Alya Putri Khairani | 130110110220 | A4

Major Complication of Cirrhosis

The clinical course of patients with
advanced Cirrhosis is often
complicated by a number of important
sequelae that can occur regardless of
the underlying cause of the Liver
Disease

PORTAL HYPERTENSION

DEFINITON
Defined as the elevation of the hepatic venous pressure gradient (HVPG) to >5 mmHg. Portal hypertension is
caused by a combination of two simultaneously occurring hemodynamic processes:
1. Increased intrahepatic resistance to the passage of blood flow through the liver due to cirrhosis and
regenerative nodules
2. Increased splanchnic blood flow secondary to vasodilatation (vasodilatory substances, most importantly
Nitric Oxide Synthase) within the splanchnic vascular bed
CLASSIFICATION
The causes of portal hypertension are usually subcategorized as prehepatic, intrahepatic, and posthepatic
Prehepatic
Affecting the portal venous system before it enters the liver; they include Portal vein thrombosis and Splenic vein
thrombosis. Posthepatic
Encompass those affecting the Hepatic veins and venous drainage to the heart; they include BCS, Venoocclusive
disease, and Chronic right-sided cardiac congestion
Intrahepatic
Represented by the major forms of Cirrhosis

Postsinusoidal causes include venoocclusive disease

Presinusoidal causes include congenital hepatic fibrosis and schistosomiasis

Sinusoidal causes are related to cirrhosis from various causes

CLINICAL FEATURES
Physical findings in cirrhosis that might suggest the presence of portal hypertension include muscle wasting, spider
angiomata, jaundice, abdominal collateral vessels, and an altered mental status
The three primary complications of portal hypertension are Gastroesophageal Varices with Hemorrhage,
Ascites, and Hypersplenism.

Alya Putri Khairani | 130110110220 | A4

So, in endoscopy, we will find: esophageal or gastric varices, with the development of ascites along with peripheral
edema, or with an enlarged spleen with associated reduction in platelets and white blood cells on routine
laboratory testing
* Gastroesophageal Varices with Hemorrhage
Approximately 515% of cirrhotics per year develop varices, and it is estimated that the majority of
patients with cirrhosis will develop varices over their lifetime. Furthermore, it is anticipated that roughly
one-third of patients with varices will develop hemorrhage
Several factors predict the risk of bleeding, including the severity of cirrhosis (Childs class); the height of
wedged-hepatic vein pressure; the size of the varix; the location of the varix; and certain endoscopic
stigmata, including red wale signs, hematocystic spots, diffuse erythema, bluish color, cherry-red spots, or
white-nipple spots
DIAGNOSIS

Presence of thrombocytopenia; the appearance of an enlarged spleen; or the development of ascites,

encephalopathy and/or esophageal varices with or without bleeding

Interventional radiologic procedures can be performed to determine wedged and free hepatic vein
pressures that will allow for the calculation of a wedged-to-free gradient, which is equivalent to the portal
pressure. The average normal wedged-to-free gradient is 5 mmHg, and patients with a gradient >12
mmHg are at risk for variceal hemorrhage
PREVENTION AND MANAGEMENT
Nonselective -blockers (propranolol, nadolol, and timolol) are the
cornerstone of long-term management in patients with portal
hypertension.
The use of -blockers in patients with cirrhosis is limited by their sideeffect profile, which includes hypotension, fatigue, lethargy, depression,
and dyspnea in patients with associated
pulmonary disease. Due to concomitant diseases such as reactive airway
disease, congestive heart failure, bradycardia, and heart block, 1520% of
patients are unable to take -blockers.
In patients who are candidates for -blocker therapy, dose titration
should be adjusted to patient tolerance

2 SPLENOMEGALY & HYPERSPLENISM

Congestive splenomegaly

Clinical features: presence of an enlarged spleen on physical examination and the development of
thrombocytopenia and leukopenia in patients who have cirrhosis

Some patients will have fairly significant left-sided and left upper quadrant abdominal pain related to an
enlarged and engorged spleen
Hypersplenism with the development of thrombocytopenia is a common feature of patients with cirrhosis and is
usually the first indication of portal hypertension

3 ASCITES

Five major factors are involved in the pathogenesis of

cirrhotogenic
DEFINITION
ascites:
Portal hypertension,
Hypoalbuminemia,
Sodium
The
accumulation
of fluid within
the peritoneal cavity
retention, Water retention, and increased lymph formation.
PATHOGENESIS
Development
of Cirrhotogenic
{) Intrahepatic
resistance Ascites
{) Portal pressure +
Vasodilatation of the Splanchnic arterial system = {)
Production of Splanchnic
lymph.
Vasodilating factors such as nitric oxide Causing activation
of the Renin-Angiotensin-Aldosterone system with the
development of Hyperaldosteronism Sodium retention
The renal effects of {) Aldosterone Sodium retention

Alya Putri Khairani | 130110110220 | A4

Sodium retention fluid accumulation and expansion of the extracellular fluid volume Formation of peripheral
Edema and Ascites.
Hypoalbuminemia and reduced plasma oncotic pressure also contribute to the loss of fluid from the vascular
compartment into the
peritoneal cavity. Hypoalbuminemia is due to decreased synthetic function in a cirrhotic liver.
CLINIAL FINDINGS

In abdominal girth that is often accompanied by the development of peripheral edema. The development
of ascites is often insidious

Hepatic hydrothorax may contributing to respiratory symptoms

Patients with massive ascites are often malnourished and have muscle wasting and excessive fatigue and
weakness
DIAGNOSIS

Abdominal imaging

Bulging flanks, fluid wave, or may have the presence of shifting dullness.
This is determined by taking patients from a supine position to lying on either their left or right side and
noting the movement of the dullness top percussion

Diagnostic paracentesis be performed to characterize the fluid, include the determination of total protein
and albumin content, blood cell counts with differential, and cultures. In the appropriate setting, amylase
may be measured and cytology performed

4 SPONTANEOUS BACTERIAL PERITONITIS

DEFINITION
A common and severe complication of ascites characterized by spontaneous infection of the ascitic fluid without an
intraabdominal source
ETIOLOGY & PATHOGENESIS
Bacterial translocation is the presumed mechanism for development of SBP, with gut flora traversing the intestine
into mesenteric lymph nodes, leading to bacteremia and seeding of the ascitic fluid. The most common organisms
are Escherichia coli and other gut bacteria; however, gram-positive bacteria, including Streptococcus viridans,
Staphococcus aureus, and Enterococcus sp., can also be found
DIAGNOSIS

Fluid sample has an absolute neutrophil count >250/mm3

Bedside cultures should be obtained when ascitic fluid is tapped

May present with fever, altered mental status, elevated white blood cell count, and abdominal pain or
discomfort, or they may present without any of these features

Peritoneal taps are important for making the diagnosis

TREATMENT
Use of a third-generation cephalosporin such as cefotaxime or ceftazidime, given at a dosage of 2 g/8 h. Other
third-generation cephalosporins, such as ceftizoxime or ceftriaxone, are also suitable antibiotics. The
cephalosporins have been shown to be as effective
as, if not more effective than, combinations of ampicillin and an aminoglycoside

5 HEPATORENAL SYNDROME
DEFINITION
Characterized by functional kidney failure in patients with end-stage liver disease. It results in intense renal
vasoconstriction without any other identifiable kidney pathology

Type 1 hepatorenal syndrome

Characterized by rapid and progressive impairment of renal function defined by a doubling the initial serum
creatinine to a level higher than 2.5 mg/dL or a 50% reduction of the initial 24-hour creatinine clearance to
a level lower than 20 mL/min in less than 2 weeks

Alya Putri Khairani | 130110110220 | A4

Type 2 hepatorenal syndrome

Impairment in renal function (serum creatinine > 1.5 mg/dL) that does not meet the criteria for type 1.
Prerenal failure is a preischemic state and may lead to ischemic tubular necrosis

PATHOGENESIS
Cirrhosis Activation of the Renin-Angiotensin and sympathetic nervous systems {) Levels of renin,
aldosterone, and norepinephrine.

If undergo diuresis successfully () Levels of renin, aldosterone, norepinephrine, and antidiuretic

hormone
In patients with end-stage liver disease complicated by hepatorenal syndrome () Systemic vascular
resistance and splanchnic arteriolar vasodilation
and norepinephrine

() Levels of renin, aldosterone, antidiuretic hormone,

DIFFERENTIAL DIAGNOSIS
Acute tubular necrosis and other forms of renal disease such as glomerulonephritis and vasculitis

CLINICAL FINDINGS

TREATMENT

Preventive measures
Hepatorenal syndrome develops in patients with systemic
bacterial infections (ie, spontaneous bacterial peritonitis or
severe alcoholic hepatitis, or both), and it is important to
provide prophylactic treatment
to guard against its development. This includes the
administration of IV albumin (1.5 g/kg) at the time of
diagnosis of spontaneous bacterial peritonitis or sepsis, and
another dose of albumin (1.0 g/kg) after 48 hours of
antibiotic treatment

Vasopressor therapy
Accumulating data suggest that combination therapy with
midodrine and octreotide may be effective and safe. The
rationale for such therapy is that midodrine is a systemic
vasoconstrictor and addresses the question of inappropriate
vasodilation, and octreotide is an inhibitor of endogenous
vasodilators

6 HEPATIC ENCEPHALOPATHY
DEFINITION
An alteration in mental status and cognitive function occurring in the presence of liver failure. In acute liver injury
with fulminant hepatic failure, the development of encephalopathy is a requirement for a diagnosis of fulminant
failure. Encephalopathy is much more commonly seen in patients with chronic liver disease
PATHOGENESIS

Alya Putri Khairani | 130110110220 | A4

Although the precise pathogenesis of hepatic

encephalopathy is unknown, accumulation of nitrogenous
products derived from the gut can have adverse effects on
brain function and is believed to play a major role
CLINICAL FINDINGS

Physical examination
Fetor hepaticus; this is a pungent breath odor caused
by the breakdown products of sulfur-containing amino
acids such as cysteine and methionine and consisting of
dimethyl sulfides methanethiol and ethanethiol
Asterixis or a metabolic flapping tremor
Focal neurologic abnormalities such as increased deep
tendon reflexes, unilateral or bilateral Babinski sign, and
other findings such as ataxia,
dysarthria, tremor, or myopathy, usually with longstanding
chronic systemic shunting

Mental status changes

TREATMENT

7 MALNUTRITION IN CIRRHOSIS
Because the liver is principally involved in the regulation of protein
and energy metabolism in the body, it is not surprising that
patients with advanced liver disease are commonly malnourished.
Once patients become cirrhotic, they are more catabolic, and
muscle protein is
Metabolized

8 ABNORMALITIES IN COAGULATION
There is decreased synthesis of clotting factors and impaired
clearance of anticoagulants. In addition, patients may have
thrombocytopenia from hypersplenism due to portal hypertension.
Vitamin Kdependent clotting factors are Factors II, VII, IX, and X.
Vitamin K requires biliary excretion for its subsequent absorption; thus, in patients with chronic cholestatic
syndromes, vitamin K absorption is frequently diminished.
More commonly, the synthesis of vitamin Kdependent clotting factors is diminished because of a decrease in
hepatic mass, and under these circumstances administration of parenteral vitamin K does not improve the clotting
factors or the prothrombin time. Platelet function is often abnormal in patients with chronic liver disease, in
addition to decreases in platelet levels due to hypersplenism.

Alya Putri Khairani | 130110110220 | A4

9 BONE DISEASE IN CIRRHOSIS

Osteoporosis is common in patients with chronic cholestatic liver disease because of malabsorption of vitamin D
and decreased calcium ingestion. The rate of bone resorption exceeds that of new bone formation in patients with
cirrhosis resulting in bone loss

10 HEMATOLOGIC ABNORMALITIES IN CIRRHOSIS

Numerous hematologic manifestations of cirrhosis are present, including anemia from a variety of causes including
hypersplenism, hemolysis, iron deficiency, and perhaps folate deficiency from malnutrition. Macrocytosis is a
common abnormality in red blood cell morphology seen in patients with chronic liver disease, and neutropenia may
be seen as a result of hypersplenism

References:
Harrison Internal Medicine 17th edition
Current Diagnosis and Treatment in Gastroenterology, Hepatology, and
Endoscopy