Vitamins, Minerals, &

Trace Elements

Chemical Pathology I
Vitamins
• Defined as essential organic
micronutrients that are involved in
fundamental functions of the body,
such as growth, maintenance of health,
and metabolism.
• Must be supplied completely or
partially by the diet.
• The broad classifications of the water
and fat soluble vitamins are due to the
fact that fat soluble vitamins are
closely associated with the absorption
and transport of lipids and are stored in
Fat Soluble
Vitamins
 Vitamin A
 Vitamin D
 Vitamin E
 Vitamin K
Water Soluble
Vitamins
B Complex Vitamins
(B1, B2, B3, B5, B6, B9,
B12)
 Biotin
 FolicAcid
 Vitamin C
Vitamin deficiencies

Can arise as a result of:

 Inadequate intake
 Impaired absorption
 Impaired metabolism
 Increased requirements
 Increased losses
 Vitamin A (Retinol)
RDA: 2,700-3,000 IU

 Is a constituent of the retinal pigment

Rhodopsin, necessary for vision in
poor light.
 Essential for the normal synthesis of
mucopolysaccharides and growth of
epitelial tissue
 Is present in diet, can also be
synthesized from dietary carotenes
Vitamin A
Deficiency
 Night blindness (Nictalopia)
 Degenerative changes (squamous
metaplasia) in the eye with
complete loss of vision.
 Dry, rough (hyperkeratosis) skin
 Lowered resistance to infection
Vitamin A

Overdose  Joint & bone

 Headaches pain
 Blurred vision  Dry, cracked
 Fatigue skin
 Diarrhea
 Rashes
 Irregular
 Loss of hair
periods  Vomiting
 Liver damage
 Testing plasma retinol concentration.
 Also can be measured the
concentration of retinol-binding
globulin in plasma
 A low binding protein concentration
can cause the plasma concentration
of Vitamin A to be low and impair its
delivery to tissues, even when
hepatic stores are adequate.
 Deficiency diagnosis is usually
clinically
 Vitamin D
RDA: 100 IU

 Obtained from endogenous synthesis,

by the action of UV light on 7-
dehydrocholesterol in the skin to form
cholecalciferol (Vitamin D3) and from the
diet (Vitamin D2-ergocalciferol)
 Cholecalciferol is hydroxilated first in
liver (25-hydroxycholecalciferol=
calcidiol) and then, in kidney
(1,25 dihydroxycholecalciferol=calcitriol)
 Vitamin D
 Deficiency
– Rickets in children,
bone softening in
adults (osteomalacia),
osteoporosis
 Overdose
– Calcium deposits in
organs, fragile bones,
renal and
cardiovascular damage
 Vitamin D status can be assess in
the laboratory by measurement of
the plasma concentration of
calcidiol, the major circulating
metabolite.
 This can undergoes seasonal
variation, being higher in summer
than in winter.
Vitamin E
RDA: 9-10 mg

 Antioxidant, particularly in cell

membranes, protecting
unsaturated fatty acids
residues from free radicals
attack
 Vitamin E
 Deficiency
– Rare, primarily in premature or low
birth weight babies/severe
malabsorption
– Causes haemolytic anaemia and
neurological dysfunction.
 Overdose
– Unknown
Vitamin E
 Deficiency can be assessed in
laboratory by measure plasma
vitamin E levels (alpha-
tocoferol)
 Sometimes increased

erythrocyte haemolysis can be

measured in laboratory as an
index of vitamin E deficiency
Vitamin K
RDA: Estimated at 0.03 mcg/kg

 Required for the γ-carboxylation

of glutamate residues in
coagulation factors II
(prothrombin), VII, IX and X.
 Those factors are synthesized in
the liver and this process confers
physiological activity by
permitting the binding of calcium.
 Vitamin K
 Also synthesized by bacteria in the
ileum
 Deficiency
– Defective blood coagulation (increases
the prothrombin time)
– In the newborn, plasma vitamin K is low
(very little can be transport across the
placenta, GI no completely colonized by
bacteria) and this can cause
haemorrhagic disease of the newborn
 Overdose
– Is rare, sometimes may produce
haemolytic anaemia
 Laboratory assessment of the
deficiency, is usually indirect by
measuring prothrombin time.
 Blood vitamin K or its metabolites
can be measured in specialized
laboratories but is very rarely
indicated.
Water soluble
vitamins
 Vitamin B1 (Thiamin)
 Nicotinic acid
 Folic acid.

 Vitamin B
12
 Vitamin C (Ascorbic
acid)
Thiamin
RDA: 0.8-1.3 mg

 Vitamin B1
 Necessary for carbohydrate

metabolism and muscle

coordination
 Promotes proper nerve

function
Thiamin pyrophosphate is a
cofactor in the metabolism
of pyruvate and 2-
oxoglutarate to acetyl CoA
and succinyl CoA
respectively, and in a
reaction of the pentose
shunt pathway catalyzed by
the enzyme transketolase.
 Thiamin
 Deficiency cause a primarily sensory
polyneuropathy (dry beri-beri), cardiac
failure (wet beri-beri), Wernicke´s
encephalopathy (ophthalmoplegia and
ataxia, which leads to stupor and
death) and Korsakoff´s psychosis. Due
to diet high in polished rice but also
frequently in alcoholics.
 Overdose: Unknown, although excess of
one B vitamin may cause deficiency of
others
 The method to assess thiamin
deficiency is measurement of
transketolase in a red cell haemolysate.
 The enzyme activity being measured
both with and without the addition of
thiamin pyrophosphate to the reaction.
 Enzyme activity may be normal in
subclinical deficiency but is increased
by the addition of the coenzyme. If the
deficiency is clinically obvious, the
basal enzyme activity will be low.
Niacin
(Nicotinamide)
RDA: 16-23 mg
 Vitamin B3
 Nicotinic acid is the precursor of
nicotinamide, a constituent of the
coenzymes NAD+ and NADP+ which
are essential to glycolysis and
oxidative phosphorilation.
 Part of the body's nicotinic acid
requirement is met by endogenous
synthesis from tryptophan
 Niacin
 Deficiency
Pellagra:
Characterized by
dermatitis
(erythematous
skin) diarrhoea
and dementia (3
D’s)
– Due to diet high
in maize (low in
tryptophan)
Assessment in laboratory,
either by a microbiological
assay of the vitamin in
plasma or by measurement
of its urinary metabolites (n-
methyl-nicotinamide)
concentration.
Vitamin B12
RDA: 2 mcg
 Also called cobalamin
 Almost exclusively in animal
products
 Essential for maturation of
erythrocytes and synthesis of
genetic material.
 Deficiency
– Pernicious anemia; nerve damage
Vitamin B12
 Two enzymatic reactions are
known to be dependent on
vitamin B12
 In the first reaction, homocysteine
is converted to methionine by
using vitamin B12 and folic acid as
cofactors
 In the second reaction,
methylmalonic acid is converted
to succinyl-CoA using vitamin B12
Biochemical reactions

methionine THF thymidine

Methyltranferase(vitB12)
DNA

homocysteine
N5M-THF
 Biochemical reactions

Propionyl CoA

Methylmalonyl CoA
Methylmalonyl CoA mutase(VitB12)
Succinyl CoA
 Malabsorption
syndromes
 The classic disorder of
malabsorption is pernicious anemia,
an autoimmune disease that affects
the gastric parietal cells.
 Destruction of these cells decreases
the production of intrinsic factor
and subsequently limits vitamin B12
absorption
 Malabsorption
syndromes
 The widespread and prolonged use of
histamine H2-receptor blockers and
proton pump inhibitors for ulcer
disease also may cause impaired
breakdown of vitamin B12 from food,
causing malabsorption and eventual
depletion of B12 stores.
 Recent studies have confirmed that
long-term use of omeprazole can lead
to lower serum vitamin B levels
 Malabsorption
syndromes
 Atrophic gastritis , with resulting
hypochlorhydria, is another major
cause, especially in the elderly.
 Subtotal gastrectomy, once
common before the availability of
effective medical therapy for peptic
ulcer disease, also can lead to
vitamin B12 deficiency by this
mechanism.
 Pathogenesis

Hematologic
A failure of DNA abnormalities

A deficiency of synthesis Megaloblasts

Pancytopenia
VitB12

hyperhomocysteinemia Promotion of
atherosclerosis
Heart disease
stroke
 Pathogenesis

A deficiency of Accumulation of
methylmalonyl CoA
VitB12 and propionyl CoA

Disorder of the synthesis of

even-chain fatty acids
Lesions of myelinated Anomalous insertion of odd-
fibers chain fatty acids into
membrane lipids(myelin
sheaths)
Clinical Manifestations
 Hematologic System:
megaloblastic anemia,
pancytopenia (leukopenia,
thrombocytopenia)
 Neurologic System: (the spinal
cord, brain, optic nerve, and
peripheral nerves may all be
affected)
 Psychiatric disorders
 Cardiovascular System
 Folic Acid
RDA: 160-220 mg
 Essential for purine and pyrimidine
synthesis as well as protein
metabolism and red blood cell
formation
 Adequate amounts of this nutrient
in the first stage of pregnancy may
reduce the risks of the neural tube
birth defects
 Folic Acid
RDA: 160-220 mg
 Deficiency
– Relatively common. Macrocytic
anaemia with megaloblastic bone
marrow changes
 Overdose
– Convulsions in epileptics, may
mask pernicious anemia
 It is essential to diagnose the cause
of megalobastic anaemia before it is
treated. Giving folate alone to
patients with vitamin B12 deficiency
can precipitate or exacerbate the
neurological manifestations of
vitamin B12 deficiency.
 Folic acid is usually measured by
immunoassay. The concentration in
red cells reflects the body's folate
more accurately than that in plasma.
 Vitamin C
RDA: 40 mg
 Ascorbic acid
 Antioxidant. Synthesis of collagen,
scar tissue, bone matrix
 Hydrogen carrier, increases absorption
of iron
 Vitamin C
 Deficiency
(Scurvy)
– Muscle
weakness,
bleeding
gums, easy
bruising, skin
petechiae
Vitamin C toxicity:

 Diarrhoea
 Cramps
 Kidney stones
 Haemolytic anaemia
 Rebound scurvy
Minerals and
trace elements
Calcium
RDA: 800-1000mg

 Deficiency
– Rickets in children; osteomalacia
(soft bones) and osteoporosis in
adults
 Overdose
– Constipation, kidney stones,
calcium deposits in body tissues,
hinders absorption of iron & other
minerals
Magnesium
RDA: 230-250 mg

 Deficiency
– Nausea, irritability, muscle
weakness, twitching, cramps,
cardiac arrhythmias
 Overdose
– Nausea, vomiting, low blood
pressure, nervous system disorders
Iron
Men: 8-10 mg & Women: 8-13 mg

 Deficiency
– Skin pallor, weakness, fatigue,
headaches, shortness of breath (all
signs of iron-deficiency anemia)
 Overdose
– Toxic buildup in liver and in rare
instance the heart
(haemocromatosis)
 Zinc
RDA: 9 mg

 Cofactor for more than 100

enzymes, including several involved
in nucleic acid and protein synthesis
(polymerases), also carbonic
dehydratase and alkaline
phosphatase
 Zinc
RDA: 9 mg
 Deficiency
– Slow healing of wounds, loss of taste,
retarded growth and delayed sexual
development in children, dermatitis.
– Zinc deficiency is a well-recognized
potential complication of artificial
(particularly parenteral) nutrition.
Patients who are hypercatabolic lose
large amounts of zinc in the urine.
– Acrodermatitis enteropathica is an
inherited disease with low intestinal zinc
absorption
 Useful laboratory tests for
deficiency include the
measurement of plasma or urinary
zinc levels.
 The plasma zinc-carrying protein
metallothionine concentrations may
also be useful.
 Low plasma concentrations are also
seen in malignant disease and
chronic liver disease.
 Plasma zinc concentration must be
interpreted carefully: blood should
be collected in fasting (zinc
concentration may fall by up to 20
% following a meal).
 Because zinc is partially bound to
albumin, this concentrations should
be considered in relation to that of
albumin.
 Selenium
RDA: 0.05 – 0.2 mg
 Antioxidant. Is the prosthetic group
for the enzyme Glutation
peroxidase
 Interacts with Vitamin E to prevent
breakdown of fats and body
chemicals in cell membranes
 Deficiency only seen as result of
low intake (endemic in some parts
of China)
 Can be measured from Glutation
Copper
RDA: 2 – 3 mg
 Component of several enzymes.
 Stimulates iron absorption,
haematopoiesis, connective
tissue and nerve fibers formation
 For deficiency status, the
laboratory measurement of
plasma Copper and the level of
caeruloplasmin (carrier protein)
and acute phase reactant.
 Copper
RDA: 2 – 3 mg
 Deficiency
– Rare in adults (cardiac arrhythmias,
neutropenia, hypochromic anaemia),
infants may develop a type of anemia
marked by abnormal development of
bones, nerve tissue, lungs and
leucopenia.
 Overdose
– Liver disease, vomiting, diarrhea.
Wilson's disease is an inherited
disorder characterized by excessive
tissue deposition of copper
 Conclusions:
 Vitamins are essential for
biochemical processes and can be
divided into those that are fat
soluble (A, D, E, K) and water
soluble (B complex and C).
 Vitamin A and E deficiency are more
common in developing countries.
Vitamin K deficiency can cause
bleeding disorders, Vitamin B
deficiency is associated with beri-
 Cont.
 Vitamin B12 deficiency can be seen
in pernicious anaemia meanwhile
Vitamin C deficiency causes scurvy.
 Trace elements are also essential.
Deficiency can occur usually if the
patient has poor dietary intake.
 Laboratory assessment requires
most of the time, sophisticated
methods of enzymatic assay.
 Assignment:
 To review Schilling test for vitamin
B12 deficiency.
 To review Wilson’s disease in
copper metabolism,
 To review main sources of vitamins,
minerals and trace elements.