Intern Tutorial

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. 2. 3. 4.

Are normal P waves present? Are the QRS complexes narrow? What is the relationship between the P wave and the QRS complexes? 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

PJ C

PJC  Premature QRS complex (usually narrow QRS)  Absent P wave

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 250350/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 ~350500/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  Multiple

ventricular foci rapidly discharge producing a totally erratic ventricular rhythm without identifiable waves

Bradyarrhythmia Sinus node dysfunction Sinus arrest /pause Sinus exit block Sinus bradycardia Tachy-brady syndrome

AV block 1st degree AV block 2nd degree AV block 2nd degree AV block type I 2nd degree AV block type II 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  Rate

30-40 /min  Wide QRS complex

Accelerated Idioventricular rhythm  Rate

50-100/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 

Acces sory Pathw

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

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, V56

ST segment deviations

J point elevation

Common causes of ST segment depression 1. 2. 3. 4.

Ischemia “Strain” Digitalis effect 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 LVH Cardiomyopathy Mitral valve prolapse Drug effect (digitalis, antiarrhythmic agents) Electrolyte disorder (i.e.,hypokalemia, hypomagnesemia) CNS disorder (stroke, intracerebral bleed,etc.)

      



Hyperventilation Severe medical illness Severe emotional stress Exercise Hypoxemia Acidosis Temporature extremes (hypothermia,hyperthermi a) Many others...

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 Q MI Normal ECG

Basic Lead Groups  Inferior  Septal

leads - II, III, aVF leads - V1, V2

 Anterior  Lateral

leads - V1 to V4

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  Serum

TT4 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  T3 suppression test

uptake

 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  Serum lipid levels  EKG

duration

 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  TRH

(Thyrotropin) (Thyrotropin releasing hormone )test

(T4) circulates ~ 99.97% bound to the plasma proteins

 Thyroxine

-TBG (60-75%); -TTR/TBPA (15 -30%) - and Albumin (10%); [Thyroxine Binding globulin (TBG), Transthyretin (TTR)/Prealbumin (TBPA)]

(T3) is ~ 99.7% bound, primarily to TBG

 Triiodothyronine

 TT4

and TT3 circulate at nanomolar concentrations,  FT4 and FT3 are measured in the picomolar range

 The

inter-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  Drug  Disease  Genetic

state

 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-thyroid

peroxidase (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 &receptor TBII) Ab; (TRAb= (TSAb Thyrotropin 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.

 This

assay 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 



 

Non invasive method of screening liver dysfunction Pattern of laboratory test abnormalities to recognize the type of liver disorder Assess the severity of liver dysfunction Follow the cause of liver disease

Disadvantage 

 

Lack sensitivity: normal results in serious liver disease Not specific for liver dysfunction Seldom lead to a specific diagnosis

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 Coagulation factors

• Bilirubin • Alkaline phosphat -ase • GGT



Aminotransferases

 

 

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 •Coagulation • Alkaline factors phosphatase • GGT



Aminotransferas es

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 Ischemia

Hepatocyte

Exogenou s Infection (virus, bacteria)

Immune reaction (AIH,PBC,PSC)

Medications

Copper/Iron overload (Wilson’s disease/ Hemochromatosis)

Aminotransfera

Toxin / Alcohol

  

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

Scola RH, et al. Arg Neurosiquiatr 20 Lin YC, et al. Taiwan Erch Ko I Hsueh Hut Tsa Chili 19 1

2

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 to 10

>10

<2 -3

Factor

AST

Time of day

ALT 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 index (BMI)

40-50% higher with high BMI

40-50% higher with high 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 storage

Stable at room temp for 3 d, in refrigerator for Stable at room temp for 3 d, in 3 wks (<10% decrease); stable for years refrigerator for 3 wks (10-15% frozen (10-15% decrease) decrease). Marked decrease with freezing/thawing

Hemolysis, hemolytic anemia

Significant increase

Moderate increase

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 (x URL)

Viral Hepatitis

10-40

X- times, URL - upper reference limit

Alcoholic

2-8

A

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

Zhov S-L, et al. Hepatology 19 Luding S, et al. Gastroenterlogy 19 1

2

3. Rate 

Rapid declination of aminotransferase    



of aminotransferase declination

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

AST LDH

8000

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 drugs  Aminotransferases  Albumin • Bilirubin 

Blood-clothing • Alkaline factors

phosphatas e • GGT

Hem e

Heme Oxygenase

Biliverdin IXα Biliverdin reductase NADPH

Conjugated bilirubin IXα Water-soluble Normally in bile

Bilirubin UGT

Unconjugated bilirubin IXα Lipid-soluble, Normally in plasma

Alkaline Phosphatase(ALP) Upper reference limit (relative to 25-35 yrs, Males)

6 5 4 Female Male

3 2 1 0

0 80

10

20

Age

40

60

Age and Gender effects on URL for ALP: The URL for 25-35 year old male is set at 1.0.ALP 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 (BMI)

25% higher with increased BMI

Exercise

No significant effect

Hemolysis

Hemoglobin inhibits enzyme activity

Pregnancy

Increases up to 2-3 fold in third trimester

Smoking

10% higher

Oral contraceptives

20% lower

Specimen storage

Stable for up to 7 d in refrigerator, months in freezer

Due to placental and bone isoenzymes

 

 

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

Normal

Hepatic image Normal Dilated duct

Confirm check GGT

GGT normal ↑GGT bone continue

NASH ERCP Specific disease work up accordingly

Drug or alcohol repeat 2-8 wks after withdrawal

Parenchymal disease



Infiltrative lesion • •

  

TBc, fungal, other granulomatous, malignancy PBC

Liver mass (s) Partial biliary tract obstruction (Stone, PSC) Drugs – Anti - convulsants, Warfarin