Water and electrolyte balance

What is the goal of this course

• Describe the role and control of water and electrolyte
homeostasis

• Discuss the role of the kidneys in the regulation and control

of body fluid and electrolytes

• Hormonal control of water and electrolyte balance

(Antidiuretic hormone, Renin-Angiotensin-Aldosterone,
Parathyroid hormone)

• Case studies.
Cellular function
1. For normal cellular function, the osmolality - the electrolyte concentration per
kilogram of solvent - and the pH of the fluid medium in which chemical
reactions take place must be carefully controlled within tolerable ranges.

2. In the absence of these controls, life-threatening disorders of cellular function

may result.

3. Thus the body uses several mechanisms to maintain homeostatic balance

 Regulating water balance such that intake and loss are almost equal
 Regulating electrolytes balance between absorption from the small
intestine to that lost by mainly urine
 Acid base balance through respiration and kidney action to rid the
body of excess hydrogen ions so as to maintain the pH

4. Many systems including urinary, digestive, integumentary, endocrine amongst

others maintain the balance.

5. Since the balance is so crucial, fluid therapy is recommended for fast

restoration as and when necessary.
 Water
1. Water is the solvent for all processes in the human body and is located in both
intracellular and extracellular compartments.

2. It determines cell volume by its transport into and out of cells, transports
nutrients to cells, removes waste products by way of urine and acts as the
body’s coolant by way of sweating.

3. Water divides itself into Intracellular fluid (ICF) – which is the fluid inside the
cells and account for about two-thirds of the total body water.

4. Extracellular fluid (ECF) is outside the cell and accounts for the other one-third.
ECF can be subdivided into plasma and interstitial cell fluid.

5. Because most biological membranes are freely permeable to water but not ions
or proteins, the concentration of ions on one side of the membrane will
influence the flow of water across a membrane.
 Water is distributed between intracellular and
extracellular fluid compartments
Component Percentage Notes
Water ~ 60 – 70 This is about 40L. Children have about 70%
more water. Women, obese people and the
old have less than men, slim and young
people respectively.
Intracellular fluid (ICF) ~ 60 About 25L – this is the fluid within cells
which is used to make and utilize energy,
repair itself and replicates
Extracellular fluid (ECF) ~ 40 About 15L and is distributed between
plasma and interstitial fluids
Interstitial Fluid ~ 70 Fluid in tissue spaces between cells and
includes (i) the lymph – network of vessels
around interstitial tissues transporting cell
secreted to the bloodstream and (ii)
transcellular water - gastrointestinal
secretions, urine and sweat.
Blood plasma ~ 30 Blood without the red blood cells
 Movement of water in the body - osmosis
1. By way of osmosis, water moves from the digestive tract to the bloodstream and
then by capillary filtration, water moves from the blood to the interstitial fluid,
which fills tissue spaces between all their living cells.

2. From the interstitial fluid, the water can be reabsorbed by the capillaries again,
enter the lymphatic system and eventually return to the blood or can be
osmotically absorbed into the surrounding cells.

3. The ease of water movement ensures that within seconds there is osmolarity
balance between the intracellular and extracellular fluids.

4. Osmosis is controlled by the concentration of electrolytes especially sodium

salts in the ECF and potassium salts in the ICF.

5. Thus osmosis plays an important role in governing the body’s water distribution
and total water content.
 Water gain and loss
1. The body gains water though metabolic activities in all reactions that has
products of water. This is metabolic water constitutes about 200mL in a day.

2. Then there is preformed water in the food we eat (700mL) and then water that we
drink. (1600mL). The total of preformed and metabolic water is about 2500mL.

3. We lose water from urine (1500mL), feaces (200mL), breathing (300mL), sweat
(100mL) and cutaneous transpiration (400) – water that diffuses through the
epidermis and evaporates.

4. However, water loss or gain is influenced by a variety of factors such as weather

conditions, daily activities, work load etc.

5. Water loss through breathing is referred to as insensible water loss because we

are unaware of it.

6. Sensible water loss is noticeable such as urine and prolonged sweating.

7. Obligatory water loss is unavoidable output and includes both sensible and
insensible and even dehydrated people cannot avoid it.
 Fluid deficiency
Dehydration
1. This is when the body eliminates more water than sodium thus increasing the
ECF osmolarity.

2. It is caused mainly by lack of drinking water, diabetes mellitus, ADH hypo-

secretion, profuse sweating amongst others.

3. Dehydration affects all the fluid compartments and the serious effect of fluid
deficiency is circulatory shock and possible coma.

Volume depletion
1. Otherwise known as hypovolemia occurs when significant amounts of both
water and sodium are lost without replacement.

2. It occurs when there is for example chronic vomiting, chronic diarrhoea and
severe burns.

3. It can also be due to Addison’s disease, where there is inadequate sodium and
water reabsorption by the kidneys.
 Thirst and water intake
1. The desire to take in fluids is dependent on how thirsty the person is.
Once our output exceeds our intake, the extracellular fluid volume is
reduced leading to a reduction of blood volume.

2. Decrease in blood volume will lead to increase plasma osmolality, which

leads to decreased venous return and decreased cardiac output which in
turn decreases arterial blood pressure. Thus the blood pressure will fall.

3. The increased plasma osmolality is detected by the osmoreceptors in the

hypothalamus, which then activates the renin-angiotensin II aldosterone
system (RAAS), which is a powerful thirst stimulant

4. In addition, the osmoreceptors stimulate the production of anti-diuretic

hormone (ADH), which promotes water conservation.

5. Furthermore salivation is reduced to give the dry feeling in the mouth and
hence increases the desire to drink.
1. The satiation of thirst is finally achieved when water is absorbed from the
small intestine to increase blood volume and lower plasma osmolarity.

2. If there is no food in the stomach, then it takes between 5-10mins from

drinking to absorption

3. It takes more time after drinking to when there is food in the stomach (30-
45mins), however the cooling and moistening of the mouth is an initial
step satisfies the thirst.

4. Secondly, distension of the stomach and later small intestine is another

contributor to the satiation of thirst.

5. Lastly, the absorption of water into the bloodstream will eventually reduce
the thirst pangs.

6. It is thus better to drink cold water if available than warm water after
prolong thirst as it cools and moistens the mouth better and reduces
desire.
 Dehydration
Dehydration
Increased blood Reduced blood
osmolarity pressure

Renin

Angiotensin II

Stimulation of Stimulation of
osmoreceptors osmoreceptors
Thirst
Reduced salivation

Dry mouth

Sense of thirst

Ingestion of
water Distends
stomach and Short term
Cools and inhibition of thirst
Rehydration moistens mouth
intestines

Long term inhibition

Rehydrates blood
of thirst
 Fluid excess & sequestration
Fluid excess
1. Not so common as the kidneys does a good job of excreting more dilute urine.

2. It occurs when there is renal failure.

3. It can either be excess water over sodium (water intoxication) or volume

excess where both water and sodium are retained in excess.

Fluid sequestration
1. In this case, excess fluid accumulate in a particular location of the body.

2. Examples are oedema – abnormal accumulation in the interstitial spaces,

haemorrhage – where blood pools and clots in certain tissues

3. With haemorrhage, total body water may be normal but blood volume could
drop and result in circulatory shock.
 Hormonal regulation of water output
Vasopressin
o One way to control water loss is to regulate urine volume by the kidneys. The
kidneys however cannot prevent water loss or replace lost water, but can slow
down the loss processes in response to hormonal action.

o One such hormone is vasopressin, also known as anti-diuretic hormone (ADH). It

is synthesized in the hypothalamus and travels through nerve axons to the
posterior pituitary, where they are stored.

o Increased blood osmolality stimulates the release of ADH. The main biological
activity of vasopressin in response to decreased blood volume or increased [Na],
is to stimulate the resorption of water filtered by the kidney resulting in the
concentration of urine.

o At the distal tubes of the kidneys, ADH increases permeability of the tubules to
water by binding to receptors on the plasma membrane leading to activation of
adenylyl cyclase and therefore the cAMP signal transduction pathway which
eventually increases the permeability of the tubule to water.

o The signal leads to the regulation of proteins called aquaporins which serve as
water channels that allow water to be reabsorbed by moving down the
concentration gradient thereby restoring of plasma osmolality
o Overproduction of vasopressin results in the syndrome of inappropriate
antidiuretic hormone (SIADH). It can be caused by head trauma, tuberculosis,
or more likely ectopic production of ADH by tumours and several drugs.

o SIADH manifests with expansion of body fluids and dilution of electrolytes

such as sodium, potassium and chlorides. There is also reduced serum
osmolality and inability to produce dilute urine.

o When plasma sodium concentration and osmolality falls below 110mEq/L and
240mOsm ([Na] ~140mEq/L; osmolality of 290-295 mOsm), the patient may
develop seizures, and further lowering can lead to eventual death.

o Lack/loss of vasopressin production leads to diabetes insipidus where

patients drink large volumes of water and consequently excrete large
volumes of dilute urine (10-20L a day).

o This condition is either hereditary or caused by tumours or masses in the

hypothalamus, trauma or infections.
A 41 year old woman who had an head accident two weeks ago complains of
excessive thirst (drinks 5 gallons of water a day). She also urinates large volumes
every hour. On physical examination, she was well developed, coherent with her
surroundings and had a temperature of 38.5ºC (37ºC).

Lab examination showed plasma sodium, chloride and osmolality levels of

151mEq/L, 108mEq/L and 302mOsm respectively. [138-145mEq/L, 95-105mEq/L
and 290-295mOsm respectively]. Her blood sugar level and kidney tests were
normal.

1.Describe briefly three abnormalities that can cause excessive urination. (1 mark
each)
2.From the information given above, what will be your diagnosis? (1 mark)
3.How did you arrive at such diagnosis mentioning two medical conditions that
can be ruled out? (3 marks each)
4.How can this condition be treated? (1 mark)
 Excessive urination can be cause by

i. Diabetes insipidus – Absence of vasopressin leading to inability to re-

absorb water in the distal renal tubules so there is excretion of large
amounts of dilute urine.
ii. Diabetes mellitus – high glucose in the blood that exceeds the renal
absorption capacity, so it is excreted in the urine and to maintain
isotonicity is excreted with a large amount of water (polyuria)
iii. Kidney disease, medication such as diuretics and kidney damage from
say sickle cell anaemia
iv. Renal resistance - lack of response by the kidneys cells to presence of
hormones such as vasopressin.
v. Psychogenic water intoxication – a psychological condition where
patients compulsively drink excessive amounts of water that could be
fatal due to severe hyponatremia.
 Diabetes insipidus

 One can easily exclude kidney disease on the basis of the normal kidney test.
One can also exclude diabetes mellitus on the basis of the normal blood
glucose. We are left with diabetes insipidus and water intoxication. One of the
causes of diabetic insipidus is a head trauma which can damage part of the
pituitary responsible for synthesis of vasopressin. She recently experienced a
head trauma. Her plasma osmolality, sodium and chloride levels are elevated
are high, characteristic observation with the condition. These plasma levels
will be lowered if she was suffering psychogenic polydipsia. She also did not
show any signs of psychological disorder (coherent). She most likely has
diabetes insipidus secondary to the head trauma.

 Diabetes insipidus in this case can be treated by administering intranasal

vasopressin (desmopressin), since the head trauma most likely resulted in the
inability to produce vasopressin. Within one hour, there should be signs of
normalization of the plasma levels due to normal concentration of the urine
and subsequent reduction in the polydipsia and polyuria.
 Electrolytes
1. Electrolytes are ions capable of carrying an electric charge and are
classified as anions or cations.

2. The majority cations are Na+, K+ and Ca2+ ions and anions are Cl- , HCO3- and
PO42-.

3. Ions participate in many metabolic reactions, determine electrical potential

across cell membranes, affect osmolarity and distribution of body fluids.

4. Some specific examples include volume and osmotic regulation (Na, K, Cl);
myocardial rhythm and contractility (K, Mg, Ca); blood coagulation (Ca, Mg),
amongst others.

5. All functions involving electrolytes require the concentrations to be held

within narrow ranges, so just like water, the body uses complex
mechanisms to monitor and maintain concentration of electrolytes.

6. Blood is the most accessible for fluid measurements so concentrations are

given with respect to blood, and normal plasma electrolyte is 300mOsm/L
 Electrolyte Imbalance
In the body, electrolytes dissolve in water and separate into positively and negatively
charged ions.

If for some reason (i) the electrolytes become deficient, (ii) there is no proper
exchange of the ions between ICF and ECF or (iii) the control systems fail to regulate
the concentrations within narrow ranges, then we have electrolyte imbalance.

Electrolyte imbalance can be caused by

Loss of body fluids from prolonged vomiting, diarrhea, sweating

Malnutrition even though they are required in small quantities
Malabsorption – Inability to absorb these electrolytes due to stomach disorders
Acid base imbalances
Hormonal or endocrine disorders
Kidney disease
Drugs and other medications

The symptoms from this imbalance varies. For example altered sodium, potassium
or calcium levels may cause muscle spasm, weakness, twitching, or convulsions
amongst others.
 Sodium
1. Sodium is the most abundant cation in the ECF representing 90% of all
extracellular cations and largely determines the osmolality of the plasma.
Normal plasma levels are between 135 – 145 mmol/L.

2. Whilst sodium is concentrated in the ECF, potassium is concentrated in

the ICF. Natural diffusion should cause equilibrium in these two fluids.

3. However, to maintain this separation, the Na-K ATPase pump exchanges 3

sodium ions for 2 potassium ions whilst ATP is converted to ADP.

4. Since water follows sodium, its continuous removal from the cell prevents
osmotic rapture of cells. Sodium is thus the most significant solute in
determining total body water and distribution.

5. Sodium serves as one of the principal ions responsible for formation and
maintaining the plasma membrane potential and its gradient provides
energy for co-transport of other solutes.
 Sodium imbalance
1. The plasma sodium concentration depends on water levels in the body
obtained (i) in response to thirst (ii) retention of water due to ADH release
and (iii) blood volume status which affects sodium excretion.

2. Hyponatremia is when blood levels fall below 130mmol/L. It is more as a

result of increased water imbalance, increased water retention, increased
sweating with fast replacement by drinking rather than sodium loss.

3. Normally hyponatremia is quickly resolved by excretion of excess water or

replacement of sodium slowly in normal cases.

4. Hypernatremia results from excessive loss of water relative to sodium loss,

decreased water intake or increased sodium intake or retention such as
intravenous saline.

5. Its major consequences are water retention, hypertension and oedema.

6. Cases greater than 145mmol/L are serious and correction should be done
slowly at say 0.5mmol/L.
 Sodium and blood pressure
1. Adults need only 0.5g of sodium a day and we typically eat about 3-7g sodium
daily thus putting pressure on the kidneys for excretion.

2. Water and sodium go together so where there is sodium, water will move
towards that direction so high sodium means high water retention and
therefore higher amount of fluid circulating in the body.

3. This increases the pressure on the blood vessels especially the delicate blood
vessels to the kidneys resulting in some kidney damage.

4. The arteries in order to cope with the high blood pressure have their walls
becoming stronger and thicker reducing the inner diameter causing a further
increase in BP.

5. The heart then has to work harder to pump blood to all areas in addition to
possible damage to the arteries to the heart.

6. Eventually some of the arteries to the brain may be affected and less than
normal blood will reach the brain reducing nutrients and oxygen to the brain.
 Hospital-acquired hyponatremia
 Severe hyponatremia (<120mmol/L) is the most common electrolyte
abnormality among hospitalized individuals especially elderly individuals
and children due to hypotonic intravenous fluids.

 Death or brain damage may range from 50 – 83% and it is related to

cerebral oedema, increased intracranial pressure and cerebral
hypoxemia.

 Symptoms include seizures, respiratory arrest, coma and finally death.

 Frequent monitoring of the elderly and kids is a must when symptoms

appear and early treatment normally improves outcomes.
 Potassium
1. This is the major cation of the ICF and therefore the determinant of
intracellular osmolality and cell volume.

2. Since many reactions require low ECF concentration of potassium, only

2% of body’s total potassium circulates in plasma. Thus blood levels of
potassium is between 3.4 – 5.0 mmol/L.

3. Potassium functions include regulation of (i) neuromuscular excitability,

(ii) contraction of the cardiac muscles, (iii) a co-factor for protein
synthesis and (iv) maintenance the ICF volume.

4. Potassium is also important to the Na-K ATPase pump and functions in

co-transporting and thermogenesis.

5. It is also critical for many biochemical cellular reactions including protein

synthesis and thermogenesis.
 Regulation of potassium
1. Factors that influence potassium distribution between cells and ECF include
(i) inhibition of the Na-K ATPase pump (ii) β-blockers which impair cellular
entry and (iii) exercise causes the release of potassium due to repetitive
action potentials and loss from sweat.

2. Potassium imbalances are the most dangerous of all electrolyte imbalances

as it helps with nerve function, muscle contraction including cardiac
muscles and movement of materials into and out of cells.

3. Hyperkalemia (> 5.5mEq/L) may result from increased intake, decreased

renal excretion (renal failure) and cellular shift during injuries. Treatment
should be initiated immediately when potassium levels increase to greater
the 6.0mmol/L.

4. It can also arise quickly from crush injuries or from haemolytic anaemia
where large amounts are released from raptured cells.

5. In the hospitals the greatest risk of causing hyperkalemia is stored

intravenous blood as potassium leaks from the cells into the plasma during
storage.
 Elevated potassium means more remain in the cell thereby decreases
resting membrane potential to threshold especially of the cardiac muscles.
This lowers the threshold and increases cell excitability leading to muscle
weakness, paralysis, arrhythmia and heart stoppage.

 For lethal injections, sodium thiopental is used to induce unconsciousness,

pancuronium bromide (Pavulon) to cause muscle paralysis and respiratory
arrest, and potassium chloride to stop the heart

 Slow rise in potassium from aldosterone hyposecretion or renal failure is

also bad as nerve and muscle become less excitable due to longer times for
repolarization
 Hypokalemia
1. Hypokalemia (<3.5mmol/L), is not really from diet but can occur in people
with depressed appetite.

2. Common causes of hypokalemia are heavy sweating, vomiting and

diarrhoea for GI and diuretic and nephritis for urinary and aldosterone
hypersecretion. Alkalosis and insulin overdose may induce the cellular shift.

3. As potassium level drops the body become more sensitive to effects by

sodium.

4. Furthermore if more potassium moves from ICF to ECF, this loss makes the
cells hyperpolarized and nerves and muscles become less excitable.
resulting in muscle weakness and cramping, paralysis, constipation and
arrhythmia leading to cessation of heart contraction.

5. Treatment includes oral or intravenous replacement over several days or

foods with high potassium content such as cereals, bananas and fruits.
 Hormonal regulation of sodium and potassium
 The hormonal regulation of both potassium and sodium homeostasis are
closely linked and is performed by the kidneys.

 The controlling of the cations and its effects on blood pressure and osmolality
are coordinated by aldosterone, antidiuretic hormone and natriuretic peptides.

 Decreased blood volume, hyponatremia and hyperkalemia stimulates the

renin-angiotensin-aldosterone system (RAAS) to secrete renin from pro-renin.

 Stimulated renin catalyzes conversion of angiotensinogen to angiotensin I.

Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II.
Angiotensin II causes vasoconstriction which increases blood pressure and
also stimulates the secretion of aldosterone - the salt retaining hormone.

 Aldosterone activates transcription of Na-K pumps and this causes the DCT to
absorb more sodium and excrete more potassium. Water and chloride ions
follow sodium so there is increase in blood volume and therefore BP.
 Angiotensin II also constrict small arteries, and these two effects raises the
blood pressure and volume. With elevated blood pressure, RAAS is inhibited
and almost no sodium is reabsorbed.

 When the atria of the heart are stretched due to increased blood volume,
cardiac cells release atrial natriuretic hormone (ANH), which inhibits the
secretion of renin and therefore aldosterone to reduce the blood pressure.

 ANH also inhibits ADH production so the kidneys eliminate more sodium
and water with a resultant lowering of the blood pressure.

 ACE inhibitors or angiotensin receptor blockers (ARBs) e.g. losartan are

used in treating high blood pressure. They block angiotensin II resulting in
less or no aldosterone production, vasodilation and subsequently
decreased BP.
 Chloride ions
1. This is the major anion of the ECF and therefore its determinant of
extracellular osmolality. Normal values range between 95 – 110mEq/L.
Chloride ions shift secondarily to movement or bicarbonate ions.

2. Chloride ions are required for the formation of HCl in the stomach for
proper functioning of stomach enzymes.

3. Chloride ions are used in the haemoglobin buffering system to maintain

electroneutrality by exchanging for bicarbonates when the RBCs become
too alkaline

4. Together with bicarbonates, it is also an essential component for the

determination of the anion gap, as they offset the cations charges

5. Chlorides ingested are almost completely absorbed in the intestinal tract,

filtered at glomerulus and passively reabsorbed in conjunction with
sodium at the proximal tubules. Excess chloride is excreted in the urine
and sweat.
 Homeostasis of chloride ions
1. Chloride ions are strongly attracted to sodium so chloride homeostasis
depends on sodium – as sodium is maintained or excreted, chloride ions
passively follow. It is also partially attracted to potassium and calcium
ions

2. Hyperchloremia (>110mEq/L) may occur when there is hypernatremia

and also when there is kidney failure or kidney disorders, diabetes and
certain drugs. It can also result form dietary excess or from intravenous
saline or through excessive loss of bicarbonate ions from the GI.

3. Hypochloremia may occur from excessive vomiting, diabetic

ketoacidosis or aldosterone deficiency.

4. Hypochloremia can also be as a result of hyperkalemia or hyponatremia

where the excretion of sodium is accompanied by chloride ions.
 Calcium ions
1. Calcium was first found to be essential for myocardial contraction and thus
maintaining calcium to near normal concentration was necessary for survival.

2. Calcium was then later found to have other functions including activating the
sliding mechanism of muscle contraction and providing strength to bones.

3. Calcium also serves as a secondary messenger during signal transduction of

certain hormones, plays a role in communication among neurons, and is
involved in blood clotting and as a cofactor for many enzymes.

4. The adult body contains about 1100g of calcium and 99% are in the bones. The
bone reserves of calcium serve (i) as a stable form of calcium which is
converted to hydroxyapatite and not available (ii) exchangeable calcium, of
which only 1-5% is easily released so technically is also not available.

5. Calcium concentration in blood is about 9.2 - 10.4mg/dL. About 45% of this

circulates as free calcium in the blood (ionized calcium), another 40% is bound
to proteins mainly albumin, and the remaining 15% is bound to anions and
proteins.
 Homeostasis of calcium ions
1. Cells maintain very low intracellular concentrations of calcium due to
the presence of high phosphate ions which the body needs.

2. High calcium and phosphates will lead to the formation of calcium

phosphate crystals, which will precipitate.

3. Cells therefore pump out calcium ions and keep it at a low intracellular
concentration, or better still sequester it into the ER/SR stores.

4. Within these stores, the protein calsequestrin binds to calcium ions in

these stores and render them chemically unreactive and release it only
when needed.

5. Three hormones – parathyroid hormones (PTH), calcitriol and calcitonin

regulate calcium by altering their secretions in response to changes in
ionized calcium.
 Parathyroid hormone (PTH)
 PTH is secreted by the parathyroid gland when there is a decrease in ionized
calcium in order to raise blood calcium.

 In the bone, PTH binds to receptors on the oesteoblasts, which releases a

chemical messenger called RANKL. RANKL raises oesteoclasts numbers,
which then activates a process known as bone resorption where oesteoclasts
break down bone and release calcium from bone.

 Since it is involved in bone resorption, PTH reduces osteoblast activity and

inhibits bone deposition.

 In the kidneys, PTH conserves calcium by increasing tubular reabsorption of

the calcium ions.

 PTH also promotes the final steps in the production of active calcitriol.

 PTH also promotes more phosphate excretion to prevent hydroxyapatite

formation and therefore less bone deposition.
 Calcitriol and
 Calcitriol calcitonin
increases calcium absorption in the intestine and enhances the
effect of PTH on bone resorption.

 Calcitriol weakly promotes the reabsorption of calcium ions by the kidneys.

 In addition to absorption, calcitriol is also necessary for bone deposition.

Without it, the levels of calcium in the blood are either too low for- or cannot
position- normal deposition.

 This net effect of the absence of calcitriol is reduced deposition and softness
of bones leading to rickets in children and oesteomalacia in adults.

 Calcitonin is secreted by the thyroid gland and is very active in children. It is

released when blood calcium levels rises too high. It lowers the concentration
of calcium by

 Oesteoblast stimulation – so calcium can be incorporated into the skeleton.

 Oesteoclast inhibition - so that they liberate less calcium from the bones
 Causes of hypocalcemia
o Reduced or absence of PTH - serum calcium levels are not properly regulated.
Bones tend to hang on to its storage pool and the kidney increases excretion
of calcium.

o PTH is also necessary for normal production of vitamin D. Lack of vitamin D

leads to a decreased calcium absorption from the intestines.

o Hypomagnesemia which is common in hospitalized patients due to increased

tissue depletion causes hypocalcemia by (i) inhibiting the secretion of PTH, (ii)
impairs PTH action in bones and (iii) inducing vitamin D resistance.

o Other known causes are vitamin D deficiency, hypoalbuminemia and renal

disease.

o Hypocalcemia occurs in critically ill patients suffering from sepsis and burns.
These patients have losses of protein and albumin and abnormalities of acid-
base regulation.

o Pregnancy and lactating put women at risk because of demand to synthesize

milk and the formation of the foetal skeleton.
o Rhabdomyolysis as with major crash injury and muscle damage may causes
hypocalcemia due to increased release of phosphates which binds to the
calcium ions.

o Surgery and intensive care – Because appropriate calcium concentrations

promote good cardiac output and maintain adequate blood pressure,
controlling and maintaining calcium concentrations is important for heart
operations and transplants.

o In addition such patients receive large amounts of electrolytes which can

generate discrepancies between total and ionized calcium so ionized
measurements should be closely monitored.
 Hypocalcemia - Symptoms and effects
 Hypocalcemia (7.5mg/dL) causes excessive excitability of the nervous system
and leads to tremours, spasms or tetany – inability of muscles cells to relax.
With the cardiac system, symptoms include arrhythmia (fast or slow).

 Calcium normally binds to and neutralize negative charged groups on cell

surface, contributing to the membrane potential charge difference.

 With hypocalcemia the charge difference changes so sodium ions can enter
freely. Inflow of sodium ions is necessary for nerve excitement and muscle
contraction.

 In hypocalcemia, this excitation is excessive and results in convulsions,

tetany and other symptoms

 At very low concentrations e.g. 5mg/dL, the muscles of the larynx contracts
tightly (laryngospasm), which can shut off airflow and cause suffocation.
 In treating hypocalcemia, oral and parenteral calcium therapy can be given
depending on severity and cause. Vitamin D can also be added to increase
absorption and phosphate must be reduced in the diet.

 If the hypocalcemia is secondary to hypomagnesemia, the magnesium

therapy should be provided.
 Hypercalcemia
1. Hypercalcemia occurs when calcium concentrations exceed 11.5mg/dL,
and primary hyperparathyroidism is the main cause of excess calcium.

2. Excessive binding to cell surface anions will again change the charge
difference making sodium channels less responsive, therefore muscle
cells are less excitable.

3. Hypercalcemia can thus cause muscle weakness, sluggish reflexes,

cardiac arrest, depression of the nervous system and emotional
disturbances.

4. Impaired renal function occurs and kidney stones form as precipitates of

calcium salts.

5. With treatment, when renal function is normal, oral phosphate

administration may be effective. Also intravenous administration of large
amounts of normal saline will enhance renal excretion of calcium.
 Phosphates
1. The average adult has about 800g of phosphorus of which 90% is in the
bones. It is thus an intracellular ion.

2. Phosphorus occurs in two principal forms – the dihydrogen phosphates

(H2PO4) and the monohydrogen phosphates (HPO4).

3. Phosphate are common components of nucleic acids as phosphodiesters

and in phospholipids of cell membranes and as inorganic phosphates.

4. They are also components of the most important reservoirs of energy

including ATP, GTP, creatine phosphate etc.

5. Phosphates activate many metabolic pathways by phosphorylating enzymes

and most coenzymes are also esters of phosphoric acids.

6. They are also buffers in acid-base balances to maintain a constant pH.

 Phosphate homeostasis
1. The average diet provides enough phosphates and excess phosphates
are excreted by the kidneys. The kidneys can also reabsorb phosphates
if necessary.

2. Plasma concentrations range between 3.5-4mg/dL and exists

predominantly as an intracellular anion.

3. PTH increases excretion of phosphates in order to increase

concentration of free calcium ions by reducing the formation of calcium
phosphates.

4. Phosphate regulation is not tight as the body tolerates wide changes,

however loss of regulation by the kidneys has the most profound effect.

5. Unless there is severe hypophosphatemia, administration of phosphate

salts is dangerous. Rather strict monitoring is recommended.
 Hypophosphatemia
1. Hypophosphatemia occurs in about 1-5% of hospitalized patients and
increases to about 30% in patients with diabetic ketoacidosis, chronic
obstructive pulmonary disorder (COPD), alcoholism, etc. It increase further
to 50% in ICU patients with sepsis.

2. It can also be caused by increased renal excretion (hyperparathyroidism),

decreased intestinal absorption as with Vitamin D deficiency or magnesium
and aluminum containing antacid use and long term alcohol abuse.

3. The consequences of phosphate deficiency include reduced capacity of

oxygen transport by RBCs (2,3-diphosphoglycerate) and disturbed energy
metabolism (ATP).

4. There are also associated leukocyte and platelet dysfunction leading to a

greater risk of infection and blood-clotting impairment and possible
haemorrhage.

5. Muscle weakness that may lead to respiratory failure, convulsion and coma
may develop with severe hypophosphatemia.
 Hyperphosphatemia
1. Patients with the greatest risk for hyperphosphatemia are those with chronic
renal failure with significant loss of glomerular filtration.

2. Then also, exogenous or endogenous addition of phosphorus to the ECF or

an increased intake of phosphates may cause hyperphosphatemia.

3. Cell destruction by any means or chemotherapeutic treatment can release

large amounts of phosphates into the serum.

4. High serum levels of phosphates reduce serum calcium levels and this may
induce the symptoms of hypocalcemia especially tetany.

5. Hyperphosphatemia also promotes the deposition of increased amounts of

calcium and phosphates into bone and soft tissues.

6. In severe forms, calcification of soft tissue occurs in lungs, kidneys and

joints.
 Magnesium
1. Magnesium is the fourth most abundant cation and the second most abundant
intracellular ion in the body.

2. The average human contains 24g of magnesium with about 50% stored in bones,
46% in the muscles and other cells and the rest in the serum.

3. Of this serum, 30% is bound to plasma proteins (albumin), 60% in the free or
ionized form and 5% complexed with other ions such as phosphates and
citrates.

4. Magnesium is an essential co-factor of more than 300 enzymes involved in

glycolysis, neuromuscular transmission etc.

5. There is a strong relationship between abnormal serum magnesium levels and

cardiovascular, metabolic and neuromuscular disorders.

6. The overall regulation of magnesium is by the kidney which can reabsorb or

excrete in deficiency and overload states respectively.

7. Normal levels range from 1.5 – 2.4mEq/L.

 Hypomagnesemia
1. This is observed in hospitalized individuals with severe illness due to overall
tissue depletion.

2. Other causes are due to reduced intake (poor diet, starvation, chronic
alcoholism) and decreased absorption (vomiting, diarrhoea, malaborption
syndrome).

3. More causes are due to increased excretion either from renal (tubular
disorders), endocrine hormones (hyperparathyroid, hyperaldosterone) or drug
induced (antibiotics, diuretics).

4. Hypomagnesemia may result in cardiovascular and neuromuscular

abnormalities due to ATPase enzyme’s requirement for Mg. A faulty Na-K
pump will change RMP, increase excitability and cardiac arrhythmias.

5. Patients with hypokalemia, hyponatremia, hypocalcemia and

hypophosphatemia are also hypomagnesemic. Mg deficiency impairs PTH and
Mg therapy can restore these conditions.

6. Treatment includes oral intake of Mg lactate, chloride or oxide. In severe cases

Mg sulphate parenterally is recommended.
 Hypermagnesemia
1. This is less frequent and the most common cause is renal failure and becomes
severe due to decreased renal function and increased intake of Mg containing
medications e.g. antacids and enemas.

2. Other hormonal disorders such as thyroxine and growth hormone deficiency

decrease tubular reabsorption.

3. Symptoms associated are cardiovascular changes such hypotension or in

severe cases life threatening situations such as heart block, respiratory
arrest , paralysis and coma.

4. In addition, there are associated neuromuscular, metabolic and neurological

abnormalities.

5. Treatment includes reducing intake and in severe cases supportive therapy for
cardiac, respiratory and neuromuscular abnormalities.
 Electrolytes and renal function
 Phosphate reabsorption is inhibited by PTH and increased calcitriol.

 Calcium is absorbed under the influence of PTH and calcitriol. Calcitonin

stimulates excretion of calcium.

 Magnesium absorption occurs largely in the ascending limp of Henle.

 Sodium reabsorption occurs through (i) 70% is absorbed in the proximal

tubules. (ii) Na ions can also be absorbed in exchange for hydrogen ions, a
reaction linked to acid based disorders

 Stimulated by aldosterone, sodium ions are reabsorbed in exchange for

potassium ions in the distal tubules. Hydrogen ions competes with potassium
ions for this exchange.

 Chloride is reabsorbed in part, by passive transport in proximal tubule along

the concentration gradient created by sodium ions.
 Electrolytes and renal function
 Potassium is reabsorbed by (i) active reabsorption in the proximal tubule to
conserve potassium ions and (ii) exchange with sodium ions is stimulated by
aldosterone. Hydrogen ions competes with potassium ions for this exchange.

 Bicarbonate is recovered from the glomerular filtrate and converted to CO 2

when hydrogen ions is excreted in the urine.

 With varying concentrations of ADH, an osmotic gradient is created that

enables water reabsorption to be increased or decreased in response to body
fluid changes.
Distribution of electrolytes in body compartments
ECF (mEq/L) ICF (mEq/L)
Cations
Sodium 142 10
Potassium 5 156
Calcium 5 4
Magnesium 2 26
Totals 154 196
Anions
Bicarbonates 24 12
Chlorides 104 4
Phosphates 2 40 - 95
Proteins 18 54
Other anions 8 31 - 86
Totals 154 196 (average)
 When kidney breaks down
 End stage renal disease occurs when kidney function declines to less than 10%
of normal.

 Kidneys can fail due to diabetes, chronic high blood pressure, bacteria or viral
infection, exposure to drugs and poisons. As kidney function drops, waste
metabolic products from proteins build up in the blood.

 This uremic toxicity causes electrolyte imbalance, nausea, vomiting and

diarrhoea, which affects the mental state and impairs blood clotting.

 A dialysis machine is required in end stage renal failure as it adjusts solutes

selectively to restore proper solute balances. In haemodialysis, the machine is
connected to the vein or artery . As blood flows through the tubes, waste
diffuses out and salts, glucose and other vital substances diffuse in.

 In peritoneal dialysis, fluid of suitable composition is pumped into the patient’s

abdominal cavity and later drained out.

 Kidney stones are hard deposits formed from uric acids, calcium and other
waste. They settle out of the fluids and collect in the renal pelvis by becoming
lodged in the ureter or urethra and must be broken up or surgically removed.
Question 1
ADH binds to receptors on distal tubes and collecting ducts making them ____________
permeable to __________ .

a. More; water
b. Less; water
c. More; sodium
d. Less; sodium

Question 2

Which of these is not an effect of PTH

a. Rise in blood phosphate level

b. Reduction of calcium excretion
c. Increased number of oeteoclasts
d. Increased calcitriol synthesis
Question 3
Calcitriol is made from

a. calcitonin
b. 7-dehyrocholesterol
c. hydroxyapatite
d. PTH

Question 4
What is the second major intracellular cation

a. calcium
b. magnesium
c. sodium
d. potassium
Question 5
Osmolality can be defined as a measure of the concentration of a solution based on the

a. Number of ionic particles present

b. Number and size of dissolved particles
c. Number of dissolved particles
d. Density of the dissolved particles

Question 6
Hyperchloremia is most likely to result in

a. alkalosis
b. acidosis
c. hypernatremia
d. hypovolemia
a, a, b, a, d, b