Pathophysiology
II-7. Chronic alcoholism
慢性アルコール症
Chronic Alcoholism
- Definition: 4 units/day or 14 units/week.
- Differs from acute intoxication: CYP2E1 induction ↓reductive stress; excess acetaldehyde more prominent.
- Ethanol = high energy but “empty calories” (7 kcal/g; no essential nutrients).
Malnutrition
- GI inflammation + pancreatitis worsen malabsorption.
- Vitamin B1 (thiamine), folate deficiency: alcoholics are hypoglycemic → given glucose, BUT glucose alone → pyruvate → lactate → fatal lactic acidemia. Always give glucose with thiamine (directs pyruvate to oxidative pathway).
- Lack of essential amino acids, nervous system impairment, liver damage.
- Faster steroid hormone metabolism → altered secondary sex characteristics, ↓libido.
Other Consequences
- Mitochondrial dysfunction: ↓energy efficiency (used for heat), damaged enzymes (incl. ALDH) → acetaldehyde accumulation (toxemia), ↑oxidative stress.
- Vitamin A deficiency: night blindness (nyctalopia), malignant transformation.
Types of Alcoholic Liver Damage
- Fatty liver disease (steatosis): ↑TAG + ↓VLDL; reversible (stop drinking). Lipid droplets in hepatocytes; enlarged, soft, yellow, oily.
- Steatohepatitis: from continued drinking (or severe exposure from healthy liver); potentially reversible. Enlarged spherical hepatocytes, necrosis, Mallory bodies, neutrophil infiltration.
- Cirrhosis: completely irreversible; from long-term heavy use. Induced CYP2E1 → ROS/lipid peroxidation/oxidative stress → hepatocyte damage; stellate cells → myofibroblasts → fibrosis (worsening blood flow) → chronic liver failure → HCC.
Progressive Liver Damage Mechanism
- Oxidative stress + membrane damage + acetaldehyde cytotoxicity → chronic cell damage → chronic inflammation; acute reconstruction inhibited (no renewal) → stellate → myofibroblast → early fibrosis → disturbed blood flow → hypoxia (vicious cycle) → advanced fibrosis → cirrhosis.
Pancreas
Acute Pancreatitis
- Prevalence 10–20:100,000; reversible pancreatic damage from inappropriate enzyme secretion/activation → necrosis + acute inflammation.
- Symptoms: nausea, vomiting, fever, abdominal pain; ↑amylase + lipase.
- Outcome: spontaneous healing if no complications.
- Etiology: alcoholism, ductal obstruction (gallstones); also trauma, drugs (furosemide, estrogen, azathioprine), metabolic (hypercalcemia, hypertriglyceridemia), gene mutations (trypsinogen, CFTR).
- Severe: steatonecrosis, vessel/organ damage, ARDS, DIC, sepsis, shock.
Chronic Pancreatitis
- Chronic inflammation → progressive exocrine damage + fibrosis → eventually endocrine damage.
- Etiology: chronic alcoholism (oxidative damage); rarely inherited, ductal obstruction, autoimmune.
- Repeated acute episodes → fibrosis around acinar cells; pro-inflammatory/pro-fibrogenic mediators → stellate cells → myofibroblasts → further fibrosis. Prognosis = bad.
一問一答
▶How is chronic alcoholism defined?
4 units/day or 14 units/week.
▶Why is alcohol called 'empty calories'?
It is high energy (7 kcal/g) but provides no essential nutrients.
▶Why must glucose be given with thiamine in alcoholics?
Glucose alone is converted pyruvate → lactate causing fatal lactic acidemia; thiamine directs pyruvate to the oxidative pathway.
▶Which vitamin deficiencies are common in chronic alcoholism?
Thiamine (B1), folate, and vitamin A deficiency.
▶How does chronic alcoholism affect mitochondria?
Reduced energy efficiency (energy used for heat), damaged enzymes including ALDH (acetaldehyde accumulation/toxemia), and increased oxidative stress.
▶What is the consequence of vitamin A deficiency in alcoholics?
Night blindness (nyctalopia) and malignant transformation.
▶What characterizes alcoholic fatty liver disease (steatosis)?
Increased TAG with decreased VLDL; reversible on stopping drinking; lipid droplets in enlarged, soft, yellow, oily hepatocytes.
▶What are the features of alcoholic steatohepatitis?
Potentially reversible; enlarged spherical hepatocytes, necrosis, Mallory bodies, and neutrophil infiltration.
▶Is alcoholic cirrhosis reversible, and how does it develop?
Completely irreversible; induced CYP2E1 → ROS/lipid peroxidation/oxidative stress → hepatocyte damage → stellate cells become myofibroblasts → fibrosis → chronic liver failure → HCC.
▶What is acute pancreatitis and is it reversible?
Reversible pancreatic damage from inappropriate enzyme secretion/activation causing necrosis and acute inflammation.
▶What are the symptoms and lab findings of acute pancreatitis?
Nausea, vomiting, fever, abdominal pain, with raised amylase and lipase.
▶What severe complications can acute pancreatitis cause?
Steatonecrosis, vessel/organ damage, ARDS, DIC, sepsis, and shock.
▶What are the two main etiologies of acute pancreatitis?
Alcoholism and ductal obstruction (gallstones); also trauma, drugs, metabolic causes, and gene mutations.
▶How does chronic pancreatitis progress and what is its prognosis?
Chronic inflammation → progressive exocrine damage + fibrosis → eventual endocrine damage; prognosis is bad.
▶How does chronic alcoholism differ from acute intoxication metabolically?
CYP2E1 induction reduces reductive stress, so excess acetaldehyde becomes more prominent.
▶Why does chronic alcoholism alter sex characteristics?
Faster steroid hormone metabolism alters secondary sex characteristics and reduces libido.
▶What is the main cause of chronic pancreatitis?
Chronic alcoholism (oxidative damage); rarely inherited, ductal obstruction, or autoimmune.
▶Why does chronic pancreatitis develop fibrosis around acinar cells?
Repeated acute episodes plus pro-inflammatory/pro-fibrogenic mediators activate stellate cells into myofibroblasts, driving further fibrosis.
▶Why does malabsorption worsen in chronic alcoholism?
GI inflammation plus pancreatitis impair nutrient absorption.
▶Outline the progression from chronic alcohol liver damage to cirrhosis.
Oxidative stress/membrane damage/acetaldehyde toxicity → chronic cell damage and inflammation → inhibited renewal → stellate-to-myofibroblast fibrosis → disturbed flow/hypoxia (vicious cycle) → advanced fibrosis → cirrhosis.