NUTRITIONAL DISEASES

Malnutrition
o
protein energy malnutrition or PEM
o
consequence of

inadequate intake of proteins and calories

deficiencies in the digestion or absorption of

proteins

resulting in the loss of fat and muscle tissue,

weight loss, lethargy, and generalized weakness.
o
In the industrial world and, more recently, also in developing
countries, obesity has become a major public health
problem, associated with the development of diseases such
as diabetes and atherosclerosis
DIETARY INSUFFICIENCY
o
an appropriate diet should provide:
a.
sufficient energy in the form of carbohydrates, fats
and proteins, for the body's daily metabolic needs
b.
amino acids and fatty acids to be used as building
blocks for synthesis of structural and functional
proteins and lipids
c.
vitamins and minerals which function as
coenzymes or hormones in vital metabolic
pathway ; Ca and Phosphate - structural
components
o
Primary malnutrition - one or all of the mentioned
components are missing
o
Secondary malnutrition

supply of nutrient is adequate

malnutrition results from insufficient intakes,

malabsorption impaired utilization or storage,
excess loss, or increased need for nutrients.
o
Conditions that may lead to dietary insufficiencies:
a.
Poverty
b.
Infections
c.
Acute and chronic illnesses. The basal metabolic rate
becomes accelerated in many illnesses resulting in
increased daily requirements for all nutrients. Failure to
recognize these nutritional needs may delay recovery.

PEM is often present in patients with wasting

diseases such as advanced cancers and AIDS
d.
Chronic alcoholism

Alcoholic persons may sometimes suffer PEM but

more frequently have deficiency of several
vitamins, especially thiamine, pyridoxine, folate,
and vitamin A, as a result of dietary deficiency,
defective gastrointestinal absorption, abnormal
nutrient utilization and storage, increased
metabolic needs, and an increased rate of loss.
e.
Ignorance and failure of diet supplementation.
f.
Self-imposed dietary restriction.
PROTEIN-ENERGY MALNUTRITION (PEM)
o
o

occurs in the spectrum of Kwashiorkor to Marasmus

2 differentially regulated protein compartments in the body:
1.
Somatic compartment
proteins in the skeletal muscle
more affectred severely in marasmus
2.
Visceral compartment
protein stores in the visceral organs,
primarily the liver
severely depleted in kwashiorkor
Kwashiorkor
disease of the displaced child
deficiency in priotiens but not in carbohydrates
(calories)
apathy
peripheral edema
subcutaneous fat
moon face
enlarged liver/ fatty liver -- due to reduced
synthesis of the carrier protein component of
lipoproteins
low serum albumin
alert, hungry, eat ravenously when given with food
marked protein deprivation severe loss of the
visceral protein compartment hypoalbuminemia
generalized or dependent edema
may be caused by fad diets or replacement of milk
by rice based beverages
protein deprivation is relateiley greater than the
reduction in total calories
loss of weight is masked by the increased fluid
retention

relatie sparing of subcutaneous fat and muscle

mass
characteristic skin lesions with alternating zones of
hyperpigmentation, areas of desquamation and
hypopigmentation = flaky paint appearance
hair changes - overall loss of color or alternating
bands of pale and darker hair
Marasmus
deficiency of proteins and carbohydrates
starvation
wasting
stundted growth and total loss of subcutaneous
fath with atrophy of the muscles, broomstick arms
nd legs from which skin hang oose
loss of muscle results from catabolism and
depletion of the somatic protein compartments
adaptive response that provides the body with AA
as a source of energy
prematurelyaged face
no edema and hepatomegaly
serum albumin levels are either normal or slightly
reduced
production of leptin is low stimulate the
hypothalamic pituitary-adrenal axis produce
high levels of cortisol contribute to lypoysis
head appears too large for the body
immune deficiency - T-cell mediated immunity
gnaw endlessly on their cloting to appease the
insatiable hunger that plagues them day and night
Causes:

maternal death

inadequate milk substitute

cutting of food supply

MORPHOLOGY (OVERLAPPING CHARACTERISTICS, HYBRID FORMS)

Central anatomic changes in PEM are:

1.
growth failure
2.
peripheral edema in kwashiorkor
3.
loss of body fat and atrophy of muscle, more
marked in marasmus

liver in kwashiorkor, but not in marasmus, is enlarged and

fatty. superimposed cirrhosis is rare

Small bowel
kwashiorkor (rarely in marasmus): decrease in
mitotic index in the crypts of the glands,
associated with mucosal atrophy and loss of villi
and microvilli.
loss of SI enzymes occurs, most often manifested
as dissacharidase deficiency

Bone marrow in both Kwashiorkor and marasmus may be

hypoplastic - result of decrease
numbers of red cell
precursors;
peripheral blood commonly reveals mild to
moderate anemia (multifactorial in origin)
deficiency of iron, folate and protein as well as the
suppressive effects of infection
red cells may be microcytic, normocytic or
macrocytic

brains in infants who are born to malnourished mothers -and

who suffer PEM during the first 1 to 2 years of life has been
reported to show cerebral atrophy, a reduced number of
neurons, and impaired myelinaztion of white matter

Other changes:
thymic
and
lymphoid
atrophy
(more
in
kwashiorkor)
anatomc alterations
deficiencies of other required nutrients
KWASHIORKOR
Apathy
Moon faced
Subcutaneous fat
Edema
Red hair
Growth failure ++

1.
2.
3.

COMPARE AND CONTRAST

MARASMUS
Alert
Wizened
Loss of body fat, loose skin
No edema
No hair changes
Growth failure ++++

Secondary PEM
develops in chronically ill, elderly and bedridden
patients
most obvious signs are:
depletion of SQ fat in the arms, chest wall shourlders or
metacarpal regions
wasting of the quadriceps femoris and deltoid muscles
ankle or sacral edema

Marasmus-Like

Kwashiorkor
like

SETTING
Chronic

Acute

FEATURES
Weight
loss,
muscle
wasting,
decrease
SQ
fat
Normal fat and
muscle edema

LAB
Normal

Albumin
<2.8

is

CACHEXIA
o
Cachexia - PEM, complication in patients with AIDS or
advanced cancers
condition caharacterized by:

extreme weight loss

fatigue

muscle atrophy

anemia

anorexia

edema
Mortality: atrophy of the diaphragm and other
respiratory muscles
Cachetic agents produced by tumors:
a)
PIF (proteolysis inducing factor)
glycosylated peptide excreted in the urine of
weight losing patients with pancreatic, breast,
colon and other cancers
b)
LMF (lipid mobilizing factor)
increases fatty acid oxidation
pro inflammatory cytokines: TNF, IL-2 and IL 6;
TNF and IL-6 acute phase response from the
host increase secretion of C reactive protein and
fibrinogen decreasing plasma concentration of
albumin
o
PIF and pro inflammatory cytokines causes skeletal muscle
breakdown through the NF-kB- induce activation of the
ubiquitin-proteasome pathway degradation of myosin
heavy chain
o
induction of ubiquitin-proteosome pathway involves the two
muscle ubiquitin ligases: MuRFI and MAFBx

o
o

VITAMIN DEFICIENCIES
Fat-soluble vitamins

Primary

Vitamin A and D - very common in

underprivileged tropical areas and
among the poor industrialized contries

Vitamin E and K is less common

Secondary

sporadic

biliary tract/ pancreatic dysfunction or

intestinal malabsoprtion

more readily stored in the body

may be poorly absorbed in fat malabsorption

disorders, caused by disturbances of digestive
functions

Certain
vitamins
can
be
synthesized
endogenously:

vitamin D from precursor steroids

vitamin K and biotin by the intestinal

microflora, and

niacin from tryptophan, an essential

amino acid.
Notwithstanding this endogenous synthesis, a dietary supply
of all vitamins is essential for health.
A deficiency of vitamins may be
a.
primary (dietary in origin)
b. secondary

because of disturbances in

intestinal absorption

transport in the blood, tissue storage, or

metabolic conversion.

FAT SOLUBLE VITAMINS

VITAMIN A
o
group of related compounds that include

retinol (vitamin A alcohol)

etinal (vitamin A aldehyde), and

retinoic acid (vitamin A acid

o
Retinol

is the chemical name given to vitamin A.

transport form

as retinol ester - storage form.

o
The generic term retinoids encompasses vitamin A in its
various forms and both natural and synthetic chemicals that
are structurally related to vitamin A, but may not necessarily
have vitamin Alike biologic activity
o
Animal-derived foods such as liver, fish, eggs, milk, and
butter are important dietary sources of preformed vitamin A.
o
Yellow and leafy green vegetables such as carrots, squash,
and spinach supply large amounts of carotenoids, which are
provitamins that can be metabolized to active vitamin A in
the body.
o
Carotenoids contribute approximately 30% of the vitamin A
in human diets

the most important of these is -carotene, which is

efficiently converted to vitamin A.
o
The Recommended Dietary Allowance for vitamin A is
expressed in retinol equivalents, to take into account both
preformed vitamin A and -carotene.
Absorption
o
Vit A absorption requires bile, pancreatic enzymes and some
level of antioxidants
o
Retinol (ingested as retinol ester) and B-carotene are
absorbed in the intestines B-carotene is converted to
retinol Retinol is transported in chylomicrons to the liver
for esterification and torage
o
Uptake in liver cells takes place through apolipoprotein E
receptor
o
90% of the vitamin A reserves are stored in the liver,
predominantly in the perisinusoidal stellate (Ito) cells)
o
Retinol - stored in the peripheral tissues as retinol ester;
oxidized to form retinoic acid
Function
o
Maintenance of normal vision
The visual process involves four forms of vitamin
Acontaining pigments:
1.
rhodopsin in the rods, the most lightsensitive
pigment
and
therefore
important in reduced light, and
2.
three iodopsins in cone cells, each
responsive to specific colors in bright
light
provision of critical prosthetic group in the visual
pigments in the retina
o
Cell growth and differentiation
Vitamin A and retinoids play an important role in
the orderly differentiation of mucus-secreting
epithelium
All trans-retinoic acid - potent acid derivative of
vitamin A - holds the highest affinity for RARs
o
Metabolic effects of retinoids
The retinoic X receptor (RXR), believed to be
activated by 9-cis retinoic acid, can form
heterodimers with other nuclear receptors, nuclear
receptors involved in drug metabolism, the
peroxisome
proliferator-activated
receptors
(PPARs), and vitamin D receptors
o
Host resistance to infections
The beneficial effect of vitamin A in diarrheal
diseases may be related to the maintenance and
restoration of the integrity of the epithelium of the
gut.
may reduce the bioavailability of vitamin A by
inhibiting retinol binding protein synthesis in the
liver through the acute-phase response associated
with many infections
o
In addition, the retinoids, -carotene, and some related
carotenoids can function as photoprotective and antioxidant
agents
o
Retinoids are used clinically for the treatment of skin
disorders such as severe acne and certain forms of psoriasis,
and also in the treatment of acute promyelocytic leukemia
Deficiency
o

Vitamin A deficiency:
1.
Xeropthalmia
2.
Keratomalacia - epithelium is replaced by
squamous; substantia propria of the cornea breaks
down and liquefies
3.
Corneal scarring and blindness
4.
impaired maintenance of epithelium
5.
impaired immune response
In children, stores of vitamin A are depleted by infections,
and the absorption of the vitamin is poor in newborn infants

o
o

o
o
o

o
o
Toxicity
o

Adult patients with malaborption syndromes, such as celiac

disease, Crohn's disease, and colitis, may develop vitamin A
deficiency, in conjunction with depletion of other fat-soluble
vitamins
Bariatric surgery and, in elderly persons, continuous use of
mineral oil as a laxative may lead to deficiency
Consequences of Vitamin A deficiency:
a.
impaired reproduction
b.
impaired skeletal growth
c.
inccreasd predisposition to cancer of the skin,
lungs and other sites
Night blindess - earliest manifestation of vitamin A
deficiency; impaired vision in reduced light
Persistent deficiency gives rise to a series of changes
involving epithelial metaplasia and keratinization
The most devastating changes occur in the eyes and are
referred to as xerophthalmia (dry eye)

First, there is dryness of the conjunctiva (xerosis

conjunctivae) as the normal lacrimal and mucussecreting epithelium is replaced by keratinized
epithelium

buildup of keratin debris in small opaque plaques

(Bitot spots)

erosion of the roughened corneal surface with

softening and destruction of
the cornea
(keratomalacia) and total blindness
Squamous metaplasia - epithelium lining the upper
respiratory passge and urinary tract is replaced by
keratinizing squamous cells (squamous metaplasia)
Hyperplasia and hyperkeratinization of the epidermis with
plugging of the ducts of the adnexal glands may produce
follicular or papular dermatosis.
Acute toxicity of vvitamin A:
headache
dizziness
vomiting
loss of hair
stupor, and
blurred vision

symptoms that may be confused with

those of a brain tumor (pseudotumor
cerebri)
Chronic toxicity is associated with
weight loss
anorexia
nausea
vomiting, and bone and joint pain
lymphadenopathy and painful bony hyperostosis
premature closure of the fontanels
congenital malformation
Retinoic acid stimulates osteoclast production and activity,
which lead to increased bone resorption and high risk of
fractures

4.

Conversion of 25-OH-D into 1,25-dihydroxyvitamin D,

[1, 25(OH)2D3] in the kidney, the most active form of
vitamin D, through the activity of 1-hydroxylase
o
The production of 1,25-dihydroxyvitamin D in the kidney is
regulated by three main mechanisms:
a.
hypocalcemia stimulates secretion of parathyroid
hormone (PTH), which in turn augments the
conversion of 25-OH-D into 1,25-dihydroxyvitamin
D by activating 1-hydroxylase
b. hypophosphatemia
directly
activates
1hydroxylase, increasing the production of 1,25dihydroxyvitamin D
c.
through a feedback mechanism, increased levels
of 1,25dihydroxyvitamin D down-regulate its own
synthesis through inhibition of 1-hydroxylase
activity
Mechanism of Action
o
1,25-dihydroxyvitamin D, the biologically active form of
vitamin D, is best regarded as a steroid hormone
o
It binds to the high-affinity vitamin D receptor (VDR)
o
The receptors for 1,25-dihydroxyvitamin D are present in
most cells of the body and transduce signals that regulate
plasma levels of calcium and phosphorus, through action on
the small intestine, bones, and kidneys
Effects of Vitamin D on Calcium and Phosphorus Homeostasis
o
Stimulation of intestinal calcium absorption
o
Stimulation of calcium reabsorption in the kidney
o
Interaction with parathyroid hormone (PTH) in the regulation
of blood calcium
o
Mineralization of bone.
o
When hypocalcemia occurs in vitamin D deficiency, PTH
production is elevated, causing
(1)
activation of renal 1-hydroxylase, increasing the
amount of active vitamin D and calcium absorption;
(2)
increased resorption of calcium from bone by
osteoclasts
(3)
decreased renal calcium excretion; and
(4)
increased renal excretion of phosphate

VITAMIN D
o

Vitamin
o

sources of vitamin D include:

a)
Endogenous synthesis in the skin
7-dehydrocholesterol converted to D3 by
UV light
b)
Exogenous dietary surface
Ergosterol converted to D2
The major function of the fat-soluble vitamin D is the
maintenance of adequate plasma levels of calcium and
phosphorus
to
support
metabolic
functions,
bone
mineralization, and neuromuscular transmission
Vitamin D is required for the prevention of
bone diseases known as rickets (in children whose
epiphyses have not already closed), osteomalacia
(in adults)
hypocalcemic tetany: convulsive state caused by
an insufficient extracellular concentration of
ionized calcium, which is required for normal
neural excitation and the relaxation of muscles
D Metabolism
Main steps of Vitamin D metabolism are:
1. Photochemical synthesis of vitamin D from 7dehydrocholesterol in the skin and absorption of
vitamin D from foods and supplements in the gut
2. Binding of vitamin D from both of these sources to
plasma 1-globulin (D-binding protein or DBP) and
transport into the liver
3. Conversion of vitamin D into 25-hydroxycholecalciferol
(25-OH-D) in the liver, through the effect of 25-OHases
(25-hydroxylases that include CYP27A1 and other CYPs)

Deficiency States
o
The normal reference range for circulating 25-(OH)-D is 20 to
100 ng/mL; concentrations of less than 20 ng/mL constitute
vitamin D deficiency
o
equally important cause of vitamin D deficiency is limited
exposure to sunlight.
o
vitamin D deficiency can be prevented by a diet high in fish
oils
o
less common causes of rickets and osteomalacia include
renal disorders causing decreased synthesis of 1,25dihydroxyvitamin D, phosphate depletion, malabsorption
disorders, and some rare inherited disorders
Morphology
o
The basic derangement in both rickets and
osteomalacia is an excess of unmineralized matrix:

Overgrowth of epiphyseal cartilage due to inadequate

provisional calcification and failure of the cartilage
cells to mature and disintegrate

Persistence of distorted, irregular masses of cartilage,

which project into the marrow cavity

Deposition of osteoid matrix on inadequately

mineralized cartilaginous remnants

Disruption of the orderly replacement of cartilage by

osteoid matrix, with enlargement and lateral
expansion of the osteochondral junction

Abnormal overgrowth of capillaries and fibroblasts in

the disorganized zone resulting from microfractures

and stresses on the inadequately mineralized, weak,

poorly formed bone

Deformation of the skeleton due to the loss of

structural rigidity of the developing bones
Rickets is most common during the first year of life

During the nonambulatory stage of infancy, the

head and chest sustain the greatest stresses.

The softened occipital bones may become

flattened, and the parietal bones can be buckled
inward by pressure

with the release of the pressure, elastic recoil

snaps the bones back into their original positions
(craniotabes)

An excess of osteoid produces frontal bossing

and a squared appearance to the head

Deformation of the chest results from overgrowth

of cartilage or osteoid tissue at the costochondral
junction, producing the rachitic rosary.

The weakened metaphyseal areas of the ribs are

subject to the pull of the respiratory muscles and
thus bend inward, creating anterior protrusion of
the sternum (pigeon breast deformity)

When an ambulating child develops rickets,

deformities are likely to affect the spine, pelvis,
and tibia, causing lumbar lordosis and bowing
of the legs
In adults, the lack of vitamin D deranges the normal
bone remodeling that occurs throughout life.

newly formed osteoid matrix laid down by

osteoblasts is inadequately mineralized, thus
producing the excess of persistent osteoid that is
characteristic of osteomalacia

Although the contours of the bone are not

affected, the bone is weak and vulnerable to gross
fractures or microfractures, which are most likely
to affect vertebral bodies and femoral necks.

NONSKELETAL EFFECTS OF VITAMIN D

o
production of 1,25-dihydroxyvitamin D then stimulates the
synthesis of cathelicidin, an antimicrobial peptide from the
defensin family, which is effective against infection by
Mycobacterium tuberculosis
VITAMIN D TOXICITY
o
Prolonged exposure to normal sunlight does not produce an
excess of vitamin D
o
megadoses of orally administered vitamin can lead to
hypervitaminosis
o
In children, hypervitaminosis D may take the form of
metastatic calcifications of soft tissues such as the kidney
o
in adults it causes bone pain and hypercalcemia
VITAMIN E
o
o

US RDA = 10 mgs/day
prevents breakdown of the body tissues

vitamin E does not combine with O2 which is

beneficial to polyunsaturated fats and vitamin A.

Both polyunsaturated oils and vitamin A combine

with O2 and break down

Vitamin E interferes with the break down process

VITAMIN K
o
produced in the intestines - this function is improved with
the presence of cultured milk, like yogurt in the diet
o
Vitamin K is found in nature in 2 forms:
1. K1 (Phylloquinone) - found in plants and
vitamins
2. K2 (Menaquinone) - can be synthesized by many
bacteria
o
K3 (Menadione) is a synthetic form of vitamin K
o
Functions of Vitamin k
a) control blood clotting and is essential for
synthesizing the liver protein that controls the
clotting
b) involve in creating prothrombin, which is a
precursor to thrombin , an important factor in blood
cotting
c)
involed in bone formation and repaor
d) in the intestines: assits in converting glucose to
glycogen - can be stored in liver
o
Deficiency of Vitamin K

Deficiency in newborn: results in hemorrhagic

disease as well as postoperative bleeding and
hematuria while muscle hematomas and intercranial hemorrhages have been reported

Dosage

Toxicity

Males: 80 ug/day
Females 70 ug per day
Dietary fat is necessary for the absorption of this
vitamin
and Symptoms of High Intake
Does not easily occur with normal dietary intake of
this vitamin, but can happen if synthetic
compound (Vit K) is taken
Flushing and sweating
jaundice and anemia

Water Soluble Vitamins

Folate/Folic Acid
Thiamin (Vitamin B1)
Riboflavin (Vitamin B2)
Niacin (Vitamin B3)
Pyridoxine (Vitamin B6)
igue
insomnia
Cobalamin (B12)
Panthotenic Acid
Vitamin C
THIAMINE (VITAMIN B1)
o
B1 is a pyrophosphate; coenzyme in decarboxylation
reactions
o
RDA for adults is 1.1 mg for females and 1.5 mg for males
o
During pregnancy: amount increases to 1.5 mg
o
1.6 mg during breastfeeding
o
Functions:
a)
helps produce energy in all cells of the body
b)
promotes growth and good muscle tone
c)
stabilizes appetite
d)
aids in energy (carbohydrate) metabolism
e)
Essentianl for the normal functioning of the
nervous system, muscle and heart
o
deficiency symptoms of Thiamine

poor appetite

weakness

nerve damage

opinds and needles in les

fatigue

insomnia

loss of weight

vague aches and pains

Beriberi - affects the nervous and cardiovascular

systems, and muscle wasting

Wernicke-Korsakoff syndrome - results in mental

confusion, amnesia and muscular incoordination
RIBOFLAVIN (VITAMIN B2)
o
converted to coenzyme flavin mononucleotide and flavin
adenine dinucleotide, cofactors for many enzymes in
intermediary metabolism
o
RDA for adults is from 1.2 to 1.7 mg

adult men need 1.7 mg daily through age 50; from

age 51, the RDA decreases to 1.4 mg

Adult women need 1.3 mg daily through age 50;

1.2 mg daily from 51 onwards

pregnancy: RDA is 1.6 mg

breastfeeding: increases to 1.8 mg daily for the

first 6 months; 1.7 mg for the second 6 months
o
Functions of Riboflavin
a)
necessary for carbohydrate, fat and protein
metabolism
b)
involved with the action of other B vitamins (folate
and pyridoxine)
c)
essential for growth and general health
d)
promotes smooth skin
e)
necessary for the maintenance of vision, nails and
hair
f)
aids in the formation of antibodies and red blood
cells
o
Deficiency symptoms of Riboflavin

itching and burning eyes, which becomes sensitive

to ight

cracks and sores in moith and lips

bloodshot eyes

dry, flaky skin

retarded growth

sore, red tongue

skin rash

digestive disturbances

b)

emotional changes, such as depression and

hypochondria
o
Excessive intake and toxicity symptoms of riboflavin - may
interfere with anticancer medications
FOLIC ACID
o

RDA:

200 ug for men

180 ug for women
increased to 400 ug during pregnancy
280 ug during breastfeeding
o
of Folic Acid
necessary for DNA and RNA synthesis
Essential for growth and reproduction of all body
cells
c)
works with vitamin B12 in the formation of red
blood cells
d)
ains in amino acid metabolism
o
Deficiency symptoms in Folic Acid

pernicious anemia (large cell type)

depression

impairs growth

in pregnancy: greater risk of delivering a baby with

neural tube deficits such as spina bifida
o
Excessive intake and toxicity symptoms

(400 to 1000 ug)

may mask the symptoms of vitamin B12

deficiency

may interfere with other medications

intestinal problems
NIACIN/VITAMIN B3
o
incorporated into NAD; redox
o
comes from two sources:
1.
niacin
2.
amino acid tryptophan, part of which converts into
niacin
o
Niacin recommendations are given in NE or niacin equivalent
o
RDA for Niacin:

13-20 mg NE

Adult men need 19 mg NE daily through age 50;

age 51, the RDA decreases to 15 mg NE

Adult women need 15 mg NE daily through age 50;

13 mg NE daily from 51 on

pregnancy, the RDA is 17 mg NE

breastfeeding. the RDA increases to 20 mg NE

daily

Functions
a)
b)

Functions
a)
b)
c)
d)
e)

of Niacin
helps metabolize protein, carbohydrates and fat
maintains the NS
may reduce high blood pressure
reduces the cholesterol level in the blood
helps maintain healthy skin, tongue and digestive
system
f)
improves circulation
Deficiency symptoms of niacin

pellagra, characterized by: DERMATITIS, DIARRHEA

and DEMENTIA

weakness

irritability

insomnia

headaches

muscular weakness

loss of appetite

gastronintestinal disturbance
Excessie intake and toxicity symptoms

300 to 600 mg

flushed skin

raskes

ulcers

doses exceeding 2.5 grams/day can cause liver

damage and glucose intolerance

PYRIDOXINE (VITAMIN B6)

o
RDA

2.0 mg daily for adult males

1.6 mg for adult females

pregnancy: the RDA increases to 2.2 mg

2.1 mg during breast-feeding.

o
Dietary requirements increase with increased protein intake
o
Functions of Vitamin B6
a)
aids in protein metabolism

helps in the conversion of tryptophan (an amino

acid) to niacin (vitamin B3)
c)
helps with normal brain function
d)
essential for normal growth
e)
helps maintain a proper balance of sodium and
phosphorous in the body
f)
aids in the formation of antibodies
g)
aids in the production of hormones and the
formation of RBC
deficiency symptoms of vitamin B6

anemia

nerve dysfunction

dermatitis (inflammation of the skin)

nervousness

flaky or greasy skin

fatigue

insomnia

arm and leg cramps

dermatitis

irritability or depression

mental convulsions among infants

loss of hair

loss of muscular control

Excessive intake and toxicity symptoms

250-1000 mg

nerve damage

COBALAMIN (VITAMIN B12)

o
the RDA is 2.o ug daily for adults

2.2 micrograms during pregnancy

2.6 ug during breastfeeding

o
Function of Vitamin B12
a)
necessary for carbohydrate, fat and protein
metabolism
b)
helps in the formation and regeneration of RBC
c)
helps maintain the CNS
d)
necessary for folate activity
e)
promotes growth in children
f)
needed for Ca absorption
g)
increases energy
o
Deficiency symptoms of Cobalamin

weakness and fatigue

poor appetite

red sore tongue or smooth tongue

growth failure in children

nerve damage

pernicious anemia (large cell type)

degeneration of peripheral nerves leading to

paralysis
o
Causes of Vitamin B12 deficiency:

inadequate intake - vegans

absorption defects - blind loop syndrome, tropical

sprue

intrinsic factor deficiency - pernicious anemia,

gastrectomy and others
ASCORBIC ACID (VITAMIN C)
o
protects the body by attacking free radicals in body fluids,
not in fat tissue like the fat soluble antioxidant which may
protect different parts of the body
o
Vitamin C is sensitive to heat
o
RDA for Vitamin C

adults: 60 mg daily

during pregnancy, RDA is 70 mg

people who smoke need about twice as much as

vitamin C; a nonsmoker at least 100 mg daily
o
Major functions of vitamin C
a)
essential for healthy teeth, gums, skin, blood and
bones
b)
helps heal wounds, scar tissue and fractures
c)
aids in the absorption of iron from plant sources of
food
d)
builds resistance to infection, maintains WBC
function
e)
aids in the formation of collagen
f)
provides antioxidant protection. - prevents
conversion of nitrates
into cancer causing
substances
g)
aids in the treatment of the common cold
o
Deficiency symptoms of Vitamin C

scurvy

disease that cuses excessive bleeding,

loose teeth, and swollen gums

slow healing of wounds and fractures

swollen or painful joints

bruising and petichae

nosebleeds

impaired digestion

loss of appetifte

aching jounts
o
excessive intake and toxicity

(1000 to 5000 mgs)

diarrhea

may cause kidney stones

impaired immune function

withdrawal symptoms
PANTHOTENIC ACID
o
incorporated in Coenzyme A
o
no specific RDA for panthotenic acid
o
adults: 4-7 mg is estimated to be safe and adequate
o
Functions:
a)
helps convert proteins, carbohydrates, fats into
energy
b)
synthesizes hormones and cholesterol
c)
fights infections by building antibodies
d)
improves the body's resistance to stress
o
Deficiency symptoms of panthotenic acid:

retards growth

infertility

fatigue

irritability

skin abnormalities

weakness

depression

decreased resistance to infection

muscle cramps
o
Excessive intake and toxicity symptoms

10-20 h

occasional diarrhea

water retention
TRACE ELEMENTS
Selected Trace Elements and Deficiency Syndromes
Element

Function

Zinc

Component of
enzymes,
principally
oxidases

Basis of Deficiency
Inadequate
supplementatio
n in artificial
diets
Interference
with absorption
by other
dietary
constituents
Inborn error of
metabolism

Clinical Features
Rash around
eyes, mouth,
nose, and anus
called
acrodermatitis
enteropathica
Anorexia and
diarrhea
Growth
retardation in
children
Depressed mental
function
Depressed wound
healing and
immune response
Impaired night
vision
Infertility

Iron

Essential
component of
hemoglobin as
well as several
iron-containing
metalloenzyme
s

Inadequate diet
Chronic blood
loss

Hypochromic microcytic
anemia ( Chapter 14 )

Iodine

Component of
thyroid
hormone

Inadequate supply in
food and water

Goiter and
hypothyroidism
( Chapter 24 )

Copper

Component of
cytochrome c
oxidase,
dopamine -

Inadequate
supplementatio
n in artificial
diet

Muscle
weakness
Neurologic

Element

Fluoride

Function

Basis of Deficiency

hydroxylase,
tyrosinase,
lysyl oxidase,
and unknown
enzymes
involved in
cross-linking
collagen

Interference
with absorption

Mechanism
unknown

Inadequate
supply in soil
and water

Clinical Features
defects
Abnormal
collagen crosslinking

Dental caries ( Chapter

16 )

Inadequate
supplementatio
n
Selenium

Compo
nent of
glutathi
one
peroxid
ase

Inadequate amounts
in soil and water

Myopathy
Cardiomyopathy
(Keshan
disease)

Antioxid
ant with
vitamin
E
NUTRITIONAL EXCESSES AND IMBALANCES
o
OBESITY

obese

men with more than 25% body fat

women with more than 30% body fat

most accurate measures are to weigh a person underwater

or to use an X ray test call Dual Energy X-Ray absorptiometry
(DEXA)
o
o
o
o
o

body mass index - medical standard used to measure

overweight and obesity
uses mathematical formula based on a person's height and
weight
BMI = weight in kg/height in meters squared
BMI of 25 to 29.9 indicates a person is overweight
BMI of 30 or higher is obese

Body Shape
women typically collect fat in their hips and buttocks, giving
them a pear shape

men usually build up fat stores around their belies, giving

them more of an apple shape

waist measurement of more than 35 inches; men more than

40 inches have higher health risk because of their fat
distribution
Causes of Obesity

Genetic Factors
Environemental Factors
Psychological Factors
Otehrs:

Hypothyroidism

Cushings syndrome

depression

neurological problems that can lead to overeating

drugs sucha s steroids and some antidepressants

may cause weight gain

POTENTIAL
OBESITY

PATHWAYS

IN

THE

HYPOTHALAMIC

REGULATION

OF

OBESITY
GAIN OF WEIGHT
INCREASE IN THE
AMOUNT OF LEPTIN
SIGNALLING TO THE
HYPOTHALAMUS
INCREASE EXPRESSION
OF MELANOCYTE
STIMULATING HORMONE;
BINDING TO THE AGOUTI
MELANOCORTIN 4
RECEPTOR
INCREASED ENERGY
EXPENDITURE AND
DECREASED FOOD
INTAKE

STARVATION
LOSS OF WEIGHT
DECREASE IN THE
AMOUNT OF LEPTIN
SIGNALLING TO THE
HYPOTHALAMUS
DECREASE IN THE
NEUROPEPTIDE Y
PRODUCTION; BINDING
TO THE NEUROPEPTIDE Y
RECEPTOR
DECREASED ENERGY
EXPENDITURE AND
INCREASED FOOD INTAKE

The

peripheral or afferent system

o
generates signals from various sites.
o
Its main components are

leptin and adiponectin - produced by fat cells,

ghrelin from the stomach

peptide YY (PYY) from the ileum and colon, and

insulin from the pancreas.

The arcuate nucleus in the hypothalamus
o
processes and integrates neurohumoral peripheral signals
o
generates efferent signals.
o
It contains two subsets of first-order neurons:
(1) POMC (pro-opiomelanocortin) and CART (cocaine
and amphetamine-regulated transcripts) neurons

enhance energy expenditure and weight

loss through the production of the
anorexigenic -melanocyte-stimulating
hormone (MSH), and the activation of
the melanocortin receptors 3 and 4
(MC3/4R) in second-order neurons.
(2) neurons containing NPY (neuropeptide Y) and
AgRP (agouti-related peptide)

NPY/AgRP neurons promote food intake

(orexigenic effect) and weight gain,
through the activation of Y1/5 receptors
in secondary neurons.
These first order neurons communicate
with second order neurons
The efferent system that carries the signals generated in the second
order neurons of the hypothalamus to control food intake and energy
expenditure.
The hypothalamic system also communicates with forebrain and
midbrain centers that control the autonomic nervous system
LEPTIN
o

leptin secretion is stimulated when fat stores are abundant.

insulin-stimulated glucose metabolism is an important factor

in the regulation of leptin levels
o
Leptin levels are regulated by multiple post-transcriptional
mechanisms that affect its synthesis, secretion, and turnover
o
eptin stimulates POMC/CART neurons that produce
anorexigenic
neuropeptides
(primarily
melanocytestimulating hormone) and inhibits NPY/AgRP neurons that
produce feeding-inducing (orexigenic) neuropeptides
o
Humans with loss-of-function mutations in the leptin system
develop early-onset severe obesity, but this is a rare
condition
o
Mutations of melanocortin receptor 4 (MC4R) and its
downstream pathways are more frequent, being responsible
for about 5% of massive obesity.

In
these
individuals,
sensing
of
satiety
(anorexigenic signal) is not generated, and hence
they behave as if they are undernourished
o
Leptin regulates not only food intake but also energy
expenditure, through a distinct set of pathways.

Thus, an abundance of leptin stimulates physical

activity, heat production, and energy expenditure
ADIPONECTIN
o
fat-burning molecule and the guardian angel against
obesity, directs fatty acids to muscle for their oxidation.
o
It decreases the influx of fatty acids to the liver and the total
hepatic triglyceride content
o
decreases the glucose production in the liver, causing an
increase in insulin sensitivity and a protection against the
metabolic syndrome
o
Binding of adiponectin to its receptors triggers signals that
activate cyclic adenosine monophosphateactivated protein
kinase, which in turn phosphorylates and inactivates acetyl
coenzyme A carboxylase, a key enzyme required for fatty
acid synthesis.
ADIPOSE TISSUE
o
Cinderella cells of metabolism
o
increased production of cytokines (TNF, IL6 and IL1, IL8,
chemokines and steroid hormones) by adipose tissue creates
an asymptomatic inflammatory state that includes high
levels of circulating C reactive protein
GUT HORMONES
o
include ghrelin, PYY, pancreatic polypeptide, insulin, and
amylin among others
o
Ghrelin

is produced in the stomach and in the arcuate

nucleus of the hypothalamus.

It is the only known gut hormone that increases

food intake (orexigenic effect);

acts by binding the growth hormone secretagogue

receptor, which is abundant in the hypothalamus
and the pituitary.

stimulates NPY/AgRP neurons to increase food

intake.

Ghrelin levels rise before meals and fall between 1

and 2 hours after eating

in obese individuals the postprandial suppression

of ghrelin is attenuated, leading to maintenance of
the obesity
o
PYY

is secreted from endocrine cells in the ileum and

colon.

Plasma levels of PYY are low during fasting and

increase shortly after food intake.

Intravenous administration of PYY reduces energy

intake, and its levels generally increase after
gastric bypass surgery.

By contrast, levels of PYY generally decrease in

individuals with the Prader-Willi syndrome (caused
by loss of imprinted genes on chromosome 15q11
q13)

may
contribute
to
the
development
of
hyperphagia and obesity in these persons
o
Amylin

a peptide secreted with insulin from pancreatic cells

reduces food intake and weight gain, is also being

evaluated for the treatment of obesity and
diabetes.

Both PYY and amylin act centrally by stimulating

POMC/CART neurons in the hypothalamus, causing
a decrease in food intake.
o

Consequences OF Obesity
Type 2 diabetes
heart disease

high blood pressure and stroke

obesity is also linked to higher rates of certain types of
cancer:

obese men are more likely than non obese men to

die from colon cancer, recutum or prostate

obese women are more likely than non obese

women to die from cancer of the gallbladder,
breast uterus, cervix or ovaries
Other Diseases Associated with Obesity
gallbladder disease and gallstones
liver disease
osteoarthritis, a disease in which the joints deteriorate
gout
pulmonary problems including sleep apnea
reproductive problems in women, including menstrual
irregularities and infertility
ANOREXIA NERVOSA
o
refusal to maintain the body in <85% of the ideal body
weight
o
overvaluation of weight and shape; denial of low body
weight
o
amennorheic
o
self induced starvation
o
risks:

females

teens to 20s

oldest daught

middle to upper class

well educated

perfectionist

high achievers
o
distorted body perception
o
restriction of food/purging
o
exercise
BULIMIA
o
binge-purge syndrome
o
clinical manifestations

fluid electrolyte imbalance

sore throat

dental decay

vomiting becomes automatic

death is possible
o
behavior modification and counseling
o
treatment prognosis is good
o
more prevalent than anorexia nervosa in 10-15% of college
age females

Anorexia VS Bulimia

Anorexia nervosa - self induced starvation

Bulimia - self induced vomiting purging after binge eating

SYMPTOMS
Excessive weight loss
Diet even when thin
Believe when they
are fat even when
severely underweight
Amenorrhea
>
3
months
Binging
Purging

ANOREXIA

BULIMIA

DIETS, CANCER and ATHEROSCLEROSIS

o

Three aspect of diet are of major concern in carcinogenesis:

1.
content of exogenous carcinogens
2.
endogenous synthesis of carcinogens from dietary
components
3.
lack of protective factors

EXOGENOUS CARCINOGENS
o
Aflatoxin

involved in the development of hepatocellular

carcinoma

exposiure to aflatoxin mutation in codon 249 of

the p53 gene
ENOGENOUS CARCINOGENS
o
gastric carcinoma
o
Nitrosamine and nitrosamide - induce gastric cancer in
animals