Download Clinical Biochemistry MDL 474

Clinical Biochemistry
MDL 474
Introduction
Assessment
Week
Assessment
Grade
4
Quiz 1
5
11
Quiz 2
10
7-8
Mid-term
20
14-15
Final Laboratory Exam
15
16-17
Final Exam
40
Laboratory attendance – 5 Marks
Laboratory continuous assessment – 5 Marks
Homeostasis
• Ability to maintain stable internal state.
Clinical biochemistry
• Branch of laboratory medicine in which
chemical and biochemical methods are
applied to the study of disease.
• Comprise over 1/3 of all hospital laboratory
investigations.
How biochemical tests are used?
Fluid and electrolyte balance
Fluid and electrolyte balance
• The major body constituent is
water.
• The body has two main fluid
compartments, the intracellular
fluid (ICF) and the extracellular
fluid (ECF, interstitial fluid and
plasma).
• The ICF is twice as large (~28 L)
as the ECF (14 L).
• Water retention will cause an
increase in the volume of both
ICF and ECF.
• Water loss (dehydration) will
result in a decreased volume of
both ICF and ECF.
•Sodium ions are the main ECF cations, anions are chloride and bicarbonate.
•Potassium ions are the main ICF cations, anion is phosphate (and proteins).
•The volume of the ECF and ICF are estimated from knowledge of the patient's
history and by clinical examination.
Concentration
• Ration of two variables (i.e amount of Na
(solute) and the amount of water).
• A concentration can change because either or
both variables have changed. For example, a
sodium concentration of 140 mmol/L may
become 130 mmol/L because the amount of
sodium in the solution has fallen or because
the amount of water has increased.
Osmolality
• Measurement of particles concentration in kg of
solvent.
• Body fluids vary greatly in their composition.
• However, while the concentration of substances
may vary in the different body fluids, the overall
number of solute particles, the osmolality, is
IDENTICAL.
• The osmolality of the ICF is normally the same as
the ECF.
• Osmotic pressure must
be the same at both
side of the semi-permeable
membrane
Determination of Osmolality
• Specimen: Serum or Urine.
• Na, K, Cl, and biocarbonate provide the largest
contribution to the osmolality value of serum.
• Plasma is not recommended because
osmotically active substances may be
introduced into the specimen from the
anticoagulant.
Determination of Osmolality
• Freezing point depression and vapor pressure
decrease are the most frequently used
methods of analysis.
• Sample must be free of particulate matter to
obtain accurate results.
• Turbid serum or urine samples should be
centrifuged before analysis.
Freezing point depression
Osmometers
• Used to measure the concentration of solute
particles in a solution.
Osmolal gap
• Is the difference between measured serum
osmolality and calculated serum osmolality.
• If this gap falls within an acceptable range,
then it is assumed that sodium, glucose, BUN
are indeed the major dissolved ions and
molecules in the serum. If, however, the
calculated gap is above an acceptable range,
then it is an indication that there is something
else dissolved in the serum.
Osmolal gap
• Increased in cases of
- Alcohol (ethanol intoxication, methanol
ingestion)
- Sugar (Mannitol and sorbitol)
- Lipid (hypertriglycaemia)
- Protein (Hypergammaglobinemia)
Osmolality disorders
• Increased urea in renal disease.
• Hyperglycemia in diabetes mellitus.
• The presence of ethanol or some other
ingested substances (methanol or ethylene
glycol).
Reference ranges for osmolality
Serum
275-295 mOsm/kg
Urine (24 h)
300-900 mOsm/kg
Urine/serum ratio
1.0 -3.0
Random urine
50-1200 mOsm/kg
Osmolal gap
5-10 mOsm/kg
Homework
• What is the difference between the oncotic
pressure and the hydrostatic pressure?
Water and sodium balance
• Failure to maintain ECF volume, with the
consequences of impaired blood circulation,
rapidly leads to tissue death due to lack of
oxygen and nutrients, and failure to remove
waste products.
Water balance
• Water intake largely
depends on social habits
and is very variable.
• Water loss is normally seen
as changes in the volume
of urine produced.
• Water excretion by the
kidney is tightly controlled
by the antidiuretic
hormone (ADH) or Arginine
vasopressin (AVP).
ADH and the regulation of osmolality
• Specialized cells in the
hypothalamus sense
differences between
their intracellular
osmolality and that of
the extracellular fluid,
and adjust the
secretion of ADH from
the posterior pituitary
gland.
• ADH causes water to
be retained by the
kidneys.
Sodium balance
• Most of the sodium is in
the ECF.
• The sodium concentration
is tightly regulated around
140 mmol/L.
• In disease, the
gastrointestinal tract is
often the major route of
sodium loss (infantile
diarrhoea may result in
death from salt and water
depletion.
Sodium balance the effect of
Aldosterone
• Decreases urinary Na
secretion.
• Increases Na re-absorption
in the renal tubules at the
expense of K and hydrogen
ions.
• Stimulate Na conservation
by the sweat glands and
the mucosal cells of the
colon.
• ECF volume is the major
stimulus to Aldosterone
secretion.
Sodium balance the effect of
Aldosterone Cont.
• Specialized cells in the
juxtaglomerular
apparatus of the
nephron, sense
decreases in the
blood pressure and
secrete renin, the first
step in a sequence of
events that leads to
the secretion of
aldosterone by the
glomerular zone of
the adrenal cortex.
Homework
• What is the effect of the Atrial natriuretic
peptide to sodium balance?
• A patient who has been vomiting and has
diarrhoea from a gastrointestinal infection. With
no intake?
- The patient becomes fluid depleted.
- Water and sodium have been lost.
- Because the ECF is low, aldosterone secretion is
high. Thus, as the patient begins to take fluids
orally, any salt ingested is maximally retained.
- As this raised the ECF osmolality, ADH action then
ensures that water is retained too.
- This aldosterone and ADH interaction continues
until ECF fluid volume and composition return to
normal.
Hyponatraemia
• Defined as a serum sodium concentration
below the reference intervals of 133-146
mmol/L.
• It is the electrolyte abnormality most
frequently encountered in clinical
biochemistry.
• Two causes:
- Water retention
- Sodium loss
1- Water retention
• Usually results from impaired water excretion,
and rarely from increased intake.
• Syndrome of inappropriate antidiuresis (SAID).
- Infection
- Malignancy
- Chest disease
- Trauma (including surgery)
- Drug-induced
SIAD
• Inappropriate secretion of ADH.
• ADH normal 0-5 pmol/L. in SAID up to 500
pmol/L.
• Non-osmotic stimuli including hypovolaemia
and/or hypotension, nausea, vomiting,
hypoglycemia, and pain determine the wide
spread of SIAD.
2- Sodium loss
• Sodium depletion occurs ONLY when there is
pathological sodium loss, either from the
gastrointestinal tract or in urine.
• Gastrointestinal losses: vomiting, diarrhoea,
patients with fistulae due to bowl disease.
• Urinary losses: mineralocorticoids deficiency
(aldosterone), drugs that antagonize
aldosterone (spironolactone).
Sodium loss
• Does sodium
concentration by itself
could provide
information about
presence or severity of
sodium depletion?
• Hyponatraemia
indicates that the ration
of sodium to water is
reduces.
3- Pseudohyponatraemia
• In patients with severe
hyperproteinaemia or
hyperlipidaemia.
• More protein or lipoprotein
and less water in plasma.
• Na and other electrolytes
distributed only in water.
• Normal Na concentration in
the plasma.
• Normal osmolality! And low • Assessed by osmolal
sodium concentration (110
gap?
mmol/L).
Hyponatraemia clinical examination
Oedema (Edema)
• Accumulation of fluid in the interstitial
compartment.
Treatment
• Increase sodium intake (sodium depleted
patients)
• Fluid restriction (normovolaemic and - likely
water retention).
• Oedematous patients should be given a
diuretic to induce natriuresis and be fluid
restricted.
• Severe cases (hypertonic solution).
Hypernatraemia
• Is an increase in the serum sodium
concentration above the reference interval of
133-146 mmol/L.
• Causes:
- Water loss
- Sodium gain
1- Water loss
• Decreases water intake in elderly patients.
Stop drinking voluntarily, or because of unable
to get something to drink – unconscious
patient after a stroke.
• Less common, Diabetes insipidus
- Failure of ADH secretion or action (Central)
- Renal tubules do not respond to ADH
(Nephrogenic).
2- Sodium gain
• Less common than water loss.
• Salt poisoning.
• High sodium bicarbonate intake is life-threatening
acidosis.
• Increase NaCl intake in infants.
• Conn’s syndrome: excess aldosterone secretion causes
increase Na retention by the renal tubules.
• Cushing’s syndrome: excess cortisol secretion (weak
mineralocorticoid activity).
• Na concentration in both cases is rarely above 150
mmol/L.
Clinical features
• Decrease skin turgor
because of dehydration.
Treatment
• Increase water intake. Intravenously, 5 %
dextrose. Not recommended with salt
poisoning patients ?
• Dehydration with sodium loss, sodium should
be administered.
• Salt poisoning can be managed by diuretics.
The End