain physiology mechanism of how insulin is released
- GLUT2 transporters on the surface of beta cells allow influx of glucose into cells
- metabolism of glucose generates ATP in the cell cytoplasm > closes ATP-sensitive K cells
- causes depolarisation of the membrane and opening of voltage-gated Ca channels
- influx of Ca into cells which activates the mechanisms of exocytosis of insulin-containing vesicles
diagnostic criteria for T1DM
random BM > 11.1
fasted BM > 7
DR types linked to T1DM
HLA DR3 and DR4
suspected diabetes - not in DKA, appropriate management
refer on same day to paediatric diabetes service
annual monitoring done for T1DM
thyroid disease
eye screening
HbA1c (target <59)
From age 12:
albuminuria by urine albumin:creatinine ratio
+
hypertension screening
what is ‘somogyi effect’
night-time hypoglycaemia that manifests as fits, tremors, nightmares
causes rebound hyperglycaemia with glycosuria and ketonuria
what is the ‘dawn phenomenon’
morning hyperglycamia caused by GH secretion, which peaks 4-5am
what is acanthosis nigricans and what does it signify
signifies insulin resistance
dry, dark patches of skin in the axilla, neck or groin
what causes acanthosis nigricans
increased circulating insulin acting at insulin-like growth factor (IGF-1) receptors, causing keratinocyte and fibroblast proliferation
annual monitoring in T2DM
triglycerides (usually up)
HDL (low)
non-HDL cholesterol (normal)
urine dipstick for albuminuria
diabetic retinopathy
most common in inherited defect in monogenic diabetes
defect in hepatocyte nuclear factor (HNF)-1-alpha
what % of T1DM present with DKA as their first feature
40%
pathophysiology of DKA
insulin deficiency»_space; increase in counter-regulatory hormones e.g. glucagon, cortisol, GH, catecholamines
no glucose is being metabolised so amino acid metabolism and lipolysis occur»_space; incr leavels of protein and free fatty acids
the deficiency of insulin results in more glucose being produced (both gluconeogenesis and glycogenolysis)
the free fatty acids are converted by glucagon to ketones»_space; metabolic acidosis
2 main ketones in DKA
acetoacetic acid & beta-hydroxybutyric acid)
what causes the pear drop smell on breath in DKA
metabolism of acetoacetic acid > acetone
diagnostic criteria for DKA
- acidosis
- pH < 7.3 or bicarb < 15
- ketonaemia (blood beta-hydroxybutyrate > 3)
classifications of DKA severity
- MILD
> pH 7.2 - 7.29 +/- bicarb < 15 - MODERATE
> pH 7.1 - 7.19 +/- bicarb < 10 - SEVERE
> pH < 7.1 +/- bicarb < 5
Rx DKA
- IVF (normal saline)
> Fluid bolus 10ml/kg or 20ml/kg if shocked
> Replacement fluids
(deficit (over 48h) + maintenance (over 24h))
> Hourly rate = (deficit - initial fluid bolus) / 48 + hourly maintenance rate - INSULIN
> Commence 1-2h after fluids
> rate 0.05 - 0.1 units/kg/hr
> stop continuous insulin pumps but keep long acting going
Presumed fluid deficits in different severity of DKA
mild - 5%
moderate - 5%
severe - 10%
when should dextrose be introduced into fluids in the management of DKA
when BM <14
timings of stopping IV insulin and starting regular subcut insulin in Rx of DKA
Give the regular long acting insulin and stop the IV Insulin infusion 30 mins later
major severe complication of DKA
cerebral oedema - consequence of fluid therapy
what is included in a hypo screen
free fatty acids
insulin & c-peptide levels
beta-OH butyrate
cortisol
lactate
ammonia
acylcarnitines
urinary organic acids
plasma amino acids
Rx hypo if no IV Access
Not drowsy - oral carbohydrate
Drowsy - IM glucagon
Rx hypo if has IV access
2ml/kg 10% dextrose followed by IV maintenance fluids
Rx of neonates with BM <1
IV 10% dex bolus 2.5ml/kg then 10% dextrose maintenance fluids
mechanism of action - sulphonylureas
Act on the ATP sensing K+ channels in the beta cells
normally an increase in glucose leads to generation of ATP which is sensed by the ATP-K+ channels. Closure of the channels leads to increase in K which depolarises the membrane and leads to influx of Ca through the voltage gated channels with subsequent exocytosis of insulin
sulphonylureas increase the likelihood of the ATP-K channel closing, so augmenting the release of insulin
mechanism of action - DPP4 inhibitors
decreases the action of incretins, hormones which lower blood glucose
mechanism of action - GLP1 agonists
increases insulin sensitivity in peripheral cells
mechanism of action - SGLT2
SGLT2 is a renal transports of glucose > reabsorbs 80-90% of glucose in the proximal convoluted tubule
