Clinical manifestations of Cirrhosis

Jennifer Kong

Learning Objectives

By the end of this section, you will be able to:

  • Explain the clinical manifestations associated with loss of hepatocyte number and function
  • Define portal hypertension and possible consequences

Cirrhosis causes many signs and symptoms, beyond the liver. As it all begins with liver damage, nausea and abdominal pain are often the most common complaint – particularly in the right upper quadrant.

As such, these manifestations can be classified as problems with increased liver pressure due to the fibrotic scarring (portal hypertension) and loss of hepatocyte number and function.

Manifestations due to loss of hepatocyte number and function :

  • Bleeds due to inability to clot:  the liver makes many of the clotting factors needed for blood clotting. It also makes the hormone thrombopoietin which stimulates the daily production of platelets – also needed for clotting.  Thus, cirrhosis has easier chance to bleed and can look like small pinpoint bruises (petechiae), cm large bruises (purpura), or large areas (ecchymoses).  Areas with frequent trauma may also have bleeds (e.g. bleeds within the GI tract will look like vomit that is bloody or the appearance of coffee grounds;  stool that is black and tar-like or bright red)
  • Swelling of all tissue (peripheral edema), especially in lower limbs:  liver makes the plasma protein albumin  which has many functions:  one of which is being the major osmotic solute to help retain water within the blood.  A lower amount of albumin in the blood means there is less osmotic pressure (i.e. less of an osmotic pull of water) from the tissues into the blood. The result is tissue swelling known as edema.  Given the effects of gravity and venous return, this edema will be most noticeable in the lower limbs but will be occuring in all parts of the body during hypoalbuminemia & cirrhosis.
  • Fatigue and weakness due to low storage of nutrients and vitamins: as the liver stores nutrients (e.g. starch) and minerals (e.g. iron), cirrhosis leads to poor availability of these storage items.  Fatigue and weakness are common complaints – due to the anemia (low iron) and hypoglycemia (low sugar availability).
  • Low blood sugar (hypoglycemia):  the liver is responsible for making glucose available from its conversion of starch to glucose (glycogenolysis) or fats/proteins to glucose (gluconeogenesis).  Without hepatocytes, the body may not be able to maintain a constant level of blood sugar (i.e. blood glucose).  Signs of low blood sugar affect the brain as a result of neurons being poorly equipped to store glucose and heavily reliant on a constant supply of blood glucose.  Symptoms therefore can include:  confusion, irritability, fatigue, depressed levels of consciousness, shaking, sweating leading to cold clammy skin.  Low blood glucose levels induce a sympathetic response and increased heart and respiratory rate.
  • Vitamin and hormone activation/removal:  the liver activates certain hormones (e.g. Vitamin D) and removes others when in excess (e.g. estrogen).  Loss of hepatocytes will manifest in deficiencies in vitamins (e.g. susceptibility to bleeding from Vit K deficiency; decreased bone density from Vit D deficiency) and possible disturbances in the balance of sex hormones. Excessive estrogen in males may manifest as gynecomastia, whereas excessive hormones in pre-menopausal females will result in disturbances to the menstrual cycle.

Another problem can occur involving bilirubin.  In this case, there are sufficient hepatocytes to conjugate bilirubin but not drain it efficiently into the bile ductules, conjugated bilirubin can enter the central vein within the lobule, and eventually the hepatic vein and IVC. This conjugated bilirubin will be excreted through the kidneys – but due to the high amount of bilirubin, the urine will look dark brown akin to the colour of steeped tea.

  • Jaundice:  hepatocytes are responsible for elimination of the heme group when RBCs die and components are recycled.  The liver performs an enzymatic modification to the hydrophobic bilirubin (unconjugated) in a process called conjugation.  Conjugated bilirubin is water soluble and can now travel in the blood for elimination through the kidneys.   However, with less hepatocytes, unconjugated bilirubin can’t be conjugated and excreted:  as such, the unconjugated bilirubin continues to circulate the bloodstream and is deposited in fat stores such as the hypodermic layer of skin (see Metastatic melanoma).  As unconjugated bilirubin is a yellow pigment, the skin will appear yellow – giving rise to the term jaundice. Similarly, the bilirubin pigment has a high affinity to the elastin in the sclera of eyes – giving rise to a yellowing of the white of the eyes known as scleral icterus.
  • Loss of bile production and/or impaired bile flow:  hepatocytes combine cholesterol, salts, and conjugated bilirubin to form bile salts.  These bile salts form bile which normally drains to the duodenum. There, the bile will emulsify fats in the GI tract, making many small lipid droplets to help provide ample surface area for lipid digestion.   Loss of hepatocytes will cause less bile to be made and thus, less fat digestion.  Fatty stools and diarrhea may result.    Similarly, if the scar tissue within the liver fully blocks bile flow into the duodenum,  the lack of bile in the GI tract will manifest as pale, grey/white stool as bilirubin in stool gives stool its distinctive colour.  This can lead to malabsorption of fat-soluble vitamins (e.g. vitamins D, E, and K) as well as lipid building blocks which can affect the function of cells and tissues throughout the body.
  • Confusion & changes in cognition:  the liver is responsible for the breakdown of proteins which creates ammonia from the amine group of amino acids.  When produced, this dangerous ammonia is converted into the safer, transportable form of urea which can then be excreted through the kidneys.  Less hepatocytes mean less conversion, and ammonia can build up in the blood and irritate all tissues.  The brain is particularly sensitive to ammonia and will have impaired function when ammonia levels are too high (hepatic encephalopathy).   Confusion, sudden change in behaviour, decline in cognition or consciousness may result.

Manifestations due to Portal hypertension:

Due to the fibrotic scarring, the large diameter, low pressure portal vein does not have the blood pressure to overcome the resistance caused by the scarring.  As a result, flow backs up into all of the intestinal veins which normally drain into the portal vein.  An example of such vessel back up are:
  • Splenic vein:  due to its function, the spleen has a great capacity to store blood and will do so during portal hypertension. This causes an enlarged spleen (splenomegaly).   However, blood that resides the in spleen will undergo the natural function of sequestration (hoarding of blood cells, especially platelets) and removal of RBCs when they become damaged. An abnormal amount of blood staying the spleen will result in low circulating numbers of blood cells:  thrombocytopenia, anemia, and possibly leukopenia.
  • superior & inferior mesenteric veins:  collectively, these are the veins which drain the small and large intestine.  These veins travel within the peritoneal membrane which lines the external surface along the length of the intestines.  When these veins become congested with blood, it is easy for that backup pressure to push fluid out of the veins into the peritoneal space that separate the two layers of the peritoneum.  There are litres worth of potential space, between these layers of peritoneal membrane:  fluid accumulating in this peritoneal space is called ascites.  During cirrhosis, as much as 4L of ascitic fluid can accumulate within the abdomen, causing a sudden increase in abdominal girth and weight gain, over the course of a few days.  As the peritoneal space fills the abdomen, it becomes more difficult for the diaphragm to lower during inhalation – thus breathing will become more difficult.

Collateral circulation

As the portal hypertension is preventing the drainage of intestinal venous blood into the IVC, the body takes advantage of some naturally-occurring collateral vessels to detour around the liver.  There are 3 portosystemic collaterals which divert blood from portal vein to the inferior and superior vena cava.  Thus, during portal hypertension, one will see dilation and tortuosity (varices) of one or more of these 3 portosystemic collaterals:

  • esophageal varices:  intestinal venous blood can flow via the gastroesophageal collaterals which drain into the azygos vein and then SVC.  When congested with blood, these veins can become distended and visualized with a scope as esophageal varices. Esophageal varices will make it difficult to swallow (narrowed opening) and prone to bleed since vasculature is not normally exposed in the esophagus and the swelling leads to vessel wall fragility.  Rupture of these varices will cause a serious GI bleed seen as hematemesis (vomiting blood)
  • anorectal varices:  intestinal venous blood can flow via collateral circulation at the rectum which drain into the iliac veins and then IVC.   These varices will cause anorectal itching, discomfort and pain upon defecation.  There is possibility of bleeding (hematochezia)
  • paraumbilical varices:  there are vestigial umbilical veins within the abdomen, leftover from being in utero. Normally, these veins are not in use unless needed as a collateral pathway in portal hypertension.   When congested with blood, these veins drain into superficial abdominal wall veins near the umbilicus. This gives the appearance of tortuous, engorged veins emanating from the navel.  This feature is known as Caput Medusae (head of Medusa), named after the mythical creature which had snakes for hair.

Compensation for perceived low blood volume (hepatorenal syndrome)

As mentioned, fluid is shifting out of the blood into other compartments during cirrhosis (e.g. ascites, peripheral edema, splenomegaly).  However, the fluid has not left the body but they are not in the blood vessels – manifesting in possible decrease to blood flow to the kidneys.  In response to low blood volume, the kidneys will activate the renin-angiotensin-aldosterone system to retain Na+ and water which acts to increase the blood volume. However, this increased blood volume will exacerbate the problem, causing more portal hypertension, and worsening of the symptoms previously listed including edema, ascites, venous distension, etc.

Section summary

Cirrhosis causes manifestations in many other body systems, classified on the 3 biggest consequences:  loss of hepatocytes, portal hypertension, and renal compensation.  Loss of hepatocytes will manifest as lack of bilirubin processing, evident as jaundice.   Loss will also lead to decreased detoxification  (leading to changes in cognition) and hormone activation/inactivation (leading to disturbances in fertility and sex characteristics).  Nutrient and iron storage will be low causing possible issues with metabolism and red blood cell production.  Portal hypertension involves the back up of blood to the spleen leading to many blood cells and platelets ‘trapped’  and removed from circulation. This trapping of platelets and RBCs will cause poor clotting, propensity to bleed, and anemia.  Portal hypertension causes back up pressure in all of the intestinal veins  resulting in a leakage of plasma-like fluid from the intestinal capillaries into the peritoneum (ascites) and distension of rectal, esophageal, and umbilical veins as blood tries to get back to the heart via collateral circulation.   As fluid leaves the general circulation (e.g. accumulating in peritoneum, spleen), the kidneys will assume that the body is fluid deficient and activate the RAAS system – resulting in retention of more fluid which will have to pass through the cirrhotic liver  (hepatorenal syndrome).

Review questions


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Pathology Copyright © 2022 by Jennifer Kong is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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