Carbs and Lipid Metabolism Lecture 20 Flashcards
Hyperglycemia
Glucose is above reference limit
Hypoglycemia
Glucose is below reference limit
Euglycemia
Glucose is within reference interval
How is glucose measured?
Glucose is measured in heparinized plasma (green‐top tube) or serum (red‐top or tiger‐top tube) as part of a routine biochemical profile.
What are some common glucose measuring devices and what would be the proper sample for each?
Glucometer –> whole blood
Blood gas instruments –> whole blood
Chemistry instruments on routine biochem panels –> plasma (or serum)
Freestyle libre monitor –> interstitial fluid, type of continuous glucose monitoring
What is plasma-equivalent glucose?
100 microL plasma has more glucose than 100 microL whole blood so when you use modern glucometers they report a “plasma-equivalent” glucose of the whole blood sample used.
Modern glucometer plasma-equivalent reporting assumes:
the patient has an approximately
normal PCV.
Particular distribution of glucose in RBCs and plasma
What is the purpose of plasma-equivalent glucose?
decreases bias between glucometers and central lab
Should you use human glucometers for animals?
no they falsely decrease results in animals. Also ensure you chose the correct species on your glucometer
What sample should you use for glucometers?
whole blood
Not effusions
- low PCV of effusion –> falsely high glucose
How do you minimize pre-analytical error?
- Cells don’t die immediately upon removal from the body! If you draw a blood sample, the cells in that sample will continue to live (and carry on metabolism) for at least several hours. Living cells use glucose.
- Because of this, it’s crucial to separate plasma (or serum) from cells in a timely fashion for accurate glucose measurement. Plasma should be harvested following sample collection within 30 minutes. Blood in clot tubes should be allowed to clot fully before centrifugation; ideally serum is harvested within 60 minutes following blood collection.
- At room temperature, glucose concentration drops by 5 to 10% per hour if cells and plasma (or
serum) are not separated; marked erythrocytosis or leukocytosis only accelerate this process.
If you have unexpected hypoglycemia why?
Think about how the sample was handled
Urine dipsticks: Should glucose ever be present in health?
It should be negative because glucose is freely filtered amd reabsorbed
Glucosuria will occur if:
Resorption mechanisms are overwhelmed (due to hyperglycemia)
Tubular damage or defect –> animal is typically euglycemic
What are some common causes of hyperglycemia?
- Increased intestinal absorption –> Post‐prandial (is expected following a meal!)
- Catecholamine release –> fight or flight response
- Increased gluconeogenesis &
glycogenolysis –> Corticosteroid excess (can be endogenous, as with stress or disease; or exogenous, as with corticosteroid drug administration) - Absolute insulin deficiency –> Diabetes mellitus (type I; any cause of islet cell destruction resulting in diabetes)
- Increased insulin resistance (with relative insulin deficiency) –> Diabetes mellitus (type II), Obesity in horses/ponies (“metabolic syndrome”), Corticosteroid excess, sick camelids
- Impaired insulin release –> Bovine milk fever (partly due to hypocalcemia; calcium is needed for cleavage of proinsulin to insulin)
- Pharmacologic (various mechanisms) –> Many drugs cause hyperglycemia. Besides corticosteroid
drugs and progestins, common drugs include xylazine,
detomidine, ketamine, thyroxine, and propranolol.
What species are very prone to hyperglycemia?
- Llamas and alpacas
- Very common when sick
- Presumed due to stress
hormone release + insulin
resistance - Stress hyperglycemia can be
marked (> 400 mg/dL) - May require insulin treatment
What are some common causes of hypoglycemia?
- Pre‐analytical error –> Delayed separation of plasma/serum from cells
- Insulin excess –> Iatrogenic (excess insulin administration)
- Decreased gluconeogenesis –> Liver insufficiency/failure (can be acute or chronic), Hypoadrenocorticism (Addison’s Dz) (decreased cortisol), Neonatal or juvenile hypoglycemia (immature liver)
- Increased tissue utilization of glucose –> sepsis
If an animal is held off food or is anorexic for a few days should they get hypoglycemic?
NO not if if liver function (gluconeogenesis, glycogenolysis) and glycogen stores are
normal! Think of the liver as a “thermostat” for maintaining euglycemia.
What animals are specifically vulnerable to hypoglycemia during fasting?
- Animals suffering from prolonged anorexia or starvation, whose dietary carbohydrate
intake is reduced and whose liver glycogen stores are depleted - Neonates (particularly neonatal piglets and toy breed dogs) –> this is due to underdeveloped enzymes for gluconeogenesis. aka immature livers
- Animals with decreased gluconeogenesis due to a liver disorder, e.g., portosystemic
shunt (liver under‐developed) or severe liver disease with loss of functional hepatic
mass (e.g., cirrhosis, end‐stage chronic liver disease, severe acute hepatocellular
necrosis).
What are the medically important ketones?
Acetoacetate, acetone, Beta‐hydroxybutyrate (BHB)
Ketone measurement is part of routine…
urine dipstick analysis
If we suspect….we measure ketones.
- diabetes mellitus
- negative energy balance (eg dairy cow)
What samples are used to measure ketones?
urine or milk
Is there a device used to measure the ketone BHB?
Handheld meters can measure BHB (mg/dL) (for use with whole blood). BHB usually measured in ruminants, sometimes in cats.
Not used often in cats
How does prolonged negative energy balance lead to ketosis?
- High metabolic energy demand + carb poor diet OR
- Insulin lack/resistance (diabetes mellitus)
–> Fats get catabolized for energy by undergoing beta-oxidation in mitochondria
–> then ketones accumulate (ketosis)
Increase in ketones is called
ketosis
Increase of ketones in blood, urine, or milk is called? and call lead to?
- Ketonemia
- ketonuria
- ketolactia
- Can lead to Titrational metabolic acidosis with a high AG
In small animals whats the most common cause of ketosis?
Ketosis with hyperglycemia due to untreated or poorly regulated diabeted mellitus leading to Titrational metabolic acidosis with a high AG. Its called Diabetic ketoacidosis.
In health the urine dipstick should be what for ketones?
negative
The urine dipstick detects what ketones?
acetone and acetoacetate but NOT BHB, you have to use a BHB meter with whole blood to measure that or send sample to referral lab
What are some causes of ketosis?
- Untreated or poorly regulated diabetes mellitus
- Diabetic ketoacidosis (DKA, complication of #1)
- Hypoglycemia of lactation (in cows) or pregnancy (in small ruminants, e.g., ewes) with
inadequate carb intake –> particularly when carrying twins - Endurance athletes with inadequate carb intake
Describe the mechanism of ketosis with hyperglycemia?
- Untreated or poorly
controlled diabetes
mellitus - Body “starving” (even if
patient is eating) because
cells cannot utilize glucose
without insulin! –> glucose cant get into cells so body uses fat for energy
What are the chronic findings of ketosis with hyperglycemia?
PU/PD, polyphagia, &
weight loss
(fasting hyperglycemia &
glucosuria)
- PU/PD due to osmotic diuresis –> extra renal causes of inability to concentrate urine
ketosis with hyperglycemia is a form of what negative energy balance?
chronic negative energy balance
due to insulin lack
(carbs available but can’t be
used by cells!)
Describe the mechanism of ketosis with hypoglycemia.
Think excess energy demand.
Happens when there is inadequete carbs in the diet.
- Lactational hypoglycemia
(a.k.a. Bovine ketosis)
Energy demand = lactation - Pregnancy hypoglycemia (a.k.a. Pregnancy toxemia) Energy demand = fetal growth
(small ruminants) - Endurance athletes
Energy demand =
sustained muscular
activity
Describe Milk fever (parturient paresis)
- Lactation (milk rich in calcium) –> Calcium loss –> Hypocalcemia –> Insulin activation impaired –> HYPERGLYCEMIA –> +/- Hyperglycemia due to stress
Describe Lactational Hypoglycemia (Bovine Ketosis)
- Poor feed quality or decreased food intake –> Lactation –> Increased tissue demand for glucose –> liver cant keep up –> HYPOGLYCEMIA & ketosis
T/F Lactational Hypoglycemia (Bovine Ketosis) and Milk fever (parturient paresis) are mutually exclusive.
False
Describe Pregnancy Hypoglycemia (Pregnancy “Toxemia”) in Sheep
- Poor feed quality or decreased food intake –> Carrying twins –> increased tissue demand for glucose –> Liver can’t keep up–> HYPOGLYCEMIA & ketosis
What is fructosamine?
- This is protein (mostly albumin) irreversibly bound to
glucose (“glycated protein”) - Reflects blood glucose over lifespan of the albumin
molecule (approx. 2 to 3 weeks)
How is fructosamine measured?
Measured in serum. Unit is micromol/L.
What is fructosamines value if we have sustained hyperglycemia vs transient?
Increased with sustained hyperglycemia (NOT
transient hyperglycemia due to fight/flight response).
How do we use fructosamine value?
- Transient, physiologic hyperglycemia (“stress”) vs.
true diabetes mellitus
Especially useful in cats! - Also used to monitor response to insulin treatment
in diabetics
An increased fructosamine suggests?
prolonged hyperglycemia
(i.e., untreated or poorly controlled diabetes mellitus)
What are some causes of altered fructosamine: Increased? Decreased?
Increased:
- Persistent hyperglycemia (diabetes mellitus)
- Hypothyroidism (in dogs)
Decreased:
- Persistent hypoglycemia
- Hypoproteinemia (hypoalbuminemia)
- Hyperthyroidism (in cats)
Things that affect albumin can cause fructosamine to also be affected
What lipids are commonly measured?
cholesterol, triglycerides, and NEFAs (non‐esterified fatty acids, a.k.a. free fatty acids)
What tests measure the lipoproteins in animals?
Note that there are no routinely available veterinary tests that directly measure plasma (or
serum) concentrations of the different lipoprotein classes (VLDL, LDL, etc.). You should be
able to infer which lipoproteins are increased in a patient based on cholesterol and triglyceride concentrations.
Cholesterol on a biochemical panel is composed of
“total cholesterol” (HDL + LDL + VLDL)
Remember, HDL and LDL are the most cholesterol-rich lipoproteins
How is cholesterol measured?
- Measured in plasma or serum
- Conventional unit is mg/dL.
- Ideally measured in a fasted sample (not typical in
veterinary medicine unless suspected lipid disorder being
investigated)
Triglycerides on a biochemical panel is composed of
Chylomicrons + VLDL
How are triglycerides measured?
- Measured in plasma or serum.
- Conventional unit is mg/dL.
- Ideally measured in a fasted sample (not typical in
veterinary medicine unless suspected lipid disorder being
investigated).
In a fasting sample triglycerides are
mostly VLDL (endogenous lipids)
In post-prandial sample triglycerides are
mostly chylomicrons (dietary lipids)
What is a common lipid interferent?
Lipemia
What is lipemia?
opaque, white, “milky” plasma
(or serum) due to excess lipid
(VLDL, chylomicrons, or both).
Error example: didn’t fast patient
Dz example:
- Endocrine disease
- Idiopathic hyperlipidemias
- Pancreatitis
How does lipemia interfere with TP? Hgb? MHC/MCHC?
Lipemia falsely increases TP as measured with
refractometer and falsely increases Hgb &
MCH/MCHC. It is an important interferent for
chemistry panels also.
How do labs deal with lipemia?
- Labs consider lipemia an interferent & deal with
lipemic samples by “ultrafugation”
(high‐speed centrifugation that allows removal of
lipid) - Ultrafugation done routinely in most labs
- If you are doing a medical assessment of [TG],
make sure lab knows you want them to measure
unaltered (lipemic) sample!
What is the refrigeration test?
- a crude assessment of chylomicron presence
- 16 hrs in the fridge —> positive test (cream layer formed)
Suggests chylomicron presence
not done often
is low cholesterol common?
no
Disorders causing low cholesterol
Hepatic insufficiency
(especially portosystemic shunting)
Protein‐losing enteropathy
(especially lymphangiectasia)
Hypoadrenocorticism (Addison’s Disease)
Certain cancers (histiocytic sarcoma, multiple myeloma)
What are NEFAs (Free fatty acids)?
- Biomarker of negative energy balance (like BHB!)
- Measured in plasma or serum.
Conventional unit is mEq/L.
(More common in research than in routine practice.) - Typically measured in dairy cattle –> increased NEFAs
suggests need for better management
