Alcoholic Liver Disease - Gastrointestinal

Introduction

Chronic use results in three main disease processes
- steatosis (fatty change)
  - reversible state with cessation of alcohol
  - macrovesicular fatty change that can develop over the short term with moderate alcohol intake
    - contrast this from non-alcoholic fatty liver disease (NAFLD)
      - Patient's do not abuse alcohol, tend to be overweight and usually have an ALT > AST
- hepatitis
  - reversible state with cessation of alcohol
  - hepatocytes are enlarged with eosinophilic inclusions (Mallory bodies)
    - Mallory bodies are damaged intermediate filaments (cytokeratin) in hepatocytes
      - neutrophils are present
      - damage mediated by acetaldehyde
      - requires many years of continuous alcohol intake
    - cirrhosis

Pathophysiology
- ethanol metabolism
  - presence of decreased NAD levels play a major role in altered metabolism
Risk factors
- length of use
- amount
- women > men

Presentation

Symptoms and physical exam
- fatty change
  - tender hepatomegaly
  - afebrile
- hepatitis
  - tender hepatomegaly
  - fever
  - acities
- cirrhosis
  - abdominal distention
  - altered mental status
  - tremor
  - fetor hepatis (foul smell of amines)

Evaluation

Labs
- elevated AST and ALT
  - AST:ALT > 2 suggests alcoholic hepatitis
    - other liver pathologies have ALT > AST
    - inversed because AST is found in the mitochondria and EtOH is a mitochondiral toxin
- absolute neutrophilic leukocytosis
  - seen in hepatitis but not fatty change
- fasting hypoglycemia
- ↑ anion gap metabolic acidosis
- hypertriglyceridemia
- hyperuricemia
- thrombocytopenia
- ↑ γ-gluamyltransferase
  - secondary to EtOH induced hyperplasia of the smooth ER

Treatment

Lifestyle
- cessation of alcohol
Pharmacologic
- steroids
Operative
- transplant

Prognosis, Prevention, and Complications

Prognosis ranges from good to poor depending on early intervention and alcohol cessation
Early alcoholic liver changes (i.e. fatty liver) are reversible with lifestyle changes
Chronic hepatitis increases risk of hepatocellular carcinoma
Death from fulminant liver failure

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum
Total (recumbent)	6.0-7.8 g/dL
Albumin	3.5-5.5 g/dL
Globulin	2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma	.5-5.0 μU/mL
Thyroidal iodine (¹²³I) uptake	8%-30% of administered dose/24h
Thyroxine (T4), serum	5-12 μg/dL
Triglycerides, serum	35-160 mg/dL
Triiodothyronine (T3), serum (RIA)	115-190 ng/dL
Triiodothyronine (T3) resin uptake	25%-35%
Urea nitrogen, serum	7-18 mg/dL
Uric acid, serum	3.0-8.2 mg/dL

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²

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(M1.GI.134) A 39-year-old Caucasian male presents for a physical exam. It is noticed that he has slight hepatomegaly. During the history, the patient states he drinks 7-8 beers daily. Biopsy of the liver is shown in Figure A. What is the primary mechanism for the abnormality seen in Figure A? Review Topic

QID: 101191

FIGURES:

Increased production of NAD

14%

(12/84)

Decreased production of NAD

43%

(36/84)

Increased fatty acid oxidation

18%

(15/84)

Increased synthesis and exportation of lipoproteins

(5/84)

Increased uptake of fat

17%

(14/84)

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