CIRRHOSIS

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CIRRHOSIS

• Dr. Aaron Rabinovich
• January 8, 2008

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PORTAL SYSTEM
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PORTAL SYSTEM

• The venous blood from the GI tract drains into
  the superior and inferior mesenteric veins
  these two vessels are then joined by the splenic
  vein just posterior to the neck of the pancreas
  to form the portal vein.
• On entering the liver, the blood drains into the
  hepatic sinusoids, where it is screened by
  Kupffer cells.
• The plasma is filtered through the endothelial
  lining of the sinusoids and bathes the
  hepatocytes
• The portal venous blood contains all of the
  products of digestion absorbed from the GI tract,
  so all useful and non-useful products are
  processed in the liver before being either
  released back into the hepatic veins which join
  the inferior vena cava just inferior to the
  diaphragm, or stored in the liver for later use.

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Portal Hypertension

• DEF Increased pressure in the portal vein.
• With the right atrial pressure as a zero
  reference, normal portal venous pressure is
  approximately 4-8 mm Hg.
• The portal vein is formed by the confluence of
  the splenic and superior mesenteric veins.
• Its flow rate normally averages about 1-1.2
  L/min.
• The simple phenomenon of increased pressure in
  this venous circulation unleashes a wide array of
  hemodynamic and metabolic consequences

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Etiology

• Any condition causing an increase in flow or
  resistance will increase portal pressure.
• An example of a "pure" flow increase is post
  surgical or traumatic splenic arteriovenous
  fistula. The marked increase in splenic and thus
  portal venous flow leads to the development of
  portal hypertension.
• Almost all other causes of portal hypertension
  are mediated predominantly by increasing
  resistance, although evidence indicates that most
  high-resistance syndromes are also accompanied by
  increases in portal venous flow.

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Etiology

• In many conditions, the cause of the increased
  resistance is evident
• inflammation and fibrosis lead to vascular
  distortion,
• architectural disturbance
• impingement of the intravascular spaces.
• Other less evident factors are predominant in
  other conditions.
• For example, in acute alcoholic hepatitis,
  hepatocyte cell swelling and collagen deposition
  in the space of Disse lead to narrowing and
  distortion of sinusoidal spaces.

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P Q X R
PORTAL HYPERTENSION
INCREASED PORTAL VENOUS INFLOW
INCREASED HEPATIC VASCULAR RESISTANCE
FIBROSIS REGENERATION THROMBOSIS
SPLANCHNIC AND SYSTEMIC VASODILITATION ( NO AND
OTHERS)
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Causes of portal hypertension

• SINUSOIDAL
• SARCOIDOSIS
• SCHISTOSOMIASIS
• NODULAR REGENERATIVE HYPERPLASIA
• CONGENITAL HEPATIC FIBROSIS
• IDIOPATHIC PORTAL FIBROSIS
• EARLY PRIMARY BILIARY CIRRHOSIS
• CHRONIC ACTIVE HEPATITIS
• MYELOPROLIFERATIVE DISORDER
• GRAFT VS HOST DISEASE

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Causes of portal hypertension

• SINUSOIDAL
• ESTABLISHED CIRRHOSIS
• ALCOHOLIC HEPATITIS

• PRESINUSOIDAL
• SPLENIC AV FISTULA
• SPLENIC/VEIN THROMBOSIS
• MASSIVE SPLENOMEGALY

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Causes of portal hypertension
Post sinusoidal -ALCOHOLIC TERMINAL HYALINE
SCLEROSIS -VENO-OCCLUSIVE DISEASE -BUDD CHIARI
SYNDROME -MEMBRANOUS IVC WEB -RIGHT HEART
FAILURE -CONSTRICITIVE PERIDARDITIS
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Pathophysiology

• Portal pressure can be measured by several
  methods.
• A catheter inserted into a hepatic vein and then
  wedged provides a good estimate of the upstream
  portal venous pressure, unless the site of
  resistance is proximal to the intrahepatic portal
  vein (as in portal vein thrombosis wherein the
  wedged hepatic vein pressure will be normal in
  the presence of significant portal
  hypertension).
• The spleen, liver or portal vein can be directly
  percutaneously punctured by small-gauge (19-22
  gauge) needles to obtain reliable estimates of
  portal pressure.

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Pathophysiology clinical complications

• Ascites is directly related to the development of
  sinusoidal or postsinusoidal hypertension.
• Portal-systemic collateral vessels form in an
  attempt to decompress the portal hypertension
• The most troublesome site of collateral formation
  is around the proximal stomach and distal
  esophagus (gastroesophageal varices).
• Bleeding from such varices (or the gastric
  mucosa) and hepatocellular failure are the two
  commonest causes of death in cirrhosis.

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Child-Pugh Classification

• Score Bilirubin (mg/dl) Albumin (gm/dl)
  PT (Sec) Encephal Ascites
• 1 lt 2 gt 3.5
  1 - 4 None None
• 2 2 - 3 2.8 - 3.5
  4 6 1 - 2 Mild
• 3 gt 3 lt 2.8
  gt 6 3 4 Severe
• Child class
• A 5 6
• B 7 9
• C gt 9.

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Pathophysiology clinical complications

• Indeed the mortality rates for variceal bleeding
  range from 15-50 depending on the degree of
  hepatic function
• Child-Pugh class
• A B C
• 15 20-30 40-50

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• The risk of bleeding from gastroesophageal
  varices is related to several factors.
• A threshold minimum level of portal pressure of
  approximately 12 mm Hg appears necessary for
  varices to form. However, above this level it is
  unclear whether absolute height of portal
  pressure affects the bleeding risk.
• intrathoracic pressure gradients and damage to
  the variceal wall by acid reflux into the
  esophagus appear not to play a role.
• The two factors most important in determining
  bleeding risk are variceal size and local
  variceal wall Characteristics.

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• Several studies have shown that small varices
  almost Never bleed, while the bleeding risk of
  medium-sized varices is approximately 10-15 over
  two years, and that of large varices,
  approximately 20-30 over the same period
• Approximately 30-50 of upper GI bleeding
  episodes in patients with portal hypertension
  originate from nonvariceal sources.
• The majority of nonvariceal upper GI bleeding in
  cirrhosis is due to a peculiar form of
  gastropathy seen in the stomach in portal
  hypertension
• Portal hypertensive gastropathy may also produce
  brisk bleeding, but can occasionally cause
  low-volume oozing manifested only by melena.

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DIAGNOSIS IS EASY

• The patient often has concomitant ascites and
  splenomegaly, along with the stigmata of chronic
  liver disease.
• caput medusae,
• Dilated abdominal wall veins
• Anorectal varices masquerading as hemorrhoids.
• Gastroesophageal variceal bleeding produces
  large-volume, brisk bleeding with hematemesis
  and, later, melena or hematochezia
• However, it should be remembered that all the
  prehepatic and many of the presinusoidal
  conditions have well-preserved liver function and
  no ascites.

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Management

• general resuscitative measures
• Vasoconstrictive drugs
• vasopressin and somatostatin or their
  longer-acting analogues such as glypressin and
  octreotide, respectively.
• Vasopressin infusions induce generalized
  arteriolar and venous constriction, with
  resultant decreased portal venous flow and thus
  pressure, and at least temporary cessation of
  bleeding in 50-80 of cases

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Management

• general resuscitative measures
• Vasoconstrictive drugs
• Somatostatin or octreotide.
• Their mechanism of action is still unclear but
  probably relates to a suppressive effect on the
  release of vasodilatory hormones such as
  glucagon, leading to a net vasoconstrictive
  effect.
• Side effects are minimal.
• Whatever drug is used, it is generally
  inadvisable to continue drug therapy for more
  than one to two days.

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Management

• Mechanical modes of therapy include inflatable
  balloons for direct tamponade.
• The Sengstaken-Blakemore tube has both an
  esophageal and a small gastric balloon
• the Linton-Nachlas tube, with only a large
  gastric balloon, is attached to a small weight to
  stanch the cephalad flow of blood in the varices.
  
• Both tubes carry significant complication rates
  (15), especially in inexperienced hands.
• The most common complications of esophageal
  balloon therapy for varices include aspiration,
  esophageal perforation and ischemic (pressure)
  necrosis of the mucosa.

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Management

• The most common and probably the most effective
  nonsurgical therapies are endoscopic variceal
  sclerotherapy and ligation.
• Highly irritant solutions such as ethanolamine,
  polidocanol or even absolute ethanol are injected
  through endoscopic direct vision into and around
  the bleeding varix.
• The subsequent inflammation leads to eventual
  thrombosis and fibrosis of the varix lumen.
• Possible complications include chest pain,
  dysphagia, and esophageal ulceration and
  stricturing.

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Management

• Safer method of endoscopic therapy is ligation or
  banding, similar to the rubber band ligations
  used to fibrose anorectal hemorrhoids.
• Initial studies suggest that its efficacy is
  similar to sclerotherapy, with fewer esophageal
  complications.
• The combination of endoscopic therapy and either
  balloon tamponade or drug therapy to control
  actively bleeding varices is successful in 80-95
  of cases.

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Management

• When all the above measures fail, emergency
  surgery may be tried. 10-20 patients continue
  to bleed with medical management and there is a
  90 risk of death from blled
• Emergency portacaval shunt surgery has been
  abandoned because of a 30-50 operative mortality
  rate.
• The simplest and probably best choice in the
  emergency situation is esophageal transection, in
  which a mechanical device transects and removes a
  ring of esophageal tissue, and then staples the
  ends together.

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Management

• Another type of "surgery" is the transjugular
  intrahepatic portal-systemic shunt (TIPS).
• In this procedure, an intrahepatic shunt between
  branches of the hepatic and portal veins is made
  by balloon dilation of liver tissue, and then an
  expandable metal stent of approximately 1 cm
  diameter is lodged into the fistula.
• The procedure can be done by a radiologist using
  fluoroscopy- guided catheterization, and requires
  only light sedation and local anesthesia.

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Management

• Success 90-100 with a 10 recurrence of bleeding
• 6months --92 1yr--82
• goal reduce hv-pv gradient lt12mmhg
• mortality is still high 40-60 at 6-7wks

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Management

• transjugular intrahepatic portal-systemic shunt
  (TIPS).
• Complications
• 25 encephalopathy
• 3-5 increase of liver failure
• 50-60 stents stenosis and occlude

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Management

• Once the acute bleeding episode has been treated,
  how do we reduce the risk of future rebleeding?
• Before considering any other therapy, some
  obvious common-sense measures should be taken.
• Prophylactic therapy to prevent bleeding may be
  divided into primary (to prevent the first bleed
  in a patient with varices who has never bled) and
  secondary prophylaxis (to prevent rebleeds).

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Management

• Patients with large varices that have never bled
  should be started on beta blocker therapy at
  doses sufficient to reduce the resting heart rate
  by 20-25.
• Beta-adrenergic, B1 B2, antagonists are thought
  to produce arteriolar and venous constriction and
  significantly reduce blood flow through
  portal-systemic collaterals while modestly
  reducing portal pressure. Goal is to reduce the
  hepatic vein-portal vein gradient to lt12 mmhg or
  gt20 below baseline
• 40 reduction of bleeding episodes noted overall

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Management

• Nitrates
• vasodilator -gt reduced portal pressure
• reflex splanchnic vasoconstriciton secondary to
  peripheral venodilation and venous pooling
• arterial vasodilation--gt decrease collateral
  resistance
• decrease hepatic ressistance
• if used with b-blockers there was a 8 rebeed
  rate vs 18 rebleed rate with b-blocker alone

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Management

• Perform enough endoscopic sclerotherapy/banding
  sessions (usually 3-6) to obliterate varices or
  reduce them to small size.
• Treatment failures on this regime (e.g., those
  with recurrent bleeding) could be considered
  either for TIPS or surgery.
• TIPS should not be done in patients with a
  history of, or active, encephalopathy.

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Management

• Prehepatic causes of portal hypertension such as
  portal vein thrombosis generally respond well to
  some type of portal-mesenteric diversion
  procedure such as mesocaval or portacaval
  shunting.
• In these cases, normal liver function protects
  against the development of encephalopathy or
  hepatic insufficiency when portal blood is
  diverted away from the liver..

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Management

• Of course the definitive treatment for most of
  the complications of end- stage liver disease,
  including recurrent GI bleeding due to severe
  portal hypertension,
• orthotopic liver transplantation.
• Since the presence of a surgical portacaval or
  mesocaval shunt greatly complicates the
  transplantation procedure, we have generally
  abandoned these types of shunting operations in
  patients with cirrhosis.

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1945 Whipple and Blakemore in Columbia performed
1st shunt
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SURGERY

• 1- LIVER TRANSPLANTATION
• ONLY DEFINITIVE PROCEDURE
• primary in Childs C
• 2- SHUNT PROCEDURE
• 3- DEVASCULARIZATION

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Child-Pugh Classification

• REDUCTION FUNCTION SHUNT OPERATIVE
  MORTALITY
• A 30 0-5
• B 50 10-15
• C 90 gt15

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SURGERY-SHUNT

• 1- TOTAL DIVERTING SHUNTS
• END-SIDE PORTACAVAL SHUNT
• gt10MM SIDE-TO-SIDE PORTOCAVAL SHUNT
• MESOCAVAL
• CENTRAL SPLENORENAL SHUNT

COMPLICATIONS 1- WORSEN LIVER FUNCTION 2-
ENCEPHALOPATHY 3- PORTA HEPATIS DISSECTED MAKES
VERY DIFFUCLT FOR OLT
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SURGERY-SHUNT
2- PARTIAL DIVERTING A- DECOMPRESSED WHILE
MAINTAINS HEPATOPETAL FLOW REDUCE TO 12MMHG AND
MAINTAIN 80-90 OF PATIENTS -INTERPOSITION
MESOCAVAL SHUNTS (8 MM SIDE TO SIDE ) -
PORTACAVAL SHUNT ( SARFEH) 1- COMPONENT IS LEFT
GASRTIC V. LIGATION AS WELL AS GASTROEPIPLOIC AND
OTHER COLLATERALS
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SURGERY-SHUNT

• 3- SELECTIVE DIVERTING SHUNTS
• Two separate drainage systems with in portal
  venous system
• high pressure in portcaval system
• low pressure in esophagogastric system

• 3- SELECTIVE DIVERTING SHUNTS ADVANATGES
• 90 stop bleeding
• no porta hepatis dissection
• hepatopetal flow maintained
• encephalopathy 5-24
• liver failure is lower
• distal splenorenal contradindicated in ascites

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Devascularization

• Sugiura procedure
• mortality is 10-35
• 5 recurrence rate of rebleeding
• thoraco abdominal incision
• splenectomy, devasc. Stomach, esopsophagus,
  transect the esoph with reanastamosis, ligate all
  collaterals

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DIRECT MESOCAVAL SHUNT
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MESOCAVAL H-GRAFT SHUNT
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LIGATED CORONARY VEIN
LIGATED GASTROEPIPLOICVEIN
LIGATED IMV
DISTAL SPLENORENAL SHUNT- WARREN
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SPLENORENALSHUNT
SPLENECTOMY
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SIDE TO SIDE PORTACAVAL SHUNT
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END TO SIDE PORTACAVAL SHUNT