NUTRITION

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NUTRITION and DISEASE
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NUTRITIONAL DEFICIENCIES

• Protein-Energy Malnutrition

• refers to a range of clinical syndromes
  characterized
• by inadequate dietary intake of protein
  calories

• two protein compartments somatic protein
  compart-
• ment (skeletal muscles) visceral compartment
  ( pro-
• tein stores in visceral organs, primarily the
  liver)

• A child whose weight falls to lt80 of normal is
  con-
• sidered malnourished

- Marasmus malnutrition caused primarily by
severe reduction in caloric intake
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infections common

• Kwashiorkor occurs when protein deprivation is
• greater than the reduction in total calories

most common form seen
in children who have been weaned early due to
arrival of another child fed exclusively CHO
diet
more severe than
marasmus marked protein deprivation associated
with severe loss of vis- ceral protein
compartment resulting to hypoalbumine- mia giving
rise to generalized or dependent edema
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child with marasmus suffers
growth re- tardation loss of muscle loss of
muscle results from catabolism depletion of
the somatic protein compart- ment
visceral protein compartment
is depleted only marginally, serum albumin
levels are either normal or only slightly
reduced
subcutaneous fat is also
mobilized used as a fuel
head appears too large for the
body ex- tremities are emaciated presence of
anemia multivi- tamin deficiencies immune
deficiency (T cell mediated
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relative sparing of
subcutaneous fat muscle mass skin lesions with
alternating zones of hy- perpigmentation, areas
of desquamation hypopig- mentation (flaky
paint appearance)
hair changes include loss
of color or al- ternating bands of pale darker
hair, straightening, line texture, loss of firm
attachment to the scalp
other features include
enlarged, fatty liver (reduced synthesis of
carrier proteins), early apa- thy, listlessness
loss of appetite

• Secondary PEM seen in chronically ill or
  hospita-
• lized patients common complication in advanced
  can-

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cer patients in patients with AIDS also
called cache- xia
px with chronic GI disease
elderly px who are weak bedridden will show
physical signs of PEM (1) depletion of
subcutaneous fat in the arms, chest wall,
shoulders or metacarpal regions (2) was- ting of
the quadriceps femoris deltoid muscles
(3) ankle or sacral edema
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Comparison of Severe Marasmus-Like and
Kwashiorkor Like Secondary Protein-Energy
Malnutrition
SYNDROME CLINICAL TIME CLINICAL
LAB PROGNOSIS
SETTING COURSE FEATURES
FINDINGS Marasmus Chronic illness mos
hx of wt N or mildly depends Like PEM
(chr lung ds CA) loss muscle reduced
on under
wasting ab- serum Pr
lying ds
sent subcu fat Kwashior-
Acute, catabo- wks N fat serum
poor Kor like lic illness
muscle albumin PEM
(severe trauma, edema
lt2.8 gm/dl burns, sepsis)
easily
pluckable hair
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• Morphology

• Central anatomic changes in PEM are (1) growth
  fai-
• lure (2) peripheral edema in kwashiorkor (3)
  loss of
• body fat atrophy of muscle more severe in
  maras-
• mus

kwashiorkor
marasmus Liver
enlarged fatty
normal Small bowel mucosal atrophy loss
rare of
villi microvilli disa-
ccharidase deficiency BM
hypoplastic (?red cell precursors) folate
deficiency (
microcytic-macrocytic anemia) Brain
cerebral atrophy cerebral
atrophy
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• Anorexia Nervosa and Bulimia

• Anorexia nervosa self-induced starvation
  resulting in
• marked weight loss

similar clinical
findings with severe PEM with prominent endocrine
effects.
a. Amenorrhea dxtic feature results
from decreased secretion of gonadotropin-releasin
g hormone and decreased secretion of luteinizing
and FSH.
b. Cold intolerance, bradycardia,
constipation
c. Skin changes dry, scaly yellow
due to ex- cess carotene in the blood
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d. Decreased bone density due to low
estro- gen level
major complication is increased
susceptibi- lity to cardiac arrhythmia and sudden
death resulting from hypokalemia
- Bulimia condition in which the patient binges
on food and then induces vomiting occur
primarily in previous- ly healthy young women
with obsession of attaining thinness.
amenorrhea occurs in lt 50 of cases
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major medical complications is related
to con tinual induced vomiting and include 1)
electrolyte im- balances (hypokalemia) 2)
pulmonary aspiration of gastric contents 3)
esophageal cardiac rupture
Vitamin Deficiencies

• Fat soluble A, D, E and K
• Water soluble

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• Fat Soluble Vitamins
• Vitamin A

• functions a component of visual pigment
  (retinal)
• maintains normal vision in
  reduce light
• maintenance of specialized
  epithelia, mainly
• mucus-secreting cells
• maintenance of resistance to
  infection, esp
• in children

• Visual process involves four forms of vit A
  containing
• pigments rhodopsin (rods) most light
  sensitive pig-
• ment impt in reduced
  light

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3 iodopsins (cone cells)
each responsive to
specific colors in bright light
- synthesis of rhodopsin from retinol involves
(1) oxi- dation to all-trans-retinal (2)
isomerization to 11-cis- retinal during dark
adaptation (3) interaction with op- sin to
form rhodopsin

• retinoic acid regulates the expression of genes
  enco-
• ding a number of cell receptors secreted
  proteins,
• including receptors for growth factors

• ability of vit A to stimulate the immune system
  through
• formation of 14-hydroxyretinol bioavailability
  of vit A
• is reduced during infections

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- Deficiency state

• impaired vision in reduced light ( night
  blindness)

• xerophthalmia (dry eyes) lacrimal
  mucus-secreting
• epithelium is replaced by keratinized
  epithelium
• causing dryness of conjunctivae (xerosis)
  build-up
• of keratin debris in small opaque plaques
  (Bitot
• spots) erosion of the roughened corneal
  surface
• with softening destruction of the cornea
  (kera-
• tomalacia) total blindness
  

• epithelium lining the upper respiratory passages
  
• urinary tract is replaced by keratinizing
  squamous
• cells ( squamous metaplasia) causing
  pulmonary

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infections renal urinary bladder
stones

• immune deficiency causing common infections such
  
• as measles, pneumonia infectious
  diarrhea

- Toxicity

• acute toxicity- headache, vomiting, stupor
  papille-
• dema

• chronic toxicity- associated with weight loss,
  nausea
• vomiting dryness of the lip mucosa
  bone
• joint pain hyperostosis hepatomegaly
  with
• parenchymal damage fibrosis
  osteoclast forma-
• tion causing ? bone resorption
  osteoporosis
• leading to fractures

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• Vitamin D

- Metabolism

• two sources endogenous synthesis in the skin
  diet

• (1) absorption of vit D in the gut or synthesis
  from pre-
• cursors in the skin

(2) Binding to a plasma a1- globulin (D binding
protein) transport to liver
(3) Conversion to 25-hydroxyvitamin D by
25-hydroxy- lase in the liver
(4) Conversion of 25(OH)D to 1,25(OH)2D by
a1-hydro- xylase in the kidney most
active form of vit D
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• 3 mechanisms regulating production of 1,25(OH)2D
• (1) feedback loop, ? 1,25(OH)2D down-regulate
  synthe-
• sis by inhibiting action of
  a1-hydroxylase, ? levels
• have the opposite effect

(2) Hypocalcemia stimulates secretion of PTH
which converts 25(OH)D to 1,25(OH)2D by
activating a1- hydoxylase
(3) Hypophosphatemia activates a1-hydroxylase,
in- creasing 1,25(OH)2D
- Functions

• maintenance of normal plasma level of calcium
• phosphorous

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• stimulates intestinal absorption of Ca
  phosphorous

• with hypocalcemia , collaborates with PTH in
  the mo-
• bilization of Ca from the bone

• stimulates the PTH-dependent reabsorption of Ca
  in
• the distal renal tubules

- Deficiency States

• rickets in growing children
• osteomalacia in adults

- Morphology

• basic derangement in both rickets osteomalacia
  is
• excess of unmineralized matrix

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• gross skeletal changes depends on the severity
  of ra-
• chitic process, its duration the stresses to
  which in-
• dividual bones are subjected

• Softened occipital bones are flattened, parietal
  bones
• buckled inward by pressure release of pressure,
  elas-
• tic recoil snaps the bones back into their
  original po-
• sitions (craniotabes)

• Excess of osteoid produces frontal bossing
  squared
• appearance to the head

• Rachitic rosary overgrowth of cartilage or
  osteoid ti-
• ssue at the costochondral junction causing
  deforma-
• tion of the chest

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• Pigeon breast deformity anterior protrusion of
  the
• sternum due to inward bending of the respiratory
  mus-
• cles due to weakened metaphyseal areas of the
  ribs

• Harrisons groove inward pull at the margin of
  the dia-
• phragm, girdling the thoracic cavity at the
  lower margin
• of the rib cage

• Rickets in ambulating child, deformities affect
  the
• spine, pelvis long bones (tibia) causing
  lumbar lordo-
• sis bowing of the legs

• Osteomalacia in adults excess of persistent
  osteoid
• due to inadequate mineralization of newly formed
• osteoid matrix by osteoblasts bone is weak
  vulne-
• rable to fractures microfx (vertebra femoral
  neck)

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• histo unmineralized osteoid appears a thickened
  la-
• yer of of matrix arranged about the more
  basophilic,
• normal mineralized trabeculae

• Osteoporosis results from reduced production of
  os-
• teoid whish is the protein matrix of the bone

• Vitamin E

• Metabolism related to 4 tocopherols 4
  tocotrienols
• which exhibit vit E biologic activity
  a-tocopherol is the
• most active most widely available

• Absorption of tocopherols requires normal biliary
  tract
• pancreatic function

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• After absorption, Vit E is transported in the
  blood (chy-
• lomicrons) Vit E accumulates throughout the
  body,
• mostly in fat depots, liver muscle

- Functions

• antioxidant that scavenges free radicals formed
  in
• redox reactions throughout the body

• role in termination of free-radical-generated
  lipid pe-
• roxidation chain rxns (cellular subcellular
  membra-
• nes rich in polyunsaturated lipids)

• together with selenium, they metabolize
  peroxides be-
• fore they can cause membrane damage

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- Deficiency States

• nervous system is the target of vit E
  deficiency neurons
• with long axons are vulnerable due to their
  large mem-
• brane surface area

• mature red cells also affected in Vit E def due
  to oxida-
• tive injury by generation of superoxide
  radicals during
• oxygenation of hemoglobin

• hypovitaminosis E occurs in (1) fat
  malabsorption seen
• in cholestasis, cystic fibrosis primary small
  intestinal
• disease (2) infant low BW with immature liver
  GIT
• (3) abetalipoproteinemia (4) rare autosomal
  recessive
• syndrome of impaired Vit E metabolism

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- Morphology

• degeneration of axons in the posterior columns
  of the
• spinal cord, with accumulation of lipopigment
  loss
• of nerve cells in the dorsal root ganglia ( due
  to dying-
• back type of axonopathy)

• myelin degeneration in sensory axons of
  peripheral
• nerves degenerative changes in the
  spinocerebellar
• tracts

• denervation muscle disease in skeletal muscle

• Neurologic manifestations of Vit E def are
  depressed/
• absent tendon reflexes ataxia dysarthria loss
  of po-
• sition vibration sense loss of pain sensation

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• Muscle weakness impaired vision eye movement
• disorders leading to total ophthalmoplegia

• Protective effects of Vit E other antioxidants
  against
• atherosclerosis cancer Vit E inhibits
  atheroma for-
• mation by reducing LDL oxidation scavenge free
  ra-
• dicals?prevents DNA damage mutagenesis? ? CA

• Vitamin K

- Functions

• required cofactor in hepatic carboxylation of
  procoa-
• gulants factors II (prothrombin), VII, IX
  X protein
• C protein S

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• Carboxylation provides Ca dependent interaction
  of
• the clotting factors with a phospholipid
  surface in-
• volved in generation of thrombin

• Carboxylation of osteocalcin, a noncollagenous
  pro-
• tein sereted by osteoblasts, facilitates
  binding to
• calcium vit K may favor calcification of bone
  proteins

- Deficiency

• occurs (1) in fat malabsorption syndromes
  (biliary tract
• ds) (2) after destruction of the endogenous
  vit K
• synthesizing flora from ingestion of
  broad-spectrum
• antibiotics (3) in neonatal period, when liver
  reserves
• are small, bacterial flora not yet developed
  vit K in
• breast milk is low (4) in diffuse liver ds

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• development of bleeding diathesis hemorrhagic
  ds
• of the newborn intracranial hemorrhage,
  bleeding
• in the skin, umbilicus viscera

• in adults, bleeding diathesis characterized by
  hemato-
• mas, hematuria, melena, ecchymoses bleeding
  from
• the gums

• Thiamine (Vitamin B1)

• gut absorption?phosphorylation?thiamine
  pyrophos-
• phate ( active form)

• 3 major functions (1) regulates oxidative
  decarboxyla-
• tion of a-ketoacids ? adenosine triphosphate
  (2) acts
• as cofactor for transketolase in the pentose
  phosphate

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pathway (3) maintains neural membranes
normal nerve conduction (peripheral nerves)
- Deficiency

• seen in chronic alcoholics, precocious vomiting
  of
• pregnancy, from debilitating illnesses that
  impair the
• appetite, predispose to vomiting or cause
  diarrhea

• major targets are the peripheral nerves, the
  heart and
• brain

• 3 distinctive syndromes
• A polyneuropathy (dry beriberi)
• A cardiovascular syndrome (wet beriberi)
• Wernicke-Korsakoff syndrome

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• polyneuropathy is symmetric takes the form of
  non-
• specific peripheral neuropathy with myelin
  degenera-
• tion disruption of axons (motor, sensory
  reflex arcs)
• first appears in the legs extend to the arms
  (toe drop,
• foot drop wrist drop) sensory loss with
  muscle
• weakness, hyporeflexia or areflexia

• beriberi heart disease- associated with
  peripheral va-
• sodilation?AV shunting of blood?high output
  car-
• diac failure?peripheral edema

- heart is markedly
enlarged globular (four-chamber dilation) with
pale, flabby myocardium mural thrombi present
in the dilated atria
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• Wernicke-Korsakoff syndrome- in severe
  deficiency
• states Wernicke encephalopathy is marked by
  oph-
• thalmoplegia, nystagmus, ataxia, mental
  derangement
• (confusion, apathy, listlessness
  disorientation)

• Korsakoff psychosis serious impairment of
  remote
• recall (retrograde amnesia), inability to
  acquire new
• information confabulation CNS lesions affect
  the
• mamillary bodies, periventricular regions of
  the tha-
• lamus, floor of the fourth ventricle anterior
  region
• of the cerebellum

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• Riboflavin (Vitamin B2)

• Functions converted to coenzymes flavin mononuc-
• leotide flavin adenine dinucleotide, cofactors
  for
• many enzymes in intermediary metabolism

• Distributed in meat, dairy products vegetables
  as
• free riboflavin or riboflavin phosphate
  absorbed in
• the upper gastrointestinal tract

- Deficiency

• seen in alcoholics, chronic infections, advanced
  can-
• cer, debilitating diseases anorexia nervosa

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• Cheilosis first most characteristic sign
  begins as
• areas of pallor at the
  angles of the mouth
• later, cracks or fissures
  appear from cor-
• ners of the mouth become
  secondarily
• infected

• Glossitis tongue becomes atrophic, colored
  magenta
• hue resembling red-blue
  color of cyanosis

• Eye change superficial interstitial keratitis
  early sta-
• ges, superficial layers
  of cornea are inva-
• ded by capillaries
  interstitial inflammato-
• ry infiltration
  exudation ?opacities
• ulcerations of the cornea

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• greasy, scaling dermatitis on the nasolabial
  folds ?
• butterfly distribution involving the cheeks
  ears
• atrophy of the skin

• presence of erythroid hypoplasia in the bone
  marrow

• Niacin

• generic designation for nicotinic acid its
  active deri-
• vative, nicotinamide

• essential component of 2 coenzymes, NAD NADP,
• important in cellular intermediary metabolism

• NAD coenzyme involved in fat metabolism, CHO
• amino acids

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• NADP involved in dehydrogenation rxns, hexose-
• monophosphate shunt of glucose
  metabolism

• derived from diet or synthesized endogenously
  grains
• legumes, seed oils meat synthesized
  endogenously
• from tryptophan

• Pellagra result from either niacin or
  tryptophan def.
• usually in combination with other vit
  deficiencies seen
• among alcoholics, with chronic debilitating
  diseases,
• like HIV infection seen with long term drug
  intake of
• isoniazid 6-mercaptopurine

• Morphology - Pellagra refers to rough skin
  three Ds

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• Dermatitis bilaterally symmetric found on ex-
• posed areas of the body redness,
  thickening
• roughening of the skin extensive
  scaling
• desquamation?fissures chronic
  inflamma-
• tion occur in mucous membranes of
  mouth
• vagina

ii Diarrhea caused by atrophy of columnar
epithe- lium of the GIT followed by
submucosal infla- mmation ulceration
iii Dementia results from degeneration of the
neu- rons in brain with degeneration
of correspon- ding tracts in the
spinal cord
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• Pyridoxine (Vitamin B6)

• Consists of pyridoxine, pyridoxal pyridoxamine
  with
• their phosphate forms

• converted in tissues to coenzyme form, pyridoxal
  
• 5-phosphate?participates as a cofactor of
  enzymes in-
• volved in transamination, carboxylations
  deaminations
• in lipid AA metabolism

• present in all foods deficiency seen in
  patients under
• isoniazid tx estrogens penicillaminein
  alcoholics be-
• cause of acetaldehyde (alcohol
  metabolite)?pyridoxine
• degradation

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• given to pregnant women

• vit B6 deficiency is associated with high levels
  of plas-
• ma homocysteine? risk factor for
  atherosclerosis

• clinical findings same with riboflavin niacin
  deficien-
• cy ? seborrheic dermatitis, cheilosis,
  glossitis, peri-
• pheral neuropathy sometimes convulsions

• Vitamin C (Ascorbic Acid)

• Source diet cannot be synthesized
  endogenously pre-
• sent in milk, liver, fish, fruits vegetables

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• Functions activation of prolyl lysyl
  hydroxylases
• from inactive precursors for procollagen
  hydroxylation
• antioxidant ? scavenge free radicals Vits E
  C act in
• synergistic fashion

• Deficiency

• Scurvy characterized by bone disease in growing
• children hemorrhages healing defects in
  both
• children adults

• morphology (1) hemorrhages defect in collagen
  syn-
• thesis ? inadequate support of walls of
  capillaries
• venules ? purpura ecchymoses in skin
  gin-
• gival mucosa

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loose attachment of periosteum
to bone with vascular wall defects
?subperiosteal hematomas bleeding into
joint spaces with mild trauma
retrobulbar, subarachnoid
intracerebral he- morrhages are fatal
(2) skeletal changes insufficient production
of osteoid matrix by osteoblasts ?failure or
slow resorprtion of cartilaginous matrix ?
cartilaginous overgrowth and widening of the
epiphysis ? stress on the scorbutic bone ?
bowing of long bones of lower legs abnor-
mal depression of the sternum with outward
projec- tion of the ribs
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in severely scorbutic children
adults ? gin- gival swelling,
hemorrhages scondary bacterial
periodontal infection perifollicular,
hyperkeratotic, papular rash ringed by
hemorrhages
defect in collagen synthesis ?
impaired wound healing localization of focal
infections anemia is common due to bleeding
? in iron absorption

• Folate

• essential cofactors in nucleic acid synthesis
  conver-
• sion of 5-methyltetrahydrofolate to
  tetrahydrofolate
• requires vit B12 deficiency of either folate
  or vit B12
• ? megaloblastic anemia

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• folate supplements have been shown to ? the risk
  of
• neural tube defects in the fetus during the
  first trimes-
• ter of pregnancy

• low plasma folate is associated with high levels
  of plas-
• ma homocysteine, same with vits B6 B12

• Sources whole-wheat flour, beans, nuts, liver
  green
• leafy vegetables

• Metabolism oral contraceptives,
  anticonvulsants, etha-
• nol, cigarette smoking interfere with folate
  absorption
• metabolism

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• chronic diseases (intestinal malabsorption
  metasta-
• tic cancer

• combined folate vit B12 deficiency contribute
  to the
• development of colon cancer mechanisms (1)
  altered
• DNA methylation (2) accumulation of cells in S
  phase
• with ? susceptibility of DNA damage (3)
  alterations of
• nucleotide pools ? impair DNA synthesis repair

• vit B12 deficiency is associated with myelin
  degenera-
• tion in both sensory motor pathways of the
  spinal
• cord, in contrast to folate deficiency

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Mineral Deficiencies

• Iron essential component of hemoglobin and of
• iron containing metalloenzymes
• - hypochromic microcytic anemia

• Zinc component of enzymes, principally
  oxidases
• - acrodermatitis enteropathica ,
  anorexia with
• diarrhea, growth retardation, impaired wound
  
• healing, hypogonadism with diminished
  reproduc-
• tive capacity, altered immune function,
  impaired
• night vision, depressed mental function,
  increased
• incidence of congenital malformations in
  infants

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• Iodine component of thyroid hormone

- goiter and hypothyroidism

• Selenium component of glutathione peroxidase

- myopathy, rarely cardiomyopathy

• Copper component of cytochrome c oxidase,
  dopa-
• mine ß-hyrdoxylase, tyrosinase, lysyl
  oxidase
• unknown enzyme involved in cross-linking
  keratin

- muscle weakness, neurologic
defects, hy- popigmentation, abnormal
collagen cross-linking
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• Manganese component of metalloenzymes, inc-
• luding oxidoreductases, hydrolases and
• lipases

• Fluoride unknown mechanism
• - dental caries