NUTRITIONAL
PATHOLOGY
By Dr.sujatha Udupa

An adequate diet should provide
 Energy
in the form of carbohydrates
 Essential and nonessential aminoacids ,and
fatty acids to be used as building blocks
 Vitamins and minerals ,which function as
coenzymes or hormones in vital metabolic
pathways
Malnutrition
Primary: inadequate food intake
 Secondary: result of disease

Causes of malnutrition
Ignorance and poverty
 Chronic alcoholism
 Acute and chronic illness
 Self imposed dietary restriction

Protein energy malnutrition(PEM)
Range of clinical syndromes
charercterised by an inadequate dietary
intake of protein and calories to meet
body’s needs
 A child whose weight is less than 80% of
normal is called malnourished

Protein compartment
Somatic comparment:represented by
skeletal muscles
 Visceral compartment:represented by
protein stores in visceral compartment
,primarily liver

Definitions of Malnutrition
Kwashiorkor: protein deficiency
 Marasmus: energy deficiency
 Marasmic/ Kwashiorkor: combination of
chronic energy deficiency and chronic
or acute protein deficiency
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Marasmus
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Marasmus < 1 year
Severe reduction in calorie intakecatabolism
of and depletion of somatic protein
compartment aminoacids act as source of
energy Child suffers from growth retardation
and loss of muscle mass
Visceral compartment is depleted marginally
>60%reduction in body weight
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Serum albumin levels are either normal or
slightly reduced
In addition to muscle proteins subcutaneous fat
is also used as source of energyextremities
are emaciated
Anaemia and multivitamin deficiencies
Immune deficiency,T cell mediated
immunityconcurrent infections
kwashiokar
More severe form of malnutrition
 Occurs when protein deprivation is greater
than reduction in total calories
 Seen commonly in Africaan children who
have been weaned with exclusively
carbohydrate diet
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Kwashiorkor
 Skin
lesions,with alternating zones of
hyperpigmentation,desquamatiuon,and
hypopigmentationflaky paint appearence
 Severe loss of visceral protein
compartmenthypoalbuminemiageneralized Soft
pitting edema, starting in feet and legs
 Preserved fat layer, small weight deficit, ht may be
normal
 Weight reduction is masked due to fluid retention
 Dry brittle hair, alternating bands of pale and darker
hair, loss of firm attachment to scalp
 Anorexia, with vomiting and diarrhea
Biologic differences

Marasmus
 Weight
loss
 Nl or low serum
albumin
 No water retention
 Boarderline hgb, hct
 NL
enzymes

Kwashiorkor
 NO
weight loss
 Very low serum
albumin
 High extracellular
water
 Low hgb, hct
 Low enzymes
Morphology of PEM
LIVER :enlarged and fatty in kwashiokar
 GIT:in kwashiokar small bowel shows in
mitotic index in crypts and glands,
associated with mucosal atrophy and loss
of villiloss of enzymes
 Bone marrow:hypoplastic due to
decreased number of erythrocyte
precursorsdimorphic anaemia

Brain:cerebral atrophy,reduced number of
neurons,and impaired myelinization
 Thymic and lymphoid atrophy
 Deficiency of other nutrients like iodine
and vitamins

Diagnosis
Evaluation of fat stores by measuring skin
fold thikness(skin+subcutaneous fat)
 Evaluation of muscle mass by measuring
mid arm circumferance
 Measurment of serum proteins like
albumin and transferrin which indicate
adequacy of visceral protein compartment

Anorexia nervosa
Resembles severe PEM
 Amenorrhea due to decreased secretion of
GnRH
 Bradycadia
 intolerance
 Hypokalemia
 cardiac arrhythmia

Bulimia
Metaplasia and increased risk of
neoplasia
 Electrolyte imbalance
 Cardiac arrhythmias
 Pulmonary aspiration of gastric contents
 Esophageal and stomach, cardiac rupture

What are vitamins (“vital amines”)?
 Organic compounds distinct from fats, carbohydrates and
proteins
 Natural components of foods usually present in minute
amounts
 Essential for normal physiological function
 Absence causes specific deficiency syndromes
Other useful terms:
Vitamer - chemically-related family of compounds with
same “vitamin activity”
Pro-vitamin – a precursor which is metabolised to the active
vitamin
VITAMINS

“VITAMIN” means “vital for life”
* Nutrients
required in very
small amounts mg or µg
VITAMINS are *Micronutrients
which are necessary for everyday healthy
functioning of the body

Lipid soluble and water soluble vitamins
Trace elements
Thiamin
Niacin
Pantothenic acid
Copper
Iron
Biotin
Selenium
Iodine
Folate
Vitamin E
Manganese
Zinc
Vitamin C
Molybdenum
Cobalt
Vitamin K
Riboflavin
Vitamin A
Vitamin D
Vitamin B6
Vitamin B12
Essential Micronutrients
VITAMINS Two main categories
Water soluble
Fat Soluble
B
C
A
D
E
K
Water soluble
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Cannot be stored in body
- regular supply needed
Excess is excreted in
urine - no danger of toxic
levels
Unstable to heat and
light, leach into cooking
liquids
Fat Soluble
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Can be stored in body regular supply not needed
Can accumulate to toxic
levels if large amounts
ingested
Fairly stable at normal
cooking temperatures
Fat soluble vitamins-properties
Necessary for function or structural
integrity of body tissues and membranes
 Can be retained in the body
 A polar hydrophobic compounds that can
only be absorbed efficiently when there is
normal fat absorption

Vitamins, vitamers and pro-vitamins
Vitamin
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Vitamin C
Vitamin B1
Vitamin B2
Niacin
Vitamin B6
Folic acid
Biotin
Pantothenic acid
Vitamin B12
Vitamer
retinol
retinal
retinoic acid
cholecalciferol (D3)
ergocalciferol (D2)
-tocopherol
-tocopherol
phylloquinones (K1)
menaquinones (K2)
menadione (K3)
ascorbic acid
dehydroascorbic acid
thiamin
riboflavin
nicotinamide
nicotinic acid
pyridoxal
pyridoxal
pyridoxamine
Folic acid
polyglutamyl folacins
biotin
pantothenic acid
cobalamin
Pro-vitamin
-carotene
-cryptoxanthin
Vitamin deficiency
• Primary deficiency (most common) due to
malnutrition
 • Secondary due to:
– Malabsorbation
– Storage disturbance
– Impaired metabolic conversion
– Distorted blood transport

VITAMIN A
 Vitamin A is a group of related natural and
synthetic compounds
 Active forms of preformed vitamin A (retinoids):
Retinol,retinal,retinoic acid
 Body can convert -carotene to retinol,
thus called provitamin A.
Retinol is stored in the liver, which makes it
available to cells, which then convert it to the other
two active forms
Retinol (vit A)
STORAGE AND TRANSPORT FORM
B-carotene(provitamin)
Intestinal mucosa
Retinal(all-trans form)
Isomer of visual pigment
Irreversible oxidation
Retinoic acid.affects growth and
Differentiation of cell
Retinal(cis form)visual pigment
RICH DIETARY SOURCES
Animal Foods
Plant Foods
Cod liver oil
Sweet potato
Liver & kidney
Carrots
Egg
Cantaloupe
Butter
Spinach
Milk & cheese
Apricot
Fish & meet
Papaya
•Animal sources of vit A: milk ,butter
,fish oils ,liver,meat, egg yolk
•Vegetables: green leafy vegetables
,carrots
•Fruits: mango , papaya
•Oils : palm oil
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Vitamin A - normal function
90% stored in liver
Maintaining normal vision in reduced light
Potentiating differentiation of mucus producing epithelial
cells
Enhancing immunity to infections
Antioxidative effect
Photoprotective effect
Visual Cycle (night vision)
 When light falls on retina
 Rhodopsin--conformational changealltrans retinol+opsin nerve impulse is
generatedtransmitted to brain
 Some retinal is recycled and rhodopsin is
re-formed,but most is lost
 Without adequate intake of vitamin A, one
loses night vision (the first sign of vitamin
A deficiency)
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Cell differentiation
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Vit-A plays a very important role in ordrely
differentiation of mucus –secreating epithelium
Mechanism: retinoic acid regulates the
expression of the genes encoding a number of
recetors and secreted proteins including
rerceptors for growth factors
Deficiency state :the epithelium undergoes
squamous metaplasia
Immunity
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Vit A plays a role in host resistance to infections
It stimulates the immune system by forming a
metabolite 14-hydroxyretinol
during infections the bioavailability of vit –A is
reduced
Mechanism:Infectionsacute phase
responsedecreases retinol binding protein in
liverdepression of circulating levels of
retinolreduced tissue availability of retinol
Supplements of vitA during course of infections
like measels will improve clinlical outcome
Deficiency state
Earliest manifestationimpaired vision
during reduced light(night blindness)
 Persistant vit-A deficiency affect
epithelium
 ocular changesxerophthalmia
 Dryness of conjunctivae(xerosis)

dryness of conjunctivae
as normal lacrimal and mucus secreting glands are
replaced by keratinised epithlium
Deposition of keratin debris
Small opaque plaques(Bitot spot)
Erosion of corneal surface(corneal ulcer)
softening of cornea(keratomalacia)
total blindness
1. Bitot
1. Fine line of Bitot spots
spots
2. Wrinkled
Conjunctiva
1. Bitot spots and
rough Conjunctiva
1. Foamy
Bitot spots
Bitot spot
Corneal ulcer
Vitamin A Deficiency
Xerotic Keratitis
keratomalacia
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The epithelium lining the upper respiratory tract
and urinary tract epithelium undergoes
squamous metaplasia
Loss of mucociliary epitheliumsecondary
pulmonary infections
Desquatiom of keratin debris in urinary
tractrenal and bladder stones
Avitaminosis-Aimmune deficiencyprone to
common infections like measles, pneumonia,
and infectious diarrhea
Vitamin A toxicity
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6.9.1 Acute hypervitaminosis
Ingestion of large dose can give rise to
transient signs and symptoms of toxicity,
which are self limiting and completely
reversible..
Common complaints include headaches
and bulging fontanellae in young children.
Nausea, vomiting, dizziness, headaches
have been described in adults.
Desquamation of the skin, bone pains and
hair loss can occur in the following days.
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9.2 Chronic hypervitaminosis
Is due to ingestion of large doses on a
daily basis. This can lead to hepatitis,
cirrhosis, hair loss, dry scaly skin,
hyperpigmentation, hyperostosis and bone
pains, hepato-splenomegaly.
It is therefore recommended not to
exceed a daily intake of 3000 mcg in
children and 7500 mcg in adults
Vitamin
E
VITAMIN E
The term vitamin E describes a family
of 8 antioxidants,
4 tocopherols (,, , & d) and
4 tocotrienols.
-tocopherol is the active form of
vitamin E in the human body.
Vitamin E
 Absorbed with dietary lipids
 Transported in LDL
 Stored in cell membranes,liver and muscle
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Mechanism
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It plays a role in termination of free radiclegenerated lipid peroxidation of chain reactions
Protects cellular and subcellular membranes
that are rich in polyunsaturated lipids
Neurons with long axons are vulnerable to vit E
deficiency because of their large surface area
Mature red cells are also vulnerable because of
oxidative injury during oxygenation of
hemoglobin
Functions
 Primary lipid-soluble antioxidant
 Protects polyunsaturated fatty acids in cell
membranes, red blood cells, and
lipoproteins from oxidative damage
 Especially important in cells exposed to oxygen
- RBCs, lung, mitochondrial membranes
 Prevents the alteration of cell’s DNA and risk
for cancer development
 Prevents LDL oxidation and risk for
atherosclerosis
 Needed for normal nerve development
 May play a role in immune function
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Deficiency –morphology in
nervous system
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Degeneration of axons in the posterior column of
the spinal cord,with focal accumulation of
lipopigment
loss of nerve cells in dorsal root ganglia,and
axonopathy
Myelin degeneration in sensory axons of
peripheral nerves
In marked cases, degenerative changes in
spinocerebellar tracts
Morphology in erythrocytes
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Vit-E deficient erythrocytes are more
susceptible to oxidative stress and have
shorter half life in circulating blood
VITAMIN -D
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The major function of vitamin-D is the
maintenance of plasma levels of calcium and
phosphorus
It is required for the prevention of metabolic
bone diseases and hypocalcemic tetany
Vit D maintains correct concentration of ionised
calcium in extracellular fluid
Insufficient concentration of calciumcontinous
exitation of muscleconvulsive statetetany
Sources of Vitamin D
 Two possible sources :1)endogenous synthesis in
skin 2)DIET
Sunlight is the most important source which
converts 7 dehydrocholesterol to vit D3
 Fish liver oil
 Fish & sea food (herring & salmon)
 Eggs
 Plants do not contain vitamin D3,but contain its
precursor ergosterol,which can be converted to vit D2
Sources of Vitamin D
 Two possible sources :1)endogenous synthesis in
skin 2)DIET
Sunlight is the most important source which
converts 7 dehydrocholesterol to vit D3
 Fish liver oil
 Fish & sea food (herring & salmon)
 Eggs
 Plants do not contain vitamin D3,but contain its
precursor ergosterol,which can be converted to vit D2
VITAMIN D
 Vitamin D comprises a group of sterols; the
most important of which are cholecalciferol
(vitamin D3) & ergosterol (vitamin D2).
 Humans & animal utilize only vitamin D3 &
they can produce it inside their bodies from
cholesterol.
 Cholesterol is converted to 7-dehydrocholesterol (7DC), which is a precursor of
vitamin D3.
Metabolism of vitamin D
Functions of vitamin D
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The maintenance of of normal plasma levels of
calcium and phosphorus
Is required for normal mineralisation of
epiphyseal cartilage and osteid matrix
Favours differentiation of osteoclasts from their
precursors(monocytes)helps in resorptive
function of bone
increases synthesis of calcium binding proteins
like osteocalcin and osteonectin
Vitamin D deficiency
•Deficiency of vitamin D leads to:
 Rickets in small children.
 Osteomalacia in adults
 Osteoporosis

deficiency of vit-D
hypocalcemia
activates renal a1- hydroxylase
in creasing active vit D and calcium absorption
mobilises calcium from bone
decreases renal calcium excretion
Increases excretion of phosphorus
GROUPS AT RISK
•Infants
•Elderly
•Covered women
•Kidney failure patients
•Patients with chronic liver disease
•Fat malabsorption disorders
•Genetic types of rickets
•Patients on anticonvulsant drugs
Morphology
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An excess of unmineralised matrix
Inadequate provisional calcificationovergrowth
of epiphyseal cartilage
Persistance of distorted irregular masses of
cartilage
Disruption of orderly replacement of cartilage by
osteoid matrix,with enlargement of lateral
expansion of osteochondral junction
Deformation of skeleton due to loss of structural
regidity of developing bones
Skeletal changes in rickets

Non ambulatory stage: head and chest
sustain greatest stresses
Occipital bone become flattened
 Parietal bone can be buckled in by pressure,which
recoil back with the release of
pressure(craniotabes)
 An excess of osteoid frontal; bossing and
squared appearance of head
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Chest deformities
 Overgrowth
of cartilage or osteid tissue at the
costochondral junctionrichitic rosary
 Weakened metaphyseal areas of the ribs are subject
to pull of respiratory musclespigeon breast
deformity
 Inward pull at the margin diaphragmHarrison’s
groove
 Ambulating child:lumbar lordosis,bowing of legs
In adults vitamin D deficiency affects
normal bone remodelling that occurs
throughout life
 The newly formed osteid matrix is
inadequately mineralisedproducing
excess of persistant osteidosteomalacia
 The bone is weak and vulnerable to
microfractures, especially of vertebral
bodies and femoral necks

Histopathology

Unmineralized osteid appear as thickened
layer of matrix ( appear pink in H and E)
arranged about the more basophilic
normally mineralized trabeculae
TOXICITY
•Hypervitaminosis D
causes hypercalcemia, which manifest as:
Nausea & vomiting
Excessive thirst & polyuria
Severe itching
Joint & muscle pains
Disorientation & coma.