Download nutritional disorders

FARHANA ZAKARIA
 An adequate diet should contain
1- Energy in the form of carbohydrates , fats , proteins
2- Essential aminoacids and fatty acids to be used as building
blocks for synthesis of structural and functional proteins
and lipids.
3- Vitamins and minerals- as coenzymes or hormones in vital
metabolic pathways
 Common causes of undernutrition :
1- Ignorance and poverty
2- Chronic alcoholism
3- Acute and chronic illnesses
4- Self- imposed dietary restriction
Other less common causes are malabsorption
syndromes, genetic diseases, specific drug therapies
and total parenteral nutrition .
PEM
 Severe PEM is a serious, often lethal disease.
 It is common in third world countries, where up to 25% of
children may be affected, and where it is a major factor in
the high death rates among children younger than 5 years.
 PEM refers to a range of clinical syndromes characterized
by a dietary intake of protein and calories inadequate to
meet the body's needs.
 The two ends of the spectrum are known as Marasmus
and Kwashiorkor.
PEM inadequate dietary intake of protein and calories .
Diagnosis of PEM:
 Body weight for a given height
 Fat stores
 Muscle mass
 Thickness of skin folds
 Measurement of serum proteins
 There are two protein compartments in the body:
the somatic protein compartment, represented by skeletal
muscles, if the somatic protein is catabolized,resultant
reduction in muscle mass is reflected by reduced
circumference of the midarm.
2. the visceral protein compartment, represented by protein
stores in the visceral organs, primarily the liver.
Measurement of serum proteins provides a measure of
adequacy of visceral proteins compartment .
1.
 The diagnosis of PEM is obvious in its most severe form.
 In mild to moderate forms, the usual approach is to
compare the body weight for a given height with standard
tables; other parameters are also helpful, including
evaluation of fat stores, muscle mass, and serum proteins.
 With a loss of fat, the thickness of skinfolds (which
includes skin and subcutaneous tissue) is reduced.
 A child whose weight falls to less than 80% of normal is
considered malnourished
 Marasmus refers to malnutrition caused primarily by
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severe reduction in calorie intake.
Results in greater than 60% reduction in body weight
adjusted for height and sex.
Child with marasmus suffers growth retardation and a loss
of muscle
Subcutaneous fat is also mobilized
The extremities appear emaciated , by comparison , the
head appears too large for the body .
 Anemia and manifestations of multivitamin deficiencies
are present, and there is evidence of immune deficiency,
particularly T cell- mediated immunity.
 Hence, concurrent infections are usually present .
Kwashiorkor
 Protein deprivation is relatively greater than the
reduction in total calories.
 Marked protein deprivation is associated with severe
loss of the visceral protein component and the
resultant hypoalbuminemia gives rise to generalized
or dependent edema.
 Weight is typically 60% to 80% of normal.
 The true loss of weight is masked by the increased fluid
retention (edema)
 Relative sparing of subcutaneous fat and muscle mass.
 Characteristic skin lesions with alternating zones of
hyperpigmentation , areas of desquamation and
hypopigmentation , giving a flaky paint appearance.
 Hair changes include overall loss of colour or alternating
bands of pale and darker hair, straightening, line texture,
and loss of firm attachment to the scalp.
 Enlarged fatty liver
 Apathy , listlessness , loss of appetite.
 Other vitamin deficiencies present
 Defects in immunity and secondary infections.
Secondary PEM
 Common complication in advanced cancer and AIDS
Physical signs include:
 Depletion of subcutaneous fat in the arms , chest wall ,
shoulders or metacarpal regions
 Wasting of the quadriceps femoris and deltoid
muscles
 Ankle or sacral edema.
Morphology in PEM
Central anatomic changes include:
 Growth failure
 Peripheral edema in kwashiorkor
 Loss of body fat and atrophy of muscle more marked
in marasmus
Kwashiorkor
 Liver is enlarged and fatty , superimposed cirrhosis is rare.
 Small bowel shows a decrease in the mitotic index in the
crypts of the glands , associated with mucosal atrophy and
loss of villi and microvilli.
 Concurrent loss of small intestine enzymes occur most
often manifested as disaccharidase deficiency .
 Thus infants may initially not respond to a full strength
milk based diet.
 With treatment mucosal changes are reversible.
 Bone marrow in both are hypoplastic mainly because of
decreased no. of red cell precursors.
 Anaemia is usually present , most often microcytic
hypochromic.
 But a concurrent deficiency of folates may lead to a mixed
microcytic macrocytic anaemia.
 Brain: In some infants who suffer PEM during the first 1-2
years show cerebral atrophy, reduced number of neurons,
impaired myelination of the white matter.
 Other changes:
1. Thymic and lymphoid atrophy (More marked in
kwashiorkor).
2. Anatomic alterations induced by intercurrent infections,
3. Deficiencies of other required nutrients such as iodine
and vitamins
KWASHIORKOR
 The infant shows generalised
oedema, seen in the form of
puffiness of the face, arms
and legs.
Anorexia Nervosa and Bulimia
 Anorexia nervosa is self-induced starvation, resulting in
marked weight loss.
 Bulimia is a condition in which the patient binges on food
and then induces vomiting.
 These eating disorders occur primarily in previously
healthy young women who have developed an obsession
with attaining thinness.
Clinical findings:
 Amenorrhea,
 Other common findings, related to decreased thyroid
hormone release, include cold intolerance, bradycardia,
constipation, and changes in the skin and hair.
 The skin becomes dry' and scaly and may be yellow owing
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to excess carotene in the blood.
Body hair may be increased but is usually fine and pale
(lanugo).
Bone density is decreased
As expected with severe PEM, anemia, lymphopenia, and
hypoalbuminemia may be present.
A major complication of anorexia nervosa is an increased
susceptibility to cardiac arrhythmia and sudden death,
resulting in all likelihood from hypokalemia.
BULIMIA
 In bulimia, binge eating is the norm. Huge amounts of
food, principally carbohydrates are ingested, only to be
followed by induced vomiting.
 Although menstrual irregularities are common,
amenorrhea occurs in less than 50% of bulimic patients
 The major medical complications (1) electrolyte
imbalances (hypokalemia),which predispose the patient to
cardiac arrhythmias; (2) pulmonary aspiration of gastric
contents; and (3) esophageal and stomach cardiac rupture.
Vitamin Deficiencies
 Thirteen vitamins are necessary for health; four-A, D,
E, and K-are fat-soluble, and the remainder are water
soluble.
 Certain vitamins can be synthesized endogenouslyvitamin D from precursor steroids, vitamin K and
biotin by the intestinal microflora, and niacin from
tryptophan, an essential amino acid.
VITAMIN A
 The fat-soluble vitamin A is actually a group of related
natural and synthetic chemicals that exert a hormone-like
activity or function.
 Retinol is the most important form of vitamin A; it is the
transport form and, as the retinol ester, also the storage
form. It is oxidized in vivo to the aldehyde retinal (the form
used in visual pigment) and retinoic acid.
 Important dietary sources of vitamin A are animal-derived
(e.g., liver, fish, eggs, milk, butter). Yellow and leafy green
vegetables such as carrots, squash, and spinach .
 Retinoids, refers to both natural and synthetic chemicals
that are structurally related to vitamin A but do not
necessarily have vitamin A activity.
 As with all fats, the digestion and absorption of carotenes
and retinoids require bile, pancreatic enzymes, and some
level of antioxidant activity in the food.
 Retinol, whether derived from ingested esters or from βcarotene , is transported in chylomicrons to the liver for
esterification and storage.
 More than 90% of the body's vitamin A reserves are stored
in the liver, predominantly in the perisinusoidal stellate
(lto) cells.
 In healthy persons who consume an adequate diet, these
reserves are sufficient for at least 6 months' deprivation.
 Retinoic acid, on the other hand, can be absorbed
unchanged; it represents a small fraction of vitamin A in
the blood and is active in epithelial differentiation and
growth but not in the maintenance of vision.
 When dietary intake of vitamin A is inadequate, the retinol
esters in the liver are mobilized, and released retinol is
then bound to a specific retinol-binding protein (RBP),
synthesized in the liver.
 The uptake of retinol by the various cells of the body is
dependent on surface receptors specific for RBP, rather
than for the retinol.
 Retinol is transported across the cell membrane, where it
binds to a cellular retinol-binding protein, and the RBP is
released back into the blood.
 In humans, the best-defined functions of Vitamin A are:
Maintaining normal vision in reduced light
2. Potentiating the differentiation of specialized epithelial
cells, mainly mucus-secreting cells
3. Enhancing immunity to infections, particularly in
children and particularly measles
 The retinoids, β-carotene, and some related carotenoids
have shown to function as photoprotective and antioxidant
agents.
1.
 The visual process involves four forms of vitaminA-
containing pigments: rhodopsin in the rods, and three
iodopsins in cone cells,
 The synthesis of rhodopsin from retinol involves (1)
oxidation to all-trans-retinal, (2) isomerization to 11-cisretinal, and (3) interaction with the rod protein, opsin, to
form rhodopsin.
 When a photon of light impinges on the dark-adapted
retina, rhodopsin undergoes a sequence of configurational
changes to ultimately yield all-trans-retinal and opsin.
 In the process, a nerve impulse is generated (by changes in
membrane potential) that is transmitted via neurons from
the retina to the brain.
 During dark adaptation, some of the all-trans-retinal is
reconverted to 11-cis-retinal. but most is reduced to retinol
and lost to the retina,
 Vitamin A plays an important role in the orderly
differentiation of mucus-secreting epithelium; when a
deficiency state exists, the epithelium undergoes squamous
metaplasia and differentiation to a keratinizing epithelium.
 Host resistance to infections, stimulate the immune
system, possibly through the formation of a metabolite
called 14-hydroxyretinol.
Vitamin A deficiency
 One of the earliest manifestations of vitamin A deficiency
is impaired vision, particularly in reduced light (night
blindness).
 Because vitamin A and retinoids are involved in
maintaining the differentiation of epithelial cells,
persistent deficiency gives rise to a series of changes,
 Collectively, the ocular changes are referred to as
xerophthalmia (dry eye).
 First, there is dryness of the conjunctiva (xerosis
conjunctivae) as the normal lachrymal and mucussecreting epithelium is replaced by keratinized epithelium.
 This is followed by the build-up of keratin debris in small
opaque plaques (Bitot spots) and, eventually, erosion of the
roughened corneal surface with softening and destruction
of the cornea (keratomalacia) and total blindness.
VITAMIN A DEFICIENCY
 The epithelium lining the upper respiratory passage and
urinary tract is replaced by keratinizing squamous cells
(squamous metaplasia).
 Loss of the mucociliary epithelium of the airways
predisposes to secondary pulmonary infections, and
desquamation of keratin debris in the urinary tract
predisposes to renal and urinary bladder stones.
 Hyperplasia and hyperkeratinization of the epidermis with
plugging of the ducts of the adnexal glands may produce
follicular or papular dermatosis.
Vitamin A Toxicity
 Both short- and long-term excesses of vitamin A may
produce toxic manifestations
 The clinical consequences of acute hypervitaminosis A
include headache, vomiting, stupor, and papilledema,
symptoms suggestive of brain tumor.
 Chronic toxicity is associated with weight loss, nausea, and
vomiting,
 Although synthetic retinoids used for the treatment of acne
are not associated with the complications listed, their use
in pregnancy should be avoided owing to a, wellestablished increase in the incidence of congenital
malformations.
VITAMIN D
 The major function of the fat-soluble vitamin D is the
maintenance of normal plasma levels of calcium and
phosphorus.
 With respect to tetany, vitamin D maintains the correct
concentration of ionized calcium in the extracellular fluid
compartment required for normal neural excitation and
relaxation of muscle.
 Insufficient ionized calcium in the extracellular fluid
results in continuous excitation of muscle, leading to the
convulsive state, hypocalcemic tetany.
Metabolism of Vitamin D
 The major source of vitamin D for humans is endogenous
synthesis in the skin by photochemical conversion of a precursor,
7-dehydrocholesterol, via the energy of solar or artificial
ultraviolet (UV) light.
 Depending on the skin's level of melanin pigmentation, which
absorbs UV light, and the amount of exposure to sunlight, about
90% of the vitamin D needed is endogenously derived.
 Only the small remainder must be obtained from dietary
sources, such as deep-sea fish, plants, and grains; this requires
normal fat absorption.
 In plant sources, vitamin D is present in its precursor form
(ergosterol), which is converted to vitamin D in the body.
 Metabolism of vitamin D as follows
Absorption of vitamin D along with other fats in the gut
or synthesis from precursors in the skin.
2. Binding to plasma α1-globulin (D-binding protein) and
transport to liver.
3. Conversion to 25-hydroxyvitamin D (25-0H-D) by 25hydroxylase in the liver.
4. Conversion of 25-0H-D to 1,25-dihydroxyvitamin D
[1,25(OH)2-D] by α1-hydroxylase in the kidney;
biologically this is the most active form of vitamin D.
1.
 The production of 1,25(OH)2-D by the kidney is regulated
by three mechanisms:
1. In a feedback loop, increased levels of 1,25(OH)2-D
down-regulate synthesis of this metabolite by inhibiting
the action of α1-hydroxylase, and decreased levels have
the opposite effect.
2. Hypocalcemia stimulates secretion of parathyroid
hormone (PTH), which in turn augments the conversion
of 25-0H-D to 1,25(OH)2-D by activating α1-hydroxylase.
3. Hypophosphatemia directly activates α1-hydroxylase and
thus increases formation of 1,25(OH)2-D.
 The active form of vitamin D
Stimulates intestinal absorption of calcium and
phosphorus
2. Collaborates with PTH in the mobilization of calcium
from bone
3. Stimulates the PTH-dependent reabsorption of calcium
in the distal renal tubules
1.
 The effects of vitamin D on bone depend on the plasma
levels of calcium. On the one hand, with hypocalcemia,
1,25(OH)2-D collaborates with PTH in the resorption of
calcium and phosphorus from bone to support blood
levels.
 On the other hand, vitamin D is required for normal
mineralization of epiphyseal cartilage and osteoid matrix.
 Vitamin D favors the formation of osteoclasts from their
precursors (monocytes)
 The main function of vitamin D may be to maintain
calcium and phosphorus at supersaturated levels in the
plasma.
 Vitamin D clearly activates osteoblasts to synthesize the
calcium-binding protein, osteocalcin, involved in the
deposition of calcium into osteoid matrix and may thus
contribute to bone mineralization.
Vitamin D-deficiency
 Rickets in growing children and osteomalacia in adults are
worldwide skeletal diseases.
 They may result from deficient diets, but probably more
important is limited exposure to sunlight (heavily veiled
women, children born to vitamin D-deficient mothers,
northern climates with scant sunlight).
 Rickets : The bowing of
legs in a toddler due to
the formation of poorly
mineralized bone
A deficiency of vitamin D tends to cause hypocalcemia.
 When hypocalcemia occurs, PTH production is increased,
which
1) activates renal α1-hydroxylase, thus increasing the
amount of active vitamin D and calcium absorption;
2) mobilizes calcium from bone;
3) decreases renal calcium excretion; and
4) increases renal excretion of phosphate.
 Thus, the serum level of calcium is restored to near normal,
but hypophosphatemia persists, and so mineralization of
bone is impaired.
CAUSES OF RICKETS OR OSTEOMALACIA
1. Decreased endogenous synthesis of vitamin D
 a. Inadequate exposure to sunlight
 b. Heavy melanin pigmentation of skin (blacks)
2. Decreased absorption of fat-soluble vitamin D in the intestine
 a. Dietary lack
 b. Biliary tract, pancreatic, or intestinal dysfunction
3. Enhanced degradation of vitamin D and 25-0H-D
 a. Phenytoin, phenobarbital, rifampin induction of cytochrome P-450
enzymes
4. Impaired synthesis of 25-0H-D
 a. Diffuse liver disease
5. Decreased synthesis of 1,25(OH)2-D
 a. Advanced renal disease with failure
 b. Vitamin D-dependent rickets type I (inherited deficiency of
renal α1-hydroxylase)
6. Target organ resistance to 1,25(OH)2-D
 a. Vitamin D-dependent rickets type II (congenital lack of or
defective receptors for active metabolite)
7. Phosphate depletion
 a. Poor absorption-long-term use of antacids, which bind
phosphates and render them insoluble
 b. Renal tubular disorders, acquired or genetic, causing
increased excretion
Morphology
 There 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,
many of 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 because of microfractures and stresses
on the inadequately mineralized, weak , poorly formed
bone.
 Deformation of the skeleton due to loss of structural
rigidity of the developing bones.
 Craniotabes
 Frontal bossing due to excess osteoid
 Squared appearance of the head
 Rachitic rosary
 Pigeon breast deformity
 Harrison’s groove
 Lumbar lordosis
 Bowing of the legs
In adults
 Osteomalacia: The newly formed osteoid matrix laid down
by osteoblasts is inadequately mineralized producing
excess of persistent osteoid .
 The contours of the bone are not affected but the bone is
weak and vulnerable to gross fractures or microfractures.
 On histological examination the unmineralized osteoid can
be visualised as a thickened layer of matrix arranged about
the more basophilic, normally mineralized trabeculae.
HYPERVITAMINOSIS D
 Most common cause is excess consumption of vitamin
preparations.
 Abnormal conversion of vit D to biologically active
metabolites is occasionally seen in granulomatous diseases
such as sarcoidosis.
 Response to excess vitamin D is hypercalcaemia resulting
in nephrolithiasis, nephrocalcinosis, ectopic calcification
Vitamin E
 Vitamin E is one of the group of antioxidants that serve to
scavange free radicals formed in redox reactions
throughout the body.
 The activity of this vitamin is found principally in αtocopherol.
Causes of deficiency :
 Fat malabsorption that accompanies cholestasis , Cystic
fibrosis ,
 Low birth weight infant with immature liver and GIT
 Abetalipoproteinemia
 Rare autosomal recessive syndrome of impaired vitamin E
metabolism.
Nervous system:
• Degeneration of the axons in the posterior columns of the
spinal cord, with focal accumulation of lipopigment and
loss of nerve cells in the dorsal root ganglia, attributed to a
dying-back type of axonapathy.
• Myelin degeneration in sensory axons of peripheral nerves
• Features of both primary and degenerative muscle disease
of skeletal muscle may be present .
 Vitamin E-deficient erythrocytes are more susceptible
to oxidative stress and have a shorter half-life in the
circulating blood.
Vitamin K
 Vitamin K is a cofactor for a liver microsomal carboxylase
that is necessary to convert glutamyl residues in certain
protein precursors to γ-carboxyglutamates.
 Clotting factors VII, IX, and X and prothrombin all require
carboxylation of glutamate residues for functional activity
 Activation of anticoagulant proteins C and S also requires
glutamate carboxylation
 Sources
 endogenous intestinal bacterial flora
 diet
Vitamin K Deficiency
 Causes
 Fat malabsorption
 Reduced gut bacterial flora
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administration of wide spectrum antibiotics
neonatal period before gut is colonized
 Liver disease with reduced recycling of vitamin K
 Effects of vitamin K deficiency
 Bleeding diathesis characterised by hematomas ,
hematuria , malena , ecchymoses , and bleeding from
the gums.
 Estimated 3% prevalence of vitamin K-dependent
bleeding diathesis among neonates warrants routine
prophylactic vitamin K therapy for all newborns
B-Complex Vitamins
 B 1 (thiamine), B 2 (riboflavin), B 3 (niacin), B 5
(pantothenic acid), B 6 (pyridoxine), B 7 (biotin), B 12
and folate
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All function as coenzymes
Thiamine (B 1 ) Deficiency
 Uncommon on a dietary basis in developed countries
(widely available in diet) seen in alcoholics.
 Still occurs in developing countries where polished
(white) rice is main diet.
 During absorption from the gut , thiamine undergoes
phophorylation to produce thiamine pyrophosphate, the
functionally active coenzyme form of the vitamin.
Thiamine pyrophosphate has 3 major functions;
1. Regulates oxidative decarboxylation of α ketoacids ,
leading to the synthesis of adenosine triphosphate.
2. Acts as a cofactor for transketolase in the pentose
phosphate pathway.
3. Maintains neural membranes and normal nerve
conduction.
Beriberi (Thiamine Deficiency)
 Common in alcoholics (25% of those admitted)
 May also occur in
 Pernicious vomiting of pregnancy
 Debilitating diseases that impair appetite,
 Extended iv glucose therapy without supplemental
vitamins
 Major targets of deficiency are nerves, heart and brain
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Dry beriberi (polyneuropathy)
Wet beriberi (cardiovascular)
Wernicke-Korsakoff syndrome
Dry beriberi
 Polyneuropathy is usually symmetric and takes the form of
a nonspecific peripheral neuropathy with myelin
degeneration and disruption of axons involving the motor,
sensory and reflex arcs.
 Classically presents with toe drop , foot drop , and wrist
drop .
 The progressive sensory loss is accompanied by muscle
weakness and hyporeflexia or areflexia.
Wet beriberi
 Peripheral vasodilatation , leading to more rapid arterio
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venous shunting of blood,
High output cardiac failure and
Peripheral edema.
The dilatation thins the ventricular walls.
Mural thrombi are often present in the dilated atria.
 In severe deficiency states ,most often in chronic alcoholics
 Wernicke – korsakoff’s syndrome appear
 Wernicke encephalopathy is marked by ophthalmoplegia ;
nystagmus ; ataxia of gait and stance ; and derangement of
mental function , characterized by global confusion, apathy,
listlessness, and disorientation
 Korsakoff’s psychosis takes the form of serious impairment
of remote recall, inability to acquire new information, and
confabulation.
Riboflavin (B 2)
 Riboflavin is a critical component of the coenzymes
flavin mononucleotide and flavin adenine dinucleotide ,
which participate in wide range of oxidation-reduction
reactions.
 Sources: meat, dairy, vegetables
 Absorbed in upper GI tract
 Ariboflavinosis
Persons in economically deprived developing
countries
 Alcoholics, chronic infections, advanced cancer and
other debilitating diseases, anorexics and
individuals who avoid milk
Morphology
 Cheliosis (cracks and fissures at angles of mouth)
 Glossitis (atrophic tongue)
 Corneal opacities and ulcerations
 Dermatitis
 Erythroid hypoplasia in the bone marrow
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Niacin (B 3 )
 Niacin refers to 2 chemically distinct compounds :
Nicotinic acid and nicotinamide. Which are derived
from dietary niacin or biosynthesized from available
tryptophan.
Niacin plays a major role in the formation of NAD and
its phosphate NADP.
NAD functions as a coenzyme for a variety of
dehydrogenases involved in the metabolism of fat ,
carbohydrates and amino acids
NADP – dehydrogenases reactions.
 Sources
Grains, legumes, seed oils (small quantities in meats)
 Niacin in corn is in a bound form and unabsorbable
 Deficiency can be seen where corn is most of the
diet
 A deficiency of tryptophan can mimic niacin
deficiency
 Deficiency (pellagra)
 Alcoholics, chronic debilitating diseases ( e.g ., HIV)

Niacin (B 3 ) Deficiency (Pellagra)
 Three D’s:
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Dermatitis
 Thickened red rough skin, bilaterally symmetric on
exposed areas of the body
Diarrhea
 Atrophy of columnar epithelium of GI tract
Dementia – results from degeration of the neurons in
the brain accompanied by degeneration of the
corresponding tracts in the spinal cord.
Pyridoxine (B 6 )
 Vitamin B6 activity is found in three related , naturally
occuring compounds : pyridoxine , pyridoxal , and
pyridoxamine.
 Pyridoxine is converted to pyridoxal phosphate ., a
coenzyme for many enzymes , including transaminases
and carboxylases.
 Clinically overt deficiency of vitamin B 6 is rare in
humans
 Findings resemble riboflavin (B 2 ) and niacin (B 3 )
deficiency . –seborrheic dermatitis, cheilosis, glossitis,
peripheral neuropathy and sometimes convulsions.
Vitamin C (Ascorbic Acid)
 Ascorbic acid is a powerful biological reducing agent
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involved in many oxidation-reduction reactions and in
proton transfer.
Chondroitin sulfate synthesis
Proline hydroxylation to form the hydroxyproline of
collagen.
Prevents oxidation of tetrahydrofolate and augments
absorption of iron from the gut.
Wound healing and immune functions.
Scurvy (Vitamin C Deficiency)
 Poor wound healing – poor collagen synthesis
 Ecchymoses and purpura in skin and gingival mucosa
(small vessels have defective collagen)
 Swollen , bleeding gums – classical.
 Sub-periosteal hematomas and hemarthrosis after
minimal trauma
 Retrobulbar, subarachnoid and intracerebral
hemorrhages (can be fatal)
 Skeletal changes due to insufficient osteoid matrix
 Growing children: bowing of long bones, depression
of the sternum with outward projection of the ends
of the ribs
 Longitudinal section of
scorbutic costochondral
junction with widening of
epiphyseal cartilage and
projection of masses of cartilage
into the adjacent bone
Folate
 Deficiency is commonly dietary in origin
 Sources
Whole-wheat flour, beans, nuts, liver, green leafy
vegetables .
Depleted in cooked and processed foods
 Requirement is increased during pregnancy!
Deficiency can predispose to fetal neural tube defects .
Vitamin B 12 Deficiency
 Deficiency of vitamin B12 are almost always seen in cases of
pernicious anemia and result from lack of secretion of
intrinsic factor in the stomach , which prevents absorption
of vitamin in the ileum.
 Sources – animal foods- meat , milk , eggs
 Parasitization of the small intestine by the fish tapeworm
diphyllobothrium latum may lead to vitamin B12
deficiency.
 Deficiency of both vitamin B12 and folic acid are associated
with megaloblastic anemia.
 Pernicious anemia is complicated by subacute combined
degeneration of the spinal cord.
 Subacute combined degeneration of the spinal cord
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Potentially reversible
Numbness and tingling in the lower extremities progressing to
spastic weakness and then paraplegia
Degeneration of both ascending and descending tracts of the
spinal cord
Mineral Deficiencies
 Many trace minerals are found within the body
 Deficiencies can occur due to
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Inadequate supplementation in total parenteral nutrition
(TPN)
Interference with absorption by dietary constituents
Inborn errors of metabolism leading to abnormal absorption
Mineral Deficiencies
 5 minerals are associated with well-characterized
deficiency states
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Iron, zinc, copper, selenium and iodine
 Iron deficiency is most common in U.S.
 In children, usually inadequate intake
 In adults, usually blood loss or pregnancy
 Hypochromic microcytic anemia (defective heme synthesis)
Zinc Deficiency
 Abundant in the diet: meat, shellfish, fish, whole-grain
cereals, legumes
 Deficiency usually due to
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TPN unsupplemented by zinc
Congenital zinc deficiency (auto recessive, rare)
 Findings
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Acrodermatitis enteropathica
 Rash around eyes, nose mouth and anus
 Anorexia, diarrhea, growth retardation Hypochromic
microcytic anemia (defective heme synthesis)
Impaired night vision, depressed mental function
Selenium Deficiency
 Anti-oxidant (like vitamin E and C) , protects against
oxidative damage of membrane lipids.
 Deficiency is known as Keshan disease
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Results from low level in soil, water and food
Congestive cardiomyopathy
 Mainly in children and young women
Obesity
 Over half of Americans between20 and 75 years of age are
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overweight.
obesity is highly correlated with an increased incidence of
several diseases (e.g., diabetes, hypertension)
Obesity is defined as a state of increased body weight, due
to adipose tissue accumulation, that is of sufficient
magnitude to produce adverse health effects.
Methods to measure fat accumulation
body mass index (BMI)
Skinfold measurements
 Various body circumferences, particularly the ratio of the waist
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hip circumference
The BMI, expressed in kilograms per square meter, is closely
correlated with body fat.
A BMI of approximately 25 kg/m2 is considered normal.
Individuals with BMI >30kg/m2 = obese
The untoward effects of obesity are related not only to the total
body weight but also to the distribution of the stored fat.
Central, or visceral, obesity, in which fat accumulates in the
trunk and in the abdominal cavity is associated with a much
higher risk for several diseases than is excess accumulation of fat
diffusely in subcutaneous tissue.
 The etiology of obesity is complex .
 Involved are genetic, environmental and psychologic
factors.
 The two sides of the energy equation, intake and
expenditure are finely regulated b y neural and hormonal
mechanisms .
 Apparently, this fine balance is maintained by an internal
set point, or "lipostat," that can sense the quantity of the
energy stores (adipose tissue) and appropriately regulate
the food intake as well as the energy expenditure.
 Several "obesity genes" have been identified. That encode
the molecular components of the physiologic system that
regulates energy balance.
 A key player in energy homeostasisis the Db gene and its
product, leptin. This unique member of the cytokine
family, secreted by adipocytes, regulates both sides of the
energy equation- intake of food and expenditure of energy.
 Neurohumoral mechanisms that regulate energy
equation and thus influence the body weight
 The afferent system that generates humoral signals
from the adipose tissue (leptin), pancreas ( insulin )
and stomach (ghrelin).
 Central processing unit , located in the hypothalamus
which integrates the afferent signals.
 Effector system that carries out orders from the
hypothalamic nuclei in the form of feeding behaviour
and energy expenditure.
 Leptin exerts its actions through a complex cascade of
signaling pathways referred to as the leptin-regulated
central melanocortin circuit.
 Leptin actions are initiated by binding to specific receptors
on two classes of neurons in the hypothalamus.
 One class of leptin-sensitive neurons produces the feedinginducing (orexigenic) neuropeptides, neuropeptideY
(NPY) and agouti-related protein (AgRP).
 The other class of leptin receptor-bearing neurons
produces anorexigenic peptides, a melanocyte-stimulating
hormone (a-MSH) and cocaine and amphetamine related
transcript (CART).
 These two molecules reduce food intake.
 The actions of the orexigenic and anorexigenic
neuropeptides are exerted by binding to another set of
receptors, the two most important being the NPY receptor
and the melanocortin 4 receptor.
Complications of Obesity
 Syndrome X (metabolic syndrome)
Abdominal obesity, insulin resistance,
hypertriglyceridemia, low HDL, hypertension, coronary
artery disease
Gallstones, pancreatitis, fatty liver,
Congestive heart failure, arrhythmias, deep vein thrombosis
(and subsequent pulmonary embolus), ischemic stroke
Obesity hypoventilation syndrome, sleep apnea
Osteoarthritis, gout
Endometrial cancer (excess estrogen, difficulty in screening)
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