Download ch24b_wcr

Document related concepts

Myokine wikipedia , lookup

Thermoregulation wikipedia , lookup

Homeostasis wikipedia , lookup

Glucose meter wikipedia , lookup

Hyperthermia wikipedia , lookup

Exercise physiology wikipedia , lookup

Lipid wikipedia , lookup

Basal metabolic rate wikipedia , lookup

Transcript
Chapter 24B
Nutrition, Metabolism,
Body Temperature
Slides by Barbara Heard and W. Rose.
figures from Marieb & Hoehn 9th ed.
Portions copyright Pearson Education
Protein Metabolism
• Proteins deteriorate, so continually broken
down and replaced
• Amino acids recycled  new proteins or
different compound
• Protein not stored in body
– When dietary protein in excess, amino acids
• Oxidized for energy
• Converted to fat for storage
© 2013 Pearson Education, Inc.
Protein Synthesis
• Amino acids most important anabolic
nutrients
– Form all proteins; bulk of functional molecules
• Hormonally controlled
• Requires complete set of amino acids
– Essential amino acids required in diet
• Synthesize 225 – 450 kg protein during
lifetime
© 2013 Pearson Education, Inc.
Catabolic-Anabolic Steady State
• Dynamic state in which
– Organic molecules (except DNA) continuously
broken down and rebuilt
– Organs have different fuel preferences
– Uses nutrient pools
• Stores of amino acids, carbohydrates, fats
© 2013 Pearson Education, Inc.
Nutrient Pools
• Three interconvertible pools
– Amino acids
– Carbohydrates
– Fats
• Amount and direction of conversion
directed by liver, adipose tissue, skeletal
muscle
© 2013 Pearson Education, Inc.
Amino Acid Pool
• Body's total supply of free amino acids
• Proteins lost in urine, hair, skin cells
• Source for
– Resynthesizing body proteins
– Forming amino acid derivatives
– Gluconeogenesis
© 2013 Pearson Education, Inc.
Carbohydrate and Fat Pools
• Easily interconverted through key
intermediates
• Differ from amino acid pool
– Fats and carbohydrates oxidized directly to
produce energy; amino acids first converted
to carbohydrate
– Excess carbohydrate and fat can be stored;
amino acids not stored as protein
© 2013 Pearson Education, Inc.
Figure 24.17 Interconversion of
carbohydrates, fats, and proteins.
Proteins
Proteins
Carbohydrates
Glycogen
Fats
Triglycerides (neutral fats)
Glucose
Amino acids
Glucose-6-phosphate
Keto acids
Glycerol and fatty acids
Glyceraldehyde 3-phosphate
Pyruvic acid
Lactic acid
Acetyl CoA
Ketone
bodies
Urea
Excreted in urine
© 2013 Pearson Education, Inc.
Krebs
cycle
Catabolic-Anabolic Steady State of the Body
• Blood concentrations of energy sources
equalized between absorptive state and
postabsorptive state
– Absorptive state during and 3-5 hours after
each meal; absorption of nutrients occurring
– Postabsorptive state late morning, late
afternoon, all night; GI tract empty; energy
sources supplied by breakdown of reserves
© 2013 Pearson Education, Inc.
Absorptive State
• Anabolism exceeds catabolism
• Nutrients stored
• Carbohydrates
– Glucose major cellular energy fuel
– Glucose converted in liver to glycogen or fat
• Synthesized fat + protein released to blood for
storage by adipose tissue as very low density
lipoproteins (VLDLs)
© 2013 Pearson Education, Inc.
Absorptive State
• Triglycerides
– Lipoprotein lipase catalyzes lipids of
chylomicrons in muscle and fat tissues
– Most glycerol and fatty acids converted to
triglycerides for storage
– Triglycerides used by adipose tissue, liver,
and skeletal and cardiac muscle as primary
energy source
© 2013 Pearson Education, Inc.
Absorptive State
• Amino acids
– Excess amino acids deaminated and used for
ATP synthesis or stored as fat in liver
– Most amino acids used in protein synthesis
© 2013 Pearson Education, Inc.
Figure 24.18a Major events and principal metabolic pathways of the absorptive state.
Major metabolic thrust:
anabolism and energy storage
Amino acids
Glucose
Glycerol and
fatty acids
Major energy fuel:
glucose (dietary)
Glucose
Liver metabolism:
amino acids deaminated and
used for energy or stored as fat
Amino acids
Keto acids
Proteins
Glycogen
Triglycerides
Triglycerides
Major events of the absorptive state
© 2013 Pearson Education, Inc.
Figure 24.18b Major events and principal metabolic pathways of the absorptive state.
In all tissues:
In muscle:
Glycogen
Glucose
Gastrointestinal
tract
Glucose
Protein
Glucose
Amino acids
In liver:
Triglycerides
Glycogen
Keto acids
Protein
Fatty
acids
In adipose
tissue:
Glucose
Glyceraldehyde
3-phosphate
Glycerol
Triglycerides
Fatty
acids
Glycerol
Fatty
acids
Triglycerides
Principal pathways of the absorptive state
© 2013 Pearson Education, Inc.
Absorptive State: Hormonal Control
• Absorptive state primarily controlled by
insulin
• Insulin secretion stimulated by
– Elevated blood levels of glucose and amino
acids
– Intestinal GIP and parasympathetic
stimulation
© 2013 Pearson Education, Inc.
Insulin Effects on Metabolism
• Insulin, a hypoglycemic hormone, enhances
– Facilitated diffusion of glucose into muscle and
adipose cells (brain and liver take up glucose without
insulin)
– Glucose oxidation for energy
– Glycogen and triglyceride formation
– Active transport of amino acids into tissue cells
– Protein synthesis
– Inhibits glucose release from liver, and
gluconeogenesis
© 2013 Pearson Education, Inc.
Homeostatic Imbalance
• Diabetes mellitus
– Inadequate insulin production or abnormal
insulin receptors 
– Glucose unavailable to most body cells 
– Blood glucose levels high
– Glucose lost in urine
– Fats and proteins used for energy 
metabolic acidosis, protein wasting, weight
loss
© 2013 Pearson Education, Inc.
Postabsorptive State
• Catabolism of fat, glycogen, and proteins
exceeds anabolism
– Net synthesis of fat, glycogen, proteins ends
• Goal - maintain blood glucose between
meals
– Makes glucose available to blood
– Promotes use of fats for energy (glucose
sparing – save glucose for organs that need it
most)
© 2013 Pearson Education, Inc.
Sources of Blood Glucose
• Glycogenolysis in liver
• Glycogenolysis in skeletal muscle
• Lipolysis in adipose tissues and liver
– Glycerol used for gluconeogenesis in liver
• Catabolism of cellular protein
– Major source during prolonged fasting
• Amount of fat in body determines how long
can survive without food
© 2013 Pearson Education, Inc.
Figure 24.20a Major events and principal metabolic pathways of the postabsorptive state.
Major metabolic thrust:
catabolism and replacement of fuels in blood
Proteins
Glycogen
Triglycerides
Major energy fuels:
glucose provided by glycogenolysis and
gluconeogenesis; fatty acids, and ketones
Glucose
Fatty acids
and ketones
Liver metabolism:
amino acids converted to glucose
Amino acids
Keto acids
Amino
acids
Glucose
Glycerol and
fatty acids
Glucose
Major events of the postabsorptive state
© 2013 Pearson Education, Inc.
Figure 24.20b Major events and principal metabolic pathways of the postabsorptive state.
In adipose
tissue:
Glycogen
2
In muscle:
Protein
4
Triglycerides
Pyruvic and
lactic acids
3
Amino acids
In most tissues:
4
2
Triglycerides 3
In liver:
Glycerol
Amino acids Pyruvic and
lactic acids
4
Keto acids
3
2
Glucose
Fatty
acids +
glycerol
Fatty acids
Ketone
bodies
Keto
acids
Blood glucose
1
Stored
glycogen
(b)
In nervous
tissue:
Principal pathways of the postabsorptive state
© 2013 Pearson Education, Inc.
Postabsorptive State: Hormonal and Neural
Controls
• Glucagon - hyperglycemic hormone
– Release stimulated by
• Declining blood glucose
• Rising amino acid levels
© 2013 Pearson Education, Inc.
Effects of Glucagon
• Glucagon promotes
– Glycogenolysis and gluconeogenesis in the
liver
– Lipolysis in adipose tissue  fatty acids and
glycerol to blood
© 2013 Pearson Education, Inc.
Postabsorptive State: Hormonal and Neural
Controls
• Adipose tissue innervated by sympathetic
nervous system
– Quickly supplies glucose if blood levels low
– Low plasma glucose, fight-or-flight response,
or exercise  fat mobilization and
glycogenolysis
• Initiated by sympathetic nervous system and
epinephrine from adrenal medulla
© 2013 Pearson Education, Inc.
Metabolic Role of the Liver
• Hepatocytes
– ~500 metabolic functions
– Process nearly every class of nutrient
– Play major role in regulating plasma
cholesterol levels
– Store vitamins and minerals
– Metabolize alcohol, drugs, hormones, and
bilirubin
© 2013 Pearson Education, Inc.
Cholesterol
• Structural basis of bile salts, steroid
hormones, and vitamin D
• Major component of plasma membranes
• 15% of blood cholesterol ingested; rest
made in body, primarily liver
• Lost from body when catabolized or
secreted in bile salts
• Part of hedgehog signaling molecule that
directs embryonic development
© 2013 Pearson Education, Inc.
Cholesterol Transport
• Lipoproteins
– Transport water-insoluble cholesterol and
triglycerides in blood
– Regulate lipid entry/exit at target cells
– Contain triglycerides, phospholipids,
cholesterol, and protein
• Higher percentage of lipids  lower density, hence
VLDLs, LDLs, HDLs
© 2013 Pearson Education, Inc.
Lipoproteins
• Types of transport lipoproteins
– HDLs (high-density lipoproteins)
• Highest protein content
– LDLs (low-density lipoproteins)
• Cholesterol-rich
– VLDLs (very low-density lipoproteins)
• Mostly triglycerides
– Chylomicrons
• Lowest density
© 2013 Pearson Education, Inc.
Figure 24.22 Approximate composition of lipoproteins that transport lipids in body fluids.
From intestine
Made by liver
10%
20%
Returned to
liver
5%
30%
55–65%
80–95%
20%
45%
15–20%
45–50%
10–15%
© 2013 Pearson Education, Inc.
25%
3–6%
2–7%
5–10%
1–2%
Chylomicron
VLDL
Triglyceride
Cholesterol
Phospholipid
Proteinl
LDL
HDL
Lipoproteins
• VLDLs
– Transport triglycerides from liver to peripheral tissues
(mostly adipose)
• LDLs
– Transport cholesterol to peripheral tissues for
membranes, storage, or hormone synthesis
• HDLs
– Transport excess cholesterol from peripheral tissues
to liver to be broken down and secreted into bile
– Also provide cholesterol to steroid-producing organs
© 2013 Pearson Education, Inc.
Recommended Total Cholesterol, HDL, and
LDL Levels
• Total cholesterol = 200 mg/dl or less
– Levels > 200 mg/dl linked to atherosclerosis
• Form in which cholesterol transported in
blood important to measure
• High HDL thought to protect against heart
disease; >60 good; <40 not good
• High LDL  cholesterol deposits in
vessels; 100 or less good; 130 or above
not good
© 2013 Pearson Education, Inc.
Plasma Cholesterol Levels
• The liver produces cholesterol
– At a basal level regardless of dietary
cholesterol intake
– In response to saturated fatty acids
© 2013 Pearson Education, Inc.
Plasma Cholesterol Levels
• Ratio of saturated/unsaturated fatty acids
affects blood cholesterol levels
• Saturated fatty acids
– Stimulate liver synthesis of cholesterol
– Inhibit cholesterol excretion from body
• Unsaturated fatty acids
– Enhance excretion of cholesterol
– Enhance cholesterol catabolism to bile salts
© 2013 Pearson Education, Inc.
Plasma Cholesterol Levels
• Trans fats
– Healthy oils forced to be solids
• E.g., margarine
– Worse effect on cholesterol levels than
saturated fats
– Increase LDLs and reduce HDLs
© 2013 Pearson Education, Inc.
Plasma Cholesterol Levels
• Unsaturated omega-3 fatty acids (found in
cold-water fish)
– Lower proportions of saturated fats and
cholesterol
– Make platelets less sticky  help prevent
spontaneous clotting
– Antiarrhythmic effects on heart
– Lower blood pressure
© 2013 Pearson Education, Inc.
Non-Dietary Factors Affecting Cholesterol
• Stress and cigarette smoking lower HDL
levels
• Aerobic exercise and estrogen increase
HDL levels and decrease LDL levels
© 2013 Pearson Education, Inc.
Homeostatic Imbalance
• Statins
– Cholesterol-lowering drugs
– Estimated >10 million Americans take statins
© 2013 Pearson Education, Inc.
Energy Balance
• Bond energy released from food must
equal total energy output
• Energy intake = energy liberated during
food oxidation
• Energy output
– Immediately lost as heat (~60%)
– Used to do work (driven by ATP)
– Stored as fat or glycogen
© 2013 Pearson Education, Inc.
Energy Balance
• Nearly all energy from food eventually
converted to heat - cannot be used to do
work
• Heat energy
– Warms tissues and blood
– Helps maintain homeostatic body temperature
– Allows metabolic reactions to occur efficiently
• If energy intake = energy output – weight
stable
• If not equal – gain or loss of weight
© 2013 Pearson Education, Inc.
Monitoring weight
Body mass index (BMI) is one measure
• BMI = Weight in kg / (Height in m)2
• Traditional definitions have negative
connotations*. Don’t use.
• Minimal risk: 18-25
• Slightly increased risk: 25-30
• Increased risk: <18, >30.
• Incidence of overweight is increasing in USA
and other developed nations
*underweight, normal, overweight, obese, morbidly obese.
Department of Kinesiology and Applied Physiology
Regulation of Food Intake
• Various nuclei of hypothalamus
– Release peptides  influence feeding behavior
• neuropeptide Y (NPY) enhances appetite
• pro-opiomelanocortin (POMC) and cocaine/amphetamine-regulated transcript (CART) 
suppress appetite
© 2013 Pearson Education, Inc.
Regulation of Food Intake
• Feeding behavior and hunger regulated by
–
–
–
–
Neural signals from digestive tract
Bloodborne signals related to body energy stores
Hormones
To lesser extent, body temperature and psychological
factors
• Operate through brain thermoreceptors,
chemoreceptors, and others
© 2013 Pearson Education, Inc.
Short-Term Regulation of Food Intake
• Neural signals from GI tract
– High protein content of meal increases and
prolongs afferent vagal signals
– Distension sends signals along vagus nerve
that suppress hunger center
© 2013 Pearson Education, Inc.
Short-Term Regulation of Food Intake
• Nutrient signals related to energy stores
– Increased nutrient levels in blood depress
eating
• Rising blood glucose
• Elevated blood amino acid levels
• Blood levels of fatty acids
© 2013 Pearson Education, Inc.
Short-Term Regulation of Food Intake
• Hormones
– Gut hormones (e.g., insulin and CCK)
depress hunger
– Glucagon and epinephrine stimulate hunger
– Ghrelin (Ghr) from stomach stimulates
appetite; levels peak prior to mealtime
© 2013 Pearson Education, Inc.
Long-Term Regulation of Food Intake
• Leptin
– Hormone secreted by fat cells in response to
increased body fat mass
– Indicator of total energy stores in fat tissue
– Protects against weight loss in times of
nutritional deprivation
© 2013 Pearson Education, Inc.
Long-Term Regulation of Food Intake
• Leptin
– Acts on certain neurons in hypothalamus
– Suppresses secretion of NPY which is a
potent appetite stimulant
– Stimulates expression of appetite
suppressants (e.g., CART peptides)
© 2013 Pearson Education, Inc.
Leptin
• Rising leptin  some weight loss; not
"magic bullet" for obese patients
• High leptin levels in obese patients;
resistant to its action
© 2013 Pearson Education, Inc.
Additional Factors in Regulation of Food
Intake
•
•
•
•
•
Temperature – cold activates hunger
Stress – depends on individual
Psychological factors
Sleep deprivation
Composition of gut bacteria
© 2013 Pearson Education, Inc.
Metabolic Rate and Heat Production
• Metabolic Rate = rate of energy consumption
by the body
• Units: energy per unit time (=power), i.e.
kilocalories per day, kilocalories per hour
• Measure by heat production or O2 consumption
– Heat production: If no external mechanical work is
being done, all energy used by body is eventually
released as heat. Measure the heat released, in a
calorimeter.
– O2 consumption: About 4.83 kcal/(L O2).*
• Basal versus Total MR – see next slides
*Fuel source: glucose: 5.01 kcal/(L O2), starch 5.06, fat 4.70, protein 4.60.
Department of Kinesiology and Applied Physiology
Metabolic Rate and Heat Production
Basal Metabolic Rate = power needed to
perform activities essential for life
breathe, pump blood, maintain body temperature,
maintain the internal environment of cells in a nonequilibrium state
Measure BMR with patient relaxed and supine in
post-absorptive state.
BMR per kg tends to be lower in women than
men and to decrease as we age.
Thyroxine, chronic cold exposure increase BMR.
Physical training has little effect on BMR.
Department of Kinesiology and Applied Physiology
Metabolic Rate and Heat Production
Total Metabolic Rate
• Power needed to perform all daily activities
including exercise
• Skeletal muscle activity is the main difference
between basal and total metabolic rate
• Total includes external mechanical work
• Metabolic rate rises after a meal, due to
energy used to digest, transport, store
nutrients. Up more with protein meal.
Department of Kinesiology and Applied Physiology
Regulation of Body Temperature
• Body temperature reflects balance
between heat production and heat loss
• At rest, liver, heart, brain, kidneys,
endocrine organs generate most heat
• During exercise, heat production from
skeletal muscles increases dramatically
© 2013 Pearson Education, Inc.
Regulation of Body Temperature
• Normal body temperature = 37C  5C
(98.6F)
– Optimal enzyme activity at this temperature
• Increased temperature denatures proteins
and depresses neurons
– Children <5  convulsions at 41C(106F)
– ~43C (109F) - limit for life
• Tissues tolerate low body temperatures
© 2013 Pearson Education, Inc.
Core and Shell Temperature
• Core (organs within skull, thoracic &
abdominal cavities) has highest
temperature
– Rectal temperature best clinical indicator
• Core temperature regulated; fairly
constant
– Blood - major agent of heat exchange
between core and shell
• Shell (skin) – lowest temperature
– Fluctuates between 20C – 40C
© 2013 Pearson Education, Inc.
Mechanisms of Heat Exchange
• Four mechanisms of heat transfer
– Radiation - loss of heat by infrared rays
– Conduction - transfer of heat by direct
contact
– Convection - transfer of heat to surrounding
air
– Evaporation - heat loss due to evaporation of
water from body surfaces
• Heat absorbed by water during evaporation – heat
of vaporization
© 2013 Pearson Education, Inc.
Mechanisms of Heat Exchange
• Insensible heat loss accompanies
insensible water loss from lungs, oral
mucosa, and skin
– Loss ~ 10% of basal heat production
• Sensible heat loss – when body
temperature rises and sweating increases
water vaporization
© 2013 Pearson Education, Inc.
Role of the Hypothalamus
• Hypothalamus receives afferent input from
– Peripheral thermoreceptors in shell (skin)
– Central thermoreceptors (some in
hypothalamus) in core
• Initiates appropriate heat-loss and heatpromoting activities
© 2013 Pearson Education, Inc.
Heat-Promoting Mechanisms
• Constriction of cutaneous blood vessels
– Sympathetic nervous system stimulates
• Shivering – heat from skeletal muscle
activity
• Increased metabolic rate via epinephrine
and norepinephrine
– Chemical (nonshivering) thermogenesis infants
– Brown adipose tissue in adults
• Enhanced thyroxine release - infants
© 2013 Pearson Education, Inc.
Heat-Promoting Mechanisms
• Behavioral modifications (voluntary)
measures include
– Putting on more clothing
– Drinking hot fluids
– Changing posture (clasping arms across
chest)
– Increasing physical activity (jumping up and
down)
© 2013 Pearson Education, Inc.
Heat-Loss Mechanisms
•
•
•
•
Heat-promoting center inhibited
Dilation of cutaneous blood vessels
Enhanced sweating
Voluntary measures include
– Reducing activity and seeking a cooler
environment
– Wearing light-colored, loose-fitting clothing
© 2013 Pearson Education, Inc.
Homeostatic Imbalance
• Hyperthermia
– Elevated body temperature depresses
hypothalamus
– Positive-feedback mechanism (heat stroke)
begins at core temperature of 41C 
increased temperatures
• Skin hot and dry; organs damaged
– Can be fatal if not corrected
© 2013 Pearson Education, Inc.
Homeostatic Imbalance
• Heat exhaustion
– Heat-associated collapse after vigorous
exercise
– Due to dehydration and low blood pressure
– Heat-loss mechanisms still functional
– May progress to heat stroke if not cooled and
rehydrated promptly
© 2013 Pearson Education, Inc.
Homeostatic Imbalance
• Hypothermia
– Low body temperature from cold exposure
• Vital signs decrease
– Shivering stops at core temperature of
30 - 32C
– Can progress to coma and death by cardiac
arrest at ~ 21C
© 2013 Pearson Education, Inc.
Fever
• Controlled hyperthermia
• Due to infection (also cancer, allergies, or
CNS injuries)
• Macrophages release cytokines (also
called pyrogens)
– Cause release of prostaglandins from
hypothalamus
© 2013 Pearson Education, Inc.
Fever
• Prostaglandins reset hypothalamic
thermostat higher
–  heat-producing mechanisms – temperature
rises
• Natural body defenses or antibiotics
reverse disease process
– Cryogens (e.g., vasopressin) reset thermostat
to lower (normal) level  heat-loss
mechanisms  temperature falls
© 2013 Pearson Education, Inc.