Lecture 26 - Lipids and Glucose Flashcards
- Hyperlipidemia = increase in _________ _______
- NOT synonymous with _______ –> refers to turbidity of sample due to lack of fasting before obtaining blood.
- Includes increased _________ ____/__ _______
- Hyperlipidemia = increase in circulating lipids
- NOT synonymous with lipemia –> refers to turbidity of sample due to lack of fasting before obtaining blood.
- Includes increased cholesterol and/or triglycerides
- Hypolipidemia = __________ in circulating lipids
- Includes decreased ___________ _____/____ _______
- Hypolipidemia = decrease in circulating lipids
- Includes decreased cholesterol and/or triglycerides
- Cholesterol → ?
hyper-/hypo- cholesterolemia
- Triglycerides →
hyper-/hypo- triglyceridemia
Lipid Functions
* Physical — - Fat is very important for _________, ________ insulation, _____ absorption. Some animals may have to accumulate more fat than others, depending on where they _____.
* Energy Source — _________ and ______ _____ are the most important.
* Structural components to cell membranes — _________, __________
* Substrates for ________ and other messengers
* Precursors for synthesis of ______ hormones, Vitamin _____, and ______ acids
* Immunity
Lipid Functions
* Physical — - Fat is very important for thermogenesis, thermal insulation, shock absorption. Some animals may have to accumulate more fat than others, depending on where they live.
* Energy Source — triglycerides and fatty acids
* Structural components to cell membranes — phospholipids, cholesterol
* Substrates for hormones and other messengers
* Precursors for synthesis of steroid hormones, Vitamin D, and bile acids
* Immunity
- Ingested dietary lipids are digested by pancreatic lipase and
emulsified by bile salts to monoglycerides and fatty acids
What are the 5 major types of lipids in plasma?
- Cholesterol <– important
- Cholesterol esters
- Triglycerides <– important
- Phospholipids
- Non-esterified fatty acids (NEFAs)
Triglycerides
* Comprises stored _____; metabolized for _______
* Most common and efficient form of energy storage in _________
* Comes from ______ or synthesized in the _____
Triglycerides
* Comprises stored fat; metabolized for energy
* Most common and efficient form of energy storage in mammals
* Comes from diet or synthesized in the liver
Cholesterol (free and esterified)
* Component of cell _________
Building blocks for _______ hormones
Used in synthesis of ?
Comes from ______ or synthesized in the _____
Cholesterol (free and esterified)
* Component of cell membranes
Building blocks for steroid hormones Used in synthesis of bile acids
Comes from diet or synthesized in the liver
Lipids of Importance: Non-Esterified Fatty
Acids (NEFAs)
Source of _______; metabolic _______ _______
A. Come from the ____ or mobilized from ___ stores
* Breakdown product of ____
B. Form ______ _____
* Enters the _____ cycle for ____ production or Converted into ? or Reformed into _____
C. Incorporated into ________
Lipids of Importance: Non-Esterified Fatty
Acids (NEFAs)
Source of energy; metabolic building blocks
* Come from the diet or mobilized from fat stores
* Breakdown product of TGs
* Form acetyl CoA
* Enters the TCA cycle for ATP production
* or Converted into ketone bodies
* or Reformed into TGs
* Incorporated into triglycerides
Lipids are ________ in water, so they travel attached to ________ that stabilize and solubilize them in the _______ phase of blood
Lipids are insoluble in water, so they travel attached to apoproteins that stabilize and solubilize them in the aqueous phase of blood
Proteins (________) + _______ = Lipoproteins
Proteins (apoproteins) + Lipids = Lipoproteins
Lipoproteins
* Large in size spherical in shape particles
* Hydrophobic core containing TGs and Chol
* Hydrophilic surface composed of phospholipids, free
Chol, apoproteins
Lipoproteins
* Large in size spherical in shape particles
* Hydrophobic core containing TGs and Chol
* Hydrophilic surface composed of phospholipids, free
Chol, apoproteins
Normal = clear
Milky appearance = lipemia
- presence of chylomicrons or VLDLs present aka animal has not been fasted enough. It does NOT tell us other changes
Lipemia
* Visibly hazy to white/opaque serum or plasma
* Lipemia indicates either chylomicrons or VLDLs
are present
- The feature of visible lipemia is related to particle size
(large lipoproteins block light transmission)
* Expect to see ↑ TGs +/- ↑ Chol on a chemistry
(both CM and VLDLs contain some cholesterol)
* Serum plasma with ↑Chol w/o ↑TGs will appear
normal (aka. not lipemic)
NOT caused by hypercholesterolemia alone
Lipemia effects in vitro
* CBC artifacts due to lipemia, which mostly occurs in vitro, the lipemia can be acting as a detergent on cell membranes –> RBC hemolysis
Results:
* Falsely elevated Hgb, MCH, MCHC
* Can also have falsely elevated plasma protein (using refractometer method)
* Indistinct demarcation line on refractometer scale may be interpreted as an increased value
Lipemia Interferes with
refractometer total protein reading
What are the lipemia effects in vitro?
[Marked as important]
When you have a lipemic sample?
Chemistry panel artifacts
* Hyperglycemia
* Hypercalcemia
* Hyperphosphatemia
* Hyperbilirubinemia
* Hyponatremia
* Hypokalemia
* Hypoproteinemia
- Hypoalbuminemia
What are the primary causes of Hyperlipidemia?
Hyperlipidemia: Either the increase of TG AND/OR Cholesterol
Primary causes
* Hereditary alterations in lipoprotein metabolism or production
What are the secondary causes of Hyperlipidemia?
Secondary causes
* Postprandial
* Diabetes Mellitus
* Acute necrotizing pancreatitis (dogs)
* Equine hyperlipidemia of ponies,
horses, and donkeys
* Hypothyroidism
* Hyperadrenocorticism
* Anorexia (horses)
* Obstructive cholestasis in dogs and cats
* Nephrotic syndrome and protein-losing
enteropathy
* Endotoxemia and inflammation
these causes are more common
Postprandial (after animal has eaten a meal)
A. Triglycerides are ______ to ________ _________
B. May seen mild ________ in _________
C. Dogs and Cats –_________-
* Occurs ___-___ hours after eating a _____ meal
* Transient and peaks at ___-___ hours
* Blood samples may appear _____ to ______
* Cleared by ___-____ h
D. Persistent hyperlipidemia: presence of ______ lipids in blood after a ____-hour fast
Postprandial (after animal has eaten a meal)
A. Triglycerides are mildly to markedly increased
B. May seen mild increases in cholesterol
C. Dogs and Cats –monogastrics-
* Occurs 1-2 hours after eating a meal
* Transient and peaks at 2-8 hours
* Blood samples may appear hazy to lipemic
* Cleared by 8-16 h
D. Persistent hyperlipidemia: presence of excess lipids in blood after a 12-hour fast
Diabetes mellitus
* Hyperlipidemia will be caused by a mild to moderate increase in TG or mild increase in cholesterol
* Lack of insulin release induced a defective VLDL processing the LPL (LPL inhibition)
* Hypertriglyceridemia is mildly to moderately
* Hypercholesterolemia is mild
* Seen in monogastric animals Cat, dogs, horses
* Complex pathogenesis, lipid profile can be highly variable.
Acute pancreatitis
* Hypertriglyceridemia is mild to moderate
* +/-Hypercholesterolemia –if does, tend to be Mild-
* Seen in Cat, dogs
* The mechanism might possibly be due to
↓ insulin production → ↓ LPL activity … and then inflammatory cytokines are also likely involved
* Cholesterol increases due to decreased biliary excretion (patient will have cholestasis), and increased hepatic production.
Equine hyperlipidemia Syndrome
* Mainly have Hypertriglyceridemia can be Marked!
* Seen in Shetland ponies, miniature horses, donkey mares
* Causes: Mainly caused by a decrease in feed consumption or negative energy balance; anorexia, obesity, pregnancy, lactation, renal failure, endotoxemia
Mechanism: negative energy balanceàmobilization of Fatty acids –> ↑ fatty acids to liver–> ↑ synthesis of TG in hepatocytes –> ↑VLDL (thus ↑ [TG])
Division of 2 groups = FYI info
Will have FATTY liver with cholestasis & decreased liver function
Hypothyroidism
* Lack of thyroid hormones (T3, T4) → induces a ↓LPL activity and also a ↓hepatic lipase activity
- These patients will have a ↑TGs, ↑-↑↑↑ Chol
- This is due to an Increase in cholesterol synthesis –> hypercholesterolemia
* +/- concurrent hypertriglyceridemia
Hyperadrenocorticism
* Causes by endogenous or exogenous steroids
* Usually will have hypercholesterolemia, but +/- hypertriglyceridemia
* Increased VLDL synthesis, and insulin resistance
Obstructive cholestasis
* Seen in dogs and cats
* Hypercholesterolemia without hypertriglyceridemia
* Increased cholesterol content of hepatocytes
- Reduced biliary cholesterol excretion
Nephrotic syndrome and PLN
* Hypercholesterolemia
* Hypoalbuminemia
* Proteinuria
* Ascites
* Hypercholesterolemia +/- hypertriglyceridemia
* Increased VLDL production, defective lipolysis, defective conversion of cholesterol to bile acids
In cases of Endotoxemia and inflammation
* Hyperlipidemia occurs due to reduced TG’s clearance from actions of Pro-inflammatory cytokines
Primary hyperlipidemia
Hereditary
* Hereditary alterations in lipoprotein metabolism or production
* Hyperlipidemia of Miniature Schnauzers
* Hypertriglyceridemia +/- hypercholesterolemia
* Also rarely seen in Briards, Beagles, Brittany Spaniels, and cats
* Mechanism unknown
Hypocholesterolemia
* Decreased cholesterol production
* Portosystemic shunts (dogs and cats)
* Liver insufficiency/failure
* Malabsorption/maldigestion: PLE
* Unknown / Multiple Mechanisms
* Hypoadrenocorticism (Addison’s)
Hypotriglyceridemia
* Significance is uncertain
* Maybe associated with severe malnutrition
Glucose metabolism
* Sources of blood glucose
* Main source: Intestinal absorption of carbohydrates
* Other source: Hepatic production (hepatocytes and myocytes) via
- Gluconeogenesis = formation of lyocen from non-carb soures, such as AA and lactate
- Glycogenolysis = glycogen braks down into glucose.
* Kidney production (minor)
- Blood glucose levels are dependent upon:
- Time since last meal
- Hormonal influences
- Utilization of glucose by peripheral tissues
–> Hormonal regulation: [Important]
A. Insulin – decreases BG by:
* Promoting tissue glucose uptake
* inhibiting gluconeogenesis
* Promoting glycogen synthesis
B. Glucagon – increases BG by:
* Promoting gluconeogenesis
* Promoting glycogenolysis
* Inhibiting glycogen synthesis
A. Glucocorticoids – increase BG by:
* Antagonizing insulin – inducing “insulin resistance”
* Promoting gluconeogenesis and glucagon release
B. Catecholamines – increase BG by:
* Inhibiting insulin secretion
* Promoting glycogenolysis
C. Growth hormone – increases BG by:
* Inhibiting insulin action
* Promoting gluconeogenesis
What are the causes of hyperglycemia?
CAUSES OF HYPERGLYCEMIA
1. Postprandial
2. Excitement/fright (epinephrine)
3. Diabetes mellitus
4. Endogenous or exogenous corticosteroids
5. Pancreatitis
6. Drugs/chemicals
- Postprandial
* Blood glucose increases for 2-4 hours after a meal in monogastrics
* Cleared by 12 hours
* May be prolonged in hepatic disorders (reduced glycogenesis)
- Excitement/fright (epinephrine)
* Promotes glycogenolysis
* Typically mild hyperglycemia
* Dogs: glucose usually < 150 mg/dL
- Diabetes mellitus
* Type 1: decreased insulin production (dogs)
* Type 2: insulin resistance (cats)
- Endogenous or exogenous corticosteroids
* Hyperadrenocorticism
* Corticosteroids antagonize insulin –> decreased glucose uptake and utilization (decreased glycogenolysis)
- Pancreatitis
* Decreased insulin production –> decreased glucose uptake and utilization
- Drugs/chemicals
* Ethylene glycol
* Glucose-containing fluids (e.g. Dextrose)
* Ketamine
* Phenothiazine
* Xylazine
What are the causes of Hypoglycemia?
CAUSES OF HYPOGLYCEMIA
* Excessive insulin administration (exogenous)
* Excessive endogenous insulin
- Insulinoma [Marked as important = exam question]
* Hypoadrenocorticism
* Hepatic disease
* Excessive glucose utilization
- Sepsis
- Pregnancy
- Neoplasia
- Extreme physical exertion
- Reduced glucose intake or inadequate gluconeogenesis can also lead to Hypoglycemia.
- Neonates (hepatic immaturity)
- Severe malnutrition
- Severe malabsorption
- Starvation
- Ketosis in cattle
- Artifactual hypoglycemia (pseudohypoglycemia) caused by manipulation of samples. If we do not run our serum in a timely manner, we can see this.
- Prolonged contact of serum with erythrocytes in vitro
- RBCs utilize glucose in the serum for metabolism
- May see concurrent in vitro hemolysis
What drugs/chemicals can cause hypoglycemia?
- Drugs/chemicals
- Xylitol toxicosis –> severe hepatic insuffiency; mechanism is still unknown
- Ethanol
- Mitotane
- Salicylates
