(W4) Blood Glucose Flashcards
What are the different ways in which glucose is formed and what is the main source of glucose in ruminants?
- breakdown from glycogen in the liver; maintain glucose in fasting or food-deprived states (glycogenolysis)
- AA precursors in the liver (gluconeogenesis)
Ruminants - main source of glucose is gluconeogenesis from VFAs absorbed form rumen by bacterial fermentation
What is the uptake of glucose mediated by and what do they require (are there any exceptions)?
- mediated by a group of membrane transport proteins, called glucose transporters (GLU)
- some are insulin dependent (particularly muscle and fat), e.g. GLU 4
- some glucose transporters in liver, RBCs and brain don’t require insulin (preserving metabolic function of these vital organs)
What is hyper/hypoglycaemia?
hyperglycaemia - increased blood glucose concentration
hypoglycaemia - decreased blood glucose concentration
What is the renal tubular transport maximum (definition/for dogs and cats) and what are the clinical implications of this threshold?
highest rate at which the renal tubules can transfer a substance either from the tubular luminal fluid to the interstitial fluid or from the interstitial fluid to the tubular luminal fluid
Dogs - 1012 mmol/L
Cats - 12-16 mmol/L
If the threshold is exceeded (i.e. when [blood glucose] exceeds these values), glucosuria (glucose present in the urine) will occur
- increased presence of glucose in the urine can
be a predisposing factor for the development
of urinary tract bacterial infections (glucose metabolised/is substrate for bacteria)
What hormones affect glucose concentration and what are their effects?
Increase Glucose:
- glucagon
- glucocorticoids
- adrenalin
- growth hormone
- progesterone
Decrease Glucose:
- insulin
What is the effect of catecholamines on glycogen, gluconeogenesis, glucose uptake and glucose concentration?
Glycogen - breakdown
Gluconeogenesis - indirect increase by insulin inhibition
Glucose uptake - indirect increase through GH/insulin inhibition
glucose concentration - transient increase
What is the effect of growth hormone (GH) on glycogen, gluconeogenesis, glucose uptake and glucose concentration?
Glycogen - breakdown
Gluconeogenesis - N/A
Glucose uptake - decrease
Glucose concentration - increase
What is the effect of corticosteroids on glycogen, gluconeogenesis, glucose uptake and glucose concentration?
Glycogen - synthesis
Gluconeogenesis - increase
Glucose uptake - decreases
Glucose concentration - increases
What are the main causes of hyperglycaemia?
Post prandial: causes mild physiologic hyperglycaemia (should normalize within a few hours)
- Dogs/cats must be fasted ≥12h to avoid post prandial hyperglycaemia
Excitement/Stress: Occurs in all species species and can be mediated by epinephrine (transient) or corticosteroids
(more sustained increase as long as the corticosteroids are still increased in blood)
- Cats and cattle tend to
produce marked stress hyperglycaemia
Iatrogenic: Various drugs such as xylazine, ketamine, megestrol acetate, etc. can induce hyperglycaemia
through inducing a state of insulin resistance
- Intravenous glucose administration can also cause
hyperglycaemia
Diabetes mellitus: Type I diabetes mellitus is due to destruction of β cells in pancreatic islets (leading to lack of insulin and need for supplementation) and Type II diabetes mellitus is due to insulin resistance (non insulin dependent)
- Cats are prone to non-dependent insulin dependent diabetes mellitus (thought to be associated with deposition of pancreatic amyloid related to pancreatic islet dysfunction)
Hyperadrenocorticism: in dogs with Cushing’s disease, hyperglycaemia is due to insulin resistance from excess corticosteroids (also with excessive supplementation of corticosteroids)
What are the less common causes of hyperglycaemia?
Acromegaly - hyperglycaemia due to insulin resistance from high concentrations of growth hormone.
Hyperglucagonemia - insulin resistance from high concentrations of glucagon, e.g. glucagon secreting tumours (glucagonoma)
Hyperpituitarism/pituitary par intermedia dysfunction (PPID) in horses - tumours in the pituitary gland can
cause hyperglycaemia through excess production of growth hormone or ACTH
Pheochromocytomas: Some animals with these catecholamine producing tumours are hyperglycaemic.
Transient hyperglycaemia - Many causes (e.g. hyperthyroidism in cats, acute pancreatitis, etc.)
What are the main causes of hypoglycaemia?
Improper sample handling - not separating serum from cells, not submitting sample in fluoride container (if serum not separated form cells, the cells use up glucose for metabolic needs so there is artefactual hypoglycaemia)
Bacteria in the sample - this can occur with bacterial contamination of the sample or bacterial infection
Iatrogenic:
Insulin administration
Decreased production - decreased production of glucose by the liver can occur secondary to inherited defects in
gluconeogenic or glycogenolytic enzyme pathways
Liver disease:
Severe liver disease and PSS can produce hypoglycaemia, however this is uncommon, particularly with shunts (more than 70% of the functional liver mass must be lost before hypoglycaemia
ensues)
Increased insulin secretion:
Insulin secreting tumours (insulinoma) or tumours secreting insulin like growth
factors*
Xylitol consumption - stimulating insulin
release and occurs mostly in the dog (can occur quite rapidly - within 30 minutes - of ingestion)
What are the less common causes of hypoglycaemia?
Sepsis:
Hypoglycaemia occurs due to liver dysfunction, impairment of insulin degradation and enhanced glucose use secondary to endotoxemia
Bovine ketosis (type I) and ovine pregnancy toxaemia (lactational hypoglycaemia):
During pregnancy, there
are increased glucose demands from the foetus and the mammary glands (plasma glucose is the source of lactose)
- Ruminants are predisposed to hypoglycaemia in late pregnancy or early lactation as they rely on gluconeogenesis for glucose production
Exertional hypoglycaemia:
This has been identified in hunting dogs and endurance horses, where demand exceeds supply
What is artefactual hypoglycaemia and what are the causes?
Prolonged contact of plasma or serum with the cellular constituents of blood prior to centrifugation will decrease the glucose concentration due to glycolysis (use of glucose) by cellular constituents
of blood
Marked leucocytosis, erythrocytosis, or thrombocytosis - these cells consume glucose in the tube
Bacterial contamination of the sample - bacteria consume glucose
Storage temperature - glycolysis is enhanced at higher temperatures
What are the recommendations for sample submission for glucose measurement (i.e. to prevent artefactual hypoglycaemia)?
- separate plasma or serum from cells (by centrifugation) soon after sample collection
- special collection tubes containing fluoride oxalate can be used to block glycolysis (block the use of glucose by cells)
- keep serum or plasma cool until sample submission (slows down but doesn’t stop glycolysis)
What is fructosamine, what is its half life and what does it indicate?
glycated proteins formed by the post translational irreversible, non enzymatic linking of glucose to albumin or other plasma proteins (mostly IgG)
half-life = near 2-3 weeks (but it varies among species and can be altered during pathologic states)
the formation of ketoamines(?) in blood is positively correlated with the magnitude and duration of hyperglycaemia
- fructosamine is used to asses whether the hypoglycaemia is transient or persistent (persistent significant hyperglycaemia is strongly suggestive of diabetes mellitus)
- since the half-life is relatively long, it can reflect long term glucose levels
