RMU Session 7 - Diagnostic Support and EBM

Session VII
Diagnostic support and

Evidence Based Medicines
(EBM)
SESSION OBJECTIVES
By the end of this session, students should be able to:
• Cite reference ranges for biomedical and haematological parameters
• Interpret clinical lab results
The normal range must always be used with caution since it
takes little account of an individual’s age, sex, weight,
height, muscle mass or disease state and many of which can
influence the value obtained.
Reference ranges are valuable guides but must not be used as
sole indicators of health and disease.
A single test value can rarely be interpreted. A series of
values are usually required to ensure clinical relevance and
elimination of errors caused by spoiled specimens or
interference from diagnostic or therapeutic procedures .
10/27/2021 3
IMPORTANCE OF LABORATORY DATA TO SUPPORT
DIAGNOSIS AND CLINICAL FOLLOW UP.
Reference ranges for biomedical and haematological

parameters are important guides to health and disease
status.
A series of values, as opposed to a single test value, are
usually required to ensure clinical relevance and
eliminate erroneous values due to sample collection or
analysis.
Medicine therapy can induce a wide range of abnormal
biochemical results.
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• Medicine-induced hypernatraemia is often the result of a
nephrogenic diabetes insipidus-like syndrome caused by
medicines such as lithium, demeclocycline and phenytoin
• Inappropriate secretion of antidiuretic hormone underpins
many medicine-induced hyponatraemias
• Medicine-induced hypokalaemia can be caused by:
• Trans-cellular movement of potassium into the cells, e.g.
salbutamol, insulin
• Loss from the gastrointestinal tract e.g. Laxative abuse,
• Loss from the kidney due to mineralocorticoid excess e.g.
corticosteroid,
• Increased amount of sodium delivered and available for
reabsorption at the distal convoluted tubule e.g. diuretics.
10/27/2021 5
• Medicine-induced hyperkalaemia may arise due to:
• excessive intake of potassium, e.g. parenteral
infusions,
• decreased elimination of potassium e.g. angiotensin-
converting enzyme inhibitors,
• shift of potassium from cells into the extracellular
fluid, e.g. digoxin in acute overdose.
Serum creatinine provides a more accurate assessment of
renal function than urea because unlike urea, it is not
elevated following high protein intake, hypercatabolic
states or a gastrointestinal bleed.
10/27/2021 6
Through the body , there are a wide variety of enzymes in
cells that are released following insult and can be
measured in serum to provide valuable diagnostic
information.
The haematology profile is an important part of the
screening and investigation of all inpatients
10/27/2021 7
Clearance = UxV/Px
• Where,
– Ux = urine concentration of x (mg/dL)
– Px = plasma concentration of x (mg/dL)
– V = urine output (mL/min)
Relationship of clearance to GFR
• In a steady state, for a substance handled

only by the kidneys that is neither
reabsorbed nor secreted:
– Amount filtered = amount excreted
– GFR  Px = Ux  V
– GFR = UxV/Px
• Thus, the clearance of a substance that is
neither reabsorbed nor secreted is equal to
GFR
Relationship of clearance to GFR
• If X is neither reabsorbed nor secreted,

clearance = GFR
• If X is reabsorbed, clearance < GFR
• If X is secreted, clearance > GFR
Inulin clearance
• Inulin is a polymer of fructose that

meets all of the criteria for the ideal
substance to measure GFR
• Inulin clearance is the “gold standard”
for GFR determination
• Inulin must be continuously infused
into the animal to achieve a steady
state concentration in plasma
Creatinine clearance
• Creatinine is produced endogenously at a
constant rate
• It is not metabolized
• It is excreted by the kidneys by glomerular
filtration
• It is neither reabsorbed nor secreted by the
renal tubules
• Creatinine clearance can be used to estimate
GFR
Endogenous creatinine clearance
• Requirements:
– Accurately timed collection of urine
– Body weight
– Serum and urine creatinine concentrations
• Normal = 2 to 5 ml/min/kg
• Underestimates GFR (compared to inulin
clearance) due to non-creatinine chromagens
in blood (Px increased)
Exogenous creatinine clearance
• Serum creatinine increased 10-fold by

administration of creatinine
• Minimizes effect of non-creatinine
chromagens
• More closely approximates inulin
clearance
• Technically more difficult than
endogenous creatinine clearance
Anemia
Definition of anemia
• Anemia-values of hemoglobin, hematocrit or
RBC counts which are more than 2 standard
deviations below the mean
– HGB<13.5 g/dL (men) <12 (women)
– HCT<41% (men) <36 (women)
DIAGNOSIS OF ANEMIA
CLASSIFICATION OF ANEMIAS
 Anemias may be classified morphologically based on the
average size of the cells and the hemoglobin
concentration into:
 Macrocytic
 Normochromic, normocytic
 Hypochromic, microcytic
MORPHOLOGICAL CLASSIFICATION OF ANEMIAS
MACROCYTIC ANEMIAS
NORMOCHROMIC, NORMOCYTIC ANEMIAS
HYPOCHROMIC, MICROCYTIC ANEMIAS
FUNCTIONAL CLASSIFICATION OF ANEMIAS
 Anemias may also be classified functionally into:

 Hypoproliferative (when there is a proliferation defect)
 Ineffective (when there is a maturation defect)
 Hemolytic (when there is a survival defect)
FUNCTIONAL CLASSIFICATION OF ANEMIAS
Lab tests of iron deficiency of
increased severity
NORMAL Fe Fe Fe
deficiency deficiency deficiency
Without With mild With severe
anemia anemia anemia
Serum Iron 60-150 60-150 <60 <40
Iron Binding 300-360 300-390 350-400 >410

Capacity
Saturation 20-50 30 <15 <10
Hemoglobin Normal Normal 9-12 6-7
Serum 40-200 <20 <10 0-10

Ferritin
BIOCHEMICAL DATA: TYPICAL NORMAL ADULT REFERENCE VALUES
(SI UNITS) MEASURED IN SERUM
Laboratory test Reference range

ALBUMIN 35-55g/l
CALCIUM 2.20-2.55 mmol/L
CREATININE 50-120 mol/L
GLUCOSE FASTING 3.3-6.7 mmol/L
GLUCOSE NON FASTING 10.0 mmol/L
OSMOLARITY 282-295 mOsml/L
POTASSIUM 3.5- 5.0 mmol/L
SODIUM 135-145 mmol/L
UREA 3.0-6.5 mmol/L
URIC ACID 0.15-0.47 mmol/L
10/27/2021 25
LABORATORY TESTS
NORMAL VALUES
BLOOD COUNT MALE FEMALE
Haematocrit 40-54% 37-47%

Haemoglobin 13-18g/100ml 12-16g/100ml
Red cell count 4.5- 6.5 4.0-6.0 million/mm3
million/mm3
White cell count 4000-11000/mm3 4000-11000/mm3
10/27/2021 26
ENZYMES DATA: TYPICAL NORMAL ADULT REFERENCE VALUES
(CONVENTIONAL UNITS) IN SERUM
Laboratory test Reference range

Acid phosphatase 0.5-11 units/L
Alanine transaminase 0.35 units/L
Alkaline phosphatase 25-100 units/L
Aspartate transaminase 0-35 units/L
Creatine kinase 0-105 units/L
Lactate dehydrogenase 50-190 units/L
10/27/2021 27
Undesirable lipid levels
• HDL less than 40 mg/dl (1.04 mmol/L) in
men; less than 50 mg/dl (1.3 mmol) in
women
• Triglycerides greater than 150 mg/dl (1.70
mmol/L)(New AHA guidelines say 100 mg/dL)
• Think diabetes or hypothyroidism with the
above lipid profile
• Draw a FBS or HbA1C and a TSH
Diagnosis of diabetes
Interpretation of the glucose tolerance test
A 75 gram Oral Glucose Tolerance Test (OGTT) is used to
follow up people with equivocal results who may have
diabetes, Impaired Fasting Glucose (IFG) or Impaired
Glucose Tolerance (IGT).
Fasting 2 hours post load

mmol/L mmol/L
Normal < 5.5 and < 7.8

IFG 6.1 – 6.9 and < 7.8
IGT < 7.0 and 7.8 – 11.0
Diabetes mellitus ≥ 7.0 and/or ≥ 11.1
GDM ≥ 5.5 and/or ≥ 9.0
Diagnosis of diabetes, IGT and IFG

Gestational diabetes mellitus
Gestational Diabetes Mellitus (GDM) increases the risk of many
foetal and maternal complications in pregnancy and the
development of type 2 diabetes later in life (Kjos, 1999).
Screening is currently recommended for all women between 24 -
28 weeks gestation.
Screening for GDM using 50 gram load
If the one hour blood glucose is ≥ 7.8 mmol/L, a two hour OGTT
is performed.
OGTT for diagnosis of GDM
A fasting glucose ≥ 5.5 and/or a 2 hour value ≥ 9.0 mmol/L is
diagnostic of GDM.
Laboratory tests to prevent and delay
complications of diabetes
People with diabetes usually die Parameter Optimal value
from macrovascular complications of
their diabetes; namely cardiovascular Total
disease. This is influenced by all of cholesterol
< 4 mmol/L
the commonly recognised risk factors

for cardiovascular disease as well as LDL cholesterol < 2.5 mmol/L
glycaemic control. Fasting lipid levels
are measured three monthly until HDL cholesterol > 1 mmol/L
stable and then 6 - 12 monthly TC:HDL ratio < 4.5

thereafter.
Triglycerides < 1.7 mmol/L
It is important that management
should be individualised HbA1C < 7 mmol/L
Recommendations: Glycemic, Blood Pressure, Lipid
Control in Adults
A1C <7.0%*
Blood pressure <130/80 mmHg†
Lipids
LDL cholesterol <100 mg/dl (<2.6 mmol/l)‡
*More or less stringent glycemic goals may be appropriate for individual patients. Goals should be
individualized based on: duration of diabetes, age/life expectancy, comorbid conditions, known CVD or
advanced microvascular complications, hypoglycemia unawareness, and individual patient
considerations.
†Based on patient characteristics and response to therapy, higher or lower systolic blood pressure
targets may be appropriate.
‡In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l), using a high
dose of statin, is an option.
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S31. Table 12.
Summary
Summary
HEMATOLOGY TEST RESULTS
Total Lympocyte Count

Normal = 1200-1800 cells/mm 3
Moderate PCM = 800-1200

Severe PCM = < 800
SODIUM DISTRIBUTION
The body of an average 70kg man contains approximately

3000 mmol of sodium. 70% of this sodium is freely
exchangeable while the remaining is complexed in bone.
Most of the exchangeable sodium is extracellular, and
results are in a normal serum range of 135-145 mmol/L.
10/27/2021 37
TYPICAL DAILY WATER BALANCE FOR A HEALTHY 70KG ADULT
TYPE INPUT(ML) LOCATION OUTPUT(ML)
ORAL FLUIDS 1400 URINE 1500
FOOD 700 LUNG 400
METABOLIC 400 SKIN 400

OXIDATION
FAECES 200
TOTAL 2500 2500
10/27/2021 38
SYNTHESIS QUESTIONS
1. Give two consequences of non adherence
2. Give three strategies to enhance adherence
3. How are medicines use monitoring and evaluation
done
4. List 5 categories of medicines with high risk for
irrational medicine use
5. List 5 risks associated with each category of
medicines with high risk for irrational medicine use.
6. List the four categories of patients with high risk for
irrational medicine use
7. Describe the strategies to promote RMU
SYNTHESIS QUESTIONS
8. List 5 factors that influence rational use of medicines
9. Define polypharmacy;
10.Give 3 of the consequences of poly-pharmacy
11. List different types of polypharmacy;
12.Distinguish between side effects and adverse drug
reactions;
13.Propose solutions to polypharmacy problems
14.List harmful medicines interactions
15. Cite reference ranges for biomedical and haematological
parameters

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Session VII

Diagnostic support and

Reference ranges for biomedical and haematological

• In a steady state, for a substance handled

• If X is neither reabsorbed nor secreted,

• Inulin is a polymer of fructose that

• Serum creatinine increased 10-fold by

 Anemias may also be classified functionally into:

Iron Binding 300-360 300-390 350-400 >410

Hemoglobin Normal Normal 9-12 6-7

Serum 40-200 <20 <10 0-10

Laboratory test Reference range

Haematocrit 40-54% 37-47%

Laboratory test Reference range

Fasting 2 hours post load

Normal < 5.5 and < 7.8

Diagnosis of diabetes, IGT and IFG

the commonly recognised risk factors

stable and then 6 - 12 monthly TC:HDL ratio < 4.5

Blood pressure <130/80 mmHg†

Total Lympocyte Count

Moderate PCM = 800-1200

The body of an average 70kg man contains approximately

TYPE INPUT(ML) LOCATION OUTPUT(ML)

ORAL FLUIDS 1400 URINE 1500

FOOD 700 LUNG 400

METABOLIC 400 SKIN 400

TOTAL 2500 2500

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