MINERALS

MODERATOR: PRESENTER:
Dr. K. RAJANI CHANDER, M.D.(HOM) DR. NIKITHA SOMA
PG 24TH BATCH,
PROFESSOR, H.O.D.
DEPT. OF PRACTICE OF MEDICINE,
DEPT. OF PAEDIATRICS,
JSPS GOVT HOMOEOPATHIC
J.S.P.S. GOVT
MEDICAL COLEGE,
HOMOEOPATHIC MEDICAL COLLEGE,
RAMANTHAPUR,HYDERABAD.
RAMANTHAPUR,HYDERABAD.
 INTRODUCTION
 Nutrients are the chemical substances in the food that the body uses for
functions that supports growth, tissue maintenance and repair.

 There are six categories of nutrients: Carbohydrates, Proteins, Fats, Vitamins,

Minerals and Water.

 These nutrients can be grouped as Macronutrients and Micronutrients.

Macronutrients: They are needed in large quantities and are building blocks of the
body.
Ex: Carbohydrates, Fats and Proteins.

Micronutrients: They are needed in small quantities and are crucial for their role in
metabolic pathways and in enhancing immunity.
Ex: Vitamins and Minerals.
 MINERALS

 Although minerals constitute a small proportion of the human body, they

perform several vital functions which are absolutely essential for normal
metabolism.

 Most of the minerals are provided by the diet one consumes, but the
amount in food is not the amount that is actually absorbed.

 Minerals are classified as Major elements and Trace elements according to

the quantities present in the body and required by humans.
MACRO-MINERALS:
If more than 100 milligrams of an element is needed per day, it is classified as a
macro-mineral. Also, they are present in higher concentrations in the body
constituting more than 0.01% of bodyweight.
Calcium, Phosphorous, sodium, potassium and magnesium are the major macro-
minerals.

TRACE ELEMENTS:
The minerals which are needed in amounts less than 100 mg per day are classified
as trace elements. Also, they are present in concentration less than 0.01% of body
weight. They include Iron, Iodine, zinc, copper, fluorine, selenium, manganese etc.
 MACROMINERALS
 Minerals perform several vital
functions which are absolutely
essential for the very existence of the
organism.

 These include calcification of bone,

blood coagulation, neuromuscular
irritability, acid-base equilibrium, fluid
balance and osmotic regulation.

 Calcium, Phosphorous, magnesium

sodium and potassium are the major
macro-minerals.
 CALCIUM
INTRODUCTION

 It is the most abundant mineral in the body and is located primarily in bone.

 About 99% of the calcium in the body is found in bones and teeth. Only 1% is
found in the blood and soft tissues, which perform a wide variety of functions.

 Calcium levels in blood and in extracellular fluid must be maintained within a very
narrow range 9 mg/dl to 11 mg/dl for normal physiological functions. The plasma
levels range from 9 to 10.5 mg/dl in children.

 Since calcium is vital for body functions, the body tries to maintain its level even
when there is dietary calcium deficiency.

 Only 20-25% of dietary calcium is absorbed.

METABOLIC FUNCTIONS:

1) Development of bones and teeth:

Calcium along with phosphate is required for the formation and physical
strength of skeletal tissue. Osteoblasts are responsible for bone formation while
osteoclasts result in demineralization.

2) Muscle contraction: calcium interacts with troponin C to trigger muscle

contraction.

3) Blood coagulation

4) Nerve transmission

5) Membrane integrity and permeability

DIETARY SOURCES :

 Milk and milk products are the major sources of dietary calcium.

 When consumption of milk is low, cereals become the major dietary source.

 Green leafy vegetables, amaranth, Gingelly seeds, Ragi, Sea food, Fish
and Mutton are also good sources of calcium.
DIETARY REQUIREMENTS:

 Infants - 500 mg/day

 1-9 years - 600 mg/day
 10-18 years - 800 mg/day
 adult male and female - 600 mg/day
 Pregnancy and lactation - 1,200 mg/day
FACTORS PROMOTING CALCIUM ABSORPTION:

1) Vitamin D (through its active form calcitriol) induces the synthesis of

calcium binding protein in the intestinal epithelial cells and promotes Ca
absorption.

2) Parathyroid hormone enhances Ca absorption through the increased

synthesis of calcitriol.

3) Acidity (low pH) is more favourable for Ca absorption.

4) Lactose promotes calcium uptake by intestinal cells.

5) The amino acids lysine and arginine facilitate Ca absorption.

FACTORS INHIBITING CALCIUM ABSORPTION:

1) The absorption of calcium is affected by the presence of phytates, oxalates,

fatty acids and fibre.
 These form insoluble salts or chelates with calcium and make it unavailable
for absorption.
 Calcium is not well absorbed well from vegetables and cereals due to the
presence of these potent inhibitors which are present in higher
concentrations in spinach and in lower concentrations in sweet potatoes
and dried beans.
2) High content of dietary phosphate results in the formation of insoluble
calcium phosphate and prevents Ca uptake. The dietary ratio of Ca and P
between 1: 2 and 2:1 is ideal for optimum Ca absorption by intestinal cells.

3) The free fatty acids react with Ca to form insoluble calcium soaps. This is
particularly observed when the fat absorption is impaired.

4) Alkaline condition (high pH) is unfavourable.

5) High content of dietary fibre interferes with Ca absorption.

6) Vitamin D deficiency leads to improper calcium absorption.

SERUM CALCIUM LEVELS:

 The normal concentration of plasma or serum Ca is 9-11 mg/dl.

• About half of this (5 mg/dl) is in the ionized form which is functionally the most
active.
• At least 1 mg/dl serum Ca is found in association with citrate or phosphate.
• The other half of serum Ca (4-5mg/dl) is bound to proteins, mostly albumin and,
to a lesser extent, globulin.

 Ionized and citrate (or phosphate) bound Ca is diffusible from blood to the
tissues while protein bound Ca is non-diffusible.

 In the usual laboratory determination of serum Ca, all the three fractions are
measured together.
FACTORS REGULATING PLASMA CALCIUM LEVEL
 The hormones calcitriol, parathyroid hormone (PTH) and calcitonin are
the major factors that regulate the plasma calcium (homeostasis of Ca)
within a narrow range (9-11 mg/dl).

CALCITRIOL:
 The physiologically active form of vitamin D is a hormone, namely
calcitriol or 1, 25-dihydroxy- Cholecalciferol (1, 25 DHCC).
 Calcitriol induces the synthesis of a specific calcium binding protein in
the intestinal cells.
 This protein increases the intestinal absorption of calcium as well as
phosphate.
 Thus blood Ca level is increased by calcitriol (the active vitamin D).
 Also, it stimulates calcium uptake by osteoblasts of bone and promotes
calcification or mineralization.
PARATHYROID HORMONE

 Parathyroid hormone (PTH) is secreted by two pairs of parathyroid glands that

are closely associated with thyroid glands.

 The rate of formation and the secretion of PTH are promoted by low Ca2+
concentration.

 Thus, the release of PTH from parathyroid glands is under the negative
feedback regulation of serum Ca2+.

 PTH has 3 independent tissues-bone, kidneys and intestine to exert its action.
The prime function of PTH is to elevate serum calcium level.
Action on the bone :
PTH causes decalcification or demineralization of bone, a process carried out
by osteoclasts. Demineralization ultimately leads to an increase in the blood Ca
level. The action of PTH on bone is quantitatively very significant to maintain Ca
homeostasis.

Action on the kidney: PTH increases the Ca reabsorption by kidney tubules.

This is the most rapid action of PTH to elevate blood Ca levels. However,
quantitatively, this is less important compared to the action of PTH on bone.
PTH promotes the production of calcitriol (1, 25 DHCC) in the kidney by
stimulating 1-hydroxylation of 25-hydroxycholecalciferol.

Action on the intestine : The action of PTH on the intestine is indirect. It

increases the intestinal absorption of Ca by promoting the synthesis of calcitriol.
CALCITONIN
 Calcitonin is secreted by parafollicular cells of thyroid gland. The action
of CT on calcium metabolism is antagonistic to that of PTH.

 Thus, calcitonin promotes calcification by increasing the activity of

osteoblasts. Further, calcitonin decreases bone resorption and
increases the excretion of Ca into urine.

 Therefore it has a decreasing influence on blood calcium.

The blood Ca level is maintained within a narrow range by the homeostatic

control, most predominantly by PTH. Hence abnormalities in Ca
metabolism are mainly associated with alterations in PTH.
 HYPOCALCEMIA

 It is characterized by a fall in the serum Ca to below 7 mg/dl.

 Hypocalcaemia is mostly due to hypoparathyroidism. This may happen after
an accidental surgical removal of parathyroid glands or due to an autoimmune
disease.
 Other causes include chronic kidney failure, vitamin D deficiency and low
blood magnesium levels that occur mainly in cases of severe alcoholism in
addition to low dietary calcium intake.

CLINICAL FEATURES:
 Mild hypocalcaemia is often asymptomatic but, with more profound reductions
in serum calcium, tetany can occur.
 This is characterised by muscle spasms due to increased excitability of
peripheral nerves.
 Children are more liable to develop tetany than adults
HYPOCALCEMIA IN CHILDREN:

 Hypocalcemia in the older child presents with tetanic spasms of the fingers and
wrist or toes and foot, perioral numbness, tingling, or seizures

 Mental changes include irritability, impairment of memory, paranoia, depression,

and frank psychosis. Papilledema may be present.

 Chronic hypocalcaemia leads to cataracts and basal ganglia calcification.

However, in neonates, hypocalcaemia may present quite differently, with apneic
spells or laryngeal stridor, in addition to seizures
 TETANY
 Tetany has a characteristic triad of carpopedal spasm, stridor and
convulsions, although one or more of these may be found independently of
the others.
 Stridor is caused by spasm of the glottis.
 Subclinical (latent) hypocalcaemia may be elicited by the Chvostek or
Trousseau signs.

TROUSSEAU’S SIGN
 The hands adopt a position with flexion of the metacarpophalangeal joints of
the fingers and adduction of the thumb (Carpopedal spasm).
 Inflation of a sphygmomanometer cuff on the upper arm to 20mm more than
the systolic blood pressure is followed by carpopedal spasm within 3-5
minutes.
CHVOSTEK'S SIGN
Tapping over the branches of the facial nerve as they emerge
from the parotid gland produces twitching of the facial muscles.
 Adults can also develop carpopedal spasm in association with tingling of the hands
and feet and around the mouth, but stridor and fits are rare.

 Hypocalcaemia can cause papilloedema and prolongation of the ECG QT interval,

which may predispose to ventricular arrhythmias.

 Hypocalcaemia associated with hypophosphataemia, as in vitamin D deficiency,

causing rickets in children and osteomalacia in adults.

OSTEOMALACIA AND RICKETS - These conditions are characterised by defective

mineralisation of bone. They occur due to deficiency of both calcium and vitamin D.

Osteomalacia: describes a syndrome in adults of defective bone mineralisation, bone

pain, increased bone fragility and fractures.
Rickets: is the equivalent syndrome in children and is characterised by enlargement
of the growth plate and bone deformity.
OSTEOPOROSIS
 It is the most common bone disease and affects millions of people
worldwide.

 Lifelong lack of calcium plays a role in the development of osteoporosis. Low

calcium intake contributes to diminished bone density, early bone loss and
an increased risk of fractures.

 Osteoporotic fractures can affect any bone, but the most common sites are
the forearm (colles fracture), spine (vertebral fracture) and hip

 The defining feature of osteoporosis is reduced bone density, which causes a

microarchitectural deterioration of bone tissue and leads to an increased risk
of fracture.

 The prevalence of osteoporosis increases with age, reflecting the fact that
bone density declines with age, especially in women.
 HYPERCALCAEMIA
 It is one of the most common biochemical abnormalities and is often detected
during routine biochemical analysis in asymptomatic patients.

 However, it can present with chronic symptoms.

 Blood calcium levels >11mg/dl indicates hypercalcaemia.

 The determination of ionized serum calcium (elevated to 6-9mg/dl) is more useful

for the diagnosis of hyperparathyroidism.

 It has been observed that some of the patients may have normal levels of total
calcium in the serum but differ with regard to ionized calcium.

 Hypercalcemia is most commonly associated with hyperparathyroidism caused

by increased activity of parathyroid glands.
CLINICAL FEATURES:

 These include polyuria and polydipsia, renal colic, lethargy, anorexia, nausea,
dyspepsia, peptic ulceration, constipation, depression, drowsiness and impaired
cognition.

 The classic symptoms of primary hyperparathyroidism are described by the

'bones, stones and abdominal groans’

 About 50% of patients with primary hyperparathyroidism are asymptomatic while

others have non- specific symptoms such as fatigue, depression and generalised
aches and pains.

 Some present with renal calculi and it has been estimated that 5% of first stone
formers and 15% of recurrent stone formers have primary hyperparathyroidism.
 PHOSPHORUS
INTRODUCTION

 An adult body contains about 1 kg phosphate and it is found in every cell of

the body.

 Most of it (about 80%) occurs in combination with Ca in the bones and

teeth.

 About 10% is found in muscles and blood in association with proteins,

carbohydrates and lipids.

 The remaining 10% is widely distributed in various chemical compounds.

 Serum phosphorus is higher in infancy about 4.5 to 7.5 mg/dl and falls
gradually during childhood to adult levels of 2.5 to 4.5 mg/dl.
METABOLIC FUNCTIONS:

 Phosphorous along with calcium is needed for the normal growth of bone and
teeth.

 It is important in cellular metabolism, oxygen transport and acid base

balance.

 it plays a central role for the formation and utilization of high-energy

phosphate compounds. Ex: ATP, creatine phosphate etc.

 Phosphorus is required for the formation of phospholipids, phosphoproteins

and nucleic acids (DNA and RNA).

 It is an essential component of several nucleotide coenzymes e.g. NAD,

NADP+, pyridoxal phosphate, ADP, AMP.
DIETARY SOURCES:

 Cereals, pulses, nuts and oil seeds are rich sources of phosphorous.

 Milk, leafy vegetables, meat, eggs are also good sources.

 80% of phosphorous in the plant sources is present as phytate which is

not absorbed.

 Phytate levels are low in polished rice and germinated seeds.

 All protein rich foods are rich in phosphate.

DIETARY REQUIREMENTS

 The recommended dietary allowance (RDA) of phosphate is based on the

intake of calcium.

 The ratio of Ca: P of 1:1 is recommended (i.e. 800mg/day) for an adult.

 For infants, however, the ratio is around 2:1, which is based on the ratio
found in human milk.

 Calcium and phosphate are distributed in the majority of natural foods in

1:1 ratio. Therefore, adequate intake of Ca generally takes care of the P
requirement also.

 Infants - 750 mg/day,

1–9 year - 600 mg/day
10–18 year - 800 mg/day
ABSORPTION

 Calcitriol promotes phosphate uptake along with calcium.

 Absorption of phosphorus and calcium is optimum when the dietary Ca: P is

between 1:2 and 2:1.

 Acidity favors while phytate decreases phosphate uptake by intestinal cells.

 Serum phosphorus concentration is largely maintained by variable renal

reabsorption.

 Normally about 85 percent of the filtered load is reabsorbed — 75 percent in

the proximal tubules and 10 percent in distal tubules.

 Both proximal and distal reabsorption of phosphate is decreased by PTH and

calcium.
 HYPOPHOSPHATAEMIA

 Phosphate may redistribute into cells during periods of increased energy

utilisation (such as refeeding after a period of starvation) and during systemic
alkalosis.

 However, severe hypophosphataemia usually represents an overall body deficit

due to either inadequate intake or absorption through the gut, or excessive renal
losses, most notably in primary hyperparathyroidism or osmotic diuresis and
diuretics acting on the proximal renal tubule.

 Phosphorous deficiency can occur in low birth weight babies, children with
malnutrition and those on parenteral nutrition.

 Vitamin D deficient rickets is characterized by decreased serum phosphate

(1-2 mg/dl).
CLINICAL FEATURES:

 Manifestations of phosphate depletion are wide ranging, reflecting the

involvement of phosphate in many aspects of metabolism.

Defects appear in the

 blood (impaired function and survival of all cell lines),

 skeletal muscle (weakness, respiratory failure),

 cardiac muscle (congestive cardiac failure),

 smooth muscle (ileus),

 central nervous system (decreased consciousness, seizures and coma) and

 bone (Osteomalacia in severe prolonged hypophosphataemia).

 HYPERPHOSPHATAEMIA

 Phosphate accumulation is usually the result of acute kidney injury or chronic

kidney disease.

 Phosphate excretion is also reduced in hypoparathyroidism and

pseudohypoparathyroidism.

 Phosphate accumulation is aggravated in any of these conditions if the patient

takes phosphate-containing preparations or inappropriate vitamin D therapy.

 They relate to hypocalcaemia and metastatic calcification, particularly in

chronic renal failure.
 MAGNESIUM
 Magnesium is an important component of the adenylate cyclate system.

 The adult body contains about 20g – 25g of magnesium, 60 - 70% of which is
found in bones in combination with calcium and phosphorus, 25-30% in muscles,
6-8% in soft tissue and 1% in extracellular fluid.

 Like potassium, magnesium is mainly an intracellular cation.

 Magnesium has an important role to play in the structure and functioning of the
human body.
METABOLIC FUNCTIONS OF MAGNESIUM

 Magnesium is involved in more than 300 essential metabolic reactions.

 It plays a structural role in the bones, cell membranes and chromosomes.

 The metabolism of carbohydrates and fats to produce energy requires

numerous magnesium- dependent chemical reactions, such as ATP.

 It is necessary for proper calcium and vitamin D metabolism.

 It is important to the function of many enzymes, including the Na , K-ATPase,

and can regulate both potassium and calcium channels.
 Magnesium affects the conduction of nerve impulses, muscle contractions
and normal heart rhythm through the active transport of ions like potassium
and calcium across cell membranes.

 Its overall effect is to stabilize excitable cell membranes.

 Magnesium is required in cell signaling for the phosphorylation of proteins

and formation of cyclic adenosine monophosphate (cAMP).

 It is also involved in cell migration and helps in wound healing.

DIETARY SOURCES

 Magnesium is a part of chlorophyll, so plants form major source of

magnesium.

 Green leafy vegetables are rich in magnesium.

 Legumes, cereals, nuts, beans, vegetables (cabbage, cauliflower), milk, fruits

are good sources of magnesium.

 Animal products are also good sources of magnesium.

 About one-third of dietary magnesium is absorbed from the usual Indian diet.
DIETARY REQUIREMENTS

 infants below 6 months - 30 mg

 infants between 6 - 12 months - 45 mg.
 Children between 1 - 3 years - 50 mg/day,
 4-6 years - 70 mg/day;
 7-9 years - 100 mg/day.
 Adolescents - 120 - 240 mg/day.
 adult male - 340 mg/day and
 Adult female - 310 mg/day.
ABSORPTION

 Magnesium deficiency is quite rare in healthy individuals who consume a balanced

diet since it is abundant in both plant and animal foods.
 About 50% of the dietary Mg is normally absorbed.
 It is absorbed by the intestinal cells through a specific carrier system. PTH
increases Mg absorption.
 Almost the entire magnesium filtered in the kidney is reabsorbed.

FACTORS INHIBITING

 Dietary deficiency of magnesium will not occur unless associated with

malabsorption or disease states like malnutrition.
 Consumption of large amounts of calcium, phosphate and alcohol diminish Mg
absorption.
FACTORS REGULATING SERUM MAGNESIUM LEVELS:

 Normal serum magnesium level is 1.8 - 3 mg/dl.

 It is present in the ionized form (60%), in combination with other ions (10%) and
bound to proteins (30%)

 Serum magnesium is maintained in narrow range like that of calcium.

 There is close association between calcium and magnesium. They have mutually
reinforcing as opposing actions

 Renal handling of magnesium involves filtration of free plasma magnesium at the

glomerulus (about 70% of the total) with extensive reabsorption (50-70%) in the
Loop of Henle and other parts of the proximal and distal renal tubule.

 Magnesium reabsorption is also enhanced by parathyroid hormone (PTH).

 HYPOMAGNESAEMIA

Aetiology

 Hypomagnesaemia exists when plasma magnesium concentrations are below the

reference range of 0.75 -1.0 mg/dl (1.5-2.0 mg/dl).

 This is usually a reflection of magnesium depletion which can be caused by

excessive magnesium loss from the

 Gastro intestinal tract (notably in chronic diarrhoea)

 Kidney (during prolonged use of loop diuretics).

 Malnutrition, malabsorption and parenteral nutrition also results in magnesium

depletion.
 Excessive alcohol ingestion can cause magnesium depletion through both
gut and renal losses.

 Low levels of Mg may be observed in uraemia and rickets.

 Hypomagnesaemia is frequently associated with hypocalcaemia, probably

because magnesium is required for the normal secretion of PTH in
response to a fall in serum calcium, and because hypomagnesaemia
causes end organ resistance to PTH.
CLINICAL FEATURES

 Magnesium deficiency causes neuromuscular irritation, weakness and

convulsions. These symptoms are similar to that observed in tetany (Ca
deficiency).

 It may also cause cardiac arrhythmias, notably Torsades de pointes.

 Torsades de pointes : Ventricular tachycardia (more than 100 beats a minute). It

can be seen in malnourished individuals and chronic alcoholics, due to a
deficiency in potassium and/or magnesium.

 Central nervous excitation, seizures, Vasoconstriction and hypertension may also

occur.

 Magnesium is also associated with hyponatraemia and hypokalaemia.

 HYPERMAGNESEMIA

 This a much less common abnormality than hypomagnesaemia.

 Predisposing conditions include acute kidney injury, chronic kidney disease and
adrenocortical insufficiency.

 The condition is generally precipitated in patients at risk by an increased intake of

magnesium, or through the use of magnesium-containing medications, such as
antacids, laxatives and enemas.

 Clinical features include bradycardia, hypotension, reduced consciousness and

respiratory depression.
 SODIUM

INTRODUCTION
 Most of the body’s sodium is located in the ECF, where it is by far the most
abundant cation. Accordingly, total body sodium is the principal determinant of ECF
volume.
 About 50% of the sodium present in the body is in the bones, 40% in extracellular
fluid (ECF) and about 10% in soft tissues.

Metabolic Functions of Sodium

 The Na-K ATPase pump moves three sodium ions out of the cell in exchange for
two potassium ions moving into the cell, and during this process ATP is hydrolysed
to ADP.
 Sodium ions play a special role at sinoatrial node to generate and maintain the
heart beat and transmission of nerve impulse.
 Sodium is required for the maintenance of osmotic pressure and
fluid balance.
 It is necessary for the normal muscle irritability and cell permeability.
 Sodium is involved in the intestinal absorption of glucose, galactose
and amino acids.

DIETARY SOURCES
 The common salt (NaCl) used in the cooking medium is the major
source of sodium.
 The ingested foods also contribute to sodium.
 The good sources of sodium include bread, whole grains, leafy
vegetables, nuts, eggs and milk.
DIETARY REQUIREMENTS

 For normal individuals, the requirement of sodium is about 5-10 g/day which
is mainly consumed as NaCl (10 g of NaCl contains 4 g of sodium).
 The daily consumption of Na is generally higher than required due to its
flavour.
 A strong relationship between hypertension and dietary salt intake has been
observed and intake of more than 10g of salt per day is considered to have
definitive tendency to raise blood pressure.
 For persons with a family history of hypertension, the daily NaCl intake should
be less than 5g per day.
 For patients of hypertension, around 1 g/day is recommended.
PLASMA SODIUM

 In the plasma (serum), the normal concentration of sodium is 135-145 mEq/l.

 Sodium is an extracellular cation, therefore, the blood cells contain much less of
it (35 mEq/l).
 The sodium pump operates in all cells to maintain sodium extracellular in an
ATP- dependent mechanism.
 The mineralocorticoids, secreted by adrenal cortex, influence sodium
metabolism.
 A decrease in plasma sodium and increase in its urinary excretion is observed
in adrenocortical insufficiency.

ABSORPTION
 Sodium is readily absorbed in the gastrointestinal tract and, therefore, very little
of it (<2%) is normally found in feces.
EXCRETION

 Kidney is the major route of sodium excretion from the body.

 As much as 800 g Na/day is filtered by the glomeruli, 99% of this is
reabsorbed by the renal tubules by an active process. This is controlled
by Aldosterone.
 Extreme sweating also causes considerable amount of sodium loss from
the body. There is, however, individual variation in sodium loss through
sweat.
 A number of interrelated mechanisms serve to maintain whole-body
sodium balance, and hence ECF volume, by matching urinary sodium
excretion to sodium intake.
 The enzyme renin is released from juxtaglomerular apparatus.

 Renin release is stimulated by:

• Reduced perfusion pressure in the afferent arteriole,
• Increased sympathetic nerve activity,
• Decreased sodium chloride concentration in the distal tubular fluid.

 Renin released into the circulation activates the effector mechanisms for
sodium retention, which are components of the renin-angiotensin-
aldosterone (RAA) system.
 Renin acts on the peptide substrate, angiotensinogen (manufactured in the
liver), producing angiotensin I in the circulation.

 This in turn is cleaved by angiotensin-converting enzyme (ACE) into

angiotensin II, largely in the pulmonary capillary bed.

 Angiotensin II has multiple actions: it stimulates proximal tubular sodium

reabsorption and release of aldosterone from the zona glomerulosa of the
adrenal cortex, and causes vasoconstriction of small arterioles.

 Aldosterone amplifies sodium retention by its action on the cortical collecting

duct. The net effect is to restore ECF volume and blood pressure towards
normal, thereby correcting the initiating hypovolaemic stimulus.
(ACE = angiotensin-converting enzyme; ACTH = adrenocorticotrophic hormone; JGA =
juxtaglomerular apparatus; MR = mineralocorticoid receptor
 HYPONATREMIA

ETIOLOGY:

 This is a condition in which the serum sodium level falls below the
normal (<135 mEq/L).

 Hyponatremia may occur due to diarrhoea, vomiting, chronic renal

diseases, adrenocortical insufficiency (Addison's disease).

 Administration of salt free fluids to patients may also cause

hyponatremia due to overhydration.

 Decreased serum sodium concentration is also observed in oedema

which occurs in cirrhosis or congestive heart failure.
CLINICAL FEATURES

 Hyponatraemia is a common electrolyte abnormality, which is often

asymptomatic but which can also be associated with profound disturbances
of cerebral function, manifesting as anorexia, nausea, vomiting, confusion,
lethargy, seizures and coma.

 The likelihood of symptoms occurring is related more to the speed at which

electrolyte abnormalities develop rather than their severity.

 When plasma osmolality falls rapidly, water flows into cerebral cells, which
become swollen and ischaemic.

 In such cases, sodium levels can be restored to normal rapidly by infusion of

hypertonic sodium chloride.
 However, when hyponatraemia develops gradually, cerebral neurons
have time to respond by reducing intracellular osmolality, through
excreting potassium and reducing synthesis of intracellular organic
osmolytes.

 The osmotic gradient favouring water movement into the cells is thus
reduced and symptoms are avoided.

 Rapid correction of hyponatremia that has developed slowly (over

weeks to months) can be hazardous, since brain cells adapt to slowly
developing hypo-osmolality by reducing the intracellular osmolality, thus
maintaining normal cell volume.
 Under these conditions, an abrupt increase in extracellular
osmolality can lead to water shifting out of neurons, abruptly
reducing their volume and causing them to detach from their
myelin sheaths.

 The resulting 'myelinolysis' can produce permanent structural

and functional damage to mid-brain structures, and is generally
fatal.

 Hyponatremia also causes reduced blood pressure and

circulatory failure.
 HYPERNATREMIA

ETIOLOGY

 This condition is characterized by an elevation in the serum sodium level

(plasma Na> 148 mmol/L).

 It may occur due to hyperactivity of adrenal cortex (Cushing's syndrome),

prolonged administration of cortisone, ACTH and/or sex hormones.

 Loss of water from the body causing dehydration, as it occurs in diabetes

insipidus, results in hypernatremia. Rapid administration of sodium salts also
increases serum sodium concentration.

 It may be noted that in pregnancy, steroid and placental hormones cause

sodium and water retention in the body leading to oedema.
CLINICAL FEATURES

 Patients with hypernatremia generally have reduced cerebral function, either

as a primary problem or as a consequence of the hypernatremia itself, which
results in dehydration of neurons and brain shrinkage.

 In the presence of an intact thirst mechanism and preserved capacity to obtain

and ingest water, hypernatremia may not progress very far.

 If adequate water is not obtained, dizziness, confusion, weakness and

ultimately coma and death can result.

 Increase in blood volume and blood pressure (hypertension) also occurs.

 Treatment of hypernatremia depends on both the rate of development
and the underlying cause.

 If there is reason to think that the condition has developed rapidly,

neuronal shrinkage may be acute and relatively rapid correction may
be attempted.

 However, in older, institutionalised patients it is more likely that the

disorder has developed slowly, and extreme caution should be
exercised in lowering plasma sodium to avoid the risk of cerebral
oedema.
 POTASSIUM

 Potassium is one of the major intracellular cations which help to maintain

the intracellular osmotic pressure.

 About 75% of the body potassium is present in the skeletal muscles.

 Normal levels of plasma potassium range from 3.5 mEq/L to 5mEq/L.

METABOLIC FUNCTIONS

 Potassium maintains intracellular osmotic pressure.

 It is required for the regulation of acid-base balance and water balance in

the cells.
 The enzyme pyruvate kinase (of glycolysis) is dependent on K for
optimal activity.

 Adequate intracellular concentration K is necessary for proper

biosynthesis of proteins by ribosomes.

 Extracellular K influences cardiac muscle activity.

 The steep concentration gradient for potassium across the cell

membrane of excitable cells plays an important part in generating the
resting membrane potential and allowing the propagation of the action
potential that is crucial to normal functioning of nerve, muscle and
cardiac tissues.
Dietary sources

 Banana, orange, pineapple, potato, beans, chicken, liver.

 Tender coconut water is a rich source of potassium.

Dietary requirements

 About 3-4 g/day

Absorption

 The absorption of K from the gastrointestinal tract is very efficient

(90%) and very little is lost through feces. However, in subjects
with diarrhea, a good proportion of K is lost in the feces.
Plasma potassium

 The plasma (serum) concentration of potassium is 3.4-5.0 mEq/l.

 The whole blood contains much higher level of K (50 mEq/l), since it is
predominantly an intracellular cation.

Excretion

 Potassium is mainly excreted through urine.

 The maintenance of body acid-base balance influences K excretion.

 Aldosterone increases excretion of potassium.

 A negative feedback relationship exists
between the plasma potassium concentration
and aldosterone.

 In addition to its regulation by the renin-

angiotensin system, aldosterone is released
from the adrenal cortex in direct response to
an elevated plasma potassium.

 Aldosterone then acts on the kidney to

enhance potassium secretion, hydrogen
secretion and sodium reabsorption, in the late
distal tubule and cortical collecting ducts.

 The resulting increased excretion of

potassium maintains plasma potassium within
a narrow range (3.3-4.7 mmol/L).
 HYPOKALAEMIA

 Decrease in the concentration of serum

potassium is observed due to overactivity
of adrenal cortex (Cushing's syndrome),
prolonged cortisone therapy, intravenous
administration of K- free fluids, treatment
of diabetic coma with insulin, prolonged
diarrhoea and vomiting.

 The symptoms of hypokalaemia include

irritability, muscular weakness,
tachycardia, cardiomegaly and cardiac
arrest.

 Changes in the ECG are observed

(flattened T wave).
 HYPERKALAEMIA

 Increase in the concentration of serum

potassium is observed in renal failure,
adrenocortical insufficiency (Addison's
disease), diabetic coma, severe
dehydration, intravenous administration of
fluids with excessive potassium salts.

 The manifestations of hyperkalaemia

include depression of central nervous
system, mental confusion, numbness,
bradycardia with reduced heart sounds
and, finally, cardiac arrest.

 Changes in ECG are also observed

(elevated T wave).
 CHLORIDE

 Chloride concentration in plasma ranges from 96 mEq/L to 106mEq/L.

 The homeostasis of sodium, potassium and chloride are inter-related.
 Chloride is excreted through urine and sweat.
 Renal threshold is about 110 mEq/L, and excretion of chloride is about 5 g
to 8 g per day.

Metabolic Functions of Chloride

 Chloride is the major extracellular anion.

 It is involved in maintaining osmolality, blood volume, and electric neutrality.
 Chloride is important in the formation of hydrochloric acid in gastric juices.
 The enzyme salivary amylase is activated by chloride.
Dietary Sources

 Common salt as cooking medium, whole grains, leafy vegetables,

eggs and milk.

Dietary requirements

 The daily requirement of chloride as NaCl is 5-10 g. Adequate intake

of sodium will satisfy the chloride requirement of the body.

Absorption

 In normal circumstances, chloride is almost totally absorbed in the

gastrointestinal tract.
Plasma chloride

 The normal plasma concentration of chloride is 95-105 mEq/l.

Cerebrospinal fluid (CSF) contains higher level of Cl (125 mEq/l).

Excretion

 There exists a parallel relationship between excretion of chloride and

sodium.

 The renal threshold for Cl- is about 110 mEq/l.

Hypochloraemia

 A reduction in the serum Cl level may occur due to vomiting,

diarrhoea, respiratory alkalosis, Addison's disease and excessive
sweating.

Hyperchloremia

 An increase in serum Cl concentration may be due to dehydration,

respiratory acidosis and Cushing's syndrome.
 SULPHUR

 Sulphur is present in the body in the form of sulphur containing amino acids
cysteine and methionine in body proteins.

 Hence, the source of sulphur is mainly the amino acids, cysteine and
methionine.

 Proteins contain about 1% sulphur by weight.

 Inorganic sulphates of sodium, potassium and magnesium though available in

food are not utilised by the body.

 All sulphur groups are ultimately oxidised in the liver to the sulphate (sulphuric
acid) group and excreted in urine.

 The total quantity of sulphur in urine is about 1 g per day.

Dietary sources

 Amino acid cysteine and methionine.

Dietary requirement - 850mg.

Metabolic Functions of Sulphur

 Sulphur-containing amino acids are important constituents of body proteins.

The di-sulphide bridges keep polypeptide units together, e.g. insulin,
immunoglobulin, etc.

 Keratin, rich in sulphur, is present in hair and nails.

 Sulphates play an important role in detoxification mechanisms.