Lecture 26 - Lipids and Glucose

Question 1

• Hyperlipidemia = increase in _________ _______
• NOT synonymous with _______ –> refers to turbidity of sample due to lack of fasting before obtaining blood.
• Includes increased _________ ____/__ _______

Answer 1

• 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

Question 2

• Hypolipidemia = __________ in circulating lipids
• Includes decreased ___________ _____/____ _______

Answer 2

• Hypolipidemia = decrease in circulating lipids
• Includes decreased cholesterol and/or triglycerides

Question 3

• Cholesterol → ?

Answer 3

hyper-/hypo- cholesterolemia

Question 4

• Triglycerides →

Answer 4

hyper-/hypo- triglyceridemia

Question 5

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

Answer 5

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

Question 6

• Ingested dietary lipids are digested by pancreatic lipase and
  emulsified by bile salts to monoglycerides and fatty acids

Question 7

What are the 5 major types of lipids in plasma?

Answer 7

• Cholesterol <– important
• Cholesterol esters
• Triglycerides <– important
• Phospholipids
• Non-esterified fatty acids (NEFAs)

Question 8

Triglycerides
* Comprises stored _____; metabolized for _______
* Most common and efficient form of energy storage in _________
* Comes from ______ or synthesized in the _____

Answer 8

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

Question 9

Cholesterol (free and esterified)
* Component of cell _________
Building blocks for _______ hormones
Used in synthesis of ?
Comes from ______ or synthesized in the _____

Answer 9

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

Question 10

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 ________

Answer 10

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

Question 11

Lipids are ________ in water, so they travel attached to ________ that stabilize and solubilize them in the _______ phase of blood

Answer 11

Lipids are insoluble in water, so they travel attached to apoproteins that stabilize and solubilize them in the aqueous phase of blood

Question 12

Proteins (________) + _______ = Lipoproteins

Answer 12

Proteins (apoproteins) + Lipids = Lipoproteins

Question 13

Lipoproteins
* Large in size spherical in shape particles
* Hydrophobic core containing TGs and Chol
* Hydrophilic surface composed of phospholipids, free
Chol, apoproteins

Answer 13

Lipoproteins
* Large in size spherical in shape particles
* Hydrophobic core containing TGs and Chol
* Hydrophilic surface composed of phospholipids, free
Chol, apoproteins

Question 14

Question 15

Question 16

Answer 16

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

Question 17

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

Question 18

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

Question 19

Lipemia Interferes with
refractometer total protein reading

Question 20

What are the lipemia effects in vitro?
[Marked as important]

When you have a lipemic sample?

Answer 20

Chemistry panel artifacts
* Hyperglycemia
* Hypercalcemia
* Hyperphosphatemia
* Hyperbilirubinemia
* Hyponatremia
* Hypokalemia
* Hypoproteinemia
- Hypoalbuminemia

Question 21

What are the primary causes of Hyperlipidemia?

Answer 21

Hyperlipidemia: Either the increase of TG AND/OR Cholesterol

Primary causes
* Hereditary alterations in lipoprotein metabolism or production

Question 22

What are the secondary causes of Hyperlipidemia?

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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.

Answer 24

Question 25

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.

Question 26

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

Question 27

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

Question 28

Hyperadrenocorticism * Causes by endogenous or exogenous steroids * Usually will have hypercholesterolemia, but +/- hypertriglyceridemia * Increased VLDL synthesis, and insulin resistance

Question 29

Obstructive cholestasis * Seen in dogs and cats * Hypercholesterolemia without hypertriglyceridemia * Increased cholesterol content of hepatocytes - Reduced biliary cholesterol excretion

Question 30

Nephrotic syndrome and PLN * Hypercholesterolemia * Hypoalbuminemia * Proteinuria * Ascites * Hypercholesterolemia +/- hypertriglyceridemia * Increased VLDL production, defective lipolysis, defective conversion of cholesterol to bile acids

Question 31

In cases of Endotoxemia and inflammation * Hyperlipidemia occurs due to reduced TG's clearance from actions of Pro-inflammatory cytokines

Question 32

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

Question 33

Question 34

Hypocholesterolemia * Decreased cholesterol production * Portosystemic shunts (dogs and cats) * Liver insufficiency/failure * Malabsorption/maldigestion: PLE * Unknown / Multiple Mechanisms * Hypoadrenocorticism (Addison’s)

Question 35

Hypotriglyceridemia * Significance is uncertain * Maybe associated with severe malnutrition

Question 36

Question 37

Question 38

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)

Question 39

* Blood glucose levels are dependent upon: * Time since last meal * Hormonal influences * Utilization of glucose by peripheral tissues

Question 40

--> 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

Question 41

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

Question 42

What are the causes of hyperglycemia?

Answer 42

CAUSES OF HYPERGLYCEMIA 1. Postprandial 2. Excitement/fright (epinephrine) 3. Diabetes mellitus 4. Endogenous or exogenous corticosteroids 5. Pancreatitis 6. Drugs/chemicals

Question 43

1. 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)

Question 44

2. Excitement/fright (epinephrine) * Promotes glycogenolysis * Typically mild hyperglycemia * Dogs: glucose usually < 150 mg/dL

Question 45

3. Diabetes mellitus * Type 1: decreased insulin production (dogs) * Type 2: insulin resistance (cats)

Question 46

4. Endogenous or exogenous corticosteroids * Hyperadrenocorticism * Corticosteroids antagonize insulin --> decreased glucose uptake and utilization (decreased glycogenolysis)

Question 47

5. Pancreatitis * Decreased insulin production --> decreased glucose uptake and utilization

Question 48

6. Drugs/chemicals * Ethylene glycol * Glucose-containing fluids (e.g. Dextrose) * Ketamine * Phenothiazine * Xylazine

Question 49

What are the causes of Hypoglycemia?

Answer 49

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

Question 50

* Reduced glucose intake or inadequate gluconeogenesis can also lead to Hypoglycemia. * Neonates (hepatic immaturity) * Severe malnutrition * Severe malabsorption * Starvation * Ketosis in cattle

Question 51

* 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

Question 52

What drugs/chemicals can cause hypoglycemia?

Answer 52

* Drugs/chemicals * Xylitol toxicosis --> severe hepatic insuffiency; mechanism is still unknown * Ethanol * Mitotane * Salicylates