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Liver Disease Overview: Cirrhosis & Portal Hypertension

Notes

Liver Disease Overview: Cirrhosis & Portal Hypertension

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Liver Pathophysiology Overview

Liver disease is a failure of liver function and/or the consequence of portal hypertension.

Injury can be acute, or it can be chronic. A liver undergoing chronic damage is less capable of recovery from acute injury.

Stages of Liver Disease:

Damage from liver disease is accumulative and progressive, and we can describe it according to stages:

  • Stage 1 is characterized by inflammation; hepatic tissues are inflamed from fighting infection or healing injuries.
  • Stage 2 is characterized by fibrosis, in which scar tissue replaces normal hepatic tissue.
  • Stage 3 is characterized by cirrhosis, which is scarring is so extensive that liver function is impaired; at this point, signs and symptoms of liver damage might start to appear (sometimes referred to as decompensation).
  • Stage 4 is liver failure, which requires urgent medical attention.

Be aware that some authors consider liver cancer to be the fifth stage.

It was previously thought that only stages 1 and 2 were reversible, but denote that newer research indicates that cirrhosis (stage 3) is also reversible.

Signs/Symptoms:

Early stages of liver disease are asymptomatic; later stages can present with jaundice, abdominal pain and swelling, edema, dark urine, pale stool, and other signs of liver dysfunction and/or portal hypertension.

We'll focus on these complications in the second part of the tutorial.

Diagnosis:

Early diagnosis is key for proper treatment, and even reversal, of damage.
The Child-Pugh score is used to grade liver functioning.

Treatments:
Vary according to the cause and extent of damage; in cases of cirrhosis or failure, transplants may be the best option.

Complications:
Complications of liver damage involve multiple organ systems and have far-reaching implications for a patient's health; let's quickly review key functions of the liver to better understand liver disease pathophysiology – and even predict it.

Pathophysiology

Liver Functions:

Energy metabolism – the liver plays key roles in carbohydrate and lipid metabolism.

Plasma protein synthesis – albumin and other binding proteins, clotting factors, angiotensinogen, IGF-1 and other proteins are synthesized by the liver.

Storage – glucose, vitamins B12, D, and K, copper, and iron are stored by the liver.

Degradation, detoxification, and clearance – the liver breaks down and/or clears several substances, including ammonia (to form urea), bilirubin, drugs, and other toxins.

Sources of Liver Injury:

Infections, such as viral hepatitis and Schistosomiasis.

Fatty liver disease, including alcoholic and nonalcoholic forms.

Genetics and hereditary disorders, such as hereditary hemochromatosis.

Autoimmune hepatitis.

Biliary tract diseases, such as primary sclerosing cholangitis, primary biliary cholangitis, and secondary biliary cholangitis.

Cirrhosis & Portal Hypertension:

Hepatic injury results in hepatocellular dysfunction and/or vascular changes, and that, as we've discussed, chronic injury can lead to:

Cirrhosis, which is characterized by the presence of fibrosis and regenerative nodules with fatty changes, and,

Portal hypertension, which is increased hepatic blood pressure (above 6 mmHg).

Cirrhosis

Complications of Chronic Liver Disease/Damage

Impaired synthesis and storage can lead to coagulopathy, which results from decreased storage of vitamin K and synthesis of clotting factors.

Impaired hepatic degradation, detoxification and clearance can lead to hepatic encephalopathy and asterixis.

Hepatic encephalopathy is the result of toxin build-up in the blood; ammonia, specifically, is thought to be a key culprit.

Asterixis, aka, "flapping hand tremor" or "liver flap" is the inability for a patient to sustain a posture due to involuntary, brief, "shock-like" movements.

To test for this, have a patient sit with closed eyes, outstretched arms, dorsiflexed wrists, and spread fingers – if they suddenly "flap" their hands, this is asterixis (which is indicative of metabolic encephalopathy, and not specific to hepatic dysfunction).

Drug reactions and sensitivities can lead to, for example, elevated estrogen levels, which can cause spider angiomas (spider-looking collections of blood vessels visible beneath the skin), palmar erythema (reddening of the palms and fingers), and gynecomastia (enlargement of breast tissue in males).

Impaired bile flow can lead to hyperlipidemia, jaundice, and malabsorption of GI contents.

Glucose metabolism is dynamically altered in liver damage so that patients can be hyper- or hypoglycemic.

The complications we've addressed so far are largely the result of hepatic tissue dysfunction.

Next, let's consider vascular changes that result from portal hypertension, which causes systemic vasodilation and hypotension (via complicated mechanisms that are beyond the scope of this tutorial).

  • Varices are collateral blood vessels that form to provide alternative blood flow routes; these pose a
    significant risk for hemorrhage, and are an important cause of GI bleeding.
  • Ascites & Edema: Ascites refers to the accumulation of fluid in the peritoneum caused by systemic dilation that allows fluid leakage. Ascites is a main complication of cirrhosis, and can lead to peritonitis.
  • Spontaneous Bacterial Peritonitis (SBP) is an acute infection resulting from bacteria and endotoxins leaking from the GI tract, and can lead to septic shock if not treated promptly.
  • Renal insufficiency and failure are the result of local vasoconstriction (in response to systemic hypotension) and inflammatory processes that reduce filtration. New research shows that spontaneous bacterial peritonitis is often a trigger for renal failure, as it induces the release of pro-inflammatory molecules that contribute to renal dysfunction.
  • Hepatopulmonary syndrome, in which pulmonary vasodilation leads to a ventilation/perfusion mismatch, reduced oxygenation, and hypoxemia.
  • Increased risk of liver cancer.

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