dietary balances; regulation of feeding; obesity and starvation
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Dietary Balances; Regulation of Feeding; Obesity and Starvation. Prof. dr. Zoran Vali ć Department of Physiology University of Split School of Medicine. Energy Intake and Output. used or stored for later use (fat) - PowerPoint PPT PresentationTRANSCRIPT
Dietary Balances; Regulation of Feeding; Obesity and Starvation
Prof. dr. Zoran ValićDepartment of PhysiologyUniversity of Split School of Medicine
Energy Intake and Output
used or stored for later use (fat) appropriate balanced intake (proteins,
carbohydrates, fats, minerals, and vitamins) 1 g carbohydrates – 4.1 Cal (98% – 4(17
kJ) 1 g fats – 9.3 Cal (95% – 9 (38 kJ)) 1 g proteins – 4.35 kJ (92% – 4 (17 kJ)) 45%, 40%, 15% (average Americans)
30-50 g of protein per day (20-30 g are degraded)
partial proteins (inadequate quantities of certain essential amino acids)
protein of corn has almost no tryptophan protein-deficiency syndrome – kwashiorkor carbohydrates and fats – protein sparers
nitrogen excretion can be used to assess protein metabolism (16% nitrogen)
90% of nitrogen is excreted in the urine (urea, uric acid, creatinine), 10% by feces
rate of protein breakdown (g) = N2(urine) x 1.1 x 6.25 (100/16)
negative or positive nitrogen balance
“respiratory quotient” – ratio of CO2 production to O2 utilization (1h and more)
fat utilization (0.7), carbohydrates (1.0), proteins (0.8)
excess hydrogen atoms right after meal close to 1.0; 8-10 h after
meal about 0.7; in diabetes melitus always about 0.7
Regulation of Food Intake and Energy Storage
only 27% of the energy ingested normally reaches the functional systems of the cells
food intake, energy expenditure and fat storage – environmental, cultural and genetic factors + physiological control
“epidemics” of obesity (64% & 33%) 2000 Cal daily expenditure of energy
(6000-7000 Cal)
Neural Centers Regulate Food Intake
sensation of hunger (rhythmical contractions of stomach and restlessness)
appetite –desire for particular type of food feeling of satiety
lateral nuclei of the hypothalamus – feeding center (hyperphagia, inanition)
operates by exciting the motor drives to search for food
ventromedial nuclei of the hypothalamus – satiety center (aphagia, hyperphagia)
other centers also play a major role (arcuate!), hormonal secretion (thyroid and adrenal glands, pancreatic islet cells)
integration of neural signals from the gastrointestinal tract (stomach filling), chemical signals from nutrients in the blood, signals from gastrointestinal hormones, hormones released by adipose tissue and signals from the cerebral cortex (sight, smell, and taste)
feeding behavior orexigenic and anorexigenic substances and
receptors – therapeutic sites
Neurons and Neurotransmitters in the Hypothalamus
1) pro-opiomelanocortin (POMC) neurons1) α-MSH (α-melanocyte-stimulating hormone)2) CART (cocaine and amphetamine related transcript)
2) neurons that produce orexigenic substances1) NPY (neuropeptide Y)2) AGRP (agouti-related protein)
activation of POMC neurons decreases food intake and increases energy expenditure
activation of NPY-AGRP neurons increases food intake and reduces energy expenditure
major targets for: leptin, insulin, cholecystokinin (CCK), and ghrelin
POMC neurons release α-MSH (acts on melanocortin receptors found especially in neurons of the paraventricular nuclei)
at least five subtypes of melanocortin receptors
MCR-3 and MCR-4 are especially important in regulating food intake and energy balance
activation of these receptors reduces food intake while increasing energy expenditure
inhibition has an opposite effect
MCR activation is mediated by activation of nucleus tractus solitarius (sympathetics)
defective signaling of the melanocortin pathway is associated with extreme obesity
mutations of MCR-4 – most common known monogenic (single-gene) cause of human obesity (5-6% of early-onset severe obesity in children)
AGRP is a natural antagonist of MCR-3 and MCR-4 receptors
role of AGRP in normal physiologic control of food intake is unclear
excessive formation of AGRP in mice and humans, due to gene mutations, is associated with increased food intake and obesity
NPY (arcuate nuclei) – when energy stores of the body are low – stimulates appetite + firing of the POMC neurons is reduced = decreased activity of the melanocortin pathway and further stimulated appetite
Factors That Regulate Quantity of Food Intake
short-term regulation – preventing overeating at each meal
long-term regulation – maintenance of normal quantities of energy stores in the body
Short-Term Regulation
What turns off the eating? 1) distending of gastrointestinal tract (stomach
and the duodenum – vagus nerve)2) humoral and hormonal factors
1) cholecystokinin (CCK) – fat2) peptide YY from the ileum and colon – fat, ??3) glucagon-like peptide (GLP) from intestines – enhances
glucose-dependent insulin production and secretion from the pancreas – suppress appetite
3) ghrelin – oxyntic cells of the stomach and intestine, concentrations rise during fasting, fall rapidly after a meal; administration of ghrelin increases food intake in experimental animals; ?
4) oral receptors (experiment with esophageal fistula; chewing, salivation, swallowing, and tasting – shorter duration (20-40 min))
Intermediate and Long-Term Regulation
depends on nutritional status of the body glucostatic, aminostatic and lipostatic
theories of regulation glucoreceptor ( GUK increases the rate of
firing) and glucosensitive ( GUK decreases the firing) neurons in the hypothalamus
Temperature Regulation and Food Intake
exposition to cold – increased feeding interaction within the hypothalamus:1) increases metabolic rate2) provides increased fat for insulation
Feedback from Adipose Tissue hypothalamus senses energy storage
through the actions of leptin, a peptide hormone released from adipocytes
POMC neurons of the arcuate nuclei and neurons of the paraventricular nuclei:
1) appetite stimulators (NPY i AGRP)2) activation of POMC neurons (α-MSH)3) substances that decrease apetite (CRH)4) increased sympathetic nerve activity 5) insulin secretion by the pancreatic β cells
in mice or humans with mutations that render their fat cells unable to produce leptin or mutations that cause defective leptin receptors in the hypothalamus – marked hyperphagia and morbid obesity
in most obese humans – no deficiency of leptin production
many other mechanisms, questionable summary
Obesity – excess of body fat
BMI = mass (kg) / hight2 (m2) 25-30 – overweight, 30 – obese measurment of total body fat (skin-fold
thickness, bioelectrical impedance, or underwater weighing; 25% & 35%)
obesity results from greater energy intake than energy expenditure
for each 9.3 Cal (38,9 kJ ) of excess energy – 1 gram of fat is stored
1/3 energy used each day by the average person goes into muscular activity (2/3)
increase in physical activity!
Psychological factors
three meals a day and that each meal must be filling
during or after stressful situations (death of a parent, a severe illness, or even mental depression)
eating can be a means of releasing tension
Childhood Overnutrition
rate of formation of new fat cells number of fat cells in obese children is
often as three times that in normal children hyperplastic and hypertrophic obesity new adipocytes can differentiate from
fibroblast-like preadipocytes at any period of life
Neurogenic Abnormalities
lesions in the ventromedial nuclei of the hypothalamus – tumors
functional organization of the hypothalamic or other neurogenic feeding centers in obese individuals may be different
abnormalities of neurotransmitters or receptor mechanisms
Genetic Factors
obesity definitely runs in families identical twins mass is usually within 1.5,
or 2.5 kg 20-25% of cases of obesity may be caused
by genetic factors1) mutations of MCR-42) congenital leptin deficiency3) mutations of the leptin receptor
Treatment of Obesity
reducing energy intake or/and increasing energy expenditure
large quantities of "bulk“ (non-nutritive cellulose substances, distention)
prevent vitamin deficiencies amphetamines, sibutramine – dangerous,
overexcite sympathetic nervous system and raise pressure, addiction
altering lipid metabolism orilistat (a lipase inhibitor) – reduces the
intestinal digestion of fat loss of fat-soluble vitamins in the feces increase in physical activity various surgical procedures (gastric bypass
surgery and gastric banding surgery)
Inanition
lack of food, or psychological and hypothalamic disorders anorexia nervosa – reduction in food intake
caused primarily by diminished appetite, nauseated by food
cachexia – weight loss greater than that caused by reduced food intake alone (tumors, AIDS)
Starvation
tissues preferentially use carbohydrate for energy
protein depletion: rapid depletion at first, then greatly slowed depletion, and, finally, rapid depletion again shortly before death
gluconeogenesis decreases to 1/5 state of ketosis (β- hydroxybutyrate – brain)
Body Temperature Regulation and Fever
Normal Body Temperatures
“core” temperature = ± 0,6 ºC (± 1 ºF) (nude person exposed to air temperatures 10-55 ºC, beautifully designed control system)
skin temperature rises and falls with the temperature of the surroundings (ability to lose heat to the surroundings)
Normal Core Temperature
range of normal temperatures (36-37,5 ºC) average normal core temperature 36,5-37
ºC (measured orally; rectally 0,5 ºC higher) regulatory mechanisms are not perfect:
temperature increases during exercise and varies with temperature extremes of the surroundings
balance between heat production and heat loss
Heat Production
heat – principal by-product of metabolism metabolic rate of the body:
1) basal rate of metabolism2) muscle activity3) effect of thyroxine, (hGH, testosterone)4) effect of sympathetic stimulation5) increased chemical activity in the cells6) thermogenic effect of food
Heat Loss
heat is generated in deep organs: liver, brain, and heart, and in the skeletal muscles
heat is lost to the air via skin rate at which heat is lost:
1) how rapidly heat can be conducted from where it is produced to the skin
2) how rapidly heat can then be transferred from the skin to the surroundings
Insulator System of the Body
skin, subcutaneous tissues (fat) – insulator conduction of heat through fat = 1/3
conduction through other tissues insulator properties of female body are
better than male body
Blood Flow to the Skin from the Body Core
enables heat to be conducted from the core of the body to the skin
especially important is a continuous venous plexus
rate of blood flow into the skin venous plexus can vary tremendously (0-30% CO)
skin is an effective controlled "heat radiator" system
flow of blood to the skin is a most effective mechanism for heat transfer from the body core to the skin
vasoconstriction of the arterioles and the arteriovenous anastomoses that supply blood to the venous plexus of the skin is controlled almost entirely by the sympathetic nervous system
Basic Physics of How Heat Is Lost from the Skin Surface radiation (about 60%, infrared heat rays, a
type of electromagnetic wave (5-20 μm), in all directions)
conduction (about 3% direct conduction from to solid objects, about 15% to air – convection (currents), suspension in water!)
evaporation (evaporation of 1g water – 0.58 Cal (2,5 kJ) heat, insensibly and evaporation of sweat, necessary cooling mechanism at very high air temperatures)
Effect of Clothing
increasing the thickness of the so-called private zone of air + decreasing air currents
rate of heat loss from the body by conduction and convection (to 1/2, or 1/6 – arctic-type clothing)
coating the inside of clothing with a thin layer of gold – reflects radiant heat back
extreme caution against allowing the clothing to become wet
Sweating
starts by stimulation of the anterior hypothalamus-preoptic area in the brain by electricity or by excess heat
nerve impulses are transmitted in the autonomic pathways to the spinal cord and then through sympathetic outflow to the skin everywhere in the body
sweat glands are innervated by cholinergic nerve fibers (but that run in the sympathetic nerves along with the adrenergic fibers)
they can also be stimulated by epinephrine or norepinephrine circulating in the blood
Mechanism of Sweat Secretion
1) deep subdermal coiled portion – secretes the sweat (primary or precursor secretion)
2) duct portion (modify concentrations of constituents)
Primary secretion
active secretory product of the epithelial cells
composition is similar to that of plasma (Na+ = 142 mmol/L, a Cl- = 104 mmol/L), does not contain plasma proteins
Reabsorption of ions
slight stimulation – most of Na+ and Cl- are reabsorbed (concentration of each falls to as low as 5 mmol/L)
this reduces the osmotic pressure of the sweat fluid to such a low level that most of the water is also reabsorbed, which concentrates most of the other constituents (urea, K+, lactic acid)
strong stimulation – Na+ and Cl- are reabsorbed to concentrations of 50-60 mmol/L, little of the water is reabsorbed – significant loss of NaCl
Acclimatization. Role of Aldosterone
normal unacclimatized person ~ 1L/h sweat after 1-6 weeks ~ 2-3 L/h sweat removing 10x more heat from the body change in the internal sweat gland cells to
increase their sweating capability better conservation of body salt – increased
secretion of aldosterone (decreases loses from 15-30 g/day to 3-5 g/day)
Loss of Heat by Panting
substitute mechanism due to:1) surfaces often covered with fur2) skin of most lower animals is not
supplied with sweat glands panting center is associated with
pneumotaxic respiratory center in the pons evaporation of saliva from the tongue,
without increase in alveolar ventilation
Role of the Hypothalamus
experiments with use of a thermode principal areas in the brain for temperature
control are the preoptic and anterior hypothalamic nuclei of the hypothalamus
large numbers of heat-sensitive neurons about one-third as many cold-sensitive
neurons heating of preoptic area – profuse sweating
and vasodilation in the skin
Detection of Temperature
temperature receptors in skin and in a few specific deep tissues (spinal cord, abdominal viscera, around the great veins)
in the skin: cold receptors (far more) and warmth receptors
in deep tissues: function differently from the skin receptors because they are exposed to the body core temperature, they detect mainly cold
Integration of the Central and Peripheral Temperature Signals
area of the hypothalamus that is located bilaterally in the posterior hypothalamus approximately at the level of the mammillary bodies
combination and integration of signals from the preoptic area and from elsewhere in the body
Temperature-Decreasing Mechanisms
vasodilation in the skin (inhibition of the sympathetic
centers in the posterior hypothalamus), 8x rate of heat transfer to the skin
sweating rise above 37 ºC (critical level), 1 ºC 10x
removal of heat by evaporation decrease in heat production
inhibition of shivering and chemical thermogenesis
Temperature-Increasing Mechanisms
vasoconstriction in the skin (stimulation of the posterior
hypothalamic sympathetic centers) piloerection
hairs "standing on end", not important in humans, thick layer of "insulator air"
increase in thermogenesis promoting shivering, sympathetic excitation of
heat production, and thyroxine secretion
Hypothalamic Stimulation of Shivering
primary motor center for shivering located in the dorsomedial portion of the posterior hypothalamus near wall of the 3rd ventricle
normally inhibited by signals from the heat center in anterior preoptic area
cold signals from the skin and spinal cord body heat production can rise 4-5x normal
transmits signals to anterior motor neurons signals are nonrhythmical and do not cause
the actual muscle shaking they increase the tone of the skeletal
muscles throughout the body when the tone rises above a certain critical
level, shivering begins
results from feedback oscillation of the muscle spindle stretch reflex mechanism
Sympathetic "Chemical" Excitation
ability of norepinephrine and epinephrine to uncouple oxidative phosphorylation
foodstuffs are oxidized but do not cause ATP to be formed – release of heat
directly proportional to the amount of brown fat (acclimatization)
adults do not have brown fat ( rate of heat production 10-15%, in infants 100%)
Increased Thyroxine Output
cooling preoptic area – increases production of TRH TSH tiroksina activates uncoupling protein
yet another mechanism of chemical thermogenesis
requires several weeks' exposure to cold humans seldom allow themselves to be
exposed to the same degree of cold
Concept of a "Set-Point"
critical body core temperature 37,1 °C called the "set-point" of the temperature
control mechanism feedback gain of the temperature control
system = (ratio of the change in environmental temperature to the change in body core temperature) - 1
changes about 1°C for each 25° to 30°C change in environmental temperature (~ 27)
extremely high gain (baroreceptor feedback gain < 2)
Skin Temperature Can Slightly Alter the Set-Point
decrease in skin temperature – increase in set-point for sweating
decrease in skin temperature – increase in set-point for shivering
Behavioral Control
even more potent person makes appropriate environmental
adjustments to re-establish comfort
there are local skin temperature reflexes after cutting the spinal cord in the neck
above the sympathetic outflow from the cord regulation becomes extremely poor
Fever
body temperature above the usual range of normal
1) abnormalities in the brain itself2) toxic substances that affect the
temperature-regulating centers
Resetting the Hypothalamic Temperature-Regulating Center
many proteins, breakdown products of proteins, lipopolysaccharide toxins released from bacterial cell membranes – pyrogens
some pyrogens act directly and immediately
other pyrogens function indirectly and may require several hours of latency (endotoxins from gram-negative bacteria)
phagocytizion of bacteria – release of interleukin-1 (IL1, leukocyte or endogenous pyrogen)
IL1 in 8-10 min significantly increases temperature (in nanograms)
IL1 inducing formation of prostaglandin E2
drugs that impedes the formation of prostaglandins from arachidonic acid – antipyretics (aspirin)
Fever Caused by Brain Lesions
almost always after surgery in the region of the hypothalamus
compression of the hypothalamus by a brain tumor
Characteristics of Febrile Conditions
chills – extremely cold feeling, vasoconstriction in the skin, shivers
crisis or “flush” – after factor is removed, intense sweating and the hot skin
heatstroke body temperature rises beyond a critical temperature – 40-42 °C (105° to 108°F, dizziness, abdominal distress, vomiting, delirium, loss of consciousness)
local hemorrhages and parenchymatous degeneration of cells
especially in the brain, but also liver and kidneys
acclimatization
Exposure of the Body to Extreme Cold
person exposed to ice water for 20 to 30 minutes ordinarily dies because of heart standstill or heart fibrillation
once the body temperature has fallen below about 85°F (30 °C), the ability of the hypothalamus to regulate temperature is lost
sleepiness, coma – depresses the activity of the central nervous system
frostbites (lobes of the ears and in the digits of the hands and feet) – formation of ice crystals – permanent damage – gangrene
artificial hypothermia (heart surgery)