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YEAR 5: Chemical Pathology JK > ChemPath: Hypoglycaemia > Flashcards

ChemPath: Hypoglycaemia Flashcards

1
Q

Outline the first step in the management of hypoglycaemia patients in the following states:

  1. Alert and orientated
  2. Drowsy/confused but swallow intact
  3. Unconscious or concerned about swallow
A
  1. Alert and orientated
    • Oral sarbohydrates (e.g. juice/sweets or long-acting forms such as a sandwich)
  2. Drowsy/confused but swallow intact
    • Buccal glucose (e.g. glucogel)
  3. Unconscious or concerned about swallow
    • IV 50 mL 50% glucose
    • NOTE: or 100 mL 20% glucose
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2
Q

What should be considered if a hypoglycaemic patient is deteriorating or does not appear to be responding to the first step in their management?

A

IM/SC 1 mg glucagon

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3
Q

What is the benefit of giving glucose sublingually?

A

Bypasses hepatic first-pass metabolism

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4
Q

How long is it likely to take for IM glucagon to cause an increase in blood glucose?

A

15-20 mins

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5
Q

Which group of patients may not respond to IM glucagon?

A
  • Starving
  • Anorexic
  • Hepatic failure
  • These patients will have poor liver glycogen stores that can be accessed by glucagon
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6
Q

What are some possible consequences of extravasation of IV dextrose?

A
  • Irritation
  • Phlebitis
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7
Q

Describe the triad of features that is used to define hypoglycaemia.

A
  • Low glucose
  • Symptoms
  • Relief of symptoms by administration of glucose
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8
Q

List some symptoms of hypoglycaemia.

A
  • Adrenergic: tremors, palpitations, sweating
  • Neuroglycopaenic: confusion, coma
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9
Q

What is a consequence of recurrent episodes of hypoglycaemia?

A

Hypoglycaemia unawareness (loss of adrenergic symptoms with hypoglycaemia)

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10
Q

Describe the order in which physiological compensatory changes in response to hypoglycaemia take place.

A
  • Suppression of insulin
  • Release of glucagon
  • Release of adrenaline
  • Release of cortisol
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11
Q

What effect do these measures have on blood glucose and FFA production?

A
  • Increases blood glucose
  • Increases FFAs
  • Not all FFAs can be used to generate ATP by beta-oxidation so some of them will become ketone bodies
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12
Q

What investigation may need to be performed to demonstrate hypoglycaemia in an otherwise healthy person?

A

Prolonged fast

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13
Q

What is the gold standard for measuring blood glucose?

A

Lab glucose

NOTE: this is collected in a grey top container that has fluoride oxalate

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14
Q

What is the disadvantage of using a blood glucose meter?

A

Poor prevision at low levels

NOTE: however, it does produce an instant results

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15
Q

List some causes of hypoglycaemia in people without diabetes.

A
  • Fasting
  • Paediatric
  • Critically unwell
  • Organ failure
  • Hyperinsulinism
  • Post-gastric bypass
  • Drugs
  • Extreme weight loss
  • Factitious (artefact)
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16
Q

List some causes of hypoglycaemia in diabetics.

A
  • Medications (inappropriate insulin)
  • Inadequate carbohydrate intake (missed meal)
  • Impaired awareness
  • Excessive alcohol
  • Strenous exercise
  • Co-existing autoimmune conditions
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17
Q

List some diabetic medications that can causes hypoglycaemia.

A
  • Oral hypoglycaemics: sulphonylureas, meglitinides, GLP1 analogues
  • Insulin
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18
Q

List some non-diabetic medications that can cause hypoglycaemia.

A
  • Beta-blockers
  • Salicylates
  • Alcohol
19
Q

How could co-morbidities in a diabetic patient lead to increased risk of hypoglycaemia?

A
  • Renal/liver failure could lead to impaired drug clearance
  • Concurrent Addison’s disease could result in hypoglycaemia (polyglandular autoimmune syndrome)
20
Q

What is continous glucose monitoring?

A

The device is applied to the abdominal wall with a small cannula that sits in the interstitial space in the subcutaneous fat

21
Q

What is the main issue with continoues glucose monitoring?

A

The sensor does not accurately read blood glucose when < 2.2. mmol/L

22
Q

List some biochemical tests that may help differentiate between causes of hypoglycaemia.

A
  • Insulin levels (NOTE: exogenous insulin can interfere with assays)
  • C-peptide (marker of endogenous insulin production)
  • Drug screen
  • Autoantibodies
  • Cortisol/GH
  • Free fatty acids/ketone bodies
  • Lactate

NOTE: it is important to perform these tests at the time of the hypo (but try not to delay treatment)

23
Q

What would you expect the insulin and C-peptide levels to be in a hypoglycaemic patient who has anorexia nervosa but not diabetes?

A
  • Low insulin and low C-peptide
  • The patient is hypoglycaemic because of poor liver glycogen stores (not an issue with insulin) so their insulin response will be normal
24
Q

List some causes of Hypoinsulinaemic hypoglycaemia.

A
  • Fasting/starvation
  • Strenous exercise
  • Critical illness
  • Endocrine deficiencies (adrenal failure, hypopituitarism)
  • Liver failure
  • Anorexia nervosa

NOTE: this is a normal response to hypoglycaemia

25
Q

What does hypoglycaemia with a high insulin and low C-peptide suggest?

A

Exogenous insulin is responsible for the hypoglycaemia

26
Q

Name 3 ketone bodies.

A
  • 3-hydroxybutyrate
  • Acetone
  • Acetoacetate
27
Q

What does hypoglycaemia with high FFAs and low ketones suggest?

A

Fatty acid oxidation defect

28
Q

List some physiologically explicable causes of neonatal hypoglycaemia.

A
  • Prematurity
  • IUGR
  • Inadequate glycogen/fat stores

NOTE: this should improve with feeding

29
Q

What is a pathological cause of neonatal hypoglycaemia?

A

Inborn errors of metabolism

30
Q

List some tests that may be useful in the investigation of neonatal hypoglycaemia.

A
  • Insulin/C-peptide
  • FFA
  • Ketone bodies
  • Lactate
  • Hepatomegaly
31
Q

List some causes of neonatal hypoglycaemia with high FFAs and low ketones.

A
  • Fatty acid oxidation defects
  • MCAD deficiency
  • Carnitine disorders
  • HMG-CoA lyase deficiency
  • GSD type 1
32
Q

List some causes of neonatal hypoglycaemia with low FFAs and low ketones.

A
  • Hyperinsulinism
  • Hypopituitarism
33
Q

List some causes of neonatal hypoglycaemia with high FFAs and high ketones.

A
  • Galactosaemia
  • Glycogen storage disease
  • Neonatal haemochromatosis
  • GH deficiency
  • Glucocorticoid deficiency
  • Septicaemia
34
Q

List some causes of inappropriately high insulin levels in neonates.

A
  • Islet cell tumours (eg. insulinoma)
  • Drugs (e.g. insulin, sulphonylureas)
  • Islet cell hyperplasia
    • Infant with diabetic mother
    • Beckwith-Wiedemann syndrome (overgrowth disorder)
    • Nesidioblastosis (excessive function of beta cells with abnormal microscopic appearance)
35
Q

State two causes of Hyperinsulinaemic hypoglycaemia with a high C-peptide.

A
  • Insulinoma
  • Sulphonylurea abuse
36
Q

What test could help differentiate between these two causes?

A

Urine or serum sulphonylureas

37
Q

Describe the mechanism by which beta cells release insulin in response to blood glucose.

A
  • Glucose crosses the membrane of beta cells and enters glycolysis via glucokinase
  • Glycolysis produces ATP
  • The rise in ATP leads to the closure of ATP-sensitive K+ channels
  • This leads to membrane depolarisation, calcium influx and insulin exocytosis
38
Q

Describe the mechanism of action of sulphonylureas.

A

They bind to the ATP-sensitive K+ channel making it close independently of ATP

39
Q

What proportion of insulinomas are malignant?

A

10%

40
Q

State two causes of Hyperinsulinaemic hypoglycaemia with a low C-peptide.

A
  • Factitious result
  • Oral hypoglycaemic usage (not sulphonylureas)
41
Q

What can cause the following: low glucose, low insulin, low C-peptide, low FFAs and low ketones?

A
  • This suggests that something is pretending to be insulin
  • This is non-islet cell hypoglycaemia caused by secretion of big IGF-2
  • Big IGF-2 binds to IGF-1 receptors and insulin receptors
  • It behaves like insulin, so it causes hypoglycaemia and suppresses insulin and FFA/ketone production
  • It is a paraneoplastic syndrome usually caused by mesenchymal tumours (e.g. mesothelioma, fibroblastoma) and epithelial tumours (carcinoma)
42
Q

Describe two autoimmune causes of hypoglycaemia.

A
  • Autoimmune conditions - antibodies against insulin receptors can cause insulin resistance and hypoglycaemia (rarely)
  • Autoimmune insulin syndrome - antibodies are directed towards insulin so sudden dissociation of the antibodies can precipitate hypoglycaemia (could be caused by drugs e.g. hydralazine, procainamide)
43
Q

List some genetic causes of hypoglycaemia.

A
  • Glucokinase activating mutation
  • Congenital hyperinsulinism (GLUD-1, HNF4A, HADH, KNJJ11)
44
Q

What is reactive hypoglycaemia?

A
  • Hypoglycaemia following food intake (post-prandial)
  • Can occur after gastric bypass
  • May be suggestive of early diabetes
  • May occur in insulin-sensitive individuals after exercise or large meals
  • May be due to hereditary fructose intolerance

YEAR 5: Chemical Pathology JK (26 decks)

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