Os214 Complications Of Cirrhosis

OS 2 14

COMPLICATIONS OF CIRRHOSIS

DIGESTIVE BLOCK B Trans? | Exam 1

Dr. Melflor Atienza OUTLINE: I. COMPLICATIONS OF CIRRHOSIS a. Portal hypertension b. Ascites c. Spontaneous bacterial peritonitis d. Hepatic encephalopathy e. Hepatocellular carcinoma f. Hepatorenal syndrome II. GENERAL PRINCIPLES OF

I

Complications of Cirrhosis Degeneration Fibrosis

Parenchymal dissection into nodules Rearrangement of blood circulation CIRRHOSIS Diffuse process characterized by fibrosis and conversion of normal liver architecture into structurally abnormal nodules which lacks normal lobular organization

∗

In normal liver histology, one can appreciate the elements of the Portal Triad (bile duct, central vein, and artery); however, in cirrhosis, these can’t be found except in small islands of sinusoids The liver is able to regenerate, but only up to a certain limit Major Etiologic Agents of Cirrhosis in the Philippines

• • •

Hepatitis B Hepatitis C Alcohol

Recognizing Patients with Cirrhosis 1. Clinically silent in many cases 2. Non-specific symptoms Weakness, fatigue, weight loss 3. Manifestations of hepatocellular dysfunction Jaundice Liver size: normal, enlarged, small Palmar erythema, spider angioma, clubbing, parotid/lacrimal gland enlargement Assessing Risk of Patients with Liver Disease

Formation of fibrovascular membranes

∗

separated by wider scars and irregularly distributed throughout the liver usually due to an infectious agent 3. Mixed type

(posthepatitic) (posthepatitic) (Laennec’s)

Child-Turcotte-Pugh Criteria ∗ Variables: Bilirubin Albumin Protime Ascites Encephalopathy ∗ Scoring system for each variable ∗ Grading based on total score ∗ Prognosis depends on grade A: best prognosis (10%) B: 30% C: worst prognosis 82%

Child-Pugh Criteria VARIABLE

1POINT

2POINTS

3POINTS

Bilirubin(mg/dl)

<2.0

2.0– 3.0

>3.0

Albumin (g/dl)

>3.5

2.8– 3.5

<2.8

Protime(sec. prolonged)

1– 3

4– 6

Ascites

none

slight

Encephalopathy (Stage)

none

1– 2

Functions of Liver Chemistries ∗ ∗ ∗ ∗

Assess hepatic damage (ALT/AST) Detect cholestasis (ALP/GGT) Assess liver function (Albumin/Protime) Albumin has a long half-life ~ 3wks; sign of chronic liver disease Measure liver excretion Bilirubin

>6 moderate 3– 4

Grades: A= 5-6 points; B= 7-9 points; C= 10-15 points

Major Complications of Cirrhosis 1. Portal hypertension 2. Ascites 3. Spontaneous bacterial peritonitis 4. Hepatic encephalopathy 5. Hepatorenal syndrome 6. Hepatocellular carcinoma

Morphologic Classification of Cirrhosis not discussed but in o9 trans

1. Micronodular uniform nodule < 3mm in size; separated by thin fibrous septa usually due to chemical agent like alcohol 2. Macronodular larger nodules

November 13, 2006, Monday

A

Portal Hypertension

Portal: Doorway Heart  Artery  Organ  Vein  Heart Gut  Portal Vein  Liver  Heart Functions of the Liver include detoxification and metabolism

The End

Page 1 of 5

OS 2 14

COMPLICATIONS OF CIRRHOSIS

DIGESTIVE BLOCK B Trans? | Exam 1

Dr. Melflor Atienza

b.) Control of bleeding  Medical management ∗ Vasoconstrictors (somatostatin, octreotide or vasopressin) ∗ Balloon tamponade  Endoscopic treatment ∗ Sclerosing agent ∗ Endoscopic band ligation / loop  Endoscopic ligation or sclerotherapy

Causes of Portal Hypertension 1. Pre-sinusoidal Portal vein thrombosis Schistosomiasis 2. Sinusoidal Cirrhosis – most common cause of Portal HPN 3. Post-sinusoidal Budd-Chiari syndrome - occlusion of the hepatic vein, associated with polycythemia vera, pregnancy, postpartum state, oral contraceptives, paroxysmal nocturnal hemoglobinuria, and intra-abdominal cancers, particularly hepatocellular carcinoma

IVC

Aorta

Heart

Hepatic artery

Hepatic POSTSINUSOIDAL veins

Blockatthe level of hepatic vv. or IVC

Budd-Chiari syndrome

SIN US OIDAL SO Liver

Blockatthe level of thesinusoids (Cirrhosis)

Portal vein PRESINUSOIDAL

Blockproximal to hepatic sinusoids schistosomiasis

Blockinthe presinusoidal venous compartment (Portal vein thrombosis)

Figure: Portal Hypertension Causes Treatment of Portal Hypertension

1. Low albumin ascites –decrease oncotic pressure = HIGH (>/= 1.1g/dl) Cirrhosis Alcoholic hepatitis Massive liver metastasis Fulminant hepatic failure Portal vein thrombosis Cardiac disease 2. High albumin ascites – increase hydrostatic pressure = LOW (<1.1g/dl) Peritoneal carcinomatosis TB peritonitis Biliary leak Nephrotic syndrome Serositis

∗ ∗

Surgical Management 1. Reduction of pressure in the portal venous system Surgical decompression procedures (portalsystemic shunt surgery)  Liver would be bypassed by creating a shunt from the portal vein to the hepatic vein, and as a consequence, there would be no detoxification, which may lead to encephalopathy Transjugular intrahepatic portosystemic shunt (TIPS) Beta adrenergic blocker (propranolol or nadolol) to reduce resting PR by 25%

November 13, 2006, Monday

Serum-ascites albumin Gradient (Albumin serum – Albumin ascites)

Treatment of Ascites

Medical Management Beta blockers: decrease PR by 25% (propanolol or nadolol) Spironolactone, furosemide Somatostatin, ocreotide Nitrates

2. Treatment of variceal bleeding a.) Management of blood loss  Replacement of blood loss (blood / I.V. fluids)  Replacement of clotting factors with fresh frozen plasma  Monitoring of central venous pressure, urine output, mental status

Ascites

B

Na+ restriction; Fluid restriction Diuretics: Spironolactone + Furosemide Stepwise increase as needed to maximal dose Large volume paracentesis for tense ascites TIPS Liver transplant

∗ ∗ ∗ C

Spontaneous Bacterial Peritonitis Proposed pathogenesis

Low albumin ascites

Normal gut flora

Dec. serum complement Dec. RE function Decreased protection Transmigration thru bowel wall Transversing lymphatics Bacteremia Spontaneous bacterial peritonitis

different from secondary peritonitis/infections peritonitis without any secondary cause

The End

Page 2 of 5

OS 2 14

COMPLICATIONS OF CIRRHOSIS

DIGESTIVE BLOCK B Trans? | Exam 1

Dr. Melflor Atienza

Signs & Symptoms of SBP 1. Signs of infection Fever, chills Hypotension Confusion* 2. Signs / symptoms referable to involved site: Abdominal pain Abdominal tenderness Jaundice (-) guarding = with severe peritonitis

Proposed pathogenesis

↑ NH3

↑CSF glutamine

 Rebound tenderness – very sensitive sign for severe peritonitis; but in patients with cirrhosis, may be absent  fluids will separate the two surfaces, thus preventing contact

∗ ∗ ∗

∗

Lab findings Increased WBC, segmenter predominance Ascitic fluid neutrophil count >250/L Suspect secondary bacterial peritonitis (2/3) Total protein >10g/L (ascitic fluid) Glucose <2.8 mmol/dL LDH >ULN for serum (+) culture of pathogens Common etiologic agents  E. coli  Klebsiella  Streptococci  Enterobacteriaceae

Treatment of SBP

∗ D ∗ ∗ ∗ ∗

Initiate for ascitic fluid PMN ≥ 250/mm3 Broad Spectrum antibiotic – by IV Cephalosporins (cefoperazone, cefuroxime, cefazolin) Quinolones Co-amoxiclav Avoid Aminoglycosides

Hepatic Encephalopathy Reversible neuropsychiatric abnormalities No uniformly accepted criteria for diagnosis of hepatic encephalopathy Asterixis and abnormal EEG Occurs in patients with hepatic failure

November 13, 2006, Monday

Tryptophan

↑ GABA Benzodiazepine

↑monoamine neurotoxin

↑inhibitory transmission

Neurotransmission Failure

 It is important to distinguish between SPB and Secondary peritonitis - SPB requires 2 weeks of antibiotics treatment - Secondary peritonitis requires surgical intervention and 2wks antibiotics; there’s also the risk of viscus rupture

∗ ∗

↑

HEPATIC ENCEPHALOPATHY Figure: Pathogenesis of Hepatic Encephalopathy Precipitating Factors ∗ ∗ ∗ ∗ ∗ ∗ ∗ ∗

Gastrointestinal bleeding Infections (e.g., spontaneous bacterial peritonitis, UTI, pneumonia) ↑ Protein intake Surgery/TIPS Alcohol Sedatives/tranquilizers Diuretics Constipation Stages of hepatic coma

MENTAL STATE

NEUROLOGIC SIGN

Stage I mild confusion; attention; inverse sleep pattern Stage II Drowsiness, personality changes, intermittent disorientation Stage III Somnolence; marked confusion; slurred speech Stage IV Coma

Incoordination, tremors Impaired hand writing Asterixis; ataxia; dysarthria; (+) EEG changes Hyperreflexia; Babinski sign; muscle rigidity; (+) EEG changes No response to pain Decerebrate posture

Difference bet II & III: more marked neurologic abnormalities in III

∗ ∗

The End

Management of Hepatic Encephalopathy Identify & correct precipitating event Lower NH3 and other toxin levels in the blood Restrict dietary protein Lactulose – osmotic laxative (READ on two more functions) Page 3 of 5

COMPLICATIONS OF CIRRHOSIS Dr. Melflor Atienza Metronidazole / Neomycin Branched chain amino acid supplement, flumazenil (benzodiazepine inhibitor, associated with third theory – increase in GABA, benzodiazepine)

∗

E ∗

∗

∗ ∗ ∗ ∗ ∗ ∗

Hepatocellular Carcinoma One of the most common tumors in the world Hepatitis B Vaccine can prevent 3rd most common CA in Philippines 20% - 56% of patients presenting with HCC have undiagnosed cirrhosis 70% - 90% of HCC is on cirrhotic background + of modifications of cellular gene expression by insertional mutagenesis, chromosomal rearrangements Philippine Cancer Facts and Estimates 3rd leading CA for both sexes Ranks 2nd among males Ranks 9th among females Incidence increases at age 40

∗ ∗

∗

∗ ∗ ∗ ∗ ∗ ∗

∗ F ∗

∗ ∗

osmolality Increased decreased

Identify other causes Establish circulatory volume Restrict Na+ and water Avoid nephrotoxic agents (aminoglycosides) Consider dialysis Evaluate for liver transplantation

General Principles of Management

I I

∗ ∗ ∗

Treatment of Hepatocellular Carcinoma Liver transplantation Surgical resection Hepatic artery embolization, chemoembolization Percutaneous ethanol injection or radiofrequency ablation Chemotherapy

∗

creatinine Increased decreased

Management of Hepatorenal Syndrome

Similar to cirrhosis Common features Abdominal pain RUQ mass Friction rub / bruit over the liver Blood-tinged ascites Jaundice Elevated alkaline phosphatase, PT AFP > 500 ug/L Mass on imaging modalities (US, CT, MRI) Biopsy Severe weight loss

∗ ∗ ∗

DIGESTIVE BLOCK B Trans? | Exam 1

Occurs after hospitalization Death within weeks; Recovery is unusual Clinical features progressive ascites hypotension oliguria jaundice Azotemia Hyponatremia Urine sediments unremarkable Urine Na+ <10meq/L Urine / plasma creatinine ratio > 30 Urine /plasma osmolality ratio > 1

Urine plasma

Clinical Features of Hepatocellular Carcinoma ∗ ∗

OS 2 14

Therapy of underlying liver disease is largely supportive. Treatment is directed toward specific complications. Further liver damage should be prevented

Prevention of further liver damage ∗ Alcohol should be absolutely forbidden! ∗ All medicines must be given with caution: Aspirin should be avoided due to its effects on coagulation and the gastric mucosa Acetaminophen should be used sparingly, If at all and at no more than 2 g/day Diuretics may lead to hypovolemia and coma (liver disease with portal HPN) Even modest sedatives may worsen encephalopathy (Stage I)

Hepatorenal Syndrome Progressive renal failure associated with advanced cirrhosis and ascites (↓ creatinine, ↓ urine output) No other cause of renal failure COURSE

November 13, 2006, Monday

The End

Page 4 of 5

COMPLICATIONS OF CIRRHOSIS Dr. Melflor Atienza

Portal HPN

Leakage of plasma To liver lymphatics

Leakage of plasma out of BV to liver tissue

Vasocongestion in intestinal BV

Inc. lymph production

Leakage of plasma from liver to abdominal cavity

Transudation of plasma into abdominal cavity

Dilatation lymph channels Leakage of lymph into abdominal cavity Osmotic gradient bet. lymph & ECF Leakage of fluid to abdominal cavity

ASCITES Dec. intravascular oncotic pressure Decreased albumin Hepatocyte dysfunction

Diagram of Portal Hypertension

The secret in the care of the patient is in caring for the patient… ****PEEEEEEWWEEEEE!**** this last diagram was not shown in ma’am’s presentation. However, baka gusto ng mga people yung diagram, so, sama nalang siguro natin? Hmm. Hindi ko din alam kung magdagdag pa tayo dapat sa mga pinapabasa ni ma’am. Eto yun: Pathophysiology CTP SAAG Hepatorenal Syndrome

OS 2 14

DIGESTIVE BLOCK B Trans? | Exam 1

So what will matter? How will the value of your days be measured? What will matter is not your success, but your Collateral significance. venous channels What will matter is not what you learned, but what you Persistence of NT taught. What will matter is every act Redistribution of of integrity, compassion, blood flow courage or sacrifice that enriched, empowered, or Increased encouraged others to aldosterone emulate your example. What will matter is not your Na & H2O competence, but your retention character. What will matter is not how many people you knew, but how how many will feel a lasting loss when you're gone. What will matter is not your memories, but the memories that live in those who loved you. What will matter is how long you will be remembered, by whom and for what. Living a life that matters doesn't happen by accident. It's not a matter of circumstance but of choice. Choose to live a life that matters. Hehe. Haba. Kung di kasya, wag nalang. Hello na lang to my friendly friends!  thanks for bringing light and laughter to my life… and for making Med more bearable. Haha.

Eto Greeting ko: Lifelong Impressions Ready or not, someday it will all come to an end. There will be no more sunrises, no minutes, hours or days. All the things you collected, whether treasured or forgotten, will pass to someone else. Your wealth, fame and temporal power will shrivel to irrelevance. It will not matter what you owned or what you were owed. Your grudges, resentments, frustrations, and jealousies will finally disappear. So, too, your hopes, ambitions, plans, and to-do lists will expire. The wins and losses that once seemed so important will fade away. It won't matter where you came from, or on what side of the tracks you lived, at the end. It won't matter whether you were beautiful or brilliant. Even your gender and skin color will be irrelevant.

November 13, 2006, Monday

The End

Page 5 of 5