Portal Hypertension and Bleeding Varices

Dr/ Mohammed Hussien Assistant Lecturer of

Gastroentrology & Hepatology Kafrelsheik University

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Physiology of the portal system:

The portal blood flow is about 1000-1200 ml/min (75% of total hepatic blood volume). giving 72% of the total oxygen supply to the liver.

Normally 100% of the portal blood extracted from Hepatic veins which decreased to 13% in L.C.

The mean portal vein pressure varies between 6 and 10 mm Hg (8.5-14 cm Saline).

Anatomy of Portal vein

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DR Mohammed

Husien

Sites of Collaterals

esophageal and gastric veins

inferior rectal-anal veins

anterior abdominal wall veins retroperitoneal venous plexus

Caput Medusae

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Persistent increase in portal vein pressure above its normal range. Also wedge hepatic venous pressure (WHVP) of more than 4 mm Hg above inferior vena caval pressure is a reliable indicator of portal hypertension

What's Portal hypertension

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I- Morphological alteration:A- Diffuse hepatic fibrosis associated with constriction of hepatic vascular bed was implicated as the major factor,

In Schistosomiasis the gradual shutdown of the portal venous flow due to the presence of schistosoma eggs, granulomata, scar tissues around them and micorthrombi within the venules result in portal hypertension, congestive splenomegaly and the development of porto-systemic collaterals.

1- Increased portal vascular resistance (Backward theory):

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B- Regenerating cirrhotic nodules: Regenerating nodules and transmission of hepatic arterial pressure to portal bed via perisinusoidal arterio-portal shunts

C- Increased collagen deposition: within Disse space hepatic fibrosis/cirrhosis (PDGF) stimulates proliferation of Ito cells and their change to myofibroblasts. Transforming growth factor (TGFB-1) stimulates the production of collagen from myofibroblasts which deposited not only around portal and centrilobular veins but also in Disse spaces leads to capillarisation and to irreversible increase in portal pressure.

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D-Hepatocytes enlargment:2- Dynamic Interaction: In precirrhotic stage the

hepatic portal resistance is increased as a result of increase in spontaneous vascular tone (Grossmen et al, 1990) which appear to be a factor in the obstruction of flow through the liver is established in liver cirrhosis. This suggested the possibility of treating portal hypertension with appropriate vasodilator agents

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The current concepts explaning hyperdynamic circulation implicate the combination of:

1-

Increased plasma levels of gastrointestinal endogenous vasodilators may result from porto-systemic shunting coupling with a reduction in hepatic elimination.

II- Hyperdynamic circulation (Forward hypothesis)

Enhanced vasodilators:

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a- Prostanoids:PGI2 production (a potent vasodilator) is increased in portal system of rat models and cirrhotic patients (Wernez et al., 1986). PGI2 and NO contribute to splanchnic hypraemia in portal hypertensive rats, and both may interact, promoting splanchnic hypraemia in portal hypertension. Fernendez et al. (1996)

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b- 5 HT2Both 5HT2 inhibitors Ketanserin and ritanserin decrease high portal pressure due to changes in intrahepatic vascular resistance (Matsai, 1990).

c- Glucagon:May attenuate catecholamine-induced vasoconstriction (Farah, 1983). It is increased in patients with portal hypertension and portosystemic shunts (Sikular and Grossman, 1980). Somatstatin and octeriotide which inhibit glucagon release produce vasoconstriction of the splanchnic and systemic circulation (Albilos 1992).

It appears that glucagon may contribute to the circulatory changes observed in early or compensated cirrhosis.

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d- Adenosine: It induce vasodilatation via direct vascular smooth muscle relaxation by interacting with membrane bound purine receptors or by attenuation of catecholamine induced vasoconstriction (Spark and Gorman, 1987).

e- GABA (Gama aminobuteric acid):Is proposed to influence systemic haemodynamics in

patients with liver cirrhosis (Minuk and MacCannel, 1988). Its level increased with increasing severity of liver disease.

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2-

- Sympathetic nervous system activity, increase with the progression of hepatic disease (Henriksen et al., 1984) due to decrease in -adrenergic receptor sensitivity.

- A reduced vascular smooth muscle response to endogenous catecholamines might augment the systemic and splanchnic vasodilatation accompanied enhanced vasoactive mediator production.

- Glucagon and adenosine may attenuate catecholamins. -Induced vasoconstriction. -Endothelin Derived Relaxing

Factor (EDRF):

Reduced Sensitivity to vasoconstrictors:

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Role of Nitric oxide (NO)NO synthesis, activity and release are enhanced at the level of splanchnic vasculature and more important in haemodynamic changes in patients with liver cirrhosis and portal hypertension. Chu et al., (1997)In liver cirrhosis endotoxins or other mediators (the cytokines IL-1, TNF and INF-) are provided for inapproprate NO formation, which contribute to the hyperamic state and general hyporespponsiveness to vasoconstrictors associated with LC. (Vallance and Moncarda, 1991).

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At the time of diagnosis of cirrhosis, varices are present in about 30% of compensated and 60% of decompensated patients (D’Amico et al., 1995).

Risk factors of Bleeding Varices i- Portal pressure:

Although a minimum portal pressure of 12 mmHg is needed for the development of varices, above this level there is no linear relation between the severity of portal hypertension and variceal size or risk of bleeding (Vinel et al., 1986). Several cross sectional studies showed that HVPG of about 12 mmHg is needed for varices to bleed (Tsao et al., 1985). Pharmacological treatment to decrease HVPG by 20% or more abolished rebleeding from varices (Feu et al., 1992).

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ii- Variceal size:Variceal dilatation was related to the degree of incompetence in the perforating veins (McCormack et al., 1983). There is a relation between variceal size and the risk of bleeding in those who have never bled (Kleber et al., 1991) and those who have already bled (Ready et al., 1991). This has prognostic importance for patients selection for prophylcetic treatment.

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iii- Variceal wall structure/tension:Labplace’s law, variceal wall tension is defined as: Wall Tension=(P1-P2)X r/w. An interaction between variceal wall tension, thickness and transmural pressure as predictors of variceal rupture (Polio and Grosszman, 1986). Cherry red spot is an index of potenial varix rupture and bleeding (NIEC, 1988 and Kleber et al., 1991). The level of varical pressure is a major predictive factor for variceal bleeding

IV- Hepatic function:The degree of hepatic dysfunction have been shown to be of predictive value in assessing the risk of initial bleeding

Portal Hypertension Congestive Gastropathy

Mild form in (20-94 % ) of cases of portal hypertension.

Sever form in (7-14%) of cases. Only, the severe form of congestive gastropathy is clinically important as it can lead to occult and or overt bleeding.

Propranolol prevent both acute and chronic bleeding in congestive hypertensive gastropathy, whatever the triggering factor for this bleeding

History 1.Determining the cause of portal hypertension :

History of jaundice History of blood transfusions, intravenous drug use ( hepatitis C ) Pruritus Family history of hereditary liver disease (hemochromatosis, Wilson disease)History of alcohol abuse

2.Determining the presence of the complications of portal hypertension :

Determining the presence of the complications of portal hypertension :

Haematemasis or Melena (gasterooesophageal varices bleeding or bleeding from portal gastropathy )

Mental status changes such as lethargy, increased irritably, and altered sleep patterns (presents of portosystamic encephalopathy)

1. Sings of portaosystamic collateral

formation :

Dilated veins in the another abdominal wall ( umbilical epigastric vein shunts) Venous pattern on the flanks (portal-parietal peritoneal shunting) Caput medusa (tortuous collaterals around the umbilicus

) Rectal hemorrhoids Ascites – shifting dullness and fluid wave (if significant

amount of ascetic fluid is present ) (4) Paraumblilical hernia

Physical

Signs of liver disease :

• Ascites (4) • Jaundice • Spider angiomas • Gynecomastia • Duoutytern contracture • Muscle wasting • Palmer erythema• Asterixis• Testicular atrophy• Splenomagly

3. Signs of hyperdynamic circulatory sate :

Bounding pulses Warm, well-perfused extremities Arterial hypotension

• Types1. Prehapatic

• Portal vein thrombosis.• Splenic vein thrombosis . • Congenital atresia or stenosis of portal vein • Extrinsic compression ( tumors ) • Splanchnic arteriovenous fistula

2. Interahepatic, predominantly presinusoidal:

Schistosomisis ( early stage ) Primary billiary cirrhosis ( early stage ) Idiopathic portal hypertension ( early stage ) Nodular regenerative hyperplasia : Pathogenesis

probably is obliterative venopathy Myeloproiferative disease: These act by direct

infiltration by malignant cells Polycystic disease Hepatic metastasis Granulomatous disease ( sercodiosis, tuberculosis )

3.Intrahepatic , predominantly sinusoidal and /or postsinusoidal :

Hepatic cirrhosis Acute alcoholic hepatitis Schistosomisis ( advanced stage ) Primary billiry cirrhosis ( advanced stage ) Ldiopathic portal hypertension ( advanced stage ) Acute and fulminant hepatitis Congenital hepatic fibrosis Peliosis hepatitis Venoocclusive disease Budd-chiari syndrome

4. Posthepatic : Inferior vena cava (IVC) obstruction Right heart failure Constrictive pericarditis Tricuspid regurgitation Budd-chiari syndrome Arterial –portal venous fistula Increased portal blood flow

Laboratory studies:Liver function test Prothrombin time Albumin Viral hepatitis serologies Platelet count Antinuclear antibody, antimitochonderial antibody , anistmooth muscle antibody Iron indices Alpha1-abtitrypsin deficiency Cerulopasmin ,24hour urinary copper – to be considered only in individuals aged 3-40 years who have unexplained hepatic, neurologic or psychiatric disease

Differential Diagnoses:

Budd-chiari syndrome Schistosomiasis

Cirrhosis Tricuspid regurgitation

Myeloproiferative disease Tuberculosis

Pericarditis constrictive Vitamin A toxicity

Sarcoidosis

Laboratory studies:

Liver function test Prothrombin time Albumin Viral hepatitis serologies Platelet count Antinuclear antibody, antimitochonderial antibody ,

anistmooth muscle antibody Iron indices Alpha1-abtitrypsin deficiency Cerulopasmin ,24hour urinary copper – to be

considered only in individuals aged 3-40 years who have unexplained hepatic, neurologic or psychiatric disease

Imaging studies :

1. Duplex- Doppler ultrasongraphy 2. CT scan /

Wich improvement of sprial CT scan and 3-dimensional angiographic reconstructive techniques, portal vasculature may be visualized more accurately. Findings suggestive of portal hypertension include the following:

Collaterals arising from the portal system are suggestive of portal hypertension Dilatation of the IVC also is suggestive of portal hypertension.

3. MRI 4. Liver–spleen scan

Grading of Varices by Endoscopy

Although numerous methods have been described for grading varices, the simplest method is to divide them into three grades:

• Grade 1: varices that collapse to inflation of the oesophagus with air.

• Grade 2: varices between grades 1 and 3.• Grade 3: varices which are large enough to

occlude the lumen.vented by medical therapy. 05/03/23

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• What's PrePrimary Prophylaxis of Variceal Bleeding in Cirrhosis

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Primary Prophylaxis of Variceal Bleeding in Cirrhosis

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Primary Prophylaxis of Variceal Bleeding in Cirrhosis

What is the best method for primary prophylaxis?• Pharmacological therapy with propranolol is the best available

modality at present.• Aim of therapy with propranolol: Reduction in hepatic

venous pressure gradient to less than 12mmHg. • Dose: (Starting dose, Long acting propranolol)• In case of contraindications or intolerance to propranolol,

variceal band ligation is the treatment of choice. • In difficult situations where neither propranolol nor variceal

band ligation can be used, isosorbide mononitrate is the treatment of first choice (20 mg twice daily). 05/03/23

Primary Prophylaxis of Variceal Bleeding in CirrhosisWho should have surveillance for variceal bleeding?

• All patients with cirrhosis should be endoscoped at the time of diagnosis.

How often should cirrhotic patients be endoscoped?

• If at the time of first endoscopy no varices are observed, patients with cirrhosis should be endoscoped at three year intervals.

• If small varices are diagnosed, patients should be endoscoped at yearly intervals.

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Primary Prophylaxis of Variceal Bleeding in Cirrhosis

Which patients with cirrhosis should have primary prophylaxis?

• If grade 3 varices are diagnosed, patients should have primary prophylaxis irrespective of the severity of the liver disease.

• If patients have grade 2 varices and Child class B or C disease, they should have primary prophylaxis.

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No varices Repeat endoscopy in 3 years (sooner if decompensation occurs)

Small varices In a CTP B / C patient or variceswith red signs Nonselective b -blockers(propranolol or nadolol)Start propranolol (20 mg b.i.d.) or nadolol (20 mg q.d.)Titrate to maximal tolerable dose or a heart rate of 55 – 60.No need to repeat EGD

Management strategy after results of screening endoscopy in patients with cirrhosis

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In a CTP A patient, without red signsNonselective b -blockers optional If no b-blockers are given, repeat endoscopy in 2 years (sooner ifdecompensation occurs)Same as aboveMedium / large varices All patients independent of CTP classNonselective _ -blockers(propranolol, nadolol)or Endoscopic variceal ligationSame as aboveLigate every 1 – 2 weeks until variceal obliterationFirst surveillance endoscopy 1 – 3 months after obliteration, then every 6 – 12 months indefinitely

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Diagnosis and management strategy of patient with

acute variceal hemorrhageDiagnosis.Any of the following findings on upper endoscopy performed within 12 h of admission:Active bleeding from a varix orStigmata of variceal hemorrhage (white nipple sign) orPresence of gastroesophageal varices without another source of hemorrhage

(1 )RESUSCITATION

Site: Where haemodynamic monitoring is possible .Methods:

• 16 gauge peripheral cannulae, at least 2.• Cross match 6 units of blood.• Correct prothrombin time, platelet count.• Central venous access.• Protection of the airway by elective intubation:(i) severe uncontrolled variceal bleeding;(ii) severe encephalopathy;(iii) inability to maintain oxygen saturation above

90%;(iv) aspiration pneumonia. 05/03/23

HemodynamicsHemodynamics Blood loss(% of Blood loss(% of intravascular volume)intravascular volume)

Severity of Severity of bleedingbleeding

normalnormal < 10< 10 minorminor

Orthostatic Orthostatic hypotension or hypotension or tachycardiatachycardia

10-2010-20 moderatemoderate

shockshock 20-2520-25 massivemassive

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General management *Cautious transfusion of fluids and blood products, aiming to maintain a hemoglobin of ~ 8 g / dl*Antibiotic prophylaxis (3 – 7 days) with:Ciprofl oxacin 500 mg b.i.d. (p.o.) or 400 mg b.i.d. (i.v.) orCeftriaxone 1 g / day (i.v.) ((particularly infacilities with known quinolone resistance and in patients with two or more of the following : malnutrition, ascites, encephalopathy, serum bilirubin > 3 mg / dl

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*Specific initial managementPharmacological therapy initiated as soon as diagnosis is suspected Octreotide 50 mcg i.v. bolus followedby continuous infusion 50 mcg / h (3 – 5 days) andEndoscopic therapy (ligation preferable) performed at time of diagnostic endoscopy (performed within 12 h ofadmission)Rescue management.Considered in patients with bleeding esophageal varices who have failed pharmacological + endoscopic therapyor in patients with bleeding gastric fundal varices who have failed one endoscopic therapy:TIPS or Shunt therapy (CTP A patients whereavailable) b.i.d., twice a day, CTP, Child Turcotte Pugh; i.v., intravenous; p.o., orally;Balloon tamponade is very effective in controlling bleedingtemporarily with immediate control of hemorrhage in > 80 % of patients

)2 (TIMING OF UPPER GIT ENDOSCOPY

As soon as the patient is haemodynamically stable.

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Esophageal varices

•multiple irregular filling defects as

“string of beads” or “earthworm”

Fail to achieve hemostasis or rebleeding

Balloon tamponadeTransjugular Intrahepatic Portosystemic Shunt (TIPS)

Surgery for shunt

After endoscopic treatment…

balloon tamponade

Sengstaken-Blakemore tube(1950) esophageal balloon l) 100-150) gastric balloon (150-200) one lumen to gastric balloon one lumen for gastric aspiration one lumen to esophageal balloon

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TIPSS

Transjugular intrahepatic portasystemic stent-shunt TIPSS is a small, tubular metal device commonly called a stent that is placed in veins in the middle of the liver to permit blood flow to bypass the liver. In a TIPSS procedure, interventional radiologists use image guidance to make a tunnel through the liver to connect the portal vein to one of the hepatic veins. A stent is then placed in this tunnel to keep the pathway open.

TIPSS

Transjugular intrahepatic portasystemic stent-shunt A TIPSS is used to treat the complications of portal hypertension, including:

variceal bleeding, bleeding from any of the veins that normally drain the stomach, esophagus, or intestines into the liver. portal gastropathy, an engorgement of the veins in the wall of the stomach, which can cause severe bleeding. severe ascites (the accumulation of fluid in the abdomen) and/or hydrothorax (in the chest). Budd-Chiari syndrome, a blockage in one or more veins that carry blood from the liver back to the heart

Surgical treatment

◈ splenectomy ◈ portosystemic shunt or bypass◈ extensive devascularization around the cardia◈ liver transplantation

portacaval end-to-side shunt portacaval side-to-side shunt

mesocaval shunt splenorenal shunt

Limited Side-to-Side Portacaval Shunt

Secondary Prophylaxis of Variceal

Bleeding in Cirrhosis

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Management strategy in the prevention of recurrent variceal hemorrhage (secondary

prophylaxis)First-line therapy Nonselective β -blockers (propranolol, nadolol) Start propranolol (20 mg b.i.d.) or nadolol (20 mg q.d.)Titrate to maximum tolerable dosage or a heart rate of 55 – 60 b.p.m. No need for repeat endoscopy andEndoscopic variceal ligation Ligate every 1 – 2 weeks until variceal obliterationFirst surveillance endoscopy 1 – 3 months afterobliteration, then every 6 – 12 months

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Second-line therapy (if combined pharmacologic+ endoscopic treatment has failed)TIPS or Shunt surgery (CTP class A patients, where available) b.i.d., twice a day; b.p.m., beats / min; CTP, Child – Turcotte – Pugh; TIPS, transjugular intrahepatic portosystemic shunt; q.d., once daily.

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