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Steven William Halim - 00000021045

Gastrointestinal Block

Clinical Pathology

Laboratory of Liver Disease

Functions of the Liver:

Bile Synthesis Used for emulsifying fats and binding them (micelles)
Carbohydrate Gluconeogenesis, Glycogenesis, Glycogenolysis
Metabolism
Detoxification Detoxification of toxins, drugs, alcohol, and the urea cycle
Hormone Metabolism Breakdown of insulin and steroid hormones
Lipid Metabolism Cholesterol Synthesis and Fat Storage
Coagulation Factors I, II, V, VII, IX, X, XI as well as protein S and C
Storage Glycogen, vit B12, Iron, Copper
Immunology RES system

Liver Function Tests (LFT)

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 = AST, GLDH

Mitochondrial damage ONLY appears if the cell membrane integrity is disrupted  ONLY
happens if the cell undergoes NECROSIS

If ALT and AST are found together in elevated amounts in the blood, liver damage is most
likely present
 AST > ALT (complete cell destruction)
Steven William Halim - 00000021045

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

De Ritis Ratio: AST/ALT (usually <1)

2. Test for Cholestasis – Alkaline Phosphatase and GGT (Gamma Glutamyl Transpeptidase)
ALP increases significantly for extra-hepatic blockage BUT only mildly increase in hepatocyte
destruction

GGT = MOST SENSITIVE in finding biliary obstruction, cholangitis, or cholecystitis


If GGT is raised more than ALP = cholestasis
 ALP elevation also seen in normal childhood, pregnancy and bone disease

3. Synthetic Function Tests


a. Albumin
Decreases  impaired synthesis (more common due to chronic disease rather than acute)

b. Protein Electrophoresis
useful as additional information to make differential diagnosis

c. Cholinesterase
Reduced activity in hepatocyte destruction

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

4. Excretory Function Tests


a. Bilirubin
Unconjugated, Conjugated, and Total Bilirubin

b. Gamma GT and ALP

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 in liver diseases

6. Coagulation Tests – PT and INR


Steven William Halim - 00000021045

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 Primary Biliary Cirrhosis
SMA/Smooth Muscle Antibody Chronic Active Hepatitis
ANA/Anti Nuclear Antibody Lupus

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
 Ritis Ratio 0.4 (ALT>AST)  due to rapid destruction
 AST ALT can reach hundreds and even thousands

Acute Hepatitis B
 Ritis Ratio 0.6
 AST ALT rises 5x normal
 Antibodies titer can signify immunity if anti HBs titer is > 100 IU/mL

Chronic Hepatitis B
Chronic Persistent : slight raise of AST ALT GGT (2-4x normal), de Ritis ratio < 1
Moderate Chronic Active : like chronic persistent, GGT and Ab rises more
Highly Chronic Active : enzymes >10x normal, de Ritis Ratio >1, Bilirubin & GLDH up

Chronic Hepatitis C
 AST ALT 5-15x normal, GGT increases more than other viral hepatitis
 ANA and SMA usually present
 Examination Steps:
Anti HCV (+)  HCV RNA/HCV Immunoblot (+)  Viral Load
Steven William Halim - 00000021045

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

Liver Disease Etiology

1. Alcoholic Liver Disease


GGT > over AST and ALT, de Ritis Ratio >2 (ALT<AST)
MCV > 95 fL

2. Autoimmune Liver Disease


Increased AST and ALT without obvious cause  raised Ig levels (IgG > 1.5x normal)

3. Metabolic Liver Disease


a. Wilson’s Disease
Disorders of excretion and transport of copper lead to accumulation in the liver and various
organs

Serum ceruloplasmin low + urinary copper extremely high

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


Steven William Halim - 00000021045

b. Inorganic Compounds
Poisoning by metals or metal salts  measurement the metal in urine serum organ tissue or
hair

c. Medication and Mushroom Poisoning

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

6. Non-Alcoholic Fatty Liver Disease (NAFLD)


In overweight patients with hypercholesterolemia and high IGT
ALT AST slight increase, de ritis ratio <1

7. Liver Cirrhosis
Hypoalbuminemia, normal or slightly low AST, ALT, GGT, cholinesterase decrease, ammonium
concentration increase

8. HCC
Golden Standard: imaging and biopsy
- Supported by  AFP > 500 µg/L + symptoms of the liver
- AFP used for monitoring therapy of HCC

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:
a. Trypsinogen  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
Steven William Halim - 00000021045

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

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)

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
Fever, jaundice, and shock  indicates infection and abscess

Diagnosis
(+) Murphy Sign
Elevated ALP, Conjugated Bilirubin, WBC, Acute Phase Reactants
USG
Steven William Halim - 00000021045

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 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
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


Steven William Halim - 00000021045

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

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

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

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