PATHOLOGI KLINIK EDITED BY MEMEME

Gastrointestinal Block

Clinical Pathology

Laboratory of Liver Disease

Functions of the Liver:

Bile Synthesis Produced by liver to used for emulsifying fats and binding them (micelles)
Carbohydrate Gluconeogenesis, Glycogenesis, Glycogenolysis
Metabolism
Detoxification Detoxification of toxins, drugs, alcohol, and the urea cycle.
Comverts ammonia to urea which excreted by kidney as urine
Hormone Metabolism Breakdown of insulin and steroid hormones
Lipid Metabolism Cholesterol Synthesis and Fat Storage
Coagulation Factors I (fibrinogen), II (prothrombin), V, VII, IX, X, XI as well as protein S and C
and anti thrombin (TEST PT)
Storage Glycogen, vit B12, Iron, Copper
Immunology RES system

Liver Function Tests (LFT) – Detect inflammation and damage to liver

Functions:

- To see if there is damage to the liver

- Assess sluggish bile flow (cholestasis)
- Assess synthetic functions of the liver

Indications:

- Hepatobiliary System Disease

- Medical Check Up
- Alcohol Drinker and Medication Use (check liver function e.g. in pyrazinamide)

1. Alanine Aminotransferase (ALT/SGPT) and Aspartate Aminotransferase (AST/SGOT)

Enzymes in the Cytoplasm = ALT, AST, LDH5
Enzymes in the Nucleus, Mitochondria = AST, GLDH (Glutamate dehydrogenase)

AST in serum is less than ALT because only 20% in cytoplasm 80% in mitochondria
Mitochondrial enzymes ONLY appears if the cell membrane integrity is disrupted  ONLY
happens if the cell undergoes NECROSIS or COMPLETE CELL DESTRUCTION
PATHOLOGI KLINIK EDITED BY MEMEME

If ALT and AST are found together in elevated amounts in the blood, liver damage is most
likely present
 AST > ALT (complete cell destruction – karena AST banyak di nucleus)

AST = found in muscles and many other tissues besides the liver (NOT SPECIFIC)
ALT = almost exclusively found in the liver (SPECIFIC)

De Ritis Ratio: describe ratio between AST/ALT ( <1 for acute viral hepatitis where ALT was
usually higher than AST,>1 for alcoholic hepatitis where AST was higher than ALT)

2. Test for Cholestasis – Alkaline Phosphatase, 5NT (Nuleotidase) and GGT (Gamma Glutamyl
Transpeptidase)
ALP increases significantly for extra-hepatic blockage BUT only mildly increase in hepatocyte
destruction
ALP= MOST SENSITIVE FOR CHOLESTASIS BUT LESS SPECIFIC
(ALP elevation also seen in normal childhood, pregnancy and bone disease)
GGT = MOST SENSITIVE in finding biliary obstruction, cholangitis, or cholecystitis
If GGT > ALP = cholestasis

3. Synthetic Function Tests

a. Albumin Concentrations
Decreases  impaired synthesis – Hypoalbuminemia
(more common due to chronic disease rather than acute, less sensitive but good for making
prognosis)

b. Protein Electrophoresis
(separate into fragment Alfa 1 glob, Alfa 2 glob, Beta glob, Gamma glob)
Protein profile useful as additional information to make differential diagnosis e.g Polyclonal
gammopathy

c. Cholinesterase enzyme activity

Reduced activity in hepatocyte destruction ; good for prognosis

d. Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)

Impaired synthesis function : Prolong prothrombin time
PATHOLOGI KLINIK EDITED BY MEMEME

4. Excretory Function Tests

a. Bilirubin
Unconjugated, Conjugated, and Total Bilirubin
Urinary bilirubin, urinary and fecal urobilinogen, urinary urobilin, fecal stercoblilin

b. Gamma GT and ALP

Gamma GT sensitive buat biliary obstruction, cholangitis, cholecystitis

c. Icterus Test (rarely Used)

estimates serum bilirubin concentration by comparing serum color to potassium bichromate
solution color

5. Detoxification Function Tests

Increased levels of ammonium (blood ammonia level) in liver diseases

6. Coagulation Tests – PT and INR

PT – test for production of coagulation factors
INR - Can monitor how much medicine (commonly warfarin) to take.
Increased levels of INR means blood is taking more time than usual to clot
 INR 1.0 Normal
 INR 2.0-3.0 Normal Therapeutic Range for Most Indications
 INR 4.0-5.0 Prevention of Arterial Thromboembolism, Hypercoagulable State

7. Etiology Testing
Auto Antibodies
AMA/Anti Mitochondrial Antibody
SMA/Smooth Muscle Antibody
ANA/Anti Nuclear Antibody
Primary Biliary Cirrhosis
Chronic Active Hepatitis
Lupus, Lupoid type chronic active hepatitis

Serology – Virus Markers

Hepatitis A Anti-HAV IgM
Hepatitis B HBsAg, HBeAg, HBcAg, anti HBs, anti HBe, anti HBc (IgM, IgG), HBV DNA
Hepatitis C HCV RNA, anti HCV total (IgM, total)
Hepatitis D HDAg (Delta Antigen), anti HD (IgM, IgG)
Hepatitis E Anti VHE (IgM, IgG)

Acute Hepatitis A
 Spread through contaminated food or water
PATHOLOGI KLINIK EDITED BY MEMEME

 Ritis Ratio 0.4 (ALT>AST)  due to rapid destruction on cytoplasmic enzyme more than
mitochondrial enzyme
 AST ALT can reach hundreds and even thousands
 Anti HAV IgM
 Usually heals slowly with no complications

Acute Hepatitis B
 Its virus contain several antigens such as
o HBsAG = surface
o HBcAG = core
o HBeAG = epsilon – marker for inefectivity
 Ritis Ratio AST/ALT 0.6
 AST ALT rises 5x normal
 80-85% patient with infectious HBV will make antibody : Anti HBs, Anti HBc, Anti HBe
 Anti HBc early appears in serum and remain positive for years in acute and chronic
hepatitis B even after resolution of infection
 Last to appear HBs which becomes detectable after 6 months
 Antibodies titer can a signifies immunity if anti HBs titer is > 100 IU/L

Chronic Hepatitis B
 Present if HBsAG and HBV DNA remains detectable for more than 6 months
 Classification according to histologial criteria : Chronic Active and Chronic Presistent
Hepatitis
Chronic Persistent : slight raise of AST ALT GGT (2-4x normal), de Ritis ratio < 1
Moderate Chronic Active : like chronic persistent, GGT and IG rises more
Highly Chronic Active : enzymes >10x normal, de Ritis Ratio >1, Bilirubin & GLDH up,
Albumin decrease
 Anti HBs (+), anti HBc (+) = Previous Hep B
 Anti HBc IGM, HBsAG (-) = Resolved Case
 HBeAG (+) = High infectivity
 HBeAG (-) = Clinically active

Chronic Hepatitis C
 Often runs unremarkable or even silent – Very dangerous if become chronic 75-85% of
cases – Could risk for cirrhosis and hepatoma
 Lab :
o Transaminase (AST/ALT) 10-15x from normal (if chronic may raised 3-5 fold)
o ALP and GGT higher than other viral hepatitis
PATHOLOGI KLINIK EDITED BY MEMEME

o ANA and SMA often present

o Detected 3-6 months after infection (BECAREFUL OF WINDOW PERIOD)
 Examination Steps:
Anti HCV (+)  HCV RNA/HCV Immunoblot (+)  Viral Load

HCV RNA (+) after 6 days infection

HCV RNA (-) disease has resolved
HCV RNA (+) ANTI HCV (+) chronic hepatitis C

Hepatitis D

 Coinfection with HepB

 Acute phase – anti HDV IgM become positive after 4-5 weeks (higher in super infection
rather than co-infection)

Hepatitis E

 Transmitted enterally like hepatitis A (fecal oral)

 ALT > AST
 In uncomplicated case, enzymes return normal within 4-6 weeks
 Anti HEV IgM detected
 CONFIRMED DIAGNOSIS : detection of HEV RNA using PCR

Notes:

- GLDH increase in chronic liver diseases and especially hepatoma

- AFP increase in chronic liver disease progressing to hepatoma

Monitoring Therapy of Chronic Hepatitis

Interferon Therapy

1. ALT and AST, Blood Count every 14 days in the first 2 months, then every 4-6 weeks
2. PCR for virus detection repeated every 3 to 6 months
3. TSH every three month because possibly thyroid dysfunction

Active Chronic Hepatitis :

 Transferase increase
 Protein synthesis reduced
 AFP increase
 If progression to liver cirrhosis GLDH increase
 If carcinoma occur : GLDH and AFP will rise very high
PATHOLOGI KLINIK EDITED BY MEMEME

Liver Disease Etiology

1. Alcoholic Liver Disease

 Excessive alcohol acts as endogenous toxin to liver (necrosis + inflammation – chronic)
 GGT > AST/ALT
 ALP normal, AST > ALT (de ritis ratio >2 )
 MCV > 95 fL -> characteristic for alcohol related damage
 GLDH, IgA – increase , CHE decrease

2. Autoimmune Liver Disease

 Characterized by disturbed immune tolerance to liver and biliary tissue : AIH, PSC
(Primary sclerosing cholangitis), PBC (primary biliary cirrhosis)
 First sign : Increased AST/ALT without obvious cause
 First evidence : Raised Ig levels (IgG > 1.5 times), small increase IgM

3. Metabolic Liver Disease

a. Wilson’s Disease
Disorders of excretion and transport of copper lead to accumulation in the liver and various
organs. Inherited liver disease : Cystic fibrosis, Acute and chronic porphyria, Disorder
metabolism bilirubin, Hemochromatosis, Wilson disease, Alpha 1 antitrypsin deficiency
Serum ceruloplasmin low + urinary copper extremely high. High Copper content in liver

b. Hemochromatosis
Deposit of Fe in the liver
Transaminase, GGT, GLDH are midlly elevated, BSP and SI raised

c. Alpha-1-Antitrypsin Deficiency
non secretable variant of α 1 antitrypsin leads to accumulation this protein in hepatocytes 
decreased serum alpha-1 antitrypsin

4. Toxic Liver Diseases

a. Organic Compounds
Poisoning with halogenated hydrocarbon compounds ( eq carbon tetrachlroride, chloroform,
vinyl chloride)
Extreme reduction in serum cholinesterase activity

b. Inorganic Compounds
Poisoning by metals or metal salts to liver damage  measurement the metal in urine serum
organ tissue or hair
PATHOLOGI KLINIK EDITED BY MEMEME

c. Medication (non specific lab pattern, mild liver damage) and Mushroom Poisoning
(varies clinical feature)
d. Others e.g cytomegalovirus, herpes simplex, various zoster, eb virus, adeno entervirus,
ebola virus

5. Miscellaneous
CMV, EBV, HSV, Adenovirus, Ebolavirus

6. Non-Alcoholic Fatty Liver Disease (NAFLD) and NASH (non alcohol steatohepatitis)
 In overweight patients with hypercholesterolemia (hyperlipoproteinemia) and high IGT
 ALT AST slight increase, de ritis ratio <1
 GGT, ALP, ferritin, transferrin saturation slight increase
 Diagnosis through histological exam

7. Liver Cirrhosis
 Hypoalbuminemia, normal or slightly low AST, ALT, GGT, cholinesterase decrease,
ammonium concentration increase
 AFP slight increase, continuous increase sugest liver cell ca development

8. HCC
Golden Standard: imaging and biopsy
- Supported by  AFP > 500 µg/L + symptoms of the liver
- Extremely high AFP (AFP low sensitivity and low specificity)
- AFP used for monitoring therapy of HCC combined with USG

9. Tumor of the Liver

 Benign and Malignant
 Golden key : IMAGING (CT) and Histology

Laboratory of Acute Abdomen

1. Acute Pancreatitis
Symptoms and Signs:
Severe pain radiating to the back Steatorrhea
Reduced bowel sounds Hemodynamic instability
Tachycardia and Tachypnea

Pathogenesis
Leakage of pancreatic enzymes to surrounding structures:
PATHOLOGI KLINIK EDITED BY MEMEME

a. Trypsinogen  active trpsin -> autodigestion of the Pancreas  PAIN

b. Lipase  autodigestion of bodily and mesenteric fat
c. Amylase

Etiology
Most Common : gallstones and excessive alcohol intake, idiopathic
Others : hypertriglyceridemia, hypercalcemia, viral infection (mumps), trauma,
autoimmune, vasculitis, pregnancy and diabetes
Diagnosis – 2 out of 3 criteria
a. Abdominal Pain characteristic of acute pancreatitis
b. Serum amylase and lipase >3x normal value
Lipase > 2.5x Amylase = alcoholic liver disease
Serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14
days after treatment (LIPASE BETTER THAN AMYLASE FOR DIAGNOSIS)
c. Characteristic finding on CT scan

AMYLASE AND LIPASE

 Serum lipase rises 4-8 hours from the onset, normalize within 7-24 days (MORE
SPECIFIC AND SENSITIVE THAN AMYLASE)
 Serum amylase normal in 10% cases for chronic pancreatitis and
hypertriglyceridemia
 False positive elevated serum amylase : Salivary gland disease, macroamylasemia
 Lipase 2.5-3x than amylase – indication of pancreatitis due to alcohol
 Normal Lipase : 4-43 u/L – Normal Amylase : 20 – 96 u/l

2. Chronic Pancreatitis
inflammation of the pancreas that is characterized by recurring or persistent abdominal pain
with or without steatorrhea or diabetes mellitus

Causes: Unknown (autoimmune, genetics, diseases e.g. cystic fibrosis, heavy alcohol use)

Symptoms
Upper abdominal pain that become worse with eating or drinking, and become constant and
disabling (+ vomiting and nausea, diarrhea, steatorrhea, weight loss even with regular eating)

Diagnosis
USG or CT or MRCP (blood tests are not helpful)
PATHOLOGI KLINIK EDITED BY MEMEME

3. Cholecystitis
Inflammation of the gallbladder

Causes
often caused by cholelithiasis that blocks the bile duct  leads to thickening of bile and
cholestasis and secondary infection by GI tract organisms (particularly E. coli and Bacteroides) 
inflammation of gallbladder  extreme cases may lead to necrosis and rupture

Symptoms
Pain in the RUQ that may refer to the right scapula or right flank, low fever
Constant, Severe pain
Fever, jaundice, and shock  indicates infection and abscess

Diagnosis
(+) Murphy Sign
Elevated ALP, Conjugated Bilirubin, WBC, Acute Phase Reactants
Elevated CRP
USG (sensitive and specific)

4. Ectopic Pregnancy
fertilized ovum is implanted in any tissue other than the uterine wall (most common: fallopian
tubes)  A MEDICAL EMERGENCY

Pain and Bleeding (vaginal and internal)

- (+) pregnancy  PID is excluded
- May mimic other conditions
Diagnosis
Elevated beta-hCG (β-human chorionic gonadotropin) levels in the serum (1500 IU/mL) and
USG

Fecal Occult Blood Test (FOBT)

May indicate various diseases

ACS recommends  screening every 5 years >50 years old (along with sigmoidoscopy)

Methods:

1. Benzidine Base
2. Benidine Dihydrochloride
PATHOLOGI KLINIK EDITED BY MEMEME

3. Guaiac
4. Hematest

1,2,3  carcinogenic!

Principle (ColoScreen)

ColoScreen is a Guaiac Impregnated Paper enclosed in a cardboard frame  oxidation of Guaiac produces
the color blue

1. Hemoglobin + Developer Solution

Hb + 2H2O2  2H2O + O2

2. Oxidation of Guaiac
O2 + Guaiac  Oxidized Guaiac (Blue)

False Positive = sisa serat daging, produk mikroba usus (peroksidase), iron therapy

False Negative = intake vitamin C

Pemeriksaan Tinja

Parameter Pemeriksaan:

1. Makroskopis
Warna Coklat-Coklat Tua = Normal
Kuning = Susu Jagung atau Unconjugated Bilirubin
Hijau = Sayur
Pucat = Tidak ada Urobilin
Merah Muda = perdarahan distal ATAU makan bit dan buah naga
Hitam = melena
Bau Normal karena indol, skatol, dan asam butirat
Konsistensi Agak lunak dan berbentuk
Diare = sangat lunak dan cair (Bristol 6 atau 7)
Konstipasi = keras (Bristol 1 atau 2)
Peragian Karbohidrat = lunak bercampur CO2
Lendir Inflamasi atau Rangsangan pada dinding usus
Parasit Cacing, telur cacing, kista protozoa, trofozoit, dsb
Darah Proximal = kehitaman
Distal = merah (bahkan bisa merah segar)

2. Mikroskopis
Purpose = finding undigested food contents, parasites and microbes, etc
PATHOLOGI KLINIK EDITED BY MEMEME

a. Prepare microscope and 2 object glass

b. First Object Glass
- Drop 1 tetes Lugol
- Smear feces and mix on the object glass
- Cover with deck glass
- Objective 10x  look for parasites and amylum
LUGOL = PARASITES AND AMYLUM

c. Second Object Glass

- Drop 1 tetes Eosin
- Smear feces and mix on the object glass
- Cover with deck glass
- Objective 10x  look for erythrocyte, leukocyte, egg of worms
EOSIN = ERYTHROCYTE, LEUKOCYTE, EGG OF WORMS

DD BLOOD IN STOOLS

 Anal fissure
 Colorectal cancer
 Crohns disease
 Ulcerative colitis
 Internal hemorrhoids
 Inflammatory enteritis – inflammation of small intestine can be caused by :
o E.coli enteritis ETEC (Traveller’s diarrhea)
o Campylobacter enteritis
o Shigellosis
o Salmonellosis
o Gastroenteritis (dysentery)
o Staphylococcus aureus
o Radiation enteritis
 Diverticulosis
 Upper GI bleeding
 Peptic ulcer disease
 Esophageal varices
 Gastric Cancer
 Constipation