ACID-BASE BALANCE DISORDERS

AND CALCIUM AND PHOSPHATE

BY
PROF. IDOGUN E.S
(MB.Ch.B, MSc,MWCP, MPH, FMCpath)
PROFESSOR OF CHEMICAL PATHOLOGY
DEPARTMENT OF CHEMICAL PATHOLOGY
COLLEGE OF MEDICINE,
UNIVERSITY OF BENIN.
Introduction

 ‘’Homeostasis is necessary for

maintenance of cell
vitality’’
 Welcome to Acid-base balance /
H+ Homeostasis.
OBJECTIVES

 1. What are acids and bases?

 2. H+ generation in the body
 3. Maintenance of H+ homeostasis
 4. Disorders of acid-base balance.
ACID-BASE CONTROL

 Definition: An acid is defined as a

substance that releases protons or
hydrogen ions (H+).
 A base is defined as a substance
that accepts protons or H+.
CHARACTERISTIC OF ACID AND BASE

 A strong acid has little affinity for H+

and so readily dissociates,
whereas a weak acid has strong
affinity for H+ and thus less readily
dissociates .
 A strong base has high affinity for H+
and a weak base has low affinity for
H+.
BUFFERING

 Is a process by which a strong acid

(base) is replaced by a weaker one,
with consequent reduction in the
number of free hydrogen ions and
therefore the change in pH, after
addition of acid is less than would be
in the absence of the buffer.
 H+Cl- + NaHCo3 - H2Co3 +
NaCl
(weak acid) (Neutral salt)
PH

 PH is a measure of hydrogen ion activity. It

is log10 of the reciprocal of the hydrogen
ion concentration (H+) in mol/L.
 The log10 of a number is the power to
which the number must be raised to
produce the number.
 PH expresses the acidity or alkalinity of a
solution, 7.0 is the neutral point.
 PH is –log10C, where C is H+
concentration in moles per litre
WEAK ACID AND CONJUGATE BASE

Physiological examples of a weak

acid and its conjugate base are
carbonic acid (H2CO3) and
bicarbonate (HCO3). The equilibrium
reaction is as follows;
H2CO3 – H+ HCO3-
This equilibrium lies to the right at
physiological pH because
bicarbonate, the conjugate base, has
a weak affinity for hydrogen.
PHYSIOLOGICAL BUFFERS

 Normal human whole blood is

buffered at a slightly alkaline pH in a
range of 7.35 to 7.45, which
corresponds to H+ concentration of
4.5 x 10-8 M to 3.5 to 10-8 M.
Buffering capacity depends on the
concentration of the buffer and the
relationship between the pKa of the
buffer and the desired pH.
pKa and buffering
capacity
 A buffer is considered most effective within
+ or – 2 pH units of its pKa. It has maximum
buffering capacity when its pKa equals the
pH. For maximum blood buffering the pKa of
the buffers should therefore be near
physiological pH, that is, pH7.4
 (pka value is one method used to indicate
the strenght of an acid, it is the negative
base -10 logarithm of the acid dissociation
constant(ka) of a solution, the lower the pka
value, the stronger the acid eg AC =4.8,
LA=3.8)
EXAMPLES OF BLOOD BUFFERS

 The physiological important buffers

that maintain this narrow pH range
observed in the body are
haemoglobin, bicarbonate,
phosphate and proteins.
TABLE 1

 physiological important buffers and

their concentration, pKa and
buffering capacity.
 Buffer Pka Conc(mmol/L
Buff. Cap
 Bicarb 6.33 25
1.0
 Haemogl 7.2 53
40
 Phosphate 6.8 1.2
Bicarbonate buffer system

 The Henderson-Hasselbalch equation

for the bicarbonate-carbonic acid
buffer system is as follows:
 pH =pKa + log [HCO3-]
RATIO 20:1

 This 20:1 ratio is maintained

primarily by the lungs, which expel
CO2 produced during the
metabolism of nutrients.
HYDROGEN ION HOMEOSTASIS

 About 50 – 100 millimoles of

hydrogen ions are released from the
cells into extracellular fluid each day.
Despite the fluctuations in the rate
release throughout the day , due to
varying loads, the extracellular
hydrogen ion concentration (H+) is
maintained between 35 – 45
nanomol/L (40nmol/L =pH 7.40).
SECRETION OF H+

 control of hydrogen ion balance

depends ultimately on the secretion
of H+ from the body, mainly into the
urine. Renal impairment causes
acidosis.
SOURCES OF H+ IN THE BODY

 Dietary and metabolic sources of

acids and bases.
 Two types of acids are dealt with in
physiological states: fixed acids and
volatile acids. Fixed acids are non
gaseous acids such as phosphate
(HPO42-) and sulfate (HSO4-) ions or
organic acids such as lactic acid,
acetoacetic acid and beta-
hydroxybutyric acid.
Volatile Acids

 Physiological important volatile acid

is carbonic acid (H2CO3). The
volatility of carbonic acid arises from
its ability to dissociates into water
and carbon dioxide (CO2), which can
be released a gas. The reaction
scheme for carbonic acid is as
follows:
 CO2(gas) – CO2 (dissolved) +H20 =
H2C03 == H+ + HCO3
H+ CONTROL SYSTEMS

 Acid-base balance:
 The maintenance of a constant pH is
important because changes in pH will
alter the functioning of enzymes, and
minerals, the conformation of
biological structural components and
the uptake and release of oxygen.
 Parameters
NEUTRALIZATION OF Fixed
Acid
 In the body, physiological buffers act
to maintain a constant pH in the
following manner. Fixed acids enter
into the body and are immediately
neutralized by the bicarbonate
buffering system.
 H+A- (fixed acid) + HCO3- - H2CO3
+ A-
 (unmeasured anions) H2O + CO2
Neutralization of
volatile Acids:
 However, the volatile acid CO2 is
neutralized by the haemoglobin
buffering system, because all the
buffering system are at equilibrium
with each other. It is this overall
equilibrium that gives the blood the
relative buffering capacities.
Volatile Acids and Change
in PH:
 Changes in respiratory rate will alter
the bicarbonate-carbonic acid ratio
and pH. A decrease in the ventilation
rate will cause a decrease in release
of CO2 from the blood in the lungs.
The increased blood CO2 will result
in the formation of more carbonic
acid and the release of H+.
Ventilation and PH
Changes
 If the ventilation rate increases ,
more CO2 is released from the blood
by the lungs and the bicarbonate –
carbonic acid ratio and pH increase.
Ventilation and PH
Changes
 Thus, when the rate of ventilation is
increased, excess acid in the form of
CO2 is quickly removed. Similarly,
when the rate of ventilation is
decreased, acid (CO2) is added to
neutralize excess alkali (HCO3-).
Hemoglobin Buffer

 The other important blood buffer,

hemoglobin, which is vital for the
regulation of blood pH, buffers the
CO2 from the tissues. The major
function of hemoglobin is the
transport of oxygen through the
blood to the cells of the body.
Hemoglobin Buffer

 Oxygenated hemoglobin is
transported in the blood to cells that
have relatively low PO2 tension and
are releasing metabolic products,
such as CO2 and organic acids, into
the blood, thus raising PCO2 and
TCO2 and lowering the pH.
Oxygen and HbO2

 The relatively low PO2 causes

dissociation of O2 from HbO2 and
the consequent delivery of O2 to the
cells. The high CO2 pressure in the
cells drives the CO2 along a
concentration gradient into the red
cells. Carbonic anhydrase rapidly
converts the CO2 into H+ and HCO3.
Deoxygenated Hemoglobin

 Deoxygenated hemoglobin is a
weaker acid than oxygenated
hemoglobin. It neutralizes the H+ to
raise the pH causes the dissociation
reaction of carbonic acid to proceed
to the right
Summary of buffer systems of the body

 1. Respiratory cells/lungs
 2. Phosphate buffers – plasma,
erythrocytes and urine
 3. RBC buffering system
 4. Plasma proteins
 5. Kidney regulation.
ACID-BASE
DISORDERS:Definitions
 When the pH of the blood is less than
the reference range, the imbalance is
term acidaemia. When the pH is
greater than the reference range, the
imbalance is termed alkalaemia.
Acidosis and Alkalosis

 Respiratory acidosis or alkalosis is

due to primarily respiratory
component.
Metabolic Acidosis

 Metabolic acidosis or alkalosis is due

to a change in the bicarbonate level,
renal or metabolic function.
Mixed Disorders

 Mixed disorders can occur.

COMPENSATORY MECHANISMS

 If the imbalance is of a non

respiratory origin, the body will
compensate by altering of
ventilation. For disturbances of the
respiratory component, the kidneys
will compensate by selectively
excreting or re-absorbing anions and
cations.
ACIDOSIS

 1. Respiratory acidosis
 2. Metabolic acidosis
Metabolic Acidosis

 In metabolic acidosis, there is

decrease in bicarbonate (less than
24 mmol/L) resulting in a decrease
pH –pH is low and ratio is less than
20:1
CAUSES OF METABOLIC ACIDOSIS

 Diabetic Keto Acidosis

 Ingestion of ammonium chloride or
calcium chloride
 Renal Tubular Acidosis
 Diarrhoea
 Fistula
 Acute renal failure e.t.c
 Chronic renal failure
COMPENSATION OF METABOLIC ACIDOSIS

 Is through hyper ventilation, blowing

off CO2.
 Secondary compensation is by the
kidneys retaining more bicarbonate.
RESPIRATORY ACIDOSIS

 A decrease in the rate of alveolar

ventilation, (hypoventilation).
CAUSES OF RESPIRATORY ACIDOSIS

 Lung diseases(bronchial asthma)

 Emphysema
 Pneumonia

 Drug e.g barbiturates, morphines,

alcohol
 Asphyxiation/aspiration
 Congestive Cardiac Failure
COMPENSATION-Respiratory
Acidosis
 For primary respiratory acidosis, the
compensation occurs through
metabolic processes. The kidneys
increase the excretion of H+ and the
reabsorption of bicarbonate ions, till
pH returns to normal.
ALKALOSIS

 1. Respiratory
 2. Metabolic
 Metabolic Alkalosis- is due to a gain
in bicarbonate causing an increase in
the pH.
 pH > 20
CAUSES 0F METABOLIC
ALKALOSIS
 Administration f sodium bicarbonate
 Sodium lactate ingestion, citrate or
acetate
 Excess loss of acid through vomiting,
 Nasogastric suction
 Diuretics that excrete H+
COMPENSATION IN METABOLIC ALKALOSIS

 The body responds by depressing the

respiratory centre. The resulting
hypoventilation increases the
retention of CO2.
RESPIRATORY ALKALOSIS

 Is from an increased rate of alveolar

ventilation causes excessive
elimination of CO2 by the lungs. E.g
excitement, crying, shouting
 Over ventilation(manual or
mechanical)
 pH > 20
CAUSES 0F RESP. ALKALOSIS

 Chemical stimulation of the

respiratory center e.g salicylates
 Increase temperature
 Fever, hysteria, pulmonary embolism
COMPENSATION OF RESP. ALKALOSIS

 The kidneys compensate by

excreting bicarbonate and retaining
H+
OUTLINE

 Calcium Distribution and Function

 Calcium and Phosphorus
Homeostasis
 Disorders of Calcium
 Phosphate Distribution and Function
 Disorders of Phosphate
 Magnesium Distribution and Function
 Disorders of Magnesium
CALCIUM

 Calcium is the the most prevalent cation in

the body.
 An average human body contains about 1
kg, or ≈25 mol, of calcium , ≈99% of
which resides in the skeleton,
predominantly as extracellular crystals of
unknown structure and a composition
approaching that of hydroxyapatite
[Ca10(PO4)6(OH)2].
 Soft tissues and extracellular fluid contain
about 1% of the body’s calcium.
CALCIUM

 The bone calcium content is rapidly

exchangeable with the extracellular
fluid (ECF) whenever it is necessary
to maintain balance.
 Total ECF calcium content is about
22mmol/L and about 9mmol of that
is in the plasma.
CALCIUM

 Calcium exists in the blood as:

 Free (ionized) calcium ; the
physiologically active
45%
 Protein bound calcium (80% to
albumin and 20% to globulin)
45%
 Complex with small diffusible anions:
citrate, lactate PO₄, HCO₃
10%
CALCIUM: Effects of blood
PH,low plasma Albumin
 The reference interval of plasma total calcium is 2.1 –
2.55 mmol/L
 A 1g/L difference in plasma albumin of 40g/L produces
a corresponding difference of 0.02 mmol/L of total
plasma calcium.
 Because calcium binds to negatively charged sites on
proteins, its binding is pH dependent.
 Alkalosis leads to an increase in negative charge and
binding and a decrease in free calcium; conversely,
acidosis leads to a decrease in negative charge and
binding and an increase in free calcium.
 In vitro, for each 0.1 unit change in pH, approximately
0.2 mg/Dl (0.05 mmol/L) of inverse change occurs in
the serum free calcium concentration.
CALCIUM requirements

 An average adult requires about 25mmol/L

calcium daily; up to 30mmol/L is required
during pregnancy, lactation and growth in
children.
 A balance is maintained between dietary
intake and loss through the urine, faeces and
sweat.
 The active metabolite of vitamin D,1,25-
dihydroxycholecalciferol (1,25-(OH)2D3, also
called calcitriol) stimulates the production of
calcium-binding protein , thus promoting the
absorption of calcium in the jejunum.
FUNCTIONS OF CALCIUM

FUNCTION EXAMPLE
Neuromuscular Control of excitability
Release of neurotransmitters
Initiation of muscle contraction

Structural Main component of bone and teeth

Signaling Has hormonal functions in that it acts as an

intracellular second messenger

Enzymatic Coenzymes for coagulation factors

CALCIUM AND PHOSPHORUS HOMEOSTASIS

 Normal serum calcium concentration

is maintained within a very narrow
range by a balance between the
intestinal tract, bone and the
kidneys.
 Calcium homeostasis follows the
general rule that extracellular
concentrations are controlled rather
than the total body content.
CALCIUM AND PHOSPHORUS HOMEOSTASIS

 The hormonal regulators of calcium

and phosphorus include:
 Parathyroid Hormone
 Vitamin D
 Calcitonin
PARATHYROID HORMONE

 Parathyroid hormone (PTH) is a single-

chain polypeptide containing 84 residues,
with its 34 N-terminal amino acids largely
determining its biological activity.
 It is metabolized by renal, hepatic and
bone cells.
 The secretion of parathyroid hormone is
controlled by the blood level of ionized
calcium in a simple negative feed-back
loop.
PARATHYROID HORMONE

 The biological actions of PTH include:

 1.Bone: stimulation of osteoclastic bone
resorption, so releasing both free ionized
calcium and phosphate into the ECF; this
action increases the plasma concentrations
of both calcium and phosphate,
 2.Kidneys: stimulates reabsorption of
calcium and the excretion of phosphate;
this action tends to increase the plasma
calcium concentration but to decrease the
phosphate.
VITAMIN D

 Vitamin D acts on the

 1. Gut: stimulates the absorption of calcium
and phosphate independently against a
concentration gradient.
 2. Kidney: stimulates the action of
parathyroid hormone on calcium and
phosphate retention
 3. Bone: the number and activity of the
osteoclasts, with parathyroid hormone to
mobilise calcium and phosphate from bone.

 CALCITONIN
 Calcitonin is synthesized by the parafollicular
(C) cells of the thyroid gland. It is also
produced in the pituitary gland, the
gastrointestinal tract and the liver.
 The secretion of calcitonin is regulated by the
level of ionized calcium in the blood; it
increases with the level of ionized calcium and
decreases when serum ionized calcium is low.
 Gastrin promotes the secretion of calcitonin;
hence pentagastrin stimulation is used as a
provocative test for the secretion of calcitonin.
CALCITONIN

 Action of calcitonin:
 Calcitonin inhibits osteoclastic bone
resorption, producing a decrease in
serum calcium and phosphate.
DISORDERS OF CALCIUM METABOLISM

 HYPERCALCEMIA
 Causes of Hypercalcemia include:
 Malignancy :
 Bony metastases, e.g. breast, lung, prostate, kidney,thyroid
 Solid tumours with humoral effects
 Haematological tumours, e.g. multiple myeloma and leukemia
which invade the bone and cause bone resorption
 Parathyroid hormone abnormalities :
 Primary hyperparathyroidism (adenoma, hyperplasia, carcinoma
or associated with multiple endocrine
 neoplasia)Tertiary hyperparathyroidism ,Lithium-induced
hyperparathyroidism
 High bone turnover :
 Thyrotoxicosis
 Immobilization, e.g. with Paget’s disease
Causes of Hypercalcemia
 High levels of vitamin D :
 Vitamin D toxicity
 Granulomatous disease, e.g. sarcoidosis, tuberculosis
 Drugs :
 Thiazides (reduced renal calcium excretion)
 Vitamin A toxicity
 Milk–alkali syndrome
 Familial hypocalciuric hypercalcaemia
 Other endocrine causes :
 Adrenal insuffi ciency
 Acromegaly
 Rarer causes :
 Williams’ syndrome
 Human immunodefi ciency virus (HIV) infection
 Leprosy
 Histoplasmosis
 Berylliosis
CLINICAL FEATURES OF HYPERCALCEMIA

 Weakness, tiredness, lassitude and

muscle weakness.
 Generalized bone demineralization
 Mental changes ranging from depression
and impaired concentration to psychosis
and coma.
 Nausea, vomiting,
constipation ,anorexia, peptic ulceration
abdominal pain.
 Polyuria , dehydration, thirst
CLINICAL FEATURES OF HYPERCALCEMIA

 Urolithiasis,
 nephrocalcinosis and renal colic
 Hypertension.
 Cardiac arrythmias, hypertension,
Shortening of QT interval and
broadening of T waves
TREATMENT OF HYPERCALCEMIA

 Mild cases of hypercalcemia require no treatment.

Treat moderate to severe cases as follows:
 Give adequate hydration
 Increase salt intake: increased sodium and
calcium excretion results
 Forced diuresis with frusemide
 Give bisphosphonate e.g etidronate or
pamidronate. These analogues of pyrophosphate
get into the bones and inhibit osteoclastic action
 Admnistration of calcitonin decreases skeletal
release of calcium, phosphate and
hydroxyproline; it acts within 10 minutes.
TREATMENT OF HYPERCALCEMIA

 Picamycin given intravenously is useful in

acute cases. It inhibits bone resorption.
Gallium nitrate also inhibits bone resorption
and alters the structure of bone crystals.
Glucocorticoids decrease intestinal absorption
and increase urinary excretion of calcium.
 Dialysis: if there is renal failure
 Phosphate therapy in primary
hyperparathyroidism
 Surgical removal of the primary malignancy or
adenoma
HYPOCALCEMIA

 Causes of Hypocalcemia includes:

 Drugs and chemicals
 Furosemide
 Enzyme-inducing drugs, e.g. phenytoin
 Ethylene glycol poisoning (rare)
 Causes of hypocalcaemia usually with
hypophosphataemia
 Vitamin D deficiency
 Rickets in children, Osteomalacia in adults due to:
 Decreased exposure to sunlight
 Decreased intake or Malabsorption
 Alterd metabolism of Vitamin D
 Decreased renal synthesis of calcitriol due to defect in renal 1α
hydroxylase activity; this is type1 rickets.
 Defective cytosolic receptors for calcitriol; this is type 2 rickets
Causes of Hypocalcemia
 Parathyroid abnormalities, manifesting as hypocalcaemia
usually with
 hyperphosphataemia
 Hypoparathyrodism (low parathyroid hormone levels)
 Idiopathic or autoimmune
 Surgical removal of parathyroid glands
 Congenital absence of parathyroid glands, e.g. DiGeorge’s
syndrome
 Infiltration of parathyroids, e.g. tumours,
 haemochromatosis
 Pseudohypoparathyroidism (rare)
 Parathyroid hormone (PTH) resistance (raised PTH levels)
 Chronic kidney disease
 Calcitonin/overzealous therapy for hypercalcemia using
mythriamycin.
 Decreased calcium intake or malabsorbtion
Causes of Hypocalcemia

 Miscellaneous causes of hypocalcaemia

 Acute pancreatitis: fatty acid/calcium
complex precipitate in the pancreas.
 Hypomagnesaemia and
hyperphosphatasemia give rise to
hypocalcemia.
 Sepsis
 Rhabdomyolysis
 Severe hypomagnesaemia
 Autosomal dominant hypercalciuric
hypocalcaemia
CLINICAL FEATURES OF HYPOCALCEMIA

 Increased neuromuscular activity:

tetany, carpopedal spasm and
muscle pain.
 Positive Chvotstek’s and Trousseau’s
signs
 Depression and other psychiatry
symptoms
 ECG changes: arrhythmias and
pronloged QT interval.
TREATMENT
 No treatment is indicated PTH is stimulated in cases
of mild hypocalcemia but PTH is stimulated
 Calcium and Vitamin D: chronic hyperthyroidism,
chronic renal failure, hereditary defects in vitamin D
metabolism
 Calcium supplements: postoperative hypocalcemia
with tetany
 Calciferol: Long term hypocalcemia
 Oral aluminium hydroxide to bind the calcium, then
administer vitamin D with caution and continuous
monitoring in asymptomatic hypocalcemia with
hyperphosphataemia
 Intravenous calcium gluconate: severe hypocalcemia
PHOSPHATE

 Phosphate is a divalent anion, approximately 80

per cent of which is found in the bony skeleton
and 20 per cent is distributed in the soft tissues
and muscle.
 Phosphate is the major intracellular anionand
shifts between the intracellular and extracellular
compartments.
 The inorganic fraction in the extracellular fluid
exists as mono and dihydrogen phosphates and
takes part in high-energy transfer reactions.
 At physiological pH the ration of the mono- to the
di- is about 4:1 the ratio decreases under acidic
conditions and increases under alkaline conditions.
PHOSPHATE
 The total body content is 20 to 22 mol (620- 630g) and
the plasma total phosphate is 3.9mmol/L; 0.83 –
1.3mmol/L of this is inorganic phosphate.
 There is diurnal variation; low in the morning and high at
night.
 The diurnal variation is abolished by fasting.
 Protein-rich food is a major source of phosphate intake, as
are cereals and nuts.
 The daily phosphate intake is about 30 mmol, with
approximately 80 per cent being absorbed in the jejunum.
 Absorption is passive except at low concentrations when
it is absorbed actively (vitamin D-dependent).
 It is reduced by ingestion of antacids, glucocorticoids and
in hypothyroidism.
PHOSPHATE

 The output is largely renal, with more

than 90 per cent being excreted by
this route.
 Most of the phosphate filtered at the
glomeruli is reabsorbed by the
proximal tubules.
 Gastrointestinal loss of phosphate
accounts for only 10 per cent of the
body’s phosphate excretion.
FUNCTIONS OF PHOSPHATE

 Phosphate is an important intracellular buffer as well as being

essential for buffering hydrogen ions in urine.
 It has a structural role as a component of phospholipids,
nucleoproteins and nucleic acids.
 Phosphate plays a central role in cellular metabolic pathways,
including glycolysis and oxidativephosphorylation. For
example, 2,3-diphosphoglycerate (2,3-DPG) , a by-product of
glycolysis regulate
 haemoglobin oxygen dissociation
 Participate in the formation of high energy bonds
 Phosphate also has a role in the optimal function of
leucocytes, for example chemotaxis and phagocytosis, and for
platelets in clot retraction.

HYPERPHOSPHATEMIA
 Causes of Hyperphosphatemia include:
 1. Acute kidney injury or chronic kidney disease
 2. Increased tissue breakdown
 3. Tumour lysis syndrome
 4. Malignant hyperpyrexia
 5. Crush injuries
 6. Acidaemia (metabolic or respiratory acidosis)
 7. Diabetic ketoacidosis
 8. Hypoparathyroidism
 9. Acromegaly
 10. Excess vitamin D intake
 11. Artefact due to in vitro haemolysis or old blood sample
 12. Inappropriately high phosphate intake, usually
intravenously
CLINICAL FEATURES

 Hypocalcemia and tetany

 Hypotension
 Increased level of 1,25
dihydroxycholecalciferol in prolonged
cases
 Soft tissue calcification in lungs,
myocardium and liver.
TREATMENT OF HYPERPHOSPHATEMIA

 Oral phosphate-binding agents, for example

magnesium hydroxide or calcium carbonate
 Magnesium or calcium containing antacids
 Saline infusion and diuretics must be given in severe
cases e.g tumour lysis
 Insulin and glucose infusion causes a shift of
phosphate into the cell
 Ensure good hydration to increase renal output
during chemotherapy
 Haemodialysis or peritoneal dialysis is indicated
when there is poor kidney function or persistent
hyperphosphatemia
HYPOPHOSPHATEMIA

 Cellular redistribution
 Intravenous glucose
 Alkalaemia (metabolic or respiratory alkalosis)
 Administration of insulin
 Refeeding syndrome
 Poor intake, e.g. total parenteral nutrition
 Malabsorption states
 Chronic alcoholism
 Post-trauma or myocardial infarction or
operation
 Renal tubular loss
 Isolated phosphate disorder
 Hypophosphataemic osteomalacia
 X-linked hypophosphataemia
 Oncogenic hypophosphataemia
 Paracetamol poisoning
 As part of Fanconi’s syndrome
 Miscellaneous:
 Liver disease
 Septicaemia
 Hyperparathyroidism or parathyroid hormone-
related peptide release
CLINICAL FEATURES

 Rhabdomyolysis
 Respiratory insufficiency
 Cardiomyopathy
 Anaemia, thrombocytopenia, impaired
clotting processes and reduced
 leucocyte function.
 CNS abnormalities: irritability,
confusion, seizures
TREATMENT

 Treat underlying cause :

 Measure arterial pH, PCO2, and PO2
 Give skimmed milk, contains 30mmol/L
phosphate
 Oral phosphate: effervescent phosphate
contains 16mmol/tablet
 Monitor serum phosphate to 0.3 mmol/L
 Give dipyridamole to reduce
hyperphosphaturia
 If hyperphosphatemia is mild and of short
duration, no treatment is needed.
MAGNESIUM

 Magnesium is predominately an intracellular

divalent cation, important for optimal cell function.
 It is an essential cofactor to many enzymes, as
well as being important for membrane function.
 The total magnesium content of a normal man is
0.3g/Kg body weight:
 Extracellular 1% ( 55% free, 30% associated with
proteins, especially albumin, 15% forms a complex
with phosphates, citrates and other forms)
 Intracellular 44%
 Bone 55%
MAGNESIUM

 The daily intake of magnesium in an adult is

15 to 25 mmol/day
 Recommended daily allowance of
magnesium for adults is about 4.5 mg/kg;
Rich dietary sources include cereal, nuts
and vegetables.
 Serum magnesium ranges between 0.7 to
1.1 mmol/L (1.70 to 2.70mg/ dL)
 The unbound diffusible fraction in plasma is
about 0.6 mmol/L (1.4 mg/dL)
MAGNESIUM

 Intracellular magnesium exists in two

forms:
 Fraction bound to organic
components: mainly to ATP
 Free fraction in equilibrium with the
free diffusible form in plasma
 When intracellular concentration of
ATP falls, magnesium diffuses out of
the cell into the plasma.
MAGNESIUM

 About 30 to 40% of dietary magnesium

is absorbed in the jejunum and ileum
but the large intestine may also be
important; unlike calcium, its
absorption is not vitamin D dependent.
 Absorption increases in magnesium
deficiency and it is aided by vitamin D.
 As much as 70 per cent of
magnesiumfrom dietary intake is not
absorbed but eliminated in the faeces.
MAGNESIUM

 The major excretory route is via the

kidneys, and about 65 per cent of
glomerular-filtered magnesium is
reabsorbed in the loop of Henle.
 Loop diuretics increase magnesium
excretion while distally acting
diuretics e.g amiloride and
chlorothiazide enhance magnesium
entry into cell
FUNCTIONS OF MAGNESIUM

 Serves as coenzymes for many enzymes in

metabolism e.g adenylate cyclase, creatinine
kinase and phosphofructokinase.
 Plays roles in oxidative phosphorylation,
glycolysis, cell replication, nucleotide
metabolism and protein biosynthesis.
 Stabilises nerves actions and influences the
release of neurotransmitters at nerve
junction.
 Forms part of the mineral lattice in bone.
DISORDERS OF MAGNESIUM

 HYPOMAGNESAEMIA
 Magnesium deficiency may be caused by:
 Deficient intake:
 Protein-energy malnutrition
 Total parenteral nutrition
 Excessive loss:
 Prolonged diarrhea
 Intestinal Fistulae
 Prolonged nasogastric sunction
 Drugs e.g gentamycin, cisplatin, cyclosporine, loop
diuretics e.g frusemide, ethacrynic acid; these
cause impaired renal reabsorption
Causes of Hypomagnesimia
 Renal loss:
 Renal magnesium transport defect
 Multiple dialysis
 Renal transplantation
 Osmotic diuresis (glucose, mannitol, urea)
 Endocrine:
 Hypoparathyroidism
 Hyperaldosteronis
 Batter’s syndrome
 Giltelman’s syndrome
 Diabetic ketoacidosis
Causes of Hypomagnesimia

 Hypokalaemia: magnesium moves in

and out of cells with potassium; this
could occur during diuretic therapy
or in hyperaldosteronism
 Chronic alcohol intake
 Neonatal primary hypomagnesaemia
CLINICAL FEATURES OF HYPOMAGNESAEMIA

 These include: nausea, vomiting,

anorexia, lethargy and general weakness
 In severe deficiency, there is
paraesthesia, muscular cramps,
irritability decreased attention and
mental confusion. The physical signs are
largely due to hypocalcemia and this
includes: positive Trousseau and
Chvostek’s signs. There may be tetany.
TREATMENT OF HYPOMAGNESAEMIA

 Treat underlying cause.

 In severe cases, intravenous
magnesium sulphate should be
given. It must not be given to
patients with renal dysfunction.
 Magnesium salts have been used as
adjuncts in the treatment of ashma,
acute myocardial infarction and
ventricular arrhythmias.
HYPERMAGNESAEMIA

 Renal glomerular dysfunction leading to magnesium retention

 Increased intake of magnesium e.g in the treatment of pre-
eclampsia.
 Intake of antacids containing magnesium in mild renal
dysfunction
 Release from injured muscle in rhabdomyolysis
 Adrenal insufficiency
 Hypermagnesaemia often occurs in benign hypocalciuric
hypercalcemia
 Drowning in a sea with high magnesium content e.g River
Jordan
 Dehydration
 Addison’s disease
CLINICAL FEATUREs

 These includes: nausea, facial

paraesthesia, sedation,
hypoventilation with respiratory
acidosis, decreased deep tendon
reflexes and muscle weakness.
 In severe cases, there may be
hypotension, diffuse vasodilation,
bradycardia, areflexia and coma.
TREATMENT OF HYPERMAGNESAEMIA

 Infuse calcium salts in severe cases;

the ions electrically oppose each
other at their sites of action.
 Promote renal magnesium excretion
with diuretics and saline infusion
 Haemodialysis
CONCLUSION

 Calcium, Phosphate and Magnesium

are essential for optimum body
physiology.
 Their metabolism are often related.
 Adequate measures should be taken
to ensure treatment when disorders
of calcium , phosphate and
magnesium occur.
REFERENCES
 1. Crook M. Clinical Biochemistry And Metabolic
Medicine. 8th ed. London: Holder Arnold; 2012
 2. Afonja O.A. Chemical Pathology and Metabolic
Medicine Teachers. 1st edition
 3.Bishop M.L., Fody E.P., Shoeff E.L., editors.
Clinical Chemistry Techniques Principles And
Correlations. 6th ed Baltimore: Lippincolt W & W.
2010
 4. Nduka N. Clinical Biochemistry for Students of
Pathology.1st ed Lagos: Longman; 1999
 5. Scott M.G, Gronowski A. M, Eby C.S., editors.
Tiez’s Applied Laboratory Medicine. 2nd ed. New
Jersey: John Wiley &Sons;2007
 N
IO
N T
TE
AT
UR
YO
R
FO
K S
A N