Cardiac Function Right Atrium - collects blood from

Prepared by: Jing Gernale, RMT systemic circulation and pumps it into
the right ventricle.
CARDIAC FUNCTION Right Ventricle - pumps blood to the
BASIC ANATOMY OF THE HEART lungs for reoxygenation.
Heart Left Ventricle - pumps blood to the rest
-Is a muscular organ, approximately of the body, including the heart itself.
size of a fist and 12 cm in length
● Male weighs 325g
● Female weighs 275g
- Its location is in the middle of the chest
cavity between lower lobes of each lung
and slightly to the left of the sternum
- It is enclosed in a double-layered
fibrous membrane (sac) called
pericardium
- Visceral pericardium (inner layer of
the pericardium) and the Parietal
pericardium (outer layer) are separated
by a coating of pericardial fluid that
prevents friction between two layers
Interatrial Septum
when the heart moves as it beats.
- Portion of the septum that
separates two upper chambers of
Cardiac wall is composed of:
the heart.
1. Epicardium - outermost layer
near to the Visceral Pericardium
Interventricular Septum
2. Myocardium - middle layer
- Portion of the septum that
3. Endocardium - inner layer near
separates two lower chambers of
the heart chamber, it is prone to
the heart.
ischemia

Semilunar Valves
Heart is divided into two upper and
- Controls blood flow out of the
two lower chambers:
ventricles
1. Upper chamber: Right and Left
- Aortic Valve: opening of the
Atria (RA/LA)
aorta
2. Lower chamber: Right and Left
- Pulmonary valve: opening of the
Ventricles (RV/LV)
pulmonary artery
 ● A typical cardiac cycle
Diastolic Systolic consists of two intervals known as
systole and diastole
Blood vessels Relaxed Contracted
During systole: peak pressure and
Blood pressure Represents the Represents the
ventricles contract (BP in aorta is
minimum maximum
pressure in the pressure exerted 120 mmHg)
vessels and in the vessels During diastole: atrial diastole and
arteries and arteries ventricular diastole are filled with
blood, falls about 70 mmHg
Heart Atria and Left ventricles At rest:
ventricles are contract
- Heart pumps between 60 -80
filled with blood
times/min
Importance Particularly As age - Stroke volume: about 50 mL
with age important in increases, so (volume of blood expelled)
monitoring blood does the - Cardiac output per minute:
pressure in importance of 3L each contraction *corrected with
younger their systolic
BSA 2.5-3.6 L/min/m2
individuals blood pressure
measurement PHYSIOLOGY: CARDIAC
CONDUCTION SYSTEM
Lower number in Higher number - It initiates the heartbeat
reading in reading
and determines heart rate
Atrioventricular Valves - Synchronization of the pumping
- Attaches each atrium to its function of the heart is performed
ventricle which controls blood through the specialized
flow from the atria to the conducting system which
ventricles consists of the Sinoatrial node
- Mitral Valve/Bicuspid valve: (SA), followed by the
connects upper and lower Atrioventricular node (AV) and
chambers on the left side the His-Purkinje System.
- Tricuspid Valve: connects upper
and lower chambers on the right SA node
side - Acts as a pacemaker and creates
electrical impulses that initiate
**Semilunar and Atrioventricular valves contractions within the atria
prevent backflow of blood - These impulses travel to the AV
node, then are distributed
through the His-Purkinje System
PHYSIOLOGY: CARDIAC CYCLE
to the ventricles to begin
(flow of blood in the heart)
contraction.
● Its pumping action is the prime factor
in the maintenance of body’s Electrocardiogram (ECG)
circulation
 - Records changes in electrical
potential
- A graphic tracing of the variations
in electrical potential caused by
the excitation of the heart muscle
- Surface of ECG is a recording of
the electrical potential as
detected at the body surface
It is composed of 12 leads:
● 6 are limb leads (I, II, III, aVR,
aVL & aVF) because these are
recorded between arm and leg
electrodes
● 6 are precordial or chest leads
(V1,V2,V3, V4, V5, V6)
Used to identify changes:
1. Anatomic
2. Metabolic
3. Hemodynamic
Pattern of each cardiac cycle’s
electrical potential changes (each
complex) is similar to that of every
cycle, includes three major
components:
1. P wave - atrial depolarization,
start of SA node triggering
2. QRS - ventricular depolarization
3. ST segment and T wave -
repolarization
___________ determined primarily by
the volume of blood pumped, heart rate,
by the systemic blood pressure and by
the contractile force developed in the
wall of the left ventricle.
ENERGY METABOLISM:
Embden Meyerhof glycolytic pathway
- Pivotal compound: Glucose-6-
phosphate
- Product: Pyruvate → Acetyl
CoA ( if O2 is present, enters the
Krebs cycle)
↓
Lactate ( if O2 is
insufficient)
Krebs Citric acid cycle
- End product: CO2 and H2O
Pentose Monophosphate SHunt
- Glucose-6-phosphate → ribose
and CO2
Fatty acid oxidation
Muscle cells maintain a high
ATP/ADP ratio to perform its
functions
→ synthesis of Creatine
Phosphate which functions as an energy
reservoir source of ATP

CK
Creatine phosphate + ADP ↔ ATP +
Creatine
MK
2ADP ↔ ATP + AMP
AD
AMP ↔ IMP + NH3
** if too much ATP, converts back to
creatine phosphate and ADP
** AMP - adenosine monophosphate
**AD - adenosine deaminase
** CK & MK enzymes are needed to
maintain an equilibrium concentration of
ATP, ADP, creatine phosphate
ENERGY DEMANDS:
● Heart uses free fatty acids as its
predominant fuel
● Consumes significant quantities
of glucose, and lactate, lesser
amounts of pyruvate, ketone
bodies, and amino acids
● Most of the energy for cardiac
function is obtained from the
breakdown of metabolites
through citric acid cycle and
oxidative phosphorylation
FUNCTION TESTS:
➢ Electrocardiogram (ECG)
- Non-invasive recording of
electrical impulse through
the heart, but not perfect
means of assessing
cardiac rhythm
abnormalities and
diagnosing MI.
➢ Myocardial Imaging techniques
- Technetium 99m (99mTc
and Thallium 201)
- Used to assess cardiac
output and wall motion
abnormalities and to
detect non-functioning
regions of the myocardium
caused by infection.
DIAGNOSIS OF HEART DISEASE -
Laboratory Diagnosis of Myocardial
Infarction
Myocardiocyte Biomarkers
★ In tissue necrosis, they lose
membrane integrity and
intracellular macromolecules
diffuse into the cardiac
interstitium and ultimately into the
cardiac microvasculature and
lymphatics.
★ The Ideal cardiac marker
should be:
A. High specificity for
myocardial damage in the
presence of skeletal
muscle injury (abundant in
myocytes and low in blood
& marker present in blood
for a sufficient length of
time to allow high rate of
diagnosis)
B. HIgh sensitivity to detect
very minor heart damage
 and released early after
injury
C. Absent or not detectable in
patients without
myocardial damage
(absent from non-
myocardial tissue)
D. Capability to differentiate
reversible from irreversible
cardiac damage (should
have direct relation
between plasma level and
extent of myocardial injury)
E. Ability to be used as
monitor of prognosis and
therapy
F. Availability of rapid, easy
to perform and cost
effective quantitative
assays
HISTORICAL DEVELOPMENT
➢ Serendipitous discovery of
transaminase enzymes
➢ “Cell death will cause release of
cellular proteins into the
circulation”
AST and ALT
➢ Abundant in liver, skeletal
muscles, and other tissues
1. Myoglobin
- Released immediately
after MI because of low
MW
- Heme-containing protein
that binds oxygen within
cardiac and skeletal
muscles
- Only a single form is
common to both muscles
(skeletal and cardiac)
- MW of only 18kDa, leaks
from damaged cells more
rapidly than other proteins
- Rises as early as 1-4
hours after onset of
symptoms
- Found in all AMI patients
between 6-9 hours
- Peaks about 6 hours after
MI and returns to baseline
within 18-24 hours
- Although myoglobin may
offer some advantage in
early detection of
myocardial damage, its
value is limited by its lack
of specificity.
2. Lactate Dehydrogenase
(LD/LDH)
- Not specific
- L-lactate: NAD
oxidoreductase
- EC: 1.1.1.27
- Zinc-containing enzyme
that is part of glycolytic
pathway
- LD activity in cells draws
off excess pyruvate
produced by anaerobic
glucose metabolism
- Contributes to the
production of NADH,
which the cell uses in the
electron transport chain
- Catalyzes the reversible
oxidation of lactate to
 pyruvate with cofactor electrophoresis in to 5 major
NAD as the oxidizing fractions
agent (coenzyme) ➢ Isoenzyme number 1 travels
- Rises at 12-24 hours, farthest toward the anode, and
peaks about 48-72 hours, the rest are number
and remains elevated in in order (2,3,4,5) back toward the
10 days cathode.
➢ LD-1: HHHH (high in cardiac
TISSUE SOURCES: Present in tissue and RBCs)
all cells, and found in high LD-2:HHHM (major isoenzyme)
concentration in muscle cells LD-3: HHMM
(cardiac & skeletal), liver, kidney, LD-4: HMMM
erythrocytes and leukocytes, LD-5: MMMM
lungs, lymph nodes, spleen,
smooth muscles and brain.

DIAGNOSTIC SIGNIFICANCE: LD ISOENZYME AS A PERCENTAGE

➢ Not specific for a disease OF TOTAL LD
because of its widespread activity
in numerous body tissue
Isoenzyme %
➢ Increased levels are found in
cardiac, hepatic, skeletal muscle, LD-1 14-26%
and renal disease, as well as in
LD-2 29-39%
several hematologic and
neoplastic disorders LD-3 20-26%
➢ AMI and pulmonary infarct show
slight elevations of 2-3 times ULN LD-4 8-16%
➢ Moderately increased in
Pneumocystis carnii Relative amounts: LD-2 > LD-1 > LD-3 >
➢ Skeletal muscle disorders and LD-4 & LD > 5
some leukemia (Acute LD-1 and LD-2 are present to approximately
the same extent in the tissue.
Lymphoblastic leukemia)
➢ It requires the association of 4
 Flipped Pattern (LD-1 > LD-2)
peptides for activity with a MW of
o Suggestive of AMI
128,000 daltons (32,000 each
o Conditions involving
subunit)
cardiac necrosis (AMI)
✔Is a tetramer of 2 active
and intravascular
subunits: H (heart), M (muscle)
hemolysis, the serum
➢ LD tetramers differ in their net
levels of LD-1 will
charge and can be separated by
increase to a point at
 which they are present
in greater
concentration than LD-
2
o LD is not specific to
cardiac tissue and is
not a preferred marker
of diagnosis of AMI
 METHOD OF ASSAY:
 LD catalyzes the
interconversion of lactic and
pyruvic using the coenzyme
NAD+
FORWARD REACTION: Wacker
Method
- Measures the NADH in
absorbance at 340 nm as
_______ is produced.
- Colorimetric: mixture of
phenazine methosulfate and
nitroblue tetrazolium eacts with
the NADH to produce a blue-
purple color (the absorbance of
which is proportional to the
amount of NADH present)
REVERSE REACTION: Wroblewski-
LaDue Method
- Three times faster allowing
smaller sample volumes; shorter
reaction time
- More susceptible to substance
exhaustion and loss of linearity
 SPECIMEN CONSIDERATION
and SOURCES OF ERROR
 Nonhemolyzed serum or
heparinized is appropriate.
o RBC contains an LD
concentration of
approximately 100-
150x that found in
serum.
 Red blood cells should be
removed to prevent artifactual
leakage of LD into the serum.
 If the sample cannot be
analysed immediately, it
should be stored at 25C/RT
and analysed within 48 hours.
 Refrigeration and especially
freezing should be avoided
because they cause instability
of M peptide and its
isoenzymes.
o LD-5 is the most labile
enzyme (affected in
freezing temp)
o Loss of activity occurs
more quickly at 4C
than at 25C
 LD isoenzyme analysis should
be stored at 25C and
analysed within 24 hours of
collection
 REFERENCE RANGE
  Forward reaction: lactate
to pyruvate: 35-90 U/L
 Reverse reaction: pyruvate
to lactate: 95-200 U/L
 Infants and children have
values up to four times
higher.
CREATININE KINASE
- CK | EC 2.7.3.2 | ATP: creatine
N-phosphotransferase
- MW of approximately 82,000 that
is generally associated with ATP
regeneration in contractile or
transport systems.
- Catalyzes the reversible
phosphorylation of creatine using
ATP as a cofactor
- The active form of the cofactor is
actually Mg-ATP4 which explains
the requirement of Mg2+ as
activator
- Appears to have sulfhydryl
groups that are required for its
active shape because samples
that are not analysed promptly
lose their activity, but activity can
be restored by the addition of
N-acetyl-cysteine.
- In muscle cells, creatine
phosphate acts as a temporary
form of stored energy so that,
when the cell is using energy
rapidly, it can react with ADP for
continued cintractions.
 TISSUE SOURCE:
 Present in highest
concentration in skeletal
muscle, cardiac music]le,
and brain tissue
 Present in much smaller
quantities in the bladder,
placenta, gastrointestinal
tract, thyroid, kidney,
uterus, lung, liver, spleen,
pancreas, and prostate.
 It is absent from
erythrocytes
 DIAGNOSTIC SIGNIFICANCE:
 Levels of CK also vary with
muscle mass, and may depend
on gender, race, degree of
physical conditioning, and age.
 Two genes code for
peptides that combine to
form active CK dimer
resulting in 3 isoenzymes
that can be separated by
electrophoresis on
agarose at pH 8.6 (from
anode to cathode)
o CK 1 (BB) – brain
tissue
o CK 2 (MB) –
indicator of
myocardial damage
(cardiac muscle)
o CK 3 (MM) – major
isoenzyme (skeletal
muscle)
 The two subunits are
termed M (for muscle) and
B (for brain)
1. CK-1 (brain type) /
CK-BB
 Found in
brain and
 intestinal  Short half-life
cells and (1-5 hours)
also has  Is
been found approximatel
as a tumor y 20% of all
marker. CK-MB in the
 Found in cardiac
association tissue
with
Myocardium is essentially the only
untreated
tissue from which CK-MB enter the
prostatic
serum in significant quantities
carcinoma
 A good
and other
indicator of
adenocarcin
myocardial
omas
damage,
 Rarely seen
particularly
in
AMI
electrophoret
a. Rise
ic pattern of
within
CK due to its
4-6
inability to
hours
cross the
b. Peak
blood-brain
at 24
barrier (MW
hours
of 80,000)
c. Retur
 Migrate
n to
fastest
norma
toward the
l
anode
within
2. CK-2 (hybrid type;
48-72
<6% of total CK) /
hours
CK-MB
or 2-3
 Characteristi
days
c of cardiac
3. CK-3 (muscle type;
muscle cells;
major isoenzyme;
presentin
94-100% in normal
small amount
sera)
in the
skeletal Present in high
concentration in both skeletal muscle
cells and cardiac muscle cells; present
in small amount in the lung, thyroid,
liver, spleen, placenta
Exhibits the slowest motility
 SPECIMEN CONSIDERATIONS
 MEASUREMENT OF TOTAL
ACTIVITY
 Most common method is
the reverse reaction
 REVERSE REACTION:
Oliver-Rosalki Method
o Measures the
increase in
absorbance at
340nm as NADH or
NADPH is produced
o Cofactor/enzyme: 1.
Hexokinase (a
transeferase), 2.
G6P
 FORWARD REACTION:
Tanzer-Gilvarg Method
o CREATINE is
converted to DIAGNOSTIC USE OF CARDIAC
CREATINE TROPONIN T AND CARDIAC
TROPONIN I
PHOSPHATE
o Measures the
dcrease in
absorbance at 340
nm as NAD is
produced
o Optimal ph is 9.0
AND SOURCES OF ERROR
 Serum is stable for:
o Several hours at
room temperature
o Overnight at
refrigerator
temperature
o At least one month
at -20C
 Calcium-binding
anticoagulants are
prohibited because of the
requirement for Mg 2+
activator
 Inactivation can be
partially reversed by the
additional sulfhydryl
compounds to the assay
reagent such as
Meratoethanol,
Thioglycerol, Dithiothreitol
 Serum should be stored in
a dark place
Troponin (Tn)
o Is a regulatory complex of
three proteins that resides
at regular intervals in the
thin filament of striated
muscle
o The three individual
proteins are:
 I. Tropomyosin the 2-3 day window
binding subunit when CK-MB is
(TnT, 37 kDa) elevated
II. Inhibitory subunit  Peaks at 2 days
(TnI, 24 kDa) and remain
III. Calcium binding elevated for 7-10
subunit (TnC, 18 days
kDa) o cTnI (Inhibitory subunit)
o Function: binds calcium  Increases between
and regulate muscle 4-6 hours after
contraction chest pain onset
o High specificity and  Peaks at 12-18
sensitivity for myocardial hours
damage  Returns to within
 Rise: 3-12 hours reference limits in
 Peaks: 24 hours about 6 days
 Remains elevated  Monitoring patients
for: 4-10 days after reperfusion
**Not found in the treatment
serum of healthy  Cardiac specific
individuals due to presence of
**Localized in additional amino
myofibrils (94-97%) acid residue on the
**Smaller amino terminal
cytoplasmic fraction  Post translational
(3-6%) 31-amino acid
**Cardiac troponins residue as
(TnT, TnI) have compared in
different amino acid skeletal muscle
sequences encoded  Not expressed in
by different genes, normal,
different from regenerating on
predominant diseased human or
troponins in skeletal skeletal muscle
muscle  Has THREE forms:
o cTNT (Tropomyosin 1. Free
binding subunit) 2. Bound as
 Useful in patients two unit
who do not seek complexes
medical attention in (cTnI-cTnC)
 3. Bound as
three unit
complexes
(cTnT-cTnI-
cTnC)
o cTnC (Calcium binding
subunit)
 two major isoforms
(heart and skeletal
muscle)
 not cardiac specific
Cardiac Myosin Light Chain
(MLCs)
o No more specific for
cardiac injury than CK-MB
o Does not offer any
advantage over cardiac
troponin assays
Markers of Congestive Heart
Failure
 ANP
 BNP
 CNP
 DNP
Other Markers
Carbonic Anhydrase III (CA III)
- is an enzyme present in skeletal
but not in cardiac muscle, hence
it can serve as a sort of ‘negative’
cardiac marker
- released from damaged muscle
at a fairly fixed ratio to myoglobin
- thus myoglobin is a more specific
indicator of myocardial damage
when its ratio to CA III is also
elevated.
Glycogen Phosphorylase (GP)
- catalyzes first step in
glycogenolysis
- a dimer of identical subunits, has
three isoenzymes:
1. GPLL (liver)
2. GPMM
(muscle)
3. GPBB (brain)
- GPBB is released earlier than
other markers, and may be
released under conditions of
reversible ischemia that do not
give rise to comparable
elevations in other markers
Heart Fatty Acid Binding Protein
(HFABP)
- A low molecular weight (15 kDa)
protein that is relatively early
marker of myocardial damage,
with kinetics similar to myoglobin
- Not cardiac specific
- However, the ratio of myoglobin
to HFABP is much lower in heart
than in skeletal muscle and may
have diagnostic applicability
Ischemia Modified Albumin (IMA)
- Theoretical advantage: Defects
ischemia before irreversible cell
damage occurs
- The change in albumin appears
to occur within minutes of
ischemia and lasts for about 6
hours
- The test is not specific for cardiac
ischemia, but appears to have a
clinical sensitivity of 80-90% for
 ACS at the time of presentation –
greater than that of the ECG
B-type Natriuretic Peptide or Brain
Natriuretic Peptide (BNP)
- Act as a dual natriuretic system in
regulating blood pressure and
fluid balance
- Heart releases BNP in response
to ventricular volume expansion
and pressure overload
- Diagnostic tool for heart failure:
substantial release from the
failing heart into the plasma
- A protein released from the heart
in response to cardiac stretch
receptors (differentiate between
CHF and other conditions similar
clinical presentations to guide
therapy
- Released in left ventricle if there
is presence overload.
CARDIAC FUNCTION continuation ...
Schematic depiction of cardiac
biomarkers after onset of chest pain
image source: Henry’s Clinical
Diagnosis…
PATHOLOGICAL CONDITIONS
Five Components of a Complete
Cardiac Diagnosis
1. Etiologic Diagnosis
2. Anatomic Diagnosis
3. Physiologic Diagnosis
4. Functional capacity
5. Prognosis
CARDIOVASCULAR DISEASE (CVD)
• Four major types based on the location
in which it occurs:
1. Coronary heart disease (CHD)
2. Cerebrovascular disease
3. Peripheral arterial disease
4. Aortic atherosclerotic disease
“Atherosclerosis” – common
theme in pathogenesis of CVDs
THE CARDIOVASCULAR DATA
BASE:
1. Patient History
a. General Data (Risk Factors)
· Age: Elderly || Sex: Male
b. History of Present Illness
· Symptoms of cardiovascular
disease
· Patient’s functional capacity
· History of febrile illness
· Pregnancy
 c. Past Medical History
· History of systemic illnesses
(Hypertension, DM,
Dyslipidemia, CVD, Thyroid
diseases, peripheral
vascular disease, bronchial
asthma or chronic
obstructive lung disease)
· Medications and allergies
d. Family History
· Up to a first degree relative
(hypertension, ischemic heart
disease, DM, Dyslipidemia)
e. Personal and Social History
· Cigarette smoking (>10 sticks
2. Physical Examination
per day as a risk factor)
a. General appearance of the
· Alcohol intake
patient
· Illicit drug use
b. Blood pressure
· Obesity
c. examination of head, neck,
· Athletic history (lack of exercise)
lungs, abdomen, extremities
· Dietary intake (high in fat or
d. jugular venous pulse, arterial
salt)
pulse, heart sounds
· Type A personality (workaholic
e. grading, kinds and duration of
& obsessive compulsive type)
murmurs

3. Electrocardiogram
4. Chest X-ray
5. Routine Blood exams: CBC, FBS,
Lipid Profile, Creatinine
6. Additional tests
a. Two dimensional
echocardiography with Doppler
studies
b. Exercise treadmill ECG test
c. Ambulatory 24-hour holter
ECG monitoring
d. Nuclear imaging
e. Cardiac catheterization
CARDIOVASCULAR DISEASE 2. male sex
3. hypertension
Symptoms of Heart Disease 4. diabetes mellitus
Observance of the presence 5. dyslipidemia
of any of the symptoms in 6. smoking
conjunction with person’s 7. family history of
age, family history may lead ischemic heart disease
to an accurate and early
B. Other Risk Factors
diagnosis
Seven classic symptoms: 1. obesity (overeating)
Dyspnea 2. decrease physical
Chest pain (Angina activity/ lack of exercise
pectoris) 3. type A personality
Manifests as (workaholic)
uncomfortable pressure, 4. diet high in cholesterol
squeezing in the
center of the chest
1. Prinzmetal or Variant Angina
Palpitation
1. atypical chest pain with
Syncope transient ST elevation by ECG
Edema with normalization of the
retained fluid tracing after chest pain
accumulates in the feet disappears
and ankles) 2. negative exercise stress test
edema absent in 2. Silent Ischemia
morning but worsened in absence of chest pains
the day 3. Microvascular Angina
Cyanosis occurs usually in pre-
bluish discoloration of menopausal women
skin
Fatigue may be due to constriction of
may be due poor small coronary arteries
cerebral & peripheral (microvascular angina) or
perfusion, poor enhance pain sensitivity
oxygenation of blood) 4. Sudden Cardiac Death
unexpected death occurring
within one hour from the onset
of symptoms
OVERVIEW OF CORONARY ARTERY ventricular fibrillation (V-FIB)
The lower chambers quiver
DISEASE
and the heart can't pump any
blood, causing cardiac
Risk Factors Influencing the arrest. The heart's electrical
development of CAD activity becomes disordered.
A. Major Risk Factors: When this happens, the
1. Older age heart's lower (pumping)
 chambers contract in a rapid, (radiates to the left inner
unsynchronized way. arm or to the lower jaw)
Collapse and sudden cardiac severity (mild, moderate
arrest follows or severe)
5. Chronic Stable Angina timing (usually in the
Features for diagnosis: morning with exertion)
typical exertional angina
pectoris
presents as pain &
discomfort in the chest
only when engaged in
moderate activity (running
or walking)
objective evidence of
myocardial ischemia by
ECG, exercise stress test
or nuclear scan
(myocardial thallium
perfusion scanning)

Pathogenesis of Atherosclerosis:
Epithelial injury theory:
some injurious stimulation
(hypertension,
hypercholesterolemia)
causes endothelial
damage resulting in
smooth muscle cell
proliferation and migration
of macrophages
into the vessel wall
Coronary angiography –
gold standard of diagnosis
Clinical History: (description of chest
pain)
Precipitating factor
(exertion, anger,
excitement, cold
weather)8B
palliative factor (relieved
by rest and nitroglycerine
intake)
quality (heavy, deep,
crushing)
radiation and location
6. Unstable Angina
pathophysiology:
· presents with pain and
discomfort unpredictably at
rest
· Plaque ruptures, allowing
blood clots to precipitate
and further
decrease the lumen of the
coronary vessel
· ruptured unstable plaque:
fissuring or rupture of its
fibrous cap
leading to thrombosis with
platelet aggregation and
the exposure
of the tissue factor
· increased vasoconstrictor
response
Features for diagnosis:
· new or worsening symptoms
(angina, pulmonary edema) or
ECG changes of myocardial
ischemia
· absence of creatinine kinase
and its MB fraction elevation,
consistent with myocardial
infarction
7. Myocardial Infarction
● Caused by the death of part of
the heart muscles due to lack of
blood flow
3. any of the ff criteria satisfy the
diagnosis of an acute, evolving or
recent MI
a. Typical rise and gradual fall (troponin)
or more rapid rise
and fall (creatine kinase-MB) of
biochemical markers of
myocardial necrosis with at least one of
the ff:
* ischemic symptoms
* development of pathological Q-
waves on ECG
* ECG changes indicative of
myocardial ischemia
* coronary artery intervention
b. pathological findings of an acute
myocardial infarction
Anatomical Types of MI (based on the
extent of involvement)
1. Transmural or ST elevation MI: Total
thrombotic occlusion with whole
thickness of the myocardium infarcted
2. Non transmural of Non ST elevation
MI: subtotal thrombotic occlusion with
only the subendocardium infarcted
Pathophysiology of MI:
1. Acute thrombosis
2. Rupture of unstable plaque
3. Vasospasm
4. Embolism
5. Non-thrombotic MI (related to shock
or arrhythmia)
Clinical History:
Characteristics of Chest Pain in MI:
Severe chest pain at
test for usually >30
minutes
Same character and
location as previous
angina pain but more
severe in intensity & not
relieved by nitroglycerine
Three Subsets of Patients with Painless
MI:
Elderly patients (most
common presenting
symptom is dyspnea and
not chest pain)
Diabetic patients
Patients with CNS
disease
Rapid clinical response
to myocardial ischemia is
essential to limit the
extent of necrosis that
occurs and central view of
treating MI. The faster
cardiac interventions are
performed to restore
perfusion to the heart, the
greater reduction in infarct
size.
Strategies for
 reperfusion (restoring
blood flow to tissue):
1. Use of intravascular
balloons & stents to clear
coronary artery
blockages and prevent
recurrence
2. coronary artery bypass
grafting (CABG or bypass
surgery)
3. use of chemical
thrombolytics
PATHOPHYSIOLOGY OF
ATHEROSCLEROSIS, THE DISEASE
PROCESS
UNDERLYING MYOCARDIAL
INFARCTION
Complete Pathophysiology read:
Bishop, M. L., Fody, E. P., & Schoeff, L.
E. (Eds.). (2013). Clinical Chemistry:
Principles, Techniques, and
Correlations. Lippincott Williams &
Wilkins.
Refer to Seventh edition, Chapter 26
1. Endothelial cells and inflammatory
cells interact with chemical &
inflammatory mediators to promote the
development of atherosclerotic
plaques.
2. This process begins with vascular
injury which is initiated when endothelial
cells are damaged or rendered
dysfunctional by vascular abnormalities
such as turbulent blood flow,
hyperlipidemia and
hyperhomocysteinemia.
3. A damaged vascular endothelium
has an increased permeability to
circulating lipids so having cholesterol
(hyperlipidemia) in the wake of a
damaged endothelium favors the
accumulation of lipoproteins, LDL, VLDL
within arterial intima. Apo-B containing
LDL has high affinity for arterial
wall proteoglycans.
 Retention of lipids in arterial walls
due to hypercholesterolemia and/or
elevated levels of apo-B containing
lipoproteins – critical step in
pathogenesis. The central role of
cholesterol accumulation in the
progression of atherosclerosis is the
reason treating high cholesterol is
such priority in preventing and
attenuating heart disease.
4. Once lesion initiation has begun, LDL
deposited within the intima is
oxidized by endothelial cells,
lipoxygenase and free radicals
generated by
auto-oxidation of homocysteine.
Oxidized LDL is toxic to endothelial
cells causing additional intimal damage
and subsequent retention of cholesterol-
rich lipoproteins and it elicits
inflammatory cells to early lesion.
Neutrophils and monocytes plays
role in early atherogenesis by
maintaining pro inflammatory state
around the initial lesion.
5. Macrophage scavenger receptors
recognize oxidized LDL, but not native
LDL and activated macrophages rapidly
phagocytose cholesterol-rich
lipoproteins that have been oxidized
within the vessel wall.
 Excessive uptake of oxidized LDL
transforms macrophages into
bloated, cholesterol filled cells called
foam cells.
6. Rupture of foam cells and release of
their contents cause further damage
to the vascular endothelium stimulating
more inflammation. Additional cell types
are recruited in the plaque (T & B
lymphocytes & macrophages)
7. Interactions of T cells & foam cells
promote a chronic inflammatory state
and help recruit smooth muscle cells
into the intima. Growth factors
(fibroblast & tissue growth) further
stimulate smooth muscle cell migration
& activation.
8. Once smooth muscle cells migrate
into the core of the atheroma, they
proliferate and deposit extracellular
matrix components that give stability &
strength to the plaque.
9. As the atheroma grows, its core
becomes increasingly isolated from
surrounding blood supply, leading to
hypoxia that stimulates release of
pro-angiogenic cytokines. This causes
neovascularization around periphery of
the plaque.
10. Vessel occlusion, thrombosis,
plaque rupture or combination of three
predisposes to organ ischemia.
Ischemia and hypoxia pose an
immediate risk of cellular injury due to
high metabolic activity and oxygen
demand of the myocardium.
Acute Coronary Syndromes (ACS) –
resulting from coronary heart disease
(CHD)
Represent the following continuum of
events:
Symptoms include: chest pain,
referred pain (pain referred to the
arm, jaw, neck, back or abdomen),
nausea, vomiting, dyspnea,
diaphoresis and lightheadedness
● Main symptom: Unstable Angina
- angina at rest or frequent
angina caused by moderate
physical activity
 Major cause: thickening and
hardening of the artery walls caused by
deposits of cholesterol-lipid-calcium
plaque in the lining of arteries
Blood flow in ACDs are severely
reduced or completely blocked
● Atherosclerosis – build-up of a
fatty substance called plaque can
narrow the coronary arteries. If
this plaque ruptures a blood clot
will form and block the arteries. A
 blood clot is the most common
cause of coronary artery
blockage.
● Other less common causes:
○ Coronary artery spasm
■ Triggers such as
drugs, cold
weather, smoking
or extreme stress
and emotions can
cause a temporary
and sudden
tightening of the
coronary artery.
○ Dissection
■ Inside wall of one of
the coronary
arteries separates
which can block
blood flow
- Regardless of the cause, a
blockage of the coronary artery
prevents oxygen and nutrients in
the blood from reaching the part
of the heart supplied by the
artery. As a result, heart muscle
in that area starts to die.
 Narrowing of arteries leads to reduced
blood supply to the heart referred to
ischemia
 Doctors may prescribe
● oxygen therapy to get more
oxygen in the blood
● Aspirin or other prescription blood
thinner drugs to prevent blood
clots
● Thrombolytics (clot buster drugs)
may be used to break up any
existing blood clots
● Drugs such as nitroglycerine and
morphine will relax the coronary
arteries and relieve the pain of
angina
● Beta blockers that can slow down
the heart and reduce its need for
oxygen
● Immediate surgical procedures
such as:
○ Coronary Angioplasty - a
balloon tipped catheter
inflates in the blocked
coronary artery to open it.
After inflating, it may leave
behind a mesh like device
called a stent to hold the
artery open
○ Coronary Artery Bypass
Graft - the blocked areas if
the coronary arteries are
bypassed by veins or
artificial graft material
Ischemic Heart Disease
Ischemia
 is a condition in which the organ has
an inadequate blood supply for
maintaining its essential functions
 Coronary atherosclerosis – most
common cause
 inflammatory condition of arterial
vessels that generally progresses
over many years
 causes the arteries that supply blood
to the heart to gradually narrow
 (occlude) because of deposition of
cholesterol and other substances
in the arterial wall
 Plaques - most common cause of
 ischemia is related to unstable lipid-
filled deposits
Effects of Occlusion on Myocardium
 Cessation of blood flow produces a
complex series of metabolic
consequences for the cells deprived of
blood flow.
 Sever hypoxia occurs because of:
 tissue oxygen concentration drops
 delayed clearance of toxic cellular
metabolites from ischemic tissue
 production of free radicals after
reperfusion of damaged tissues
 Hypoxia prevents aerobic metabolism:
switches to anaerobic Embden
Meyerhof pathway à end product of
pyruvate, reduced to lactate
 During ischemia, three major factors:
§ Elevated potassium
§ Acidosis
§ Anoxia
 all contribute to abnormalitles of the
action potential conduction in the
heart  lead to ventricular fibrillation
(VF) (if not treated immediately, results
in cessation of blood pumping to brain,
and other vital organs death
 At the point at which reversible
ischemic injury becomes irreversible,
the cell is no longer able to maintain
membrane integrity and the intracellular
contents are released into the
extracellular environment. The rate of
cellular proteins release depends on:
 clearance mechanism
rate and extent of reperfusion of the
damaged myocardium
 size of protein molecule
 Release of proteins can be used as
biomarkers for the evaluation and
confirmation of irreversible ischemic
injury
 Three things may result from ischemia
to the heart:
MI
 CHF
 Angina pectoris
MARKERS OF CARDIAC DAMAGE
A. Initial markers of Cardiac Damage
(AST, LD, CK)
v First cardiac markers used were
glutamic oxaloacetic transaminase
(AST/SGOT), lactic dehydrogenase and
malic dehydrogenase
B. Newer & cardiac specific marker:
Troponins
C. Recommendation: Measure troponins
ASAP as after onset of symptoms of
MI. If troponin assays are not available,
next best alternative is CK-MB
OTHER MARKERS OF ACS, CHD, MI
1. Myoglobin
2. Heart type fatty acid-binding
protein (H-FABP)
3. Ischemia modified albumin (IMA)
 doesn’t detect myocardial tissue
damage but instead measures
changes that occur in albumin in the
presence of ischemia, giving it
advantage that might detect ischemia
before damage of heart has to
occur
 The free radical formation occurs
during ischemia modifies albumin;
these modifications in albumin alters its
ability to bind metals such as
cobalt by its N-terminal domain
 the amount of IMA is measured by
spectrophotometric determination
of albumin’s binding to cobalt
 Not specific for cardiac damage,
Clinical sensitivity to ACS
4. Myeloperoxidase (MPO) , Myeloid-
related protein (MRP)-8/14 and
Pregnancy associated plasma
protein-A (PAPP-A)
 early diagnosis and stratification of
acute MI but still inferior to troponins
5. high sensitive-C-reactive protein
(hs-CRP)
 analyte of choice when using
inflammatory markers to assess CHD
risk
 measured using nephelometry
MI is among the acute illnesses
associated with elevation of plasma
CRP
 The inflammatory response
associated with atheromatous lesions
may
trigger enough cytokine production to be
associated with a
measurable rise in plasma CRP, CRP
may, in turn, through its
pro inflammatory effects, increase
plaque vulnerability or have other
effects that worsen the severity of CHD.
11. homocysteine (hcy)
 increase levels of hcy, also increases
risk to CHD
 “elevated levels is the common factor
leading to arterial damage”
à homocysteine-induced expression of
chemokines promotes proinflammation
that may contribute general vascular
inflammation that drives atherosclerosis
 measured by chromatographic
techniques
Heart Failure (HF)
Definition of Terms:
Heart Failure
 due to decrease in pumping function
 the heart is no longer able to pump an
adequate supply of blood in relation
to the venous return and in relation to
the metabolic needs of the body
tissues at that particular moment.
 All forms of heart disease may lead to
decomposition and failure
 most common symptom: shortness of
breath, fatigue & lower extremity
edema
LAB & Clinical test for suspected HF:
Complete blood count
- help determine if anemia or infection
may be cause of heart
failure
 Serum electrolyte levels
- an imbalance of fluid electrolytes can
cause fluid retention while it
may play a role in severity of heart
failure
 BUN/Creatinine
- determination can determine if damage
to kidneys due to hypoperfusion, may be
occurring secondary to heart failure
 Fasting glucose
- increased glucose in both diabetic
patients and non-diabetic put
them at risk for HF
 Liver function test
- increased enzymes may indicate if
liver function is affected due to
heart failure, congestion of the liver can
occur secondary to the
inefficiency with which heart is able to
move the venous
circulation
 BNP/NT-proBNP levels
- both are elevated after being released
in the heart secondary to
the stretch induced by heart failure. their
levels correlate closely
with the severity of heart failure and can
be used to differentiate
cardiac causes of shortness of breath
from primary lung disease
 ECG
- 12lead ECG can detect ischemia,
infarction and arrhythmia as a
cause for heart failure
 Urinalysis
- research studies have described
relationship between amount of
protein excreted in urine and
Cardiovascular risk
Lipid profile
- includes HDL, LDL, total cholesterol
and triglyceride
determination should be performed to
determine the risk of CHD
TSH
- should be measured as both hypo &
hyperthyroidism can be a
primary cause of heart failure or can
contribute to its severity
Congestive Heart Failure
 The state in which abnormal
circulatory congestion occurs as the
result of heart failure
 Disease related to decreased
capability of the heart to pump blood
 Clinical syndrome that results from
any structural or functional cardiac
disorder that impairs the ability of the
ventricle to fill with or eject blood
· Produces pulmonary edema and
reduced output of blood to
systemic circulation
· kidneys respond by retaining
excess fluid, making HF worse
· When the right side of heart is
unable to pump, excess fluid
accumulates in systemic circulation
and generalized edema occurs
 Contributing factors: increased age,
hypertension, coronary
 Atherosclerosis • CNP: c-type natriuretic peptide
(endothelial cells)
• DNP: Dendroaspis angusticeps (green
mamba snake)

 Important therapy: treatment with furin

ACE inhibitors
proBNP (108 amino acid prohormone)
 Use of beta-adrenergic blockers –
1. active BNP
symptomatic heart failure
2. N-BNP or NT-proBNP
 Diuretics – patients with sodium
• BNP half life: (22 mins)
retention
• N-BNP (60 – 120 mins)
 Digitalis – for patients with
• Specimen used: EDTA whole blood
symptomatic heart failure to reduce
progression of disease and
BNP
hospitalization
• exert their effects through two types of
 Digoxin - treatment of CHF
G protein–coupled receptors:
Mechanism of action: causes release
• resulting in release of the second
of Ca++ in the myocardium;
messenger cyclic guanosine
slows AV node conduction
monophosphate.
Inhibits Na K ATP pump à Decreases
 downregulate the RAAS,
intracellular potassium resulting to
ü decrease sympathetic nerve activity in
increased intracellular calcium;
the heart and
Increases calcium  cardiac
kidney,
contractility
 increase renal blood flow
increase sodium excretion via a direct
Markers of CHF: Cardiac Natriuretic
effect on the
Peptides
renal collecting duct
• Natriuretic peptides are secreted in the
heart in response to increased
Arrhythmias
pressure & volume load.
 Refers to distortion of the
• ANP: Atrial natriuretic peptide
transmission of cardiac nerve impulses
• BNP: brain natriuretic peptide
which produces abnormal, irregular and
self- sustaining contractile activity of the
heart
 Bradycardia (decreased heart rate, <
60 beats/min)
 Tachycardia (increased heart rate, >
100 beats/min)
Cardiomyopathy
 Characterized by inadequate muscle
contraction caused by direct damage
to myocardial cells and results in
hemodynamic overload and heart failure
 Two categories:
- disease originating in heart tissue
- disease related to non-myocardial
disorders
 Manifests as an enlargement of all
four chambers of the heart and as
cardiac failure
Congenital and Valvular Heart
Disease
 all components of the heart can be
affected by mal-development or
infectious disease
 Rubella infection of the mother during
1st trimester of pregnancy,
associated with high risk for fetal cardiac
malformation
 Valvular disease: rheumatic carditis
- patients affected by hemolytic
streptococcus
Congenital Cardiovascular Defects
(CCVDs)
 Signs and Symptoms
· Cyanosis, pulmonary hypertension,
clubbing of the fingers,
embolism, reduced growth and syncope
 All defects develop before week 10 of
pregnancy
 Includes:
· Tetralogy of Fallot
 Combination of four defects:
o VSD (ventricular septal defects)
o Right ventricular outflow obstruction
o Abnormal positioning of the aorta
above the VSD
o Right ventricular hypertrophy
· Transposition of the great arteries
two main arteries going out of the
heart—the pulmonary artery
and the aorta—are switched in position,
or “transposed”.
· Atrioventricular septal defects
· Coarction of the aorta - is the
narrowing of the aorta
heart must pump harder to force blood
through the narrow part
of aorta.
· hypoplastic left heart syndrome
left ventricle and other structures are
poorly developed
· ventricular septal defects (VSDs)
 Most common type; “hole of the
heart”
Defect, large opening between the
ventricles of the heart
 Consequences: increases blood
flow to the lungs 
increases pulmonary venous
return into the left atrium and into
the left ventricle. This increased
volume results in left ventricular
dilation and then hypertrophy. It
increases the end diastolic
pressure and then pulmonary
venous pressure. Finally, as
 blood is shunted through
the VSD away from the aorta,
cardiac output decreases,
and compensatory mechanisms
are stimulated to
maintain adequate organ
perfusion. These mechanisms
include increased catecholamine
secretion, and salt and
water retention by means of
renin-angiotensin system
HYPERTENSION
Five Major complications of
hypertension:
1. Heart: Ischemic heart disease and
heart failure
2. Brain: Stroke
3. Kidney: Kidney failure
4. Blood vessels: Peripheral vascular
disease
5. Eyes: Hypertensive retinopathy
Infective Endocarditis
 It is a microbial infection of the heart
valves or of the endocardium
 Rheumatic heart disease – infection
Group A streptococci
PULMONARY EMBOLISM
• is an acute and serious condition in
which embolus (circulating mass of
solid, liquid or gas) becomes lodged
within the pulmonary arteries,impairing
blood flow through pulmonary
vasculature and increasing ventricular
pressure
• Measurement of D-Dimer
• Product of plasmin-mediated fibrin
degradation
• Serves as an indirect marker of
coagulation & fibrinolysis
• Abnormal levels in Pulmonary
embolism
• Is measured by:
 ELISA, Enzyme linked fluorescent
assay & Latex quantitative
assays
Trace Elements the need for
Prepared by: Arbee Mae Castro, RMT increased vanadium
when there is either
WHAT ARE TRACE ELEMENTS? an experimentally
➔ Term was originally used to induced deficient or
describe the residual amount of excess supply of
inorganic analyte determined in a dietary iodine
sample quantitatively ➔ They are part of the micronutrients
➔ Associated with an enzyme of the body and can be subdivided
(metalloenzyme) or another into four (4) major groupings
protein (metalloprotein) as based in their physiologic
component or cofactor function:
➔ Present in very low amounts
1. Essential trace element
(usually microgram/gram of tissue
for which a recommended daily
CLASSIFIED into: allowance (RDA) has been
established.
➔ Pharmacologically Beneficial
● Shown to be
● includes fluoride (for
essential for normal
dental caries)
growth,
● Lithium (manic
development and
depressions)
maintenance and a
● Dosage of these
specific biological
elements greatly
role has been
exceed their
identified.
amounts normally
● Includes zinc,
found in food
iodine, selenium
➔ Nutritionally beneficial or
and iron
Possibly essential
2. Trace elements for
● For some elements
which there is definite evidence of
suboptimal dietary
an essential role in human
intake may
metabolism but for which an RDA
eventually have a
has not yet been established
detrimental effect
● Additional dietary ● These include
supplements may copper,
have a “health manganese,
restorative” effect chromium, cobalt,
● E.g effects of boron molybdenum and
in the presence of fluorine.
Vit. D depletion, or
 3. Trace elements that are
consistently found in tissues or
biological fluids in “ultra trace”
amounts but that have not yet
been shown to be essential or
detrimental at these levels of
concentration.
● These include
lithium, nickel, tin,
silicon and
vanadium
4. Trace elements that
have no known biological
function in humans but
that, if present at relatively
low levels, cause
pathologic changes.
● These toxic trace
elements include
aluminum,
beryllium, cadmium,
mercury, lead and
arsenic.
A. CHROMIUM (Cr)
● Transitional element
● Used extensively in the
manufacture of stainless steel,
chrome plating, leather tanning,
dye for printing, and as an
anticorrosive in cooling systems
(Cr6+)
● Discharged into the environment
as industrial waste
● Occurs in Cr3+ or Cr6+
CHROMIUM (III)
• enhances the action of
insulin, glucose and lipid
metabolism
• Low toxicity, poorly
absorbed, rapid excretion in
urine
• Component of GTF
CHROMIUM (VI)
• Strong oxidant (cause liver
damage)
• Carcinogen
• More efficiently absorbed
• Normally reduced to Cr3+
when in contact with
foodstuffs and gastric contents
• Toxicity and carcinogenic
effects involve its reduction to
Cr5+ and Cr3+ by cysteine
ABSORPTION
• Binds with plasma transferrin
• Concentrates in liver, spleen,
heart, other soft tissues and
bone
DIETARY SOURCES
• Amount in foodstuffs vary
• Processed meats
• Whole grain products
• Green beans
• Broccoli
• spices
DEFICIENCY
• No need to determine
• Impaired glucose tolerance in
Type 2 Diabetes
• insulin resistance
• Hyperglycemia
• Peripheral neuropathy
 • hyperlipidemia
TOXICITY
• Associated with hexavalent
chromium
• Industrial exposure to metal
fumes and dust is associated
with lung cancer, dermatitis,
and skin ulcers
• Contaminates the soil by
Cr6+ waste left by the leather
tanning and dyestuff industries
REFERENCE VALUES
● Serum:0.1 to 0.2ug/L (2-
3nmol/L)
● Urine: <0.2ug/L (<3nmol/L)
LABORATORY EVALUATION
● Specimen: plasma, serum
and urine
B. COPPER (Cu)
● 3rd most abundant trace element
in the human body
● Present in both Cu1+ and Cu2+
forms
● Involved in electron transport Ø
Oxidation reactions Ø Essential
for:
● Cellular respiration
● Neurotransmitter regulation
● Collagen synthesis
● Nutrient metabolism
● Forms alloys with zinc, tin, and
nickel
● Has the highest concentration
found in liver, brain, heart, and
kidneys. Also found in cornea,
spleen, intestine and lungs.
● Involved in the synthesis of
hemoglobin
● Component of several
metalloenzymes:
➢ Cytochrome C-oxidase
➢ Superoxidase dismutase
➢ Tyrosinase
➢ Dopamine-ɞ-hydroxylase
➢ Lysil oxidase
➢ Ascorbate oxidase
➢ Peptidylglycine α-
amidating monoxygenase
➢ Monoamine oxidase
➢ Metallothionein
➢ Clotting factor V
➢ Ceruloplasmin
DIETARY SOURCES
● Organ meats (liver, kidney)
● Shellfish
● Nuts
● Whole grain cereals
● Bran
● Cocoa-containing products
ABSORPTION
● Mainly occurs in the small
intestines
● Gastric uptake (smaller extent)
● Inhalation
● Skin absorption
● Intestinal uptake=pH dependent
● Transported to the liver by
binding with albumin
● Liver= key organ in copper
metabolism
● 90% of copper exported from
liver to peripheral blood-
ceruloplasmin
DEFICIENCY
● Malnourished infants
 ● Premature infants- hematological
abnormalities and fractured brittle
bones
● Nutritional status
● Malabsorption syndromes- celiac
disease, tropical sprue, cystic
fibrosis, and short bowel
syndrome
● Cardiovascular disease
● MENKES’ SYNDROME
• Inborn error
• Rare
• Congenital defect
• X-linked mutation
• Male infants (2-3
months)
• Pili torti
• Low levels of Cu in
plasma, liver, brain
• Plasma Cu = <10
umol/L
• Ceruloplasmin =
<220 umol/l
• Demo of pili torti mx
• Characterized by:
1. Poor mental
development
2. Failure to
keratinize hair
3. Skeletal
problems
4. Degenerative
changes in the
aorta
TOXICITY
● WILSON’S DISEASE
• Hepatolenticular
degeneration
• Genetic disorder
• Plasma Cu and
ceruloplasmin= low
• Deposition of Cu in
liver, brain, eyes and
kidneys
• Kayser-Fleischer rings
(Cu deposits in the eye)
• Detected by slit eye lamp
examination
• Chronic form- tx by
chelating agents:
➢ Penicillamine
➢ Trientine
• Oral administration of
Zn salts and Ammonium
molybdate- successful
• Cu contamination in diet
and water supplies
• Acute poisoning: ingestion
of CuSO4
REFERENCE INTERVALS
● ADULTS: 70-140 ug/dL (10-22
umol/L)
• Women in
childbearing age esp. pregnant-
values are higher
● Urine Cu output- less than 60
ug/24hr
LABORATORY EVALUATION:
● Specimen: serum and urine
● Instrumentation: FAAS (most
widely used)
C.MANGANESE (Mn)
● Twelfth most abundant element
in the earth’s crust in the form of
Ferromanganese, used in the
production of steel and dry cell
batteries; component in copper
and aluminum alloys.
 ● Mn2+ or Mn3+
● Other compounds are widely
used in fertilizers, animal feeds,
pharmaceutical products, dyes,
paint dryers, catalysts, wood
preservatives, glass, ceramics
and gasoline.
● Manganese containing enzymes:
arginase, pyruvate carboxylase,
manganese superoxide
dismutase
● Manganese activated enzymes:
decarboxylases, hydrolases,
kinases and transferases.
● Dietary manganese is poorly
absorbed in the small intestine
and it’s affected by iron, calcium,
phosphates and fiber
FUNCTIONS:
● Responsible for the oxidative
phosphorylation, fatty acid
metabolism; synthesis of protein,
cholesterol and
mucopolysaccharides
● Improve brain and nerve function
● Enables the body to utilize
Vitamin C, biotin and choline
● Prevents diabetes and stimulate
growth of connective tissue
DEFICIENCY
Can cause:
● Impaired growth
● Reproductive function
● Skeletal abnormalities
● Impaired glucose tolerance
● Impaired cholesterol synthesis
TOXICITY
● Occupational health hazard
● Acute Exposure: can cause
nausea, vomiting, headache,
disorientation, memory loss,
anxiety, compulsive laughing or
crying
● Chronic Exposure: can cause
psychiatric disorders,
hallucinations,
● syndrome resembles Parkinson’s
disease with akinesia, rigidity,
tremors and mask-like faces
LABORATORY EVALUATION:
● Specimen: serum, urine and
whole blood
REFERENCE INTERVALS:
● Serum: 0.43-0.76 ug/L
● Whole blood: 10-11 ug/L
● Urine: <2.0 ug/L
D.MOLYBDENUM (Mo)
● Most stable state- Mo6+ as found
in Molybdate
● Has the highest atomic number of
the essential trace elements
DIETARY SOURCES
● Legumes (peas, lentils, and
beans)
● Grains
● Nuts
● Meats, fruits and many
vegetables= poor sources
ABSORPTION
● Mainly as molybdate
● Competitive inhibition of
absorption by sulfate
● 80%-90% found in whole blood
are bound to red cell proteins
 ● Transport of small amts via α2 -
macroglobulin
● Urine output directly reflects
dietary intake of molybdenum
DEFICIENCY
● Naturally occurring deficiency not
known
● Growth depression
● Hypercuprinemia
● Defective keratin form
● Goiter
● Cretinism
TOXICITY
● Low toxicity in humans
● Excess molybdenum intake
induces copper deficiency
LABORATORY EVALUATION
● Whole blood, serum and plasma
are too low to be used for
detection of deficiency
● Urine output- responsive to
increase and decrease
● Measuring urate or sulfite in the
urine is the most valuable means
of confirming molybdenum
cofactor disorders or possible
molybdenum deficiency
REFERENCE INTERVALS
● PLASMA/SERUM: 0.5ug mol/L
● Whole blood: 1ug mol/ L
● Urine (det by ICP-MS): 40-60 ug/l
E. SELENIUM (Se)
● Constituent of the enzyme
glutathione peroxidase
● Closely associated with Vitamin E
● Nonmetal
● Selenocysteine- where selenium
is substituted for sulfur in
cysteine.
● Enters the food chain mainly as
SELENOMETHIONINE
● (plants)
● Cofactor in iodothyronine
deiodinase and thioredoxin
reductase
ABSORPTION
● well absorbed in gastrointestinal
tract in the form of inorganic
● sodium selenate or sodium
selenite.
EXCRETION
urine, feces, sweat, exhalation of volatile
forms of Selenium
DEFICIENCY
● Associated with cardiomyopathy,
skeletal muscle weakness
and osteoarthritis; cancer of the large
intestine, rectum,
prostate, breast, ovary and lungs;
leukemia
KESHAN DISEASE
● Endemic cardiomyopathy in
children and women in
● childbearing age in China
● Signs and Symptoms: dizziness,
malaise, loss of appetite,
● nausea, chills, abnormal
electrocardiogram, cardiogenic
● shock, cardiac enlargement and
congestive heart failure
KASHIN-BECK DISEASE
Endemic osteoarthritis in adolescents
and preadolescents in
northern China, North Korea and • Used as treatment for Acute
Eastern Siberia promyelocytic leukemia (APL)
in US
TOXICITY • It is odorless and tasteless white
● Acute Exposure: causes nausea, powder
vomiting, diarrhea, and • Doses of 0.01 – 0.05g produce toxic
cardiovascular symptoms symptoms; lethal dose:
● Chronic Exposure: causes hair 0.12 – 0.3g
and nail loss, skin lesions, tooth
decay, fatigue, neurological abnormality, TYPES:
abdominal cramps,
watery diarrhea, male infertility, garlic 1. Organic Arsenic
odor in breath • Relatively non-toxic and occur
primarily in fish, seaweed and
LABORATORY EVALUATION shellfish
• Includes Arsenocholine and
Specimen: Plasma, serum, whole blood Arsenobetaine
2. Inorganic Arsenic
Instrumentation: ICP-MS (Inductively- • Highly toxic and occur naturally in
induced Mass Spectrophotometry) , rocks, soil and
Atomic Absorption Spectrophotometry groundwater.
(HGAAS - Hydride generation atomic • Used in the production of pesticides,
absorption spectrometric or GFAAS- preservatives, metal
Graphite furnace atomic absorption alloys, glasses, enamels and
spectroscopy) or NAA semiconductors
• Pentavalent/ Arsenate [As(V)] and
REFERENCE INTERVALS Trivalent/ Arsenite [As(III)]
Plasma: 46-143 ug/L are more toxic
Serum: 95-165 ug/L • Methylated (monomethylarsonic acid
Whole blood: 58-234 ug/L [MMA]) and
RBCs: 75-240 ug/L Dimethylarsinic acid (DMA) are less
toxic and formed by
F. ARSENIC (As) hepatic metabolism of As(III) and As(V)
· With both metallic and nonmetallic
properties TOXICITY
· Ubiquitous, its content in earth’s
crust is estimated at 1.5 – 2.0 ● Acute Exposure
-Can result in death
· mg/kg
-Symptoms include
· Used as a wood preservative
gastrointestinal (nausea, emesis,
· Arsenic trioxide
abdominal
pain, rice water diarrhea); bone marrow
(pancytopenia, anemia,
basophilic stippling); cardiovascular
(Electrocardiograph changes); CNS
(encephalopathy, polyneuropathy); renal
(renal failure, renal insufficiency);
hepatic and dermatologic
● Chronic Exposure
-Include dermatologic,
cardiovascular, CNS, and
malignant changes
LABORATORY EVALUATION
Specimen: Urine, Serum, Hair and
Nails
REFERENCE INTERVALS
● Blood
Normal: <23 ug/L
Critical value for Acute poisoning: 100-
500 ug/L
o Critical value for Chronic poisoning:
600-9,300 ug/L
Urine
Normal: <50 ug/L or <0.50 ug/day
Chronic industrial exposure: >100 ug/L
Critical value: toxic >850 ug
G.CADMIUM (Cd)
● A soft, bluish-white metal, which
is easily cut by knife
● Used in manufacturing of
pigments, batteries, metal plating
and plastics
● Primary organs affected are liver
and kidney. Accumulations
● are found at urinary bladder,
muscles, lungs, glottis, and
● placenta.
● Reference dose: water (0.0005
mg/kg/day); dietary (0.001
● mg/kg/day)
● Absorption: higher in females
than in males; cigarette smoke
(10-
● 50%); gastrointestinal (5%)
● Excretion: feces (90%); urine
(0.001%); body burden per 24hrs
● (0.01%)
TOXICITY
● Acute Exposure: Respiratory
distress; severe nausea, vomiting
and abdominal pain
● Chronic Exposure: Renal
dysfunction; nasal epithelial and
lung damage; affects the liver,
bone, immune and blood system
LABORATORY EVALUATION
Specimen: blood and urine
REFERENCE INTERVALS:
Urine: <2.6 ug/L or <3.3 ug/day
Blood: <5.0 ug/L
H. LEAD (Pb)
● Metallic lead is soft, bluish white,
highly malleable and ductile.
● It is poor conductor of electricity
and heat and resistant to
corrosion.
● The main lead ores are galena,
cerrusite and anglesite
Uses:
o Tetraethyl lead: additive in gasoline
(petrol) which increases the fuel’s
octane rating
o Production of batteries, ammunitions,
foils, paints, and toys
-Inhalation results in 30-40% absorption
efficiency; enhanced gastrointestinal
absorption may occur in children
younger than 6 years of age. Also
enhanced if person has low dietary zinc,
ascorbic acid and citric acid.
-Iron, calcium, magnesium, fat and
alcohol may impair lead absorption
-94% is bound to hemoglobin and about
6% is in the plasma.
-Primarily distributed and stored in soft
tissues (5%) and bone (95%) Excreted
in urine (76%), feces (16%) and hair,
sweat, nails (8%)
TOXICITY:
● Children: headache, clumsiness,
gait abnormalities, seizures,
severe cognitive and behavioral
changes, abdominal pain,
constipation, colic, anemia, acute
nephropathy and decline of IQ.
● Adults: peripheral neuropathy,
motor weakness, chronic renal
insufficiency, systolic
hypertension, anemia.
LABORATORY EVALUATION:
Specimen: whole venous blood; hair,
nails, urine
Tests: plasma aminolevulinic acid,
whole blood zinc protoporphyrin, free
erythrocyte protoporphyrin, X-ray
fluorescence
Instrumentation: ICP-MS (Inductively-
induced Mass Spectrophotometry), ICP-
AES (Inductively-induced Atomic
Emission Spectrophotometry) and AA
(Atomic Absorption)
REFERENCE INTERVALS:
Blood
-Toxic for children and child-bearing
females: >10 ug/dL
-Non-pregnant adults: >30 ug/dL
Urine
Normal: < 80 ug/day
Critical value: >125 ug/day
I.MERCURY (Hg)
● Also called as quicksilver, is a
heavy, silvery metal. Liquid at
● room temperature and pressure.
● Widely used in production of
mascara and used in electrical
● switches, fungicide
● Oxidation states: Hg(O), Hg(I),
Hg(II)
● Half life: blood (5 days); urine (90
days)
● Storage: kidney, liver, spleen,
pituitary gland, thyroid,
● pancreas, reproductive organs,
brain
● Excretion: fecal and urinary;
crossing through the placenta
 FORMS: Instrumentation: CVAAS (Cold Vapor
● Dimethyl mercury: extremely Atomic Absorption Spectrophotometry)
toxic compound and ICP-MS (Inductively-coupled Mass
● Mercury (I) chloride: used as Spectrophotometry)
diuretic, topical disinfectant, and
laxative REFERENCE INTERVALS:
● Mercurochrome: organohalide Urine
● Thiomersal-mercury: used as a Normal: 0-15 ug/day or <35 ug/L
vaccine preservative Toxic: >150 ug/L
Blood: 0-60 ug/L
ROUTE OF EXPOSURE:

● Inhalation: primarily as elemental J. IRON (Fe)

mercury vapor; retained in the
lungs to about 80%; produce
harmful effects in CNS, digestive,
immune, lungs and kidneys
● Ingestion: as HgCl2 in meat and
fishes; dietary intake of
approximately 3ug/day
● Cutaneous: methyl mercury
● Injection: liquid mercury and
tattoo pigments
● Dental amalgams
TOXICITY
● Primarily through reaction with
sulfhydryl groups (MSH) by
inactivating proteins by binding to
cysteine groups in proteins
● Signs and Symptoms: headache,
tremor, impaired coordination,
abdominal cramps, diarrhea,
dermatitis, polyneuropathy,
proteinuria, hepatic dysfunction
● Fourth most abundant element in
the earth’s crust
● Carrier of biochemical active
substances; agent in redox and
electron transfer reactions;
● constituent of hemoglobin and
myoglobin.
● Free iron ions participate in
catalyzing the formation of toxic
free radicals. May play a role as
pro oxidant, by contributing to
lipid peroxidation,
atherosclerosis, DNA damage,
carcinogenesis and
neurodegenerative diseases.
● Body Iron Compartments:
Hemoglobin 68.3%
Myoglobin 3.3%
Ferritin 12.7%
Hemosiderin 11.7%

Transferrin 0.17%
LABORATORY EVALUATION
Enzyme Iron 0.19%
Specimen: blood and urine
Remaining Organic Iron 5.65%
Iron Absorption and Transport
The major role of iron in mammals is to
carry O2 as part of hemoglobin. Iron is
mostly in the Fe3+ (ferric) state and must
first be reduced to Fe2+ (ferrous) iron by
ferrireductases, such as B Cytochrome.
Fe2+ iron is then transported across the
apical membrane by divalent metal
transporter 1 (DMT1). Heme iron is
moved across the apical membrane into
the cytoplasm through transporters that
are incompletely characterized. Here, it is
metabolized to release Fe2+ iron, which
enters a common pool with non-heme
Fe2+ iron.
Iron that enters the duodenal cells can
follow one of two pathways: transport to
the blood or storage as mucosal iron.
This distribution is influenced by body
iron stores. Fe2+ iron destined for the
circulation is transported from the
cytoplasm across the basolateral
enterocyte membrane by ferroportin.
This process is coupled to the oxidation
of Fe2+ iron to Fe3+ iron, which is carried
out by the iron oxidase like hephaestin.
Newly absorbed Fe3+ iron binds rapidly
to the plasma protein transferrin, which
delivers iron to red cell progenitors in the
marrow.
Iron absorption is regulated by hepcidin,
a small circulating peptide that is
synthesized and released from the liver
in response to increases in intrahepatic
iron levels. Hepcidin inhibits iron transfer
from the enterocyte to plasma by binding
to ferroportin and causing it to be
endocytosed and degraded.
Major influences of iron absorption:
state of body’s iron stores,
erythropoiesis, recent iron uptake
● Iron is excreted in feces,
desquamation of skin, menstrual
loss and urine.
DEFICIENCY
● IRON DEFICIENCY ANEMIA
o Results in anemia due to
impaired hemoglobin
synthesis
o Higher risks: pregnant
women, young children,
women of reproductive age,
& adolescents
o 3 stages of Iron deficiency
have been identified
o Can be caused by:
decrease intake,
accelerated loss, block
in mobilization of stored
iron, parasitic infection.
o Symptoms: Koilonychia,
glossitis, fatigue, pallor, pica
TOXICITY
● HEMOCHROMATOSIS
 o A single gene ● TOTAL IRON BINDING
homozygous recessive CAPACITY
disorder leading to o Measures the capacity of
abnormally high Fe, serum transferrin to bind
absorption by inhibiting iron
hepcidin o Performed in the same
o Accumulation of iron, way as serum iron
affects the liver and o Adding of excess ferric
pancreas function; ions. Unbound ferric ions
impotence, are precipitated with
hypothyroidism, magnesium carbonate.
hyperpigmentation of
skin; Bronze diabetes ● PERCENT SATURATION
o Treatment: therapeutic o Also called the Transferrin
phlebotomy, chelators Saturation
(deferoxamine) o The ratio of serum iron to
● HEMOSIDEROSIS TIBC
o Designate condition of ● TRANSFERRIN
iron overload but without o As an indicator of nutritional
tissue damage status; negative acute
o Increased serum iron, phase protein
TIBC and transferrin o Instrumentation:
nephelometry
LABORATORY EVALUATION
● Complete Blood Count ● FERRITIN
● Peripheral Blood Smear o Test of choice for assessing
● Bone Marrow Examination iron stores
● SERUM IRON o Instrumentation: IRMA,
o Measurement of the ferric ELISA, RIA, IFA, EIA
ions bound to transferrin ● ZINC PROTOPORPHYRIN/
o Specimen: serum and HEME RATIO
heparinized plasma with o Functional test for iron
12hr fasting status
o Principle: Colorimetric o Measured in whole blood
Spectrophotometric using hemato-fluorometer
o Chromogens: ferrozine,
ferene and Reference Intervals
bathophenanthroline PATIENT SERUM TIBC PERCENT TRANS
POPULA IRON (ug/dL) SATURA FERRIN
TION (mg/dL) TION (mg/dL)

Newborn 100-250 100-400 12-50 130-275

Infant 40-100 100-400 12-50 200-360 alcoholism, inflammatory bowel
disease, celiac disease, cystic
Child 50-120 100-400 12-50 200-360
fibrosis, nephritic syndrome,
Adult 50-160 250-425 20-55 200-380
Male
hemolytic anemia and anorexia
nervosa.
Adult 45-150 250-425 15-50 200-380
Female ● Symptoms: slow growth, weight
loss, altered taste, delayed
puberty, dwarfism, night
K. ZINC (Zn) blindness, alopecia, skin lesions,
● A bluish white, lustrous metal; emotional instability and tremors,
stable in dry air testicular atrophy.
● Used in the production of alloys, ● ACRODERMATITIS
galvanizing steel, die casting, ENTEROPATHICA
paints, skin lotions; treatment of o A rare genetic disorder
Wilson’s disease characterized by intestinal
● The main biochemical role of zinc abnormalities that lead to the
is its influence on the activity of inability to absorb zinc in
more than 300 enzymes intestine.
● Influences the synthesis and o Skin inflammation, diarrhea
metabolism of proteins, and nail dystrophy
participates in glycolysis and o If untreated: include growth
cholesterol metabolism, retardation, impaired T-cell
maintains membrane structures, immunity, insufficient
affects functions of insulin and wound healing, delayed
affects growth factor testicular development and
● Distributed in muscles (60%), early death
skeleton (30%) and in eyes,
prostate and hair. TOXICITY
● Factors that promote absorption: ● Gastrointestinal symptoms,
presence of exogenous amino decrease in heme synthesis and
acids, calcium and unsaturated hyperglycemia
fatty acids ● ZINC FUME FEVER
● Factors that decrease o Exposure to ZnO fumes
absorbance: intake of iron, taking and
zinc on empty stomach, presence dust
of copper at high levels and age o Can cause chemically
induced
DEFICIENCY pneumonia, severe
● Zinc deficiency is often pulmonary
associated with: burn patients, inflammation, fever,
 hyperpnea, pains in legs
and
chest, emesis.
LABORATORY EVALUATION
● Specimen: serum, urine and
plasma
● Instrumentation: AAS, ICP-AES
and ICP-MS
REFERENCE INTERVALS
● Serum: 70-120 ug/dL
● Urine: 140-800 ug/day
L. IODINE (I)
● The sea is the major source;
similar concentration in humans.
● Integral component of thyroid
hormones (T3, T4) which are
synthesized by iodination of
tyrosine
● Rapidly absorbed and
transported to thyroid gland
● Main excretory route: urine
● DEFICIENCY: hypothyroidism
characterized by dwarfism and
mental retardation; spontaneous
abortions, stillbirths and
congenital abnormalities
● TOXICITY: high levels of thyroid
hormones, high metabolic rates,
weight loss, nervousness; iodide
goiter and myxedema
● Instrumentation: Ion Selective
Electrode
● Reference Value: 100-200 ng/mL
M. FLUORINE (F)
● May substitute for the hydroxyl
ion in the hydroxyapatite crystal
structure in calcified tissues,
bone and teeth
● May also play a role in
maintaining adult bone structure
and in treating osteoporosis with
combination of vitamin D
● DEFICIENCY: dental caries,
impaired growth
● TOXICITY: dental fluorosis
characterized by discolored and
mottles teeth, affects the nerve
and muscle function
● Excretion: urine
● Specimen: Plasma and Urine
● Instrumentation: ISE, Gas-liquid
Chromatography
N. COBALT (Co)
● Essential only as an integral part
of Vitamin B12 (cobalamin)
● Functions in Hgb synthesis
DEFICIENCY
● Lack of vitamin B12
● Anemia
● Anorexia
● Growth depression
TOXICITY
● Cardiomyopathy
● Heart failure
● Goiter
● Hypothyroidism
● Warm sensation
● Vomiting
● Diarrhea