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Lecture 5:Laboratory exploration in
gastrointestinal pathology
2011-2012
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Content of lecture 5:
A. Liver exploration: tests indicating an inflammatory process;
tests indicating liver cytolysis,
tests indicating synthesis of proteins,
tests indicating cholestasis.
Features of bilirubin metabolism.
B. Pancreas exploration. C. Gastrointestinal exploration.
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A. Liver exploration
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Liver function.
Role of the liver in: -proteic synthesis -carbohydrates metabolism -lipid metabolism -biliary secretion
-coagulation and fibrinolysis -inactivation of some hormones -detoxification (metabolites, drugs) Morphopathological lesions in the liver -a. Inflammation -b. necrosis
-c. fibrosis -d. steatosis -e. cholestasis -f. tumoral procesess
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a. Tests indicating an inflammatory process
Causes: Rubella, CMV, Epstein Barr Chemical poisoning Chloroform, Pyrimidifen Hepatitis (A,-B,-C,-D,-E) Toxic mushrooms Yellow fever Gallstones Porphyria Cutanea Tarda Alcoholic hepatitis
Tests indicating an interstitial inflammationplasmocytesinfiltration Ig synthesis gamma globulines
Chronic Hepatitis Ig G Biliary cirrhosis- Ig M Alcoholic Hepatopathy- IgA
Positive tests for disproteinemia (Takata, Tymol, sulfat de Zn)
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b. Tests indicating liver cytolysis
Tests indicating increase of cell permeability ASAT, ALAT intracellular LDH 4,5 OCT(ornithine carbamoyltransferase), SDH (succinate dehydrogenase), ICDH (isocitrate
dehydrogenase)
Degree of increase depends on:
nr. of involved cells Cell damage Vascularisation of the damaged tissue Existance of an inflammatory barrier Half-life time of the enzyme Viral acute hepatitis increases of 10-50x; ALAT especially Chronic hepatitis- increases in range of 5-20x - stabil increases- 2-3x; - acute - increase of ASAT Alcoholic Hepatopathy 5-10 x, especially ASAT Liver cirrhosis uncompensated parenchymal normal values or slight increase Tumoral processess- slight increase only; more ASAT (necrotic lesions) Acute Necrosis (intoxication with fungus, organophosphoric solvents)- high increase 100x
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c. Tests indicating synthesis of proteins
Tests that evaluate the proteic synthesis of proteines Albumines Not useful in acute liver insuficiency In liver cirrhosis with ascites, part of albumines pass in ascitic fluid (than they decrease in
blood) Colinesterase (Che) Broad interval for individual values; one determination is not relevant
Decrease of Che reveals a decreased hepatic proteosynthesis -decreased values may appear in severe anemia
malnutrition, malabsorbtion acute phase reaction Hypothiroidism intoxication with organophosphorics
-increased values may appear in abdominal type of obesity HLP type IIb, IV, V nephrotic syndrome hyperthiroidism
Prothrombin time (PT) or Quick time (QT)- (fVII) T/2 short 6-8 hours. useful in acute liver insufficiency.
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d. Tests indicating cholestasis
ALP (Alkaline phosphatase)
Serum bile acids- sensitive test of hepatobiliarydisease
GGT (Gamma glutamyl transpherase) Biliary obstruction
Hepatocellular damage
Elevated serum levels occur in: alcohol,
phenobarbitone, phenytoin, rifampicin 5Nt (5 nucleotidasis)
Biliary obstruction
Unlike GGT is not affected by enzyme inducing agents
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e. Test indicating liver fibrosis - Fibrotest
FibroTest, known as FibroSure in the US, is a patented biomarkertest that uses the results of six blood serum tests to generate ascore that is correlated with the degree ofliverdamage in peoplewith a variety of liver diseases.
FibroTest has the same prognostic value as a liver biopsy. FibroTest has been evaluated in relation to liver biopsy (the current
gold standard in liver disease assessment) in a large number ofpatients with hepatitis C, hepatitis B, alcoholic liver disease,Non-alcoholic fatty liver disease and in the general population.
By 2008 it had been used in over 350,000 patients. FibroTest has been validated for the initial diagnosis offibrosis
In 2006, the French National Authority for Health recommended theuse of FibroTest as a first-line assessment tool for fibrosis withuntreated chronic hepatitis C.
http://www.answers.com/topic/biomarker-1http://www.answers.com/topic/blood-serumhttp://www.answers.com/topic/liverhttp://www.answers.com/topic/liver-biopsy-1http://www.answers.com/topic/gold-standardhttp://www.answers.com/topic/hepatitis-chttp://www.answers.com/topic/hepatitis-chttp://www.answers.com/topic/gold-standardhttp://www.answers.com/topic/liver-biopsy-1http://www.answers.com/topic/liverhttp://www.answers.com/topic/blood-serumhttp://www.answers.com/topic/biomarker-17/28/2019 Lecture 5 Liver and Gastrointestinal Tract
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FibroTest score
The FibroTest score is calculated from theresults of a six-parameter blood test:
Alpha-2-macroglobulin,
Haptoglobin,
Apolipoprotein A1,
Gamma-glutamyl transpeptidase(GGT),
Total bilirubin, and
Alanine transaminase (ALT). ALT isused in a second assessment called
ActiTest that is part of FibroTest.
The FibroTest score (in thiscase 0.88) may indicate thepresence ofcirrhosis.
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FibroTest derivatives
Four other tests derive from FibroTest, and are part of theFibroMax package of tests:
ActiTest: diagnostic ofnecrotico-inflammatory for hepatitis;
SteaoTest: diagnostic for liversteatosis;
NashTest: diagnostic forNASH (Non-alcoholic fatty liverdisease) inflammation;
AshTest: diagnostic forAlcoholic liver diseaseinflammation.
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The tests are not applicable in 1 to 5% of cases.
Acute hepatitis- e.g., acute viral hepatitis A, B, C, D, E; drug-inducedhepatitis
Extrahepatic cholestasis, e.g., pancreatic cancer, gallstones
Severe hemolysis, e.g.
Gilbert's syndrome with high unconjugated hyperbilirubinemia
Acute inflammatory syndrome (the blood test may be postponed)
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f. Specific tests that are modified in hepatic diseases
Hematological: Target cells (hepatic disease), megalocytes (alcohol), hemolysis Prothrombin time (PT) and activated partial thromboplastin time (APTT):
PT is testing extrinsec pathway Sintrom, Trombostop treatment
APTT testing intrinsec pathway (VIII; IX;XI;XII) Heparin treatment
Antibody titres: Mithocondrial Ab primary biliary cirrhosis Antinuclear factor+ Smooth muscle Ab- autoimmune disease of liver and bilary
channels
Antigens and Antibodies for viral hepatitis: Ab HVA, Ag HBs, Ag Hbe, Ab Hbe, Ab HBs, Ab HVC, C viremia
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g. Tests indicating specific disorders affecting the liver
Wilson disease Serum copper and ceruloplasmin
Urinary copper
Hemocromatosis Serum iron and total iron binding capacity
Serum ferritin
Alpha-1 antitrypsin deficiency
Serum alpha-1 antitrypsin
Primary liver cell cancer Alpha fetoprotein
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Jaundice
2011-2012
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EXTRAVASCULAR DEGRADATION OF HEM
Eritrocitul n circulaie 120 zile
Eritrocitele mbtrnitesunt fagocitatesau lizate
Liza celulelor are locintravascular sauextravascular(sistemulreticulohistiocitar)
(Liver, Bone marrow,& Spleen)
Hemoglobin
Globin
Amino acids
Amino acid pool
Heme Bilirubin
Fe2+
Excreted
Phagocytosis & Lysis
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FATE OF INTRAVASCULAR HEMOGLOBIN
Haptoglobin: hemoglobin-haptoglobin complex is metabolized in theliver and spleen, forming a complex iron-globin that prevents theloss of iron through urine.
Hemopexin: binds the free HEM. The complex hem- hemopexin isovertaken by the liver, iron being deposited in the form offerritin.
Methemalbumin: oxidized hem-albumin complex.
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METABOLISMUL NORMAL AL BILIRUBINEI
Preluarea bilirubinei (indirecte,neconjugate) de ctre ficat este
mediat de o protein ligandin.
Bilirubina se conjug cu acidulglucuronic, xiloz, sau riboz.Acidul glucuronic este majoritar reacia e catalizat de UDP
glucuronil transferaz. (rezultbilirubina direct, conjugat).
Bilirubina conjugat estehidrosolubil, secretat dehepatocite la polul biliar n
canaliculele biliare.
n intestin este convertit lastercobilinogen (urobilinogen)(incolor) de ctre flora microbian.
Oxidarea la stercobilin (colorat
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HYPERBILIRUBINEMIA
Jaundice:
Total Bilirubin > 3 mg/dL)
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PREHEPATIC JAUNDICE
Excess of unconjugated bilirubin(above the liver capacity toconjugate bilirubin) - afterhemolysis.
Excess of hemolysis:-autoimune diseases,-Hemolytic diseases of newborn (Rh,ABO group incompatibility)-Abnormal RBC (talasemie),
- large, extended hematomas.
Unconjugated bilirubin < 0.5 mg/dL
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HEPATOCELLULAR JAUNDICE
deficit of : Uptake, conjugation, secretion of bilirubin.
Reflects generalized hepatic disfunction
In this case hiperbilirubinemia is associated withincrease of other hepatic markers: AST, ALT.
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POSTHEPATIC JAUDICE
Caused by obstruction of biliarycanaliculs
Bilirubina is conjugated, otherbiliary metabolites biliary acids
increase in plasma
Stools are weak colored,characterized by the absence ofstercobilin and urobilin anddark urine (conjugated bilirubin).
In complete obstruction urobilinis absent in urine.
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JAUNDICE
JAUNDICE------Bilirubin In urine?
YES HEPATOCELLULAR DAMAGE POST-HEPATIC CHOLESTASISINTRAHEPATIC CHOLESTASIS
SDR. ROTOR/ DUBIN-JOHNSON
NO: PHYSIOLOGICAL JAUNDICESDR. GILBERT
HEMOLYSISGLUCURONIL- TRANSFERASE
DEFICIENCY
BIL I BIL D BILUrin
FA ASAT Alb GGT
Physiological jaundice + N - N N N N
Hemolysis + N - N N N N
Gilbert syndrome + N - N N N N
Hepatitis ++ ++ + N / + +++ N ++
Hepatitis - colestatic + +++ + ++ ++ N ++
Ciroz - incipienta N N - N N N +
Ciroz finala ++ ++ + ++ ++ DECREASE
++
Icter obstructiv + +++ + +++ N/ + N +++
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Genetic diseases in connection with bilirubin metabolism:
1. Gilbert syndrome uptake deficiency of indirect bilirubin- increased indirect bilirubin
- Normal hepatic function, including gamma GT- bilirubin negative in urine2. Glucuronil transferase deficiency - rare
- unconjugated bilirubin (indirect) is increased- bilirubin negative in urine- apear usually in newborns- severe forms known under name Crigler-Najar syndrome
3. Dubin-Johnson and Rotor syndromes - rare
- Causes: decreased excretion of direct bilirubin from hepatocytes to biliarycanaliculs. Result:hyperbilirubinemia conjugated and positive bilirubinein urine.
- in Dubin-Johnson syndrome accumulation of a black pigment in thehepatocytes
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NEONATAL JAUNDICE
Apears more frequently in premature newborn
Appears in the first 10 days of life, usually in the 4th or 5th day
Causes: enzymatic immaturity involved in bilirubin conjugation
Increased indirect bilirubin are toxic in newborns. The indirect form of bilirubin ishydrophobic, passes hemato-encefalic barrier and may lead to nuclear jaundice(kernicterus)
Tratment: fototherapy with UV. In skin indirect bilirubin (insoluble) will betransformed in direct bilirubin (hydrosoluble) nontoxic, which is eliminated inurine.
Phenobarbital administered preventive to mothers, with risk of early birth. ThePhenobarbital passes the placenta and induces the synthesis of UDP glucuroniltransferases
Unsolved jaundice after 10 days, rises a pathological cause.
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B. Pancreas exploration
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Pancreas exploration
Assessment of pancreatic function:
1. Serum enzymes:1. amylase (serum+urine). Total amylase represent the sum of pancreatic and salivary
enzymes (may be increased in salivary pathology: infections with urlian virus parotidites,tumors, calculus)
- may increase in neighborhood pathology (ulcer penetrant in pancreas, infarct intestinomezenteric,
acute colecistitis, intestinal occlusion)- may increase in gynecological pathology (extrauterin pregnancy, ovarian tumour)
2. Trypsin
3. Lipase
2. Functional tests:
Exocrine:1. Secretin test (measure bicarbonate output)
2. Lundth test (measure pancreatic digestive capacity)3. PABA test (oral adm of bentiromide, followed by measurement ofp-aminobenzoic acid in
the urine or blood)4. Faecal fat
Endocrine:1. Glucose tolerance test
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Acute pancreatitis
Acute Pancreatitis Amylase increases in the first 6 hours after onset and stays increased about 2 days; after
that period amylase is increased in urine only Patients that develop acute Kidney Insufficiency, hyperamilasemia may stay longer
increased Other parameters: glycemia, triglicerides, renal function (urea, creatinine), Calcium Associated with: alcoholism, biliary tract disease May be precipitated by: hyperchylomicronaemia Biochemical tests:
Serum amylase Urinary amylase Serum trypsin Serum lipase
Secondary: hypocalcemia, hyperglycemia, hyperbilirubinemia
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Chronic pancreatitis
Chronic Pancreatitis Clinical features:
Severe epigastric pain Weight loss steatorrhoea
Aetiology: Alcoholism Calcification of pancreas Recurrent acute pancreatitis -increased or normal amylase values
Laboratory investigation: -microscopic examination of digestion faeces Functional exocrine tests: secretin, Lundth, PABA, OGTT
Pancreatic cancer- cc de cap de pancreas colestasis Pancreatic lipase specific for pancreas microscopic examination of digestion - faeces
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C. Gastrointestinal exploration
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Gastrointestinal exploration
Gastric exploration
Basal and stimulated gastric acidity
Infection with Helicobacter pylori urease test, Ag HP, Ab HP (IgG)
Occult Blood Test- Gregersen test.Attention to diet, drugs, gingivalhemorrhagies
In case of digestive hemorrhagies-complete hemogramm
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Biliary ducts exploration
Biliary drieinage aspectmacroscopic
Bila A - intestinal
Bila B - vesicular Bila C hepatic Turbid, purulent aspect Microscopic examination-
leucocytes, epithelial cells,
cholesterol cristals, tumoralcells, lamblia (giardia) chysts
Biliculture
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Exploration of intestines
Occult Blood test
Complete Hemogramm
Microscopic examination of digestion muscularfibres, lipid droplets, starch granules
Coproparazitologic examination- parasites, eggs ofparasites
Coproculture Shigella, Salmonella, E.coli(enterotoxigen, enteropatogen, enterohemoragic)