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Aspek Laboratorium Usia Lanjut

Dr. dr. Nyoman Suci W, M.Kes, SpPK


Bagian Patologi Klinik FK UNDIP
2019
• Blood profiles in the elderly provide an
important addition to the underwriting
information obtained from the attending
physician and other sources.
• This is because clinical diagnosis is more
difficult in the elderly. Older patients often
give a poorer history concerning their health
and interpretation of physical signs is
sometimes less clear
• Multiple diseases may complicate the
diagnostic process and atypical presentations
of disease are especially common in old age.
• Elderly people with an undiagnosed
impairment may simply experience a gradual
decline in well-being whose features are no
more striking than deterioration in energy,
increasing frailty, and mild confusion or
memory impairment.
Laboratory aspects
• Pre-analytical factors
Pre-analytical factors
• When a patient in this age group seeks health
services, the first concern will be how to welcome
the patient. Clinicians should also treat the
physical facilities involved as a primary concern.
Each unit should be equipped with devices that
provide ease and comfort, ensuring the safety of
the patients.
• It is important to remember that in this age
group, difficulties with mobility, hearing, and
vision are not uncommon. Clinics should be
designed with these possible limitations in mind.
• The accessibility of the units should be developed
to the fullest. Handrails and grips at appropriate
heights should be available in corridors, collection
rooms, and bathrooms.
• Furthermore, toilet bowls should be set at
appropriate heights, and security handles
should be provided.
• The floor should be as uniform as possible,
with ample provision of ramps and non-slip
flooring, avoiding stairs and slopes.
• The visual and auditory signals must be clear
and prominent. Protocols should use large
letters for easy viewing
• The process of sample collection should go
beyond a collector well trained in the collection
technique.
• A tourniquet should be applied to the minimum
degree necessary, and extended use should be
avoided.
• When a tourniquet is applied for more than three
minutes, it can raise cholesterol by 5% and
aspartat aminotranferase (AST) by almost 10%.
• It is important to remember that patients of
this age have to be treated with respect and
care but not as children.
• Calmness and patience in this type of care are
essential.
• The clinical status of these patients may be
extremely variable. Their state depends not
only on the coexistence of multiple diseases,
but also on aspects related to treatment of
the patients past medical problems and to
how the patient has been followed.
• Therefore, trying to set standards in terms of
benchmarks and their consequences, such as
communication or panic levels, becomes a
complicated task.
• These patients also present with
polypharmacy. Drugs can interact with each
other not only in vivo, but also in vitro.
• Insisting on obtaining information about the
current drugs being used can solve many
problems related to treatment.
• Variations in clinical status are also affected by
genetic factors and aspects of body
composition.
• We know, for example, that levels of creatine
kinase (CK) enzyme are generally higher in
populations of African descent because
individuals in these populations have more
muscle mass.
• By contrast, white women have lower muscle
mass.
• Substances produced by the muscles (such as
CK and creatinine) may change
• Environmental factors also influence these
patients and the results of their laboratory tests.
Inpatients hospitalized for long periods or under
inappropriate conditions should be evaluated
carefully.
• Patients exposed to constant cold may have
increased thyroid-stimulating hormone (TSH)
and decreased thyroxine hormone (T4).
• Constant stress can alter corticotropin-releasing
hormone (CRH) , aldosterone, and renin.
Additionally, stress can also lower thyroid
hormones (TSH, triiodothyronine [T3] , and T4
• In immobilized patients (forced postures), the
plasma volume falls between 5% (on the first
day) and 8% (on the sixth day).
• Calcium, urea, and T4 rise, while cortisol and
metanephrine decrease.
• Diet is also an important consideration
because these patients often have chewing
and swallowing problems and, therefore, opt
for a diet with a higher proportion of
carbohydrates and fats.
• Malnutrition is common, and one study
showed that up to half of admitted patients
have low transferrin.
• The state of hydration must also be taken into
consideration, and adequate hydration should
be ensured.
• The circadian rhythm can also change, and
sleep disturbances are common.
• Cortisol, aldosterone (which depends on
movement), TSH, metanephrines, and peptide
C may be altered in the elderly.
• Even healthy habits can affect test results.
Exercise, for example, leads to higher protein
turnover and increases the levels of circulating
enzymes and stress hormones (cortisol,
metanephrines, aldosterone, B-type
natriuretic peptide [BNP]).
• However, it reduces cholesterol and
triglycerides.
Endocrine changes
• The most relevant changes are thyroid and
metabolic syndromes.
• Thyroid function remains stable, despite the
decrease in T3 due to reduced peripheral
conversion of T4 into T3. T4 remains stable
because reduced synthesis is offset by lower
clearance.
• There is an increase in the peripheral
resistance of these hormones, and this
resistance explains the fact that the TSH
remains within the reference range.
• Thyroid disorders are also common in this
population.
• Hypothyroidism appears in 4% of the
population, and it is present in subclinical
form in 5%.
• Approximately two thirds of the population in
this age group tested positive for anti-thyroid
antibodies
• Hyperthyroidism also presents with vague
symptoms, such as cardiac abnormalities :
(tachycardia, atrial fibrillation, angina,
congestive heart failure [CHF]), neurological
abnormalities (weakness, emotional
disorders), and gastrointestinal abnormalities .
• Hypothyroidism can also be frustrating to identify
because the symptoms are not always clear to
the doctor.
• It can present as debility, cold intolerance,
constipation, dry skin, mental confusion, chronic
anemia, or other autoimmune manifestations.
The aspect of confusion can be difficult to
differentiate from symptoms of dementia.
• Dementia resulting from hypothyroidism has
been shown to be an important cause of debility.
Other serious illnesses can present similarly, and
therefore, the laboratory plays an important role
in diagnosis
Hypothyroidism
∞ TSH not a part of routine insurance
lab testing
∞ Seniors are most likely to have
undiagnosed thyroid disease
∞ Reason: some of the symptoms
are common in seniors (feeling
cold when it’s hot out, depression,
dry skin, fatigue, forgetfulness,
insomnia)
Case for Thought
∞ 78 yr. old woman brought to
M.D. by her daughter
∞ C/O tiredness, dry skin,
forgetfulness
∞ M.D. found no striking physical
findings—felt normal signs and
symptoms for age
∞ Routine blood profile –normal
∞ Severalyears of
undiagnosed thyroid failure
can increase the risk for
elevated cholesterol levels
and heart disease for
seniors
Assessment of renal function
• Kidney function declines with age, falling
about 1% per year.
• Renal plasma flow begins to decrease earlier
than the glomerular filtration rate, which
leads to a delay in clearance measures for
assessing the extent of renal function
BUN, Creatinine
• The levels of BUN (blood urea nitrogen) and
creatinine are largely determined by renal
function. Both are also influenced by other
factors.
• Urea is the primary end product of protein
breakdown. The rate of urea production can
vary considerably, being increased when
dietary protein intake is high or if protein
breakdown is increased in disease.
• Steroids, nonsteroidal anti-inflammatory
medications, and certain other drugs can also
elevate the BUN.
• In contrast, creatinine is unaffected by protein
intake since it is produced by the breakdown of
muscle proteins.
• Instead, it is related to muscle mass and body
weight. This is particularly important in the
elderly.
• For example, a tiny elderly woman may have
significant renal impairment even with an
apparently normal creatinine.
• Creatinine values needto be corrected for body
weight before they can be safely interpreted at
the older ages.
• In younger people, creatinine is generally
considered to be a more reliable guide to
overall kidney function than BUN. This is not
the case in the elderly.
• Studies have demonstrated that BUN is
slightly superior to creatinine as a predictor of
renal impairment even when the latter is
corrected for variations in body weight.
• Creatinine remains stable because the
production and excretion rates fall together,
i.e., the loss of muscle mass (responsible for
the production of creatinine) follows the
reduction in excretion
• Three factors directly influence the plasma
concentration of creatinine: muscle mass, age,
and diet.
• We know that an overload of animal protein in
the diet can raise the levels of serum
creatinine from 10% to 20%.
• Renal function shows a steady decline with
age. Even so, BUN and creatinine are usually
normal among healthy older individuals.
• For risk assessment, screening values may
extend to the upper limits of the normal range
or perhaps be minimally elevated in an
unimpaired elderly applicant.
• Greater elevations usually indicate underlying
renal impairment.
• The formulas most commonly used for
estimation (Cockcroft-Gault and Modification
of Diet in Renal Diseases [MDRD]) can be used
with good accuracy, but purification of less
than 60 ml/min is not recommended .
• The use of cystatin C may be considered
Albumin, Globulin
• The normal range of values for serum albumin
in the healthy elderly is similar to that of a
younger population because the liver is able
to maintain normal production thoughout life
in the absence of illness.
• Nonetheless, screening blood profiles are
more likely to identify low albumin levels in
the elderly.
• This is usually due to the general effects of
illness rather than a specific disease
Disorders associated with a low albumin include
myocardial infarction, infections, inflammatory
disease, burns, trauma, surgery, cirrhosis, other
liver diseases, nephrotic syndrome,
glomerulonephritis, ulcerative colitis and other
gastrointestional impairments, pressure sores,
and leg ulcerations.
Values tend to mirror the severity of illness: low
values have considerable adverse prognostic
significance
Globulin
• Globulin levels are also normal in the healthy
elderly.
• Within the broader group of all old er aged
people -- impaired and unimpaired -- there is
a gradual increase in serum globulins with age
due to impairments such as acute or chronic
infections, tumors, rheumatoid arthritis,
benign monoclonal gammapathy and multiple
myeloma.
• For underwriting purposes, a low albumin or
elevated globulin in the elderly applicant may
provide an indication of the severity of illness
but seldom permits a specific diagnosis.
• Unexplained values warrant further
investigation.
Alkaline phosphatase
• There are conflicting opinions in the medical
literature concerning the effects of aging on
alkaline phosphatase. Some authors report
mild elevations -- up to 20% above the top of
the normal range -- with normal aging,
primarily in women.
• Others conclude that alkaline phosphatase is
no higher in the elderly if the diseases which
might affect this test are carefully excluded.
• Part of this uncertainty exists because the
impairments that can elevate the alkaline
phosphatase are so common in the elderly:
osteomalacia, liver disease, fractures,
malignancies with bone involvement, Paget’s
disease, inflammation of the bone (periostitis)
due to chronic leg ulcerations, and
rheumatoid arthritis. Worthy of special note is
the lack of elevation due to degenerative joint
disease (osteoarthritis).
• For cases where the cause is definitely known,
it is reasonable to "rate for cause" as long as
there are no other laboratory abnormalities
and the alkaline phosphatase is no more than
twice the upper limit of normal.
• A liberal approach can also be justified for
elevations of unknown cause where the
alkline phosphatase is within 20% of the top
of the normal range and there are no other
suspicious factors.
• Other cases should be referred to the medical
director.
GGTP
• GGTP (Gamma Glutamyl Transpeptidase)
increases between ages 6 and 60, then
decreases thereafter. These fluctuations are
more striking in males than in females.
• Nonetheless, values above the published
normal range are usually due to some cause
other than advancing age. Factors most often
identified are medications, alcohol
consumption, and obesity.
Bilirubin, AST, ALT

• Bilirubin, AST (Aspartate Aminotransferase


/SGOT), and ALT(Alanine Aminotransferase/
SGPT) are not affected by aging
Cholesterol, Triglycerides

• Total cholesterol LDL (low-density lipoprotein)


cholesterol and triglyceride values increase
with age from 20 to 65 years and then
plateau or fall.
• HDL (high-density lipoprotein) cholesterol
increases slowly and plateaus after age 65.
Uric acid

• Uric acid is affected by renal function.


• The normal range of this test is somewhat
higher in the elderly for this reason, and thus
is not useful for routine screening of older age
applicants.
Hematological features
• Hematological problems are common in the
elderly .
• Bone marrow also undergoes characteristic
changes over time.
• Values that would be considered appropriate in
other age groups can take on a different clinical
significance in the elderly.
• Leukocyte counts of approximately 10,000/mm3
may be normal for a youth, but in the elderly, this
count may be highly indicative of infection
• Anemia is a disease that is more prevalent in
the elderly .
• Its prevalence increases with age and other
comorbidities. These include iron deficiency,
chronic disease, bleeding, and injuries to the
spinal cord (myelodysplasia and
myeloproliferative disorders).
• A suggested strategy is to administer ferritin
to differentiate between anemia caused by
iron deficiency and that caused by chronic
disease.
• Anemia in geriatric population are due to lack of
sufficient dietary iron intake or iron loss due to
bleeding in the intestinal tract
• Anemia in the geriatric population may, in part,
be explained by the age-related decreases in
stomach hypochloric acid (HCl) which is
responsible for iron absorption in the intestine
• Vitamin B12 deficiency also prevalent due to age
related decreases in serum vitamin B12
concentration
Glycosuria
• Glycosuria (glucose in the urine) is far less useful as
a screening test for diabetes in older individuals.
• In one study, almost half of the elderly patients
with hyperglycemia did not exhibit glycosuria. This
is due to elevation of the renal threshold for
glucose at older ages.
• In other words, glucose will not appear in the urine
of an elderly person until the blood glucose
becomes significantly elevated. This has important
implications in risk assessment.
• Glycosuria in an elderly applicant Means that
diabetes is likely. And the absence of glycosuria is
No guarantee that diabetes is not present.
Proteinuria
• Proteinuria is no more common in the elderly
than in younger individuals. It usually
indicates some form of kidney disease.
• Glomerulonephritis, pyelonephritis,
nephrosclerosis, and diabetic nephropathy are
most often responsible.
General considerations

• The factors that must be considered when


interpreting abnormal blood profile results in
the elderly applicant are applicable at all ages.
Technical factor
• Did the test sample actually come from the
applicant, i.e., was the specimen mislabeled
by the paramedical or laboratory?
• Did an unusual delay occur before the test was
performed that could have affected the
results? Was there an error in the test
procedure itself?
Medications
• The elderly take more medications than younger
populations. These may interfere with test
procedures, cause side effects within the body
that are detected by screening tests, or
precipitate other diseases.
• For instance, many medications elevate liver
enzymes, hyperglycemia may be precipitated by
thiazide diuretics or steroids, and aspirin and
non-steroidal anti-inflammatory medications may
elevate BUN and creatinine in the elderly due to
unrecognized renal impairment.
Interpretation of laboratory findings in the
geriatric population is challenging due to
multiple confounding factors :
• Phisiologic changes that naturally occur with healthy
aging
• Acute and chronic conditions (kidney disease,
diabetes and cardiovascular disease)
• Diets
• Lifestyle
• Medication regimens
• After the age 60 years, albumin concentration
decline each decade, with significant decrease
noted > 90 yr
• Low calcium concentration in geriatric population
is most commonly causes by low serum albumin
concentration
• Calcium consentration increases in age 60 – 90 yr
in the normal albumin concentration
• Hypocalsemia may due to asimultaneus drop
in serum pH and increase in parathyroid
hormone concentration.
• Protein concentration changes may be entirely
due to compromised liver function or poor
dietary regimens
• Individual > 90 yr may have decreased total
cholesterol and calcium concentration
• Geriatric exhibit 2 hr postprandial glucose
concentration (after 40 yr increase 30-40
mg/dL per decade)
• A steady increase in serum glucose
concentrations and a decrease in glucose
tolerance are prevalent
• Lower glucose concentartion in geriatric may
be due poor diet and reduced body mass.
• Higher serum insulin concentrations are
prevalent and may be associated with insulin
resistence
• Elderly > 75 yr, insulin resistance is reportedly
responsible for impaired glucose tolerance
• The capacity of insulin receptors may be lower
in elderly
CONCLUSION

Clinicians need to consider any test result in an older


person in the context of their individual illnesses.
Abnormal results in biochemical and haematological
parameters should not be attributed to age but to age-
related diseases.
Therefore, when results outside the reference intervals
are found, identification of disease states should be
made.

Margaret R Janu1 , Helen Creasey2 , David A Grayson2,3, John S Cullen2 , Scott Whyte2,4, William S Brooks2 , Louise M Waite2 and G
Anthony Broe. Laboratory results in the elderly: the Sydney Older Persons Study. Ann Clin Biochem 2003; 40: 274–279
As the older population often suffers from
multiple comorbid chronic illnesses, the use of
intra-individual ranges, which permit better
clinical interpretation of values in the setting of
acute illness, may enhance patient assessment
and management.

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