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YR5 Chemical Pathology > Hypoglycaemia > Flashcards

Hypoglycaemia Flashcards

1
Q

What is the acute management of hypoglycaemia in an alert and orientated adult?

A

Oral Carbohydrates

Rapid acting: Juice/sweets

Longer acting: Sandwich

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2
Q

What is the acute management of hypoglycaemia in a drowsy/confused but swallow intact?

A

Buccal glucose e.g. Hypostop/glucogel

Start thinking about IV access

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3
Q

What is the acute management of hypoglycaemia in an unconscious or concerned about swallow adult?

A

IV access

100 ml 20% glucose

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4
Q

What is the acute management of hypoglycaemia in a deteriorating/refractory/insulin induced/difficult IV access adult patient?

A

Consider IM /SC 1mg Glucagon

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5
Q

What are 4 adrenergic symptoms of hypoglycaemia?

A

Tremors

Palpitations

Sweating

Hunger

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6
Q

What are 4 neuroglycopaenic symptoms of hypoglycaemia?

A

Somnolence

Confusion

Incoordination

Seizures, coma

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7
Q

What is the normal physiological response to hypoglycaemia?

A

Reduce peripheral uptake of glucose

Increase glycogenolysis to release glucose

Increase gluconeogenesis (from amino acids)

Increase lipolysis (free fatty acids burnt to release ATP)

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8
Q

What is the normal physiological response to low neuronal glucose sensed in the hypothalamus? When does this occur?

A

Later to the drop in insulin + rise in glucagon

Sympathetic Activation: Catecholamines

ACTH, cortisol + GH production

Further acts to increase glucose

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9
Q

What occurs first in response to hypoglycaemia?

A. Suppression of insulin

B. Release of glucagon

C. Release of adrenaline

D. Release of cortisol

A

A. Suppression of insulin

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10
Q

What are appropriate investigations for hypoglycaemia?

A

Confirm there is hypoglycaemia

Easy in pt with diabetes – usually monitor blood glucose (BG).

Difficult in an otherwise healthy person – May need to conduct a prolonged fast to demonstrate hypoglycaemia.

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11
Q

How is glucose measured in a lab?

A

Venous sample 2ml

Grey top (flouride oxalate preservative)

Gold std to make dx

Delay in results

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12
Q

How is glucose measured using a glucometer?

A

Capillary blood

Point-of-care device

Instant result

But:

Poor precision at low glucose levels

Often poorly maintained

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13
Q

What may hypoglycaemia in diabetes be related to? List 6 causes

A

Medications

Inadequate CHO intake/ missed meal

Impaired awareness (no Sx)

Excessive alcohol

Strenuous exercise

Co-existing AI conditions

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14
Q

Which diabetes medications can cause hypoglycaemia?

A

Sulphonylureas

Meglitinides

GLP-1 agents (if given with insulin as boosts insulin)

Insulin:

  • Rapid acting with meals: Inadequate meal
  • Long-acting: Hypos at night or in between meals
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15
Q

What other drugs can cause hypoglycaemia?

A

B-blockers

Salicylates

Alcohol (inhibits lipolysis)

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16
Q

Which comorbidities can result in hypoglycaemia when coexisting with diabetes?

A

Co-existing renal/ liver failure alters drug clearance, + reduced doses needed.

Rarely concurrent Addison’s can result in hypos (polygladular AI syndrome).

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17
Q

How can we differentiate the cause of hypoglycaemia?

A

Thorough hx + examination.

Biochemical Tests:

  • Insulin levels
  • C-peptide
  • Drug screen
  • Auto-antibodies
  • Cortisol /GH
  • Free fatty acids / blood ketones
  • Lactate
  • Other specialist tests – IGFBP/IGF-2/Carnitines etc.
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18
Q

When should bloods be taken when investigating hypoglycaemia?

A

Take bloods at the time of hypoglycaemia.

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19
Q

C-peptide

A. Is the cleavage product of insulin

B. Is secreted in equimolar amounts to insulin

C. Has a half-life of 2 hours

D. Interferes with insulin measurement

A

B. Is secreted in equimolar amounts to insulin

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20
Q

What is C-peptide?

A

Product of cleavage of proinsulin.

Good marker of beta cell function

Half-life, ~ 30 minutes

Renal clearance

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21
Q

Hypoglycaemia due to excess injected insulin would result in:

A. A low C-peptide

B. A high C-peptide

A

A. A low C-peptide

22
Q

What can cause a patient to be hypoglycaemic with low insulin and low C-peptide?

A

Hypoinsulinaemic hypoglycaemia

Appropriate response to hypoglycaemia:

  • Fasting/ starvation
  • Strenuous exercise
  • Critical illness
  • Endocrine deficiencies: Hypopituitarism + Adrenal failure
  • Liver failure
  • Anorexia Nervosa
23
Q

What does the absence of ketones signify (glucose 1.9, ketones negative)?

A. Insulin deficiency

B. Fatty acid oxidation defect

C. Starvation

A

B. Fatty acid oxidation defect

24
Q

What are causes of neonatal hypoglycaemia?

A

Explainable:

  • Premature, co-morbidities, IUGR, SGA
  • Inadequate glycogen + fat stores
  • Should improve with feeding

Pathological:

  • Inborn metabolic defects
25
Q

What are causes of neonatal hypoglycaemia with suppressed insulin and C-peptide?

A

FFA raised, but low ketones.

Inherited metabolic disorders:

  • Fatty acid oxidation defect (FAOD): No ketones produced
  • GSD type 1 (gluconeogentic disorder)
  • Medium chain acyl coA dehydrogenase deficiency
  • Carnitine disorders
26
Q

What are appropriate investigations for neonatal hypoglycaemia?

A
  • Expect high FFA
  • Expect detectable ketone bodies (beta-hydroxybutyrate, acetoacetate/acetone)

Good differentiators in neonatal hypoglycaemia:

  • Insulin/C-peptide
  • FFA
  • KB
  • Lactate
  • Hepatomegaly
27
Q

What are causes of increased insulin levels with hypoglycaemia?

A

Islet cell tumours: Insulinoma

Drugs: Insulin, sulphonylurea

Islet cell hyperplasia:

  • Infant of a diabetic mother
  • Beckwith Weidemann syndrome
  • Nesidioblastosis

Rare AI + genetic forms of hyperinsulinism

28
Q

What is an insulinoma?

A
  • 1-2/million/year
  • Usually small solitary adenoma
  • 10% malignant
  • 8% associated with MEN1

Dx based on biochemistry + localisation

Tx: Resection

29
Q

What is non-islet cell tumour hypoglycaemia?

A

Tumours that cause a paraneoplastic syndrome

Secretion of ‘big IGF-2’

Big IGF2 binds to IGF-1 receptor + insulin receptor effectively does the job of insulin without insulin

Mesenchymal tumours (mesothelioma/ fibroblastoma)

Epithelial tumours (carcinoma)

30
Q

What are some autoimmune causes of hypoglycaemia?

A

AI conditions = rare.

Antibodies to insulin receptors usually present with insulin resistance but rarely hypoglycaemia.

AI insulin syndrome:

Ab’s directed to insulin, sudden dissociation may precipitate hypoglycaemia. Prevalent in Japan.

Triggers: Hydralazine, procainamide

31
Q

What are some genetic causes of hypoglycaemia?

A

Glucokinase activating mutation

Congenital hyperinsulinism:

  • KCNJ11/ABCC8
  • GLUD-1
  • HNF4A
  • HADH
32
Q

What is reactive/ post-prandial hypoglycaemia?

A

Hypoglycaemia following food intake.

  • Can occur post-gastric bypass.
  • Hereditary fructose intolerance
  • Early diabetes
  • In insulin sensitive individuals after exercise or large meal.

True post-prandial hypo are difficult to define.

33
Q

Why must patients be monitored in acute management of hypoglycaemia?

A

Takes 15-20 mins to rise

The reason causing hypo may persist

34
Q

What must be considered if giving glucagon in deteriorating/ refractory/ insulin/ difficult IV hypoglycaemic patients?

A

This assumes they have glycogen stores to mobilise- some may not e.g. those with liver failure

Danger of rebound hypoglycaemia- will cause insulin release

35
Q

How is hypoglycaemia defined?

A

Variable threshold <4 - <3

Presence of adrenergic/ neuroglycopenic Sx (may be none)

Relief of Sx with glucose administration

36
Q

Why is lipolysis increased in hypoglycaemia?

A

Increases free fatty acids

Free fatty acids burnt in mitochondrial beta oxidation to generate ATP

Also produces ketone bodies

37
Q

When don’t you form ketone bodies?

A

Unless insulin is completely suppressed

Lipolysis is really sensitive to insulin- as soon as insulin in circulation, lipolysis will cease

38
Q

Give 9 causes of hypoglycaemia in those with or without diabetes

A

Fasting or reactive

Post gastric-bypass

Paeds v Adult cut off

Organ failure

Critically unwell

Hyperinsulinism

Drugs

Extreme weight loss

Factitious

39
Q

Why does organ failure predispose to hypos?

A

Liver: can’t store glycogen

Kidney: most gluconeogenesis occurs in kidneys, thus gluconeogenesis is impaired

40
Q

Why may a patient have a very good HbA1c level and poor awareness?

A

HbA1c: recurrent hypos

Autonomic neuropathy can lead to poor awareness

Serious at night: indication for continuous glucose monitoring

41
Q

Why is insulin alone not measured?

A

Half life 4-6 mins

Hepatic clearance

Exogenous insulin / factitious can’t be differentiated from pancreatic- need C peptide

41
Q

What has caused a hypo in a patient with:

high insulin

low C-peptide

A

Exogenous insulin

Inappropriate usage or factitious

42
Q

What has caused a hypo in a patient with:

low insulin

low C-peptide

A

Hypoinsulinaemic = normal counter regulatory response to hypoglycaemia

Switch off production of insulin + thus C peptide is low

43
Q

What has caused a hypo in a patient with:

high insulin

high C peptide

A

Hyperinsulinaemic

Endogenous production

Insulinoma or sulphonylurea abuse

44
Q

Which class of drug increases production of insulin?

A

Sulphonylureas

45
Q

What is the appropriate response to hypoglycaemia?

A

Hypoinsulinaemic hypoglycaemia

Glucose is low for some other reason + the body responds by suppressing insulin production

46
Q

What is an inappropriate response to hypoglycaemia?

A

Hyperinsulinaemic hypoglycaemia

Insulin driving the low insulin

47
Q

What must be done to diagnose insulinoma?

A

Sulphonylurea drug screen: urine or serum

48
Q

Describe normal insulin secretion

A

Glucose enters beta cell, undergoes glycolysis + ATP is produced

K+ channel closes, causing membrane to depolarise

Ca enters, insulin granules fuse with membrane + is released

49
Q

How do sulphonylureas increase insulin production?

A

Bind to K+ ATP channel + close it independently of the glucose

Everything downstream occurs as in normal insulin secretion

Increase insulin + C peptide

50
Q

What biochemistry would be expected in non-islet cell tumour hypoglycaemia?

A

Low glucose

Low insulin

Low C-peptide

Low FFA

Low ketones

(normally if insulin low, ketones + FFA should be really high)

51
Q

What is 3-hydroxybutyrate?

A

A ketone body

YR5 Chemical Pathology (16 decks)

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