lecture 5 liver and gastrointestinal tract

7/28/2019 Lecture 5 Liver and Gastrointestinal Tract

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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-1


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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)

lecture 5 liver and gastrointestinal tract

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