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32 yr Male from Juni Indore

Reg. No. 186989/12; Ward - 23

Yellowish Discoloration of Eyes and urine 1 yr.

Pain in Right Side of Abdomen 1 yr.

Loss of Appetite 1 yr.

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History of Present Illness Yellowish discoloration of urine and eyes 1 yr

Abdominal pain 1 yr., Right upper abdominal region

- Not radiating, Gradual in onset

- Dull aching, Present for Whole Day

- No Aggravating or Reliving factor

- Associated with vomiting

- Vomiting not blood stained

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History of Present Illness Loss of Appetite 1 yr, Fever 6 mths, On and off, Low grade

- Not associated with Chills and rigors- Relived by Drugs

Abdominal distention with swelling in lower limbs 6 mth No H/o itching, passing clay colored or dark colored stool No H/o diarrhea or constipation No H/o reversal of normal sleep cycle No H/o loss of hair

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Past History No h/o blood transfusion

No H/o surgery, drug abuse, tattooing

Not a known Tubercular, HIV, DM, HT pt.

No H/o similar illness

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Family History No other family member have similar illness

No family H/o DM, HT, Tuberculosis, HIV

Personal History Known Alcoholic and smoker past 5 yrs

Taking 750 ml wine / day

Married since 10 yr, No child

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General Examination Conscious, Orientated

Ill built, Poorly nourished, Febrile

Anemic, Jaundiced

Clubbing, Edema

No Lymphadenopathy

PR 98/min, BP 132 / 86 mmHg

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Systemic Examination Oral Cavity Normal

Tenderness Right hypochondrium

Liver not palpable, Liver span 7-8 cm

Abdominal distended, Tense

Shifting dullness present

No dilated veins, scratch marks

No Flapping tremors

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Laboratory Investigations Complete Blood Count

Hb 6.5 gm%- Total Leukocyte Count 4,000 / mm3- Differential Count Neu 75 % - Lym 22%

- Eosino 02 % - Mono 00%- Baso 01 %

- Platelets 1.00 Lkh / mm3- No Hemoparasite, Normoblast or Schictocytes seen

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Laboratory Investigations Urine Routine and Microscopy

- Apperance - S. Turbid - Protein - Trace- Color - Yellow - Sugar - Nil- Reaction - Acidic - Pus Cells - 20-25/hpf- Specific Gravity - 1.030 - RBCs - Nil- Bile Salts - Present 4+ - Casts - Nil- Bile Pigments - Present 4+ - Crystals - Nil- Urobilinogen - Present ( 1+) - Epithelial Cells - 04 to 05

Cells/hpf

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Laboratory Investigations

Liver Function Test

- Total Bilirubin 4.8 mg/dl- Direct Bilirubin 1.9 mg/dl

- Indirect Bilirubin 2.9 mg/dl

- AST (SGOT) - 452 IU/L

- ALT (SGPT) - 440 IU/L

- Alkaline Phosphates 120 IU/L

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Viral Serum Markers

- Anti HAV Ig Negative- HBs Ag Negative

- Anti HEV Ig - Negative

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Ultrasonography Mild Splenomegaly

- Moderate Degree Ascitis- Moderate Degree Hepatomegaly

- ? Early changes of Cirrhosis

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Probable Diagnosis

- Chronic Decompensated Liver Disease

- (? Alcohol Related)

- Ascitis

- Anemia

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Metabolic Function - Lipid Soluble Drugs

- Toxic Compounds

- Hormones

- Insulin

- Parathyroid Hormone

- Estrogen

- Cortisol

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Synthetic Function - Plasma Protein- Endogenous Lipid

- Lipoprotein- Coagulation Factor- Glycogen and Glucose- Hormones

- Angiotensinogen- Insulin like Growth Factor I- Triiodothyronine

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Defense Mechanism - By Kupffers Cells

Storage Function - Glycogen

- Vit. A, D, B12

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A-Ascites

C-Cyanosis/Clubbing

B-Bleeding tendency

D-DIC

Dr. Sanjeev Narang

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E-Erythema-Palmar

F-Foetor Hepaticus

G-Gall stones

H-Hyperkinetic Circ.

Dr. Sanjeev Narang

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I-Infections frequent

J-Jaundice

K-Kidney failure

CLINICAL MANIFESTATION OFLIVER DISEASEDr. Sanjeev Narang

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L-Low slurred speech

N-Naevi Spider

M-Musculoskeletal

O-Oedema


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P-Pancreatitis/Inc.PT

Q-Quivers (Tremors)

R-Respiratory Failure

S-Splenomegaly


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T-Thrombocytopinea

U-Uraemia

V-Varices

W-Weight Loss


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X-Ameno,Infert,Ov.Atro

Y-Atrophytestes,Impotence,

Feminisation


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Z-Zellweger syndr.


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METABOLIC FUNCTION

1. Determination of Bilirubin

2. Measurement of Ammonia

3. Measurement of Lipoprotein

4. Evaluation of Drug Metabolism

5. Measurement of Bile Acid

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SYNTHETIC FUNCTION

1. Measurement of Plasma Protein

- Albumin

- Alfa-1-antitrypsin- Ceruloplasmin

- Prothrombin time

- Des-gamma-Carboxy prothrombin

2. Blood glucose level

3. Lipid profile

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Plasma Enzyme

1. Aspartate Transaminase

2. Alanine Transaminase

3. Alkaline phosphates

4. Lactate Dehydrogenase

5. Gamma glutamyl Transferase

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1. Determination of Bilirubin

2. Measurement of Ammonia

3. Measurement of Lipoprotein

4. Evaluation of Drug Metabolism

5. Measurement of Bile Acid

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Bilirubin

- Major metabolite of Heme

- Source of Heme

Hemoglobin (From Senescent RBC and

Precursors)

- Myoglobin- Cytochromes

- Daily Bilirubin Production 250 to 350 mg

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Light Photoisomerization of Bilirubin to more

Water Soluble Form

Unconjugated Bilirubin Short half life ( 5 Min.)

Conjugated Bilirubin Half life (

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Delta Bilirubin (Biliprotein)

Conjugated Bilirubin + Albumine

- Normally Virtually no Conjugated Bilirubin

reach in plasma

- Half Life 17 days ( Similar to Albumin)

- Prolonged jaundice during recover fromHepatocellular Injury

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Laboratory Tests of Bilirubin

Measured using Diazotized Sulfanilic acid

Caffeine or Methanol Used as a accelerators for

Unconjugated Bilirubin

Direct bilirubin 70% to 80 % of Conjugated Bilirubin- Delta-Bilirubin- Small percentage of Unconjugated

Bilirubin

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Determinations Pre-Hepatic Hepatic Post-HepaticSerumTotal Bilirubin Very High High Very HighDirect Bilirubin Normal Mod. Increased Mod.IncreasedIndirect Bilirubin High Mod. Increased Mod.IncreasedUrineBile Pigment Normal Mod. Increased Mod.

IncreasedBile Salts Normal Mod. Increased Mod.IncreasedUrobilinogen Very High Increased Normal orAbsent

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Derived from Amino Acid Metabolism

Metabolized through Urea Cycle

Increased Cirrhosis

- Reyes Syndrome

- Acute Hepatic Failure

Increased Ammonia Glutamine increased

- GABA decreased

Leads to Hepatic Encephalopathy

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Arterial level Correlate well with Degree of

Encephalopathy

Also increased in

- Congenital deficiency of Enzyme (OCT)

- Acute Leukemia

- Following Bone Marrow Transplantation- Use of glycine irrigation for TURP

- Smoking, Exercise

- Valproic Acid

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Laboratory test For Ammonia

Arterial Blood is preferred

Kept on ice until separation of cells from plasma

Avoid tourniquets and fist clenching and relaxing

Method - Enzymatic Assay

- Ketoglutarate and Ammonia

NADPH Glutamate Dehydrogenase

NADP

Glutamate

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Synthesize Cholesterol

- Apolipoprotein

- Lipoproteins

Alcoholic Hepatitis Increase

Non Alcoholic Steatohepatitis Increased

Triglyceride Cirrhosis Decreased Lipid and Lipoprotein

Lipoprotein-X Present in Bile duct Obstruction

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Lipoprotein-X (Abnormal Lipoprotein)

Composed of - Phospholipids

- Cholesterol

- Apolipoprotein C

- Albumin

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Impaired in Liver Disease

Lipid-Soluble More Water Soluble

Phase I Reaction Oxidation- Hydroxylation

Phase II Reaction - Conjugation

Two pattern of Metabolism- Drugs with high First Pass Metabolism- Depends upon Hepatic Blood Flow- Drugs with slow clearance by Liver- Depends upon Hepatocytes Function

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Most widely used drugs are

1. Aminopyrine labeled with radioactive carbon

- Measurement of Radiolabeled CO2 in Breath- False low result in Vit. B12 and Folate Deficiency

2. Caffeine Clearance

- Increased by Smoking

- Decreased with increasing Age

Insensitive to liver injury in Chronic Hepatitis and

early cirrhosis

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Most widely used drugs are

3. Lidocaine metabolism

- Converted to Monoethyl glycinexylidide

(MEGX) by Cytochrome P-450

Depends upon hepatic Blood Flow

- To evaluate allograft viability beforeand after Transplantation

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Synthesize in liver from Cholesterol

Primary Bile Acid Cholic Acid

- Chenodeoxycholic Acid

Secondary Bile Acid - Lithocholic Acid

- Deoxycholic Acid

- Ursodeoxycholic Acid

95 % Bile Acid Reabsorbed from Small Intestine

Measurements Total Bile Acid

- Secondary : Primary Bile acid

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Increased in Hepatic dysfunction with normal ratio

Cirrhosis Cholic Acid Decreased

- Increased Sec. : Pri. Bile Acid Ratio

Cholestasis Secondary bile acid not formed

- Decreased Sec : Pri Bile Acid Ratio

Food intake Increased Bile Acid Sample - Fasting or some time after meal

Method Chromatographic Method (HPLC)

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1. Measurement of Plasma Protein

- Albumin

- Alfa-1-antitrypsin

- Ceruloplasmin

- Prothrombin time

- Des-gamma-Carboxy prothrombin

2. Blood glucose level

3. Lipid profile

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Protein Synthesis

Decreases in liver disease

Greater with Chronic Liver Disease

Half life - Factor VII (Shortest 4 to 6 Hr)

- Transthyretine (1 to 2 days)

- Transferrin ( 6 days)- Albumin (20 days)

Also due to decreased delivery of amino acid in

cirrhosis and portal hypertension

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Acute Hepatic Failure

- Normal Albumin and -globulin

- Decreased 1-, 2- and globulin

Cirrhosis- Albumin, 1-, 2-globulin and Tranferrin Decreased- Increased Ig G and Ig A

Primery Biliary Cirrhosis- Increase Ig M

Autoimmune Hepatitis Increased Ig G

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Albumin

- Liver synthesis is increased by low plasma

oncotic pressure

- Decreased by Cytokines IL-6

- Normal synthesis - 120 mg/kg/day

- Measured by Bromocresol Green MethodPrinciple

Albumin + Bromocresol Green Green colored com.

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Other serum protein

- -1 Antitrypsin

- Inhibit Trypsin and Elastin

- Gene located on Chr. 14

- Increased incidence of Emphysema and

Neonatal Hepatitis- Acute phase reactant

- 3% Cases progress to Cirrhosis

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Other serum protein

- Ceruloplasmin

- Convert Iron to Ferric state to allow binding

with Transferrine

- Decreased in Wilsons Disease

- Located on Chromosome 13- Young adult with psychiatric and neurological

symptoms

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Other serum protein

- Ceruloplasmin

- Keyser-Fleischer rings Copper deposition in

Iris

- Acute Wilsonian Hepatitis

- Increased by Estrogens, Pregnancy, Cytokines- Measured by Immunoassay

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Clotting Factors

- Prothrombin Time

- INR To monitor Oral Anticoagulant Therapy

DES- -CARBOXY PROTHROMBIN

- Vit. K Dependent Coagulation Factors

( II,VII,IX,X)- Activated by -carboxylation of glutamic acid

- Inactive factor II(Des--carboxy prothrombin)

- Measure d by Immunoassay

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DES- -CARBOXY PROTHROMBIN

- Increased in - Vit. K Deficiency

- Hepatocellular Carcinoma

- Warfarin Therapy

Other Synthetic Function

- Hypoglycemia ( Decreased Glycogen Content andImpaired Gluconeogenesis)

- Lipid Synthesis

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Plasma Enzyme Level

Cellular Location of Enzyme

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Cellular Damage Leads to Leakage of Cellular

Enzyme in Plasma

Most Common Cause Membrane Damage

Alcohol Increase Mito. AST

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Enzyme Primary Reflecting Cell Injury

Enzyme Primary Reflecting Canalicular Injury

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Cytoplasmic and Mitochondrial Enzymes

Half Life AST Cytoplasmic 17 3 hr

- AST Mitochondria 87 hr

- ALT 42 11 hr

- LDH (4&5) 4 to 6 hr AST in heptocytes 7000 times more then plasma

ALT in heptocytes 3000 times more then plasma

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Acute Hepatocellular Injury AST > ALT

Chronic Hepatocellular Injury ALT > AST

LDH Mildly increased

Alcoholic injury AST more increased

As the disease progress Fibrosis occurs- ALT Decrease

- AST : ALT Ratio Increase

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Enzyme Primary Reflecting Canalicular Injury

Gamma Glutamyltransferase Half life 10 days

Liver Alkaline Phosphatase Half life 3 days

Higher level in Obstructive injury and Space

occupying Lesion

Also increase in Cirrhosis

Microsomal enzyme inducer drugs

- Ethanol, Phenytoin and Carbmazepine

- Increase GGT and Alkaline Phosphatase

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Determinations Pre-hepatic Hepatic Post-hepaticSGPT (ALT) Normal Very High Mod.

increased

SGOT (AST) Normal Very High Mod.Increased

ALP Normal Mod.Increased

Very High

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-Fetoprotein

Fetal plasma protein

Serum level At birth 10,000 ng/ml

- At one yr of age 10 ng/ml

Increases in Hepatitis (10 to 20 times)

Main use In screening and diagnosis ofHepatocellular Carcinoma

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Antimitochondrial antibodies (AMA)

- Subtype M2 - Primary Biliary Cirrhosis

- Subtype M1 Syphilis

- M6 Isoniazide induced hepatitis

- M7 - Cardiomyopathy

Primary Sclerosing Cholengitis- perinuclear Antineutrophil Cytoplasmic Antibodies (p-ANCA)- Antinuclear Antibodies (ANAs)- Anti-Smooth muscle antibodies (ASMAs)

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Autoimmune Hepatitis

- Type 1 Antinuclear antibodies (ANA)

- Anti smooth muscle antibodies (ASMA)

- Type 2

Anti liver-kidney microsomal antibodies (anti LKM 1)

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Hepatitis A

- Picorna virus family of RNA Viruses

- Transmission Fecal-Oral Route

- Incubation period - < 1 mth

- Common in children

- Self-limiting disease

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Hepatitis B

- Hepadnavirus Family

- DNA Virus

- Transmitted by Body Fluids

- Tran placental spread

- HBV DNA Measurement

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Hepatitis B

- Outcome of Infection

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Hepatitis C

- Flavivirus

- RNA Virus

- Transmitted by Body Fluids

- Dialysis associated

- IV Drug Abuser- Tran placental spread

- More case progress to chronic Phase

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Hepatitis C

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Hepatitis D

Incomplete Virus

RNA Virus

Replicate only in presence of HBV

Co-infection or Super infection

IV Drug Abusers and Hemophiliacs Diagnostic Test Anti HDV antibody (Total and IgM)

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Hepatitis E

RNA virus

Course similar to HAV

Spread by fecal-oral route

In pregnancy Fatality Rate (About 20%)

Diagnostic Test Anti HEV Antibody

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Hepatitis G Virus and TTV

Isolated from blood donors

Also from post transfusion hepatitis (

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To predict progression to Cirrhosis

Markers that involve in production of collagen and

break down of normal matrix protein

Includes

- Circulating fragments of collagen or procollagen

- Enzymes involved in collagen synthesis and Matrix

breakdown

- Matrix Glycoprotein and Proteoglycans

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Congenital Disorder of Bilirubin Metabolism

Gilberts Syndrome

- 3% 5% of Population

- Reduced (About 30%) activity of Bilirubin-UDP-

glucuronyl transferase I

- Total Bilirubin - < 5.0 mg/dl- Diagnosed procedures - Increased by Fasting

- Decreased by Phenobarbitone

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Crigler-Najjar Syndrome- Sever deficiency of Bilirubin-UDP-glucuronyl Transferase- Type I No enzyme activity

- Sever Unconjugated Hyperbilirubinemia in Infants- Kernicterus (Bilirubin in Basal Ganglia)

- Type II 10 % of normal activity- Survival upto adulthood

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Dubin-Johnson Syndrome- Canalicular multispecific organic anion transporter defect

(cMOAT)- Increased Conjugated Bilirubin (Total Bilirubin

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Acquired Disorder of Bilirubin Metabolism

Hemolysis Unconjugated Hyperbilirubenemia

Fasting Increased Unconjugated Bilirubin

Septicemia

Total parenteral Nutrition

Androgens- Increased Conjugated Bilirubin

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Serum Total Bilirubin < 1.0 mg/dl

Serum Direct Bilirubin 0.0 to 0.3 mg/dl

Serum Indirect Bilirubin - < 0.8 mg/dl

Serum Ammonia - 15 45 g/dL

Serum AST - Upto 40 units/L

Serum ALT - Upto 40 units/Lt Serum GGT - 8-38 units/Lt

Serum Alkaline Phosphates - 26-99 units/Lt

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Serum Total Protein - 6.0 to 8.3 gm/dL

Serum Albumin - 3.4 - 5.4 gm/dL

Serum Globulin 2.3 3.5 gm/dl

Serum bile acid - 0 to 15 mol/Lt

Primary Bile Acid 68 72 %

Secondary Bile Acid

27

30 % Alpha-1 antitrypsin - 1.5-3.5 gm/Lt

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Lipid Profile

Serum Cholesterol - Upto 200 mg/dl

Serum Triglycerides -

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Asymptomatic in majority of pt.

Most common symptoms Due to Abnormal

Bilirubin Handling

Loss of stool color

Dark discoloration of urine

Jaundice

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Laboratory Tests

Elevation of Aminotransferase Hallmark of AHCI

Alkaline Phosphates No or minimal elevation

Jaundice Acute Hepatitis A 70% Cases

- Acute Hepatitis B 33% Cases

- Acute Hepatitis C 20% Cases

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Pattern of Hepatocellular injury

Two main pattern

1. Immunological Damage to Hepatocytes

2. Direct injury to Hepatocytes

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ellweger syndrome, also calledcerebrohepatorenal syndrome is a rare,

congenital disorder, characterized by the

reduction or absence of functional peroxisomes

in the cells of an individual.[1] It is one of a family

of disorders called leukodystrophies. Zellweger

syndrome is named after Hans Zellweger, a

former professor ofPediatrics and Genetics at the

University of Iowa who researched this

[2][3]
http://en.wikipedia.org/wiki/Congenital_disorderhttp://en.wikipedia.org/wiki/Peroxisomehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Leukodystrophieshttp://en.wikipedia.org/w/index.php?title=Hans_Zellweger&action=edit&redlink=1http://en.wikipedia.org/wiki/Pediatricshttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/University_of_Iowahttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Diseasehttp://en.wikipedia.org/wiki/University_of_Iowahttp://en.wikipedia.org/wiki/Geneticshttp://en.wikipedia.org/wiki/Pediatricshttp://en.wikipedia.org/w/index.php?title=Hans_Zellweger&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Hans_Zellweger&action=edit&redlink=1http://en.wikipedia.org/wiki/Leukodystrophieshttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Peroxisomehttp://en.wikipedia.org/wiki/Congenital_disorder

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Laboratory Tests of Bilirubin

- Male > Female

- Peak Value 14 to 18 yrs

- Strenuous exercise Increase Value
http://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndromehttp://en.wikipedia.org/wiki/Zellweger_syndrome

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