Endocrinology

Question 1

what embryological layer does the pancreas arise from

Answer 1

endoderm

Question 2

at what stage in embryological development does the pancreas first appear

Answer 2

week 5

Question 3

at what stage in embryological development does there start to be an increase in the secretion of pancreatic hormones

Answer 3

week 7

Question 4

at what week do the pancreatic cells start to differentiate and in what order does this happen

Answer 4

week 10

1. alpha cells (glucagon)
2. delta cells (somatostatin)
3. beta cells (insulin)

Question 5

at what week in embryological development is glucagon detectable in the fetal plasma

Answer 5

week 15

Question 6

explain physiology mechanism of how insulin is released

Answer 6

1. GLUT2 transporters on the surface of beta cells allow influx of glucose into cells
2. metabolism of glucose generates ATP in the cell cytoplasm > closes ATP-sensitive K cells
3. causes depolarisation of the membrane and opening of voltage-gated Ca channels
4. influx of Ca into cells which activates the mechanisms of exocytosis of insulin-containing vesicles

Question 7

diagnostic criteria for T1DM

Answer 7

random BM > 11.1

fasted BM > 7

Question 8

DR types linked to T1DM

Answer 8

HLA DR3 and DR4

Question 9

suspected diabetes - not in DKA, appropriate management

Answer 9

refer on same day to paediatric diabetes service

Question 10

annual monitoring done for T1DM

Answer 10

thyroid disease
eye screening
HbA1c (target <59)

From age 12:
albuminuria by urine albumin:creatinine ratio
+
hypertension screening

Question 11

what is ‘somogyi effect’

Answer 11

night-time hypoglycaemia that manifests as fits, tremors, nightmares

causes rebound hyperglycaemia with glycosuria and ketonuria

Question 12

what is the ‘dawn phenomenon’

Answer 12

morning hyperglycamia caused by GH secretion, which peaks 4-5am

Question 13

what is acanthosis nigricans and what does it signify

Answer 13

signifies insulin resistance

dry, dark patches of skin in the axilla, neck or groin

Question 14

what causes acanthosis nigricans

Answer 14

increased circulating insulin acting at insulin-like growth factor (IGF-1) receptors, causing keratinocyte and fibroblast proliferation

Question 15

annual monitoring in T2DM

Answer 15

triglycerides (usually up)

HDL (low)

non-HDL cholesterol (normal)

urine dipstick for albuminuria

diabetic retinopathy

Question 16

most common in inherited defect in monogenic diabetes

Answer 16

defect in hepatocyte nuclear factor (HNF)-1-alpha

Question 17

what % of T1DM present with DKA as their first feature

Answer 17

40%

Question 18

pathophysiology of DKA

Answer 18

insulin deficiency&raquo_space; increase in counter-regulatory hormones e.g. glucagon, cortisol, GH, catecholamines

no glucose is being metabolised so amino acid metabolism and lipolysis occur&raquo_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&raquo_space; metabolic acidosis

Question 19

2 main ketones in DKA

Answer 19

acetoacetic acid & beta-hydroxybutyric acid)

Question 20

what causes the pear drop smell on breath in DKA

Answer 20

metabolism of acetoacetic acid > acetone

Question 21

diagnostic criteria for DKA

Answer 21

1. acidosis
2. pH < 7.3 or bicarb < 15
3. ketonaemia (blood beta-hydroxybutyrate > 3)

Question 22

classifications of DKA severity

Answer 22

1. MILD
   > pH 7.2 - 7.29 +/- bicarb < 15
2. MODERATE
   > pH 7.1 - 7.19 +/- bicarb < 10
3. SEVERE
   > pH < 7.1 +/- bicarb < 5

Question 23

Rx DKA

Answer 23

1. 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
2. INSULIN
   > Commence 1-2h after fluids
   > rate 0.05 - 0.1 units/kg/hr
   > stop continuous insulin pumps but keep long acting going

Question 24

Presumed fluid deficits in different severity of DKA

Answer 24

mild - 5%

moderate - 5%

severe - 10%

Question 25

when should dextrose be introduced into fluids in the management of DKA

Answer 25

when BM <14

Question 26

timings of stopping IV insulin and starting regular subcut insulin in Rx of DKA

Answer 26

Give the regular long acting insulin and stop the IV Insulin infusion 30 mins later

Question 27

major severe complication of DKA

Answer 27

cerebral oedema - consequence of fluid therapy

Question 28

what is included in a hypo screen

Answer 28

free fatty acids
insulin & c-peptide levels
beta-OH butyrate
cortisol
lactate
ammonia
acylcarnitines
urinary organic acids
plasma amino acids

Question 29

Rx hypo if no IV Access

Answer 29

Not drowsy - oral carbohydrate

Drowsy - IM glucagon

Question 30

Rx hypo if has IV access

Answer 30

2ml/kg 10% dextrose followed by IV maintenance fluids

Question 31

Rx of neonates with BM <1

Answer 31

IV 10% dex bolus 2.5ml/kg then 10% dextrose maintenance fluids

Question 32

mechanism of action - sulphonylureas

Answer 32

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

Question 33

mechanism of action - DPP4 inhibitors

Answer 33

decreases the action of incretins, hormones which lower blood glucose

Question 34

mechanism of action - GLP1 agonists

Answer 34

increases insulin sensitivity in peripheral cells

Question 35

mechanism of action - SGLT2

Answer 35

SGLT2 is a renal transports of glucose > reabsorbs 80-90% of glucose in the proximal convoluted tubule