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Metabolism
Physio II
346
Physiology
Professional
10/16/2010

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Term
What is the purpose of food intake, digestion, & absorption?
Definition
Supply of food mol's (Glc, aa, FAs)
Term
What is the fate of food mol's?
Definition
Energy to sustain life processes; Storage; Building Blocks
Term
Give examples of food mol's as energy to sustain life processes.
Definition
Active Transport; Synthesis/Replication; Contractions; Heat Production/Thermoregulation
Term
Give examples of food mol's as storage.
Definition
Fat; Glycogen; Protein Pool
Term
Give examples of food mol's as building blocks.
Definition
Membranes; Muscle Proteins; Hormones
Term
What does the main direction of metabolism depend on?
Definition
Fuel Availability
Term
How many C is hexose?
Definition
6
Term
How many C is pyruvate?
Definition
3
Term
How many C is glycerol?
Definition
3
Term
How many C is acetyl group?
Definition
2
Term
How many C is carbon dioxide?
Definition
1
Term
What are the main directions of metabolism?
Definition
Energy Storage (Anabolic); Energy Mobilization (Catabolic); Conversions
Term
How are fuel stores interconnected?
Definition
"Spinal Column" of C compounds by a multitude of p'ways
Term
What are the directions of metabolic p'ways controlled by?
Definition
Hormones; NS; ATP/ADP Formation; Accumulation of intermediates/end-products
Term
When is hyperglycemia normal?
Definition
After a meal
Term
Normoglycemia
Definition
80-120mg/dl
Term
Glc is the _____ fuel in all tissues, but the _____ fuel in _____ tissues.
Definition
Preferred; Essential; Glc-dependent
Term
Give some examples of Glc-dependent tissues.
Definition
NS, RBCs, Retina, Renal Medulla, Gonads, Fetus, Lactation
Term
Hypoglycemia
Definition
<80mg/dl
Term
Hyperglycemia
Definition
>120mg/dl
Term
Below normal glucose levels --> _____
Definition
Irritability
Term
<80 mg Glc/dl --> _____
Definition
Seizures
Term
<50 mg Glc/dl --> _____
Definition
Coma
Term
<20 mg Glc/dl --> _____
Definition
Death
Term
What tissue suffers 1st in hypoglycemia?
Definition
Nervous tissue
Term
How is maintenance of blood Glc levels achieved?
Definition
Via eating/digesting/absorbing Glc; Storing (glycogenesis) & Releasing stored Glc (Glycogenolysis); Synthesis of new Glc from precursors (Gluconeogenesis)
Term
What tissue is the greatest consumer of Glc?
Definition
NS (~60%)
Term
What hormone(s) combat(s) hypoglycemia?
Definition
Glucagon, Cortisol, Epinephrine
Term
What hormone(s) combat(s) hyperglycemia?
Definition
Insulin
Term
How does Glc enter cells?
Definition
FD
Term
FD is ______-dependent & req's _____.
Definition
Concentration; Glc Transporters (GLUTs)
Term
Is the liver Glc-dependent?
Definition
No
Term
What tissues have GLUTs as part of their cm? When is FD active?
Definition
Glc-dependent tissues + Liver; Always
Term
What tissues have GLUTs stored intracellularly? When is FD active?
Definition
Glc-independent tissues (m., fat); Only when insulin present
Term
What is secreted in response to hyperglycemia? What does this allow?
Definition
Insulin; Fusion of GLUTs w/ cm
Term
In hyperglycemia, what cells have access to blood Glc?
Definition
All cells
Term
In hypoglycemia, what cells have access to blood Glc?
Definition
Only Glc-dependent cells
Term
In hypoglycemia, what do Glc-independent cells use for fuel?
Definition
Alternate Fuels (FFAs)
Term
Glc Trapping: ____. Is it reversible?
Definition
Upon cell entry, Glc is phosphorylated to G6P; Glc can't diffuse out of cells; Irreversible except in liver, kidney, & GI cells
Term
Can G6P pass through GLUTs?
Definition
No (too large)
Term
What does the fate of Glc depend on?
Definition
Body's Energy Situation
Term
Describe energy gain from Glc in aerobic conditions.
Definition
Glycolysis --> Acetyl CoA --> Krebs Cycle --> ETC
Term
Describe energy gain from Glc in anaerobic conditions.
Definition
Glycolysis & Lactic Acid formation
Term
Describe energy storage of Glc.
Definition
Glycogen; Conversion of Glc into FAs
Term
Where does glycolysis occur?
Definition
Cytoplasm
Term
What is glycolysis?
Definition
Splitting of a C6 into 2 C3 (Pyruvates)
Term
What is the purpose of glycolysis?
Definition
Prepare Glc for entry into Mt; Some ATP (2/Glc) generated; Some of Glc's chemical energy transferred/stored via H in form of NADH/H+ for entry into ETC
Term
After glycolysis, pyruvate enters _____ (structure).
Definition
The mitochondrion
Term
What happens to pyruvate in Mt?
Definition
Decarboxylated to acetyl group; Acetyl group attaches to Coenzyme A (Acetyl CoA) which is ready to enter Krebs Cycle
Term
Where does the Krebs Cycle occur?
Definition
Mitochondrion
Term
What is another name for the Krebs Cycle?
Definition
Citric Acid Cycle
Term
What is the Krebs Cycle?
Definition
Sequence of rxn's in which Acetyl group is degraded to 2 CO2, 1 ATP, 8 H atoms (NADH/H+)
Term
Acetyl CoA combines w/ ____ to form ____ in Krebs Cycle.
Definition
OAA; Citric Acid
Term
How many C is OAA?
Definition
4
Term
OAA
Definition
Oxaloacetate
Term
What happens to Citric Acid in the Krebs Cycle?
Definition
Undergoes a sequence of decarboxylations & dehydrations ending again in OAA
Term
What does the Krebs Cycle start & end w/?
Definition
OAA
Term
What is the most important outcome of Glc oxidation in the Krebs Cycle?
Definition
Making energy-rich H ions available for subsequent oxidation in ETC
Term
ETC
Definition
Electron Transport Chain
Term
In addition to its most important function, what is the Krebs Cycle involved in?
Definition

Synthesis & Combustion of FA & aa

Synthesis of Glc

Term
What is the ETC?
Definition
Series of e- carriers integrated into inner Mt membrane, in which the energy stored in NADH/H+ is transferred to ATP
Term
What is another name for ETC?
Definition
Oxidative Phosphorylation
Term
What does Ox Phos lead to?
Definition
Generation of ATP, Regeneration of NAD, Formation of H2O out of remaining protons & O2
Term
What is NAD needed for?
Definition
Glycolysis & Citric Acid Cycle
Term
Describe what happens to carbohydrates in anaerobic conditions/what would happen w/o anaerobic metabolism.
Definition
Lack of O2, NADH/H+ pile up, reduce Krebs Cycle activity (product inhibition), Pyruvate will pile up/could inhibit glycolysis, ATP production would seize totally
Term
What must happen to keep glycolysis open in anaerobic conditions?
Definition
Pyruvate must be removed & NAD regenerated via Lactate
Term
What reduces pyruvate to lactic acid?
Definition
Lactate Dehydrogenase
Term
What does Lactate Dehydrogenase do? Why is this important?
Definition
Reduces Pyruvate to Lactic Acid, thus regenerating NAD; Some ATP can still be generated via anaerobic glycolysis
Term
What is the main energy p'way in RBCs?
Definition
Anaerobic Glycolysis
Term
What happens to lactate?
Definition
Must be removed; Diffuses rapidly into circulation; Utilized by tissues when O2 available (heart m), where LDH converts it back to pyruvate --> aerobic p'way; Enters Gluconeogenesis in liver to produce new Glc
Term
LDH
Definition
Lactate Dehydrogenase
Term
Where is LDH present?
Definition
Muscle, Liver, RBCs, GI tract, Kidneys
Term
How does tissue damage relate to LDH?
Definition
Tissue Damage --> Leakage of LDH into plasma --> Diagnostic Significance
Term
What are 2 events that can lead to increased plasma LDH?
Definition
Hemolysis & Muscle injury
Term
What happens if excess Glc is available?
Definition
Stored in liver & m. as glycogen (glucose polymer) for later use (Glycogenesis)
Term
What is the advantage of glycogenesis?
Definition
Glycogen precipitates & is not osmotically active
Term
What are the main glycogen storing organs? Max %?
Definition
Liver, 6%; Muscle, 1%
Term
When sm Glc-chains have formed in alpha-1-4 linkages, what transfers groups of 6 Glc units as side chains in alpha-1-6 linkages? What does this form?
Definition
Branching enzyme; Branched carbohydrate
Term
What happens if Glc is needed for energy?
Definition
Glycogen broken down to G6P (Glycogenolysis)
Term
What is req'd for Glycogenolysis?
Definition
De-Branching Enzyme
Term
What is req'd to release free Glc from G6P into circulation?
Definition
Phosphatase
Term
Where is phosphatase present?
Definition
Liver & Kidney cells (Not muscle cells)
Term
What does hepatic glycogenolysis do?
Definition
Increases blood Glc levels
Term
What does muscle glycogenolysis do?
Definition
Increases muscle energy supply
Term
What stimulates glycogenesis? What stimulates glycogenolysis?
Definition
Insulin; Glucagon, Cortisol, Epi
Term
How does Glc diffuse out of the liver?
Definition
Through GLUTs
Term
What happens when blood Glc runs low & Glycogen stores are exhausted?
Definition
Glc must be synthesized to supply Glc-dependent tissues (Gluconeogenesis)
Term
Where does Gluconeogenesis occur?
Definition
Liver & Kidneys
Term
What are precursors of Gluconeogenesis?
Definition
Many aa's, Lactate, Propionate from fermentation, Glycerol from triglyceride breakdown
Term
What happens to precursors of Gluconeogenesis? What is an exception?
Definition
Enter Krebs Cycle & are pulled into cytoplasm as OAA/Malate to enter Gluconeogenesis; Glycerol
Term
Both ____ & ____ contain phosphatases & release _____ into circulation.
Definition
Liver & Kidney; Free Glc
Term
What % of Gluconeogenesis is the Liver responsible for? Kidney?
Definition
80%; 20%
Term
Dietary fats consist mostly of:
Definition
Triglycerides, Phospholipids, Cholesterol
Term
What are lipids utilized for?
Definition
Energy gain, Energy storage for later use, Building blocks (membranes), Hormones & Bile acids
Term
Are lipids hydrophilic or hydrophobic?
Definition
Hydrophobic
Term
Lipids must be made ____ for transport in plasma.
Definition
Soluble
Term
How are lipids made soluble for transport?
Definition
Combining w/ proteins --> Lipoproteins
Term
Lipoproteins
Definition
Aggregations of lipids surrounded by a shell of hydrophilic proteins, phospholipids, & specific R proteins (Apoproteins)
Term
What are the 2 classes of lipoproteins? (What are they formed by?)
Definition
Chylomicrons (Sm intestinal enterocytes after absorption of lipids); VLDLs (liver cells after production of new lipids)
Term
VLDL
Definition
Very Low Density Lipoprotein
Term
What do Chylomicrons/VLDLs do?
Definition
Circulate; their Apoproteins bind endothelial R's & activate endothelial LPLs
Term
LPL
Definition
Lipo-protein-Lipase
Term
What do LPLs do?
Definition
Dissolve shells of Lipoproteins & Hydrolyze Triglycerides --> FFAs + Glycerol Diffuse into respective tissues for Storage or Energy
Term
What is the fat storage form of lipids? How is this storage accomplished?
Definition
Triglycerides; After diffusion into Adipocytes, triglycerides reform
Term
Lipolysis
Definition
Release of stored fat
Term
When is lipolysis initiated?
Definition
When circulating fuel levels (Glc) are low & Energy is needed
Term
Describe lipolysis.
Definition
HSL hydrolyzes stored triglycerides --> FFAs & Glycerol diffuse back into circulation; FFAs bind to plasma Albumin for transport = NEFAs, which deliver FFAs to tissues for energy gain
Term
HSL
Definition
Hormone-Sensitive Lipase
Term
In fat tissues, insulin stimulates _____ & inhibits _____. (substances)
Definition
LPL; HSL
Term
What does binding of FFAs to Albumin prevent?
Definition
Re-condensation
Term
How do FFAs & Glycerol diffuse into circulation?
Definition
Down a concentration gradient
Term
What is a Non-Esterified FA?
Definition
Albumin + 1-3 FAs
Term
What does HSL respond to?
Definition
Insulin, Glucagon, Cortisol, Epi, etc.
Term
Is fat stored in muscle cells? How do muscle cells access FFAs? What do they use them for?
Definition
No; Chylomicrons, VLDLs, NEFAs; Energy
Term
How are FFAs utilized for energy gain?
Definition
By entering Beta-Oxidation, which releases Acetyl groups for use in the Krebs Cycle/ETC
Term
Where can FFAs originate from?
Definition
NEFAs, VLDLs, Chylomicrons
Term
What do FFAs do after entering a cell?
Definition
Enter Mt & undergo progressive release of C2 segments as Acetyl CoA = Beta Oxidation
Term
What happens to Acetyl CoA from Beta oxidation?
Definition
Enters Krebs Cycle for complete oxidation & ATP generation in ETC
Term
Where does Glycerol diffuse?
Definition
Into active tissues
Term
What happens to Glycerol after it diffuses into active tissues?
Definition
Can enter Glycolysis --> Krebs Cycle --> ETC when ATP is needed; or enter Gluconeogenesis when Glc is needed
Term
What is Glycerol an intermediate of?
Definition
Glycolytic p'way
Term
d/o ______, Glycerol can either _____ or _____.
Definition
Which Hormones are present; --> Energy production; --> Gluconeogenesis
Term
Lipogenesis
Definition
Making new fat out of excess energy; Excess Glc & aa's can be converted into FFAs
Term
Where does Lipogenesis occur?
Definition
Liver, Fat Tissue, Mammary Gland
Term
When is lipogenesis activated?
Definition
When stores of ATP, Glycogen, & Labile Protein are full & Glc & aa's are still available
Term
What happens in Lipogenesis?
Definition
FFAs are condensed into TGs for storage (adipocytes only) or secreted into milk
Term
Is the liver a fat storage site?
Definition
No
Term
Describe the Liver's role in Lipogenesis.
Definition
Packs newly produced TGs into Lipoproteins = VLDLs --> Exocytosis into circulation --> Fat Tissue LPLs hydrolyze VLDLs --> Fat storage
Term
What stimulates Lipogenesis?
Definition
Insulin
Term
What does the Liver do during Lipolytic phases?
Definition
Readily takes up FFAs from NEFAs w/o utilizing all for energy (acts like a "fat sponge"); Makes FFAs from NEFAs available to other tissues as VLDLs & Ketone Bodies
Term
What is the advantage of VLDL formation?
Definition
Albumin binding capacity for FFA is limited --> Liver increases lipid transport capacity via VLDLs
Term
Describe VLDL formation.
Definition
Many FFAs are resynthesized into TGs & packaged into VLDLs which are released into circulation & taken up by tissues via their endothelial LPLs for energy gain via beta oxidation
Term
Is insulin present in lipolytic phase?
Definition
No
Term
What are Ketone Bodies?
Definition
Acetyl groups condensed into Acetoacetic Acid, Acetone, & Beta-Hydroxybutyrate; A physiological & very important energy source for many tissues when Glc levels are low
Term
Many FFAs enter B-Oxidation & _____ accumulates.
Definition
Acetyl CoA
Term
Why does Acetyl CoA accumulate in B-Oxidation?
Definition
as liver ATP stores fill, Krebs Cycle activity declines; OAA/Malate are withdrawn from Krebs Cycle for Gluconeogenesis
Term
What happens to accumulating Acetyl CoA groups from B-Oxidation?
Definition
Condense into Ketone Bodies
Term
What is another name for Ketone Bodies?
Definition
Ketoacids
Term
Is hepatic KB formation reversible?
Definition
no
Term
Where are hepatic KBs released? What happens to them?
Definition
Into blood --> Taken up by other tissues --> Hydrolyzed back to Acetyl CoA --> Enter Krebs Cycle/ETC for energy gain
Term
What is an advantage of KB formation?
Definition
Liver B-oxidizes FFA for other tissues & supplies an easily usable hydrophilic substrate for energy gain, e.g. to neurons & mm.
Term
What % of body solids are proteins?
Definition
75%
Term
What are 2 types of proteins?
Definition
Essential & Non-essential aa
Term
What are the functions of proteins?
Definition
Structural components, Contractile elements, Transporters, Enzymes & Hormones, Hemostatic Factors, Ab's
Term
How many aa are essential?
Definition
8 (9 in cats)
Term
What is an amino acid?
Definition
Carb + amino group
Term
How are aa absorbed from circulation?
Definition
FD or AT (into liver & m.)
Term
Describe what happens after aa's are absorbed from circulation.
Definition
Cell entry --> Peptides + Proteins are formed = Labile Protein Pool = Temporary storage form
Term
What is the function of the Labile Protein Pool?
Definition
Temporary Storage Form/no function
Term
What happens to the Labile Protein Pool?
Definition
Rapid Proteolysis possible via lysozomal enzymes     --> constant turnover btw plasma aa's/pool; Functional proteins are formed out of Labile pool
Term
What is alpha-ketoglutarate?
Definition
An intermediate of the Krebs Cycle
Term
When are most aa's metabolized?
Definition
After deamination to Keto-Analogs
Term
Describe deamination of aa's.
Definition
Removal of amino group to their respective keto-analog (reversible)
Term
What is the keto-analog of Alanine?
Definition
Pyruvate
Term
What is the keto-analog of Glutamate?
Definition
alpha-ketoglutarate
Term
What happens to Keto-analogs?
Definition
Enter p'ways of Carbohydrate metabolism
Term
What are the 5 options of keto-analogs in carb metabolism?
Definition
Enter Krebs cycle for energy gain; Enter KC & are drawn out as Malate/OAA for gluconeogenesis; Enter KC & are shunted via Citrate into Lipogenesis; Form KBs via excess acetyl coA; intermediates leave KC for amination to NEFAs
Term
In which option for keto-analogs is the amino group utilized?
Definition
Amination to NEFAs (Detox)
Term
What keto-analog is a key branching point of metabolism?
Definition
Pyruvate
Term
Deamination of aa to keto analogs involves release of _____.
Definition
Amino Groups
Term
Where are the amino groups released during deamination transferred?
Definition
To alpha-ketoglutarate to form Glutamate, or to Pyruvate to form Alanine
Term
After amino groups are transferred to keto-analogs, what happens?
Definition
Glutamine/Alanine then transfer amino groups to other compounds (e.g. aa synthesis), which involves various amino-transferases
Term
Where are amino transferases found?
Definition
in m. tissue & liver
Term
Name 2 amino-transferases. What value do they serve?
Definition
ALT (Alanine at) & AST (Aspartate at); Increase in plasma levels of these enzymes are of diagnostic value
Term
What happens to excess amino groups that are not needed?
Definition
Liver converts excess potentially toxic ammonia to Urea --> Renal excretion
Term
Hepatic Encephalopathy:
Definition
Accumulation of NH3 (due to liver failure) --> Interference w/ GABA a/o Glutamate NTs --> Neurotoxicity --> Depression, Neurological Deficits, Coma, Death
Term
What does accumulation of NH3 do to GABA?
Definition
Enhances its function (which is inhibitory)
Term
What are some signs of hepatic encephalopathy?
Definition
Uncontrolled pacing, circling, lethargy, depression, neurological deficits, coma, death
Term
Where is ALT present? AST?
Definition
Liver; Liver & m.
Term
What amino-transferase is liver-specific in sm animals?
Definition
ALT
Term
ALT increases in parallel to ______.
Definition
Amount of liver damage
Term
AST deamination --> ____
Definition
OAA
Term
What is the detox product of ammonia?
Definition
Urea
Term
What happens to dietary carbs in ruminants?
Definition
Essentially all fermented to VFAs (Acetate, Butyrate, Propionate)
Term
In ruminants, how much Glc/maltose reaches the SI for absorption?
Definition
Very little
Term
What are the basic Glc demands in ruminants compared to monogastrics?
Definition
The same or Higher, e.g. during lactation
Term
Ruminants are potentially _____.
Definition
Hypoglycemic
Term
What do ruminants depend on to maintain adequate blood Glc levels?
Definition
Gluconeogenesis (entirely)
Term
Describe gluconeogenesis in ruminants.
Definition
Always switched on; Provides 90-100% of Blood Glc
Term
Normoglycemia (Ruminant)
Definition
40-80 mg/dl
Term
What happens if a ruminant's blood Glc drops to 20 mg/dl?
Definition
Can be tolerated for a few hours w/ no major consequence
Term
What are the main Glc precursors in ruminants? (%?)
Definition
Propionate (70%), aa's (20%), Lactate/Pyruvate/Glycerol
Term
Where do aa's as precursors to Glc come from in ruminants?
Definition
Digestion of microbes
Term
How many C is propionate?
Definition
3
Term
Propionate is extracted by _____ (Ruminants)
Definition
the liver
Term
How does propionate enter the KC? (Ruminants)
Definition
As Succinate (carboxilation req's Vit B12, which contains Co)
Term
How many C is succinate? (Ruminants)
Definition
4
Term
How does propionate leave the Mt? (Ruminants)
Definition
As Malate to enter Gluconeogenesis
Term
What is the fate of propionate in ruminants?
Definition
Propionate --> Glc
Term
(Ruminants) Glc is released into circulation for:
Definition
Glc-dependent tissues (brain); Fetus; Milk production; Fat tissue to provide glycerol
Term
What does chronic Co deficiency in soil cause in cows? Where is this a problem?
Definition
Unthriftiness; Infertility; Florida & Australia
Term
(Ruminants) What is the fate of acetate?
Definition
Absorbed by all tissues except liver; Enters KC as Acetyl CoA for energy gain (ETC) = major energy supplier; Enters Lipogenesis as Acetyl CoA in mammary gland & fat tissue
Term
How many C is acetate?
Definition
2
Term
(Ruminants) Acetate --> _____
Definition
ATP (primarily) & Lipogenesis (secondarily)
Term
What is the major VFA from fermentation?
Definition
Acetate
Term
How many C is butyrate?
Definition
4
Term
(Ruminants) What is the fate of Butyrate?
Definition
Partly converted in rumen epithelium & after liver uptake to KBs (irreversible)
Term
(Ruminants) Butyrate --> _____
Definition
KB's --> ATP/Lipogenesis
Term
What are KBs utilized for in ruminants?
Definition
Utilized in peripheral tissues for energy gain after entering KC as Acetyl CoA; Contribute to lipogenesis via Acetyl CoA in fat tissues & mammary gland
Term
What can cause metabolic disorders?
Definition
Endocrine disorders; Nutritional deficiencies; Genetic defects in enzymes or transport proteins
Term
Give examples of endocrine disorders that can cause metabolic disorders.
Definition
Diabetes Mellitus; Cushing's; Thyroids
Term
Give examples of nutritional deficiencies that can cause metabolic disorders.
Definition
Minerals, Trace elements, Vitamins, Lack of fuels, Lack of essential aa's; Fasting/Starvation
Term
Give examples of genetic disorders that cause metabolic disorders.
Definition
Glycogen storage dz's; PSSM
Term
PSSM
Definition
Polysaccharide Storage Myopathy
Term
In PSSM, what do CS d/o?
Definition
Cause
Term
What are some CS of PSSM?
Definition
Energy deficiency in mm., Hepatomegaly, Cardiomegaly, Hypoglycemia, Lactic Acidosis, Exertional Rhabdomyolysis (m. necrosis)
Term
What are the various forms of PSSM?
Definition
Glycogen is formed, but can't be broken down b/o enzyme defect; Abnormal glycogen type formed & stored, but can't be mobilized; Too much glycogen formed & released too fast
Term
What would cause glycogen to be formed but not broken down? Not to be released?
Definition
Enzyme defect (debranching enzyme); Hepatic G6Phosphatase deficiency
Term
Where can an abnormal glycogen type be formed & stored (& not mobilized)?
Definition
Liver, Muscle, Heart
Term
What can cause too much glycogen to be formed & released too fast?
Definition
Hypersensitivity to Insulin
Term
What is essential to maintain basal metabolism?
Definition
Constant energy supply
Term
What must be kept constant to supply vital tissues?
Definition
Glc levels
Term
What are some problems w/ energy supply/Glc levels?
Definition
Irregular food intake/absorption; Gut not a nutrient storage organ; Basic energy needs constant
Term
What is the solution for the need for constant energy supply/Glc levels?
Definition
Whole body metabolism is dynamic & constantly switches between 2 (3) major stages
Term
What are the 2 (3) major stages of metabolism?
Definition
Absorptive Phase; Post-Absorptive Phase; (Fasting)
Term
Absorptive Phase = _____ --> _____
Definition
Excess Energy --> Storage
Term
Post-Absorptive Phase = _____ --> _____
Definition
Low energy --> Mobilization
Term
Fasting = _____ = _____
Definition
Survival; Continued mobilization
Term
Absorptive Phase, Post-Absorptive Phase, (& Fasting) contribute to __________.
Definition
Fuel Homeostasis
Term
Fuel homeostasis is determined largely by ______.
Definition
Availability of blood Glc
Term
The _____ of fuels, esp. _____, stimulate the release of metabolic regulators (=_____), which control the flow or direction of _____.
Definition
Availability/Unavailability; Glc; Hormones; Metabolic p'ways
Term
What is included in a mixed meal?
Definition
Protein, Carbs, & Fat
Term
What is another name for the Absorptive Phase?
Definition
Post-Prandial Phase
Term
How long is the time of active digestion & absorption of fuels?
Definition
~3-5 hrs
Term
During the absorptive phase, blood levels of _____ increase. (mol's)
Definition
Glc, aa, Chylomicrons
Term
During the absorptive phase, _____ stimulates the pancreas to release _____ & inhibits release of _____.
Definition
Hyperglycemia; Insulin; Glucagon
Term
What is the insulin/glucose ratio in the absorptive phase?
Definition
High I/G ratio
Term
Hyperglycemia stimulates _____ to release insulin.
Definition
Pancreas
Term
To what tissues does insulin make Glc available? What is the consequence of this?
Definition
All tissues; All tissues take up & utilize Glc for energy (preferred fuel)
Term
What p'ways does insulin stimulate in the liver? Describe.
Definition
Glycogenesis (storage of excess Glc); aa uptake, temporary storage, PP synthesis; Lipogenesis out of excess Glc & aa's & release of VLDLs
Term
What p'ways does insulin stimulate in mm? Describe.
Definition
Glycogenesis; aa uptake, temporary protein pool, synthesis of m. proteins
Term
What p'ways does insulin stimulate in fat tissue? Describe.
Definition
Endothelial LPL: FAs/Glycerol are extracted from chylomicrons & VLDLs for fat storage; Lipogenesis
Term
Where does insulin stimulate LPLs?
Definition
Only in fat cells
Term
In the absorptive phase, what happens to Glc (preferred fuel)?
Definition
Oxidized in all tissues for energy
Term
In the absorptive phase, what happens to excess nutrients?
Definition
Stored as Glycogen, Protein Pool, Fat
Term
What is absorbed in a carnivorous diet?
Definition
aa's & chylomicrons (very little Glc)
Term
In a carnivorous diet, what do aa's stimulate?
Definition
Insulin release --> stimulates uptake of aa's into cells
Term
In a carnivorous diet, what does hypoglycemia stimulate?
Definition
Glucagon release --> stimulates gluconeogenesis using the absorbed aa's as precursors
Term
Compared to herbivores/omnivores, what are the Glc demands of carnivores?
Definition
The same
Term
What is completed during the post-absorptive phase?
Definition
Digestion & Absorption of fuels
Term
During the post-absorptive phase, what happens to blood levels of Glc, aa, & chylomicrons?
Definition
Decline as these fuels are taken up by tissues
Term
During post-absorptive phase, blood Glc levels slide toward _____.
Definition
Hypoglycemia
Term
During post-absorptive phase, what does hypoglycemia stimulate?
Definition
Pancreas to release Glucagon/inhibit release of insulin; Adrenal gland to release Cortisol & Epi
Term
What is the insulin/glucose ratio in the post-absorptive phase?
Definition
Low I/G ratio
Term
During post-absorptive phase, ______ maintain basic blood Glc levels via _____ & _____.
Definition
Glucagon, Cortisol, & Epi; Glycogenolysis (Glucagon & Epi) & Gluconeogenesis (Glucagon & Cortisol)
Term
During post-absorptive phase, what does lack of insulin do?
Definition
Makes sure remaining Glc is only available to Glc-dep tissues (NS, RBCs, etc)
Term
During post-absorptive phase, what do Glc-indep tissues use for energy gain? Provided by action of what hormone(s)?
Definition
Lipids; Epi & Cortisol
Term
During post-absorptive phase, lack of insulin & presence of G/C/E favor what p'ways in fat tissue? Describe.
Definition
Responds to E/C/G & lack of I; Lipolysis via HSL w/ release of FAs as NEFAs & Glycerol
Term
HSL
Definition
Hormone-Sensitive Lipase
Term
What is the effect of insulin on HSL?
Definition
HSL actively inhibited by insulin; Lack of insulin --> HSL activation
Term
During post-absorptive phase, lack of insulin & presence of G/C/E favor what p'ways in liver? What is the response to?
Definition
Responds to G/C/E; Glycogenolysis; Gluconeogenesis; FFA uptake from NEFAs
Term
Describe Glycogenolysis in the liver during the post-absorptive phase.
Definition
Glycogenolysis --> G6P w/ Glycolysis being inhibited by G --> Glc accumulates --> diffuses out of hepatocytes as free Glc (G & E)
Term
Describe Gluconeogenesis in the liver during the post-absorptive phase.
Definition
Gluconeogenesis from aa's & Glycerol (G & C)
Term
Describe FFA uptake from NEFAs in the liver during the post-absorptive phase.
Definition
FFA uptake from NEFAs --> for energy gain & some release of KBs & VLDLs
Term
During post-absorptive phase, lack of insulin & presence of G/C/E favor what p'ways in muslce?
Definition
Responds to C & E; Glycogenolysis for energy gain (no release of Glc); FFAs uptake from NEFAs & VLDLs & KBs for energy gain
Term
What tissues use Glc in the post-absorptive phase?
Definition
Reserved for Glc-dep tissues
Term
What happens to stored nutrients in the post-absorptive phase?
Definition
Mobilized & most tissues utilize FFAs
Term
During the post-absorptive phase, what do metabolic changes induce?
Definition
Hunger --> Next meal --> Absorptive Phase
Term
Fasting/Starving =
Definition
State of negative energy balance lasting more than a few days/weeks
Term
During fasting/starvation, what phase continues?
Definition
Post-Absorptive
Term
During fasting/starvation, what happens to glycogen stores & how long does it take?
Definition
Depleted w/i a few hrs (6-8 h)
Term
What is the top priority during fasting/starvation? What does it d/o?
Definition
Maintenance of basic blood Glc levels, w/ dependency on Gluconeogenesis from aa's (Proteolysis) & Glycerol (Lipolysis)
Term
What is the function of lipolysis during fasting/starvation?
Definition
Provides fuel for all Glc-indep tissues
Term
During fasting/starvation, what is the hormone state?
Definition
Longstanding dominance of G/C/E, while I is low
Term
During fasting/starvation, what is used for Proteolysis?
Definition
aa's from temporary pool, then structural & functional aa's (mm. & other organs)
Term
During fasting/starvation, what happens in muscle & other tissues? What is the purpose of this?
Definition
Proteolysis increases to provide aa's for Gluconeogenesis
Term
During fasting/starvation, what happens to fat?
Definition
Lipolysis increases to provide NEFAs for E & Glycerol for Gluconeogenesis; Release of NEFAs soon exceeds body's E demands, but continues b/c hypoglycemia forces hormonal situation which accelerates HSL action
Term
What are the effects of HSL on hormones?
Definition
Decrease insulin; Increase C/E/G
Term
During fasting/starvation, what happens to the liver?
Definition
Takes up many more NEFAs ("fat sponge") than needs for E; Many FFAs repackaged & exported as VLDL, more VLDLs circulate than can be used by peripheral tissues, Hyperlipidemia (horses); Liver cells eventually run out of lipotropic factors to produce VLDLs & FFA/TG accumulate, Hepatic Lipidosis (cats, cows, horses); More KBs produced & released than can be utilized by peripheral tissues, Ketoacidosis & Ketonuria
Term
What is another name for Hyperlipidemia?
Definition
Hyperlipoproteinemia
Term
In what animals is Hyperlipidemia a problem?
Definition
Horses, esp. small ones
Term
What are CS of Hyperlipidemia?
Definition
Depression, Lethargy, Lipemic Plasma
Term
During ketoacidosis, where can acetone be smelled?
Definition
Breath, Urine, Milk
Term
What are the consequences of fasting/starvation?
Definition
m. & organ wasting/malfunctions; hepatic lipidosis leading to hepatic damage; metabolic ketoacidosis
Term
What is the cause of Ketosis/Hepatic Lipidosis?
Definition
Lack or unavailability of carbs (Hypoglycemia)
Term
When is Ketosis/Hepatic Lipidosis typically seen?
Definition
Fasting/Starvation/Anorexia in cats; Excessively high Glc demands (Pregnancy) in ponies & sm rum's/(Peak Lactation) in cows; Hormonal imbalances which lead to excessive lipolysis/proteolysis (Diabetes Mellitus); Dietary imbalances (High protein/Low carbs)
Term
How long does it take for an anorexic cat to enter hepatic lipidosis?
Definition
2 wks
Term
When is ketosis/hepatic lipidosis primarily seen?
Definition
Obese Anorectic Cats
Term
What is the Tx for hepatic lipidosis/ketosis? (Excl. cats)
Definition
IV Glc infusion, insulin, buffer, electrolytes
Term
What is the Tx for hepatic lipidosis/ketosis in cats? Why isn't Glc given directly?
Definition
Give aa's so cat can synthesize own Glc; Cats convert carbs to fat & make situation worse
Term
What is the #1 reason for liver failure in cats in the US?
Definition
Ketosis/Hepatic Lipidosis
Term
What is the term for ketosis/hepatic lipidemia caused by pregnancy?
Definition
Pregnancy Toxemia
Term
When are CS of ketosis/hepatic lipidosis seen?
Definition
After a few weeks
Term
Many metabolic pways are _____-specific.
Definition
Liver
Term
Can other organs compensate for the metabolic pways disrupted in liver failure?
Definition
No
Term
What types of metabolism is the liver involved in?
Definition
Protein, Carb, Fat
Term
What are some liver functions aside from metabolism?
Definition
Blood Reservoir (EPO); Defense (Kupffer cells); Vit/mineral/trace element storage; Detox/excretion of drugs, hormones, bilirubin, urea
Term
What is bilirubin?
Definition
Main bile pigment
Term
From what does bilirubin originate?
Definition
Heme breakdown
Term
What happens to bilirubin when it leaves RES cells?
Definition
Binds to Albumin = Plasma form/U-BILI/Indirect BILI
Term
U-BILI
Definition
Unconjugated Bilirubin
Term
What happens to U-BILI?
Definition
Taken up by liver cells (carrier mediated) & conjugated w/ Glucuronic acid = C-BILI/Direct BILI
Term
C-BILI
Definition
Conjugated Bilirubin
Term
What is the rate-limiting step of bile pigment secretion in horses?
Definition
U-BILI taken up into liver cells (carrier mediated)
Term
Describe the capacity of carriers to mediate the uptake of U-BILI into liver cells.
Definition
High capacity except in horses
Term
What is the purpose of conjugating BILI?
Definition
Makes water-soluble for excretion
Term
What happens to C-BILI when it is formed?
Definition
Secreted into bile ducts; Some regurgitated into circulation
Term
What is the rate-limiting step of bile pigment secretion in all spp. except horses?
Definition
Secretion of C-BILI into bile ducts
Term
What happens to C-BILI in the intestines?
Definition
Converted via urobilinogen/stercobilinogen to Urobilin/Stercobilin (dark color of feces)
Term
What type of bilirubin is normally present in plasma?
Definition
Both U-BILI & C-BILI (50/50 in most spp; more U in horses)
Term
What is jaundice/icterus?
Definition
Yellow pigmentation of skin/mucosa/body fluids caused by deposition of bilirubin
Term
Why is jaundice dangerous in neonates?
Definition
Blood-brain barrier not fully formed; can enter brain
Term
What are the 3 types of jaundice?
Definition
Pre-Heptatic; Hepatic; Post-Hepatic
Term
What causes pre-hepatic jaundice?
Definition
Excessive breakdown of Hb (Hemolytic disorders, Massive internal bleedings; Signs of anemia)
Term
What is also seen in pre-hepatic jaundice?
Definition
Anemia
Term
What happens to bilirubin production in pre-hepatic jaundice?
Definition
U-BILI production increases beyond capacity of liver for uptake & conjugation
Term
In pre-hepatic jaundice, what is elevated initially? Later?
Definition
U-BILI; Both forms increase as secretion of C-BILI becomes saturated
Term
What type of bilirubin dominates in pre-hepatic jaundice?
Definition
U-BILI
Term
What causes hepatic jaundice? Give examples.
Definition
Damage to liver cells (inflammation, lipidosis, necrosis)
Term
In hepatic jaundice, what happens to secretion of bilirubin?
Definition
C-BILI secretion initially more impaired than U-BILI uptake & conjugation
Term
In hepatic jaundice, what is elevated initially? Later?
Definition
C-BILI in most cases (b/o regurgitation); U-BILI also increases as uptake becomes impaired
Term
What causes post-hepatic jaundice?
Definition
Obstruction of bile ducts (stones, tumors, intrahepatic cholestasis)
Term
What is the most variable type of jaundice wrt dominance of C-BILI/U-BILI?
Definition
Hepatic (Typically C>U; not always)
Term
What type of bilirubin dominates in post-hepatic jaundice?
Definition
C-BILI
Term
What happens to C-BILI in post-hepatic jaundice?
Definition
Regurgitated into circulation
Term
In post-hepatic jaundice, increased ______ can ultimately cause _____ injury.
Definition
Intrahepatic pressure; Hepatocellular
Term
In post-hepatic jaundice, what is elevated initially? Later?
Definition
C-BILI very dominant initially; Later U-BILI can also increase (cell damage)
Term
What types of bilirubin can be tested?
Definition
Total & C (U is indirect)
Term
What byproduct of metabolism is important in thermoregulation?
Definition
Heat
Term
What is fever?
Definition
Rise in the hypothalamic set point
Term
What is the normal body temperature in humans?
Definition
37C
Term
What is the normal body temperature in birds?
Definition
41-43C
Term
Where is the temperature regulating center? What is it?
Definition
Hypothalamus; Thermostat w/ fixed set point (core temperature)
Term
What informs the hypothalamus of body temperature? What does this initiate?
Definition
Superficial & Deep temperature Rs; Heat loss or conservation mechanisms
Term
What are heat losing mechanisms?
Definition
Vasodilation, Sweating, Panting, Behavior, Decreased Basal Rate, Decreased Food intake
Term
What is the most important heat losing mechanism?
Definition
Vasodilation
Term
What is the most important heat conserving mechanism?
Definition
Vasoconstriction
Term
What are heat conserving mechanisms?
Definition
Vasoconstriction, Piloerection (insulation), Increased metabolic rate, Shivering, Behavior, Increased food intake
Term
What are the 2 main causes of fever?
Definition
Pyrogens & Compression of hypothalamus
Term
What can compress the hypothalamus leading to fever?
Definition
Tumors
Term
What are some examples of pyrogens?
Definition
Bacterial toxins, protein breakdown products, Cytokines (IL1,6,8,TNF)
Term
How do pyrogens cause fever?
Definition
Reset hypothalamic thermostat to higher value (induce formation of PGE2)
Term
What type of drugs are anti-pyretic?
Definition
Those which inhibit PG synthesis, ex: NSAIDs
Term
How is fever initially a helpful response?
Definition
Increases metabolism & circulation, activates defense system, suppresses pathogen replication
Term
What are characteristics of fever?
Definition
Chill Phase & Crisis Phase
Term
What is the Chill Phase of fever?
Definition
Body attempts to reach new set pt by shivering, piloerection, vasoconstriction, behavior etc. (Heat-conserving mechanisms)
Term
What is the Crisis Phase of fever?
Definition
After removal of fever inducing factor, set pt returns to normal, Heat-losing mechanisms are initiated
Term
Describe Frostbite.
Definition
Severe vasoconstriction; Freezing of superficial areas w/ crystal formation; Permanent tissue damage
Term
Describe Hypothermia.
Definition
Heat loss>Heat production
Term
wrt Hypothermia, when do heat regulating mechanisms become impaired?
Definition
<29C
Term
wrt Hypothermia, when does cardiac arrest occur?
Definition
<20C
Term
What is another term for Hyperthermia?
Definition
Heat Stroke
Term
What is hyperthermia? Give some examples.
Definition
Heat loss cant keep up w/ heat generation; Heavy exercise in hot-humid conditions, Enclosure in hot-humid rooms or cars
Term
What happens to temperature in hyperthermia?
Definition
Body temp rises; Heavy sweating/panting, but insufficient cooling effect b/o high ambient temp & humidity
Term
What happens to fluids in hyperthermia?
Definition
Fluid loss; Dehydration; Initial BP drop; Sympathetic response; Vasoconstriction; Disables further heat loss
Term
What happens when core temp increases above 41.5-42.5C?
Definition
Impairment of cellular functions; Endothelial damage via hypoxia & protein denaturation; Plasma leakage & hemorrhages; Dizziness, Nausea, Coma, Death (CNS, Kidneys, Liver, GI, mm.)
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