1. CIRRHOSIS OF LIVER PORTAL HYPERTENSION HEPATIC ENCHEPALOPATHY
PART-ONE
1 TO 21 slides

2. Definition of cirrhosis
Cirrhosis is derived from Greek word kirros=orange or tawny and osis=condition -WHO definition :a diffuse process characterized by liver necrosis and fibrosis and conversion of normal liver architechture into structurally abnormal nodules that lack normal lobular organisation.

4. CAUSES OF LIVER CIRRHOSIS
-Infections:post hepatitic cirrhosis(B,D,C).
-Toxins:Alcohol.
-Cholestatic liver disease:PBC,PSC…
-Autoimmune diseases:autoimmune hepatitis.
-Vascular disorders: cardiac cirrhosis,Budd-Chiari syndrome ,Veno occlusive disease
-Metabolic and genetic :Wilson disease ,hemochromatosis,alpha 1- antitrypsin deficiency
-Non alcoholic steato hepatitis(NASH).
Cryptogenic.

5. Pathology of cirrhosis
-nodularity(regenerating nodules). -fibrosis(deposition of dense fibrous septa)-fragmentation of sample. -abnormal liver architecture -hepatocyte abnormalities:pleomorphism,dysplasia,hyperplasia -Gross pathology:irregular surface ,yellowish colour,small,firm

6. HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Cirrhosis
Slide 8
HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER
Histological images of two livers. On the left, a normal liver with conserved architecture. On the right, a cirrhotic liver with regenerative nodules surrounded by fibrous tissue (stained blue).
Nodules surrounded by fibrous tissue

7. HISTOLOGICAL IMAGE OF CIRRHOSIS
Fibrosis
Regenerative nodule
Slide 9
HISTOLOGICAL IMAGE OF CIRRHOSIS
Histological image of a cirrhotic liver showing regenerative nodules surrounded by fibrous tissue (stained blue).

8. NATURAL HISTORY OF CHRONIC LIVER DISEASE
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Development of complications:
Variceal hemorrhage
Ascites
Encephalopathy
Jaundice
Slide 14
NATURAL HISTORY OF CHRONIC LIVER DISEASE
Cirrhosis represents the end histological stage resulting from chronic liver injury of various etiologies. Initially, cirrhosis is compensated. The transition to a decompensated stage is marked by the development of variceal hemorrhage, ascites, hepatic encephalopathy and/or jaundice. Once decompensation occurs, the patient is at risk of death from liver disease.

9. CLINICAL FEATURES Hepatomegaly (although liver may also be small)
Jaundice
Ascites
Circulatory changes
Spider telangiectasia, palmar erythema, cyanosis
Endocrine changes
Loss of libido, hair loss
Men: gynaecomastia, testicular atrophy, impotence
Women: breast atrophy, irregular menses, amenorrhoea
Haemorrhagic tendency
Bruises, purpura, epistaxis, menorrhagia
Portal hypertension
Splenomegaly, collateral vessels, variceal bleeding, fetor hepaticus
Hepatic (portosystemic) encephalopathy
Other features
Pigmentation, digital clubbing

10. COMPLICATIONS OF CIRRHOSIS
Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency
Variceal hemorrhage
Portal hypertension
Spontaneous bacterial peritonitis
Ascites
Cirrhosis
Hepatorenal syndrome
Slide 17
COMPLICATIONS OF CIRRHOSIS
Cirrhosis leads to two clinical syndromes: portal hypertension and liver insufficiency. Development of variceal hemorrhage and ascites are the direct consequence of portal hypertension, while jaundice occurs as a result of a compromised liver function. Encephalopathy is the result of both portal hypertension (portosystemic shunting) and liver dysfunction (decreased ammonia metabolism). Ascites in turn can become complicated by infection (spontaneous bacterial peritonitis) and by the development of a functional renal failure (hepatorenal syndrome).
Encephalopathy
Liver insufficiency
Jaundice

11. Diagnosis of cirrhosis
clinical+laboratory+radiologic+liver biopsy

12. DIAGNOSIS OF CIRRHOSIS – CLINICAL FINDINGS
In Whom Should We Suspect Cirrhosis?
Any patient with chronic liver disease
Chronic abnormal aminotransferases and/or alkaline phosphatase
Physical exam findings
Stigmata of chronic liver disease (muscle wasting, vascular spiders, palmar erythema)
Palpable left lobe of the liver
Small liver span
Splenomegaly
Signs of decompensation (jaundice, ascites, asterixis)
Slide 19
DIAGNOSIS OF CIRRHOSIS – CLINICAL FINDINGS
Cirrhosis should be investigated in any patient with chronic liver disease. Various physical signs suggest the presence of cirrhosis. In particular, a palpable left lobe with a small right lobe (on percussion) and splenomegaly are highly suggestive of cirrhosis. A recent review of several studies concludes that the listed physical findings, when present in chronic liver disease, confer a high specificity for cirrhosis. However the sensitivity is generally low and the absence of these physical signs does not exclude cirrhosis.
De Bruyn G and Graviss EA, BMC Medical Informatics & Decision Making 2001; 1: 6

13. DIAGNOSIS OF CIRRHOSIS – LABORATORY STUDIES
In Whom Should We Suspect Cirrhosis?
Laboratory
Liver insufficiency
Low albumin (< 3.8 g/dL)
Prolonged prothrombin time (INR > 1.3)
High bilirubin (> 1.5 mg/dL)
Portal hypertension
Low platelet count (< 175 x1000/ml)
AST / ALT ratio > 1
Slide 20
DIAGNOSIS OF CIRRHOSIS – LABORATORY STUDIES
Tests that explore liver synthetic function are serum albumin and prothrombin time, while serum bilirubin investigates the ability of the liver to conjugate and excrete bilirubin. With liver dysfunction there is hypoalbuminemia,a prolonged prothrombin time and hyperbilirubinemia and the presence of either of these findings, in the presence of chronic liver disease, indicates the possibility of cirrhosis. However, an even earlier more sensitive finding suggestive of cirrhosis is a low platelet count that occurs as a result of portal hypertension and hypersplenism. An AST/ALT ratio >1 has also been identified as having a high specificity but a low sensitivity, therefore its absence cannot exclude cirrhosis.
Poynard and Bedossa. J Viral Hepat. 1997; 4:199
Dienstag JL, Hepatology 2002; 36 (Suppl 1): S152

15. DIAGNOSIS OF CIRRHOSIS – CAT SCAN
CT Scan in Cirrhosis
Slide 23
DIAGNOSIS OF CIRRHOSIS – CAT SCAN
This slide shows typical computed tomography findings in compensated cirrhosis. The contour of the liver is irregular, there is obvious splenomegaly and the presence of collaterals indicates portal hypertension and secures the diagnosis of cirrhosis.
Liver with an irregular surface
Collaterals
Splenomegaly

16. Liver biopsy Diagnostic Algorithm
Patient with chronic liver disease and any of the following:
Variceal hemorrhage
Ascites
Hepatic encephalopathy
Physical findings:
Enlarged left hepatic lobe
Splenomegaly
Stigmata of chronic liver disease
Laboratory findings:
Thrombocytopenia
Impaired hepatic synthetic function
Yes No
Radiological findings:
Small nodular liver
Intra-abdominal collaterals
Ascites
Splenomegaly
Colloid shift to spleen and/or bone marrow
Yes No
Slide 41
DIAGNOSTIC ALGORITHM
Diagnostic algorithm to investigate the presence of cirrhosis in patients with chronic liver disease. No
Yes
Liver biopsy not necessary for the diagnosis of cirrhosis
Liver biopsy

17. Management of cirrhosis
-Specific treatment in some pre cirrhotic lesions: Wilson’s disease—Dpenicillamine,,hemochromatosis---phlebotomy,,antiviral drugs for chronic viral hepatitis
-in established cirrhosis---treatment of complications
-screening for hepatocellular carcinoma
-liver transplantation
-maintenance of nutrition

18. CHILD-PUGH CLASSIFICATION OF PROGNOSIS IN CIRRHOSIS
Score 1 2 3
Encephalopathy
None
Mild
Marked
Bilirubin (mg/dl)
< 2.0
> 3.0
Albumin (g/dl)
> 3.5
< 3.0
Prothrombin time (seconds prolonged)
< 4
4-6
> 6
Ascites
Add the individual scores:
< 7 = Child's A 7-9 = Child's B > 9 = Child's C

19. MELD SCORE
MELD = 3.8(SERUM BILIRUBIN –MG/DL)+11.2 IN INR IN SERUM CREATININE – MG/DL+ 6.4

20. PORTAL HYPERTENSION
Definition:it is an increase in portal venous pressure. -normal portal pressure:5-10mmHg. -portal hypertension;>12mmHg -normal portal blood flow:1-1.5L/minute -- increased resistance to portal blood flow +hyperdynamic circulation-----formation of porto systemic collaterals that diver blood to systemic circulation bypassing the liver

21. MECHANISMS OF PORTAL HYPERTENSION
Pressure (P) results from the interaction of resistance (R) and flow (F):
P = R x F
Portal hypertension can result from:
increase in resistance to portal flow and/or
increase in portal venous inflow
Slide 44
MECHANISMS OF PORTAL HYPERTENSION
In fluid mechanics, Ohm’s law states that pressure (P) is dependent upon flow (F) and resistance to flow (R). Therefore, portal hypertension can result from an increase in portal venous inflow, an increase in resistance to portal flow or an increase in both flow and resistance.