Minerals

Assoc.Dr. Karolin Yanar

• Inorganic elements essential to the nutrition of humans
• Fourteen minerals are essential to body function
• Play several key roles in overall health and well being
• Help chemical reactions take place in cells
• Help muscles contract
• Keep the heart beating
• Minerals in nutrition fall into 2
categories.
• Macro/major minerals
• Trace minerals
• Major minerals are found in greater
abundance and are needed by adults
more than 100 mg per day.
• Trace elements are required about 1-
100 mg per day.
• Calcium, sodium, potassium, chloride, phosphorus,
magnesium, and sulfur-major
• Iron, zinc, copper, selenium, chromium, iodide,
manganese, molybdenum, and fluoride
Mineral Balance
• GI tract
• Regulates absorption from food based on the body’s need
• Minerals in gastric juices and that slough-off intestinal cells are either
excreted in the feces or reabsorbed through the large intestine
• Kidneys
• Excretes excess and reabsorbs the minerals when the body needs them
• Minerals work together to perform important functions in the body
• Fluid and electrolyte balance
• Blood formation
• Building healthy bones
• Maintaining a healthy immune system
• Mineral Participate as Cofactors
• Minerals play a key role in fluid balance in the cells
• Extracellular minerals – sodium and chloride
• Intracellular mineral – potassium with the help of calcium, magnesium, and sulfur
• Mineral Participate as Cofactors
• Minerals serve as cofactors inAntioxidant systems
• Energy production
• Muscle contraction
• Nerve transmission
• Minerals make up the crystalline structure (hydroxyapatite) that gives strength
to bones and teeth
• Major minerals
• Calcium, phosphorus, and magnesium
• Trace mineral: Flouride
• Adequate concentrations of major and trace
elements are critical for maintaining healthy
state in all the life stage.
• Disturbances in concentration of major and
trace elements may result development of
pathologic conditions, disease or disorders.
• Low levels of these elements are called
deficiency while excessive levels are termed
toxic.
Sources
• Dairy foods as milk, yogurt, cheese;
• vegetables as turnip, broccoli, cauliflower,
cabbage, okra, kale, legume, grains,
watercress;
• seeds as almond, sesame and chia;
• soya beans, tofu, nuts, bread, salmon,
sardines, pilchards, orange juice are rich
sources of calcium
Functions
Structural (bone mineralization) -Cell cycle and
-Muscle contraction apoptosis
-Secretion or synthesis -Protein metabolism
of hormones -Rate of translation
-Release of -Carbohydrate
neurotransmitters metabolism
-Membrane fluidity -Overall metabolic
-Blood coagulation regulator
-Intracellular -Act as Antistressor
signaling -Regulation of gene
transcription
-Enzyme cofactor
Absorpti
on
• Main organs
responsible for
calcium
absorption are
intestines and
colon.
• Calcium is
absorbed from the
small intestine
with two cellular
calcium transport
system
Paracellular absorption Transcellular absorption
 Nonsaturable  Saturable
 Depends on tight junction  It is regulated by vitamin D, calmodulin,
permeability. S100A10/Annexin 2, Nipsnap1 and Rab11a via their
 Tight junction permeability is regulatory role on transient receptor potential
regulated by claudin 2, claudin 12. vanilloid type6 (TRPV6) channel.
 Furthermore, 1,25-dihydroxyvitamin  Calcium channels, intracellular calcium-binding
D3 regulates this pathway via proteins (calbindin D9k) and calcium pumps play role
suppressing the expression of in this pathway.
claudin 3, aquaporin 8, cadherin 17  energy- dependent
and RhoA.  Responsible for 80% calcium absorption if calcium
 Energy independent process. intake is low. If calcium intake is high, this system
 It is the major pathway of calcium is downregulated. (depends on low calcium levels )
absorption if calcium intake is
high.( depends on high calcium
intake)
Transport and distribution

• Neonates contain 25 g of calcium and 70 kg

healthy adult human body contains approximately
1-1,25 kg (25000-31250 mmol) calcium.
• Ninety-nine percent of calcium is found in
skeleton as hydroxyapatite crystals.
• The remaining 0.9 percent is equally
distributed between soft tissues and teeth, and
the remainder is found in the extracellular
fluid.
• Skeleton acts as a reservoir of calcium. In
circulation calcium is present in three forms
as ionized (47%), protein bound (40%) and
complex (13%) form with substances as citrate,
lactate, and phosphate
• Ionized form of calcium is physiologically
active form which constitutes half of the total
plasma calcium concentrations (1.1 -1.3
mmol/L).
• Protein bound form constitutes 40 % of
circulating calcium (0.9-1.0 mmol/L).
• Eighty percent of this calcium binds to
albumin and remaining 20 % binds with globulin.
• Calcium is bound to negatively charged regions of
albumin, especially free carboxyl groups of the
side chains of glutamic acid and aspartic acid.
• Changes in pH and serum albumin concentrations
affect total calcium concentrations independently
of the ionized calcium concentrations.
• In acidic conditions, increased H+ concentration
neutralizes negative charges of carboxyl groups,
competes for calcium binding sites and inhibits
binding of calcium.
• Thus, adjusted calcium concentration should be
interpreted.
• Formula of adjusted calcium is given as; if
albumin concentration is lower than 40 g/dL
adjusted calcium (mmol/L)
=[Calcium]+0.02x(40-albumin),
• if albumin concentration is upper than 45;
adjusted calcium(mmol/L) =[Calcium]-
0.02x(albumin-45)
• *The plasma concentration of calcium is 2.20-
2.70 mmol/L for children younger than 12 and
2.15-2.50 mmol/L for adults.
• Decrease in albumin and globulin concentration
(approximately 1 g/dL) results in lessening of
about 0.8 mg/dL and 0.16 mg/dL, respectively in
total serum calcium concentration
• Ionized form of serum calcium reference range
is maintained between 1.20-1.38 mmol/L for
infants and 1.16-1.32 mmol/L for adult
• The steady-state extracellular calcium depends
on the balance of bone remodeling
• Plasma calcium homeostasis is regulated by
calciotropic hormones such as PTH, vitamin D
(calcitriol), calcitonin, thyroid hormone,
estrogen and growth hormone.
• Major target organs are bone, kidney and
intestine.
• The intestine regulates absorption, the kidney
modulates reabsorption and excretion, and bone
regulates mobilization of calcium via bone
formation and resorption
• Hypercalcemia, defined as the concentration of
calcium in blood above the reference interval
(>2.6 mmol/L).
Organ system Symptoms and signs
Neurologic and Lethargy, tiredness, personality changes,
neuromuscular muscle weakness, decreased alertness,
depression, confusion, forgetfulness, coma
Gastrointestinal system Anorexia, constipation, nausea, vomiting,
pancreatitis, abdominal pain, peptic ulceration
Kidney Decreased concentration of urine, dehydration,
kidney stones, polyuria, polydipsia, renal
impairment, nephrogenic diabetes insipidus
Skeletal Increased bone resorption and demineralization,
fracture risk, ache, pain
Causes of hypercalcemia
• Primary and secondary hyperparathyroidism
• Malignancy-associated hypercalcemia
• Vitamin D- mediated hypercalcemia
• Immobilization
• Addison’s disease
• Lithium usage
 HYPOCALCEMIA Hypocalcemia is characterized by
decreased levels of circulating calcium (<2.12
mmol/L). It is one of the electrolytic disorders
Organ systems Symptoms and signs
Neuromuscular Tetany, sign, coma, seizure, neuropsychiatric
symptoms such as anxiety, depression and bipolar
disorders
Central nervous system Irritability, seizure, behavioral changes,
intellectual function impairment, convulsion and
basal ganglia calcification

Cardiovascular QTc prolongation on ECG, hypotension, cardiomyopathy

and heart failure

Respiratory bronchospasm
Ophthalmic system (eye) Cataracts, cornea calcification and papilledema

Dermatological Alopecia and Xeroderma

Dental Dental enamel hypoplasia and changes in tooth
morphology
Causes of hypocalcemia
• Pseudohyperparathyroidism
• Wilson disease
• Radiation therapy
• Postsurgical hypoparathyroidism
• Rickets
• Osteomalacia
• Osteoporosis
• Diuretics
• Anticonvulsants
• Hypoalbuminemia
• Acute pancreatitis
• Hyperphosphatemia
PHOSPHORUS

• Meat, poultry, fish, egg, milk products, nuts,

legumes, cereals, grains, peanut, kidney,
whole-wheat bread are phosphorus rich
nutrients.
• Coffee and tea also contain small amount off
phosphorus.
• Organic and inorganic forms of phosphorus are
found in nutrients.
• Inorganic forms are bound to lipids, proteins
and sugar
Functions of phosphorus
Role in bone mineralization
• Ninety-five percent of the mineral phase
consists of hydroxyapatite crystals which
contains phosphorus
• Major part of total body phosphorus (85%) is
found in bone.
• It plays role in development and
mineralization of bone with calcium
Role in buffering system
• Phosphorus acts as a component of intracellular
buffering system via its monovalent and
divalent form.
• In this system, phosphorus is crucial for H+
excretion in kidneys.
• In acidic conditions, phosphorus binds to
hydrogen ions.
• This binding releases sodium, removes free H+
ions and increases pH value.
• While alkaline condition phosphorus acts as an
acidic component.
• In this condition, free H ions increase which
lead to decrease in pH value
Absorption and transport

• In nutrients phosphate is found in complex

form.
• Thus, before absorption phosphorus is digested
by some enzymes such as alkaline phosphatase
and phospholipase.
• Daily intake is 1000mg.
• Phosphorus is absorbed mainly in duodenum and
jejunum.
• The absorbed amount is approximately 50-70%.
• Phytic acid inhibits phosphorus absorption
• Like other minerals, phosphorus is absorbed by
saturable, transporter mediated active
transport and diffusion.
• In case of high inorganic phosphate levels,
phosphorus is absorbed passively by diffusion
• Acidic pH slightly facilitates passive
diffusion in the proximal duodenum.
• Sodium-phosphate cotransporter type IIb plays
role in active transport .
• This transporter carries two sodium for each
phosphate monovalent or divalent form in brush
border.
• increase absorption • Decrease absorption
• vitamin D • Magnesium
• volume depletion • aluminum
• chronic hypocalcemia • calcium
• metabolic alkalosis • parathyroid hormone
• growth hormone • acidosis
• estrogen • hyperphosphatemia
• insulin • chronic hypercalcemia
• thyroid hormone
Distribution

• Most of the phosphorus (80-85%) is found in bone

tissue as hydroxyapatite crystals, 20% in soft
tissues and approximately 1% in circulation.
• In circulation,
• 55% of phosphorus is found in the free form,
• 10% is bound to proteins
• and 35% is formed complexes with calcium,
magnesium, and sodium.
• serum reference ranges are 4.5-9.0 mg/dL for
neonates, 3.3-5.4 mg/dL for children until 15
years old, 2.4-4.4 mg/dL for adults
• Men phosphate levels are slightly higher than
women
• Inorganic phosphorus is excreted by urine (67-
90%) and feces (10-33%).
• Decrease Phosphorus • Increase phosphorus
due to due to
• PTH • Growth hormone
• Calcitonin • Calcitriol
• FGF23
Hyperphosphatemia is defined as elevated
level of serum phosphate concentration
(>4.5gram /dL).
• Causes • Symptom and Signs
- Excessive intake • Hypotension
-release of cellular • seizure
phosphate • tetani
-Hypoparathyroidism, • secondary
- hyperparathyroidism
Pseudohypoparathyroidism, • calcification of soft
-Acromegaly tissues
-Hypocalcemia
-Cell lysis
- Respiratory acidosis
-Decreased glomerular
filtration rates
When the concentrations of serum phosphate
levels below the reference interval (<2.5
mg/dL) in adults and below 4 mg/dL in
children, the condition is defined as
hypophosphatemia.
• CAUSES
• Redistribution of phosphate, renal losses of
phosphate, decreased intake
• Decreased intestinal absorption of phosphate,
• genetic disorders
• Dent disease,
-Vitamin D resistant ricket
• some drugs (Diuretics, Niacin,Anticonvulsant
Paracetamol Salicylate )
MAGNESIUM

• Nuts, legumes, oats, barley, beans, black-eyed

peas, peanut butter, sunflower seeds, whole-
grain bread, green leafy vegetables, halibut,
milk, yogurt, chocolate, black-strap molasses,
corn, rice, coffee, cocoa and tape water are
magnesium- rich nutrients
Functions
-Enzyme cofactor
-Calcium metabolism affects the binding affinity of calcium to
calmodulin, S100, troponin and parvalbumin
• Neuroprotective effects and glutamate signaling
• Proinflammatory effects
• Bone mineralization
• Effects on heart and lung/ion channels
• Nutrient metabolism Magnesium affects metabolic activation and
utilization of vitamin D, thiamine and glutathione
• Therapeutic effects (preeclampsia, migraine, asthma, super-
refractory status epilepticus, muscle cramps, stroke,
osteoporosis, subarachnoid hemorrhage, myocardial infarctions,
Role in bone mineralization
• Magnesium is essential in bone mineralization.
• It helps in the activation and inactivation of vitamin D.
• Vitamin D is vitally important in both calcium and phosphate
homeostasis and in bone.
• Furthermore, enzymes which are responsible for synthesis of
vitamin D requires magnesium in liver and kidneys.
• Magnesium is a cofactor for the vitamin D–binding protein, and
requires for parathyroid function which is indispensable for bone
health .
• It increases bone density and decreases the risk of osteoporosis.
• Its supplementation effects bone turnover biomarkers and leads to
an increase in serum osteocalcin levels and a decrease in urine
Absorption and transport

• Daily intake of magnesium is approximately 370

mg
• 100 mg (30-50%) magnesium is absorbed in the
small intestine mainly in the distal jejunum
and ileum through a non-saturable passive
pathway and in the cecum and colon of the large
intestine via saturable active transport system
• Absorption rate depends on the ingested amount.
80% is absorbed under low magnesium intake,
while 20% is absorbed when the intake is high.
• Vitamin D can stimulate absorption of
magnesium
• Decrease absorption due to • Increase absorption due to
• hypermagnesemia, • Parathyroid hormone,
• metabolic acidosis, • glucagon,
• hypercalcemia, • calcitonin,
• phosphate and potassium depletion, • vasopressin,
diuretics,
• aldosterone,
• antibiotics, antifungals,
antivirals, • insulin,
• chemotherapy agents, • epidermal growth factor, metabolic
alkalosis,
• immunosuppressants,
• fructose,
• epidermal growth factor
antagonists, phytic acid, • oligosaccharides,
• fibers, • some proteins
• excessive unabsorbed fatty acids
• mutations in various magnesium
absorption related proteins
Distribution
• Adults (70kg) contain 22-26 g of magnesium.
• Approximately, 50-60% of total magnesium amount
is located in bone tissue.
• 20% of total magnesium is present in muscle
tissue, and the remaining part exists in
intracellular compartment of blood cells and
other tissues.
• Only 1% is found in extracellular fluid .
• In plasma 30% of magnesium is bound to albumin,
55% is found free or ionized state that is
physiologically in the active form, and about
5% is bound to PO4- and citrate, bicarbonate or
sulphate
• The kidney, magnesium intake and bones are
responsible for maintaining plasma magnesium
levels within the reference range.
• Serum total magnesium concentrations are
approximately between 0.63-1.0 mmol/L
excretion
• feces and urine
Toxicity
• Toxicity of magnesium rarely occurs. High
levels of magnesium are defined as
hypermagnesemia.
Affected system Signs and symptoms
Cardiovascular Hypotension, bradycardia,
heart block
Neuromuscular Slowness of reflexes,
dysarthria, respiratory
depressions, paralysis
Dermatologic Flushing, warm skin
Electrolyte metabolism Hypocalcemia
Gastrointestinal system Nausea, vomiting
Hemostasis Reduced thrombin production
and platelet adhesion
Causes of hypermagnesemia
• Excessive oral intake
• Excessive rectal intake
• Excessive parenteral intake
• Decreased excretion
• Dehydration,
• bone carcinoma,
• bone metastases
• rhabdomyolysis,
• lithium ingestion
Deficiency
• Hypomagnesemia. It is mostly seen in
hospitalized patients. Patients may be
asymptomatic until serum magnesium levels fall
below 0.5 mmol/L.
Affected Symptoms and signs
System/condition
Psychiatric Anxiety, lethargy, weakness, agitation, depression,
hyperactivity, loss of appetite, low stress intolerance,
sleep disorders, headache, irritability, psychosis,
confusion
Muscle Spasm, cramps, back aches, neck pain, tetany
Gastrointestinal Nausea
system
Nerve Nervousness, increased sensitivity of NMDA receptors to
excitatory neurotransmitters, nystagmus, seizures,
tremor, ataxia, vertigo
Cardiovascular system Arrhythmia, hypertension, coronary spasm, reduced
function of myocardial pump
Causes Due to
Reduced intake Starvation
Chronic alcoholism
Malabsorption syndrome
Pancreatitis
Vomiting
Diarrhea
Decreased absorption Congenital
Tubular disorder
Osmotic diuresis
Hypercalcemia
Alcohol
Increased Excretion Hyperparathyroidism
Hyperaldosteronism
Hyperthyroidism
Diabetic ketoacidosis
Diuretics (furosemide)
Antibiotics
Sodium (Natrium)

• The most important source of

sodium is table salt. NaCl
• Bread and cereals, dairy products
,spinach , carrot
• Na is the major cation of
extracellular fluid.
• Its concentration in serum is
between 134-144 mEq/L
• Its metabolism closely associated
with Cl- and HCO3 -in the
regulation of acid base balance
• The average Na+content of the
human body is 60 mEq/kg,
which consists of 50% extracellular
fluid, 40% bone, and 10%
intracellular Na
Functions
• Regulation of osmotic pressure
• Water distribution
• Acid-Base balance
• Na+- K+ ATPase
• Stimulation of muscle
• Transport of glucose and amino acid
Role in osmolarity
• Natrium is one of the elements , which greatly contributes to
plasma osmolarity.
• Osmolality is the term used to express osmotic active components.
• It is a measure of the number of dissolved particles in solution.
• The normal range for plasma osmolality varies between narrow range
285-319 mOsm/kg H20
• Electrolytes such as Na+ and its counterbalancing ions Cl- , HCO3-
contribute to over90 %of the serum osmolality because they are
present in high concentrations in extracellular fluid.
• And K+, glucose, urea, proteins constitute the remaining part.
• For comparison; 1g of protein contributes 5mOsm as 1 g of salt
Water distribution
• Na+ maintains osmotic pressure of body fluids
and protect against excessive fluid loss.
• Aldosterone is responsible for retention of Na+
and water and also excretion of K+ and H+
• In aldosterone deficiency , the occurrence of
the simultaneous loss of water and Na+ can
result in decrease of serum Na+, acute
dehydration and death.
• ANP increases excretion of sodium and water
by urine
• Decrease sodium concentration in ECF
Decrease Osmolarity of ECF water
import from ECF to ICF swelling of
cells

• Increase sodium concentration in ECF

Increase Osmolarity of ECF water
export from ICF to ECF dehydration of
cells
• Vasopressin(ADH) reabsorbs water from the
renal tubules of the kidney.
Absorption and excretion
• Na+ absorbed by intestine rapidly and pass in
the plasma.
• Na+ excreted by urine, feces and sweat
• Excreted urine amount is 40-60 mEq/L
Distribution
• Healthy adult Naconcentration= 136-145 mEq/L
(reference range)
• Hypernatremia defined as higher sodium
concentration than reference range in blood
• Hyponatremia defined as lower sodium
concentration than reference range in blood
 Causes of Hyponatremia ( most
common electrolyte disorder)
-inadequate Na+ intake,
- excessive fluid loss from vomiting or
diarrhea,
-diuretic abuse,
-Inadequate aldosterone
--hospitalized patients
İncrease sweating
Severe burn
Cystic fibrosis
Symptoms and signs
• Loss of appetite
• Nausea
• Vomiting
• Headache
• Disorientation
• Decrease in deep tendon reflexes
• Lethargy
• Psychosis
• if it develops rapidly coma, constant brain damage, respiratory
standstill and death are seen
• 139 mEq/L 119 mEq/L within 2 hours death
• 139 mEq/L 122 mEq/L within 4 days it is asymptomatic
• 139 mEq/L 99 mEq/L within 16 days it is lethargic
• Underlying cause
• Development time
• Presence of symptom determine the therapy
• The presence of overhydration water intake must
restrict.
• Light and mild hyponatremia- 0.9% NaCl
treatment is adequate
• Severe hyponatremia 3-5 % NaCl solution must
use
• If Acute symptomatic hyponatremia is not
treated rapidly constant neurological damage
is seen.
• If hypotonic solutions are given, abandon to
give them immediately
• Serum sodium levels adjusted to rise 1-2 mEq/L
per house until the symptoms disappear
• During the therapy Na supplement must given
frequent intervals (once every 2-4 hours).
Causes ofHypernatremia
• loss of hypo-osmotic fluid ;
-in burns,
- fevers,
- high environmental temperature,
-exercise,
-kidney disease,
-diabetes insipidus
• Increased hypertonic Na+ intake
-administration of hypertonic NaCl solutions,
- ingestion of NaHCO3
Symptoms and signs
• Fever
• Excessive thirst
• Lethargy
• Increased reflexes
• Uneasiness
• Convulsions
• Coma
Therapy
• Put away the etiological reasons
• Use hypotonic solutions ( 5% dextrose, 0.45 %
NaCl)
• In acute hypernatremia therapy serum Na+
decrease rate adjusted to 1 mEq/L per hour.
• hypernatremia developed within days or unknown
time interval, to avoid brain edema the
decrease rate of serum Na+ is adjusted to
0.5mEq/hour
• The target of therapy: decrease the level
below 145mEq/L
Potassium
• Prune juice, avocado, apricot, banana,
cantaloupe, honeydew melon, mango, papaya,
yams, leafy green vegetables, winter squash,
legume, nut, seeds, peanut butter, potatoes,
asparagus, mushroom, okra, peaches,
grapefruits, kiwi, nectarine, milk, yogurt and
salmon are potassium-rich sources
Biological functions

• regulation of neuromuscular excitability

• electrical activity of the heart
• regulation of blood pressure (vasoactive electrolyte)
• synthesis -release of aldosterone and insulin
• acid-base homeostasis
• electrolyte-water balance
• activation of some enzymes
• healthy bones
• structure of RNA
• glycogenolysis
• Renal calcitriol production (-)
Acid- base balance
• Decreased hydrogen ion concentrations leads to
decreased potassium secretion and enhanced renal
reabsorption.
• hyperkalemia is relevant to acidosis while
hypokalemia with alkalosis
• Potassium balance affects the rate of renal
ammonia production and urinary ammonia excretion.
• In hypokalemia renal production of ammonia is
increased .
• Ammonia is important for acid -base balance
• Ammonia metabolism is the greater component of
bicarbonate production which has major role in
acid- base homeostasis
Water electrolyte balance
• The sodium-potassium pump is the chief
mechanism for maintaining water balance.
• Potassium is the major electrolyte in
intracellular fluid, and it regulates the
amount of water inside the cells.
• While sodium is the main electrolyte in
extracellular fluid, it determines the amount
of water outside the cells.
• In hyperosmolarity K+ is carried along with
water
Absorption and transport

• Daily average potassium intake is approximately

1 mmol/kg
• 85-92 % of ingested potassium is mainly
absorbed in the small intestine and to a lesser
extend in colon, proportional to water and
sodium
• After feeding, increased insulin levels enhance
Na+-K+ ATPase activity therefore stimulates
potassium uptake in hepatocyte, brain, adipose
tissue and muscle cells.
•.
• Potassium uptake also induces aldosterone
secretion which increases potassium excretion
via kidney and colon.
• On the other hand, triiodothyronine enhances
potassium
• 755 mmol of potassium which is freely filtered
by glomerulus. Proximal tubules and thick
ascending limb of the loop of Henle is mainly
responsible for reabsorption of potassium
• Proximal tubule reabsorbs 490 mmol of filtered
potassium.
Distribution

-Age,
-gender,
-muscle mass inhibition or stimulation of Na+/K+
ATPase
are the major variables that affect total body
potassium content
The intracellular amount of potassium (110-150
mmol/L) is about 20-30 times greater than the
extracellular amount (3.5-5 mmol/L).
• Physiologic factors such as
-insulin,
-triiodothyronine,
-aldosterone,
-β-adrenergic stimulation,
pathologic factors
alkalosis
hyperosmolality can increase intracellular potassium
levels via increased uptake of potassium by various
cells and decrease serum potassium levels
• Physiological factors such as α-adrenergic
stimulation and pathologic factors such as
hypoosmolality, uncontrolled Diabetes mellitus,
acidosis, strenuous exercise, and cell lysis
decrease intracellular potassium levels and
increase serum potassium levels
Life stage Potassium content in serum
Newborn 3.7-5.9 mmol/L
Infant 4.1-5.3 mmol/L
Children (3-5 years 3.9-4.6 mmol/L
old)
>6 years old 3.8-4.9 mmol/L
Potassium content in plasma
Adult Female 3.5-4.5 mmol/L
Male 3.4- 4.4 mmol/L
Potassium content in urine
6-10 years old Female 8-37 mmol/L (24 h)
Male 17-54 mmol /L (24 h)
10-14 years old Female 18-58 mmol /L (24 h)
Male 22-57 mmol /L (24 h)
Adult 25-125 mmol/day
• Hyperkalemia defined as plasma potassium
concentration of higher than the upper limit of
reference range (5.1 mmol/L).
• Hyperkalemia is a result of redistribution,
increased intake, and retention.
• Signs and symptoms are
-weakness
-nausea,
-vomiting,
-diarrhea,
- paresthesia,
-Areflexia
- tingling,
- bradycardia
- cardiac arrest
Causes Examples
Pseudohyperkalemia Hemolysis, Thrombocytosis, Leukocytosis,
Torniquet use
Metabolic acidosis
Dehydration
Massive tissue hypoxia
Insulin deficiency
Redistribution Rhabdomyolysis
Epilepticus
Severe burns
Hemolytic disorders
Insufficient sodium exchange, Decreased
Na+/K+ exchange
Addison’s disease
ACE inhibitors
Renal transplant
Hemolysis
Potassium retention Penicillin
Deficiency

• Hypokalemia defined as plasma potassium

concentration of less than the lower limit of
reference range (<3.5 mEq/L).
• Abnormal gastrointestinal and renal loss,
inadequate intake, redistribution of potassium
between intracellular and extracellular fluid
are the major causes of hypokalemia
Causes Examples
Prolonged vomiting, Diarrhea
Intestinal tumors
Excessive laxative usage
Abnormal Malabsorption
gastrointestinal loss Cancer therapy

Diuretics
Nephritis
Primary and secondary
hyperaldosteronism
Abnormal renal loss Cushing’s syndrome
Steroid therapy
Saline infusion
Renal tubular dysfunction
Malignant hypertension
Chronic metabolic acidosis
Anorexia nervosa
Inadequate intake Alcoholism
• Signs and symptoms of hypokalemia are observed
when plasma K+ concentrations are low than
3mmol/L.
• The patients are usually asymptomatic until
3.0-3.4 mmol/L
• Direct iv potassium therapy leads to death
Chloride
• It is a major extracellular anion.
• Plasma concentration= 98-110 mEq/L
• It consist of 2/3 total anions. (154mEq/L)
Functions
• Contribute to osmotic pressure
• Regulation of acid base balance
• Regulation of water balance
• Stimulates amylase activity
• Participate HCl production in gastric juice.
• Increased HCO3- in erythrocyte diffuses in
plasma and Cl- import in erythrocyte due to
maintenance of electrostatic charge balance.
This process called as Chloride shift
• Higher serum chloride levels (above the
reference range) called as hyperchloremia
• Lower serum chloride levels (below the
reference range) called as hypochloremia.
Hyperchloremia
• In dehydration, hyperchloremia may occur after
12-24 hours in infants and 36-48 hours in
adults
• Hyperchloremia may occur as a result of
excessive parenteral salt administration
Hypochloremia
• It occurs with hyponatremia
• Prolonged vomiting and diarrhea lead to gastric
juice ( HCI) and İntestinal juice ( NaCl) loss
which result in hypochloremic alkalosis.
• Edema, burn and excessive HCO3- intake also lead
to hypochloremia.
IRON
• Fe is found in abundant amounts in liver, meat,
beans, nuts, apricot, brown rice, fortified
cereals, soybean, and vegetables.
• Gender affects recommended intake of iron.
Women require more iron than man due to
menstruation, pregnancy and lactation period
which are physiological conditions.
• Fe is involved in the structures of clinically
important proteins including enzymes.
Iron
• Iron is the most abundant trace element in
human body.
• It is physiologically essential metal, because
it participate in heme biosynthesis as well as
in the structures of many enzymes with vital
importance.
• However, excessive free Fe amount favors ROS
formation reactions and lead to macromolecular
damage.
• Fe cycles between +2 and +3 states called
ferrous and ferric form, respectively
• Even very low concentrations of free iron are
toxic to the organism. For this reason, there
are specific proteins that are responsible for
the transport and storage of iron in the body.
Iron containing protein Functions
Ferritin Fe storage
Hemosiderin Fe storage
Hepcidin Main regulator of systemic iron
balance
Transferrin Fe transport
Hemoglobin Oxygen binding and transport into
blood
Myoglobin Oxygen binding and transport into
muscle
Cytochromes Electron transport systems
Some of the enzymes requiring iron
NADH dehydrogenase
Peroxidase
Tryptophan pyrolase
Nitric Oxide synthase
Succinate dehydrogenase
Cis- aconitase
Guanylate cyclase
Prostoglandin synthase
Catalase
Distribution of iron
• 65% (2.5 g) are found in hemoglobin
• 25% are found in ferritin and hemosiderin
• 3-4% are found in myoglobin
• 0.1% are found in cytochromes
• 0.1% are found in iron- enzyme complexes
• 2% interstitial fluid
• 0.1% are bind with transferrin
 Absorption of Iron
a-Non-heme form absorption:

• Inorganic iron, which is

reduced to its ferrous
form, is taken up into
enterocytes by active
transport through specific
receptors called divan
metal transporter 1 (DMT1)
on the brushy edges of
mucosal cells in the
intestinal lumen.
• DMT1 has been shown to be
involved in the absorption
of iron as well as
b-Absorption in the form of
heme:
• Up to 10% of dietary iron is
in the form of heme.
• Since iron in this form is
less affected by dietary
factors, its absorption rate
is higher.
• Heme iron is in ferrous
(FeII) form and its
absorption increases 4-6
times when iron deficiency
occurs.
• Heme enters the duedenal
enterocyte via a specialized
transporter heme transporter
protein 1.
• In the erythrocyte, iron is
Factors affect iron absorption
• Increase absorption • Decrease absorption
-Ascorbate -Oxalate
-Lactate -Phytate
-Pyruvate -Phosphate
-Succinate - Alcohol
-Fructose
-Cysteine
-Sorbitol
Transport of iron into cells
• Transferrin: Carries 2Fe 3+, is made in the
liver, plasma half-life is 8-10 days, normally
1/3 is bound by iron
• Transferrin receptor: Mostly found in bone
marrow, liver and placenta One Tf molecule
participates in the Fe transport cycle 100 or
more times
• Regulated by iron regulatory protein (IRP1 &
IRP2)
Factors affect iron absorption
Iron transport
• Fe3+ is the form of iron that binds
to transferrin, so the Fe2+
transported through ferroportin
must be oxidized to Fe3+.
• There are 2 copper-containing
proteins that catalyze this oxidation
of Fe2+: hephaestin and
ceruloplasmin. Hephaestin is found
in the membrane of enterocytes,
while ceruloplasmin is the major
copper transport protein in blood.
• Hephaestin is the primary protein
that performs this function in a
coupled manner (need to occur
together) with transport through
ferroportin.
Iron Transport
• This means that the Fe2+ needs
to be oxidized to be transported
through ferroportin.
• Evidence suggests that
ceruloplasmin is involved in
oxidizing Fe2+ when iron status
is low.
• Once oxidized, Fe3+ binds to
transferrin and is transported to
a tissue cell that contains a
transferrin receptor.
• Transferrin binds to the
transferrin receptor and is
endocytosed
Iron storage
• Once inside cells, the iron can
be used for cellular purposes
(cofactor for enzyme etc.) or it
can be stored in the iron
storage proteins ferritin or
hemosiderin. Ferritin is the
primary iron storage protein,
but at higher concentrations,
iron is also stored in
hemosiderin
ferritin
• Iron is found in ferritin structure in stores.
• Ferritin formed by binding of Fe3+ to
apoferritin
• Ferritin consists of 24 subunit.
Hemosiderin
• Another type of stored iron is the precipitated
and partially denatured form of ferritin called
as hemosiderin
• In conditions such as chronic hemolytic anemia
and excessive blood transfusion, a substance
called hemosiderin accumulates in the denatured
ferritin structure in the kupffer cells of the
liver, spleen and bone marrow.
• Hemosiderin is usually formed in cases of iron
overload and is detected microscopically.
• Reference range of iron is 90-120 g/dL
• Plasma iron concentration does not reflect the
amount of body iron. Very little of the iron is
in the plasma.
• Higher than normal serum iron level is called
as hypersideremia Lower than normal serum iron
level is called as hyposideremia
Iron deficiency
• Inadequate iron intake
• Malabsorption
• Chronic blood loss
• Frequent pregnancy lead to Hypochromic
microcytic anemia

• number of RBC ,RBC volume, Hemoglobin and

Ferritin levels decrease
Iron overload
• Iron accumulates in tissues
• HEMOSIDEROSIS: Iron excess without tissue
damage. HEMOCHROMATOSIS: Iron leads to the
destruction of the organs in the form of cell
damage and fibrosis.
• In order of frequency; The liver, pancreas,
heart muscle, pituitary, joint and skin are the
organs affected.
• In diagnosis;
• Whole blood count (Hemogram)
• Plasma ferritin,
• Iron binding capacity (TIBC),
• Plasma iron and physical findings of Anemia are
important.
• In plasma, iron is transported with
transferrin.
• Transferrin normally has an iron binding
capacity of 300 µg/dL (Total iron binding
capacity-, TIBC).
• Total iron-binding capacity can be used as an
indirect measure of transferrin level.
• Since 1 mg of transferrin binds 1.25 μg of iron
(TIBC=Transferrin x 1.25) or (Transferrin=TIBC
/ 1.25).
 HEMOGLOBIN
♂ ≤ 13g/dl A N E M IA
♀ ≤ 12 g/dl

FERRİTİN HIGH
LOW FERRİTİN

NORMAL

Demir Talasemi
Eksikliği Minor CHroniC
Iron deficiency
Anemisianemia Disease
Anemia
Iron dependent anemia
• weakness,
• dyspnea
• Cracks around the mouth and nails
• Deformity in nails: like spoon shaped…
• irritated tongue
Zinc (Zn)

• oysters, meat, liver, wheat

germ, pumpkin seeds,
sunflower seeds, all grains,
almonds and milk are zinc
rich nutrients
Functions of zinc related with
involvement of enzymes structure
• Redox homeostasis (superoxide dismutase)
• Regulation of pH (carbonic anhydrase)
• Nonspecific aldehyde synthesis (alcohol
dehydrogenase)
• Visual cycle and night vision (retinol
dehydrogenase)
• Folate digestion (polyglutamate hydrolase)
• Protein digestion(carboxypeptidase A and B )
• Phospholipid metabolism (phospholipase C)
• Hem synthesis (aminolevulunic acid dehydratase)
• Nucleic acid and nucleotide metabolism (DNA
polymerase, RNA polymerase )
• Taste (gustin)
Functions of zinc related with
matrix metalloproteinases
• MMPs initiate bone growth and remodeling
• innate immunity,
• wound repair,
• angiogenesis,
• tissue repair,
• cell migration
Other functions
• Regulation of serotonin and norepinephrine content
• Cellular adhesion
• Sperm motility and vitality
• The participation of zinc in hormone production

• zinc finger Tetrahedral zinc atoms bind with histidine and cysteine residues of protein
and form folded structures known as zing finger
• Zinc finger play roles in transcriptional regulation, ubiquitin-mediated protein
degradation, signal transduction, actin targeting, DNA repair, cell
migration, tumorigenesis, cancer progression, metastasis, regulation of hormone such as
free T4, thymulin, estrogen, testosterone, insulin, insulin like growth factor-1
• Daily zinc requirement is about 12-15 mg, Max;
50mg
• 15-30% of ingested zinc absorbed in duedenum
and upper jejenum
• Intestinal Zn2+ is absorbed by carrier mediated
transport and diffusion
• It is carried with Albumin (%60-70)and α2-
macroglobulin(30-40%) in plasma
• It is bind to metallothionein and stored that form in
tissues
• It is excreted by sweat, feces and urine
Factors enhance Zinc absorption Factors reduce Zinc absorption

High dietary protein Iron intake

Calcium intake Presence of copper

Unsaturated fatty acids Phytate /vegetarian diet

Organic acids Ageing

Prostaglandins Proton pump inhibitors

Pancreatic secretion Taking zinc in fasting

Acidic pH Alkaline pH

Glutathione and other Oxalate

tripeptides
Amino acids Polyphenol

Low dietary protein

Fibers
• In circulation, absorbed zinc is distributed
between erythrocytes, plasma, and leukocytes
with the percentage of 80, 17, 3, respectively
.
• Erythrocytes have much more concentration (x10
fold) of zinc than plasma due to high amount of
carbonic anhydrase enzyme .
• Zinc transporters have important role in zinc
homeostasis.
• Two types of solute -linked carrier are present
in human cells as membranous transporter (ZnT)
with 10 member and zinc-regulated and iron-
• ZnTs decrease intracellular zinc bioavailability
while Zips increase intracellular zinc
bioavailability .
• Not only zinc transporters but also
metallothioneins which are saturable, and cysteine
rich proteins play role in zinc homeostasis,
immunity, protection against the toxicity of
metals.
• Binding of zinc to the metal regulatory
transcription factor 1 activates metallothioneins.
• Activated metallothioneins reversibly bind to
zinc and maintain intracellular zinc amount
• DMT1, may also have a minor role in transport of
zinc from intestinal cells to blood
• Suggested reference intervals of zinc are 10.7-
18.3 µmol/L (70-120 μg/dL) for serum.
• Serum Zn2+ concentrations are 5-15% higher than
plasma due to release zinc from erythrocytes
and platelets during clotting process.
• Concentration of Zn2+ shows postprandial
fluctuation and demonstrate circadian rhythm.
• Concentration is decreased with feeding and
increased in the morning
Zn deficiency
• Physiologic
-Pregnancy
-Lactation
-Aging
• Pathologic
• liver disease ( hepatic cirrhosis)
• Malabsorption syndrome
• Prolonged parenteral feeding
• Alcoholism
• Burns
• Kidney disease
Clinical
symptoms of
zinc
deficiency
• Growth-development
retardation
• delay in wound
healing
• Increased
susceptibility to
infections
• Disorder of the
sense of smell and
taste
• hypogonadism
• Alopecia (hair
loss)
• Hepatosplenomegaly
• depression
ACRODERMATIT
IS
ENTEROPATICA
• A rare cause of
impaired zinc
absorption from the
intestine.
• A severe zinc
deficiency in which
whole body zinc stores
are depleted
• is an autosomal
recessive inborn
error that occurs
mutation of the zip
encoding gene (ZIP4)
on chromosome 8q24
toxicity
• Zinc is relatively nontoxic.
• Gastrointestinal system tract symptoms, decrease in heme
synthesis and hyperglycemia have been observed in excessive
(1gram) or repetitive doses exposure of zinc for several
months.
• Heme synthesis is decreased due to effects of excessive zinc
concentration on copper metabolism.
• Excessive zinc exposure produces some symptoms as abdominal
and epigastric pain, bloody diarrhea, nausea and vomiting,
metallic taste, decreased immune function, alteration in
• In chronic conditions it may lead to copper
deficiency, numbness, weakness, ataxia, and
spastic gait, sideroblastic anemia, neutropenia
and hyperglycemia
• Excessive levels of intracellular zinc may play
a role in cellular toxicity. Ischemia-
reperfusion injury and Alzheimer’s disease are
related to excessive zinc levels.
• Increased intracellular levels of zinc results
in loss of mitochondrial membrane potential,
generation of free radicals, cell death and
inhibition of α -ketoglutarate dehydrogenase
Copper
• Copper- rich dietary sources are liver, kidney,
shellfish, nuts, raisins, egg yolk, whole grain
cereals, cacao containing products, and legumes
• RDA 900 µg/day for adult
 Copper is core part of copper-
containing enzymes which terms as
cuproenzymes
Cuproenzyme Function
Lysyl oxidase Collagen and elastin cross-link
Indole 2,3-dioxygenase Tryptophan metabolism
Dopamine monooxygenase Norepinephrine synthesis

Superoxide dismutase 1 izoenzyme Antioxidant

Ceruloplasmin Ferroxidase activity, chaperone binding, copper and
iron transports
Hephestin Ferroxidase activity
Tyrosinase Melanin synthesis
Amine oxidase Oxidation of monoamine and diamines, detoxication of
serotonin, spermidine, putresin,1 phenyl-ethylamine
Cytochrome c oxidase ATP production
• Copper is absorbed mainly in the small
intestine and slightly in stomach.
• The intestinal uptake is dependent on pH.
• Approximately, 40%-70% of ingested copper is
absorbed
• If copper content is low(lower than 1 mg/day),
the absorption is around 50% whereas, if it is
high around(higher than 5mg/day) 20% is
•Copper can participate in oxido-reduction reactions with valences
of +1 and +2
•Steap proteins and cytochrome b reductase 1 are responsible for
the reduction of cupric form to cuprous form
• copper absorbed by mainly duodenum and small amount is absorbed
by stomach, then copper are transported to the liver by copper-
histidine and copper-albumin complexes.
Copper is transported into the cell with ceruloplasmin, albumin
and transcuprein
•0.5- 2.4 mg/day copper is excreted via bile into feces (%85).
•<60 µg/day copper is excreted via urine in healthy individuals and
small amount of copper is excreted via sweat
• It binds to metallothionein protein especially
in the cytosol of liver, kidney and intestinal
cells
• Binding to metallothioneine keeps the metal in
a non-toxic form; Cu-mediated free radical
reactions are controlled.
ceruloplasmin
• It is synthesized in the liver.
• It is an acute phase reactant.
• It has ferroxidase activity.
• It has antioxidant properties.
• It contains 6-8 copper
• Ceruloplasmin enables iron to be oxidized (Fe+3)
with its ferroxidase activity and provide to
bind transferrin
• Normal value of serum copper level in a healthy
adult is 65-165 g/dL Higher-than-normal serum
copper level hypercupremia
• Lower than normal serum copper level,
hypocupremia
Signs of copper deficiency
Neutropenia
Leukopenia
Hemorrhagic vascular changes
Bone demineralization, bone, and joint abnormalities
Iron deficiency anemia
Osteoporosis
Infections
Reduced pigmentation
Neurological abnormalities
Abnormal cholesterol metabolism
Malignancies
Disorders of
copper
metabolism
• Menkes’ disease
• Menkes disease (Menkes kinky hair syndrome),
a progressive neurodegenerative disease with
X-linked recessive inheritance starting from
early childhood
• Due to the mutation in the gene of the Cu+2 -
carrying ATPase, the transport and storage
of copper is impaired.
• Low levels of plasma copper
• The most important findings to support the
diagnosis are hair findings. Lightening in
hair color, wooly, hard and mixed hair is
typical.
• (Due to the loss of disulfide bond catalyzed
by Cu+2------ Lysyl oxidase) If untreated,
death occurs due to dysfunction of copper
Wilson’s disease

•It is a genetically determined

copper accumulation disease.
•. Loss- of- function mutation
of gene that encodes ATP7B is
lead to Wilson’s disease
•Neurological disorders, liver
cirrhosis, Kayser-Fleischer ring
(green-brown discoloration) due
to copper deposition
•Copper accumulation in all
tissues, especially liver, brain
(Basal ganglia), cornea and
Symptoms and signs
Wilson cirrhosis
• Serum ceruloplasmin levels are low.
• Total serum copper decreased due to
ceruloplasmin deficiency, but serum free copper
increased.
• Quantitative copper increase in liver biopsy
(Gold standard in diagnosis)
Copper toxicity
• It can be formed by copper pots, some burn
pomades and fungicides.
• Bleeding in the GIS, renal dysfunction, and
neurological findings are in question.
manganese
• Almond, apricot, bran, kidney, lentil, parsley, walnut,
cress, wheat extract are manganese rich nutrients
• It is absorbed through the small intestine by a
mechanism similar to iron absorption.
• It is found in many metalloenzyme structures in the
form of Mn+2, Mn+3.
• Enzymes containing Mn in their structure
-arginase
-Pyruvate carboxylase
-Superoxide dismutase;
-Transferase,
- decarboxylase,
-hydrolases;
• Bone development; It is a cofactor of
glycosyltransferase, which enables the
synthesis of proteoglycans.
• wound healing; in collagen and
glycosaminoglycan synthesis Neuromuscular
disorders and schizophrenia-like findings in
manganese intoxication
• Excess manganese activates atherosclerosis.
• Manganese Deficiency: Irregularity in balance,
infertility, decreased desire for sex, abnormal
development in the body,increase birth of a
dead child
Chromium (Cr)
• Cr +3 and Cr +6 valence forms are found in
biological systems.
• glucose tolerance factor
• It strengthens the effects of insulin.
• Facilitates the binding of insulin to its
receptors
• Insulin is ineffective as a glucose regulator
without chromium. Chromium deficiency leads to
atherosclerosis
• Trivalent Cr has low toxicity.
• Cr +6 is more toxic than Cr +3. Cr +6 is used in
steelmaking, it is carcinogenic, it also
damages liver, kidney and CNS.
• There is occupational exposure in situations
such as steel making, photography, painting.
• Acute exposure causes allergic reaction,
conjunctivitis, dermatitis, edema and ulcer.
• If chronic exposure is; G.I.S symptoms,
hepatitis, a.c cause cancer.
Selenium
• Selenium was found to prevent liver cell
• necrosis & muscular dystrophy.
• Total body content of selenium around 10 mg
• and it is present mainly in liver.
• Sources:
• Richest sources are meat, sea foods, liver,
• kidney and grains.
• RDA
• 50to200μg/ day
• Selenium is absorbed mainly from the
• duodenum.
• • Selenium after absorption is transported
• bound to plasma proteins particularly β-
• lipoproteins in humans.
• • Main route of excretion of selenium appears
• to be through urine.
• Selenium, as selenocysteine is an essential
• component of the enzyme glutathione
• peroxidase.
• • Glutathione peroxidase functions as an
• antioxidant enzyme.
• It suppresses the oxidative stress by
• converting oxygen free radicals into less
• toxic forms or non-toxic forms.
• The presence of selenium in the diet reduces
• the requirement of vitamin E, since vitamin E
• also acts as an antioxidant.
• • Selenium may exert anticancer effects
• because of its antioxidant role.
• • Selenium†containing†enzyme†5’deiodinase
• converts thyroxine (T4) to triiodo-thyronine
• (T3) in thyroid gland.
• In selenium deficiency, conversion of T4 to T3 is
• impaired resulting in hypothyroidism.
• • Selenium binds with certain heavy metals &
• protects body from their toxic effects.
• • Selenocysteine is considered as 21st standard
• amino acid since it is coded by UGA, which is a
• termination codon.
• • Selenium is incorporated to proteins as
• selenocysteine during protein synthesis.
• Causes:
• • Low soil content of selenium & malnutrition.
• • Clinical features:
• • Chronic selenium deficiency is associated with
• cirrhosis of liver, cardiomyopathy leading to
• congestive cardiac failure, muscular
• dystrophy, loss of appetite, nausea,
• abnormal electrocardiograms.
• Selenium toxicity is rare.
• • Selenosis is the toxicity due to excessive
• consumption of selenium.
• • Clinical features are hair loss, dermatitis and
• irritability.
• • Liver & neuromuscular disorders that are
• usually fatal.
ıodine

• Iodine is usually ingested as an iodide or iodate compound and is

rapidly absorbed in the intestine.
• Iodine entering the circulation is actively trapped by the thyroid
gland.
• The active transport of iodine is likely to be based on cotransport of
sodium and iodine in capillaries.
• Anion thiocyanate inhibits the active transport.
• In addition to trapping iodine in thyroid cells, follicular cells also
synthesize the glycoprotein, thyroglobulin (Tg), from carbohydrates
and amino acids (including tyrosine) obtained from the circulation.
• Thyroglobulin moves into the lumen of the follicle where it
becomes available for hormone production.
• Thyroid peroxidase (TPO), a membrane-bound hem-containing
glycoprotein, catalyzes the oxidation of the iodide to its active
form, I2, and the binding of this active form to the tyrosine in
thyroglobulin to form mono- or diiodotyrosine (MIT or DIT).
• These in turn combine to form the thyroid hormones
triiodothyronine (T3) and thyroxine (T4)
• Iodine deficiency has multiple adverse effects on growth and
development, and is the most common cause of preventable
mental retardation in the world.
• Resulted mainly from inadequate thyroid hormone production.
• During pregnancy and early infancy, iodine deficiency can
cause irreversible effects.
• Under normal conditions, the body tightly controls thyroid
hormone concentrations via TSH.
• TSH secretion increases when iodine intake falls below about 100
mcg/day.
• TSH increases thyroidal iodine uptake from the blood and the
production of thyroid hormone.
• However, very low iodine intakes can reduce thyroid hormone
production even in the presence of elevated TSH levels.
• If iodine intake falls below approximately 10–20 mcg/day,
hypothyroidism occurs.
• Goiter is the earliest clinical sign of iodine deficiency.
• In pregnant women, iodine deficiency can cause major neurodevelopmental
deficits and growth retardation in the fetus, as well as miscarriage and stillbirth.
• Chronic, severe iodine deficiency in utero causes cretinism (mental retardation).
• Stunted growth, delayed sexual maturation.
• In infants and children, less severe iodine deficiency can cause
neurodevelopmental deficits such as somewhat lower-than-average intelligence.
• Mild to moderate maternal iodine deficiency associated with an increased risk for
attention deficit hyperactivity disorder in children.
• 11