Functional and organic diseases of liver and bile ducts. Etiology, pathogenesis, clinical features, diagnostics, treatment and prophylactic Lecturer: Gorishna Ivanna Lubomyrivna

Plan of the lecture Definition of biliary dyskinesia Definition of biliary dyskinesia Biliary dyskinesia Biliary dyskinesia classification Clinical manifestation Methods of examinations biliary dyskinesia Treatment of the different kinds of biliary dyskinesia Definition of the chronic hepatitis Definition of the chronic hepatitis Hepatitis classification Clinical manifestation Methods of examinations Treatment of the different kinds of hepatitis

Definition of the Biliary Dyskinesia is a disorder of the sphincter’ tonus and kinetics of the gall-bladder and bile ducts. is a disorder of the sphincter’ tonus and kinetics of the gall-bladder and bile ducts.

Classification hypertonic-hyperkinetic dyskinesia hypertonic-hyperkinetic dyskinesia hypotonic-hypokinetic dyskinesia hypotonic-hypokinetic dyskinesia

Clinical manifestation of hypertonic-hyperkinetic dyskinesia Duration of the disease up to 1 yr. Duration of the disease up to 1 yr. Pain syndrome Pain syndrome Dyspeptic syndrome Dyspeptic syndrome Manifestations of vegetative dysfunction, neurotic symptoms Manifestations of vegetative dysfunction, neurotic symptoms

Clinical manifestation of hypotonic-hypokinetic dyskinesia Pain syndrome Pain syndrome Dyspeptic syndrome Dyspeptic syndrome Hepatomegaly Hepatomegaly Gallbladder symptoms are positive Gallbladder symptoms are positive

Plan of examination Fool blood count Fool blood count Biochemical test of blood Biochemical test of blood Serum aminotransferase Serum aminotransferase Serum bilirubin (predominantly the direct reacting fraction) Serum bilirubin (predominantly the direct reacting fraction) Serum alkaline phosphatase Serum alkaline phosphatase Albumin and globulin level Albumin and globulin level Stool test Stool test USE of the abdominal cavity + cholekynetics for functional investigations USE of the abdominal cavity + cholekynetics for functional investigations

Stool test:Norma Biliary dyskinesia indigested muscular fibers non-digestable cellulose digestable cellulose fatty acids mucous epithelium leucocytes erythrocytes

Duodenal intubation PortionphaseDuration (min) ColorSpeed of bile excretion Total volume, ml AI10-20 Golden- yellow II III3-5yellow

Duodenal intubation PortionphaseDuration (min) ColorSpeed of bile excretion Total volume, ml BIV20-30 Brown CV20-30Golden -yellow Constant

Duodenal intubation Portion ColourpHEpitheliumLeucocyteLambliaMu- cus AGolden yellow ↑ BBrown↑ CBright yellow ↑

Duodenal intubation PortionColorpHEpitheliumLeucocytesLambliaMu- cus AYellow -green BBrown -green Cyellow

USE of the abdominal cavity + cholekinetics for functional investigations cholekinetics lead to a contraction of the gallbladder for 1/2-2/3 of the previous volume cholekinetics lead to a contraction of the gallbladder for 1/2-2/3 of the previous volume hypertonic dyskinesia - contraction of the gallbladder more than 2/3 of the previous volume hypertonic dyskinesia - contraction of the gallbladder more than 2/3 of the previous volume hypotonic dyskinesia - contraction of the gallbladder less than 1/2 of the previous volume hypotonic dyskinesia - contraction of the gallbladder less than 1/2 of the previous volume

Diet 5 Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt. Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt. Foods boiled, steamed and baked are recommended; food taking 5 times daily Foods boiled, steamed and baked are recommended; food taking 5 times daily

Treatment of hypertonic- hyperkinetic dyskinesia 1. Diet N 5 2. Spasmolitics:  platyphyllini hydrotartratis (amp. 0.2 % 1 ml)  papaverini hydrochloridum (tab. 0.01, amp. 2 % 2 ml)  no-spa (tab or amp. 2 % 2 ml) 3. Choleretic:  cholagon  allocholum  cholenzynum  galstena  hepabene

Treatment of hypotonic- hypokinetic dyskinesia 1. Diet N 5 Prokinetic: motilium, domperidone (tabl g) 1 mg/kg/day Prokinetic: motilium, domperidone (tabl g) 1 mg/kg/day 3. Choleretic and cholekinetic drugs:  cholagon  allocholum  cholenzynum  galstena  hepabene  chophytol

Hepatoprotectors Essentiale (cap., amp.) 1-2 cap. 3 times a day Essentiale (cap., amp.) 1-2 cap. 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Thiotriazolinum 1 tabl. 3 times a day Thiotriazolinum 1 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day

Antioxidants (aevitum, tocopheroli acetatis) Antioxidants (aevitum, tocopheroli acetatis) Enterosortion (enterosgel) Enterosortion (enterosgel) Probiotics (linex, bifiform, bactisuptil) Probiotics (linex, bifiform, bactisuptil)

Blind Duodenal intubation with magnesii sulfatis 33 % with magnesii sulfatis 33 % xylitol or sorbitol 10 % xylitol or sorbitol 10 %

Chronic cholecystitis and cholecystocholangitis Chronic recurrent inflammatory process of gallbladder and intrahepatic bile ducts, accompanied with bile ducts motor disorders Chronic recurrent inflammatory process of gallbladder and intrahepatic bile ducts, accompanied with bile ducts motor disorders

Clinical manifestation Pain syndrome Pain syndrome Dyspeptic syndrome Dyspeptic syndrome Intoxication syndrome Intoxication syndrome Cholestasis Cholestasis Inflammatory syndrome Inflammatory syndrome Dyscholia Dyscholia Ph of bile is acidic Ph of bile is acidic USE USE

Duodenal intubation Portion ColorpHEpitheliumLeucocytesLambliamu cus Agreen BBrown- green Cyellow

Treatment of hypotonic- hypokinetic dyskinesia 1. Diet N 5 2. Prokinetic: motilium, domperidone (tabl g) 1 mg/kg/day 3. Choleretic and cholekinetic drugs:  cholagon  allocholum  cholenzynum  galstena  hepabene  chophytol

Hepatoprotectors Essentiale (cap., amp.) 1-2 cap. 3 times a day Essentiale (cap., amp.) 1-2 cap. 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Thiotriazolinum 1 tabl. 3 times a day Thiotriazolinum 1 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day

Treatment of lambliasis, girardiasis Furasolidone 8-10 mg/kg 4 times a day- 10 days (tabl. 0.05) Furasolidone 8-10 mg/kg 4 times a day- 10 days (tabl. 0.05) Tinidazole mg/kg/day (tab. 0.5, 0.15) Tinidazole mg/kg/day (tab. 0.5, 0.15) Metronidazolum mg/kg for 5 days (tabl. 0.5) Metronidazolum mg/kg for 5 days (tabl. 0.5)

Blind Duodenal intubation with magnesii sulfatis 33 % with magnesii sulfatis 33 % xylitol or sorbitol 10 % xylitol or sorbitol 10 %

Definition of the chronic hepatitis a continuing hepatic inflammatory process manifested by elevated hepatic transaminase level, lasting 6 mo or more and accompanied with pain, dyspeptic, intoxication and cholestatic syndromes a continuing hepatic inflammatory process manifested by elevated hepatic transaminase level, lasting 6 mo or more and accompanied with pain, dyspeptic, intoxication and cholestatic syndromes

Chronic hepatitis can be caused by persistent viral infection, drugs, and autoimmune or unknown factors. Approximately 15–20 % of cases are associated with hepatitis B infection; in this group of patients, unusually severe disease may be caused by superimposed infection with hepatitis D (a defective RNA virus that is dependent on replicating hepatitis B virus). More than 90 % of infants infected during the 1st year of life experience chronic hepatitis B infection compared with a rate of 5–10 % among older children and adults. Chronic hepatitis may also follow 30–50 % of hepatitis C virus infections. Patients receiving blood products or who have had massive transfusions are at increased risk. Hepatitis A virus does not cause chronic hepatitis. Drugs commonly used in children that may cause chronic liver injury include isoniazid, methyldopa, nitrofurantoin, dantrolene, and the sulfonamides.

Classification of the hepatitis Forms of chronic hepatitis: 1. В, С, D) 1. Chronic viral hepatitis (В, С, D) 2. Autoimmune hepatitis 3. Drug-induced hepatitis 4. Toxic hepatitis 5. Cryptogenic

The activity of the chronic hepatitis 1. Active period: а) mild activity (elevation of ALT < 3 times); а) mild activity (elevation of ALT < 3 times); б) moderate activity (elevation of ALT < 10 times); б) moderate activity (elevation of ALT < 10 times); в) severe activity (elevation of ALT >10 times). в) severe activity (elevation of ALT >10 times). 2. Inactive period

Stages of chronic hepatitis 0- fibrosis is absent; 1- mild fibrosis; 2- moderate fibrosis; 3- severe fibrosis; 4- cirrhosis.

Example of the diagnosis Chronic viral hepatitis B, active period, mild activity, without fibrosis Chronic viral hepatitis B, active period, mild activity, without fibrosis

Clinical manifestation Pain syndrome Pain syndrome Dyspeptic syndrome Dyspeptic syndrome Intoxication syndrome Intoxication syndrome

Objective examination shows Inadequate weight gain or failure to thrive Inadequate weight gain or failure to thrive Sexual delay Sexual delay Jaundice Jaundice Pruritus Pruritus Hyperpigmentation or hypopigmentation of the skin Hyperpigmentation or hypopigmentation of the skin Symptoms of hypovitaminosis Symptoms of hypovitaminosis Telangiectasias (spider angiomas) Telangiectasias (spider angiomas) Palmar erythema Palmar erythema Clubbing fingers Clubbing fingers

Jaundice

Objective examination shows Hepatic smell Hepatic smell Hepatomegaly Hepatomegaly Symptoms of portal hypertension Symptoms of portal hypertension Splenomegaly Splenomegaly Ascites Ascites Collateral circulation Collateral circulation Splenism Splenism Hemorrhagic syndrome Hemorrhagic syndrome Encephalopathy Encephalopathy

Hepato- spleno- megaly

Collateral circulatio n in case of biliary cirrhosis

Plan examination Fool blood count Fool blood count Biochemical test of blood Biochemical test of blood Serum aminotransferare Serum aminotransferare Serum bilirubin (predominantly the direct reacting fraction) Serum bilirubin (predominantly the direct reacting fraction) Serum alkaline phosphatase Serum alkaline phosphatase Serum γ-globulin levels Serum γ-globulin levels Albumin and globulin level Albumin and globulin level The prothrombin time The prothrombin time serum iron and serum ferritin serum iron and serum ferritin Stool test Stool test USE of the abdominal cavity USE of the abdominal cavity

Tests in case viral hepatitis ELISA test ELISA test PCR examination PCR examination Quantitative PCR Quantitative PCR Viral genotyping Viral genotyping

HBV serum markers HBsAg HBsAg HBsAb (recovering) HBsAb (recovering) HBeAg HBeAg HBeAb HBeAb HBcAb Ig M HBcAb Ig M HBc Ab Ig G (recovering) HBc Ab Ig G (recovering) HBV DNA HBV DNA

HCV serum markers HCV Ab Ig G HCV Ab Ig G HCV Ab Ig M HCV Ab Ig M HCV RNA HCV RNA

HDV serum markers HDV Ab Ig G HDV Ab Ig G HDV Ab Ig M HDV Ab Ig M HDV RNA HDV RNA HBsAg HBsAg

Autoimmune hepatitis Hypergammaglobulinemia. Hypergammaglobulinemia. Serum IgG levels usually exceed 16 g/L. Serum IgG levels usually exceed 16 g/L. Serum antiactin (smooth muscle), antinuclear, and antimitochondrial antibodies. Serum antiactin (smooth muscle), antinuclear, and antimitochondrial antibodies. Additional less common autoantibodies include rheumatoid factor, anti-parietal cell antibodies, and antithyroid antibodies. Additional less common autoantibodies include rheumatoid factor, anti-parietal cell antibodies, and antithyroid antibodies. A Coombs-positive hemolytic anemia may be present. A Coombs-positive hemolytic anemia may be present.

Treatment of the viral hepatitis   Regime  Diet 5   Interferon-therapy: (α-Interferon).

Diet 5 Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt. Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt. Foods boiled, steamed and baked are recommended; food taking 5 times daily Foods boiled, steamed and baked are recommended; food taking 5 times daily

Interferon-therapy: 1. Intron А (α 2b -), 1. Intron А (α 2b -Interferon), Form of production - vial with 3 and 5 М units 2. Viferon (α Viferon (α 2 - Interferon+ vit. E and C) Form of production rectal suppository Viferon units Viferon units Viferon 3 – units Viferon 4 – units. 3. Pegasis (peginterferon α-2а) Form of production syrette with 135 mcg and 180 mcg Form of production syrette with 135 mcg and 180 mcg

Intron А-therapy: EtiologyDoses Way of injection Duration of treatment HBV 5 М units/м 2 3 times a week i/m, s/c 6 mo. HCV 3 М units/м times a week i/m, s/c mo.

Modern treatment of viral hepatitis  HBV: +Lamivudine.  HBV: Interferon+Lamivudine. the doses of Lamivudine is 3 mg/kg (up to 100 mg) once per day  HСV:  HСV: Interferon+Ribavirin the doses of is mg once per day the doses of Ribavirin is mg once per day

Autoimmune hepatitis Prednisone is given at an initial dose of 1–2 mg/kg/day and continued until aminotransferase values return to less than twice the upper limit of normal. Prednisone is given at an initial dose of 1–2 mg/kg/day and continued until aminotransferase values return to less than twice the upper limit of normal. The dose should then be lowered in 5-mg decrements over a 4- to 6-wk period, until a maintenance dose of less than 20 mg/day is achieved. The dose should then be lowered in 5-mg decrements over a 4- to 6-wk period, until a maintenance dose of less than 20 mg/day is achieved. In patients who respond poorly, who experience severe side effects, or who cannot be maintained on low-dose steroids, azathioprine (1.5 mg/kg/day, up to 100 mg/day) may be added, with frequent monitoring for bone marrow suppression. In patients who respond poorly, who experience severe side effects, or who cannot be maintained on low-dose steroids, azathioprine (1.5 mg/kg/day, up to 100 mg/day) may be added, with frequent monitoring for bone marrow suppression.

Hepatoprotectors Heptral (tabl g, amp g) 1-2 tabl. 3 times a day (20-25 mg/kg/day) Heptral (tabl g, amp g) 1-2 tabl. 3 times a day (20-25 mg/kg/day) Ursophalk (cap. 250 mg) 8-10 mg/kg/day Ursophalk (cap. 250 mg) 8-10 mg/kg/day Essentiale (cap., amp.) 1-2 cap. 3 times a day Essentiale (cap., amp.) 1-2 cap. 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Thiotriazolinum 1 tabl. 3 times a day Thiotriazolinum 1 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day

Antioxidants (aevitum, tocopheroli acetatis) Antioxidants (aevitum, tocopheroli acetatis) Enterosortion (enterosgel) Enterosortion (enterosgel) Probiotics (linex, bifiform, bactisuptil) Probiotics (linex, bifiform, bactisuptil)