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Y5 Pathology > ChemPath - Hypoglycaemia > Flashcards

ChemPath - Hypoglycaemia Flashcards

1
Q

What is the definition of hypoglycaemia

A

Glucose < 4mmol/L
Paediatrics = <2.5mmol/L
Diabetes = <3.5mmol/L

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2
Q

What are the main physiological changes that occur in hypoglycaemia

A

(1) suppression of insulin
(2) release of glucagon
(3) release of adrenaline
(4) release of cortisol

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3
Q

Describe what happens physiologically in hypoglycaemia

A
  1. Low glucose → insulin ↓ + glucagon ↑
    - Reduction in peripheral uptake of glucose
    - Glycogenolysis → ↑ FFAs → enter the beta-oxidation cycle to make ATP (excess become ketones)
    - Gluconeogenesis
    - Lipolysis
  2. hypothalamus senses hypoglycaemia → catecholamine release + ACTH → cortisol + GH release
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4
Q

What is Wipple’s triad

A
  1. Low glucose
  2. Symptoms (adrenergic or neuroglycopaenic)
  3. Relief of symptoms upon treatment
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5
Q

What are the symptoms of hypoglycaemia

A

Asymptomatic
Adrenergic:
- Tremors
- Palpitations
- Sweating
- Hunger
Neuroglycopaenic
- Somnolence
- Confusion
- Incoordination
- Seizures, coma

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6
Q

What can be used to measure glucose if suspecting hypoglycaemia and what are the limitations

A

Venous glucose (gold standard):
- Fluoride oxalate in grey-top, 2mL blood
- Lab analyser with quality control but takes some time
Capillary glucose:
- Point of care analyser with instant results
- Poor precision at low glucose levels, not quality controlled
Continuous glucose monitoring:
- Small device attached to abdomen wall that monitors continually
- Not accurate below 2.2mmol/L

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7
Q

What is the management for hypoglycaemia in adults

A

Alert & orientated: oral carbohydrates (Rapid = juice, sweets | long = sandwich)

Drowsy/confused with swallow: buccal glucose (hypostop/glucogel)

Unconscious or swallow compromised: IV 20% glucose

Deteriorating → IM/SC 1mg glucagon (15-20mins)

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8
Q

What are the caveats to management of hypoglycaemia

A

Requires continuous monitoring
Glucagon takes 15-20 mins to mobilise glycogen stores
Glucagon not suitable for liver failure (no glycogen)
Glucagon → rebound hypoglycaemia
Recurrent hypos → hypoglycaemia unawareness

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9
Q

What are the causes of hypoglycaemia in non-diabetics

A

Fasting or reactive
Critically unwell
Organ failure i.e. renal failure
Hyperinsulinism
Post-gastric bypass
Drugs
Extreme weight loss
Factitious (i.e. an artefact)

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10
Q

What are the causes of hypoglycaemia in diabetics

A

Medications (inappropriate insulin)
Inadequate CHO intake/missed meal
Impaired awareness (autonomic neuropathy)
Excessive alcohol
Strenuous exercise
Co-existing autoimmune conditions e.g. Addison’s
Renal/liver failure alters drug clearance

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11
Q

Which medications are hypoglycaemic

A

Sulphonylureas (causes endogenous insulin production)
Meglitinides
GLP-1 agents in conjunction with insulin
INsulin
Beta-blockers
Salicylates
Alcohol (inhibits lipolysis)

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12
Q

What investigations should be done to determine the cause of hypoglycaemia

A

Insulin levels (4-6min half life, hepatic clearance)
C-peptide
Drug screen
Autoantibodies
Cortisol/GH
FFAs/blood ketones
Lactate
IGF-2
Carnitine
Ammonia

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13
Q

Describe C-peptide

A

cleavage product; secreted in equimolar amounts to insulin
good marker of beta cell function (endogenous)
Half-life is 30 mins and renally cleared

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14
Q

What are the causes of a low insulin and low C-peptide

A

Hypoinsulinaemic hypoglycaemia
Suggests that something else is causing the hypoglycaemia.
The insulin level is appropriate response to hypoglycaemia which can be caused by:
- Fasting/starvation
- Strenuous exercise
- Critical illness
- Endocrine deficiencies (i.e. hypopituitarism, adrenal failure)
- Liver failure
- Anorexia nervosa

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15
Q

What causes high insulin and high c peptide

A

Hyperinsulinaemic hypoglycaemia
Endogenous insulin production
- Drugs (sulphonylureas - will make the pancreas produce more insulin)
- Islet cell tumours (e.g. insulinoma)
- Islet cell hyperplasia

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16
Q

What are the causes of islet cell hyperplasia

A

Infant of a diabetic mother
Beckwith-Wiedemann syndrome (specific body parts overgrowth disorder usually presents at birth)
Nesidioblastosis (hyperinsulinaemic hypoglycaemia caused by excessive function of beta cells with an abnormal microscopic appearance)

17
Q

What are the causes of high insulin and low c peptide

A

exogenous insulin

18
Q

What are the causes of neonatal hypoglycaemia

A

Explainable:
- Premature, co-morbidities, IUGR, small-for-gestational-age
- Inadequate glycogen and fat stores
- Should improve with feeding
Pathological:
- Inborn errors of metabolism

19
Q

What suggests a pathological cause of neonatal hypoglycaemia and what are the causes

A

low insulin, low C-peptide, raised FFA, low ketones
Fatty Acid Oxidation Disorders (FAOD) = no ketones produced
Glycogen Storage Disease (GSD) type 1 (gluconeogenetic disorder)
Medium Chain Acyl-CoA Deficiency (MCAD)
Carnitine Disorders

20
Q

Describe the normal insulin secretion pathway and what is the role of sulphonylureas in it

A
  1. Glucose crosses membrane and enters glycolysis via glucokinase
  2. Glycolysis produces ATP
  3. Rise in ATP leads to closure of the ATP-sensitive K+ channel (a lot of genetic mutations that affect this channel)
  4. Membrane depolarisation
  5. Calcium influx
  6. Insulin exocytosis

Sulphonylureas bind to the ATP-sensitive K+ channel and makes it close, independently of ATP → insulin release even when there is no ATP around (this is why sulphonylureas can cause hypoglycaemia)

21
Q

Describe insulinomas

A

LOW glucose, HIGH insulin, HIGH c-peptide
Usually a small solitary adenoma (10% malignant, 8% associated to MEN1)
Treatment is simple resection

22
Q

Describe non-islet cell tumour hypoglycaemia

A

Glucose, insulin, C-peptide, FFA, and ketones are all low
FFA should be high but are also low here so most likely, there is something pretending to be insulin (i.e. a paraneoplastic syndrome from secretion of big IGF-2)
Big IGF-2 binds to IGF-1 receptors and insulin receptors → your own endogenous insulin production is switched off and FFA production is suppressed
Produced by mesenchymal tumours (mesothelioma, fibroblastoma) and epithelial tumours (carcinoma)

23
Q

What are the autoimmune causes of hypoglycaemia

A

Autoimmune conditions: Abs against insulin receptors (rarely causes hypoglycaemia)
Autoimmune insulin syndrome: Abs against insulin → sudden dissociation (hydralazine, procainamide) → hypoglycaemia

24
Q

What are the genetic causes of hypoglycaemia

A

LOW glucose, HIGH insulin, HIGH c-peptide (treat with pancreatectomy)

Glucokinase activating mutation
Congenital hyperinsulinism:
- KCNJ11 /ABCC8
- GLUD-1
- HNF4A
- HADH

25
Q

What are the causes of reactive/post-prandial hypoglycaemia

A

Can occur after gastric bypass
Hereditary fructose intolerance
Early diabetes
In insulin-sensitive people post-exercise or large meals

Y5 Pathology (71 decks)

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