Internal medicine hepatology 2008

INTERNAL MEDICINE DEPARTMENT – HEAMATOLOGY UNIT 1

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جبمعخ األسكىدريخ

الطت كليخ

وحد أمراض الكجد والمرارح ............... قسم األمراض الجبطىخ

------------------

التدريس ثىحدح أمراض الكجد والمرارح أسمبء أعضبء هيئخ

. (أستبذ متفرغ ). رفيق زاهر / د. أ

. (أستبذ متفرغ ). أحمد الجىهري / د. أ

. (أستبذ متفرغ ) . علً عجد المعطً/ د. أ

. السعيد حسه اثراهيم / د. أ

. محمد يسري طبهر / د. أ

. هدي عجد المجيد العجبن / د. أ

. وجالء مصطفً مشعل / د. أ

. محمد يىسف الحصبفً / د. أ

. فتح اهلل صدقً / د. أ

. (أستبذ مسبعد ). عمرو علً عجد المعطً / د. أ

. (مدرس ). أحمد السيد زيد / د

. (مدرس مسبعد ). امبوً صبلح اليمىً / د

. (مدرس مسبعد ). ايهبة مصطفً حسىوخ / د

. (مدرس مسبعد ). ثيريهبن السيجد سبلم / د

. (مدرس مسبعد ). مروح محمد رضب / د





HEPATOLOGY DEPARTMENT BOOK

TABLE OF CONTENT

VIRAL HEPATITIS ----------------------------------------------------------- 3

JAUNDICE ------------------------------------------------------------------------- 4

ASCITIS ------------------------------------------------------------------------------ 12

CIRRHOSIS ----------------------------------------------------------------------- 28

HEPATIC TUMOUR ------------------------------------------------------- 33

ACUTE LIVER FAILURE ---------------------------------------------- 37

GALL BLADDER DISEASES----------------------------------------- 43

PANCREATIC DISEASES --------------------------------------------- 46





Viral Hepatitis

Dr. Fathalla Sedky

Assistant Prof of Hepatology

Faculty of Medicine, Alex UN

Clinical types:

Asymptomatic: only elevated transaminases. Anicteric: GI and influenza like symptoms, no jaundice. Classic: 3 stages.

1- Prodromal 3-4 days. Profound malaise, fever, anorexia nausea, vomiting, abdominal Pain.

2- Icteric 1-4 weeks. - Change of urine color followed by jaundice and itching. - Patient feels generally better and appetite returns.

- Tender hepatomegaly. 3- Convalescent.

Prolonged cholestasis: - Classic acute hepatitis but the icteric stage is prolonged 8-29 weeks with

manifestations of cholestasis. - More with HAV.

Fulminant hepatitis: - Patient after a typical acute onset becomes deeply jaundiced, ominous

manifestations– persistent vomiting, fetor hepaticus, drowsiness, flappy tremors, finally coma.

- Commonly with HAV, HBV, HEV.

Relapse: - 1.8-15 % especially HAV. - Attack is usually milder. - Precipitated by premature activity.

Diagnosis: - SGOT, SGPT: Peak levels 1-2 days before or after onset of jaundice. - Useful in early diagnosis and detection of anicteric cases. - Bilirubin & ALP usually elevated. - PT prolonged. - CBC --- Leucopenia, lymphopenia in anicteric stage --- Aplastic anemia may occur weeks –months after acute attack.

Treatment - Bed rest. - Diet: low fat high carbohydrate diet more palatable to the patient. Symptomatic and supportive.

- Corticosteroids only in cholestatic HAV. Convalescence is not allowed till patient is symptom free, liver no longer tender & s

bilirubin <1.5 mg/dl. - Follow up for monthly for 3ms.





Basics of Hepatitis A - RNA Picorna virus - Acute disease and asymptomatic infection - No chronic infection - Protective antibodies develop in response to infection - confers lifelong immunity. - Rare complications—fulminant hepatitis, cholestatic hepatitis, relapsing hepatitis.

Hepatitis B Virus

Extra hepatic manifestations - Polyartritis. - Glomerulonephrits. - Essential mixed cryoglobulinemia. - Guillain-Barre syndrome.

Treatment Acute: - Symptomatic. - Liver support (silymarine). Chronic: - Interferon. - Lamivudine.

Hepatitis C Virus

Sexual Transmission of HCV

Occurs, but efficiency is low

– Rare between long-term steady partners (1.5-3%)

– Factors that facilitate transmission between partners unknown (e.g., viral titer)

Perinatal Transmission of HCV

• Transmission only from women HCV-RNA positive at delivery

– Average rate of infection 6%

– Higher (17%) if woman co-infected with HIV

– Role of viral titer unclear

• No association with delivery method

• Infected infants do well

– Severe hepatitis is rare

Household Transmission of HCV

• Rare but not absent

• Could occur through percutaneous/mucosal exposures to blood

– Theoretically through sharing of contaminated personal articles (razors, toothbrushes)

– Contaminated equipment used for home therapies ►IV therapy ►Injections





Natural History of HCV Infection Extra hepatic manifestations - Polyartritis. - Glomerulonephrits. - Essential mixed cryoglobulinemia. - Lymphocytic sialadenitis. - Thyroiditis. - Lichen plannus.

Treatment

• Acute: - Symptomatic. - Liver support. - ?? Interferon.

• Chronic: 1- Antiviral drugs (interferon, ribavirin). - Treatment might take as long as a year. - About 80% of patients get rid of the virus. 2- ?? Liver support.

• Liver transplant – For end-stage cases.

Problem III: needle stick injury from a known HCV patient.

• HCV RNA becomes positive 2 weeks after exposure and remains positive throughout the acute illness.

• Symptoms appear by week 6.

• ALT tests do not become abnormal until weeks 4-8.

• Anti-HCV antibody (ELISA) generally does not become positive until 6-8 weeks.

• Therefore, the HCV RNA test is the most valuable tool for detecting an acute infection, and we use it routinely at our institution to identify infection after a needle stick. If the HCV RNA is negative at week 2, we repeat the test 4 weeks later, and if it remains negative, the patient is advised that there has been no transmission.

• Spontaneous viral clearance occurs in the first 3 months after exposure in most cases, after that spontaneous clearance is unlikely.

• In those who remain viraemic at 12 weeks after initial seroconversion, antiviral therapy is recommended if there are no absolute contraindications to its use.

• 95% of interferon treated patients will achieve a sustained virological response with only 6 months of therapy.





Chronic hepatitis Definition: chronic inflammatory reaction in the liver for more than 6 ms.

Etiology: 1- Viral: B& D, C 2- Autoimmune. 3- Drugs. 4- Genetic.

Pathology HAI: histological activity index A scoring system based on 3 categories for necro-inflammation & one for fibrosis. Inflammation (grade): 1- Periportal necrosis ± bridging necrosis score 0-10. 2- Intralobular degeneration & focal necrosis.score 0-4. 3- Portal inflammation score 0-4. Minimal G 1-3. Mild G 4-8. Moderate G 9-12. Severe G 13-18.

Pathology Fibrosis (stage): None stage 0. Mild portal expansion stage 1. Moderate portal-portal septa stage 2. Severe bridging with distortion stage 3. Cirrhosis cirrhosis stage 4.

Clinical picture Fatigue (most common), RT hypochondrial pain, nausea, jaundice, muscle and joint

pains. Tender hepatomegaly, occasionally vascular spiders.

Investigations: CBC, liver function tests, US, liver biospy. Investigations of the cause

Autoimmune hepatitis Type 1 In most of cases. Usually in young females. Asymptomatic for long time. Endocrinal manifestations, acne, cuchingoid features, amenorrhea.

Associated conditions: prolonged fever, polyarthritis of large joints, purpura, hemolytic anemia, splenomegaly & lymphadenopathy, lupus kidney, diabetes, pleurisy, primary PH.





Type 2 2a: affects mainly girls. Extra-hepatic immunologic disease. 2b: patients are usually males and older. No clear association with other Autoimmune disease. Respond better to antiviral.

Treatment Corticosteroids: - At least 2 Y. - 1st week: 10 mg x3 daily. - 2nd & 3rd weeks: reduce to 10-15 mg/day. - Monthly check. - Full check at 6ms, no remission continues for 6m + azathioprine 50-100 mg /day. - Stop after 2 yrs, normal SGOT, SGPT, S bilirubin, negative ANA, inactive liver biopsy.

HBV 15 % chronicity. Acute HBV: no treatment. Chronic hepatitis B: antiviral - Interferon, for 6 ms. - Oral: lamivudine, adefovir, entecaver, continued for 6 m after seroconversion.

HCV Predictors of good response: - Host: age < 45, non obese, female, Duration of infection <5 yrs, ALT moderate elevation, normal GGT, no cirrhosis, low liver iron. - Virus: low HCV RNA, genotype 2, 3.

Interferon Side effects: - Early: flu like, myalgia, nausea, headache - Late: anorexia, alopecia, wt loss, anxiety & depression, diarrhoea, muscle aches,

bone marrow depression, optic neuropathy, thyroid dysfunction. Contraindications: psychatric illness, thyroid dysfunction, neutropenia,

thrombocytopenia, CHD, arrhythmia, decomensated cirrhosis, renal transplant.

Ribavirin Side effects: hemolytic anemia (dose dependent), hyperuricemia Contraindications: during pregnancy, anemia, renal insufficiency, severs heart disease.

Problems!! Problem I: needle stick injury from a known HBV patient.

• Wounds and skin sites that have been in contact with blood or bloody body fluids should be washed with soap and water. Exposed mucous membranes should be flushed with water. Squeezing the wound and treating with topical antiseptics are not recommend





Jaundice

Dr. FathAlla Sidkey Assistant Prof. of Internal Medicine

DEFINITION: Yellow color of skin, mucous membranes and sclera due increased amount of bilirubin. Also caused by carotenemia, and some drugs e.g. quinacrine.

Bilirubin is readily bound to elastic tissue. Skin ocular sclera and blood vessels have high elastic tissue content and hence become easily icteric.

PHYSIOLOGY OF BILE BILE ACID: Primary acids CA, CDCA conjugated with glycine or taurine to form bile salts. function--- lipid solubilization (mixed micelles) Canalicular secretion is an active transport process ---osmotic force--- drive bile flow

(bile salt dependent flow). Enterohepatic circulation (95%) mainly in terminal ileum. Bacterial deconjugation in intestine--- 2ry bile salts.

PHYSIOLOGY OF BILE SECRETION Total bile flow---500-600ml /day. Active Na-K-ATPase pump at the canalicular membrane. Part of the secretion is dependent on bile salts. Active secretion in the ductules (secretin) Cholecystokinin-pancerozymin--GB contraction.

CLASSIFICATION Primarily uncojugated: - CB fraction < 20 % total bilirubin. - dt increased production, defective uptake, defective conjugation. Mixed: - CB fraction = 20-50 %. - dt hepatitis, cirrhosis. Primarily conjugated (cholestatic): - CB > 50 %. Prehepatic, hepatic, posthepatic.

Normal Conjugated unconjugated





Diagnosis

OCCUPATION: Employment involving alcohol. Contact with rats in sewage disposal Wiel‘s disease.

PLACE OF ORIGIN: Mediterranean, African or Far East may suggest carriage of hepatitis B or C.

ONSET OF ILLNESS: Abrupt onset of nausea, anorexia followed by progressive jaundice---acute viral

hepatitis. Gradual onset of jaundice + pruritus---cholestasis. Intermittent rt. upper quadrant abd. Pain followed by jaundice---GS. Gradual onset of painless jaundice + wt. loss---tumor. In hepato-cellular jaundice, dark urine precedes the onset of jaundice by a few days. In hepatocellular jaundice patient feels ill, while in cholestatic jaundice patient feels

well despite deep jaundice and itching.

SYMPTOMS: Past history: -contact with jaundiced patient. -injection, blood transfusions, Operations.

Family history: -Jaundice, anemia, splenectomy---hemolytic anemia.

Drugs.

LAB INVESTIGATION: Serum bilirubin (total, direct) ALP > 3 times normal ---- cholestasis. Other cholestatic markers ---- GGT. SGOT, SGPT high in hepatocellular jaundice, lower level in cholestasis. High levels

may be found transiently with acute bile duct obstruction due to a stone. PT may be prolonged --- 10 mg vit K IV /day for 3 days --- return to normal in

cholestasis, but little change in hepatocellular jaundice. CBC for anemia (hemolysis), leucocytosis.





Gilbert‘s syndrome: • Autosomal recessive. • Deficiency UDPG enzyme, about 30 % of normal. • Mild Inc in serum bilirubin (1-5 mg/dl). • Jaundice is mild & intermittent, Inc by fasting and intercurrent infection, fall by

phenobarbitone. • Excellent prognosis, reassurance.

Crigler-Najjar syndrome Autosomal recessive.

Type I: - No conjugating enzyme. - Very high s. bilirubin since birth. - Risk of kernictrus. - No response to phenobarbitone. - Phototherapy degrades unconjugated bilirubin to products which are water soluble

and can be secreted into the bile. - Liver transplantation is the only definitive line of treatment.

Type II: - UDBG is reduced to > 10 % of normal. - Dramatic response to phenobarbitone, pat. Survive to adult life.

Dubin-johnson syndrome Mainly conjugated hyperbilirubinemia. Autosomal recessive. Defect in cMOAT transporter. Prolonged BSP retention test, serum value at 120 min >at 45 min due to regurgitation

into the circulation of the glutathione conjugate (normally excreted via cMOAT) Liver is black (black liver jaundice).

Rotor syndrome Similar to DJ syndrome. Two differences: - Liver is not pigmented. - No 2ry rise in BSP retention test. Defect is in hepatic uptake rather than excretion of

BSP.

Cholestasis Failure of normal bile to reach the duodenum. Intra-hepatic or extra-hepatic.

Intra-hepatic bile ducts Intra-hepatic cholestasis





Clinical effects: -Pruritus and malapsorption (bile salts). -Bleeding tendency (vit K). -Bone disease (vit D and Ca). -Xanthoma and xanthelasma (cholesterol). -Hyperpigmentation (melanin).

Intermittent jaundice Hemolytic anemia. Gilbert syndrome. Relapsing hepatitis. Drugs. Benign recurrent intrahepatic cholestasis. Cholestasis of pregnancy. Bilary parasites. Periampullay tumors. CBD stones. Wilson‘s disease.





ASCITES

Dr. Amr Aly Abd El Moety

Assistant professor of Hepatology

Definition

Pathologic fluid accumulation within the peritoneal cavity.

Pathogenesis of ascites

A- Cirrhotic Ascites

The most recent theory of ascites formation, the "peripheral arterial

vasodilation hypothesis," proposes that both older hypotheses, the underfill and

overflow theories, are correct, but that each is operative at a different stage.





B- Noncirrhotic Ascites

1-Peritoneal carcinomatosis:

Appears to cause ascites through the production of proteinaceous fluid by tumor

cells lining the peritoneum. Extracellular fluid enters the peritoneal cavity to reestablish

oncotic balance.

2-Massive liver metastases:

Portal hypertension due to occlusion of portal veins by tumor nodules.

3-Hepatocellular carcinoma:

Ascites forms because of the underlying cirrhosis-related portal hypertension,

tumor-induced portal vein thrombosis, or both.

4-Chylous ascites:

In patients with malignant lymphoma may be caused by lymph node obstruction

by tumor and rupture of chyle-containing lymphatics.

5-High-output or low-output heart failure or nephrotic syndrome:

As in cirrhosis, effective arterial blood volume appears to be decreased, and the

vasopressin, renin-aldosterone, and sympathetic nervous systems are activated. These

changes lead to renal vasoconstriction and sodium and water retention.

6-Tuberculosis, Chlamydia infection, and coccidioidomycosis:

Probably cause ascites through the production of proteinaceous fluid, as in

peritoneal carcinomatosis.

7-Spontaneous bacterial peritonitis (SBP):

Does not appear to cause fluid to accumulate; infection develops only in

preexisting ascites.

8-Pancreatic or biliary ascites fluid:

Forms by leakage of pancreatic juice or bile into the peritoneal cavity or by a

"chemical burn" of the peritoneum.

9-Abdominal surgery:

Especially extensive retroperitoneal dissection, lymphatics may be transected.





A-History Taking

1- History of alcohol intake, intravenous drug use, blood transfusions, sex with a

member of the same sex, acupuncture, tattoos, ear piercing, and country of origin.

2- Long-standing obesity (NASH).

3- Patients with a long history of stable cirrhosis and the sudden development of

ascites should be suspected of harboring a hepatocellular carcinoma.

4- History of cancer malignancy-related ascites. However, cancer in the past does

not guarantee a malignant cause of ascites.

5- History of heart failure may raise the possibility of cardiac ascites. Alcoholics in

whom ascites develops may have alcoholic cardiomyopathy or alcoholic liver

disease, but usually not both.

6- Tuberculous peritonitis is usually manifested by fever and abdominal pain.

7- Fitz-Hugh-Curtis syndrome caused by Chlamydia may cause inflammatory

ascites in a sexually active woman.

8- Patients in whom ascites and anasarca develop in the setting of diabetes should be

suspected of having nephrotic ascites.

1. Liver Cirrhosis

2. Non alcoholic

steatohepatitis

3. Alcohol

4. Hepatocellular

Carcinoma

5. Congestive heart

failure

6. Tuberculous

peritonitis

7. Acute hemorrhagic

pancreatitis.

8. Fitz-Hugh-Curtis

syndrome

9. Nephrotic syndrome

10. Myxedema

11. Connective tissue

disease

Causes of Ascites





9-Ascites in a patient with symptoms and signs of myxoedema should prompt

measurement of thyroid function.

10- Serositis in connective tissue disease may be complicated by ascites.

B-Physical examination

Full bulging abdomen should lead to percussion of the flanks. If they are dull then

check for "shifting." Approximately 1500 mL of fluid must be present before dullness is

detected.

A fluid wave is not worth testing for gaseous distention of the bowel, a

thick panniculus, and an ovarian mass can mimic ascites.

*Gaseous distention should be readily apparent on percussion.

*Ovarian masses usually cause tympanic flanks with central dullness. An

obese abdomen may be diffusely dull to percussion, and abdominal ultrasonography

may be required to determine if fluid is present.

The presence of;

Palmar erythema

Large pulsatile spider angiomata

Large abdominal wall collateral veins

Fetor hepaticus

Large veins on the patient's back suggests inferior vena cava blockage.

An immobile mass in the umbilicus, the Sister Mary Joseph nodule, is

suggestive of peritoneal carcinomatosis.

Congested neck veins Constrictive pericarditis.

Determination of the cause of ascites is based on the results of the

history, physical examination, and ascitic fluid analysis.

Abdominal Paracentesis

Indications:

Ascitic fluid should be sampled in all inpatients and outpatients with the new onset of

ascites and in all patients with ascites who are admitted to the hospital to exclude

infection.

Paracentesis should be repeated in patients with suspected infection.

Contraindications: Coagulopathy

Liver cirrhosis





C-Ascitic Fluid Analysis

Gross Appearance

1- Neutrophil count

If Neutrophil count >1000/mm3 fluid is clear

If Neutrophil count <5000/mm3 fluid is cloudy

If Neutrophil count < 50,000/mm3 Fluid resembles mayonnaise

2- RBC, count < 10,000 /mm3, the ascitic fluid looks pink. But more than

20,000/mm3 it will be distinctly red.

Red Ascitic fluid is due to:

a- Traumatic: Ascitic fluid will clot.

b- Rupture lymphatics in liver cirrhosis.

c- HCC

d- Peritoneal carcinomatosis

e- Tuberculous Ascites

3- Chylous Ascites: Due to increase in Triglyceride level above 200 mg/dL .

4- Dark brown colored Ascites indicates biliary perforation.

5- Black Ascites

Hemorrhagic pancreatitis

Malignant Melanoma

Ascitic Fluid Tests

A- Cell count

The WBC count in uncomplicated cirrhosis is less than 500 cells/mm3.

The absolute polymorphonuclear leukocyte count in uncomplicated cirrhosis is

less than 250/mm3.

Elevated ascitic fluid WBC count is seen in

Spontaneous bacterial peritonitis.

Tuberculous peritonitis.

Peritoneal carcinomatosis lymphocytes are mainly elevated)





B- Exudate/Transudate

Before the 1980s, the ascitic fluid total protein concentration was used to classify

ascites into exudates (>2.5 g/dL [25 g/L]) and transudates (<2.5 g/dL [25 g/L]).

Unfortunately, this classification does not work well in ascitic fluid.

C- Serum-Ascites Albumin Gradient

Serum albumin – Ascitic fluid albumin.

(SAAG) categorize ascites better than either the total protein concentration or

other parameters do.

D- Culture

Blood culture is sensitive in detecting monomicrobial infection which is a feature

of Spontaneous Bacterial Peritonitis.

E- Total protein

SAAG ratio is more sensitive in differentiating type of ascites than evaluating total

protein.

F- Glucose

In SBP and in the setting of gut perforation into ascitic fluid, the ascitic glucose

concentration usually drops to 0 mg/dL (0 mmol/L) because of large numbers of

stimulated neutrophils and bacteria.





G- Lactate Dehydrogenase

LDH enters ascitic fluid by diffusion from blood and by release from disintegrating

ascitic fluid WBCs. In SBP, the ascitic fluid LDH level rises because of the release of

LDH from disintegrated neutrophils.

H- Amylase

In patients with acute pancreatitis or gut perforation the ascitic fluid amylase

concentration is elevated markedly, usually greater than 2000 U/L

I- Gram's Stain

Bacteria are present only when there is an overwhelming infection, as in

advanced SBP or asplenic pneumococcal sepsis.

J- Smear and Culture for Tuberculosis

The direct smear of ascitic fluid to detect mycobacteria is almost never positive

because of the rarity of tuberculous peritonitis and the low concentration of mycobacteria

in ascitic fluid in tuberculous peritonitis.

In contrast to a sensitivity rate of approximately 50% for ascitic fluid

mycobacterial culture with optimal processing, laparoscopy with histology and culture of

peritoneal biopsies has a sensitivity rate of approximately 100% in detecting tuberculous

peritonitis.

K- Cytology

To detect Malignant cells.

L- Triglyceride

Chylous ascites has a triglyceride concentration greater than 200 mg/dL (2.26

mmol/L) and greater than the serum level; usually the level is greater than 1000 mg/dL

(11.30 mmol/L).

Chylous ascites has a triglyceride concentration greater than 200 mg/dL (2.26

mmol/L) and greater than the serum level; usually the level is greater than 1000 mg/dL

(11.30 mmol/L).

M- Bilirubin

Ascitic fluid bilirubin level greater than 6 mg/dL (102 μmol/L) and greater than the

serum level of bilirubin suggests biliary or upper gut perforation into ascites.





Shrunken cirrhotic liver

Surrounded by ascitic fluid

Complication of Ascites

1- Infection

1. SBP

a- Positive ascitic fluid culture.

b- Elevated ascitic fluid absolute PMN count (i.e., at least 250

cells/mm3 [0.25 × 109/L]).

c- No evidence of an intra-abdominal surgically treatable source of infection.

2. Polymicrobial bacterascites is diagnosed by;

Polymicrobial bacterascites is essentially diagnostic of gut perforation by the

paracentesis needle.





Pathogenesis of SBP





Symptoms and Signs of Ascitic Fluid Infection

Fever

Abdominal pain

Tender abdomen

Rebound

Altered mental status

Bacteriology

SBP: Escherichia coli, streptococci (mostly pneumococci), and Klebsiella .

Polymicrobial bacterascites: is by definition polymicrobial

Risk Factors of infection

1- Low ascitic fluid total protein concentrations

2- Paracentesis Needle-induced ascitic fluid infections does not occur unless the

bowel is penetrated by the paracentesis needle.

3- Gastrointestinal hemorrhage.

4- Urinary tract infections are also an under-recognized risk factor for SBP.

Diagnosis

Patient with ascites who develop;

Clinical deterioration

Fever ,abdominal pain, elevated PMN count .

Treatment

Indications for Empirical Antibiotic. Therapy of Suspected Spontaneous Ascitic.

Fluid Infection

Ascitic fluid neutrophil count ≥ 250/mm3 (0.25 × 109/L)

Convincing symptoms or signs of infection

Intravenous Albumin Plus Antibiotic

Intravenous albumin (1.5 g/kg body weight at the time the infection is detected

and 1.0 g/kg on day 3) in combination with cefotaxime reduce the risk of renal failure and

improve survival.





Treatment of Subtypes of Ascitic Fluid Infection

Diagnosis Treatment

Spontaneous bacterial

peritonitis

Five days of intravenous antibiotic to which the organism is

highly susceptible (e.g., cefotaxime 2 g every 8 hours

empirically followed by more narrow spectrum therapy after

susceptibility results are available)

Polymicrobial

bacterascites

Intravenous third-generation cephalosporin (e.g., cefotaxime

2 g q 8h) plus an antianaerobic drug such as metronidazole.

Duration is determined by clinical response and serial ascitic

fluid PMN counts and cultures

Narrowing the Spectrum of Coverage

After the results of susceptibility testing are available.

Duration of Treatment

10 - 14 days of antibiotic therapy for life-threatening infections.

Follow-Up Paracentesis in Spontaneous Bacterial Peritonitis

Not needed except after 48 hours if the course is a typical.

Prognosis

In the past, 48% - 95% of patients with a spontaneous ascitic fluid infection died.

Now less than 5% of patients die.

Paracentesis should be performed at the time of hospital admission so that

infection can be detected and treated promptly.

Paracentesis should be repeated during the hospitalization if any clinical

deterioration occurs.

Prevention

Norfloxacin 400 mg/day twice daily for 7 days. During hospital stay with

discontinuation of the drug at the time the patient is discharged from the hospital.





2-Tense Ascites

Tense ascites requires urgent therapeutic paracentesis. "Total paracentesis,"

even more than 20 L, has recently been safe.

3-Pleural Effusions

Unilateral and right-sided but occasionally may be bilateral .

A unilateral left-sided effusion suggests tuberculosis.

A large effusion in a patient with cirrhotic ascites is referred to as hepatic

hydrothorax.

It is due to small defects small defect in the right hemidiaphragm.

Symptoms

Shortness of breath.

Infection may complicate in case of SBP.

Treatment

1- Sodium restriction + Diuretics

2- TIPS.

4-Abdominal Wall Hernias

Umbilical, incisional or inguinal.

Complications; Incarceration or perforation.

Elective surgical treatment should be considered in all patients with hernias and

ascites.

Therapy of Low Albumin-Gradient Ascites

1- Nonovarian peritoneal carcinomatosis is treated by outpatient therapeutic

paracentesis.

2- Ovarian malignancy have a good response to surgical debulking and chemotherapy.

3- Tuberculous peritonitis (without cirrhosis) is cured by antituberculous therapy.

Diuretics do not speed weight loss unless the patient has underlying portal

hypertension from cirrhosis.

4- A postoperative lymphatic leak from a distal splenorenal shunt or radical

lymphadenectomy also may resolve spontaneously but on occasion may require

surgical intervention or peritoneovenous shunting.





5- Chlamydia peritonitis is cured by tetracycline.

6- Ascites caused by lupus serositis may respond to glucocorticoids.

7- Dialysis-related ascites may respond to aggressive dialysis.

Therapy of High Albumin-Gradient Ascites

Treat the underlying liver disease eg stop drinking alcohol.

Patients with other forms of treatable liver disease (e.g., autoimmune hepatitis,

hemochromatosis, or Wilson disease) should receive specific therapy for these

diseases.

Hospitalization

For Patients with large-volume ascites and those who are resistant to outpatient

treatment usually require hospitalization for definitive diagnosis and management of the

fluid overload.

Diet Education

Sodium restriction for inpatients and outpatients is 2 grams (88 mmol) per day.

Fluid Restriction

Not required

No Bed Rest

Urine Sodium/Potassium Ratio

A random urine sodium/ potassium concentration ratio greater than 1 predicts

that the patient should lose weight if the sodium-restricted diet is followed.

Diuretics

Spironolactone 100 mg + furosemide 40mg.

If the combination of spironolactone is ineffective in increasing urinary sodium or

decreasing body weight, the doses of both drugs should be increased

simultaneously as needed (e.g., spironolactone 200 mg plus furosemide 80 mg, then

300 mg plus 120 mg, and finally 400 mg plus 160 mg).

Intravenous diuretics cause acute decreases in the glomerular

filtration rate in cirrhotic patients with ascites and should be avoided.

Once the edema has resolved, a reasonable maximum weight loss is probably 0.5

kg/day.





Stop diuretics and reasse the situation if:

Encephalopathy develops.

Serum sodium concentration less than 120 mmol/L.

Serum creatinine level greater than 2.0 mg/dL.(180 μmol/L).

Reducing the quantity of fluid in the abdomen

A- Improve the patient's comfort and prevent hepatic hydrothorax and hernias.

B- Concentrating the ascitic fluid, diuresis increases the opsonic activity of fluid 10-

fold, and theoretically, may be of value in preventing spontaneous ascitic fluid

infection.

Refractory Ascites

Definition

Ascites unresponsive to a sodium-restriction diet and high-dose diuretic

treatment.

Refractoriness is manifested by

No weight loss or the development of complications of diuretics.

Treatment; liver transplantation, serial therapeutic paracenteses, TIPS, and

peritoneovenous shunts.

Abandoned procedures:

Portacaval shunts: (for encephalopathy).

Paris pump: ultrafilterates ascitic fluid and reinfuse it intravenously. Unfortunately

leads disseminated intravascular coagulation.





Liver Transplantation

Orthotopic liver transplantation should be considered among the treatment

options of patients with cirrhosis and ascites

Serial Paracenteses

Therapeutic paracentesis now appears to be first-line therapy for patients

with tense ascites and second-line therapy for cirrhotic patients who

are refractory to diuretics.

Colloid Replacement

Recent consensus statements and systematic reviews have pointed out some of

the hazards of albumin infusion.

1- Avoid serial large-volume paracenteses in patients with diuretic-sensitive

ascites.

2- Withhold albumin after taps of 5 L or less.

3- Consider albumin infusion optional after taps of larger volume in patients

with diuretic-resistant ascites.

Transjugular Intrahepatic Portosystemic Stent Shunt (TIPS)

For diuretic-resistant ascites.

Peritoneovenous Shunt

Patients who are not candidates for liver transplantation and who have a

scarred abdomen that is not amenable to repeated paracenteses or who

have failed an attempt at TIPS make up this small subset of patients.





CIRRHOSIS

DR. NAGLAA M. MASHAAL

PROFESSOR OF HEPATOLOGY HEPATOBILIARY UNIT

LEARNING OBJECTIVES:

Define Cirrhosis List Causes of Cirrhosis Outline Different Classifications Recognize the Clinical Picture Assess the Severity of Liver Disease Recognize the Complications Outline the Evolution and Prognosis Mention Different Lines of Managements

What is Cirrhosis? Cirrhosis represents the final common histologic pathway for a wide variety of chronic liver diseases. The term cirrhosis was first introduced by Laennec in 1826. It is derived from the Greek term scirrhus and is used to describe the orange or tawny surface of the liver seen at autopsy.

DEFINITION: Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.

Cirrhogenic stimulus (Injury) Necrosis (degeneration) & Parenchyma regeneration

+ Fibrogenesis Stellate cells, located in the perisinusoidal space, are essential for the production of extracellular matrix; they are activated into collagen-forming cells by a variety of paracrine factors.This lead into an alteration in the normally balanced processes of extracellular matrix production and degradation. Future drug strategies to prevent fibrosis may focus on reducing hepatic inflammation, inhibiting stellate cell activation, inhibiting the fibrogenic activities of stellate cells, and stimulating matrix degradation.





CAUSES: Schistosomal Hepatic Fibrosis & Viral Hepatitis

Alcoholic Biliary obstruction: (Primary & secondary) Outflow obstruction: Heart failure , Bud- Chiari syndrome Syphilis Autoimmune Drugs Metabolic: Haemochromatosis, Wilson's disease, Alfa 1 antirypsin deficiancy

CLASSIFICATION: Morphologic

Micronodular Macronodular Mixed

Histopathologic Portal Biliary obstruction Post-necrotic and post-hepatitis Congestive Bilharzial Hepatic Fibrosis

Functional Compensated: -No hepatic dysfunction

-No portal hypertension Decompensated:(active)

-Hepatic dysfunction -Portal hypertension

CLINICAL PICTURE:

- MANIFESTATIONS OF THE UNDERLYING ETIOLOGY Examples:

Primary Biliary Cirrhosis Congestive Heart failure Systemic Lupus Erythematosis Hemochromatosis

- ABNORMAL HEPATIC FEATURES Change in liver size: normal, enlarged or shrunken. Change in consistency: firm Abnormal edge: sharp or irregular

- MANIFESTATIONS OF CHRONIC LIVER DISEASE General Manifestations: Fatigue Anorexia, weight loss & muscle wasting Anemia Osteoporosis





Cutaneous manifestations: Spider angiomata, skin telangiectasias ―paper money skin‖, palmar erythema, white nails, and finger clubbing.

Impaired metabolic functions: -Dysproteinaemia (Edema and ascites) -Diminished clotting factors -Skin pigmentation

Impaired secretary functions: - Jaundice - Itching & gallstones

Impaired detoxification functions: -Hyperestrogenemia Gynecomastia & impotence ( in males) Loss of axillary and pubic hair is noted ( in both men and women) Spider angiomata Palmar erythema -Hepatic encephalopathy

- MANIFESTATIONS OF PORTAL HYPERTENSION Congestive gastropathy Porta-systemic collaterals Ascites Splenomegaly

- Other Manifestations: Hyperkinetic circulation Low grade fever Hypersplenism Insulin resistance and type 2 diabetes





ASSESSMENT OF THE SEVERITY OF LIVER DISEASE:

3points

2points

1 point

Clinical variable

Stage 3-4 Stage 1-2 None Encephalopathy

Moderate Slight Absent Ascites

>3 2-3 <2 Bilirubin (mg/dL)

<2. 8 2.8-3.5 >3.5 Albumin (g/dL)

>6 s or INR >2.3

4-6 s or INR 1.7-2.3

<4 s or INR <1.7

Prothrombin time (seconds prolonged or INR)

Child-Pugh Classification

Child Class A = 5-6 points Child Class B = 7-9 points Child Class C = 10-15 points

COMPLICATIONS: Esophageal varices

Spontaneous bacterial peritonitis (SBP) Portosystemic encephalopathy Hepatorenal syndrome Hepatocellular carcinoma

EVOLUTION: Progressive Regressive Stationary

Depending on: Clinical assessment Biochemical assessment Histological assessment





PROGNOSIS: Child's Classification

A Good B Moderate C Poor

DIAGNOSIS: Diagnosis should include:

Etiology Pathology & Pathophysiology Severity of liver disease Complications

Diagnosis depends on: Medical History Clinical Picture Investigations Imaging Techniques Liver Biopsy

MANAGEMENT: Depends on the Type and Stage of the Cirrhosis

Removal and/ or treatment of the cause Support liver functions Reduce portal hypertension Treat complications e.g. ascites, haematemesis Treatment of contributing factors e.g. anaemia Consider transplantation in end stage cirrhosis





HEPATIC TUMOURS

Prof. Dr/ EL-SAID IBRAHIM

Hepatobiliary Unit

I. Benign

(A) Epithelial: 1- Liver cell adenoma 2- Bile duct adenoma 3- Focal nodular hyperplesia 4- Nodular regenerative hyperplesia

(B) Mesenchymal: 1- Haemangiomas 2- Mesenchymal hamartoma

II. Malignant 1-Primary

A- Epithelial: I Hepatocellular carcinoma II Hepatoblastoma III Cholangiocarcinoma

B- Mesenchymal I Angiosarcoma II Infantile hemangioendothelioma III Other Sarcomas

2- Metastatic: The liver is the second most common site of metastasis next to lymph nodes

FOCAL NODULAR HYPERPLASIA FNH is defined as a nodule composed of benign appearing hepatocytes in a liver which is other wise normal It varies in size between 1-15 cm

Diagnosis: US, CT, MRI

Treatment: Conservative without surgery

HEPATIC ADENOMA There is an association with oral contraceptive use particularly over many years and in older women May present with right upper quadrant pain or mass, hemorrhage within the tumor, hemoperitoneium or hypovolemic shock may occur


Treatment: Surgical resection may be indicated in young women, especially when

pregnancies are desired





HEMANGIOMAS This is the commonest benign tumor of the liver being found in 5% of autopsies. Usually single or small but may be multiple or very large. The majority are asymptomatic and discovered accidentally.


Treatment: Surgery is usually unnecessary

NODYLAR REGENERATION HYPERPLASIA Monoacinar nodules of cells resembling normal hepatocytes involve liver diffusely. They are related to the obliteration of small portal veins at the level of the acinus. The commonest association is with Rheumatoid arthritis and Felty`s syndrome, myeloproliferative disorders, hyper viscosity syndrome or drug reactions cytotoxic drugs and anabolic steroids.

Diagnosis: US< CT.

Portal hypertension is marked and sometimes there is hemorrhage into the nodule.

Hepatocellular carcinoma HCC ranks as the 5th most common cancer in the world with an estimated 437000 new cases annually in 1990 7.4% of all cancers in ♂ 3.2% in all cancers in ♀

Aetiological factors: Relation to cirrhosis Cirrhosis may be premalignant irrespective of etiology. Fine nodular hyperplesia progresses to carcinoma. Liver cell dysplesia may be an intermediate step.

Relation to HBV Chronic hepatitis, progressing to cirrhosis, remain the most important precancerous factor. HBV induces cancer through integration, transactivation, mutations in tumor-suppressor genes and increases in TGF-α

Relation to HCV There is a four times higher incidence of liver cancer among anti HCV positive patients than among HBsAg carriers.

Relation to alcohol In USA, there is a four fold risk of primary HCC in alcoholics particularly in older patients. cirrhosis is always present.

Mycotoxins Aflatoxin is produced by a contaminating mould aspergillus flavus. It is highly carcinogenic to rats, guinea big. Aflatoxin can contaminate food such as ground nuts as grains specially when stored in tropical condition.





Miscellaneous factors A- Autoimmune hepatitis and cirrhosis (rare) B- Wilson`s disease (rare) C- Primary biliary cirrhosis (rare) D- Hemochromatosis E- α1- antitrypsin deficiency F- Tyrosinosis G- Type 1 glycogen storage disease

Age and sex Three times more common in male than females. Increased incidence with advanced age.

Clinical features: It is variable -Associated cirrhosis -Pain -GI symptoms -Jaundice -Ascites -Portal vein thrombosis

Systemic effects: Painful gynecomastia Hypercalcemia Hypoglycemia Hyperlipedemia Hyperthyroidism Pseudoporphyria

Serological markers AFP Serum ferritin Des gamma carboxy-prothrombin: The protein induced by vitamin K absence or antagonist II (PIVKA-II).Superior to AFP

Tumour localization: US Doplex and color Doppler sonography CT Triphasic (spiral)CT MRI Hepatic angiography Lipiodol angiography Needle liver biopsy: US or CT guided.





Screening for HCC among high risk patients: AFP- US every 4-6 months

Prognosis and risk factors: Tumor size >50% Serum bilirubin >3 mg/dl Serum albumin <3 G/dl Ascites

Treatment: Surgical 1- Resection 2- Transplantation

Non Surgical 1- Systemic chemotherapy: Mitozantrone IV/21 day , tamoxifen 2- Transcatheter arterial chemoembolization 3- Percutaneous ethanol injection 4- Radiofrequency ablation 5- Target gene transfer(Gene therapy) 6- Combined modalities.

Fibrolamellar carcinoma: Young patients (5-35 years) of both sexes. It presents with abdominal mass. The liver is not cirrhotic. Serum AFP is normal.

Prognosis is better (survival 32-622 months)

Treatment is surgical resection

Hepatoblastoma: Rare tumor affects children less than 4 years of age. Progressive enlargement of the abdomen with anorexia, failure to thrive, fever. Surgery is indicated with preoperative Cisplatin and Adriamycin to reduce tumor size





ACUTE LIVER FAILUREِِ

Prof. Mohamed Elhasafi.

Hepatobiliary Unit. Alexandria Faculty of Medicine.

“Acute liver failure is a complex medical emergency that evolves after a catastrophic insult to the liver. The liver damage is sufficiently severe to cause encephalopathy, and this develops within a matter of days or weeks of the insult to the liver. “

Definitions: Fulminant hepatic failure:

―The development of encephalopathy within 8 weeks of the onset of symptoms in patients who had no previous history of liver disease. ―

Hyper- acute liver failure:

―The development of encephalopathy within 7 days of the onset of jaundice. ―

Acute liver failure:

―The development of encephalopathy within 8 – 28 days after the onset of jaundice. ―

Sub-acute liver failure:

―The interval between the onset of jaundice and the development of encephalopathy ranges from 8 to 12 weeks. ―

Etiology: Viral hepatitis:

Hepatitis A virus

Hepatitis B virus

Hepatitis C virus

Hepatitis D virus

Hepatitis E virus Hepatitis due to other viruses:

Herpes viruses

Epstein-Barr virus

Cytomegalovirus

Drug-induced liver injury: Acetaminophen

Halothane, Sulfonamides, phenytoins, Statins.

Isoniazid/ Rifampicine

NSAIDs, Ketoconazole, methyldopa.





Toxins:

Amanita phalloides (mushrooms)

Organic solvents

Phosphorus

Herbals. Metabolic: Acute fatty liver of pregnancy.

Reye‘ syndrome

Vascular: Acute circulatory failure (cardiogenic shock).

Budd-Chiari syndrome

Veno-occlusive disease

Miscellaneous: Wilson‘ disease

Autoimmune hepatitis

Massive infiltration with tumor

Liver transplantation with graft failure

Clinical presentations: Acute liver failure causes a syndrome of multi-system failure potentially involving all

the major body systems .

Jaundice is present in most patients, but some cases of hyper-acute liver failure develop encephalopathy before jaundice becomes clinically apparent.

Most of the other signs of liver cell failure are notable by their absence.

Fetor and flapping tremors are not prominent features associated with the

encephalopathy of acute liver failure, but are more likely to be seen with sub-acute liver failure.

Ascites is also unusual . Encephalopathy is the most important sign and present in all cases.

Intracranial hypertension:

This complicates grade 4 encephalopathy and develops in up to 70% of patients who have hyper-acute liver failure and in less than 15% of patients who have sub-acute liver failure.

The clinical features of cerebral edema include systemic hypertension, decerebrate posturing, hyperventilation, abnormal pupillary reflexes, and impairment of brain-stem function.

Renal failure:

Renal failure occurs in 75% of patients who develop grade 4 encephalopathy following acetaminophen overdose and in 30% of other etiologies of acute liver failure.





Metabolic disorders: Hypoglycemia is common and can lead to impairment of consciousness before

the onset of encephalopathy. The classic symptoms of hypoglycemia are often masked and regular monitoring of blood glucose is required.

Metabolic acidosis is present in 30% of patients and is associated with high

mortality.

Hyponatremia reflect sodium depletion in patients who are vomiting or it may be dilutional due to excessive anti-diuretic hormone secretion or intracellular sodium shifts.

Hemodynamics:

The early hemodynamic profile reflects a hyperdynamic circulation with increased cardiac output and reduced systemic vascular resistance. Profound vasodilatation may cause relative hypovolemia .

Progressive disease leads to circulatory failure as a result of falling cardiac output or an inability to maintain an adequate mean arterial pressure.

Pulmonary complications :

Hyperventilation may be due to intracranial hypertension or may be due to

coexisting metabolic acidosis.

Intracranial hypertension may also suppress respiratory function by compromising the brainstem, but most patients are mechanically ventilated before this occurs.

Aspiration of gastric contents may an early risk to pulmonary status in patients who have encephalopathy who also vomiting.

Coagulopathy: The liver is responsible for the synthesis of most of the coagulation factors (except

factor VIII, which is produced by endothelial cells) and some of the inhibitors of coagulation and fibrinolysis.

In acute liver failure circulating levels of fibrinogen, and factors V, VII, IX and X are reduced, and the prothrombin time is widely used as an indicator of the severity of liver damage.

Hemorrhage is present in 75% of patients who had acute liver failure.

Gastrointestinal hemorrhage is common and was attributed to gastric erosions.

Infection :

Bacterial and fungal infections are common in acute in acute liver failure and are important factor for mortality.

Infection may be difficult to detect as there is a poor correlation between the presence of infection and body temperature or with white cell counts.





DIAGNOSIS The diagnosis of acute liver failure is a clinical one based on the detection of

encephalopathy in patients who have acute liver disease.

The etiology of acute liver failure must be accurately identified by the appropriate investigations.

Hepatitis A

Hepatitis B

Hepatitis C

Acetaminophen

Halothane

Autoimmune

Ischemic hepatitis

IgM anti-HAV

IgM anti-HBc

HCV- RNA

Drug level in blood

Antibody test

Autoantibodies

Very high transaminases.

Histologic assessment of liver tissue aid in the diagnosis of the cause of acute

liver failure, but this is often only available after death or transplantation. Confluent necrosis is the commonest histologic finding and this may be zonal or involve all of the parenchyma.

Laboratory investigations : Anemia due to hemorrhage, hemolysis. Thrombocytopenia. Leucocytosis due to sepsis. Transaminases are very variable and of no prognostic value. Serum albumin is normal early, but falls with disease progression. Prothrombin time is of strong prognostic value.

Serum sodium often low and may reflect sodium deficiency or dilution. Hyponatremia is a bad prognostic sign .

Blood glucose : Hypoglycemia is frequent.

Acid-base status: Alkalosis common but acidosis is associated with a poor prognosis.

Serum creatinine is the best indicator of renal dysfunction.





Management General measures : 1) Temperature, pulse, and blood pressure should be recorded at least hourly

and preferably continuously.

2) A naso-gastric tube is passed.

3) An H2 antagonist or proton pump inhibitor is given to reduce the risk of gastro-duodenal erosions and bleeding.

4) Enteral nutrition should be given containing appropriate calories.

5) Hypoglycemia is corrected by giving 100 ml of 50% glucose, then continuous

infusion of glucose 5% or 10 %.

6) Respiratory status is monitored using pulse oximetry. Oxygen by mask is given. Mechanical ventilation is necessary if respiratory failure is shown due to adult

respiratory distress syndrome requiring artificial ventilatory support

7) Intravenous antibiotic is given if there is systemic infection, and anti-fugal treatment is given with fungal infection.

8) Hypotension is corrected by crystalloid or albumin infusions. If not corrected, a vaso-constrictor agent such as norepinephrine may be given.

Renal failure is treated by continuous arteriovenous hemofilteration.

Coagulopathy is managed by routine intravenous vitamin K. Fresh frozen plasma and platelets are given if there is bleeding.

Hepatic encephalopathy is treated by the usual routine with no protein by mouth,

lactulose enema and by the naso-gastric tube, flumazenil (a benzodiazepine- receptor antagonist).

Cerebral edema is treated with mannitol 20% intravenously. N- acetylcystein is given intravenously in cases of acute liver failure complicating

acetaminaphen toxicty.

Artificial and bio-artificial liver support : The aim is to provide support until the native liver recovers its function

spontaneously, or until a donor liver is available. The artificial liver support system MARS ( Molecular Absorbent Recirculating

System ) uses albumin , charcoal, and resin adsorbents to remove water soluble toxins including ammonia.

The bio-artificial liver support use bio- reactor containing viable hepatocytes in culture.





Liver transplantation: Hepatic transplantation gas to be considered for patients reaching grade 3 and 4

coma due to fulminant hepatic failure.

A) Auxiliary liver transplantation : The native liver is left in place, and the donor

liver graft either placed in the right upper quadrant alongside the native liver ( heterotopic ) or part of the native liver is resected and replaced with a reduced size graft ( orthotopic )

B ) Living related liver transplantation : Either the left or the right lobe of the

living donor is transplanted to the patient. C ) Hepatocyte transplantation : Small number of cells; 0.5 to 3 % of the normal

hepatocyte mass is injected into the portal vein of the patient ( still experimental ).

Questions 1) Definition, causes, clinical presentation and management of acute liver failure.

2) What are the most important two clinical signs in the diagnosis of acute liver failure.

3) what is the most important laboratory test for the prognosis in following patients with acute liver failure.

4) Treatment of acute liver failure.

5) What are the definitions, value and uses of the artificial and bio-artificial liver support systems.

6) What are the types of liver transplantation used in the management of acute liver failure.





Gallbladder Disease

Prof Yousri Taher

Head of HPB Unit

Alexandria University

Congenital GB disease

Gallstones and inflammatory GB disease Three types of G stones: cholesterol, black pigment and brown Stones. Pigment stones Contain besides Cholesterol; Bile pigment, calcium carbonate phosphate palmitate phospholipids glycoprotein,

mucopolysaccharides Cholesterol stone: 15 % are radiopaque Black 60%; brown o %.

Factors For GB Stone Formation Impaired GB function Supersaturated bile Cholesterol nucleating factors Absorption /enter hepatic circulation of bile acids

Prevalence Of G Stones In western countries 10 %(In Egypt 20%) Prevalence in women is twice that in men Among cirrhotics 30% Prevalence is higher among diabetics after gastrectomy , ileal resection with

hyoplipaedemic drugs ,long term octreotide , and c pills

Natural History of Gall Stones

Acute and Chronic Cholecystitis In 96% cystic duct is obstructed Clinical features : sufferers are often obese , Fertile female over 40 yr Pain occur late at night ,in right hypochondrium epigatric referred to right shoulder Digestive symptoms :flatulence ,nausea vomiting Fever on occurrence of bacterial infection





ACalculus Cholecystitis 5-10 % of acute cholecystitis in adults 30% in children Factors associated with critical conditions ,after major surgery ,multiple injuries, major

burns ,severe sepsis mechanical ventilation Bacterial infection with typhoid bacilli Actinomycosis Parasitic cholecystitis

Clinical Findings: Shallow respiration , fever

Jaundice , Murphy‘s sign is positive

Tender mass at GB region

WBC is high

Clinical Presentation: Diagnostic tools Clinical

US

Cholecystography

CT Scan

MRCP

ERCP

PTC

Ultrasound Examination Accurate In More Than 95% Biliary Mud MRCP Perforated GB CBD Stricture CT scan After ERCP Gall Stones Large GB Stone with Choledochal cyst (ERCP) Shotty GB Stones With Impacted Stones At The papilla OF Vater ERCP GB stones CBD Stricture GB Perforation

Differential Diagnosis Appendicitis ‗ perforated peptic ulcer

Intestinal obstruction, pleurisy myocardial infarction

First aid Treatment antibiotics , analgesia antispasmodic

Surgery





Post Cholecystectomy Problems Wrong diagnosis

Papillary dysfunction ,stenosis

Psychosomatic disorders

IBS, Biliary stricture

Biliary stones, amputation neuroma Pancreatitis CBD Injury After Cholecystectomy with Bile Leakage Endoscopic Sphincterotomy With Stone Extraction Extraction of Fasciola Fluke from CBD after EST

Questions Enumerate congenital GB anomalies Mention clinical manifestations of GB disease Enumerate types gall stones Mention diagnostic tools for GB stones Enumerated complications of GB disease Enumerate GB and biliary parasites Enumerate postcholecystectomy problems Mention Role of endoscopy in the management of GB stones Discuss differential diagnosis of GB disease





Acute Pancreatitis

Prof. Yousri Taher Head of HPB Unit

Alexandria University

Acute Pancreatitis Is discrete episodes of inflammation resulting from intrapancreatic activation of digestive enzymes. It is a disease of wide spectrum of severity complications and outcome.

Spectrum of the disease Acute edematous or interstitial Pancreatitis : mild , self limited in most patients Inflammation results in edema of the pancreas Parenchymal damage is minimal Pancreas recovers its function after resolution.

Hemorrhagic Pancreatitis (Necrotizing Pancreatitis). May be extensive with progressive coagulative necrosis of the pancreas and surrounding tissues Auto digestion of the organ leads to hemorrhage .The mass of inflamed pancreas and surrounding tissues is termed phlegmon.

Complications Wide spread of inflammatory process Any of the following organs might be affected : CBD ,duodenum, T colon splenic artery , and vein, spleen, Para renal spaces , lesser sac posterior mediastinum, abdominal wall and diaphragm . Peritoneal surfaces leading to pancreatic ascites. Leakage of protein rich fluid from systemic circulation into peritoneal and retroperitoneal spaces lead to hypovolemia and shock. Systemic effects of these material include: cardiovascular instability respiratory failure and renal failure. Hemorrhage : Cullen‘s sign ,Turner‘s sign, and DIC. Pseudo cyst Pancreatic abscess Fat necrosis polyserositis and adult respiratory distress syndrome. Pulmonary alveolar capillary membrane may be disrupted forming hyaline lining of alveoli.





Etiology Alcoholism Biliary tract disease Surgery Trauma ERCP Infections (viral, mycoplasma, Salmonella mycobacterium cryptosporidium. *Metabolic disorders (Hypertriglyceridemia,pregancy,hypercacemia, hyperparathyroidism) *Drugs , vasculitis Anatomic abnormality annular pancreas ,choledochal cyst ,penetrating peptic ulcer ,parasites ,renal failure ,renal transplantation .

Drug induced Acute Pancreatitis Sulfonamides ,estrogen , teracycline, pills, azathioprine , furosemide, ethanol, methanol ,ACE inhibitor ,NSAID, isoniasid,rifampin,metronidazole, eryhthromycin .

Clinical Criteria for Severe Pancreatitis Cardiac : BP < 90,tachycardia,ECG changes Pulmonary : dyspnea , ARDS PO2< 60mmHg Renal output less than 50 ml/h Metabolic calcium < 8mg/dl, albumin < 3.2 mg /dl Hematological: falling hematocrite and DIC Abdominal distension, fluid wave ,and ileus

Physical examination Fever tachycardia ,hypotension Shock Jaundice Abdominal tenderness and rigidity Ileus Cullen's sign Pleural effusion ,pneumonitis subcutaneous fat necrosis ,tetany.

Laboratory Tests Elevated Serum amylase noted within 24 h persist for 3-5 days Elevated Serum lipase Urine amylase remains elevated for 7-10 days from onset. Leucocytosis Hyperglycemia Jaundice Arterial hypoxemia





Radiology Plain film ileus, air under diaphragm sentinel loop USG CT scan ERCP

Differential DIAGNOSIS ACUTE CHOLECYSTITIS BILIARY COLIC CHOLANGITIS PERFORATED VISCUS ACUTE HEPATITIS ,ACUTE INTESTINAL OBSTRUCTION MESNTERIC VENOUS OCCLUSION

Treatment 85=90 % self limited Supportive care Analgesia Maintain intravascular volume Monitor vital signs Treat complications

Drug Treatment and Nutritional Support PPI , somatostatin or octreotide (sandostatin ) Prophylactic antibiotics Intralipid Enteral feeding is much better Initial high carbohydrate diet low protein and fat.

For severe case ICU is highly indicated Necresectomy Pancreatectomy Decompress Biliary tract CT guided percutaneous drainage of necrotic pancreas , Endoscopic drainage

For Acute Biliary Pancreatitis Urgent Endoscopic Sphincterotomy is a must as soon as possible within 72 hours of

onset of symptoms





Chronic Pancreatitis Result from progressive destruction of the pancreas by inflammation and fibrosis Exocrine pancreatic tissue and function are lost earlier followed by Endocrine parenchyma And function

Classification Obstructive : Tumors, scar of Parenchymal inflammation , congenital anomalies Infiltrative and autoimmune diseases such as hemochromatosis, Sjogren syndrome. Chronic calcifying Pancreatitis Alcohol, cigarette smoking Hyperparathyroidism Hypocalcaemia Hereditary autosomal dominant CCP Cystic fibrosis

Clinical Presentation Abdominal pain Malabsorption Vitamin B12 deficiency DM Obstructive jaundice

Physical Examination Epigatric tenderness Mass, pseudocyst Weight loss bleeding tendency Jaundice

Diagnosis Serum amylase ,lipase Increased stool fat> 30 -40 g /day USG and CT scan ERCP EUS

Treatment Stop alcohol or tobacco Feedback control Percutaneous injection of alcohol Surgery Drainage procedures Acid suppressant therapy Nutritional support





Pancreatic cancer Exocrine pancreatic cancer account for 95% of pancreatic cancer 75 -85% arise from pancreatic duct epithelium Islet cell tumor represent 5 % Manifest themselves by hormone they secrete Tumors may secrete gastrin, insulin ,glucagon ,VIP, pancreatic peptide somatostatin

Warnings Signs of Pancreatic Cancer Unexplained Recent upper abdominal pain Recent upper abdominal pain with retroperitoneal lesion Jaundice with weight loss Weight loss greater than 5 % Unexplained acute Pancreatitis Unexplained onset of DM

Diagnostic Tools of Pancreatic Cancer CA19.9 CEA USG focal pancreatic lesion CT scan ERCP Angiography Fine needle Aspiration EUS Laparoscopy MRI

Treatment Options Surgery is the best if early ; 5% are respectable Chemo radiation Palliative drainage Endoscopic Percutaneous Surgical





Questions Enumerate causes of acute Pancreatitis Mention important diagnostic clinical symptoms and signs of acute Pancreatitis Discuss causes of biliary Pancreatitis Discuss complications of acute Pancreatitis Role of endoscopy in emergency management and prophylaxis of acute Pancreatitis Discuss differential diagnosis of acute Pancreatitis Mention role of imaging techniques in acute Pancreatitis Discuss role of surgery in acute Pancreatitis

Questions : Chronic Pancreatitis Describe clinical picture of chronic Pancreatitis Describe complications of Pancreatitis Discuss management of pancreatic pseudo cyst Discuss management of chronic Pancreatitis presented with obstructive

jaundice Mention diagnostics criteria of pancreatic cancer Mention endoscopic management of chronic Pancreatitis and pancreatic

cancer Discuss role of surgery in chronic Pancreatitis Mention differential diagnosis of chronic Pancreatitis

Internal medicine hepatology 2008

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Transcript of Internal medicine hepatology 2008