Alcohol things to know

1. Why do alcoholics have fasting hypoglycemia and how does this

contribute to liver disease?

Buildup of NADH inhibits Gluconeogenesis, thus fasting hypoglycemia. How

does it do this? Well, because there is excess NADH, Pyruvate is converted to
lactate instead of Acetyl-CoA (in order to consume the NADH that is produced
by alcohol metabolism). Although Acetyl-CoA is not directly a substrate for
gluconeogenesis, it MUST be present for the first enzyme of gluconeogenesis to
work. Since gluconeogenesis is impaired, you get fasting hypoglycemia. This
hypoglyecemia then triggers the release of glucagon, which mobilizes fat
stores via Hormone sensitive lipase. The fatty acids reach the liver and then
cannot be sent out again because VLDL assembly is inhibited.

2. Why do alcoholics get fatty livers?

Alcohol metabolism provides the liver with calories/ATP, so the fatty acids that
were released from glucagon (see above) do not need to be broken down by
beta-oxidation because the liver has enough energy. Instead, they are used to
make Triglycerides (TG); TG assembly into VLDL is inhibited by alcohol so the
TGs buildup in the liver instead of getting released and this leads to fatty liver
and eventually cirrhosis -- mediated by those crazy transforming stellate cells
(NOTE: Check albumin level to determine extent of liver damage, AST/ALT are
non-specific indicators of liver damage)

3. Why do alcoholics have thiamine and folate deficiencies?

Acetaldehyde Dehydrogenase consumes Thiamine and Folate

4. An alcoholic presents in with signs of hypoglycemia. You quickly

administer glucose and are feeling good about yourself when all of a
sudden the patient goes into a coma and dies. Why did this happen?

If an alcoholic has thiamine deficiency (and many do), then Pyruvate

Dehydrogenase is not working very well. So if you administer glucose, PDH is
not converting Pyruvate into Acetyl-CoA so it will be converted to lactic acid.
This patient died of lactic acidosis. Always remember to give thiamine with
glucose in a suspected alcoholic!

5. Why do alcoholics often get gout?

Increase in lactic acid --> competes with uric acid for excretion (because they
are both weak acids), thus will have hyperuricemia and increased risk for gout.
Note: Most diuretics are also weak acids and this is the same mechanism by
which they increase risk for gout! Theoretically, any weak acid that is excreted
in the urine can cause hyperuricemia (ex/ Aspirin -- but not acetaminophen,
which is metabolized in liver). Also, to be complete, anything that leads to
massive breakdown of cells (release of purines such as chemotherapy) can
lead to hyperuricemia.

6. Why do alcoholics have skinny arms and legs? Why should this
worry you?

Muscle wasting can occur in alcoholics because of the combined effects of

glucagon and cortisol. Glucagon directs amino acids to gluconeogenesis (thus
preventing them from being used in protein synthesis) and cortisol (released
because of fasting hypoglycemia) leads to a breakdown of muscle proteins. The
combination of these two effects leads to excess ammonia production. With a
faulty liver, the urea cycle is not in the best shape so this can lead to
hyperammonemia and hepatic encephalopathy (asterixis is a sign of hepatic
encephalopathy; had to look this up on youtube, it's an involuntary flicking of
the wrists -- like a bird flapping)

7. What cancers are alcoholics especially at risk for?

Squamous cell cancer of Esophagus (especially if also a smoker) and Signet

ring carcinoma of the stomach. Probably others too like Hepatocellular
carcinoma due to cirrhosis

8. Why do chronic alcoholics get pancreatitis?

Not very well known, but alcohol is thought to alter/increase digestive enzyme
activation (most importantly trypsinongen --> trypsin). These pancreatic
enzymes then eat away at the pancreas. Note: Treatment for pancreatitis is
almost always supportive, do NOT operate because this can actually kill the
patient.

9. Why do alcoholics get ascites? What are some complications of the

portal hypertension?

Liver damage leads to portal hypertension. This increases hydrostatic pressure

in capillaries due to back up of blood and thus more fluid leaves the blood and
enters the interstitum --> Note: Do not drain fluid from belly of a patient with
ascites because this will cause even more fluid to leave circulation (leads to
greater difference in hydrostatic pressure) and can lead to hypotension or even
circulatory shock. For other complications, you gotta think back to anatomy
and some of the portal-caval anastamoses: this includes internal hemorrhoids
via superior rectal vein, esophageal varicies via the left gastric vein (all these
anastomoses are easily testable), and caput medusa via paraumbilical veins.
The esophageal varices often lead to heavy bleeding and hematemisis --> are
often fatal.

10. Why is it a bad idea to drink alcohol after extreme physical

activity?

Alcohol metabolism will consume all of the NAD+ available and convert it to
NADH. In order for Lactic acid to be converted to Pyruvate, you need NAD+. If
this is not available, then lactic acid will build up and can lead to severe lactic
acidosis

11. What's up with those spider looking spots on the skin of

alcoholics?

Spider angiomas come from increased estrogen. Unfortunately for male

alcoholics, Estrogen is broken down in the liver so if the liver is not working
then there is increased estrogen (can also see spider angiomas in pregnancy
with increased estrogen levels)

12. Well, that was a mouthful. Anything else?

One last thing to consider is that the liver synthesizes a whole lot of our
proteins, most importantly clotting factors (increased tendency to bleed),
Steroid hormone binding proteins/other binding glubulins (can affect levels of
hormones/ions), Urea (hyperammonia), Albumin (edema), and probably some
others. Also, on histo if you are given a picture of hepatocytes in an alcoholic
with a bunch of pink stuff in them (eosinophilic inclusions-Mallory bodies) they
might as what those represent and it's keratin intermediate filaments of the
cytoskeleton that are damaged.