- Alcoholic liver cirrhosis
The chemical breakdown of ethanol is typically shown in freshman-level biology books as the following:
Ethanol (C2H5OH) –> Acetaldehyde (CH3COH) –> –>Acetic acid (CH3COOH) –> –>2CO2 + 2H2O
The double arrows that I’ve inserted into the pathway indicate that there are certain intermediate steps, typically overlooked, that are critical in this discussion about alcoholic endpoints, particular liver cirrhosis.
It is during these steps that highly reactive forms of oxygen are generated, which bind with and damage both protein and DNA, and in doing so, trigger chronic inflammation.
The liver is capable of repairing itself, but if the amount of alcohol consumed is great enough, over an extended period of time, the damage that ensues will become permanent leading to cirrhosis.
Wikipedia.com defines cirrhosis as the following:
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease.[6] Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis.[6][7] The disease typically develops slowly over months or years.[1] Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen.[8] As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin.[8] The fluid build-up in the abdomen may develop into spontaneous infections.[1] More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.[9]
Before the liver is irreversibly replaced with scar tissue, there is an intermediate stage, called fatty liver.
Again, from wikipedia.com:
Steatotic liver disease (SLD) a.k.a. fatty liver disease (FLD) or hepatic steatosis, is a condition where excess fat builds up in the liver.[1] Often there are no or few symptoms.[1][2] Occasionally there may be tiredness or pain in the upper right side of the abdomen.[1] Complications may include cirrhosis, liver cancer, and esophageal varices.[1][3]
Previously, classified as:
Histological examination shows the progression at the cellular level:
First, a healthy liver. Notice the clearly defined blocks of tissue with blood vessels permeating throughout. This picture reminds me of an aerial view of a pleasant residential neighborhood:
Next, a section of a fatty liver. Notice that the regular arrangement of tissue has been disrupted, and there are numerous fat cells. Even with this extensive damage, the liver can heal itself if the person ceases to drink alcohol:
If, however, the person continues to drink, the chronic inflammation and damage caused by active forms of oxygen will replace the healthy sinusoid tissue with non-functional scar tissue, in which the blood vessels, providing blood to be purified, are crushed.
The gross anatomy is just as grim. To my knowledge, the normal and fatty livers were collected individuals who died of causes other than excess drinking. The liver to the right, showing cirrhosis, is blackened, and it is hard as a brick:
Cirrhosis is irreversible, is life-threatening, and requires a liver transplant. In preparing a lecture on cirrhosis and liver transplants, I contacted the liver transplant team at the University of Southern California Medical School, and they kindly gave me permission to use the following images to show what is involved in liver transplant surgery.
1) The skin of the patient is marked for where the incisions will be made. Note that this patient’s skin is very yellow due to jaundice:
2) The diseased liver is disconnected from blood vessels and ducts, and the vena cava is clamped.
3) The new liver is inserted:
4) Vessels and ducts are attached to the new liver:
5) The bile duct is temporarily attached to a external bag so that physicians can see whether the transplanted liver is functioning properly. You can see that bag at the top of the patient’s cover. By the way, this fellow is the same guy shown in the initial image with the jaundiced skin, and he looks pretty good, considering what he just endured.
6) Of course, this is major surgery, and his body experienced a major assault. Furthermore, transplant surgeons must be concerned with organ rejection, so blood chemistry must be carefully monitored. Here are selected parameters of this patient’s blood chemistry:
ALT is an enzyme derived from liver cells, and a certain concentration of ALT in blood is normal. Excessive amounts indicate some form of liver damage which requires further investigation. Note that ALT concentrations spike shortly after surgery, but then gradually decline.
Bilirubin is a breakdown product of hemoglobin. Again, a certain concentration of bilirubin is normal, but excessive amounts indicates significant liver damage. Notice that it gradually increases to days 6-7, and then gradually declines.
Platelets are blood components which assist in blood clotting and vessel repair. Note in this figure that platelet concentrations drop (indicating their depletion due to ongoing post-surgical repair), but they gradually increase after day 4.
2. Wernicke encephalopathy and Korsakoff Syndrome are caused by a deficiency in thiamine
On page 7 of Alcoholics Anonymous, Bill Wilson is describing the grim news his wife received regarding his drinking: “My weary and despairing wife was informed that it would all end with heart failure during delirium tremens, or I would develop a wet brain (emphasis mine), perhaps within a year.”
The phrase “wet brain” refers to two interrelated conditions that arise from the depletion of thiamine that occurs after an extended period of drinking alcohol.
First, an introductory video clip: Wernicke Korsakoff Syndrome (Year of the Zebra) – YouTube
The symptoms of Wernicke encephalopathy, and its signs include the following:
- Ophthalmoplegia or ophthalmoparesis refers to paralysis or weakness of the eye muscles. It can affect one or more of the six muscles that hold the eye in place and control its movement.
2) Ataxia refers to the loss of coordination. People with ataxia lose muscle control in their arms and legs. This may lead to a lack of balance, coordination, and trouble walking. Ataxia may affect the fingers, hands, arms, legs, body, speech, and even eye movements.
3) Confabulation refers to the affected individual fabricating stories to fill in gaps in memory.
While there are certain parts of the brain, e.g. the mammilary bodies, which are involved in memory, are damaged, the symptoms of Wernicke encephalopathy are reversible with the administration of thiamine, either by infusion or by oral administration. However, if untreated, the patient will progress to Korsakoff Syndrome, a chronic memory disorder, where the symptoms and damage may be irreversible and fatal.
Symptoms include:
- Amnesia or inability to form new memories.
- Behavioral changes, such as agitation or anger.
- Confabulation.
- Delirium and disorientation.
- Fatigue or lethargy.
- Hallucinations, especially in those withdrawing from alcohol.
- Lack of focus or attention.
- /Unsteady gait.
MRI images of the brain of a person with Korsakoff Syndrome show significant damage:
Magnetic resonance imaging (MRI) scans of a healthy male (top) compared to a male of the same age with WK syndrome (bottom). The WK brain has less brain volume and larger cavities within the brain (called ventricles).
Image from Wernicke-Korsakoff Syndrome | National Institute on Alcohol Abuse and Alcoholism (NIAAA) (nih.gov) Credit: Adapted from a figure by A. Pfefferbaum, SRI International
Some symptoms may not improve, even with treatment. In severe cases, people may experience loss of consciousness (coma).
Chandrkumar, A.; Bhardwaj, A.; ‘t Jong, G.W. (2019). Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. J. Basic Clin. Physiol. Pharmacol. 30(2): 153-162. https://doi.org/10.1515/jbcpp-2018-0075 .
Addictions and Recovery 