Clinical Case Study: Booze Blues: A Case on the Liver

What other organ in Mrs. Fender's right upper quadrant, besides the liver, must be considered when investigating her abdominal pain?

gallbladder

Hepatocytes contain an extensive rough endoplasmic reticulum, Golgi apparatus, and abundant exocytotic vesicles. These cellular structures work together to ______.

manufacture and export a variety of proteins

Which function below is NOT carried out by the liver?

manufacturing and secreting insulin

Transaminases, coagulation factors, and albumin are all what kind of organic compound?

protein

Liver transaminases (leaked into the blood from damaged liver cells) remove amine groups from amino acids so that ______.

amino acids can be metabolized for energy

Why does liver dysfunction, such as cirrhosis, lead to hyperglycemia?

The liver is unable to take up glucose and store it as glycogen.

Besides the nurse's "bender" comment, and Mrs. Fender's social history, Tim suspects alcohol abuse based on many of his physical exam findings. Name at least three signs and/or symptoms that point to alcoholism, and briefly explain why each sign/symptom may occur.

Ascites: Ascites is the accumulation of fluid in the peritoneal cavity. In alcoholic cirrhosis, the portal vein becomes scarred and blocked, causing an excessive increase in hydrostatic pressure (portal hypertension). This leads to an increase in capillary hydrostatic pressure. Alcoholic cirrhosis also causes the liver to underproduce albumin proteins. This lowers osmotic pressure in the vasculature, enhancing filtration out of the capillaries. The cumulative effect is fluid leaking and accumulating in the peritoneal cavity. (Recall the affect of capillary hydrostatic pressure and osmotic pressure on net filtration.) Hepatomegaly: Alcohol abuse leads to liver scarring and swelling. The lower edge of the liver is normally barely palpable beneath the right lower ribcage, but as it swells it can be felt and sometimes observed as an enlargement in the right upper quadrant of the abdomen. Neurological changes: Mrs. Fender's incoherency and lack of coordination may be due to acute alcohol intoxication or chronic central nervous system destruction due to long-term alcohol abuse. It's probably a combination of the two. Jaundice: Jaundice is due to high bilirubin in the blood. It is the job of the liver to eliminate bilirubin. When the liver is diseased, bilirubin (a yellow pigment) spills into the bloodstream and causes skin to turn yellow. Bruising: Excessive bruising is probably the result of two problems: frequent falls when intoxicated and dysfunctional clotting. The liver normally produces most of the proteins that act as clotting factors in the blood. When it is diseased (e.g., alcoholic cirrhosis), production of these proteins diminishes and excessive bleeding occurs. Cirrhosis can also cause the liver to underproduce thrombopoietin, a protein that regulates platelet production. Platelets are vital to proper coagulation of the blood. Finally, alcoholism can lead to a vitamin K deficiency, important to forming clotting factors. Hyperglycemia: The liver is vital in glucose metabolism. In alcoholic cirrhosis, hepatocytes cannot adequately store glucose as glycogen and so it remains in the blood. Cirrhosis destroys the pancreas as well, causing insulin insufficiency. Annoyance: Annoyance when asked about alcohol drinking behavior is a classic symptom of alcoholism. A simple, four-question criteria, called CAGE, is frequently used by clinicians to screen for alcoholism: 1. Have you felt the need to Cut down drinking? 2. Have you ever felt Annoyed by criticism of drinking? 3. Have you had Guilty feelings about drinking? 4. Do you ever take a morning Eye opener (a drink first thing in the morning to steady your nerves or get rid of a hangover)? Intoxicated: Alcoholic intoxication is never healthy or normal, though in some contexts it may be more prevalent (e.g., binge drinking in a college population). Mrs. Fender's intoxication at midday is a red flag for alcoholism.

The liver is known for its ability to remove certain toxins from the blood. It can perform this function because its cells, or hepatocytes, contain large quantities of lysosomes and peroxisomes, and also have an extensive smooth endoplasmic reticulum. Briefly describe how these three organelles contribute to this major function of the liver.

Lysosomes and peroxisomes are membranous organelles that engulf toxins by endocytosis. Lysosomes contain acid hydrolases that digest the toxins so they can be safely eliminated by the cell. Peroxisomes contain oxidases and catalases that detoxify substances like alcohol and neutralize free radicals. The oxidases convert free radicals to hydrogen peroxide, while the catalases complete the process by converting the hydrogen peroxide to water. The smooth endoplasmic reticulum (ER) is part of a network of interconnecting, fluid-filled tubules. The smooth ER contains enzymes (such as the cytochrome P450 enzymatic system) that detoxify certain drugs (such as alcohol).

Mrs. Fender's jaundice is caused by the accumulation of bilirubin in her blood and tissues. What is the normal fate of bilirubin, and what role does the liver play? Explain how Mrs. Fender's cirrhosis is related to her jaundice.

Hemoglobin from worn-out erythrocytes is broken down into heme and iron. The iron is recycled, and the heme is further degraded into bilirubin, bound to albumin, and carried to the liver. The liver removes it from the blood and excretes it into the intestines as bile. When the liver is damaged (as in cirrhosis or hepatitis), bilirubin, which is a yellow pigment, spills over into tissues and the blood, thus giving tissues, blood, and the overlying skin a yellowish appearance, especially the lighter skin of the palms of the hands. Jaundice is also more apparent in the white sclera of the eyes.

Mrs. Fender's prolonged clotting times and excessive bruising are related. Again, referring to normal physiological functioning of the liver, why do these two things happen when alcohol damages hepatocytes?

The liver produces clotting proteins. When it is damaged (as in cirrhosis), clotting proteins are underproduced and it takes longer for blood to clot (prolonged prothrombin time - PT). This can be evidenced by excessive bruising as well. (It should be noted that alcoholics are also accident-prone when drinking because alcohol impairs their coordination and balance, which contributes to excessive injury and bruising.)

The liver has a portal vein as well as a hepatic vein. It also has unique exchange blood vessels similar to capillaries, called "sinusoids." How do these unique structures determine the function of the organ?

The liver has a unique circulatory system. About 75% of the blood flowing through the liver comes from the portal vein, carrying venous blood from the intestines, stomach, pancreas, and spleen. This assures direct delivery of nutrient-rich blood to the liver, which will appropriately package, store, or release these nutrients as the body needs them. The other 25% of blood flow comes from the hepatic artery, which carries arterial blood from the abdominal aorta. This blood is oxygen-rich and refreshes the highly metabolic hepatocytes. At the terminal branches of the portal vein and hepatic artery, the blood mixes and flows into the liver capillaries, which are called sinusoids. The walls of the sinusoids are highly fenestrated, discontinuous epithelial cells that allow plasma and solute to leak into the interstitial space between surrounding hepatocytes. In essence, the blood "percolates" in the sinusoids on its way to the hepatic veins, and then to the vena cava. This percolation is ideal for hepatocytes to filter the blood, process and store nutrients, detoxify (e.g., remove ammonia), and remove debris (e.g., worn-out RBCs, bacteria).

Cirrhosis leads to scarring and increased hydrostatic pressure in the hepatic portal vein. Explain why this increased venous pressure causes net filtration to increase in the hepatic capillaries, leading to ascites (swollen and fluid-filled interstitial space of the abdomen).

In alcoholic cirrhosis, the portal vein becomes scarred and blocked, causing an increase in hydrostatic pressure (portal hypertension). This leads to an increase in capillary hydrostatic pressure. Alcoholic cirrhosis also causes the liver to underproduce albumin. This lowers osmotic pressure in the vasculature, enhancing filtration out of the capillaries. (Recall the effect of capillary hydrostatic pressure and osmotic pressure on net filtration.)

Explain why the underproduction of albumin by a cirrhotic liver contributes to excessive filtration, which leads to ascites. Refer again to the forces that determine net filtration pressure in the hepatic capillaries, and to the function of albumins.

The liver is the major production site of albumins. Albumin (the main protein) is typically too large to diffuse across the capillary wall, so it remains in the blood vessels where they create an osmotic force that maintains water volume in the vasculature. In fact, albumins are the primary source of osmotic pressure, contributing to the reabsorption of water.