nutri sci - 2
LIPID SOLUBLE VITAMINS 1
vitamins - organic compounds (C, H, N, O, S, P) found in small quantities in the diet
essential for basic functions
fat-soluble vitamins
A, D, E, and K
absorption/transport similar to that of fat
can be stored (liver, adipose mostly)
toxic in high doses
vitamin E - antioxidant
several forms but alpha-tocopherol most relevant
absorption - absorbed with fats, incorporated into chylomicrons for circulation
processed in liver
excretion via bile and feces and urine after processed in liver
RDA - 15 mg/day
upper level ~1000 mg/day
deficiency - rare, generally result of insufficient fat absorption
symptoms - retinopathy, peripheral neuropathy, ataxia, lower immune function
food sources - especially vegetable oils
can be destroyed by heat and oxidation
VITAMIN A - family of compounds known as retinoids
functions - light absorbing pigment in the eye (rhodopsin)
regulation of gene expression (nuclear receptors)
retinoic acid is active form of Vitamin A
produced in small amounts locally in small tissues
regulates cell differentiation, growth, embryonic development, reproduction, immunity
opsin responsible for neuronal signals of vision
food sources
pre-formed: animal products, liver, dairy products, egg, fish, fortified foods
pro-vitamin:
carotenoids - plant pigments found in many fruits and veggies
can be converted into Vitamin A => beta-carotene, alpha-carotene
conversion of beta carotene requires the enzyme BCO1
beta-carotene oxygenase 1
high abundant in small intestine epithelium
converts beta carotene to retinal
absorption - efficiently absorbed in small intestine (70-90%) with sufficient lipid present
requires dietary fat and bile acids
deesterfied in order to be absorbed
carotenoid absorption is lower
for raw veggies ~5%
processing (cooking) can increase absorption
less absorption = less likely to experience toxicity
once absorbed, retinol and beta carotene are metabolized in the enterocytes before entering bloodstream
transport and storage
retinyl esters can be stored in hepatic stellate cells
retinol binds to binding protein (made in liver) enables circulation in the plasma (holo-RBP)
delivery mechanism for retinol to other tissues (eyes, kidneys, lungs, skeletal muscle, white blood cells)
excretion via bile and feces
RDA
Men - 900 ug RAE, women 700
pregnant 770; lactating 1300
UL - 3000
deficiency
mostly a concern in developing countries
night blindness
inability to adapt to darkness
diminished ability to generate rhodopsin
xerophthalmia
excessive dryness of eye caused by lack mucus production
leads to corneal and conjunctival scarring, blindness
toxicity
acute
single excessive dose
nausea, vomiting, double vision, headache
chronic
develops over months to years
anorexia, hair loss, skin problems, increased bone fractures, eye pain, liver damage, birth defects (accutane)
LIPID SOLUBLE VITAMINS 2
VITAMIN K
function - primarily blood clotting
essential for activation of several proteins that participate in clotting process
participates in bone calcification
gamma-carboxylation
clotting factors like Thrombin require the ability to bind Ca2+ to be active
gamma carboxylation provides this ability
Warfarin - interferes with recycling of Vitamin K, making it less available and thus reducing gamma-carboxylation of clotting factors
Vitamin K discovered in Wisconsin and based on experiments feeding fat-free diets to chickens
observed development of hemorrhagic disease
absorption, storage, and transport
absorbed in small intestine
requires fat/bile acids and pancreatic factors
supplement forms are much more highly bioavailable than those from food
transported in chylomicrons
storage is fairly limited
can use reducing power from NAD(P)H to recycle Vitamin K
RDA - 120 ug men, 90 women
gut bacteria appear to synthesize although amount bioavailable and absorbed by us is unclear
UL not established, no toxicity known
can interfere with anticoagulant drugs (warfarin)
people on blood thinners are advised to eat a diet that provides a consistent amount of Vitamin K
deficiency
primary deficiency rare
secondary deficiency - malabsorption and anticoagulant drugs
newborns given shot of vitamin K shortly after birth
poor transfer from placenta and low availability from breast milk
food sources
green, leafy veggies
plants use this an an electron acceptor in photosynthesis
gut bacteria
VITAMIN D
sources - liver, beef, veal, eggs, saltwater fish, sun, fortified foods (milk/dairy, OJ, breads/cereals)
absorption
roughly 50% efficiently
occurs in the distal ileum of small intestine
require bile acids and fat
incorporated into mixed micelles
packed into chylomicron for circulation
later circulates bound to Vitamin D binding protein
synthesis by the skin
produces the majority of the Vitamin D from sun exposure
Cholecalciferol (Vitamin D3) enter bloodstream bound to Vitamin D binding protein
activation/regulation
two step activation
liver: 25-Ohase
kidney: 1 alpha-Ohase
Final product: 1,25-(OH)2D3 [calcitriol] - active Vitamin D
regulates its own breakdown (negative feedback)
blood calcium
low blood Ca2+
parathyroid hormone is released from parathyroid gland
PTH activates enzymes in kidney that convert inactive Vitamin D to calcitriol, the active form
PTH and calcitriol stimulate production of osteoclasts
demineralize bone to release Ca2+ and phosphorus into blood
calcitriol increases Ca2+ absorption from the intestine and reabsorption from kidneys
high blood Ca2+
calcitonin - released from thyroid, stimulates addition of Ca2+ and phosphorus to build bone (mineralization)
metabolism
functions - maintain normal serum calcium and phosphorus levels
bone health
calcitriol facilitates calcium absorption from gut, which is needed for bone mineralization
increases expression of calbindin and calcium channels
similar effects on retinal tubules to increase calcium reabsorption from urine
mechanisms of action
behaves as a hormone and regulates gene expression by binding Vitamin D receptor (VDR)
VDR expressed in most cell types, suggesting broad functions
nuclear receptor
immune system
through gene expression it influences immune response and host-defense against pathogens via cAMP
disease
RDA
600 IU/day
older adults need more
not different for pregnant or lactating women
deficiency
osteomalacia - soft bones
occurs in adults
may be caused by kidney, stomach, gallbladder, intestinal, or liver disease affecting Vitamin D metabolism or absorption
treatment - sun exposure, supplements
rickets
occurs in children
bowed legs, enlarged head and rib cage, deformed pelvis
toxicity
UL = 4000 IU
toxicity most likely to result from excessive supplementation
hypercalcemia
calcification of tissues
kidney dysfunction, loss of appetite, GI distress
WATER AND ELECTROLYTES
ECF - ⅓ of body water
20% of body weight
interstitial is 75%
plasma is other 25%
ICF - ⅔ of body water
40% of body weight
NaCl
isotonic: 0.9% NaCl
water follows movement of electrolytes by diffusion
+/- charges same in each compartment
Na and K constantly using energy to exchange with ATPase
30% of total energy for cells
fluid pH - bicarbonate and proteins are pH buffers for body
affected by lung respiration and excretion of bicarbonate in kidney
plasma-interstitial space exchange
cardiovascular system is closed
hydrostatic pressure
capillaries
fluid and solute exchange
large surface area
capillary hydrostatic pressure - blood pressure
pressure high when leaving heart
drops going through arteries => capillaries => veins
arterial side - hydrostatic pressure > oncotic pressure
venous side - oncotic pressure > hydrostatic pressure
plasma oncotic pressure
liver disease, low serum albumin - oncotic pressure reduced
pregnancy - hydrostatic pressure increased
hemorrhage blood loss - hydrostatic pressure decreased
edema - fluid buildup in interstitial space
due to elevation in capillary hydrostatic pressure (heart failure)
regulation of water
partially regulated by kidneys
insensible water loss
skin, respiration,
kidneys compensate for these
sweat
WATER AND ELECTROLYTES 2
water intake should be about 1 mL water/kcal expended
must excrete at least 500 mL or urine to eliminate waste products
consistently concentrated urine is a risk for kidney stones
water loss
insensible - respiration and skin (not sweat
sensible
GI Tract
handles about 9L of water per day
dehydration
thirst sensation - excessive loss of body water leads to increase ECF osmolarity (hyperosmolarity)
hyperosmolarity - water intoxication
occurs following rapid fall is osmolarity
water from ECF moves into cells
brain cells swell causing nausea, malaise, headache, confusion, seizures, coma
increases as small as 2% will activate neural centers in the hypothalamus to produce strong desire to drink
some individuals impaired to this response - infants, elderly, diseased/vigorous states
kidneys
regulate body fluid osmolarity and volume and electrolyte balance
regulate acid/base balance
excrete metabolic waste products
produce and secrete hormones
principles of the nephron - functional unit of kidney
filtration
initial removal of solutes and water from blood
doesn’t include large proteins or blood cells
solutes in filtrate include some vitamins, minerals, and nutrients
reabsorption
selective removal of water and solutes from the glomerular filtrate back into blood
regulated by hormones (Ca2+ and PTH)
PTH induces kidney to activate more Vitamin D
increases Calcium reabsorption and lowers excretion
secretion
selective removal of certain solutes from the plasma into the tubules
occurs after blood has passed through the glomerulus
excretion
removal or final urine to bladder
tubular system involved in urine production
glomerulus - part of nephron
rich in capillaries and site of plasma filtration into the renal tubes
tubules - site of processing of the plasma filtrate to create urine
hormonal control of water/electrolytes
antidiuretic hormone (ADH)
arginine vasopressin
released by pituitary in response to increases in ECF osmolarity or decreased blood volume
predominantly acts on kidneys to increase water reabsorption
alcohol inhibits ADH secretion and causes dehydration
Renin
enzymes released from kidneys in response to decreased blood pressure
acts in blood on angiotensinogen to produce angiotensin 1
angiotensinogen made in liver
angiotensin 1 - converted to angiotensin 2 in lungs
angiotensin 2
most powerful vasoconstrictor in body
constricts blood vessels to increase blood pressure
increases vasopressin production
also causes release of the hormone aldosterone from adrenal glands
ACE inhibitors - angiotensin-converting-enzyme inhibitors
treat high blood pressure
inhibit ACE enzymes that convert angiotensin 1 to angiotensin 2
inhibit hydrolysis of bradykinin, which is a vasodilator
net effect: lower blood pressure
side effects: cough and angioedema
Sodium (Na+)
Major ECF cation
critically important for regulating body water and electrolyte balance
aids in nutrient absorption
very important for neural and muscular function
efficiently absorbed throughout the entire small intestine and colon
plasma Na+ levels are closely regulated by the kidney (intake = output)
excess amounts filtered and excreted
tubules regulate reabsorption to precisely maintain 145 mEq/L
dietary requirements
NO RDA
minimum ~ 500 mg/day
depending on physical activity and climate suggested to consume 3000mg
table salt is 40% sodium
1 g salt = 400 mg sodium
food sources
processed food contain high amounts
not always in NaCl form; sodium bicarbonate and sodium saccharin are also possible and do not taste salty
sodium sensitivity
occurs in 10% of the population
associated with chronic renal disease, diabetes, hypertension
african american over 50 are prone
sodium deficiency
vomiting, diarrhea, heavy sweating
muscle cramps, mental apathy, loss of appetite
sodium toxicity
acute toxicity causes edema and hypertension
Potassium (K+)
principal cation inside cells
plays major role in fluid and electrolyte balance
nerve and muscle function and fundamental cell processes and growth
90% of absorption in small and large intestine
renal excretion closely matched to intake
hormonal regulation
epinephrine regulates K+ uptake may be important after exercise to prevent hypokalemia
insulin increases uptake by cells after a meal
aldosterone increases K+ uptake into cells and increases urinary excretion
dietary requirements/sources
NO RDA
minimum = 2000 mg/day
DRV = 3500 mg/day
fresh unprocessed foods
fruits and veggies in particular
coffee, tea, milk, potatoes, OJ, animal products major sources in American diet
deficiency
low blood K+ termed hypokalemia
occurs because of diarrhea, vomiting, and severe dehydration
associated with use of certain diuretics, steroids, or abuse of laxatives
causes muscle weakness, paralysis, confusion, cardiac arrhythmias
Low K+ diets may cause hypertension
toxicity
hyperkalemia
mostly from overuse of potassium supplements
hard to induce from diet as kidney will accelerate excretion of excess from dietary intake
results in muscle weakness, vomiting, and heart failure in severe cases