CLINICAL DIAGNOSIS LECTURE (PATHOLOGY)

CARDIOVASCULAR DISEASES Clinical (Non-laboratory Risk Factors)

Non-modifiable
A group of disorders of the heart and blood vessels o Hereditary
Include:  Family history of premature CHD
o Coronary Heart Disease (CHD in male 1st degree relatives <55
o Cerebrovascular Disease y/o or in female <65 y/o)
o Peripheral Arterial Disease o Age
o Rheumatic Heart Disease  Men: >45 y/o
o Congenital Heart Disease  Women: >55 y/o
o DVT and Pulmonary Embolism o Gender
The most important disease affecting the heart is the Modifiable
Coronary Heart Disease which can lead to Acute o Cigarette Smoking
Coronary Heart Syndrome. o Hypertension (BP >140/90 or on hypertensive
medication)
Coronary Heart Disease o Obesity
Philippines o DM
o Deaths: 87, 881 or 16.86% of total deaths o Stress
o The age adjusted Death Rate is 161.43 per o Sedentary Lifestyle
100, 000 of population ranks Philippines #29 in o Elevated Cholesterol
the world. o Elevated TAG
o Registered deaths due to heart diseases:
 16.5% in 2000 Diagnosis of Acute Coronary Heart Syndrome
 20% in 2008 Primary tests
 21% in 2009 o Electrocardiogram (ECG)
o NCR: highest prevalence rate o Coronary Angiography
o WHO: Heart Disease is the leading cause of  Extent of atherosclerotic disease in
death in the world in 2008. the coronary circulation
o Laboratory Measurements of cardiac markers
HEART ATTACKS AND STROKE Cardiac Markers (MUST KNOW)
Usually acute events are proteins released into the circulation from
Mainly caused by a blockage that prevents blood from damaged heart muscle
flowing to the heart or brain. most important: cardiac troponin (cTn)
Most common reason: build-up of fatty deposits on the o derives only from heart muscle
inner walls of the blood vessels that supply the heart or Patients presenting to the ER with symptoms suggesting
brain Acute Coronary Syndrome must be processed rapidly
and precisely to provide life-saving interventions as
Atheroma needed
o Accumulation and swelling in artery walls o Rapid measurement of cTn and possibly other
o Contain lipids (cholesterol and fatty acids), lab markers
calcium and variable amount of fibrous Lipids
connective tissue. Cholesterol
o Chest pain TAG
o 10-20% occlusion of coronary arteries = acute Specific Lipoprotein Fractions
coronary syndrome o Homocysteine (Hcy)
o Formation of obstructive plaques, probably  Amino acid that exacerbates
begins with obstructive lesions known as fatty thrombosis
streaks. C-Reactive Protein (CRP)
o More ominous is actual rupture of the plaque, Inflammatory marker that may reflect the severity of
causing thrombosis with sufficient occlusion to CHD and may contribute to its pathogenesis.
result in Acute Coronary Syndrome. (Dra. Tan will give at least 1-2 questions daw from this.
So memorize )
Location of chest pain during angina or heart attack: hs-CRP value CVD Risk Level
o Upper chest <1 mg/L Low risk
o Substernal 1-3 mg/L Average risk
o Epigastric >3mg/L High risk
o Neck and jaw
o Left shoulder CHD and other heart diseases can impair the heart’s ability to
o Intrascapular pump blood, causing the clinical syndrome of Heart Failure (HF).

First Aid Management B-Type Natriuretic Peptide (BNP)

Recognize the signals of heart attack and take action
If patient is under medical care, assist him/her in taking
his/her prescribe medicine/s.
Have the patient stop what he or she is doing.
Have him/her sit or lie down in a comfortable position.
Do not let the patient move around.
Secreted by the cardiac ventricles in response to wall
stretch stimuli.
A marker of the presence and severity of HF
Testing is useful for aiding the differential diagnosis of
patients who present to an ER with shortness of breath.

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 CLINICAL DIAGNOSIS LECTURE (PATHOLOGY)
Markers of Myocardial Damage
Historical Development
AST (SGOT)
ALT (SGPT)
Transaminases
o Surveying a variety of hospital patients,
investigators noted that serum transaminase
levels rose sharply after a myocardial
infarction and this was born the era of
“cardiac enzymes.”
o Not endured as cardiac markers because of
their abundance in liver, skeletal muscles and
other tissues.
o Soon superseded for cardiac diagnosis by
 Lactate Dehydrogenase
 Creatine Kinase
Lactate Dehydrogenase
o Zinc-containing enzyme
o Part of the glycolytic pathway
o Found in the cells of the body
Total Serum LD
o Elevated in virtually all diseases state in which
there is cell damage or destruction
o The association of LD1&LD2 with heart muscle
is useful in confirming diagnosis of MI
o Myocardium contains more LD1 than LD2,
leading to an INVERSION or FLIP of the LD1/LD2
ratio to a value >1 in the serum after MI.
o After release from damaged myocardium,
the ratio of LD1/LD2 will stay flipped for several
days and total LD will also remain elevated.
Creatine Kinase
o Aka Creatine Phosphokinase (CPK)
o 2 subunits are termed M (for muscle) and B
(for brain)
o 3 resulting isoenzymes are
 CK1 (BB)
 CK2 (MB)
 CK3 (MM)
o Primary sources
 Brain and smooth muscle (BB)
 Cardiac Muscle (MB and MM)
 Skeletal Muscle (MM)
o Found in small amounts throughout the body
but is in high concentrations only in the
muscle and brain, although CK from brain
virtually never crosses the blood-brain barrier
to reach plasma.
o CK-MB
 Appears in the serum within 6 hours
after MI.
 Clears from the circulation within 24-
36 hours
 Persistence in the serum after that
period may indicate extension of
infarction into the other regions of
the heart or reinfarction.
o CK-MB ASSAY
 Uses monoclonal antibody
technology
 Now widely employed
 Performed rapid under 1 hour
 Offers better analytical performance
(low-end accuracy than traditional
isoenzyme separation)
 Limitation that CK-MB is not specific
for myocardium.
Myoglobin
o Heme-containing protein that binds oxygen
within CARDIAC and SKELETAL MUSCLE.
o Only a single form common to both muscle
types
o Lacking cardiac specificity
o Leaks from damaged cells more rapidly than
other proteins.
o Elevated serum levels are apparent within 2-3
hours following the onset of MI, earlier than
with troponin or other markers
o Cleared mainly by renal filtration
o Half-life is approx. 4 hours, but is longer if renal
function is impaired
o Peaks about 6 hours after MI and returns to
baseline after 24 hours
o In normal individuals, myoglobin levels are
related to muscle mass and muscle activity,
similar to the patient for CK.
o Plasma levels are higher in men
o Increases with increasing age, reflecting
decreased glomerular filtration rate (GFR).
o Occasionally useful for documenting damage
to skeletal muscle
 Other markers (total CK) are usually
more convenient for this purpose.
 Occasionally, testing for myoglobin
in serum or urine is useful to
determine whether a positive urine
DIPSTICK TEST for blood, based on
heme’s peroxidase activity, actually
reflects myoglobinuria.
Cardiac Troponin (cTn)
o Now the most important laboratory test for
cardiac diagnosis.
o Troponin is a regulatory complex of three
proteins that resides at regular intervals in the
thin filament of striated muscle.
o The 3 Individual Proteins are:
 TnT (tropomyosin-binding subunit)
 TnI (inhibitory subunit)
 Tnc (calcium-binding subunit)
o The free fraction allows early leakage from
injured myocardial cells and detection in a
time frame similar to that of CK-MB, with cTn
reaching a peak at about 24 hours following
MI.
o Circulating cTn declines to baseline levels in
about 5-10 days, depending on infarct size.
o In contrast to other cardiac markers, cTnT and
cTnI are nearly absent from normal serum.
 cTn rarely exceeds 0.1ng/mL in
healthy individuals.
o cTn elevation, though presumably indicating cardiac
myocyte damage, need not be caused by ischemic
damage.
o Elevations, though generally much smaller than those
seen with MI, have been observed with
o Pericarditis
o Myocarditis
o Pulmonary Embolism
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 CLINICAL DIAGNOSIS LECTURE (PATHOLOGY)

o Renal Failure Choose smash fish:

o Sepsis o Sardines
o Analytical artifacts o Mackerel
Markers of Coronary Risk o Anchovies
Serum Cholesterol o Salmon
o LDL o Herring
 Contains 70% of the total circulating Perform activities of kindness
cholesterol o One way to motivate yourself to get in a small
 Directly associated with the risk bouts of physical activity: do them for
o HDL someone else.
 Negative risk factor Love a pet
o Triglyceride o Pet seem to have an amazingly positive
 Significant risk factor impact on stress, cholesterol levels and blood
Markers of Coronary Risk (CRP) pressure
NORMAL INDIVIDUAL (plasma) o A pet’s calmer energy field may affect ours.
o Median CRP concentrarion: 1mg/L List something you are grateful for every day
o 99th percentile: 10mg/L o Each day, write down one or two more things
ACUTE ILLNESS you should be grateful for, and read the
o Cytokines (chiefly IL-6) stimulate hepatic journal once a week.
production of CRP) Open windows on milder days, and use a fan to
o Plasma levels increase to 300 mg/L or more circulate the air to reduce indoor air pollution levels
Markers of Congestive Heart Failure (from hairspray, candles, fumes from the nonstick
coating on cookware).
Cardiac Natriuretic Peptide Clean with kitchen staples
In humans, BNP is produced mainly in the cardiac o When possible, clean your kitchen with items
ventricle. you’d cook with such as white vinegar, lemon
The hormone is now commonly reffered to as B-type and bicarbonate soda- to remove chemicals
natriuretic peptide. on many cleaning products which have been
linked to stroke and high blood pressure.
B-type natriuretic peptide Toss your plastic containers
For diagnosing acutely ill patients presenting to o Chemicals in plastic, such as BPA and
emergency service with shortness of breath phthalates, leach into the food in these
Plasma levels of BNP are less than 100 pg/ml in most containers.
healthy individuals o Linked urine BPA levels to heart disease risks
Reference ranges depend on the age and gender o Linked phthalates to cardiovascular issues
Many other possible applications of BNP testing: o Use glass, ceramic or stainless steel storage
o Monitoring the course and treatment of containers instead.
patients with HF.
o Risk stratification of patients with ACS
o Monitoring disease severity in patients with
stable CHD.
o Screening for ventricular dysfunction in
selected populations.
o Testing for drug cardiotoxicity.
As this time it appears that the most appropriate use of
the BNP test is as an adjunct test to rule out heart failure
in the acute setting.

Choice of Cardiac Injury Markers

Specimen in 1-4 hr time frame, include:
o Myoglobin
o CK isoforms “Ang crush, nagsimula sa mata, pumasok sa Dibdib,tumambay
CTn sa Isip, naging Bukambibig, kaya sa huli, naging PAG-IBIG ♥”
o May not rise until several hours after myocyte hihi
necrosis
o A negative specimen at the time of
presentation should be ff with a:
 2nd specimen at 6-12 hours and
 At least when the index of suspicion
is high, a 3rd specimen at about 24
hours.
Heart Attack Prevention
Have at least 5 cups of vegetables a day (I know its
tough, pero tiis lang mga besh . haha)
Drink 3 cups of tea a day (green, black and oolong
varieties)

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