Dietary Minerals

Professor Dr. Syed Touqeer Abbas

 Dietary minerals

• Dietary minerals refers to inorganic

compounds necessary for life and good
nutrition
1. Some are scientific minerals like salt
2. Others are elements like K , Ca , Fe, Zn , Mg
and Cu
 Functions of Minerals

• Some participate with enzymes in

metabolic processes (cofactors)
• Some have structural functions (Ca, P in
bone; S in keratin)
• Acid-base and water balance (Na, K, Cl)
• Nerve & muscle function (Ca, Na, K)
• Unique functions (e.g., heme, B12,
thyroid hormones)
 Classification
• Contaminant Minerals
• Required in very minute amount
• If taken in large amount or stored in
excess becomes toxic
• Includes :
– Lead
– Arsenic
– Tin
– Boron
 The Major Minerals: an Overview

• Macrominerals
• Humans need >100 mg/d
– 􀂄 Calcium
– 􀂄 Phosphorus
– 􀂄 Magnesium
– 􀂄 Sodium
– 􀂄 Chloride
– 􀂄 Potassium
Micro Minerals :an Overview

• Human need < 100 mg / d

– Fe
– Zn
– Cu
–F
– Se
– Co
– Iodine
 Bioavailability & Regulation of
Minerals

• Bioavailability ( Absorption of chemicals and

substances in humans and other animals)
– Influenced by genetics, aging, nutritional status &
other food compounds
Absorption
– Small & Large Intestine
Regulation
– Kidneys & Small intestine
 Sources of Minerals

1. Naturally occurring in food

2. Added in elemental or mineral form like CaCO3 ,
NaCl, NaHCO3
3. Some of these additives come from natural
sources like ground oyster shells
4. Sometimes minerals added to diet separately
from food as vitamin & mineral supplements
 Factors Affecting Requirements
• Physiological state/level of production
• Interactions with other minerals
• Tissue storage
– 􀂄 Specific proteins to hold and transport
• Form fed
– 􀂄 inorganic vs organic forms
– 􀂄 Na selenite vs Na selenate vs selenomethionine
 Absorption of 75Se from selenite, selenate, and
selenomethionine (SeMet) was determined in
ligated loops from duodena, jejuna, and ilea of
selenium-deficient rats (0.009 ppm Se) or rats fed
selenite-supplemented diets (0.20 ppm Se).
Selenium deficiency had no effect on absorption
of any selenocompound in any intestinal segment.
SeMet was absorbed most rapidly from all
segments. Selenate and selenite were most
efficiently absorbed from the ileum. Substantial
75Se was retained within ileal tissue during
selenite and SeMet absorption but was readily
transferred to the body during ileal selenate
uptake.
 Mineral interactions may be positive (synergistic), where one mineral
enhances the bioavailability of another, or negative (antagonistic), in which
case one mineral decreases the bioavailability of another. An example of
positive interaction is that of copper and iron, where copper is essential for
iron absorption and metabolism. Copper deficiency impairs iron metabolism.
An example of negative interaction is zinc-copper antagonism, in which
excess zinc has a severely detrimental effect on the bioavailability of copper.
Multiple interactions can occur such as excess zinc inducing copper
deficiency, which, in turn, has an adverse effect on iron metabolism.
Therefore, close attention must be paid to not only the amount of mineral fed,
but also the ratio of each mineral to the others in the total ration. Organic
minerals are also called “chelates” or “proteinates”. Chelation involves the
attachment of the mineral to an amino acid or other organic component so
that the two do not disassociate in the digestive system, essentially
protecting the mineral so it can be absorbed across luminal wall intact. For
some minerals, a chelated compound is better than some other forms, but
others absorption is not improved with complexing. For those that are better
fed as a chelate, absorption is more efficient due to a neutral electrical
charge. Non-chelated inorganic minerals have either a positive or negative
charge. Both calcium and magnesium are examples where "chelated forms"
are not any better absorbed than inorganic forms such as calcium carbonate
and magnesium oxide. Both are easily separated and the calcium and
magnesium ions are well absorbed.
 Organic Vs Inorganic sources

• Dietary source of minerals can be organic like plants but

they themselves are inorganic
• Minerals in ionic form are best absorbed
• Inorganic or metallic source of minerals can be toxic like
heavy metals
• Minerals in their inorganic form are not easily absorbed
• Stored in tissues & large amounts are toxic
 Deficiencies and Excesses

• Most minerals have an optimal range

– 􀂄 Below leads to deficiency symptoms
– 􀂄 Above leads to toxicity symptoms
• Mineral content of soils dictates mineral
status of plants (i.e., feeds)
• May take many months to develop
– 􀂄 Time impacted by body stores
MACROMINERALS
CALCIUM
 Calcium

• Most abundant mineral in animal tissues

– 99 % Ca in skeleton
– Present in blood and other tissues

• Young adult contains average of 1100 g Ca

• Normal plasma concentration of Ca is 9—12 mg /

dl or 5 mEq / L
 Food Sources

• Milk and dairy products

– 􀂄 High amounts
– 􀂄 High bioavailability
(fortified with vitamin D)
• Green leafy vegetables
– 􀂄 Poor absorption
 Daily Requirements

• Infants 210 – 270 mg

• Children 1 to 8 years 500– 800 mg
• Adult female 1000– 1300 mg
• Adult male 1000– 1300 mg
 Calcium Regulation

• Three hormones involved in regulation

1. Vit D3 from kidney

– Steroid hormone
– Formed from Vit D by successive hydroxylation in liver
and kidney
– It increases Ca absorption from intestine
 Calcium regulation

2. Parathyroid Hormone (PTH )

• From parathyroid gland
• Mobilizes Ca from bone & increases urinary
phosphate excretion
3. Calcitonin
• From thyroid gland
• Inhibits bone resorption
• the mobilization of Ca from bone
Calcium Regulation

• 􀂄 PTH and Vitamin D3 act to increase

plasma Ca, while calcitonin acts to
decrease plasma Ca
 Calcium Regulation

• Ca is partly bound with proteins and partly

diffusible
Plasma or serum Ca

Non- diffusible Diffusible

• Cannot be dialyzed out Sub-divided into two
• In firm combination with
plasma proteins specially
albumin
• Level is 3.4 to 4.4 mg / dl
 Calcium Regulation

Diffusible Calcium

Ionized Calcium
• Level is 5.45 to 6.23 mg/dl
• Physiologically active
• Increases in hyper-parathyroidism
and vice versa
• Level below 4.3 mg/dl causes tetany
 Calcium Regulation

Diffusible Calcium

Complexed Calcium
• Level less than 0.6 mg/dl
• In complex form with plasma
anions like citrate and phosphate
 Ca Regulation

Calcium in Bones

1. Readily exchangeable reservoir

• Regulates plasma Ca
• Approximately 500 mmoles / day of Ca moves
into and out of the readily exchangeable
reservoir present in the bone
 Calcium Regulation

Calcium in Bones

2. Stable or slowly exchangeable Ca

• Concerned with bone remodeling
• Ca interchange between plasma and stable
pool is only about 7.5 mmol / day
 Calcium Regulation

• Large amount of Ca is filtered in kidneys

• 98 to 99 % reabsorbed
• 60 % reabsorption in proximal tubules
• Remainder in ascending loop of Henle and
distal tubules
• Distal tubular reabsorption regulated by
parathyroid hormone
 Regulatory Functions of Calcium

• Stimulates blood clotting

– factor IV blood coagulation
• Muscle contraction
– Ca activates myosin- ATP complex, motors sliding action
between actin and myosin
• Transmission of nerve impulses
– Ca necessary for transmission of nerve impulses from
presynaptic to postsynaptic region
• Vision
– Ca regulates cyclic GMP in retinal rods & has role in
adaptation

􀂄
 PTH,
Calcium &
Phosphate
 Regulatory Functions of Calcium

• Regulation of blood glucose

– Role in secretion of insulin
• Cell differentiation
• Cofactor for energy metabolism
– Cofactor for many enzymes
• Secretion of hormones
– Insulin , PTH, Calcitonin
• Ca and cyclic AMP second messengers of different
hormones
– Glucagon
 Calcitonin
• Calcitonin acts to decrease plasma Ca2+ levels.
• While PTH and vitamin D act to increase plasma
Ca2+-- only calcitonin causes a decrease in plasma
Ca2+.
• Calcitonin is synthesized and secreted by the
parafollicular cells of the thyroid gland.
• They are distinct from thyroid follicular cells by their
large size, pale cytoplasm, and small secretory
granules.
 Calcitonin
• The major stimulus of calcitonin secretion is a
rise in plasma Ca2+ levels
• Calcitonin is a physiological antagonist to PTH
with regard to Ca2+ homeostasis
 Calcitonin
• The target cell for calcitonin is the osteoclast.
• Calcitonin acts via increased cAMP
concentrations to inhibit osteoclast motility
and cell shape and inactivates them.
• The major effect of calcitonin administration is
a rapid fall in Ca2+ caused by inhibition of bone
resorption.
 Other Factors Influencing Bone and Calcium
Metabolism
• Estrogens and Androgens: both stimulate bone
formation during childhood and puberty.
• Estrogen inhibits PTH-stimulated bone resorption.
• Estrogen increases calcitonin levels
• Osteoblasts have estrogen receptors, respond to
estrogen with bone growth.
• Postmenopausal women (low estrogen) have an
increased incidence of osteoporosis and bone
fractures.
Calcium Functions
 Structural Functions of Calcium:
Bones & Teeth

• Bones
– Osteoblasts
– Bone formation
• Osteoclasts
– Breakdown of older bone
• 􀂄 Hydroxyapatite
– Large crystal-like molecule
 Calcium Deficiencies

• Rickets
– in growing animals
• Osteomalacia
(osteoporosis)
– In adult animals
• Milk fever (parturient
paresis)
– in lactating animals
• Tetany
 Calcium and Bone Health

• Bone growth is
greatest during
“linear growth”
– 􀂄 Peaks out at around
age 30
• Calcium in bones
used as reservoir for
other needs.
– 􀂄 Maintains blood
calcium homeostasis
 Bone mineral density
The T-score is the relevant measure when screening for osteoporosis. It is the
bone mineral density (BMD) at the site when compared to the young normal
reference mean. It is a comparison of a patient's BMD to that of a healthy 30-
year-old. The US standard is to use data for a 30-year-old of the same sex and
ethnicity, but the WHO recommends using data for a 30-year-old white
female for everyone. Values for 30-year-olds are used in post-menopausal
women and men over age 50 because they better predict risk of future
fracture. The criteria of the World Health Organization are:
•Normal is a T-score of −1.0 or higher
•Osteopenia is defined as between −1.0 and −2.5
•Osteoporosis is defined as −2.5 or lower, meaning a bone density that is two
and a half standard deviations below the mean of a 30-year-old man/woman.
 Primary Hyperparathyroidism

• Calcium homeostatic loss due to excessive PTH

secretion
• Due to excess PTH secreted from adenomatous or
hyperplastic parathyroid tissue
• Hypercalcemia results from combined effects of
PTH-induced bone resorption, intestinal calcium
absorption and renal tubular reabsorption
• Pathophysiology related to both PTH excess and
concomitant excessive production of 1,25-(OH)2-D.
Hypercalcemia of Malignancy

• Underlying cause is generally excessive bone

resorption by one of three mechanisms
• 1,25-(OH)2-D synthesis by lymphomas
• Local osteolytic hypercalcemia
– 20% of all hypercalcemia of malignancy
• Humoral hypercalcemia of malignancy
– Over-expression of PTH-related protein (PTHrP)
 PTHrP
• Three forms of PTHrP identified, all about
twice the size of native PTH
• Marked structural homology with PTH
• PTHrP and PTH bind to the same receptor
• PTHrP reproduce full spectrum of PTH
activities
 PTH receptor defect
• Rare disease known as Jansen’s metaphyseal
chondrodysplasia
• Characterized by hypercalcemia,
hypophosphotemia, short-limbed dwarfism
• Due to activating mutation of PTH receptor
• Rescue of PTH receptor knock-out with
targeted expression of “Jansen’s transgene”
 Hypoparathyroidism
• Hypocalcemia occurs when there is
inadequate response of the Vitamin D-PTH
axis to hypocalcemic stimuli
• Hypocalcemia is often multifactorial
• Hypocalcemia is invariably associated with
hypoparathyroidism
• Bihormonal—concomitant decrease in 1,25-
(OH)2-D
 Calcium Toxicity

• Deposition in soft tissue

• Impaired kidney function
• Interference with other
nutrient
absorption
– Iron & zinc
 Phosphorus
• Total body phosphorus 1 – 1.5 kg
– Mostly combined with Ca in bone
• Occurrence
– Component of each and every part of living system i.e.,
Cell
• Distribution
– 80 % in bones and teeth
– 10 % in lipids, proteins and carbohydrates
– 10 % in different compounds in blood and muscles
 Phosphorus

• Daily Requirements
– Infants 300 – 500 mg
– Children 500 mg
– Male ( adults ) 500 – 1200 mg
– Females 500 – 1200 mg
– During pregnancy 1200 mg
• Total plasma phosphorus 12 mg / dl
– 2 / 3 in organic compounds
– Remaining inorganic as HPO4 & H2PO4
 Phosphorus

• Dietary Sources
– Milk
– Cheese
– Liver
– Kidney
• Recommended Ca / P ratio 1 : 1
• Food adequate in Ca also adequate
in P
 Phosphorus

• Distribution
– Whole blood 40 mg / dl

• Serum
– Children 4 – 7 mg / dl
– Adults 3 – 7 mg / dl
• Muscle 170 – 250 mg / dl
• Nerve 360 mg / 100 g tissue
• Bone & teeth 3200 mg /100 g tissue
 Metabolism & Regulation of
Phosphorus in the Body

• Small intestine absorption

– Vitamin D-dependent active transport
– 􀂄Simple diffusion
• Concentrations controlled by:
– 􀂄 Calcitriol, PTH, calcitonin
• P is filtered in glomeruli
• 80 – 85 % filtrate reabsorbed by proximal tubules by
active transport
 Functions of Phosphorus

• Constituent of Phospholipids like lecithins,

cephalins, plasmalogens etc
• Component of:
– 􀂄 DNA & RNA
– 􀂄 ATP
• Protein synthesis
• Role in formation of bones and teeth
Functions of Phosphorus
• Energy metabolism like esters with sugars as
glucose 6 phosphate, fructose 6 phosphate
• Maintenance of blood pH as phosphate buffer
( ICF )
• Important constituent of cell membranes
 Phosphorus Toxicity

• Mineralization of soft tissues

• Interference with absorption of Zinc
& magnesium
• May cause kidney stones
• Very high levels
– Coma
– Cardiac arrest
Sodium and Chloride
 Sodium

• Absolutely an essential nutrient

• Most abundant in the extracellular fluid
• Values - 135-145 mEq/L in ECF and 10—12 mEq / L
in ICF
• Body usually gets rid of excess quite easily.
 Sodium and Health

• High blood sodium is

associated with high
blood pressure and
risk of heart disease
• However, high blood
sodium rarely due to
dietary excess.
• Again, genetics and
other factors are involved
 Sodium & Chloride

• Commonly found
together in foods
• Join via ionic bonds
to form salt
• Added freely to
foods during:
– Processing
– Cooking
 Did you know…

• Salt free means:

– 􀂄 Less than 5 mg sodium/serving
• Very low salt means:
– 􀂄 Less than 35 mg sodium/serving
• Low salt
– 􀂄 Less than 140 mg sodium/serving
 Dietary Sources & Bioavailability

• 􀂄 Table salt
• 􀂄 Monosodium glutamate
• 􀂄 Highly processed foods
• 􀂄 Some meats, dairy products, poultry &
seafood
• 􀂄 Bioavailability
– 􀂄 Affected by malabsorption
 Recommended Dietary Intake

• Sodium
– Infants 115—750 mg
– Children 325– 1800 mg
– Adults 1100– 3300 mg
• Chloride
– Infants 275– 1200 mg
– Children 500– 2775 mg
– Adults 1700– 5100 mg
 Regulation of Sodium & Chloride in
the Body
• Small intestine
– 􀂄 Sodium absorbed first
– 􀂄 Chloride second
• Sodium
– 􀂄 Absorbed with glucose
– 􀂄 Also actively absorbed in colon
• Water absorption
 SODIUM REABSORPTION

• Kidneys are main regulators of body sodium

• 98 % of body loss of sodium occurs in urine
• More Na is ingested its urinary excretion
increases
• Less Na ingested or plasma Na falls Na may
totally disappear from urine
 Na Absorption
• Sodium is absorbed from the intestinal lumen by several mechanisms, most prominently
by cotransport with glucose and amino acids, and by Na+/H+ exchange, both of which
move sodium from the lumen into the enterocyte.
• Absorbed sodium is rapidly exported from the cell via sodium pumps - when a lot of
sodium is entering the cell, a lot of sodium is pumped out of the cell, which establishes a
high osmolarity in the small intercellular spaces between adjacent enterocytes.
• Water diffuses in response to the osmotic gradient established by sodium - in this case
into the intercellular space. It seems that the bulk of the water absorption is
transcellular, but some also diffuses through the tight junctions.
• Water, as well as sodium, then diffuses into capillary blood within the villus.
• As sodium is rapidly pumped out of the cell, it achieves very high concentration in the
narrow space between enterocytes. A potent osmotic gradient is thus formed across
apical cell membranes and their connecting junctional complexes that osmotically drives
movement of water across the epithelium.
• Water is thus absorbed into the intercellular space by diffusion down an osmotic
gradient. However, looking at the process as a whole, transport of water from lumen to
blood is often against an osmotic gradient - this is important because it means that the
intestine can absorb water into blood even when the osmolarity in the lumen is higher
than osmolarity of blood.
 SODIUM REABSORPTION
• Na reabsorption along Nephron
• Proximal Tubule
• Reabsorbs two third of the filtered water and Na
• Early proximal tubule reabsorbs water and Na with
HCO3,glucose,amino acids, phosphate and lactate
• In the middle and late proximal tubules Na is reabsorbed with Cl
• ECF volume contraction increases reabsorption
• ECF volume expansion decreases reabsorption
• Renal reabsorption of sodium (Na+) is a part of renal physiology. It
uses Na-H antiport, Na-glucose symport, sodium ion channels
(minor). ... It is very efficient, since more than 24,000 mmoles/day
of sodium is filtered into the nephron, but only ~100 mmoles/day,
or less than 0.4% remains in the final urine.
 SODIUM REABSORPTION

– Thick ascending limb of Loop of Henle

– Reabsorbs 25 % of the filtered Na
– Contains a Na-K-2Cl co transporter in the luminal
membrane
– It is impermeable to water. NaCl is reabsorbed without
water
– Distal tubule and collecting duct
– Reabsorbs 8 % of filtered Na
– Reabsorbs NaCl by Na-Cl co transporter
– Is impermeable to water
 Sodium reabsorption is tightly coupled to
1.passive water reabsorption, meaning when sodium moves, water follows.
The movement of water balances the osmotic pressure within or across the
tubule walls, which maintains extracellular body fluid volume.
Reabsorption takes place mainly in the proximal convoluted tubule of the
nephron . ... Reabsorption occurs primarily by passive transfer based on a
concentration gradient , moving from a high concentration in the proximal
tubule to the lower concentration in the capillaries surrounding the
tubule The kidneys of a normal man filter approximately 24,000
meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq
change in 24-h urinary sodium excretion. Aldosterone increases renal
sodium reabsorption and increases renal excretion of potassium.
Hyperkalemia and increased activity of the renin-angiotensin system are the
most important factors to increase aldosterone secretion.
Hypernatremia decreases aldosterone secretion. Most of
the reabsorption (65%) occurs in the proximal tubule. In the latter part it is
favoured by an electrochemical driving force, but initially it needs the
cotransporter SGLT and the Na-H antiporter.
Renal sodium absorption
 1. Proximal tubule: Here most of the sodium is
reabsorbed (around 65-70%). Sodium without chloride is
absorbed with glucose, amino acids and phosphate (not shown)
through specific carriers. Sodium as sodium carbonate or
phosphate is resorbed in exchange for hydrogen, with a
sodium=hydrogen antiporter on the luminal side of the proximal
tubular cell membrane. When this occurs, a bicarbonate is
reclaimed (sodium carbonate) or generated (sodium hydrogen
phosphate) in exchange for hydrogen, thus sodium absorption is
linked to acid-base balance in the proximal tubules. Sodium can
also be absorbed by the proximal tubules after they generate
ammonia from glutamine (renal ammoniagenesis). This also
generates new bicarbonate (again, in exchange for hydrogen) and
is stimulated by acidemia and hypokalemia. This generates a high
concentration of luminal chloride, which is passively absorbed
with sodium in later segments of this tubule.
 2. Thin ascending limb of the loop of Henle: Sodium with
chloride is passively absorbed from the concentrated urine filtrate
(because the descending limb of the loop of Henle is relatively
impermeable to solute, but permeable to water) in the thin
ascending limb.
3. Thick ascending limb of the loop of Henle: Sodium is
absorbed with 2 x chloride and a potassium by a luminal Na-K-2Cl
cotransporter. This cotransporter is inhibited by loop diuretics,
e.g. furosemide. The sodium/hydrogen antiporter also operates in
this segment. Around 15-25% of filtered sodium is absorbed in
this segment.
4. Distal tubules: Sodium chloride is absorbed together by a
cotransporter, which is inhibited by thiazide diuretics. Around 5%
of filtered sodium is absorbed here.
 5. Collecting ducts: Here is where fine control over sodium
absorption occurs. Sodium is absorbed (in exchange for
potassium) passively through open channels in principal cells.
These open channels are increased in response to aldosterone.
Absorption of Na+ facilitates passive Cl- absorption in this
segment as well as the nearby sections of the distal tubule. The
channels are inhibited by potassium-sparing diuretics.
The kidney is extremely efficient at absorbing filtered sodium and
chloride, such that <1% of the filtered load is resorbed. Indeed, if
more than 1% of sodium and chloride are present in the urine in
an azotemic animal (particularly with hyponatremia), this
suggessts a salt-losing nephropathy. Note, the energy for sodium
absorption comes from a basolateral sodium/potassium pump,
which exchanges 3 Na for 2 K, thus creating a negative potential
within the cells, that also helps drive absorption. The luminal
sodium/hydrogen antiporter activity is stimulated by angiotensin
II (through renin), which promotes sodium resorption in response
to hypovolemia and hypo-osmolality.
Cascade for the activation of the
renin-angiotensin-aldosterone
system (RAAS)
 Functions of Sodium & Chloride

• 􀂄 Electrolytes
• 􀂄 Fluid balance
• 􀂄 Sodium
– 􀂄 Nerve function
– 􀂄 Muscle contraction
• 􀂄 Chloride
– 􀂄 HCl production
– 􀂄 Removal of carbon dioxide
– 􀂄 Immune function
 Sodium & Chloride Deficiencies

• 􀂄 Infants & children

– 􀂄 Diarrhea and vomiting
• 􀂄 Athletes
– 􀂄 Endurance sports
• 􀂄 Symptoms
– 􀂄 Nausea, dizziness, muscle cramps, coma
 Over consumption of Sodium
Chloride

• 􀂄 Increased blood pressure

– 􀂄 May be a result of low Ca intake in reality
• 􀂄 Susceptible individuals
– 􀂄 Elderly
– 􀂄 Those with:
• 􀂄 Hypertension
• 􀂄 Diabetes
• 􀂄 Chronic kidney disease
 Potassium
• Potassium is major intracellular cation
• Only 2 % of total body K located in extra cellular
space
• Normal serum concentration is 3.5 to 5.5 mEq/ L in
ECF and 100—150 mEq/ L in ICF
• Ninety percent of potassium is renally excreted ,
remainder in stools
• Major salt in ruminant sweat
– 􀂄 Increases requirement in heat stress
 Potassium (K): Dietary Sources &
Bioavailability
• Legumes, potatoes,
seafood, dairy
products, meat,
fruits/veg
• Bioavailability
– 􀂄 High
 Potassium: Daily Requirement

• Infants
350 – 1275 mg
• Children
550 – 2325 mg
• Adults
1875 – 5625 mg
 Regulation

• Absorption in small intestine & colon

• Blood potassium regulated by:
– 􀂄 Kidneys
– 􀂄 Aldosterone increases excretion
• Proximal tubule reabsorbs 67 % of filtered K+ along
with Na+ and H2O
 Regulation
• Thick ascending limb of loop of Henle
reabsorbs 20 % of the filtered K+ via Na+--
K+-- 2Cl- co transporter

• Remaining K+ is absorbed in distal tubule

and collecting duct
 Functions of Potassium in the Body

• Electrolyte
• Maintains fluid balance
• Muscle function
• Nerve function
• Energy metabolism
 Functions of Potassium in the Body

• Regulation of osmotic and acid-

base balance
• Major cation of intracellular
fluid
• Nerve and muscle excitability
• Cofactor for several reactions in
carbohydrate metabolism
 Potassium Deficiency
• Hypokalemia
• Causes: K+ wasting
diuretics
• Vomiting
• Diarrhea
• Polyuria
• S/S:
• weak, irregular pulse
– Hypotension, weakness
 Potassium Excess

• Hyperkalemia
• Causes: Renal failure
• S/S:
• Irregular slow pulse
• Weakness
• Irritability
SULPHUR
 Importance of sulphur

• Sulphur containing proteins

• Detoxification compounds
• Tissue respiration or SH groups
• High energy S bonds ( Fatty acyl S
CoA )
 Sources

• Amino acids like cysteine and methionine

containing S
• Heparin, insulin, thiamine, biotin, lipoids and
chondroitin sulphate all contain S
• Keratin rich in S
• High S in hairs
• Inorganic sources containing SO4
 Biochemical role : Sulphur

• Active part of many hormones

• Component of an active coenzyme SH group of
dehydrogenases
• Tertiary structure of proteins
• Detoxification of phenols, steroids, tryptophan
products
 Sulphur : Absorption

• Absorbed along with amino

acids
• Cysteine, methionine are
soluble & readily absorbed
• Inorganic sulphates are also
absorbable
 Sulphur : Excretion

• Main route– urinary excretion

• 1 gm / day
• Sulphur in urine excreted in three forms
1. Inorganic sulphate
2. Neutral sulphate
3. Ethereal sulphate ( detoxification compounds of
phenols formed in liver )
Magnesium
 Magnesium
• Magnesium (Mg2+)
• Principle cation present in soft tissue and
intracellular spaces
• Second most important of intracellular
fluids
• Value - 1.5 - 2.5 mEq/L
 Magnesium : Distribution

• Total body Mg 20 – 25 grams

• 70 % in bones ( combined with Ca and phosphate )
• 30 % in soft tissues and body fluids
• Blood 2 – 4 mg / dl
• Less than ½ in serum , remaining in RBC’s
• Muscle 21 mg / 100 gram
 Magnesium : Requirement

• RDA 7– 10 mg / kg
/day

• Males 350 mg / day

• Females 300 mg / day

 Dietary Sources & Bioavailability

• Green leafy vegetables, seafood,

legumes, nuts, dairy products.
• Chocolate, brown rice, whole grains
• Bioavailability influenced by:
– 􀂄 Calcium
– 􀂄 Phosphorus
 Magnesium: Functions

• Activator of many enzymes

1. Urea Cycle : Carbamoyl phosphate synthase,
dehydrogenase, transketolase
2. Purines : Phospho ribosyl pyrophosphate
synthase( conversion of purines, low energy
reaction, role in nucleotide metabolism), Ribulose
5 phosphate synthase
3. Pyrimidines : Kinases , Enolases
 Magnesium: Functions

• Stabilizes enzymes
• Neutralizes negatively charged
ions
• Energy metabolism
• Cofactor for over 300 enzymes
• DNA & RNA metabolism
• Nerve & muscle function
 Magnesium : Absorption

• Ca , proteins & vit D interefere

with Mg absorption, transport &
retention in body
• Absorption depends upon
concentration in diet
• 10 gm Mg in diet 75.5 %
absorbed
• 20 gm Mg in diet 43 % absorbed
 Magnesium Excretion

• Average urinary excretion 10

– 20 mEq / L
• Alcohol increases Mg
excretion
• Aldosterone increases Mg
excretion
 Hyper & Hypomagnesemia

• Hypomagnesemia
– Causes: malnutrition and alcoholism polyuria
– S/S: muscular tremors, hyperactive deep tendon reflexes
• Hypermagnesemia
– Causes: Renal failure
– S/S: hypoactive deep tendon reflexes, shallow and slow
respirations
 Iron ( Fe )
• RDA

– Male 10 mg
– Female 18 mg

• Total body Iron 4—5

grams
 Dietary Sources
• Animal Sources
– Meat, liver, kidney, egg
yolk, fish

• Plant Sources
– Green leafy vegetables,
spinach, nuts, dates, beans
 Iron in the Body
• 70% of iron in body is functional; found
in enzymes and other molecules
– 􀂄 >80% of this found in red blood cells
• 30% of iron is in storage depots or
transport proteins
• Iron absorption, transport, storage and
loss is highly regulated
 Distribution of Iron in Body
1. Functional Iron
• Hb 900 grams contains 3 grams of iron
• Mb 40 grams contains 0.13 grams of iron
• Enzymes 10—20 grams contains 0.04– 0.08
grams of iron
2. Storage iron
• Transferrin contains 0.04 grams of iron
• Ferritin contains 0.4– 0.8 grams of iron
 Iron
metabolism:

Reticuloendoth
l cells
 Iron Absorption
• If body needs more
iron, it increases
amount of “transferrin”
an iron carrying protein.
• Iron can also be stored
in another protein called
“ferritin
 Iron Absorption
• Transport across
– 􀂄 Brush border
– 􀂄 Basolateral membrane
• Heme iron
– 􀂄 Chemical modification not
needed
• Nonheme iron
– 􀂄 Reduced to ferrous form
• Ferritin
 Intestinal absorption of iron:
- in the duodenum
- regulation (by the synthesis of apoferritin within mucosal cells)
1. The heme iron (unknown mechanism)
2. The nonheme iron
• is not readily absorbed (chelates with oxalates, phytates, etc.)
• vit. C increases the uptake
Iron sources:
 meat, liver, fish, eggs, green vegetables, cereals

Iron loss:
- daily loss ~ 1-2 mg (cell desquamation, ♀ menstruation, pregnancy,
multiple births, lactation)
- bleeding

Recyclation of iron:
- from aged erythrocytes (~ 20 mg)
- transferrin receptors on cells
Iron absorption from the intestine:

D (DMT 1), I (Integrin), M (Mobilferrin), Fn (Ferritin), Fp (Ferroportin), H (Hephaestin), R

(Ferrireductasa)
 Absorption, cont.
• Iron from animal sources much better absorbed than
that from plant sources
• Absorption of iron from plant sources increased by
– 􀂄 Vitamin C
– 􀂄 Meat in diet
• Absorption is decreased by
– 􀂄 Phytates (grain products)
– 􀂄 Polyphenols (tea, coffee)
– 􀂄 Other minerals (calcium, zinc)
 Effect of Iron Status on Iron
Absorption
• Iron deficiency
– 􀂄 Increases production of transport
proteins
– 􀂄 Decreases ferritin production
• Adequate or excess iron
– 􀂄 Decreases production of transport
proteins
Iron can be either stored within the
enterocyte as ferritin or it can be transferred
across the basolateral membrane to the
plasma by transport protein FERROPORTIN1
and MTP1.
(Requires oxidation of Ferrous to Ferric by
hephaestin.)
Effect of Iron Status on Iron
Absorption
Hepcidin
-Is a recently discovered liver produced 25
amino-acid peptide
-Is a regulator of iron metabolism that controls
iron absorption and macrophage iron release.
-Is regulated by erythropoietic needs( ) ,body
iron stores( ) and inflammation( )
 Hepicidin, Primary regulator
Increased expression of hepicidin leads to
Decrease iron absorption and release.
Mutation :Hemochromatosis
Increased expression:Iron deficiency
Hepicidin mRna expression is increased by
erythropoetin,hypoxia & inflammation.
Also binds to ferroportin.
 Ferroportin
The only cellular iron exporter in vertebrates.
Present in macrophages,placenta and the
hepatocytes.
 Mechanism of action of hepicidin
The major mechanism of hepicidin is THE
REGULATION OF TRANSMEMBRANE IRON
TRANSPORT.
It binds to FERROPORTIN ,forms hepicidin-
ferroportin complex ,which is degraded in the
lysosomes and iron is locked inside the
cells(mainly enterocytes,hepatocytes and
macrophages).
SO

• Hepcidin lowers iron absorption in the

intestine ,lowers iron releasing from
hepatocytes and macrophages

Serum iron is decreased.

 Hepicidin Regulation
• So when hepicidin levels are low ,iron exporting cells have abundant
ferroportin and thus releases iron into plasma.When hepicidin concentration
increases it binds to ferroportin and thus iron is retained in the cells.
 Regulation of Hepicidin
Hypoxia/Anemia
Inflammation
 Regulation of Hepcidin synthesis by
anemia and hypoxia
• Oxygen Hepcidin

Uptake of diet iron

Iron release from hepatocytes
Iron release from macrophages
 Iron Circulation, Uptake Into
Cells, & Storage
• Transferrin
– Delivers iron
to body cells
– Transferrin
receptors
 Iron Circulation, Uptake Into
Cells, & Storage
• Iron storage compounds in
liver, bone marrow, and
spleen
– Ferritin
• 􀂄 Main storage form
– Hemosiderin
• 􀂄 Long-term storage
 Bioavailability of Iron
Influenced by:
• Form
– 􀂄 Heme > Ferrous > Ferric
• Iron status
• Presence/absence of other dietary
components
• Only 10 % of dietary iron is absorbed
 Excretion of iron
• Mostly in feces
• Small amount in sweat
• Very small amount in urine
• Average excretion
– < I mg/ day in males
– 1.5 –2 mg /day in females
• In nephrotic syndrome excretion increases
 Total iron binding capacity ( TIBC )

TIBC = SIBC + UIBC

• SIBC = Saturated iron binding capacity
1 / 3 of total transferrin contents
• UIBC = Unbound iron binding capacity
2 / 3 of total transferrin contents
 Functions of Iron
• 􀂄 Oxygen transport:
hemoglobin

• 􀂄 Iron reservoir:
myoglobin

• 􀂄 Cellular energy
metabolism
 Oxygen Transport: Hemoglobin
• 􀂄 Most abundant
protein in red blood
cells
• 􀂄 4 protein subunits +
4 iron-containing
heme groups
• 􀂄 Delivers oxygen to
cells
• 􀂄 Picks up carbon
dioxide
 Iron Reservoir: Myoglobin
• 􀂄 Found in muscle cells
• 􀂄 Heme group + protein subunit
• 􀂄 Releases oxygen to cells when needed
for:
– 􀂄 ATP production
– 􀂄 Muscle contraction
 Cellular Energy Metabolism

• 􀂄 Cytochromes
– 􀂄 Heme-containing complexes
– 􀂄 Function in electron transport chain
– 􀂄 Allow conversion of ADP to ATP
• 􀂄 Iron as cofactor
– 􀂄 Electron transport chain
– 􀂄 Citric acid cycle
– 􀂄 Gluconeogensis
 Other Roles of Iron
• Cytochrome P450 enzymes
• Cofactor for antioxidant
enzymes
– 􀂄 Protects DNA, cell
membranes, proteins
• Cofactor for enzyme to make
DNA
 Iron Deficiency
• Most common nutritional
deficiency
• At-risk groups
– 􀂄 Infants, growing children,
pregnant women
 Mild Iron Deficiency
• 􀂄 Signs
– 􀂄 Fatigue
– 􀂄 Impaired physical work performance
– 􀂄 Behavioral abnormalities
– 􀂄 Impaired intellectual abilities in children
– 􀂄 Body temperature regulation
– 􀂄 Influences immune system
 Severe Iron Deficiency: Iron-
Deficiency Anemia
• 􀂄 Microcytic hypochromic anemia
– 􀂄 Small, pale red blood cells
– 􀂄 Inability to produce enough heme
– 􀂄 Decreased ability to carry oxygen
– 􀂄 Decreased ATP synthesis
• 􀂄 Infants, children, pregnant and lactating
women most at risk.
 Iron Toxicity
• Excess deposited in liver, heart,
muscles
• Most common cause of childhood
poisoning
• Symptoms
– Vomiting, diarrhea, constipation, black
stools
– Death
􀂄
 Iron Toxicity
• Hemosiderosis
– Microscopically visible form is hemosiderosis
– Iron overload without tissue injury
• Hemochromatosis
– Macroscopically visible form
– Iron overload with tissue injury
– Bronze diabetes
• Bronze pigmentation of skin and tissues
 Copper ( Cu )

• Dietary sources
– Oyster
– Nuts
– Legumes
– Mushrooms
– Meat
– Dry fruit
– Potatoes
 Absorption, Metabolism, &
Regulation of Copper
• Absorbed in small intestine & stomach as free and
bound Cu
• Amino acids bound Cu is also absorbable
• Influenced by Cu status
– Body stores and requirement
– Form : Cupric or Cuprous
• Excess incorporated into bile &
eliminated in feces
 Absorption, Metabolism, &
Regulation of Copper

• Bioavailability decreases with

– Antacids
– Iron
– Ca
– Zn
• Total Cu level 100—150 mg
– Muscle 64 mg
– Bone 23 mg
– Liver 18 mg
 Transport of Cu

• Ceruloplasmin 96 %
• Remaining with albumin and
globulin

• Functions of ceruloplasmin
– Cu transport
– Conversion of iron from ferrous
to ferric form
 Functions of Copper
• Needed to absorb and utilize iron
• Part of anti oxidant enzyme superoxidase dismutase
• ATP synthesis
– Cytochrome C oxidase
– Copper is needed by the body for a number of functions
, predominantly as a cofactor for a number of enzymes
such as ceruloplasmin, cytochrome c oxidase,
dopamine β-hydroxylase, superoxide dismutase and
tyrosinase.
• Connective tissue synthesis
copper membrane tra
nsporter 1
=CMT1 Liver cells
Normal absorption and
distribution of copper.
Cu = copper, CP =
ceruloplasmin, green =
ATP7B carrying copper.
 Excretion

• Unabsorbed in feces
• Bile
• Sweat
• Urine
• Menstrual blood
 Copper Deficiency & Toxicity

• Deficiency
– 􀂄 Hospitalized patients & preterm infants
– 􀂄 Antacids
• Signs & Symptoms
– 􀂄 Defective connective tissue, anemia, neural
problems
• 􀂄 Toxicity
– 􀂄 Rare
 Copper Deficiency
• Menke’s Disease
– X-linked recessive genetic disorder
– Poor copper absorption
– Steely hair syndrome
– Growth retardationMenkes disease
(MNK), also known as Menkes
syndrome, is an X-linked
recessive disorder caused by
mutations in genes coding for the
copper-transport protein ATP7A,
leading to copper deficiency.
Common symptoms of Menkes disease
• :
• Brittle, kinky, steely, sparse, or tangled hair.
• Pudgy, rosy cheeks, sagging facial skin.
• Feeding difficulties.
• Irritability.
• Lack of muscle tone, floppiness.
• Low body temperature.
• Intellectual disability and developmental delay.
• Seizures.
Wilson’s disease
Copper Deficiency
– Autosomal recessive disorder (occurrence = about 1 in 30,000
– Increased Cu absorption in gut but low release from liver
– Liver Cu level increases
– Excessive urinary excretion of Cu
– Serum Cu level decreases
– Cu accumulates in liver , brain and kidney
– CNS lesions with muscular incoordination
Wilson's disease is caused by a mutation in the Wilson disease protein (ATP7B) gene. This
protein transports excess copper into bile, where it is excreted in waste products. The condition
is autosomal recessive; affected person inherits a mutated copy of the gene from both
parents. Diagnosis may be difficult and often involves a combination of blood tests, urine tests
and a liver biopsy. Genetic testing is used to screen family members of the affected.
Wilson's disease is typically treated with dietary changes and medication, eating a low-copper
diet and not using copper cookware. Medications used include chelating agents such as
trientine and d-penicillamine and zinc supplements.Complications of Wilson's disease can
include liver failure, liver cancer and kidney problems. A liver transplant may be helpful in
those in whom other treatments are not effective or if liver failure occurs.
Wilson's disease people. Symptoms usually begin between the ages of 5 and 35 years. It was
first described in 1854 by German pathologist Friedrich Theodor von Frerichs and is named
after British neurologist Samuel
 Copper enters the body through the digestive tract. A transporter protein on the
cells of the small bowel, copper membrane transporter 1 (Ctr1; SLC31A1), carries
copper inside the cells, where some is bound to metallothionein and part is carried by
ATOX1 to an organelle known as the trans-Golgi network. Here, in response to rising
concentrations of copper, an enzyme called ATP7A (Menkes' protein) releases copper
into the portal vein to the liver. Liver cells also carry the CMT1 protein, and
metallothionein and ATOX1 bind it inside the cell, but here it is ATP7B that links copper
to ceruloplasmin and releases it into the bloodstream, as well as removing excess
copper by secreting it into bile. Both functions of ATP7B are impaired in Wilson's
disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a
form that lacks copper (termed apoceruloplasmin) and is rapidly degraded in the
bloodstream.
When the amount of copper in the liver overwhelms the proteins that normally bind it, it
causes oxidative damage through a process known as Fenton chemistry; this damage
eventually leads to chronic active hepatitis, fibrosis (deposition of connective tissue)
and cirrhosis. The liver also releases copper into the bloodstream that is not bound to
ceruloplasmin. This free copper precipitates throughout the body but particularly in the
kidneys, eyes and brain. In the brain, most copper is deposited in the basal ganglia,
particularly in the putamen and globus pallidus (together called the lenticular nucleus);
these areas normally participate in the coordination of movement as well as playing a
significant role in neurocognitive processes such as the processing of stimuli and mood
regulation. Damage to these areas, again by Fenton chemistry, produces the
neuropsychiatric symptoms seen in Wilson's disease.
 Cu is an essential trace mineral for many important
enzymes and proteins in living organisms. Cu
homeostasis is generally well-maintained with effective
regulatory mechanisms, and Cu toxicity resulting from
disturbed homeostasis is an important contributor to
numerous different symptoms and disease conditions.
These disease states are most often linked to the role of
Cu as a redox-active transition metal that may initiate
oxidative damage. Recently, altered lipid metabolism,
gene expression, alpha-synuclein aggregation (Lewy
bodies) , activation of Acidic sphingomyelinase and
release of ceramide, and temporal and spatial
distribution of Cu in hepatocytes, and Cu-protein
interaction in the nerve system, have been suggested to
play a role in Cu toxicity.
 Acute symptoms of copper poisoning by ingestion
include vomiting, hematemesis (vomiting of blood),
hypotension (low blood pressure), melena (black "tarry"
feces), coma, jaundice (yellowish pigmentation of the
skin), and gastrointestinal distress. Individuals with
glucose-6-phosphate deficiency may be at increased risk
of hematologic effects of copper. [Hemolytic anemia
resulting from the treatment of burns with copper
compounds is infrequent.
Chronic (long-term) copper exposure can damage the
liver and kidneys. Mammals have efficient mechanisms
to regulate copper stores such that they are generally
protected from excess dietary copper levels.
Iodine
 Iodine
• Essential for the formation of thyroid hormones
• Total iodine content 20—40 mg ( 20 % in thyroid
gland)
• Plasma iodide level 0.3—0.5 micro gm/ dl
• Daily intake 500 micro gm
• Almost all absorbed
• Remaining excreted in urine
 Dietary Sources

• Seafood
• Milk/dairy products
• Iodized salt
• Cod liver oil
 Absorption, Metabolism,
&Regulation of Iodine
• Absorbed in small intestine & stomach
• Also absorbed in lungs, mucous membrane and skin
• Taken up by thyroid gland
• Thyroid-stimulating hormone regulates
uptake
 Functions of Iodine

• Component of:
– 􀂄 Thyroxine (T4)
– 􀂄 Triiodothyronine (T3)
• Regulates energy metabolism, growth,
development
• Signs of deficiency
– 􀂄 Severe fatigue
– 􀂄 Lethargy
 Iodine Deficiency

• Goiter (less
severe)
– 􀂄 Enlarged
thyroid gland due
to body’s attempt
to increase
thyroid hormone
production
 Iodine Deficiency

• Cretinism (more severe)

– 􀂄 Severe iodine
deficiency during
pregnancy, serious
problems in baby
– 􀂄 Stunted growth, deaf,
mute, mentally retarded
 Iodine Toxicity

• 􀂄 Hypothyroidism

• 􀂄 Hyperthyroidism
( Thyrotoxicosis )
• 􀂄 Formation of goiters
Chromium
 Chromium (Cr): Dietary Sources,
Bioavailability, & Regulation
• Food content depends on soil
• Whole grains, fruits/veg, processed meats, dairy and
fish
• Bioavailability affected by:
– Vitamin C
– Acidic medications
– Antacids
• Transported in blood to liver
• Excess excreted in urine & feces
 Functions of Chromium
• Regulates insulin
– Synergistic with insulin
in its action for glucose
utilization
• Growth & development
– Increases lean mass
– Decreases fat mass
 Chromium Deficiency & Toxicity

• Deficiency
– 􀂄 Hospitalized patients
– 􀂄 Elevated blood glucose
– 􀂄 Decreased insulin sensitivity
– 􀂄 Weight loss
• Toxicity
– 􀂄 Rare
– 􀂄 Industrially released chromium can be toxic at very
high levels
 Manganese (Mn):
• RDA 4 mg
• Blood 4– 20 micro
gm / dl
 Manganese (Mn): Dietary Sources &
Regulation

• Whole grains, pineapples, nuts, legumes, dark

green leafy vegetables, water
• <10% absorbed
• Excess incorporated into bile & excreted
in feces
 Functions of Manganese

• Cofactor for metalloenzymes

– 􀂄 Gluconeogenesis
– 􀂄 Bone formation
• Cofactor for superoxide dismutase
• Mn dependant enzymes: decarboxylase,
phosphatase, glycerol transferase etc
• Digestion of food
• Supports immune system
 Functions of Manganese

• Regulates blood sugar

level
• Production of energy &
cell reproduction
• Bone growth
• Supports blood clotting
along with Vitamin K
 Manganese Deficiency & Toxicity

• Deficiency
– Rare
– Scaly skin, poor bone formation, growth retardation
• Toxicity ( Total Mn content above 10 mg )
– Rare
– Mining
– Liver disease
– Psychosis
– Parkinsonism like symptoms
 Selenium
• Se is essential trace element at lower
concentrations
• Toxic at higher concentrations
• Essential for production of steroid
hormones like testosterone
• Requirement
– 3— 4 micro gm / d
Absorption, Metabolism, &
Regulation of Selenium

• Most Se enters blood

• Incorporated into selenomethionine
• Makes selenoproteins
• Stored in muscles
• Maintenance of Se through excretion in
urine
 Functions of Selenium

Component of glutathione peroxidase

– catalyzes removal of hydrogen peroxide
– GSH + H2O2 GSSG + H2O
– GSH = reduced glutathione
– GSSG = oxidized glutathione
Component of iodothyronine-5’- deiodinase
– Converts T4 to T3
Improves killing ability of neutrophils
– Reduces the prevalence and severity of mastitis
 Functions of Selenium

• Responsible for normal pancreatic function

• Digestion and absorption of fats & vitamin E
• For ATP synthesis
• For synthesis of steroids and related compounds
• Protective role against antioxidants
 Selenium Deficiency & Toxicity

• Deficiency
– Keshan disease
( cardiomyopathy )
– Muscular dystrophy
– Stiff limb disease
– Liver dystrophy
– Muscular degeneration
 Selenium Deficiency Diseases
Keshan disease, an endemic cardiomyopathy occurring in low-selenium areas of China
and Russia, is associated with low selenium intake and low blood and hair levels, and
affects mainly children and women of childbearing age. The main clinical features
of Keshan disease are cardiac insufficiency and enlargement, electrocardiographic
changes, and fibrosis. In 1979 Keshan disease was reported to be responsive to
supplementation with sodium selenite and was initially thought to be a simple selenium
deficiency. However, some features of Keshan disease (e.g., seasonal variation) could
not be explained solely by very low selenium status. Now it is proved that Coxsackie B
virus is also involved in addition to Se.
Another condition that has been associated with severe selenium deficiency is Kaschin–
Beck disease, with clinical features of osteoarthropathy and necrosis of joints and
epiphysial plate cartilage. Kaschin–Beck disease occurs during preadolescent or
adolescent years in rural areas of China, Tibet, and Siberia. However, other factors such
as iodine deficiency or presence of mycotoxins may be more important than selenium
deficiency.
Severe selenium deficiency in combination with inadequate iodine status contributes to
the pathogenesis of myxodematous cretinism. Even mild to moderate selenium
deficiency appears to be responsible for initiation and progression of autoimmune
thyroid disorders.
 Selenium Deficiency & Toxicity
• Toxicity
• Above 15 micro gm
– Garlic-like odor of breath
– Nausea
– Vomiting
– Diarrhea
– Brittleness of teeth &
fingernails
– Loss of hair
 Molybdenum (Mo):
• Dietary sources
– Food content depends on soil
– Legumes, grains, nuts, peas, cauliflower
– Low amount in fruits, sugar, oil & fish
• Absorption & regulation
– Absorbed in intestine
– Circulated to liver via blood
 Functions of Molybdenum

• Cofactor for several enzymes

• Molybdenum containing enzymes:
– Xanthine oxidase, aldehyde oxidase, nitrate reductase
– Sulfite oxidase
• Metabolism of:
– Sulfur-containing amino acids
– DNA & RNA
• Detoxifying drugs in liver
 Molybdenum Deficiency & Toxicity

• Deficiency
– Rare
– May be due to TPN (total
parenteral nutrition),
Crohn’s disease
• Toxicity
– Hair loss
– Dermatitis
 Aluminium
• Daily requirement 10
– 90 mg

• Total aluminium
content 50– 150 mg
 Aluminium
• Dietary sources
– Added sodium Al sulphate
– Al sulphate
• Absorption
– Poor
– Minute amount in jejunum
• Excretion
– Feces
 Aluminium
• Toxicity
• High Al intake
– Rickets like symptoms
• Renal toxicity in uremia
causes Al deposition
 Cadmium

• Occurs in earth crest

in elemental form
• Distribution
– Renal cortex 6 %
– Metallothionine
binds Cd and Zn
 Cadmium : Functions

• Essential component of various metalloenzymes

• Essential for normal body functions
• Assists in wound healing
• Increase immunity
• Helps in taste sensation
 Cadmium : Deficiency
• Diabetes like disease
• Decreased growth
• Reduced taste sensations
• Hypogonadism
• Delayed wound healing
 Cadmium : Toxicity

• Exposure to cadmium oxide

• Risk of lung, prostate & kidney cancer
• Anemia
• Loss of smell
• Fatigue
• Yellow staining of teeth
• RDA 15 mg / day as
ZnSO4
• Sources
– Meat
– Fish
– Dairy products
– Plants / vegetables poor
sources
• Bioavailability influenced
by:
– Phytates
– Iron
– Calcium
• Duodenum & upper jejunum
• 10 – 20 % absorbed via active transport
• Requires proteins to:
– 􀂄Transport zinc into enterocyte
• 􀂄 Metallothionine
– 􀂄 Bind zinc within cell
• Transport
– Albumin bound 60 – 70 %
– Alpha 2 macroglobin 30 – 40 %
– Small amount with tranferrin and ferritin
• Excretion
– 25 % in pancreatic juice
– Bile
– Urine
– Sweat
– Feces
• Essential mineral present in every cell
• Supports healthy immune system
• Assists in wound healing
• Insulin stored as penta & hexa Zn – Insulin complex
• Sense of taste & smell
• Needed for normal growth during pregnancy,
childhood and adolescence
• Stimulates activity of approximately 250 enzymes
– ALT
– Phophatase
– RNA / DNA polymerase
– Carboxy peptidase
– Thymine kinase
• Gustein : a protein resposible for taste sensation in
mouth
• Cofactor
– 􀂄RNA synthesis
• Stabilizes proteins
that regulate gene
expression
– 􀂄 Zinc fingers
• Antioxidant
• Stabilizes cell
membranes
• Growth failure
• Reduced taste
sensation
• Hypogonadism
• Delayed wound
healing
• Dermatitis
• Susceptibility to
infections
• Zinc deficiency even
with adequate
amounts of dietary zinc
• Supplementation
• Infants
– Growth failure
– Red/scaly skin
– Diarrhea
• Depressed levels of
HDL
• Impaired copper
status
• Nausea
• Vomiting
• Loss of appetite
• Poor immune function
• Daily requirement
0.16 – 1.2 micro gms

• 99% is found in
bones and teeth
• Not an essential nutrient
• Potatoes, tea, legumes, fish, toothpaste, added to
drinking water
• Absorbed via small intestine
• Circulates in blood to liver & then teeth &
bone
• Excess excreted in urine
• Part of bone & teeth matrix
• Stimulates maturation of osteoblasts
• Topical application decreases bacteria in mouth
– 􀂄 Fewer cavities
• To promote mineralization of Ca and phosphate
• Sodium fluoride used as preservative for blood
samples
– Inhibits glycolysis
• Deficiency
– Bone & teeth decay
• Enamel of teeth is lost
• Toxicity
– Staining & molting of enamel of
teeth
– Excessive production of saliva
– Watery eyes
• Hexafluoride component of fluorine is used for
producing uranium
• 2 phosphoglycerate Phosphoenol pyruvate
Pyurvate
– One of enzymes in above reaction is enolase and fluoride
inhibits it
• Mn activated enzymes are inhibited
• Sources
– Animal sources
• Necessary for
cyanocobalamine
• Forms core of vit B12
• Component of B 12
– Effects blood cell formation
• Essential component of enzymes like :
– Methyl malonyl CoA
– Ribonucleotide reductase
– Oxidoreductase
• Essential coenzyme for
– methylmalonyl CoA to succinyl CoA
• Bacterial synthesis of methionine
• Anemia
• Digestive disorders
• Fatigue
• Poor circulation
• Myelin sheath damage
• Slow growth rate
• Excess excreted in urine
 Cobalt poisoning
Healthy person contains 0.019 microgram/dl
blood Cadmium. It is almost 25 microgram in
whole blood stream. O.5 microgram /dl is high
toxic level.

High causes cardiomyopathy, hypothyroidism,

and neurological damage as well as impairing the
senses. It can cause neuropathy, seizures,
blindness, headaches, and liver damage. Cobalt
has also been linked to cancer.
Hyponatremia is a low sodium concentration in the blood. It is generally
defined as a sodium concentration of less than 135 mmol/L (135 mEq/L),
with severe hyponatremia being below120 mEq/L. Symptoms can be
absent, mild or severe. Mild symptoms include a decreased ability to
think, headaches, nausea, and poorbalance. Severe symptoms include
confusion, seizures, and coma. The causes of hyponatremia are typically
classified by a person's body fluid status into low volume, normal volume,
or high volume. Low volume hyponatremia can occur
from diarrhea, vomiting, diuretics, and sweating. Normal volume
hyponatremia is divided into cases with dilute urine
and concentrated urine. Cases in which the urine is dilute include adrenal
insufficiency, hypothyroidism, and drinking too much water or too much
beer. Cases in which the urine is concentrated include syndrome of
inappropriate antidiuretic hormone secretion (SIADH). High volume
hyponatremia can occur from heart failure, liver failure, and kidney
failure. Conditions that can lead to falsely low sodium measurements
include high blood protein levels such as in multiple myeloma, high blood
fat levels, and high blood sugar.
 High volume
Both sodium and water content increase:
Increase in sodium content leads to
Hypervolemia and water content to
hyponatremia. cirrhosis of the liver congestive
heart failure nephrotic syndrome in the kidneys
Excessive drinking of fluids
Normal volume There is volume expansion in
the body, no edema, but hyponatremia occurs
SIADH (and its many causes) Hypothyroidism Not
enough ACTH Beer potomania
Normal physiologic change of pregnancy
Reset osmostat
 Low volume
Hypovolemia (extracellular volume loss) is due to total body
sodium loss. Hyponatremia is caused by a relatively smaller loss in
total body water. any cause of hypovolemia such as prolonged
vomiting, decreased oral intake, severe diarrhea
diuretic use (due to the diuretic causing a volume depleted state
and thence ADH release, and not a direct result of diuretic-
induced urine sodium loss)
Addison's disease and congenital adrenal hyperplasia in which
the adrenal glands do not produce enough steroid hormones
(combined glucocorticoid and mineralocorticoid deficiency
pancreatitis
Prolonged exercise and sweating, combined with drinking water
without electrolytes is the cause of exercise-associated
hyponatremia(EAH). It is common in marathon runners and
participants of other endurance events.
The use of MDMA (ecstasy) can result in hyponatremia.
Hypernatremia, is a high concentration
of sodium in the blood. Early symptoms may
include a strong feeling of thirst, weakness,
nausea, and loss of appetite. Severe symptoms
include confusion, muscle twitching, and bleeding
in or around the brain. Normal serum sodium
levels are 135 – 145 mmol/L (135 –
145 mEq/L). Hypernatremia is generally defined
as a serum sodium level of more than
145 mmol/L. Severe symptoms typically only
occur when levels are above 160 mmol/L.
Hypernatremia is typically classified by a person's fluid
status into low volume, normal volume, and high
volume. Low volume hypernatremia can occur
from sweating, vomiting, diarrhoea, diuretic medication,
or kidney disease. Normal volume hypernatremia can be
due to fever, inappropriately decreased thirst,
prolonged increased breath rate, diabetes insipidus, and
from lithium among other causes. High volume
hypernatremia can be due to hyperaldosteronism,
excessive administration of intravenous 3% normal
saline or sodium bicarbonate, or rarely from eating too
much salt. Low blood protein levels can result in a falsely
high sodium measurement. The cause can usually be
determined by the history of events. Testing the urine can
help if the cause is unclear. The underlying mechanism
typically involves too little free water in the body.
Hypokalemia is a low level of potassium (K+) in the blood
serum. Mildly low levels do not typically cause symptoms.
Symptoms may include feeling tired, leg cramps, weakness,
and constipation. It increases the risk of an abnormal heart
rhythm, which is often too slow, and can cause cardiac arrest.
Causes of hypokalemia include vomiting, diarrhoea, medications
like furosemide and steroids, dialysis, diabetes insipidus,
hyperaldosteronism, hypomagnesaemia, and not enough intake in
the diet. Normal potassium levels are between 3.5 and
5.0 mmol/L (3.5 and 5.0 mEq/L) with levels below 3.5 mmol/L
defined as hypokalemia. It is classified as severe when levels are
less than 2.5 mmol/L. Low levels may also be suspected based on
an electrocardiogram (ECG). Hyperkalemia refers to a high level
of potassium in the blood serum.
Hyperkalemia is an elevated level of potassium (K+) in
the bloodserum. Normal potassium levels are between 3.5 and
5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined
as hyperkalemia. Typically this results in no symptoms. Occasionally
when severe it results in palpitations, muscle pain, muscle weakness,
or numbness. An abnormal heart rat can occur which can result
in cardiac arrest and death.
Common causes include kidney failure, hypoaldosteronism,
and rhabdomyolysis. A number of medications can also cause high blood
potassium including spironolactone, NSAIDs, and angiotensin converting
enzyme inhibitors.The severity is divided into mild (5.5–5.9 mmol/L),
moderate (6.0–6.4 mmol/L), and severe (>6.5 mmol/L). High levels can
also be detected on an electrocardiogram (ECG). Pseudohyperkalemia,
due to breakdown of cells during or after taking the blood sample,
should be ruled out. Hyperkalemia is rare among those who are
otherwise healthy. Among those who are in hospital, rates are between
1% and 2.5%. It increases the overall risk of death by at least ten
times. The word "hyperkalemia" is from hyper- meaning
high; kalium meaning potassium; and -emia, meaning "in the blood".
Deficiency of magnesium can cause tiredness, generalized
weakness, muscle cramps, abnormal heart rhythms, increased irritability
of the nervous system with tremors, paresthesias, palpitations, low
potassium levels in the blood, hypoparathyroidism which might result
in low calcium levels in the blood
chondrocalcinosis, spasticity and tetany, migraines, epileptic seizures,
basal ganglia calcifications and in extreme and prolonged
cases coma, intellectual disability or death. Magnesium plays an
important role in carbohydrate metabolism and its deficiency may
worsen insulin resistance, a condition that often precedes diabetes, or
may be a consequence of insulin resistance. Magnesium is a co-factor in
over 300 functions in the body regulating many kinds of biochemical
reactions. It is involved in protein synthesis, muscle and nerve
functioning, bone development, energy production, the maintenance of
normal heart rhythm, and the regulation of glucose and blood pressure,
among other important roles. Low magnesium intake over time can
increase the risk of illnesses, including high blood pressure and heart
disease, diabetes mellitus type 2, osteoporosis, and migraines. There is
a direct effect on sodium (Na), potassium (K), and calcium (Ca)
channels. Magnesium has several effects:
 Potassium
Potassium channel efflux is inhibited by magnesium. Thus
hypomagnesemia results in an increased excretion of potassium in
kidney, result is frequently the cause of hypomagnesemic
hypokalaemia. This condition is believed to occur secondary to the
decreased normal physiologic magnesium inhibition of
the ROMK channels in the apical tubular membrane.
In this light, hypomagnesemia patients failing to respond to potassium
supplementation. Thus, clinicians should ensure that both Magnesium
and Potassium is replaced when deficient. Patients with diabetic
ketoacidosis should have their magnesium levels monitored to ensure
that the serum loss of potassium, which is driven intracellularly
by insulin administration, is not exacerbated by additional urinary losses.
Release of calcium from the sarcoplasmic reticulum is inhibited by
magnesium. Thus hypomagnesemia results in an increased intracellular
calcium level. This inhibits the release of parathyroid hormone, which
can result in hypoparathyroidism and hypocalcemia. Furthermore, it
makes skeletal and muscle receptors less sensitive to parathyroid
hormone
 Arrhythmia
Magnesium is needed for the adequate function of the Na+/K+-ATPase pumps
in cardiac myocytes, the muscles cells of the heart. A lack of magnesium
inhibits reuptake of potassium, causing a decrease in intracellular potassium.
This decrease in intracellular potassium results in a tachycardia.
Pre-eclampsia
Magnesium has an indirect antithrombotic effect upon platelets and endothelial
function. Magnesium increases prostaglandins, decreases thromboxane, and
decreases angiotensin II, microvascular leakage, and vasospasm through its
function similar to calcium channel blockers.Convulsions are the result of
cerebral vasospasm. The vasodilatatory effect of magnesium seems to be the
major mechanism.
Asthma
Magnesium exerts a bronchodilatatory effect, probably by antagonizing
calcium-mediated bronchoconstriction.
Neurological effects
reducing electrical excitation
modulating release of acetylcholine
antagonizing N-methyl-D-aspartate (NMDA) glutamate receptors, an
excitatory neurotransmitter of the central nervous system and thus providing
neuroprotection from excitoxicity.
 Calcium
Deficiency: Long-term inadequate intake can
result in low bone mineral density, rickets,
osteomalacia and osteoporosis.
Toxicity: Will cause nausea, vomiting,
constipation, dry mouth, thirst, increased
urination, kidney stones and soft tissue
calcification.
Sources: Dairy, green leafy vegetables, legumes,
tofu, molasses, sardines, okra, perch, trout,
Chinese cabbage, rhubarb, sesame seeds
Hypocalcemia is common and can occur unnoticed with no symptoms or, in
severe cases, can have dramatic symptoms and be life
threatening. Hypocalcemia can be parathyroid related or vitamin D related.
Parathyroid related hypocalcemia includes post-surgical hypoparathyroidism,
inherited hypoparathyroidism, pseudohypoparathyroidism, and pseudo-
pseudohypoparathyroidism. Post-surgical hypoparathyroidism is the most
common form, and can be temporary (due to suppression of tissue after
removal of a malfunctioning gland) or permanent, if all parathyroid tissue has
been removed. Inherited hypoparathyroidism is rare and is due to a mutation
in the calcium sensing receptor. Pseudohypoparathyroidism is maternally
inherited and is categorized by hypocalcemia and hyperphosphatemia. Finally,
pseudo-pseudohypoparathyroidism is paternally inherited. Patients display
normal parathyroid hormone action in the kidney, but exhibit altered
parathyroid hormone action in the bone. Vitamin D related hypocalcemia may
be associated with a lack of vitamin D in the diet, a lack of sufficient UV
exposure, or disturbances in renal function. Low vitamin D in the body can lead
to a lack of calcium absorption and secondary hyperparathyroidism
(hypocalcemia and raised parathyroid hormone). Symptoms of hypocalcemia
include numbness in fingers and toes, muscle cramps, irritability, impaired
mental capacity and muscle twitching
 Hypercalcemia
Hypercalcemia is suspected to occur in approximately 1 in 500 adults in
the general adult population. Like hypocalcemia, hypercalcemia can be
non-severe and present with no symptoms, or it may be severe, with
life-threatening symptoms. Hypercalcemia is most commonly caused by
hyperparathyroidism and by malignancy, and less commonly by vitamin
D intoxication, familial hypocalciuric hypercalcemia and by sarcoidosis.
Hyperparathyroidism occurs most commonly in postmenopausal
women. Hyperparathyroidism can be caused by a tumor, or adenoma, in
the parathyroid gland or by increased levels of parathyroid hormone due
to hypocalcemia. Approximately 10% of cancer sufferers experience
hypercalcemia due to malignancy. Hypercalcemia occurs most
commonly in breast cancer, lymphoma, prostate cancer, thyroid cancer,
lung cancer, myeloma, and colon cancer.It may be caused by secretion
of parathyroid hormone-related peptide by the tumor (which has the
same action as parathyroid hormone), or may be a result of direct
invasion of the bone, causing calcium release. Symptoms of
hypercalcemia include anorexia, nausea, vomiting, constipation,
abdominal pain, lethargy, depression, confusion, polyuria, polydipsia and
 Phosphorus
Deficiency: Very rare. Those at risk include
premature infants, those who use antacids,
alcoholics, uncontrolled diabetes mellitus and
refeeding syndrome.
Toxicity: Very rare. May result in soft tissue
calcification.
Sources: Legumes, nuts, seeds, whole grains,
eggs, fish, buckwheat, seafood, corn, wild rice
 Magnesium
Deficiency: Very rare due to abundance of
magnesium in foods. Those with gastrointestinal
disorders, kidney disorders, and alcoholism are at
risk.
Toxicity: None identified from foods. Excessive
consumption of magnesium containing
supplements may result in diarrhea (magnesium
is a known laxative), impaired kidney function,
low blood pressure, muscle weakness, and
cardiac arrest.
Sources: Legumes, nuts, seeds, whole grains,
fruits, avocado
 Iron
Consume iron rich foods with vitamin C rich foods to
enhance absorption.
Iron Deficiency: Anaemia with small and pale red blood
cells. In children it is associated with behavioural
abnormalities.
Toxicity: Common cause of poisoning in children. May
increase the risk of chronic disease. Excessive intake of
supplemental iron is an emergency room situation.
Cardiovascular disease, cancer, and neurodegenerative
diseases are associated with iron excess.
Sources: Almonds, apricots, baked beans, dates, lima
beans, kidney beans, raisins, brown rice, green leafy
vegetables, broccoli, pumpkin seeds, tuna, flounder,
chicken meat,
 Zinc
Zinc deficiency results in decreased immunity and increases the
susceptibility to infection. Supplementation of zinc has been
shown to reduce the incidence of infection as well as cellular
damage from increased oxidative stress. Zinc deficiency has also
been implicated in diarrheal disease, supplementation might be
effective in the prophylaxis and treatment of acute diarrhea.
Deficiency: Symptoms include growth retardation, lowered
immune statue, skeletal abnormalities, delay in sexual maturation,
poor wound healing, taste changes, night blindness and hair loss.
Those at risk for deficiency include the elderly, alcoholics, those
with malabsorption, vegans, and those with severe diarrhea.
Toxicity: Symptoms that result are abdominal pain, diarrhea,
nausea, and vomiting. Long-term consumption of excessive zinc
can result in copper deficiency.
Sources: Mushrooms, spinach, sesame seeds, pumpkin seeds,
green peas, baked beans, cashews, peas, whole grains, flounder,
oats, oysters, chicken meat
 Copper
Deficiency: Relatively uncommon. Clinical sign is
hypochromic anemia unresponsive to iron therapy.
Neutropenia and leucopenia may also result.
Hypopigmentation of skin and hair is also noticed. Those
at risk for deficiency include premature infants, infants
fed only cow’s milk formula, those with malabsorption
syndromes, excessive zinc consumption and antacid use.
Toxicity: Rare. Symptoms include abdominal pain,
nausea, vomiting, and diarrhea. Long-term exposure to
lower doses of copper can result in liver damage.
Sources: Mushrooms, green leafy vegetables, barley,
soybeans, tempeh, sunflower seeds, navy beans,
garbanzo beans, cashews, molasses, liver
 Iodine
Deficiency: Impairs growth and neurological
development. Deficiency can also result in the
decreased production of thyroid hormones and
hypertrophy of the thyroid.
Toxicity: Rare and occurs in doses of many
grams. Symptoms include burning mouth, throat
and stomach. Fever and diarrhea can also result.
Sources: Sea vegetables, iodized salt, eggs,
strawberries, asparagus, green leafy vegetables
Keshan disease: A condition caused by deficiency of the
essential mineral selenium. Keshan disease is a
potentially fatal form of cardiomyopathy (disease of
the heart muscle). It was first observed in Keshan
province in China, and it has since been found in other
areas where the selenium level in the soil is low.
Selenium is also necessary for the conversion of the thyroid
hormone thyroxine (T4) into its more active counterpart,
triiodothyronine, and as such a deficiency can cause symptom
of hypothyroidism, including extreme fatigue, mental
slowing,goiter, cretinism, and recurrent miscarriage.
The most common clinical signs of chronically high selenium
intakes, or selenosis, are hair and nail loss or brittleness. Othe
symptoms include lesions of the skin and nervous
system, nausea, diarrhea, skin rashes, mottled
teeth, fatigue, irritability, and nervous system abnormalities
Wilson disease is a rare genetic disorder characterized by excess copper
stored in various body tissues, particularly the liver, brain, and corneas
of the eyes. The disease is progressive and, if left untreated, it may
cause liver (hepatic) disease, central nervous system dysfunction, and
death. Wilson disease is caused by an inherited defect in the ATP7B
gene. It is an autosomal recessive disorder. In a public health
statement, the American Thyroid Association concluded: The diagnostic
criteria for Wilson's syndrome — low body temperature
and nonspecific signs and symptoms, such
as fatigue, irritability, hair loss, insomnia,headaches and weight
gain — are imprecise. In more severe forms, copper toxicity can
lead to: Heart and kidney failure. Liver damage. Brain disease or
disorder.
...
Signs and symptoms of copper deficiency can include:
Anemia.
A low level of white blood cells called neutrophils (neutropenia)
Osteoporosis.
Paleness.
Hair with less pigment than normal.
 PEM
• In 2000 WHO estimated that 32% of <5
children in developing countries are
underweight (182 million).
• 78% of these children live in South-east Asia
& 15% in Sub-Saharan Africa.
• The reciprocal interaction between PEM &
infection is the major cause of death &
morbidity in young children.
 EPIDEMIOLOGY

• The term protein energy malnutrition has

been adopted by WHO in 1976.
• Highly prevalent in developing countries
among <5 children; severe forms 1-10% &
underweight 20-40%.
• All children with PEM have micronutrient
deficiency.
 PEM in Sub-Saharan Africa

• PEM in Africa is related to:

– The high birth rate
– Subsistence farming
– Overused soil, drought & desertification
– Pets & diseases destroy crops
– Poverty
– Low protein diet
– Political instability (war & displacement)
 PRECIPITATING FACTORS

 LACK OF FOOD (famine, poverty)

 INADEQUATE BREAST FEEDING

 WRONG CONCEPTS ABOUT NUTRITION

 DIARRHOEA & MALABSORPTION

 INFECTIONS (worms, measles, T.B)

 CLASSIFICATION

– A. CLINICAL ( WELLCOME )
– Parameter: weight for age + oedema
– Reference tandard (50th percentile)
– Grades:
• 80-60 % without oedema is under weight
• 80-60% with oedema is Kwashiorkor
• < 60 % with oedema is Marasmus-Kwash
• < 60 % without oedema is Marasmus
 CLASSIFICATION (2)

– B. COMMUNITY (GOMEZ)
– Parameter: weight for age
– Reference standard (50th percentile) WHO
chart
– Grades:
•I (Mild): 90-70
• II (Moderate): 70-60
• III (Severe) : < 60
 ADVANTAGES

 SIMPLICITY (no lab tests needed)

 REPRODUCIBILITY
 COMPARABILITY
 ANTHROPOMETRY+CLINICAL SIGN USED
FOR ASSESSMENT
 DISADVANTAGES

 AGE MAY NOT BE KNOWN

 HEIGHT NOT CONSIDERED
 CROSS SECTIONAL
 CAN’T TELL ABOUT CHRONICITY
 WHO STANDARDS MAY NOT REPRESENT
LOCAL COMMUNITY STANDARD
 KWASHIORKOR

• Cecilly Williams, a British nurse, had

introduced the word Kwashiorkor to the
medical literature in 1933. The word is taken
from the Ga language in Ghana & used to
describe the sickness of weaning.
• Kwashiorkor is an acute form of childhood protein-
energy malnutrition characterized by edema,
irritability, anorexia, ulcerating dermatoses, and an
enlarged liver with fatty infiltrates. The presence of
edema caused by poor nutrition defines kwashiorkor.
Kwashiorkor was thought to be caused by insufficient
protein consumption but with sufficient calorie
intake, distinguishing it from marasmus. More
recently, micronutrient and antioxidant deficiencies
have come to be recognized as contributory. Cases in
the developed world are rare.
 ETIOLOGY

• Kwashiorkor can occur in infancy but its

maximal incidence is in the 2nd yr of life
following abrupt weaning.
• Kwashiorkor is not only dietary in origin.
Infective, psycho-socical, and cultural factors
are also operative.
 ETIOLOGY (2)
 Kwashiorkor is an example of lack of
physiological adaptation to unbalanced
deficiency where the body utilized
proteins and conserve S/C fat.
 One theory says Kwash is a result of
liver insult with hypoproteinemia and
oedema. Food toxins like aflatoxins
have been suggested as precipitating
factors.
 CLINICAL PRESENTATION
 Kwash is characterized by certain constant
features in addition to a variable spectrum
of symptoms and signs.
 Clinical presentation is affected by:
• The degree of deficiency
• The duration of deficiency
 The speed of onset
 The age at onset
 Presence of conditioning factors
 Genetic factors
CONSTANT FEATURES OF KWASH

 OEDEMA

 PSYCHOMOTOR CHANGES

 GROWTH RETARDATION

 MUSCLE WASTING
USUALLY PRESENT SIGNS

 MOON FACE
 HAIR CHANGES
 SKIN DEPIGMENTATION
 ANAEMIA
OCCASIONALLY PRESENT SIGNS

 HEPATOMEGALY

 FLAKY PAINT DERMATITIS

 CARDIOMYOPATHY & FAILURE

 DEHYDRATION (Diarrh. & Vomiting)

 SIGNS OF VITAMIN DEFICIENCIES

 SIGNS OF INFECTIONS
 DD of Kwash Dermatitis

 Acrodermatitis Entropathica
 Scurvy

 Pellagra

 Dermatitis Herpitiformis
 Marasmus is a severe protein energy malnutrition
characterized by energy deficiency
A child with marasmus looks emaciated. Body weight
may be reduced to less than 80% of the average
weight that corresponds to the height . Marasmus
occurrence increases prior to age 1, whereas
kwashiorkor occurrence increases after 18 months. It
can be distinguished from kwashiorkor in that
kwashiorkor is protein wasting with the presence of
edema.
The prognosis is better than it is for kwashiorkor. The
malnutrition associated with marasmus leads to
extensive tissue and muscle wasting, as well as
variable edema. Other common characteristics include
dry skin, loose skin folds hanging over the buttocks
(glutei) and armpit (axillae), etc. There is also drastic
loss of adipose tissue (body fat) from normal areas of
fat deposits like buttocks and thighs. The afflicted are
often fretful, irritable, and voraciously hungry.
 MARASMUS
 The term marasmus is derived from the
Greek marasmos, which means wasting.
 Marasmus involves inadequate intake of
protein and calories and is
characterized by emaciation.
 Marasmus represents the end result of
starvation where both proteins and
calories are deficient.
 MARASMUS/2

 Marasmus represents an adaptive

response to starvation, whereas
kwashiorkor represents a
maladaptive response to starvation
 In Marasmus the body utilizes all fat
stores before using muscles.
 EPIDEMIOLOGY &
ETIOLOGY
 Seen most commonly in the first year
of life due to lack of breast feeding
and the use of dilute animal milk.
 Poverty or famine and diarrhoea are
the usual precipitating factors
 Ignorance & poor maternal nutrition
are also contributory
Clinical Features of Marasmus

 Severe wasting of muscle & fats

 Severe growth retardation
 Child looks older than his age
 No edema or hair changes
 Alert but miserable
 Hungry
 Diarrhoea & Dehydration
 CLINICAL ASSESSMENT

 Interrogation & physical exam

including detailed dietary history.
 Anthropometric measurements
 Team approach with involvement of
dieticians, social workers &
community support groups.
 Investigations for PEM
 Full blood counts
 Blood glucose profile
 Septic screening
 Stool & urine for parasites & germs
 Electrolytes, Ca, P & ALP, serum proteins
 CXR & Mantoux test
 Exclude HIV & malabsorption
 NON-ROUTINE TESTS

 Hair analysis
 Skin biopsy
 Urinary creatinine over proline ratio
 Measurement of trace elements
levels, iron, zinc & iodine
 Complications of P.E.M
 Hypoglycemia
 Hypothermia
 Hypokalemia
 Hyponatremia
 Heart failure
 Dehydration & shock
 Infections (bacterial, viral & thrush)
 TREATMENT
 Correction of water & electrolyte imbalance
 Treat infection & worm infestations
 Dietary support: 3-4 g protein & 200 Cal /kg
body wt/day + vitamins & minerals
 Prevention of hypothermia
 Counsel parents & plan future care including
immunization & diet supplements
 KEY POINT FEEDING

 Continue breast feeding

 Add frequent small feeds
 Use liquid diet
 Give vitamin A & folic acid on
admission
 With diarrhea use lactose-free or
soya bean formula
 PROGNOSIS
 Kwash & Marasmus-Kwash have greater
risk of morbidity & mortality compared
to Marasmus and under weight
 Early detection & adequate treatment
are associated with good outcome
 Late ill-effects on IQ, behavior &
cognitive functions are doubtful and not
proven
 Potomania is a word that literally means drinking (poto) alcohol excessively (mania).
In medicine, beer potomania refers to a condition in which the level of sodium in your
bloodstream drops too low due to excessive beer consumption .
There is evidence to suggest a ''reset osmostat phenomenon'' whereby in a normal pregnancy,
the average plasma-osmolality is decreased by 5–10mOsm/kg, and the sodium concentration is
decreased by 5mmol/L (sodium levels decrease from approximately 140mmol/L and is maintained
at 135–136 throughout pregnancy)

Hyperplasia, or hypergenesis, is an increase in the amount of organic tissue that results

from cell proliferation. It may lead to the gross enlargement of an organ, and the term
is sometimes confused with benign neoplasia or benign tumor. Hyperplasia is a common
preneoplastic response to stimulus.
Paresthesias =an abnormal sensation, typically tingling or pricking (‘pins and
needles’), caused chiefly by pressure on or damage to peripheral nerves
Chondrocalcinosis (plural: chondrocalcinoses) is a descriptive term indicating the
presence of gross calcium deposition within articular cartilage, i.e. both hyaline and
fibrocartilage..
Spasticity (from Greek spasmos-, meaning 'drawing, pulling') is a feature of altered
skeletal muscle performance with a combination of paralysis, increased tendon reflex
activity, and hypertonia. It is also colloquially referred to as an unusual "tightness",
stiffness, or "pull" of muscles. The renal outer medullary potassium channel (ROMK) is
an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. It
plays an important role in potassium recycling in the thick ascending limb (TAL) and
potassium secretion in the cortical collecting duct (CCD) of the nephron.s
 Pseudohypoparathyroidism (PHP) is a genetic disorder in which the body fails to
respond to parathyroid hormone. Pseudopseudohypoparathyroidism (PPHP) is
an inherited condition that causes short stature, round face, and short hand
bones. PPHP causes joints and other soft tissues in the body to harden. It also affects
how bones are formed. As a result, PPHP can cause bone, joint, and nerve damage, and
this damage can cause lasting pain. Some people with PPHP (10%) also have learning
disability.PHPP is caused by mutations in the GNAS gene and is inherited in
an autosomal dominant fashion. This condition is usually inherited from the father
(genomic imprinting). PPHP is genetically related to pseudohypoparathyroidism type Ia
(PHP-1a). Signs and symptoms are similar, however people with PPHP do not show
resistance to parathyroid hormone while people with PHP-1a do. Obesity is characteristic
for PHP-1a and may be severe, while obesity is less prominent and may be absent
among people with PPHP.
Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma
cell. Plasma cells help you fight infections by making antibodies that recognize and
attack germs. Multiple myeloma causes cancer cells to accumulate in the bone marrow,
where they crowd out healthy blood cells.
Sarcoidosis is an inflammatory disease that affects multiple organs in the body, but
mostly the lungs and lymph glands. In people with sarcoidosis, abnormal masses or
nodules (called granulomas) consisting of inflamed tissues form in certain organs of the
body Familial hypocalciuric hypercalcemia (FHH) is an inherited disorder that
causes abnormally high levels of calcium in the blood (hypercalcemia) and low to
moderate levels of calcium in urine (hypocalciuric). People with FHH usually do not
have any symptoms and are often diagnosed by chance during routine bloodwork.s