MARCH 13, 2009

CLINICAL & LABORATORY

APPROACH TO BLEEDING
PATIENT
Sinus rhythm
 Sinus rhythm= rhythm produced by
electrical impulses formed within the SA
node
 P wave is always upright in leads I, II,
aVF
 Normal sinus rhythm rate 60-100/min
Sinus Rhythm
4 Questions to identify an ectopic
rhythm
1. Are normal P waves present?
2. Are the QRS complexes narrow?
3. What is the relationship between the P
wave and the QRS complexes?
4. The rhythm regular or irregular?
Ectopic impulse: premature
beats
PAC
•Premature P wave
•Change morphology of
P wave
•Usually narrow QRS
Ectopic impulse: premature
beats
PJC
 Premature QRS
complex (usually
narrow QRS)
PJ  Absent P wave
C
Ectopic impulse: premature
beats
PVCs
•Premature QRS complex
•No premature P wave
•Usually wide QRS
complex with opposite T
wave deflection
Ectopic impulse: Rapid ectopic
rhythm
 Tachycardia group (rate~150-250/min)
Supraventricular tachycardia (SVT)
Ventricular tachycardia (VT)
 Flutter group (rate~250-350/min)
Atrial flutter
Ventricular flutter
 Fibrillation group (rate~350-450/min)
Atrial fibrillation (AF)
Ventricular fibrillation (VF)
Paroxysmal Supraventricular
Tachycardia (PSVT)
 Rate ~150-250/min,
Regular rhythm
 Abrupt onset &
termination
 Not seen sinus P
wave (usually not
seen P wave or
retrograde P wave)
 Usually narrow QRS
complex
Paroxysmal Supraventricular
Tachycardia (PSVT)

•Rate ~150-250/min, Regular rhythm

•Usually narrow QRS complex
•Abrupt onset & termination
•Not seen sinus P wave (usually not seen
P wave or retrograde P wave)
Paroxysmal atrial tachycardia
(PAT)
 Regular
 Rate 150-250/min
 Warm up period
 Visible P wave (but
not sinus P wave)
Paroxysmal atrial tachycardia
(PAT)

•Regular rhythm, rate ~150-250/min

•Narrow QRS complex
•Warm up period
•Visible P wave (but not sinus P wave)
PAT with block
 Regular or irregular (if varying block)
 2:1, 3:1, …

(2 P wave same morphology:1 QRS,

3 P wave same morphology:1 QRS)

PAT with
3:1 block
Multifocal Atrial Tachycardia
(MAT)
 Irregular rhythm
 ≥3 different P wave morphologies
 Rate >100/min (if rate
<100/min=Wandering pacemaker)
Ventricular Tachycardia
(VT)

•Regular rhythm (may be slightly irregular)

•Rate ~150-250/min
•Wide QRS complex
Polymorphic VT
 Like VT but QRS complexes different in
morphology
 Typical: QRS complexes spiral around
the baseline, changing their axis and
amplitude.
 Polymorphic VT + prolong QT interval
= Torsades de pointes
Atrial Flutter
 Regular or irregular
rhythm
 Atrial rate 250-
350/min
 Ventricular rate 1/2,
1/3, … of atrial rate
 “Saw tooth”
appearance
 AV block 2:1, 3:1,…
Atrial Flutter

•Regular or irregular rhythm

•Atrial rate 250-350/min
•Ventricular rate 1/2, 1/3, … of atrial rate
•“Saw tooth” appearance
•AV block 2:1, 3:1,…
Atrial Fibrillation (AF)
 Irregular rhythm
 Not seen P wave
(fibrillate baseline)
 Atrial rate ~350-
500/min
 Ventricular rate
variable
Atrial Fibrillation (AF)

•Irregular rhythm
•Not seen P wave (fibrillate baseline)
•Atrial rate ~350-500/min
•Ventricular rate variable
Ventricular Fibrillation
 Multipleventricular foci rapidly discharge
producing a totally erratic ventricular
rhythm without identifiable waves
 Bradyarrhythmia

Sinus node dysfunction AV block

1st degree AV block

Sinus arrest /pause
2nd degree AV block
Sinus exit block
2nd degree AV block type I
Sinus bradycardia
2nd degree AV block type II
Tachy-brady syndrome
2nd degree AV block 2:1

Advanced 2nd degree AV block

3nd degree AV block

Sinus node dysfunction
 Sinus bradycardia
 Sinus arrest /pause
 Sinus exit block
 Tachy-brady syndrome
tachyarrhythmia-atrial fibrillation
bradyarrhythmia-sinus arrest
Sinus Bradycardia

Sinus bradycardia
 Sinus rhythm
 Rate<60/min
Sinus Arrest
and SA Exit Blo
ck
Tachy-brady syndrome
Escape Rhythms
Escape beats= rescuing beats
originating outside the sinus node
 AV Node (junctional rhythm): 40 to 60
beats/minute
 Ventricles: 30 to 40 beats/minute
Junctional rhythm
Junctional rhythm
 Rate 40-60/min
 Most often not seen P wave (Occasional
retrograde P wave)
 Narrow QRS complex
Idioventricular rhythm
 Rate30-40 /min
 Wide QRS complex
Accelerated Idioventricular
rhythm
 Rate50-100/min
 Regular wide QRS complex
AV Block
 First
degree AV block
 Second degree AV block
Type I (Wenchkebach)
Type II
2:1 second degree AV block
Advanced second degree AV block
 Third degree AV block
1 DEGREE AV BLOCK
st

 PR interval >0.2 sec

 All beats are conducted through to the ventricle
2nd DEGREE AV BLOCK: Mobitz type I
(Wenckebach)

 Progressive prolongation of the PR interval until

a QRS is dropped
2nd DEGREE AV BLOCK: Mobitz type II

 QRS complexes are dropped at regular intervals

without prolongation of the PR interval
2 nd
DEGREE AV BLOCK 2:1

 2 sinus P wave: 1 QRS complex

 Constant PR interval

(Impossible to tell whether it is Mobitz I or II)

High grade AV block (Advanced
AV block)

≥ 3:1 AV block
Constant PR interval
Third degree AV block

 No beats are conducted through to the

ventricles.
 AV dissociation: atrium and ventricles are driven
by independent pacemakers
High grade AV block
(constant PR interval)

3º degree AV block
(AV dissociation)
Normal conduction
The Electrical Conduction System
Normal Bundle Branch
Conduction
Ventricular depolarization

V1 V6
Right Bundle Branch Block (RBBB)
Right Bundle Branch Block
(RBBB)

Lead V1 M-shape QRS (RSR’)

Lead I, V6 Wide S wave
Left Bundle Branch Block
(LBBB)
Left Bundle Branch Block
(LBBB)

Lead V1 QS or rS
Lead I, V6 Monophasic R wave, no Q
RBBB, LBBB, IVCD
Secondary ST-T change
Left Anterior Fascicular
Block

LAFB
1. Left axis deviation (usually>-60º)
2. Small Q in leads I & aVL, small R
in II, III, aVF
3. Usually normal QRS duration
Left Posterior Fascicular
Block

LPFB
1. Right axis deviation (usually> +120º)
2. Small R in leads I & aVL, small Q in II,
III, aVF
3. Usually normal QRS duration
Axis change in fascicular
block
Abnormal morphology
Abnormal P wave
 LAE (P mitrale)
 RAE (P pulmonale)
 Abnormal P wave Axis
Abnormal P wave axis
 Non-sinus P wave
 Arm lead reversal
 Dextrocardia
Abnormal P wave axis

Abnormal P axis : P wave is negative in I,

II, aVF, positive in aVR
Origin of P wave is not SA
node

In the same lead, there are two P wave morphology

This patient has atrial
tachycardia
Arm lead reversal

Abnormal P wave axis

QRS axis is also the same as P wave
Both P wave & QRS are normal in chest lead
Dextrocardia

Abnormal P wave axis

QRS axis is also the same as P wave
R wave regression in chest lead
Atrial enlargement

LAE RAE
PR interval
 Short PR interval
 Prolongation of PR interval (AV block)
Preexcitation syndrome
 In the preexcitation
syndrome, there are
accessory
pathways by which
the current can
bypass the AV node
and arrive at the
ventricles ahead of
time
Acces
sory
Pathw
WPW pattern

•Short PR interval
•Wide QRS complex with delta wave
•WPW syndrome= history of PSVT +
WPW pattern ECG
AF with WPW
Abnormal QRS complex
 Abnormal Q wave
 Abnormal R wave
 Abnormal S wave
Normal ECG
Abnormal Q wave
 Significant Q wave is 1 mm wide (0.04
sec in duration) or Q wave ≥1/3 of the
QRS complex
 Exclude lead aVR
 Significant Q wave = Infarction
Leads that may normally
display moderate to large-si
zed Q waves
 Lead III
 Lead aVF
 Lead aVL
 Lead V1 (and sometimes also lead V2)
 Lead aVR
Tall R in V1
 Posterior wall MI
 Pre excitation
 Dextrocardia
 Duchene Muscular Dystrophy
 Right Bundle Branch Block
 Right Ventricular Hypertrophy
 Rotation of heart
Normal ECG
RVH
Dextrocardia

Abnormal P wave axis

QRS axis is also the same as P wave
R wave regression in chest lead
Isolated posterior wall MI
Pre excitation
Normal R wave progression
Causes of poor R
progression
 LVH (left ventricular hypertrophy)
 RVH (right ventricular hypertrophy)
 Pulmonary disease (i.e., COPD, asthma)
 Anterior or anteroseptal infarction
 Conduction defects (I.e., LBBB, LAHB, IVCD)
 Cardiomyopathy
 Chest wall deformity
 Normal variant
 Lead misplacement
Poor R progression
ECG in COPD: Deep S in lead I, V5-
6
ST segment deviations
J point elevation
Common causes of
ST segment depression

1. Ischemia
2. “Strain”
3. Digitalis effect
4. Hypokalemia /
Hypomagnesemia
5. Rate-related changes
6. Any combination of the above
Various type of
ST segment depression
ST elevation
 Acute myocardial injury
 Myocardial aneurysm
 Pericarditis
 Early repolarization pattern
 Myocarditis
 Repolarization abnormality
chanellopathy : Brugada syndrome
electrolyte abnormality
drugs
Severe chest pain in a 45 yo
man
Acute IWMI with
ST depression V1-V3
Myocardial injury
Early repolarization
LBBB with STT changes
Acute pericarditis
Evolution of acute
pericarditis
ST segment elevations

Concave=pericarditis Convex=MI
Brugada pattern
T wave morphology
Inverted T abnormality
 Cardiac ischemia /injury
 Cardiomyopathy
 Brain pathology
 Repolarization abnormality
secondary repolarization
chanellopathy : LQTS
electrolyte abnormality
drugs
Leads that may normally
display
T wave inversion
 Lead III
 Lead aVF
 Lead aVL
 Lead V1 (and sometimes also lead V2)
 Lead aVR
 Causes of nonspecific ST-T
changes
 Ischemia  Hyperventilation
 LVH  Severe medical illness
 Cardiomyopathy  Severe emotional stress
 Mitral valve prolapse  Exercise
 Drug effect (digitalis,  Hypoxemia
antiarrhythmic agents)  Acidosis
 Electrolyte disorder  Temporature extremes
(i.e.,hypokalemia, (hypothermia,hyperthermi
hypomagnesemia) a)
 CNS disorder (stroke,  Many others...
intracerebral bleed,etc.)
Hyperkalemia
Tall peak T: HyperK
Hyper K
Hyper K: Tall T, wide QRS,
bradycardia
QT prolongation
Common causes of QT
prolongation
1. Drugs
○ Type I A & Type III antiarrhythmic agents
○ Tricyclic antidepressants
○ Phenothiazines
2. “Lytes”
○ Hypokalemia
○ Hypomagnesemia
○ Hypocalcemia
3. CNS
○ Stroke
○ Intracerebral or brainstem bleeding
○ Seizure
○ Coma
Hypokalemia
ECG in ischemic heart
disease
Q wave= infarction
 ST elevation= acute injury (transmural)
 ST depression= acute injury
(subendocardial)
 Inverted T wave =Ischemia

Consider for other

Differential diagnosis
 AMI
Acute Myocardial
Infarction (AMI)

ST elevated MI Non ST elevated MI

ECG:ST elevation ECG:ST
depression or
Q wave MI Non Q MI
Inverted T or
Q wave MI Non
Normal Q MI
ECG
Basic Lead Groups
 Inferior leads - II, III, aVF
 Septal leads - V1, V2
 Anterior leads - V1 to V4
 Lateral leads:
Lateral precordial leads - V4 toV6
high lateral leads - I, aVL
Basic Lead Groups
Coronary
anatomy
ECG in AMI
Dating infarction
Acute infarction - onset within hours up to a day
 ST segment elevation is hyperacute or coved,
and often marked
 Q waves are small or absent
 T wave inversion is minimal or absent
 Reiprocal ST segment depression is often
present, and may be marked.
Dating infarction
Recent (or “subacute”) infarction - onset within a day or
so, up to several days to a week.
 Q waves are often present; they may be small or large.
 ST segment elevation is minimal or absent.
 T wave inversion is often present and may be marked.
 Reciprocal ST segment depression is minimal or
absent.
Dating infarction
Old infarction - onset over a week ago
 Q waves are present and are often large.
 ST segment elevation is absent.
 T wave inversion is minimal or absent.
 There is no reciprocal ST segment
depression.
Acute MI (Anterior wall)
ST elevation:Acute inferior
wall MI
Old inferior wall MI
Summary
 Data gathering
1. Rate
2. Rhythm
3. Axis
4. Interval
5. Chamber enlargement
6. Morphology
Summary
Abnormalities
 Rate & rhythm (Arrhythmia)
Tachyarrhythmia
Bradyarrhythmia
 Morphology
P wave
QRS complex
ST segment
T wave
Interval: PR, QRS, QT
Further reading
 The Only EKG Book you’ll ever need.
Malcolm S. Thaler. Fourth edition.
 Rapid Interpretation of EKG’s.
Dale Dubin.
 Marriott’s Practical electrocardiography
Galen S. Wagner.
 ECG ทางคลินิก : ยงยุทธ สหัสกุล
 Total circulating level of thyroid hormone
 Total circulating level of free hormone
 Dynamic test of thyroid function
 Tests of peripheral tissue function
 Tests of hypothalamic-pituitary function
 Serum TT4
 Serum TT3
 Total circulating level of thyroid hormone
 Total circulating level of free hormone
 Dynamic test of thyroid function
 Tests of peripheral tissue function
 Tests of hypothalamic-pituitary function
- Direct methods:
FT4, FT3
- Indirect methods:
Calculated free thyroxine index
 Total circulating level of thyroid hormone
 Total circulating level of free hormone
 Dynamic test of thyroid function
 Tests of peripheral tissue function
 Tests of hypothalamic-pituitary function
 Thyroidal radioisotope uptake
 T3 suppression test
 Total circulating level of thyroid hormone
 Total circulating level of free hormone
 Dynamic test of thyroid function
 Tests of peripheral tissue function
 Tests of hypothalamic-pituitary function
 Ankle tendon reflex duration
 Serum lipid levels
 EKG
 Total circulating level of thyroid hormone
 Total circulating level of free hormone
 Dynamic test of thyroid function
 Tests of peripheral tissue function
 Tests of hypothalamic-pituitary function
 TSH(Thyrotropin)
 TRH(Thyrotropin releasing
hormone )test
  Thyroxine (T4) circulates ~ 99.97%
bound to the plasma proteins
-TBG (60-75%);
-TTR/TBPA (15 -30%)
- and Albumin (10%);

[Thyroxine Binding globulin (TBG), Transthyretin (TTR)/Prealbumin (TBPA)]

 Triiodothyronine(T3) is ~ 99.7%
bound, primarily to TBG
 TT4 and TT3 circulate at nanomolar
concentrations,
 FT4 and FT3 are measured in the
picomolar range
 Theinter-method variability for total
hormone measurements
TT4 10-17%
and TT3 20-30%,
 It is believed that the minute free fraction
of hormone is responsible for the biologic a
ctivity of thyroid hormones at the cellular l
evel
0.02% FT4
0.2% FT3

(Robbins J. 1996. Thyroid hormone transport proteins and the

physiology of hormone binding. In: Gray CH, James VHT, eds.
Hormones in Blood. London: Academic Press. 96-110.)
 Severe congenital TBG abnormalities
(TBG excess or deficiency)
 Familial Dysalbuminemic
Hyperthyroxinemia, FDH
 T4 and T3 autoantibodies
 Interfering substances such as
Rheumatoid Factor and Heterophilic antib
odies (HAMA)
 Salicylate, Furosemide
 Heparin
 Amiodarone, Iopanoic acid,
Propanolol > 160 mg/d
 Amphetamine
 Heroin, Methadone
 Phenytoin,
Phenobarbital,
Carbamazepine
 Dopamine (FT4 อาจปกติก็ได้)
 Lithium
 Glucocorticoid
 Dopamine
 Hyperestrogenic state
 Drug
 Disease
 Genetic
 Hyperestrogenic state
Pregnancy
Estrogen therapy
New born
Oral contraceptive pills
Estrogen producing
tumor
 Drug

Heroin
Methadone
Perphenazine
 Disease

Acute intermittent porphyria

Acute viral hepatitis
Chronic active liver disease
AIDS
Oat cell carcinoma
 Genetic

X-linked familial increase in serum TBG

 Exogenous androgens
 Major illness
 Drug
 Disease
 Genetic
 Drug

Corticosteroids
Drugs displacing thyroxine binding sites
- Salicylate
- Diphenylhydantoin
- Furosemide
 Disease

Cushing’s syndrome
Severe (Cirrhotic) liver diseases
Active acromegaly
Nephrotic syndrome
Protein-losing enteropathies
 Genetic

Familial X-linked deficiency of TBG

 Serum Tg measurement is used as a
tumor marker in the management of
patients with differentiated thyroid c
arcinomas (DTC)
 Current Tg methods are based either
on IMA or RIA techniques
 There is a trend for non-isotopic IMA
methods to replace RIA methods
 Mass of differentiated thyroid tissue
present (normal tissue + tumor)
 Any inflammation of, or injury to
thyroid tissue, such as follows fine n
eedle aspiration biopsy, surgery, radi
oiodine therapy or thyroiditis
 Degree of stimulation of TSH
receptors (by TSH, hCG or TSAb)
Tg

TSH

(DTC= differentiated thyroid carcinoma)

 Anti-thyroidperoxidase (TPO),
thyroglobulin (Tg) and TSH receptors
are used in the diagnosis of autoimm
une thyroid disorders
Thyroid Autoantibody Prevalences and
Associations with Hypothyroidism
 Antibody measurement techniques
have evolved from semi-quantitative
agglutination and complement fixati
on tests and whole animal bioassays
to specific ligand assays using recom
binant antigens and cell culture syst
ems transfected with the human TSH
receptor
 TRAb
(TRAb= (TSAb &receptor
Thyrotropin TBII) Ab;
TSAb= Thyroid stimulating Ab;
TBII = Thyrotropin binding inhibitory Ig)
 Thyroglobulin autoantibody (TgAb)
interference with serum Tg
measurements remains the most
serious problem limiting the clinical v
alue of serum Tg measurement.
 Serial TgAb measurements can be
used as an independent prognostic t
est for the presence of Tg-secreting t
hyroid tissue
Comparisons of TgAb-negative and TgAb-Positive Subjects
 TRAb tests are used in the
differential diagnosis of hyperthyroid
ism, the prediction of fetal and neon
atal thyroid dysfunction due to trans
placental passage of maternal TRAb
and prediction the course of Graves'
disease treated with antithyroid drug
s
(Michelangeli V, Poon C, taft J, Newnham H, Topliss D, and
Colman P. 1998. The prognostic value of thyrotropin receptor a
ntibody measurement in the early stages of treatment of Grave
s' disease with antithyroid drugs. Thyroid. 8:119-24.)
The relationship between serum TSH and free T4 concentration is
shown for normal subjects (N) and in the typical abnormalities of thyroi
d function: A, primary hypothyroidism ; B, central or pituitary-dependen
t hypothyroidism; C, thyrotoxicosis due to autonomy or abnormal stimul
ation of the gland; D, TSH-dependent thyrotoxicosis or thyroid hormone
resistance. Note that linear changes in the concentration of T4 correspo
nd to logarithmic changes in serum TSH.
An algorithm for the initial assessment of thyroid
function, based on initial assay of serum TSH. This
strategy also has some limitations.
TSH Reference Ranges
Measurement of serum T4, rather than serum TSH, is the more.
reliable single test of thyroid function when steady state conditi
ons do not apply, as in the early phase of treatment for thyrotox
icosis or hypothyroidism.
 Thisassay does not have a general
diagnostic role, despite previous sugges
tions that it might be useful in distinguis
hing true hypothyroidism from the hypot
hyroxinemia of severe illness.

(Burmeister LA, Reverse T3 does not

reliably differentiate hypothyroid sick synd
rome from euthyroid sick syndrome. Thyro
id 1995; 5: 435-41.)
- Grave's Disease
- Toxic nodular Goiter
- Toxic Thyroid Adenoma
- Acute viral thyroiditis
- Silent thyroiditis
- Struma ovarii
- Excessive Levothyroxine ingestion
 การส่งตรวจ Thyroid function tests จะส่ง
เมื่อมีข้อบ่งชี้ทางคลินิก
 การเลือกชนิ ดของการตรวจให้เหมาะสม จะ
เป็ นประโยชน์และประหยัดค่าใช้จ่าย
 การตรวจ TSH เพียงตัวเดียว สามารถใช้
เป็ นการตรวจคัดกรองขั้นแรกว่าผ้้ป่วยมีความ
ผิดปกติในการทำางานของต่อมธัยรอยด์หรือไม่
 ในผ้้ท่ม
ี ีการเจ็บป่ วยรุนแรงและสงสัยภาวะ
Hypothyroidism ให้ตรวจ TFT ทั้ง FT4,
FT3 และ TSH
Approach to Patients with
Abnormal LFTs
And
Viral Markers
 • Misnomer, not effectively assess the
actual function of liver
• Liver chemistry tests = biochemical

tests for hepatic injury, cholestasis,

hepatic synthesis
• Normal values do not mean “normal” eg. normal

ALT is Mean+ 2 SD and was set as early as 1950s

 Advantages Disadvantage
 Non invasive method of  Lack sensitivity: normal
screening liver results in serious liver
dysfunction disease
 Pattern of laboratory  Not specific for liver
test abnormalities to dysfunction
recognize the type of  Seldom lead to a
liver disorder specific diagnosis
 Assess the severity of
liver dysfunction
 Follow the cause of liver
disease
Chemistry Implication
ALT/AST Hepatocellular damage
Bilirubin Cholestasis, impair conjugation, biliary
obstruction
ALP Cholestasis, infiltration, obstruction
GGT Cholestasis, obstruction
5’-nucleotidase Cholestasis, obstruction
Albumin Synthetic function
PT Synthetic function
est of the biosynthetic capacity of the liv

 Albumin • Bilirubin  Aminotransferases

 Coagulation • Alkaline
factors phosphat
-ase
• GGT
 Liver synthesize factors I, II, V, VII, IX and X
 PT prolong : single or combination factors
deficiency
 Advantage of using PT more than INR
 Indicate severity and prognosis of liver disease
 PT prolong
 not specific for liver disease
 Consumptive coagulopathy, vitamin K deficiency and
ingestion of drugs
 Factor V is synthesized by liver but not affected
by vitamin K deficiency
 Vitamin K deficiency : PT improve at least 30%
after vitamin K injection 10 mg within 24 hrs
 Synthesized exclusively by the liver,
Half life 19 - 21 days
 Serum level reflects the rate of synthesis,
degradation and volume of distribution
 Hypoalbuminemia
Decreased synthesis:
-Severe liver damage or chronic liver disease
-Chronic inflammation
-Protein malnutrition
Losing albumin:
-Protein losing enteropathy
-Nephrotic syndrome
 Serum immunoglobulins are produced by
stimulated B lymphocyte
 Elevation of serum globulin level:
• Chronic liver disease:
- Indicate impaired function of RE cells
in hepatic sinusoids
- Shunting of portal venous blood
• Chronic inflammatory and malignant diseases

*Triger DR,et al,Lancet,1973

 Reverse A/G ratio
 Cronic liver disease or cirrhosis
 Chronic inflammation or infection
 Hypoalbuminemia ,hypoglobulinemia, anemia
and decrease cholesterol level
 Malnutrition
 Hypoalbuminemia ,hypoglobulinemia and
increase cholesterol level
 Protein losing enteropathy
 Nephrotic syndrome
 Test to detect injury to hepatocytes

•Albumin • Bilirubin  Aminotransferas

es
•Coagulation • Alkaline
factors phosphatase
• GGT
Hepatic Enzymes
ALT or SGPT
• Cytoplasmic
forms
• The half-life is
47+10 hrs
AST or SGOT
• Cytoplasmic and
Mitochrondial
form
• The half-life
• Total AST ~ 17
hrs
• Mitochondrial
AST ~87 hrs
Endogenous Hepatocyte
Exogenou
s
Ischemia Infection
(virus,
bacteria)
Immune
reaction Medications
(AIH,PBC,PSC)
Copper/Iron
overload Toxin / Alcohol
(Wilson’s disease/
Hemochromatosis)

Aminotransfera
 Most types of liver disease
: ALT>AST activity
 AST come from non hepatic tissue
: heart ,skeletal tissue and red blood cell
 ALT is low concentrations in tissue other than
liver
 Specific for hepatocellular injury
 Non hepatic conditions etc myopathic disease1-2 and
kidney

1
Scola RH, et al. Arg Neurosiquiatr 20
2
Lin YC, et al. Taiwan Erch Ko I Hsueh Hut Tsa Chili 19
Test Normal Mild Moderate Marked

AST 11 – 40 <2 -3 2 - 3 to 20 >20

ALT 3 - 40 <2 -3 2 - 3 to 20 >20

ALP 35 – 105 <1.5 -2 1.5 - 2 to 5 >5

GGT 2 – 65 <2 -3 2 - 3 to 10 >10

Factor AST ALT

Time of day 45% variation during day; highest in

afternoon, lowest at night
Day to day 5-10% variation from one day to next 10-30% variation from one day to next

Race/gender 15% higher in African-American men

Body mass 40-50% higher with high BMI 40-50% higher with high BMI
index (BMI)
Meals No effect No effect

Exercise 3-fold increase with strenuous exercise 20% lower in those who exercise at
usual levels than in those who do not
exercise or exercise more strenuously
than usual
Specimen Stable at room temp for 3 d, in refrigerator for Stable at room temp for 3 d, in
storage 3 wks (<10% decrease); stable for years refrigerator for 3 wks (10-15%
frozen (10-15% decrease) decrease). Marked decrease with
freezing/thawing
Hemolysis, Significant increase Moderate increase
hemolytic
anemia
Muscle injury Significant increase Moderate increase

Other Macroenzymes Macroenzymes

 Useful in narrowing the DDX for cause
of the liver injury
1) Level of aminotransferase elevation
2) Predominant AST elevation
3) Rate of aminotransferase declination
1. Level of aminotransferase elevation
 Acute hepatic injury
 Hepatocyte damage occurs abruptly and over a short
period of time
 Aminotransferase elevation : > 8 – 10 times UNL
 Chronic hepatic injury
 Hepatocyte damage occurs chronicity more than 6
months
 Aminotransferase elevation : < 5 times UNL
 Acute viral hepatitis (rarely >2000-3000
IU/L)
 Ischemic liver
 Toxic and drugs:
 Paracetamol, halothane
 Acute Budd-Chiari Syndrome
 Hepatic infarct or artery ligation
 Chronic Hepatitis B and C
 Alcohol
 Medication,Toxin
 Nonalcoholic Fatty liver Disease
 Autoimmune Hepatitis
 Wilson disease
 Hemochromatosis
 Disease Peak ALT A
(x URL)

Viral 10-40
Hepatitis
X- times, URL - upper reference limit
Alcoholic 2-8
2. Predominant AST elevation
 Alcoholic liver disease
 Extrahepatic source of AST:
 Hemolysis
 Skeletal muscle disease
 Cardiac muscle
 Cirrhosis
AST > ALT activity
 Alcohol induces release of mitochondrial AST
from cells without visible cell damage 1
 Pyridoxine deficiency decreases hepatic ALT
activity 2

1
Zhov S-L, et al. Hepatology 19
2
Luding S, et al. Gastroenterlogy 19
3. Rate of aminotransferase declination
 Rapid declination of aminotransferase
 Ischemic hepatic injury
 Drug induced hepatitis : short half life drug
 Acute biliary tract obstruction
 Fulminant hepatitis
 Slow declination of aminotransferase
 Acute viral hepatitis
 Drug induced hepatitis : long half life drug
 Autoimmune disease,Metabolic disease
The patients had a rapid striking elevation of AST and LDH, with rapid resolutio
10000

8000 AST
LDH
U/L 6000

4000

2000

0
1 2 3 4 5 6 7 8 9 10 Days

Giltin N,et al ,Am J Gastroenterol,199

 History of drugs, alcohol, co morbid conditions,
family history and PE
- consider -
HBsAgNASH (DM, obese: ALT>AST) Anti-HCV
Wilson(neuro, family: ceruloplasmin)
Autoimmune(female:ANA, SAM)
Hemochromatosis(Fe, ferritin, TIBC)

elevated > 6 months without cause

HCV-RNA
HBeAg, DNA

Biopsy
Test of the capacity of the liver to
transport organic anions and
metabolize
 Albumin drugs
• Bilirubin  Aminotransferases
 Blood-clothing • Alkaline
factors
phosphatas
e
• GGT
 Heme
Oxygenase
Hem Biliverdin
e IXα
Biliverdin
reductase
NADPH

Conjugated bilirubin Unconjugated bilirubin IXα

IXα
Lipid-soluble,
Water-soluble Bilirubin
UGT Normally in plasma
Normally in bile
Alkaline Phosphatase(ALP)
6

5
(relative to 25-35 yrs, Males)
Upper reference limit

Female
3 Male

0
0 10 20 Age 40 60
80
Age and Gender effects on URL for ALP:
The URL for 25-35 year old male is set at [Link] is many fold higher in
children and adolescents,reaching adult activities by about age 25.
Factor Change Comments
Day to day 5-10% Similar in liver disease and
health, and in elderly and young

Food ingestion Increases as much as 30 U/L In blood groups B and O;

remains elevated up to 12 hours;
due to intestinal isoenzyme

Body mass index 25% higher with increased BMI

(BMI)
Exercise No significant effect
Hemolysis Hemoglobin inhibits enzyme
activity
Pregnancy Increases up to 2-3 fold in third Due to placental and bone
trimester isoenzymes
Smoking 10% higher
Oral contraceptives 20% lower
Specimen storage Stable for up to 7 d in refrigerator,
months in freezer
 A membrane bound enzyme
 Decreasing order : proximal renal tubule, liver,
pancreas and intestine
 GGT activity in serum comes primarily from liver
 The half-life :
 7-10 days in humans
 28 days in alcohol-associated liver injury
 Increased GGT :
 diabetes, hyperthyroidism, rheumatoid arthritis, COPD,
acute myocardial infarction*
 Age-and gender related differences

*
Hedworth-Whitty RB,et al,Brit Heart J,196
 Mild elevation ALP
History and PE
Repeat to confirm Hepatic image

Normal Dilated duct

Normal Confirm
check GGT NASH

ERCP
GGT normal ↑GGT Specific disease
bone continue work up accordingly

Drug or alcohol
repeat 2-8 wks Parenchymal disease
after withdrawal
 Infiltrative lesion
• TBc, fungal, other granulomatous, malignancy
• PBC
 Liver mass (s)
 Partial biliary tract obstruction (Stone, PSC)
 Drugs – Anti - convulsants, Warfarin