Case study :

CASE
 Case 5
ชายอายุ 60 ปี อาชีพทำานา
อาการสำาคัญ : อาเจียนเป็ นเลือด
ประวัติปัจจุบัน :
• 1 ชม.ก่อนมา รพ. ผู้ป่วยอาเจียนเป็ นเลือดสด ประมาณ 2
ช้อนโต๊ะ ก่อนหน้านัน ้ อาเจียนบ่อย แต่ไม่เคยเป็ นเลือด
• 3 เดือนก่อนมา รพ. รูส ้ ึกเหน่ ือยง่าย เบ่ ืออาหาร น้ำาหนักตัวลด 8
กิโลกรัมภายในเวลา 3 เดือน สังเกตว่าท้องโตขึ้นมาก
ไม่มีอาการปวดท้อง ไม่มีถ่ายอุจจาระหรือถ่ายปั สสาวะเป็ นเลือด
ประวัติอดีต :
• ด่ ืมสุราทุกวันวันละ 2 แก้วเป็ นเวลานาน 30 ปี
• กินยาชุดแก้ปวดเม่ ือยประมาณเดือนละครัง้
• ไม่สูบบุหร่ี ไม่เคยมีประวัติเจ็บป่ วยรุนแรง
ประวัติครอบครัว : ปฏิเสธประวัติมะเร็งในครอบครัว มีบุตร 3 คน หย่ากับภรรยาได้ 30 ปี
ปั จจุบันพักอาศัยอยู่คนเดียว
Pertinent
subjective data
• Hematemesis with no Hematochezia and Melena
• Fatigue, Anorexia, Significant weight loss
• Abdominal swelling with no pain
• Chronic alcoholism
• NSAIDs
 Hematemesis
• Hematemesis is vomitus of red blood or
"coffee-grounds" material.
• It indicates an upper GI bleeding(above the
ligament of Treitz).

Harrison's Online
http://www.accessmedicine.com/content.aspx?aID=2864124&searchStr=hematemesis
 Hematochezia

• Hematochezia is defined as the passage

of bright-red blood from the rectum that
can be produced by bleeding from the
colon, rectum, or anus. However, if
intestinal transit is rapid during brisk
bleeding in the upper intestine, bright-red
blood may be passed unchanged in the
stool

CURRENT Surgical Diagnosis and Treatment, 12th Edition,Gerard M. Doherty and Lawrence
W. Way
Melena

• Black tarry stools caused

by stomach acid or
intestinal bacterial
conversion of hemoglobin
to the black pigment
hematin; suggests blood
loss of > 50–100 mL

Clinician's Pocket Reference, 11th Edition, Leonard G. Gomella, Steven

A. Haist
 Ligament of
Treitz
Upper Lower GI
GI
40-50%
Melena /
Hematochezia
No complain

Bloody vomiting Coffee – ground apperance

(RBC lyse by gastric acid)

tp://emedicine.medscape.com/article/196561-overv
Ligament of
Treitz
 Causes of Upper
•
GI bleeding
Peptic Ulcer 35-62%
• Esophageal Varices 4-31%
• Mallory – Weiss tears 4-13%
• Gastroduodenal erosion 3-11%
• Erosive esophagitis 2-8%
• Malignancy 1-4%

Chronic alcoholism and NSAIDs

Ref : Harrison’s ed.16 page 235h

 Causes of Upper
•
GI bleeding
Peptic Ulcer High incidence + NSAIDs user
• Esophageal Varices
• Mallory – Weiss tears No Massive
• Gastroduodenal erosion vomiting

• Erosive esophagitis No GERD

• Malignancy (Gastro esophageal
reflux disease)
Confirm?

Harrison’s ed.16 page 235

 Causes of Upper
•
GI bleeding
Peptic Ulcer
• Esophageal Varices
• Gastroduodenal erosion
• Malignancy

Differential Diagnosis
• Clinical presentation
• Physical Examination
• Endoscopic results

Harrison’s ed.16 page 235

Pertinent
subjective data
• Hematemesis with no Hematochezia and Melena
• Fatigue, Anorexia, Significant weight loss
• Abdominal swelling with no pain
• Chronic alcoholism
• NSAIDs
Causes of Fatigue, Anorexia
and Weight loss
• Fatigue : Hypothyroidism, Anemia, Depression, Hepatitis,
Diabetes mellitus, Cancer, Alcoholism, Chronic fatigue
syndrome, Autoimmune disease, Adrenal
insufficiency,Aging

• Anorexia : Anorexia Nervosa, Severe Depression,

Dementia, AIDS, Cancer,
Cancer Chronic renal disease

• Weight loss : Cancer,

Cancer GI disorder, Cardiac disorder,
respiratory disorder, Renal insufficiency, Rheumatologic
disease, Infection, NSAID Medication
Significant
Weight Loss
• Loss of >5% of body weight over 6–12
months (Harrison Internal Medicine 17 Ed)
th

• Loss of >10% of ideal body weight over 3

months (Schwartz's Principles of Surgery, 8th Edition)
 อ่านเสริม
• However, gastrointestinal bleeding should not be
automatically attributed to esophageal varices in a patient
with jaundice, ascites, splenomegaly, spider angiomas, or
hepatomegaly; over half of cirrhotic patients who present
with acute hemorrhage are bleeding from gastritis or peptic
ulcer.
• ดังนั้น ผู้ป่วย cirrhosis ไม่จำาเป็นเกิด Upper bleeding จาก eso varice
ซึ่งเกิดจาก portal hypertension แต่อาจเกิดจาก gastritis ก้อได้ ใน เคสนี้มีปัจจัยเรื่อง
alcohol และ analgesics ก้ออาจเป็นสาเหตุของอาการ GI bleeding ได้เหมือนกัน
(เป็นแผลที่กระเพาะ หลอดอาหารก้อได้ ) หากต้องการทราบพยาธิอยู่ที่ไหนใน GI
ต้องส่องกล้องภายใน 12 ชั่วโมง(ไม่แน่ใจนะ) เพื่อดูตำาแหน่ง
และให้การรักษาที่เหมาะสมก่อนการแยกว่า สาเหตุจาก bleed คืออาไร (แยกเป็น non-
varice and varice treatment ดูในชีทภาษาไทยที่ให้ไปง่ะ
และควรดูขอ้ จำากัดในการส่องกล้องด้วยนะ ( pt ต้อง stable ก่อนส่อง และก้อการประเมินตาม
stage ในชีท)
Pertinent
subjective data
• Hematemesis with no Hematochezia and Melena
• Fatigue, Anorexia, Significant weight loss
• Abdominal swelling with no pain
• Chronic alcoholism
• NSAIDs
Abdominal swelling
with
•
no pain
Heart Disease No complain of peripheral edema
• Liver Disease
• Renal DiseaseNo Hematuria and no facial swellin
• Abdominal Cancer
• Hypoalbuminemia
 Pertinent
subjective data
Fatigue
Hematemesi Anorexia Abdominal Swelling
s Weight loss with no pain
Upper GI Bleeding
•Cancer •Liver Disease
Clinical presentation + PE •Infection •Abdominal
•Alcoholism Cancer
•Hypoalbuminemi
Endoscopic results •NSAIDs
(confirmed) •Malnutrition a

PE, Lab results

Alcoholic Liver Diseases ?
Expected Physical
Examination
• Vital sign : BP , PR , RR
• Sclera : Jaundice
• Skin : Ecchymoses
• Stigmata of chronic liver disease : spider
nevi, liver palm, gynecomastia, testicular
atrophy
• Liver : can’t be palpable
• Spleen : palpable
• PR : hemorrhoid with no rectal shelf
• Ascites??
 Physical
System
Examination
Results Interpretations

Vital BT 37 °c Normal ( no infections )

sign PR 100 /min (80-100) Baroreceptor reflex from blood
loss
RR 20/min (12-20) Normal

BP 100/60 mmHg Blood loss

(120/80)
GA good consciousness No Encephalopathy
not pale, mild jaundice Liver damage/ Hemolytic Anemia/
Biliary Obstruction ( tumor/stone )

Skin ecchymosis both legs Decrease Coagulation factor or

plt and low Vit K absorption
 Physical
Examination
System Results Interpretations
HEENT mild icteric sclera Pre/intra/Post -hepatic
jaundice
mild enlargement of Increase estrogen
both parotid glands

no lymphadenopathy, No Metastasis
no injected pharynx No infections
Chest spider nevi at anterior Increase estrogen
chest wall,
breast enlargement
both sides
 Physical
System
Examination
Results Interpretations
Lungs normal breast sound, no No Infections
adventitious sound
Heart normal S1 and S2, no -
murmur
Genitalia Testicular atrophy both Increase estrogen
sides
PR hemorrhoid, no rectal Inferior rectal vein
shelf dilatation from portal
hypertension
or no metastasis from
Abdominal cancer
 Physical
Examination
System Results Interpretations
Abdomen • markly distended
abdomen with superficial
vein dilatation Ascites,
• shifting dullness , fluid Portal
thrill
• liver can’t be palpate
Hypertension
• mildly enlarged spleen
and hypoactive bowel
sound
• mild tender at RUQ
Ecchym
osis

P
E
Icteric
sclera

P
E
Spider
nevi

P
E
Hemor
rhoid

P
E
Shifting
Dullness
 Fluid thrill

Ref :
http://images.google.co.th/imgres?imgurl=http://imgsrc.baidu.com/baike/pic/item/2e6fa7381ce2a7d6d462
256c.jpg&imgrefurl=http://baike.baidu.com/view/1655994.htm&usg=__b1ewpP9C6zLmT5SKIsTjUdwQ8N8
=&h=640&w=480&sz=35&hl=th&start=17&um=1&tbnid=PQG0l_FOfN8FBM:&tbnh=137&tbnw=103&pre
v=/images%3Fq%3Dfluid%2Bthrill%26um%3D1%26hl%3Dth%26lr%3Dlang_th%26sa%3DX
Pertinent
subjective data
& Physical examination conclu
- Splenomegaly - Gynecomastia
- Caput Medusae - Jaundice
- Ascites - Ascites
- Hemorrhoid - Weight loss
- Anorexia
- fatigue
- Ecchymosis
- Salivary gland enlargement

Portal
hypertension Alcoholic cirrhosis
(caused Esophageal varices?)
chachexia
Confirmed by Abdominal pain
endoscopic
Suspected liver CA
Fatty liver, Alcoholic
hepatitis, Alcoholic cirrhosis
and HCC
Fatty liver Alcoholic hepatitis Alcoholic cirrhosis
Hepatocyte injury charaterise by Anorexia
balloon degeneration, Spotty
RUQ discomfort Malnutrition
necrosis, PMN infiltration
Nausea Fibrosis in perivenular and Weight loss
Jaundice perisinusoidal space of Disse
Reduction in skeletal muscle
Difficulty differentiate May develop to alcoholic cirrhosis mass
alcoholic/non alcoholic Hepatocellular dysfunction
fatty liver unless an Fever
accurate drinking history Portal hypertension
is verified Spider nevi biopsy Progressive jaundice
Jaundice
GE varices
Abdominal pain Ascites
anorexia Encephalopathy
Fatty liver, Alcoholic
hepatitis, Alcoholic cirrhosis
and HCC
Hepatocellular carcinoma
Abdominal pain with abdominal mass
in RUQ
Blood – tinged ascites (rare)

Jaundice (rare)
Significant deterioration of liver
function
AFP, ALP LFT
May include paraneoplastic syndrome
•EPO Erythrocytosis
•PTH Hypercalcemia
 Laboratory
•
Investigation
CBC : Hct WBC Plt : Infection? Anemia? Thrombocytopenia?
• Serum Electrolyte : Na K Cl HCO3
• Liver Function Test :
– Direct bilirubin
– Total bilirubin
– AST
– ALT
– Alkaline Phosphatase
– Serum albumin
– Serum globulin
– Prothrombin Time
• Serum AFP : Cancer?
• Emergency endoscopic finding : Blood loss
• Chest X-ray : Infection, Lung compression from hepatomegaly
• Abdominal X-ray : Liver span, Spleen
• CT upper abdomen : Liver span, Urolithiasis, Abdominal Fluid
• Laparoscopy : For alternative management
• Hepatic Angiography : CA liver?
• Tissue biopsy : Hepatic Parenchyma
ab investigati
• CBC
• Liver function test - synthesize protein
- status or enzyme of the liver albumin
SGOT globulin
SGPT
ALP protein
- synthesize and secrete bile - synthesize coagulation factor
Total Bilirubin PT
Direct Bilirubin
Indirect Bilirubin
• Alpha fetoprotein
• Endoscopic finding
• CT scan
• Tissue biopsy
 Lab investigation
ค่าปกติ ผลการตรวจ
CBC
- Hct 42-52 38%
- WBC 5,000-10,000 10,000 cell/mm3
- Plt 145,000-450,000 150,000 /mm3
Electrolyte
- Na 135-145 142 mmol/L
-K 3.6 – 4.8 4.3 mmol/L
- Cl 96 – 109 109 mmol/L
- HCO3 21-29 23.5 mmol/L

Ref : J.Wallach, Interpretation of Diagnotic Tests, ed 7,New York, 2000

 Lab investigation
ค่าปกติ ผลการตรวจ
LFT
- SGOT(AST) 15 - 45 300 U/L
- SGPT(ALT) 10 - 40 158 U/L
- total bilirubin 0.3 - 1.0 5.2 mg/dL
- direct bilirubin 0.1 - 0.3 4.2 mg/dL
- ALP
35 - 117 95 U/L
- total protein
6.3 - 8.6 6.4 g/dL
- albumin
- PT 3.1 - 4.3 2.2 g/dL
- FBS < 12 18 sec
75 – 115 60 mg/dL

Serum AFP 0 - 15 700 microgram/L

Ref : J.Wallach, Interpretation of Diagnotic Tests, ed 7,New York, 2000
Lab investigation
• Emergency endoscopic findings:
– Dilated and bleeding blood vessels in esophagus
• CT upper abdomen:
– Enlarged, Irregular liver with larged hypodense
mass size 5 cm involving right lobe (segment 6,7,8) with la
• Tissue biopsy of liver:
– multiple micronodular
cirrhotic nodules, size 0.2-0.3 cm with mass.
– The tumor cells resemble hepatocytes
, containing round nuclei with increased N/C ratio, promin
eosinophilic
cytoplasm and well defined cell borders.
– The trabecular
are more than three cell thick and are covered be a layer o
flattented endothelial cells.
 CBC
• Hct
• Hematemesis
• WBC ( normal )
• No infection
• Plt ( normal )
• Not cause ecchymosis
 AST & ALT
• AST (Aspartate Aminotransferase)
liver, skeletal muscle, brain, and heart.
• ALT (Alanine Aminotransferase)
liver, kidney

• Intracellular enzyme involved in amino acid metabolism.

• Released into the bloodstream when tissue is damaged,
especially in liver injury.
• The level of elevation depends on the length of time that the
blood is tested after the injury.
• Serum AST levels become elevated eight hours after cell
injury, peak at 24-36 hours, and return to normal in 3-7 days.
• If the cellular injury is chronic, AST levels will remain elevated.
 AST & ALT
• Increase in:
– Alcoholic hepatitis (AST > ALT)
– Cirrhosis (AST > ALT)
– Acute viral hepatitis (ALT > AST)
– Vascular: right-sided congestive heart failure, shock liver,
Budd-Chiari syndrome
(AST & ALT > 500-1000)
– Biliary tract obstruction
– Liver abscess
– Hepatocellular or metastatic cancer
– Drugs eg INH, statins
• AST/ALT ratio > 2:1 is suggestive of alcoholic liver
disease.

Case : AST 300 U/L , ALT 158 U/L

AST/ALT ratio = 1.9:1
 Bilirubin
• Normal
Total bilirubin 0.25-1.5 mg/dl ( 5.2 )

Direct bilirubin 0-0.3 mg/dl ( 4.2 )

Indirect bilirubin 0.3-0.7 mg/dl ( 1.0 )

Jaundice
 Bilirubin
• Type of jaundice
Type Hyperbilirubinemia Urine bilirubin

Pre hepatic Indirect bilirubin Absent

Hepatic Indirect/direct bilirubin increase

Post hepatic Direct bilirubin (+ALP ) increase

 Alkaline
• ALP : Phosphatase
เอ็นไซม์ท่ีจัดอยู่ในพวกไฮโดรเลส(hydrolase)
ทำาหน้าท่ีเร่งปฏิกริ ิยาแยกพันธะของเอซิลเอสเธอร์ (Acyl ester)
และฟอสฟอริล เอสเธอร์ (phosphoryl ester)
• bone, liver, placenta, bile canal epithelium
• ALP
- hepatociliary disease : cholestasis
- increase osteoblastic activity : children,
paget’s disease
- pregnancy

ALP normal= 39-117 U/l ( 95 )

 Serum protein
• Total protein = albumin + globulin
• In this case:
Total protein 6.4 (normal 6.0 - 8.0 g/dL)
Albumin* 2.2 (normal 3.5 - 5.0 g/dL)
Globulin 4.2 (normal 1.5 - 3.2 g/dL)
 Albumin
• The most important plasma protein
• Synthesis by the liver
• Albumin is tested to check how well the
liver and kidney are working.
• Decrease : malnutrition ( esp. protein) ,
liver dysfunction
• Increase : intake food , drug (estrogen)
Prothrombin
time ( PT )
 Prothrombin
time
• เป็ นการตรวจการทำางานของ
( PT )
extrinsic pathway
• Normal 12s ( 18s )

Bleeding disorder

• Suspected chronic liver disease

abnormal liver function
-Decrease coagulation factor
-Decrease clearance of activated
coagulation factor and plasminogen activator
 Fasting blood
sugar
• Normal80-100 mg/dl ( 60 )
• Liver function
maintain blood glucose
(glycogenolysis, gluconeogenesis)

abnormal function hypoglycemia

 Summary
FBS
AST
AST > ALT
ALT

Chronic Liver Disease

Albumin

PT Hepatic jaundice
(Plt normal)

Total bilirubin
Direct bilirubin
Indirect bilirubin
 Alpha-
•
fetoprotein
AFP is oncofetal glycoprotein
• Synthesis by embryonic liver cells, fetal
yolk sac cells, alimentary canal
• Tumor marker ( first stage of liver cancer )
• Normal: 0-15 ng/ml
( increase in pregnancy )
 Alpha-
fetoprotein
• Germ-cell tumors of the testis
• HCC & CCC
• Metastatic carcinoma
• Fetal malformations
• Benign liver disease
- Serum AFP > 500 ng/ml used to diagnosis
carcinoma of the liver
Endoscopic
findings
 Emergency
endoscopic findings
• Dilated and bleeding blood vessels in
esophagus

Esophageal varices
 CT SCAN
• CT upper abdomen:

Enlarged, irregular liver with larged hypodense

mass size 5 cm involving right lobe
(segment6,7,8) with large area of necrosis.
 CT SCAN

• http://www.wjgnet.com/1007-9327/11/200.asp
Diagnosis for
Liver Mass
• Trauma Causes
• Infectious Disorders (Specific Agent)
• Infected organ, Abscesses
• Neoplastic Disorders
• Congenital, Developmental Disorders
• Anatomic, Foreign Body, Structural Disorders
• Arteriosclerotic, Vascular, Venous Disorders
• Reference to Organ System
• Pathophysiologic
 Tissue
Biopsy

Normal hepatocytes Micronodular cirrhotic nodule

 Liver Biopsy
Tumor cell resemble hepatocyte :-
– round nuclei with increased N/C ratio
– prominent nucleoli
– granular eosinophilic cytoplasm
– well defined cell borders
– The trabecular are more than three cell thick
and are covered be a layer of flattented
endothelial cells.
 Liver tumor
(epithelial tumor)
• Hepatocellular tumor

• Cholangiocellular tumor
No glandular structure

• Combined HCC/CCC

Rare
• Biliary cystadenocarcinoma
(Common in female)

• Hepatoblastoma Common in child

 Tissue Biops

Normal hepatocytes Hepatocellular carcinoma

Ref : AASLD
(American Associated Study of Liver Disease)
 Electrolyte
Electrolyt
• Na +
• K+
Normal
• Cl -
• HCO3-
d-Pugh Classification
of Cirrhos

5.2

2.2

18

Note: Child-Pugh class is either A (a score of 5–6), B (7–9), or C (10 or above).

Ref. Harrison's Online
 AST ,ALT ดื ่ม เห ล้ า 30 Jaundice

liver cells necrosis ปี Bilirubin

Cirrhosis
Ischemia Hepatocellular carcinoma AFP

Liver dysfunction
CT & Biopsy
Enlarged spleen
Coagulation factor Ecchymosis both legs
Caput madusae
Abnormal carbohydrate metabolism FBS
Plasma protein portal hypertension Hemorrhoid
albumin
sex hormone binding protein ascites Esophageal varices

estrogen hypoactive bowel sound rupture

Hematemesis
spider nevi gynecomastia
Testicular atrophy
Hct
Basic
Science
Liver

lobe

Structural
lobule unit

acinar functional
unit
Liver
 Blood Supply
Abdominal aorta

Inferior
Celiac trunk
mesenteric artery
Superior
mesenteric artery
Celiac trunk
 Blood supply to the
liver

Celiac trunk
Hepatic
artery

Common hepatic
artery
Portosystemic anastomoses
Esophagus
: esophageal
varices

Umbilicus
: caput madusae

Rectum
: hemorrhoids
posterior

anterior
Hepatic lobule
 CYP450
Sensitive to Ischemia
Zone 3 Sensitive to toxic
Alcoholic hepatitis
Zone 2
Intermediate zone

Zone 1
Most affected by
Viral hepatitis
 Pit cell
( liver specific NK cell)

(Ito cell)
Portal vein
Hepatic artery
Bile duct

Central vein

Hepatic lobule
LIVER FUNCTIONS
Metabolism Secretion of bile
 Carbohydrate  Detoxification
metabolism  Storage of vitamins
Glycogenesis (A,D,K,B12) & minerals
Glycogenolysis (iron,copper)
Gluconeogenesis
 Fat metabolism
ketogenesis
 Protein metabolism
anabolism
deamination
urea formation
 Cholesterol

liver
Cholic acid

Chenodeoxycholic
Primary bile acids acid

intestinal bacteria
Deoxycholic
Secondary bile acids acid
Lithocholic acid
LIVER FUNCTIONS
Metabolism Secretion of bile
 Carbohydrate  Detoxification
metabolism  Storage of vitamins
Glycogenesis (A,D,K,B12) & minerals
Glycogenolysis (iron,copper)
Gluconeogenesis
 Fat metabolism
ketogenesis
 Protein metabolism
anabolism
deamination
urea formation
 Bilirubin
Heme
Fe3+ CO

biliverbin
synthesis
Reticuloendotheli
al system
Unconjugated bilirubin
Heme oxygenase Biliverdin reductase
Albumin-bound bilirubin (Plasm
a)Liver
bilirubin + UDP glocuronate

UDP-glucuronosyltransferase
bilirubin diglucuronide
(conjugated bilirubin)

(Biliary
secrete in bile
bacterial protease
system)
conjugated bilirubin
Intes
tine
enterohepatic circulation urobilinogen feces
LIVER FUNCTIONS
Metabolism Secretion of bile
 Carbohydrate  Detoxification
metabolism  Storage of vitamins
Glycogenesis (A,D,K,B12) & minerals
Glycogenolysis (iron,copper)
Gluconeogenesis
 Fat metabolism
ketogenesis
 Protein metabolism
anabolism
deamination
urea formation
 Metabolism of
alcohol
Metabolize in the liver via two pathways

• The alcohol dehydreogenase pathway

- mainly in moderate level alcohol consumption
ADH ALDH
- alcohol acetaldehyde acetate
NAD+ NADH + H+

• The microsomal ethanol-oxidizing system ( MEOS )

- mainly in high level alcohol consumption
- cytochrome P450 converts alcohol to acetaldehyde

http://www.accessmedicine.com/resourceTOC.aspx?resourceID=4
albumin
Alcoholic Liver
Diseases
Pathogen
esis Alcohol

Endotheli
Hepatocyte Kupffer
al
cell
cell
+
+
Cell damage
Stellate
Phagocyto
Proliferation Lipogenesis cell
sis
Apoptosis
Fibrosis
Hepatocellular Fatty liver + +
carcinoma
Inflammation
Cirrhosis

Hepatitis
 Pathogenesis of
Fatty liver Alcohol

acetaldehy
ROS Activate
SREBP
Inhibit
PPAR-α activity
[NADH]/[NA
D+]
Up regulation
PAP
Inhibit
PMT enzyme de
ratio
Damage hepatic Up regulation
Reacting with
lasma membraneof acetyl-CoA lysine residue
-carboxylase DHAP G-3P
of tubulin
Production
Loss of hepatic of Inhibit the synthesis of
fatty acid uptake malonyl phosphatidylcholine
triglyceri
control CoA de
Acetaldehyde-
Inhibit CPT-1 tubulin
Hepatic adduct formation
Transport
fatty acid
of VLDL
uptake β-
fatty acid formation
to oxidation
mitochondri VLDL
a secretion

Fat
SREBP = sterol regulatory element binding protein
accumulatio
n PPAR-α = peroxisome proliferators-activated
receptor alpha

Fatty liver CPT-1 = carnitine palmitoyl transferase-1

PAP = phosphatidate phosphohydrolase
PMT = phosphotidylethanolamine methyl transferase
Pathogenesis of
Cirrhosis Alcohol

Homocysteine

Kupffer cell Injury endothelial cell

infiltrate
Cytokine ⊕
Cytokine ⊕
Activate stellate cell

Proliferation (PDGF)

Contraction (endothelin)

Fibrogenesis (TGF-β)

Chemotaxis to site of injury (chemotractant)

fibrosis

cirrhosis
Homocystine

fibrosisfibrosis
fibrosi

fibrosis

fibrosis
 CYP450
Sensitive to Ischemia
Zone 3 Sensitive to toxic
Alcoholic hepatitis
Zone 2
Intermediate zone

Zone 1
Most affected by
Viral hepatitis
 Pathogenesis
+
Alcohol of- Hepatit
CYP2E1 Acetaldehy MAT
de
+
ROS Homocystin SAMe
e
Lipid
peroxidation
Transmethylati
Malondialdehyde (MDA) on reaction

MAA adduct จับ CYC

DNA adduct
(high immunogenic) oxidase

ATP depletion DNA instability

Autoimmune
+
+ Apoptosis
inflammation
MAT = methionine adenosyl
transferase
Hepatitis SAMe = S-adenosyl methionine
 Pathogenesis of
Hepatocellular carcinoma
Alcohol

Acetaldehyde DNA binding +

Expression
ROS (carcinogen)
NFKβ,AP-1

Hepatocellular
Induce cell carcinoma
apoptosis
 Hepatocellular
Normal carcinoma
liver
90-100
%

Fatty C V n 19%
8-20 % H t81 io
liver + e c%
n f
10-35% i
Cirrho
Alcoholic
sis
Hepatitis (40 %)

Percentage of heavy drinkers who have the different stages of

alcoholic liver disease.
 Fatty liv

Enlarged, soft, and Intracytoplasmic

yellow. greasy textur fat and
Perivenular
eKumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS,eds.
fibrosis
Robbins and Cotran pathologic
basis of disease, 7th ed. Philadelphia:Elsevier Saunders; 2005.
 Alcoholic
hepatitis

Yellow, greasy, easily Steatotic

fractured; later liver hepatocytes
Perivenular
becomes red with fibrosis
Mallory body
bile-stained areas; m
ay contain visible nod
Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS,eds. Robbins and Cotran pathologic
ules
basis ofand fibrosis
disease, 7th ed. Philadelphia:Elsevier Saunders; 2005.
 Alcoholic
cirrhosis

Diffuse micronodules
of regenerative Nodule
hepatocytes surrounding by
separated by fibrous tissue
depressed
Kumar areas
V, Abbas AK, Fausto of SL, Cotran RS,eds. Robbins and Cotran pathologic
N, Robbins
basis of disease, 7th ed. Philadelphia:Elsevier Saunders; 2005.
 Hepatocellular
carcinoma

Irregular nodular Cords of malignant

appearance hepatocytes with
enlarged nuclei that
contain nucleoli
Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS,eds. Robbins and Cotran pathologic
basis of disease, 7th ed. Philadelphia:Elsevier Saunders; 2005.
Pathophy
siology
2

3
4

5
 Faulty protein
synthesis

Hypoalbuminemia

Decrease
colloidal
osmotic
pressure

Portal
hypertension
Ascite
s
 Portal hypertension

Prehepatic Intrahepatic Posthepatic

•Portal vein Presinusoid Sinusoida Postsinusoi •Right heart

thrombosis al l dal
•Chronic failure
hepatitis •Constrictive
•Primary •Acute hepatitis•Budd Chiari pericarditis
biliary •Alcoholic liver syndrome •Etc.
cirrhosis disease (obstruction of
•Granuloma •Toxins the large hepatic
in •Amyloidosis veins)
•Etc.
chistosomia
sis
•Tuberculos
is
•Leukemia
•Etc.
 Dilation of
paraumbilical vein

Portal
hypertension
Peri-esophageal Splenic vein SMV&IMV
venus plexus hypertension hypertension
hypertension

Esophageal
varices

rupture

Smv= Superior mesenteric vein

Imv = Inferior mesenteric vein
 Hepatic
Cirrhosis

Protein Hepatic Blood

synthesis flow

SHBG

circulating
testosterone

Converting to E Gynecomasti
Testicular at peripheral a
atrophy tissue

Vascular dilate

Superficial
tortuous Spider nevi
arteriole
 Hepatic
Cirrhosis
Failure to secrete Conj.
bilirubin

Conjugate
bilirubin

Hyperbilirubinemi
a

Icteric sclera
 Faulty
protein
synthesis

Clotting
Factor

Factor
II,VII,IX and Prolong
X PT

Bleeding
tendency

Massive Ecchymosi
Gastrointestinal s
bleeding
 Hepatic
Cirrhosis
Liver Hepatomegaly
dysfunction

Nutrient
metabolism Gluconeogenesis

Compress
lung capacity

Energy
depletion
Fatigue Hypoxia
 ดื ่ มเ หล้ า 30 ปี
ROS
Liver cell
Stellate cell สร้าง collagen
damaged

regeneration
Fibrosis

Cirrhosis
 AST ,ALT ดื ่ม เห ล้ า 30 Jaundice

liver cells necrosis ปี Bilirubin

Cirrhosis
Ischemia Hepatocellular carcinoma AFP

Liver dysfunction
CT & Biopsy
Enlarged spleen
Coagulation factor Ecchymosis both legs
Caput madusae
Abnormal carbohydrate metabolism FBS
Plasma protein portal hypertension Hemorrhoid
albumin
sex hormone binding protein ascites Esophageal varices

estrogen hypoactive bowel sound rupture

Hematemesis
spider nevi gynecomastia
Testicular atrophy
Hct
Manag
ement
 Management
• Cirrhosis
– Cirrhosis without complication
• Adequate mixed diet and avoidance of alcohol
– Cirrhosis with complications
• Variceal bleeding
• Ascites
• Hematologic problems : Coagulopathies
• Hypoalbuminemia
• Ectopic varices : Hemorrhoid
• Hepatic encephalopathy
• Hepatorenal syndrome
• Hepatocellular carcinoma
Management of variceal bleeding
• Acute variceal bleeding
- Medical treatment
:Vasopressin, Nitroglycerin, Somatostatin
- Endoscopic treatment
:Sclerotherapy, Endoscopic variceal band ligation
- Balloon temponade
- Transjugular intrahepatic portosystemic shunt (TIPS)
- Surgical treatment
: Surgical shunt & Devascularization
Endoscopic variceal band ligation
Balloon temponade
Transjugular intrahepatic portosystemic shunt (TIPS)
Devascularization
 Management of variceal bleeding
• Prophylaxis of variceal bleeding
- Medical treatment
: Propanolol, Nadolol
- Endoscopic band ligation
 Management of Ascites
• Sodium & Water restriction
• Diuretics : Spinololactone,
Furosemide
• Paracentesis
Management of Hematologic problems
Prolonged PT

Vitamin K

Normal PT Prolonged PT

Hypofibrinogenemia and/or Deficiency of factor V

Amicar cryoprecipitate FFP

Normal PT

สมเกียรติ วัฒนศิริชัยกุล. Portal hypertension, กรุงเทพเวชสาร,กรุงเทพ, 2536

Management of Hypoalbuminemia

• A daily intake of 1 g protein/kg body weight

Management of Hemorrhoid
• Stool softener
• Steroid
• Rubber Band Ligation
• Surgical treatment
Management of Hepatocellular Carcinoma

• Curative Treatments

• Palliative Treatments
Management of Hepatocellular Carcinoma
• Curative Treatments
– Surgical treatment
– Liver transplantation
d-Pugh Classification
of Cirrhos

5.2

2.2

18

Note: Child-Pugh class is either A (a score of 5–6), B (7–9), or C (10 or above).

Ref. Harrison's Online
Management of Hepatocellular Carcinoma
• Curative Treatments
– Surgical treatment
– Liver transplantation
Management of Hepatocellular Carcinoma
• Palliative Treatments
– Systemic Chemotherapy : Mitoxantrone, 5-FU,
Doxorubicin, Mitomycin C, Cyclophosphamide
– Transarterial Chemoembolization(TACE)
: Lipiodol + Chemotherapy
– Percutaneous Ethanol Injection
– Radiofrequency Ablation (RFA)
– Immunotherapy
 References
• Harrison Internal Medicine 16thed 2007
• L.Schiff,E R.Schiff.Disease of the liver Ed 7, Philadephia,1993
• S.Silbernagl,S.Lang.Color atlas of pathophysiology ,Newyork,2006
Robbin’s Basic Pathologic Disease 8thed 2008
• Willium F.Ganong:Review of medical physiology, 17th
ed.USA,Connecticutt,Appleton & Lange, 1995
• http://www.nyp.org/health/liver_chronic.html
• http://www.mdconsult.com/das/book/body/114745804-2/0/1249/
I4-u1.0-B0-7216-0187-1..50022-5--f5.fig?tocnode=51156723
www.accessmedical.com
 References
• Anthony S. Fauci, Eugene Braunwald, Dennis L. Kasper, Stephen L.
Hauser, Dan L. Longo, J. Larry Jameson, and Joseph Loscalzo, eds.
Harrison's Principles of Internal Medicine, 17th ed. New Jersey
:McGraw-Hill, 2008.
• Erwin Kuntz and Hans-Dieter Kuntz. Hepatology principle and
practice,2th ed. Wetzlar :Springer,2006.
• Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's
diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams &
Wilkins,2003.
• Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS,eds. Robbins
and Cotran pathologic basis of disease, 7th ed.
Philadelphia:Elsevier Saunders; 2005.
• MacSween RNM, Burt AD,Portmann BC, Ishak KG, Scheuer PJ,
AnthonyPP, eds. Pathology of the Liver. 4th ed. New York: Churchill
Livingstone,2002.
• Robert K. Murray, Daryl K. Granner, Victor W. Rodwell ,eds.
Harper's Illustrated Biochemistry, 27th ed. New Jersey :McGraw-
Hill, 2006.
• http://www.niaaa.nih.gov/ResearchInformation/
ExtramuralResearch/ResourcesAppGrantees/R21liver.htm
 References
• พินิจ กุลละวณิชย์,อุดม คชินทร,วโรชา
มหาชัย.วิวัฒนาการในโรคระบบทางเดินอาหาร
7,สมาคมแพทย์ระบบทางเดินอาหารแห่งประเทศไทย,กรุงเทพ,2540
• เฟ่ อ
ื งเพชร เกียรติเสวี .มะเร็งตับ,กรุงเทพเวชสาร,กรุงเทพ,2544
• เติมชัย ไชยนุวัติ. โรคตับและทางเดินน้ำาดี.
สำานักพิมพ์กรุงเทพเวชสาร. 2529.
• ชีวเคมีทางการแพทย์:
เมตาบอลิสมของสารอาหารเชิงบูรณาการ.กรุงเทพ : บุ๊คเนท, 2546
• สมเกียรติ วัฒนศิรชิ ัยกุล. Portal hypertension, กรุงเทพเวชสาร,กรุงเทพ,
2536
 Thank you
for
your attention