Hepatic Cirrhosis (???)

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Hepatic Cirrhosis(???)

• Yu Baoping

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Introduction

• CIRRHOSIS
• Term was 1st coined by Laennec in 1826
• Many definitions but common theme is injury,
  repair, regeneration and scarring
• NOT a localized process involves entire liver
• Primary histologic features
• Marked fibrosis
• Destruction of vascular biliary elements
• Regeneration
• Nodule formation

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Definition

• Cirrhosis is a pathological diagnosis. It is
  characterized by widespread fibrosis with nodular
  regeneration. Its presence implies previous or
  continuing hepatic cell damage

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Aetiology and Pathogenesis

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Etiologic classification of cirrhosis

• Alcohol (gt70)
• Chronic infections
• hepatitis C, B, BD
• brucellosis, syphilis
• Chr. biliary obstruction
• PBC, PSC, stricture,
• stones, cystic fibrosis, cong.b.
  atresia, cysts
• Autoimmune

• Cardiovascular
• heart failure, pericarditis,
• Budd-Chiary-sy
• Metabolic/genetic errors
• Fe, Cu, a1-AT, lipids,
• Drugs and chemicals
• NASH
• Cryptogenic
• Combined

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Pathogenesis

• Diffuse liver injury leading to necrosis.
• (Alcohol, virus, drugs, toxins, genetic etc.)
• Chronic inflammation healing (hepatitis).
• Bridging fibrosis loss of architecture.
• Regeneration ? nodules.
• Obstruction to blood flow shunts.
• Portal hypertension ?spleen, varices
• Liver failure Debilitation, Jaundice, Ascitis,
  edema, bleeding, jaundice.
• Hormone imbalance spider nevi, testes atrophy
  etc..

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Pathology and Pathophysiology

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Pathology (liver)
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Classification of Cirrhosis

• WHO divided cirrhosis into 3 categories based on
  morphological characteristics of the hepatic
  nodules
• Micronodular
• Macronodular
• Mixed

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Micronodular Cirrhosis

• Nodules are lt3 mm in diameter
• Relatively uniform in size
• Distributed throughout the liver
• Rarely contain portal tracts or efferent veins
• Liver is of uniform size or mildly enlarged
• Reflect relatively early disease

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Micronodular cirrhosis
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Macronodular Mixed Cirrhosis

• Nodules are gt3 mm in diameter and vary
  considerably in size
• Usually contain portal tracts and efferent veins
• Liver is usually normal or reduced in size
• Mixed pattern if both type of nodules are present
  in equal proportions

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Macronodular cirrhosis
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Cirrhosis
Fibrosis Regenerating Nodule
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Pathology ( splenomegaly )
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Pathology (others)

• gastrointestinal tract
• varicose veins,hemorrhage,congestion
• Kidney
• glomerulonephritis
• Endocrine
• muscular atrophy,degeneration(testis,
  ovary, thyroid,adrenal cortex)

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Cirrhosis Pathophysiology

• Primary event is injury to hepatocellular
  elements
• Triggering inflammatory response with cytokine
  release-toxic substances
• Destruction of hepatocytes, bile duct cells,
  vascular endothelial cells
• Repair thru cellular proliferation and
  regeneration
• Formation of fibrous scar

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Cirrhosis Pathophysiology

• Stellate cell is activated in response to injury
  and lead to expression of fibril-forming collagen
• Above process is also influenced by Kupffer cells
  which activate stellate cells by eliciting
  production of cytokines
• Sinusoidal fenestrations are obliterated because
  of collagen

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Cirrhosis Pathophysiology

• Prevents normal flow of nutrients to hepatocytes
  and increases vascular resistance
• Initially, fibrosis may be reversible if inciting
  events are removed
• With sustained injury, process of fibrosis
  becomes irreversible and leads to cirrhosis

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Pathophysiology

• Protal hypertension
• Ascites
• endocrine
• respiratory system hepatic hydrothorax
• hepatopulmonary
  syndrome
• the urinary system hepatorenal syndrom, HRS
• hematological system
• nervous system HE

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Portal Hypertension (PH)

• Portal vein pressure above the normal range of 5
  to 8 mm Hg
• Portal vein - Hepatic vein pressure gradient
  greater than 5 mm Hg (gt12 clinically significant)
• Represents an increase of the hydrostatic
  pressure within the portal vein or its tributaries

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Pathophysiology of PH

• Cirrhosis results in scarring (perisinusoidal
  deposition of collagen)
• Scarring narrows and compresses hepatic sinusoids
  (fibrosis)
• Portal vein thrombosis, or hepatic venous
  obstruction also cause PH by increasing the
  resistance to portal blood flow
• Progressive increase in resistance to portal
  venous blood flow results in PH

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Pathophysiology of PH

• As pressure increases, blood flow decreases and
  the pressure in the portal system is transmitted
  to its branches
• Results in dilation of venous tributaries
• Increased blood flow through collaterals and
  subsequently increased venous return cause an
  increase in cardiac output and total blood volume
  and a decrease in systemic vascular resistance
• With progression of disease, blood pressure
  usually falls

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Portal Vein Collaterals

• Coronary vein and short gastric veins -gt veins of
  the lesser curve of the stomach and the
  esophagus, leading to the formation of varices
• Inferior mesenteric vein -gt rectal branches
  which, when distended, form hemorrhoids
• Umbilical vein -gtepigastric venous system around
  the umbilicus (caput medusae)
• Retroperitoneal collaterals -gtgastrointestinal
  veins through the bare areas of the liver

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Ascites

• Sodium and water retention occur due to
  renin-angiotensin release secondary to arterial
  vasodilatation, caused by vasoactive substances
  such as nitric oxide
• Portal hypertension per se causes fluid to
  accumulate in the peritoneal cavity due to
  increased hydrostatic pressure, hence further
  reduces intravascular volume and stimulates
  sodium and water retention via aldosterone.
• Low albumin in plasma

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Clinical presentation

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Clinical presentation

• There may be no abnormal clinical or biochemical
  features of liver disease in initial times
• Features of hepatocellular failure, portal
  hypertension, or both may appear in advanced
  times.

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CirrhosisClinical Features
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Symptoms of advanced cirrhosis

• Fatique, weakness
• Nausea, vomiting and loss of appetite
• Weight loss, muscle wasting
• Jaundice, dark urine
• Spider naevi, caput Medusae
• Bloody, black stools or unusually light-colored
  stools
• Vomiting of blood

• Abdominal swelling
• Swollen feet or legs
• Liver palms
• Gynecomastia
• Loss of sex drive
• Menstrual changes in women
• Generalized itching
• Sleep disturbances, confusion,desorientation,trem
  or, asterixis

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Clinical Features

• Hepatocellular failure.
• Malnutrition, low albumin clotting factors,
  bleeding.
• Hepatic encephalopathy.
• Portal hypertension.
• Ascites, Porta systemic shunts, varices,
  splenomegaly.

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Visible signs of advanced liver cirrhosis

Gynecomastia Ascites Caput Medusae Umbilical
hernia
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• Complications

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Complications

• Upper gastrointestinal hemorrhage
• Hepatic encephalopathy
• Infection
• Hepatorenal syndrome
• Hepatopulmonary Syndrome
• Primary carcinoma of the liver
• Disturbance of electrolyte and acid-base balance

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Laboratory tests and investigations

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laboratory tests
and investigations

• Blood-RT
• anaemiahyperspleniaWBC ,Plt
• Urine-RT urine bilirubin,urobilinogensometimes
  albumen,haematuria
• Stool-RT
• melena

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laboratory tests and
investigations

• liver function tests
• Compensation normal or abnormal slightly
• Decompensation
• transaminase ALT AST
• cholesterol
• albumin and globulin
• prothrombin time
• bilirubin
• P?P, and so on
• Quantitation- liver function tests IGG

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laboratory tests and
investigations

• Biochemistry can be surprisingly normal but some
  abnormality will often be present with slightly
  raised transaminases and alkaline phosphatases.
  In severe cases, all live enzymes will be
  abnormal. Low sodium and albumin are also seen.
• Coagulopathy is a very sensitive indicator of
  liver dysfunction and is reflected in the
  prolonged prothrombin time.

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laboratory tests and
investigations

• immunologic function test
• AFP
• virus hepatitis markers
• antinuclear antibody, ANA
  non-specificity
• antismooth muscle antibody autoantibody
• anti-mitochondrial antibody

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laboratory tests and
investigations

• Imaging examination
• Barium meal
• CT or MRI
• Ultrasound demonstrates fatty change, size,
  and
• fibrosis as well as
  hepatocellular carcinoma

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laboratory tests and
investigations
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laboratory tests and
investigations
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MRI Cirrhosis

• laboratory tests and
  investigations

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laboratory tests and
investigations

• Special test
• Endoscope
• Biopsy
• Laparoscope
• Hydroperitoneum test
• Measure the Pressure of Portal Vein

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Diagnosis and differential diagnosis

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Diagnosis of liver cirrhosis

• The gold standard liver biopsy histology
• Diffuse, chronic liver disease(hystory,
  physical, laboratory and US findings)
• with evidences of portal hypertension(oesophageal
  varices on gastroscopy dilated portal vein and
  its branches by US)

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Child-Pughs classification
Grade A 5-6 Grade B 7-9
Grade C 10-15
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Differential diagnosis

• Liver diseases
• chronic hepatitisprimary carcinoma of the
  liverschistosomiasisclonorchiasis
  sinensishepatic hydatidosishemopathy
• Ascites and abdomen enlarged
• tuberculous peritonitisconstrictive
  pericardium chronic glomerulonephritisovarian
  cysts
• Complications
• Upper gastrointestinal hemorrhage
  InfectionHepatic encephalopathyHepatorenal
  syndromeHepatopulmonary Syndrome Primary
  carcinoma of the liver

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Treatment

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Treatment of liver cirrhosis

• Removal of the etiological factors can stop or
  delay further progression may lead to
  regression may reduce complications
• Prevention and treatment and of complications

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Cirrhotic ascites

• Rest
• Diet
• Treatment bed rest, salt restriction,
• Water immersion
• diuretics spironolactone, furosemide under
  regular check-up (body wt, electrolyites, renal
  function)Refractory ascites
• large-volume paracentesisTIPS
• peritoneovenous shunting

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Complications

• Spontaneos bacterial peritonitis (SBP) fever,
  sepsis, hypotension, fast deteoriation of liver
  function, azotaemia, encephalopathy, deathDg.
  PMN count in the ascites gt 250/µl cultureTh.
  antibiotics paracentesis
• Hepatorenal syndrome renal failure with severe
  liver disease without an intrinsic abnormality of
  the kidneyCause reduction in RBF, GFR
  (vasoconstrictors!)Dg. urine Na lt 10 mM,
  oliguria without volume depletion Th.
  prevention of hypovolemia, hypotensionterlipressi
  n TIPS
• Prognosis lethal if the liver disease is
  untreatable

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Bleeding oesophageal and gastric varices

• Features hematemesis, melena, shock
• Dg. and treatment stabilizing BP, replacing
  fluid and blood, somatostatin
• endoscopic sclerotherapy or ligationor balloon
  tamponade eradication of varices TIPS, P-C
  shunting
• Prevention propranolol
• Liver transplantation

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Prognosis

• Liver transplantation
• Prognosis

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Thanks!
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