Chapter 10 Selected Diseases and Disorders of the Digestive System
10p19 Cirrhosis: Systemic Effects and Clinical Manifestations
Zoë Soon
Cirrhosis: Systemic Effects and Clinical Manifestations
Pathophysiology and Systemic Manifestations
1. Vascular Changes and Portal Hypertension
- Damage to blood vessels causes engorged and leaky vessels.
- Results in portal hypertension, leading to:
- Ascites: Fluid accumulation in the abdominal cavity.
- Edema from fluid leakage into tissues.
- Splenomegaly (enlarged spleen) due to blood congestion.
2. Blood Volume and Kidney Response
- Hypovolemia triggers renin-angiotensin-aldosterone system (RAAS):
- Increased aldosterone and ADH retention of water and salt.
- Worsens portal hypertension and ascites.
- Reduced plasma proteins (like albumin):
- Causes fluid shifts into tissues, worsening edema and ascites.
3. Liver Cellular Dysfunction
- Loss of hepatocyte function:
- Reduced gluconeogenesis.
- Decreased bile production → poor fat absorption and deficiency of fat-soluble vitamins (D, E, K).
- Impaired protein synthesis, affecting clotting factors, leading to bleeding.
4. Bilirubin Metabolism and Jaundice
- Inability to conjugate bilirubin results in hyperbilirubinemia.
- Yellow pigmentation of skin and eyes (jaundice).
5. Hepatic Encephalopathy
- Failure to detoxify ammonia and other toxins.
- Build-up causes:
- Tremors.
- Confusion.
- Lethargy.
- Coma and/or death.
6. Impaired Hormone Metabolism
- Estrogen not inactivated properly.
- Causes gynecomastia in men (breast development).
- Irregular menses in women.
- Impotence in men.
Clinical Signs & Symptoms (Summary Table)
| Early Signs and Symptoms: | |
| Fatigue and weakness | Hepatocytes have reduced ability to perform gluconeogenesis (contributing to less blood glucose).
Hepatocyte death is accompanied by inflammation, which can stimulate mental and physical fatigue. Hepatocytes are less able to convert protein break-down product, ammonia (toxic) to urea for excretion by the kidneys. Ammonia impairs brain function. |
| Nausea, vomiting, anorexia, and diarrhea | Toxins (e.g., ammonia) can stimulate emetic center.
Ascites creates pressure on stomach, which can stimulate nausea |
| Weight loss, malabsorption | Hepatocytes have reduced ability to produce bile, decreasing the ability to emulsify dietary fats, and therefore reducing the ability to absorb dietary fats and fat-soluble vitamins (including vitamin K which is required for the production of clotting factors). |
| Anemia | RBC production is reduced due to toxins (e.g., ammonia) and malabsorption of vitamin B12 and ability to store iron (the liver is the primary storage site for iron). |
| Pruritis (itchy skin) | Due to liver damage resulting in impaired flow of bile into gall bladder. Bile salts accumulate in blood which irritates sensory nerves in the skin. |
| Spider angiomas (nevi)
Gynecomastia, Irregular menses Testicular atrophy, Reduced libido |
Due to the liver unable to breakdown estrogen which accumulates, giving rise to vasodilation and angiogenesis.
Due to increased estrogen stimulating growth breast tissue and disrupting uterine cycle. Due to decreased testosterone |
| Pain under ribs on right side | Due to stretching of liver capsule during inflammation |
| Later Signs and Symptoms: | |
| Jaundice | Due to reduced conjugation of bilirubin by hepatocytes, leading to hyperbilirubinemia |
| Dark urine
Pale stools |
Due to hyperbilirubinemia
Due to less bile production |
| Easy bruising and bleeding (e.g., nose bleeds) | Due to reduced production of clotting factors by hepatocytes. |
| Ascites | Due to liver fibrosis pinching off blood flow to the liver, resulting in the engorgement of the portal vein, leading to portal hypertension and leakage of fluid from the portal vein into the peritoneal cavity. |
| Edema of intestinal wall | Due to portal vein hypertension. Congestion in intestinal wall can impair digestion and absorption. |
| General edema and ascites | Due to reduced blood flow to kidneys (due to leakage of fluid into peritoneum, ascites), stimulating kidneys to secrete renin and activate aldosterone and ADH, which increase water and salt reabsorption, increasing blood volume.
Due to hepatocytes reduce ability to produce plasma proteins including albumin, which are required for transport of nutrients as well as ensuring osmotic pressure within blood vessels. Without plasma proteins (solute), blood vessels are more leaky. Blocked lymphatics |
| Esophageal varices (enlarged veins) | Esophageal veins become engorged as liver fibrosis pinches off blood flow into the liver, causing blood to back up into the esophageal veins, which become engorged. |
| Vomiting blood (hematemesis), black tarry stools (melena) | Due to bleeding from esophageal or gastric varices (enlarged veins), as the esophageal/gastric blood vessels become thin and fragile and are susceptible to tears as food passes through the esophagus/stomach. Rectal varices can also occur. |
| Splenomegaly and
Leukopenia, Thrombocytopenia |
Due to portal vein hypertension, blood backs up into spleen causing damage and trapping and possible destruction of WBCs and platelets within spleen. The spleen normally stores 1/3rd of the body’s platelets. Congestion in spleen can also increase hemolysis.
Increased risk of infection |
| Hepatic encephalopathy (confusion, memory loss, forgetfulness, personality changes, irritability, disinterest in personal care) | Due to hepatocytes unable to degrade and clear toxins (e.g., ammonia, the natural break-down product of proteins) from the body. |
| Cerebral edema, kidney failure | Due to altered blood chemistry (abnormal electrolytes, increased ammonia, reduced nutrients). |
| Dyspnea
Fast heart rate |
Upward pressure from ascites on diaphragm
Activation of the sympathetic response due to poor blood flow and reduced blood oxygenation. |
Conclusion
- Cirrhosis causes widespread organ dysfunction due to fibrosis, vascular changes, and cellular impairment.
- Symptoms develop gradually but can be life-threatening if untreated.
- Management involves addressing symptoms, preventing complications, and possibly liver transplantation.
