Portal Hypertension-Pola 060810

gastro.ucsd.edu

Portal Hypertension-Pola 060810

Portal Hypertension

Core Curriculum

June 8, 2010

Suresh Pola & David Kravetz

Definition of Portal Hypertension‐ an increase in portal pressure to 6mmHg or greater

ANATOMY

Normal Portal Circulation­

Portal venous system carries capillary blood from the esophagus, stomach, intestines, pancreas,

gallbladder, and spleen to the

liver

Figure 90‐1. Anatomy of the portal

circulation. Blood vessels that constitute the

portal circulation and hepatic outflow tracts

depicted.

(Sleisenger & Fordtran 2010)

are

• Circulatory system of the

normal liver‐ high compliance,

low‐resistance system

• Able to accommodate large

blood volumes without

substantial increases in portal

pressure

• Dual supply with 75% from PV

and 25% HA, which converge

into channels “hepatic

sinusoids”

• Hepatic Arterial Buffer

Response‐ when PV is reduced

(i.e, PVT), arterial inflow

increases to maintain total hepatic blood flow. In HAT, PV inflow increases in a compensatory mechanism

as well

Figure 90‐2. Anatomy of the hepatic microvasculature. A, Normal sinusoidal microanatomy is depicted. The sinusoidal lumen is lined by fenestrated

sinusoidal endothelial cells that allow the transport of macromolecules to the abluminal space of Disse. Quiescent hepatic stellate cells reside within

this space, adjacent to hepatocytes and endothelial cells. B, In cirrhosis, a number of changes occur in the hepatic microcirculation, including loss of

fenestrae in endothelial cells (defenestration), constriction of sinusoids, and activation of hepatic stellate cells with ensuing deposition of collagen

and increased contractility. (Sleisenger & Fordtran 2010)


PATHOPHYSIOLOGY

Mediators in Portal Pressure:

• Nitric Oxide (NO) ‐derived from endothelial

NO synthase, is produced in response to

shear stress , inflammation and other stimuli

in the sinusoids and leads to hepatic

vasodilation

o In cirrhosis decreased NO availability

is thought to contribute to hepatic

vascular resistance causing portal

hypertension ; the effects are

probably minor since NO donors do

not change significantly the pressure

• Endothelin‐1 (ET‐1): also released by endothelial cells; promotes vasoconstriction and may also

paradoxically promote vasodilatation

• Carbon monoxide, norepinephrine, angiotensin, prostaglandins, thomboxane, leukotrienes, hydrogen

sulfide

Hemodynamics of Portal Hypertension

o Typically involves increases in portal resistance and inflow (Ohm’s law)

o Pressure gradient in the portal circulation is a function of portal flow are resistance to flow

o causes collaterals to form from the high pressure veins to the low pressure veins that are

insufficient for normalizing portal pressure and cause complications such as esophageal varices.

Mechanical Factors‐ difficult to fix

o fibrosis, nodularity of cirrhotic liver, distortion of vascular architecture,

remodeling in systemic and splanchnic vasculature from chronic increases in flow and shear stress

Vascular Factors ‐ important, potentially reversible, targets for therapies

o intrahepatic vasoconstriction, contributes to increased resistance

o splanchnic vasodilation

o systemic vasodilation


SEQUELAE OF PORTAL HYPERTENSION

Hyperdynamic Circulation

o Chronic liver disease + portal HTN associated with decreased peripheral vascular resistance,

increased cardiac output, and increased total blood volume

o results in increased portal venous inflow

o peripheral and splanchnic vasodilation, reduced MAP, increased cardiac output (excess NO)

Collateral circulation and varices

o portal vein‐systemic collateral circulation develops and expands in response to elevation of portal

pressure

o flow reversal (towards the systemic venous circulation)

o Anatomy of Varices/Collaterals:

• Rectal varices: IMV connects with pudendal vein

• Umbilicus/caput medusae: vestigial umbilical vein connects with L portal vein

• Distal esophagus/proximal stomach: GE varices between portal venous system and

systemic venous system

• Gastric zone‐ extends for 2‐3 cm below GE junction, come together at the upper end

of the cardia of the stomach; drain into short gastric and left gastric veins

• Palisade zone‐ extends 2‐3 cm prox to gastric zone into the lower esophagus

o most prone to bleeding because they cannot decompress into periesophageal

veins

• Perforating zone‐ connect the veins in the esophageal submucosa and the external

veins

• Truncal zone‐ 10cm long, most proximal zone, four longitudinal veins

o least likely to bleed because they can decompress into the peri‐esophageal

veins (to azygous system)

• lower esophagus and cardia drain through coronary vein‐>portal vein


• fundus drain through short gastric veins‐>splenic vein

• isolated gastric varices seen in SVT

• Because most collaterals are through the coronary vein, typically intrahepatic portal HTN

has just esophageal varices or gastric varices in continuity with esophageal varices

• GE varices‐ require 10 mm Hg portal pressure gradient to form and 12 mm Hg to bleed

MEASUREMENT OF PORTAL PRESSURE

• HVPG = WHVP ‐ FHVP

• (hepatic vein portal gradient = wedged hepatic vein pressure minus free hepatic vein pressure)

• Splenic pulp pressure measurement (invasive, cumbersome)

• Direct portal vein measurement (invasive)

• Variceal pressure measurement (not routinely done in clinical practice)

• Liver stiffness measurement (ultrasound fibroelastrography or MR elastography) to measure presence of

portal HTN (can’t measure actual pressure)

HVPG

o femoral or jugular approach

o (old way) wedge hepatic vein pressure: catheter into hepatic vein until can’t go any furtherpressure

across a water column represents sinusoidal pressure

o (new way) occlusion balloon in hepatic vein

• Potential uses of HVPG:

o monitor portal pressure in patients taking drugs used to prevent variceal bleeding

o prognostic marker

o end‐point in trials using pharmacologic agents for treatment of portal HTN

o assess the risk of hepatic resection in patients with HCC and cirrhosis

o help delineate cause of portal HTN

• Problems with HVPG:

o when using a catheter, more fibrotic areas of liver may give higher pressure measurements than

less fibrotic areas (highly unlikely in practice)

• balloon‐occluding catheter in right hepatic vein can overcome this and represent sinsuoidal

pressure over a larger area of liver

o not effective for detecting presinusoidal causes of portal hypertension (only for sinusoidal or post

sinusoidal)

• underestimates sinusoidal pressure in early PBC (typically presinsuoidal early on then

more generalized later on)

• Benefits of HVPG:

o not altered in increased intra‐abdominal pressure because both are elevated (that is why free

hepatic vein pressure is used as the zero reference)

o safe

o reproducible/accurate

• Clinical significance develops when pressure is > 10mmHg

• Results of portal hypertension: variceal hemorrhage (>12mmHg), hepatic encephalopathy, and ascites

(>10‐12mmHg)

• Table 90­1 ­­ The Use of Hepatic Venous Pressure Gradient in the Differential Diagnosis of Portal

Hypertension

TYPE OF PORTAL

HYPERTENSION

WHVP FHVP HVPG


Prehepatic Normal Normal Normal

Presinusoidal Normal Normal Normal

Sinusoidal Increased Increased Increased

Postsinusoidal Increased Normal Increased

Posthepatic

Heart failure Increased Increased Normal

Budd‐Chiari syndrome — Hepatic vein cannot be

cannulated


• FHVP, free hepatic vein pressure; HVPG, hepatic venous pressure gradient; WHVP, wedged

hepatic venous pressure.

CAUSES OF PORTAL HYPERTENSION

o Common:

• Cirrhosis

• Extra‐hepatic Portal Vein Thrombosis

• Idiopathic Portal HTN

• Schistosomiasis

o Less Common:

• Fibropolycystic liver disease

• Hereditary Hemorrhagic Telangectasia

• Malignancy

• Myeloproliferative Disorders ( usually and mainly through nodular regenerative

hyperplasia)

• Nodular Regenerative Hyperplasia

• Partial Nodular Transformation of the Liver

• Sarcoidosis

• Splanchnic AV Fistula (through development of increased sinusoidal resistance and

fibrosis)

Disease specific notes on portal hypertension

o Alcoholic liver disease‐ portal hypertension can occur without cirrhosis but is more pronounced

with it

o Autoimmune hepatitis‐ may be associated with portal hypertension in the absence of cirrhosis,

however risk of variceal bleeding is low

o Hemochromatosis‐ portal HTN can be seen prior to cirrhosis, depends on severity of fibrosis

• can have bleeding varices even if HVPG < 12mmHg suggesting a presinusoidal component of

portal HTN

• phlebotomy can reduce portal pressures

o PBC‐ may also be associated with portal HTN in absence of cirrhosis; depends on histologic stage of

disease

o Early stages: mostly presinusoidal portal HTN, later on a sinusoidal component develops

o PSC & biliary strictures‐ can cause portal hypertension if long duration of obstruction but has been

seen to develop as quickly as a few months after CBD obstruction in chronic alcoholic pancreatitis;

regresses after relief of biliary obstruction


o

o

o

Schistosomiasis

• may be the commonest cause of portal HTN worldwide

• bleeding from EV‐ major cause of death in hepatosplenic schistosomiasis

• results from presinusoidal obstruction caused by eggs of Schistosoma mansoni and

japonicum in the presinusoidal portal venules‐‐>granulomatous inflammation‐>

presinusoidal and periportal fibrosis “pipestem fibrosis”

• periportal collagen deposition leads to progressive obstruction of portal blood flow, portal

HTN, and variceal bleeding along with splenomegaly and hypersplenism

• lobular architecture preserved

• often have normal HVPG (presinusoidal nature early on)

• often treated with portosystemic shunt surgery to treat variceal bleeding.

Extrahepatic PVT

• Causes: P. vera, other hematologic/myeloproliferative disorders; hypercoagulable states;

abdominal trauma or postoperative (especially post splenectomy)

• 6% of patients with cirrhosis will get PVT (old studies before our modern imaging)

• 25% of patients with cirrhosis & HCC (old studies before our modern imaging) will get PVT

Idiopathic Portal HTN

• high portal pressures with normal liver histology (abnormal sinusoidal fibrosis on scanning

microscopy or EM)

• Rare in U.S.

• causes/contributing factors have been speculated to include: recurrent infections, HIV

(from HAART vs from HIV itself), arsenic intoxication, vinyl chloride exposure, and

hypervitaminosis A, genetic factors (HLA DR3), altered immune state, and hypercoagulable

state

• splenomegaly, hypersplenism, variceal bleeding

• ascites is uncommon

• normal HVPG (presinusoidal)

• not to be confused with incomplete septal cirrhosis‐ incomplete septa and liver nodularity

with clinical manifestations similar to cirrhosis

MANAGEMENT OF PORTAL HYPERTENSION

• Pharmacologic therapies (somatostatin/octreotide, non selective BB)

o Vasopressin‐ causes splanchnic vasoconstriction, reduces portal venous inflow, and reduces portal

pressure

• serious side effects: bowel necrosis, reduced cardiac output, bradycardia, increased

afterload, antidiuresis, hyponatremia

o Terlipressin‐ semisynthetic analog of vasopressin‐ lower systemic side effects

• survival advantage in patients with variceal bleeding

• NOT approved in US but undergoing FDA evaluation

o Somatostatin‐ short half life, synthetic analogs used (octreotide)

• inhibits glucagon release

• decreases postprandial splanchnic blood flow

• octreotide half life 80‐120min

• does not reduce portal pressures

• decreases postprandial increase in portal pressure

• evidence if mixed for variceal bleeding

o Nonselective Beta Blockade‐ reduction in portal pressures:

• B1 adrenergic receptor blockade: decreases cardiac output


• B2 adrenergic receptor blockade: vasodilation in mesenteric circulation, allows

unopposed alpha 1 adrenergic receptors‐‐>

decreased portal flow

• most effective if HVPG used but not clinically practical

• TIPS (or DIPS)

• Surgery

o Used as salvage therapy when standard management with pharmacologic and endoscopic therapy

fails in patients with Child class A cirrhosis

o live far distance from centers that can manage variceal bleeders adequately

o patients in whom cross‐matched blood products are difficult

o

o

Non shunt: esophageal transection, devascularization procedures

Shunts: selective (distal splenorenal shunt), partial portosystemic (synthetic graft from portal vein

to IVC), portacaval shunt (side to side)‐ should avoid in potential OLT candidates but can be done

during the actual OLT in concurrent bleeders

REFERENCES

• Sleisenger & Fordtran Gastrointestinal and Liver Diseases. 2010

• Up to Date “Noncirrhotic portal hypertension: Portal fibrosis and schistosomiasis”

More magazines by this user
Similar magazines