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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
What are causes of neonatal hypoglycaemia with suppressed insulin and C-peptide?
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
What are appropriate investigations for neonatal hypoglycaemia?
* Expect high FFA * Expect detectable ketone bodies (beta-hydroxybutyrate, acetoacetate/acetone) **Good differentiators in neonatal hypoglycaemia:** * Insulin/C-peptide * FFA * KB * Lactate * Hepatomegaly
27
What are causes of increased insulin levels with hypoglycaemia?
**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
What is an insulinoma?
* 1-2/million/year * Usually small solitary adenoma * 10% malignant * 8% associated with MEN1 Dx based on biochemistry + localisation **Tx:** Resection
29
What is non-islet cell tumour hypoglycaemia?
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
What are some autoimmune causes of hypoglycaemia?
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
What are some genetic causes of hypoglycaemia?
Glucokinase activating mutation **Congenital hyperinsulinism:** * KCNJ11/ABCC8 * GLUD-1 * HNF4A * HADH
32
What is reactive/ post-prandial hypoglycaemia?
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
Why must patients be monitored in acute management of hypoglycaemia?
Takes 15-20 mins to rise The reason causing hypo may persist
34
What must be considered if giving glucagon in deteriorating/ refractory/ insulin/ difficult IV hypoglycaemic patients?
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
How is hypoglycaemia defined?
Variable threshold \<4 - \<3 Presence of adrenergic/ neuroglycopenic Sx (may be none) Relief of Sx with glucose administration
36
Why is lipolysis increased in hypoglycaemia?
Increases free fatty acids Free fatty acids burnt in mitochondrial beta oxidation to generate ATP Also produces ketone bodies
37
When don't you form ketone bodies?
Unless insulin is completely suppressed Lipolysis is really sensitive to insulin- as soon as insulin in circulation, lipolysis will cease
38
Give 9 causes of hypoglycaemia in those with or without diabetes
Fasting or reactive Post gastric-bypass Paeds v Adult cut off Organ failure Critically unwell Hyperinsulinism Drugs Extreme weight loss Factitious
39
Why does organ failure predispose to hypos?
Liver: can't store glycogen Kidney: most gluconeogenesis occurs in kidneys, thus gluconeogenesis is impaired
40
Why may a patient have a very good HbA1c level and poor awareness?
HbA1c: recurrent hypos Autonomic neuropathy can lead to poor awareness Serious at night: indication for continuous glucose monitoring
41
Why is insulin alone not measured?
Half life 4-6 mins Hepatic clearance Exogenous insulin / factitious can't be differentiated from pancreatic- need C peptide
41
What has caused a hypo in a patient with: high insulin low C-peptide
Exogenous insulin Inappropriate usage or factitious
42
What has caused a hypo in a patient with: low insulin low C-peptide
Hypoinsulinaemic = normal counter regulatory response to hypoglycaemia Switch off production of insulin + thus C peptide is low
43
What has caused a hypo in a patient with: high insulin high C peptide
Hyperinsulinaemic Endogenous production Insulinoma or sulphonylurea abuse
44
Which class of drug increases production of insulin?
Sulphonylureas
45
What is the appropriate response to hypoglycaemia?
Hypoinsulinaemic hypoglycaemia Glucose is low for some other reason + the body responds by suppressing insulin production
46
What is an inappropriate response to hypoglycaemia?
Hyperinsulinaemic hypoglycaemia Insulin driving the low insulin
47
What must be done to diagnose insulinoma?
Sulphonylurea drug screen: urine or serum
48
Describe normal insulin secretion
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
How do sulphonylureas increase insulin production?
Bind to K+ ATP channel + close it independently of the glucose Everything downstream occurs as in normal insulin secretion Increase insulin + C peptide
50
What biochemistry would be expected in non-islet cell tumour hypoglycaemia?
Low glucose Low insulin Low C-peptide Low FFA Low ketones (normally if insulin low, ketones + FFA should be really high)
51
What is 3-hydroxybutyrate?
A ketone body

YR5 Chemical Pathology (16 decks)

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