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ALCOHOLIC LIVER DISEASE, NON-ALCOHOLIC FATTY LIVER DISEASE - Coggle Diagram
ALCOHOLIC LIVER DISEASE
3 major distinctive overlapping forms:
- Steatosis
- Alcoholic steato-hepatitis
- Fibrosis
Metabolism of alcohol :check:
1. Formn of acetaldehyde
- Alc. DH
- CYP2E1(microsomal)
- Catalase(peroxisome)
2. Formn. of acetic acid
- By Acetaldehyde DH ( ALDH) in mito.
- Acetic acid→ mito. resp. chain
ETIOLOGY
- Gender
○ ♀ more susceptible: estrogen ↑ permeability to gut derived endotoxins → ↑ chemokine/cytokine pdn. → injury to liver cells
- Ethnic/ Genetic factors
○ Cirrhosis ↑ for african americans than for caucasian americans
○ Polymorphisms in detoxifying enzymes & cytokine promoters
○ ALDH*2→ in 50% asians→low enz. activity→ homozygous state causes alcohol intolerance
- Comorbid conditions: Fe overload, NASH, HBV-HCV inf.
- Amount and duration of alcohol intake
PATHOGENESIS :check:
Mechanisms of liver injury by ethanol : 1. Oxd. stress/ ROS→ lipid peroxidation of cell membranes2. Immune & inflammatory mechanisms by forming chemical adducts→ neoAg→ cell injury/autoimmune like diseases3. Increased Redox ratio
- ↓ NAD⁺ in cytoplasm
- Mitochondrial dysfn. d/t depletion of glutathione
4.Increased pdn. of proinfl. cytokines
- LPS(endotoxin) from G-ve bacteria→ portal circulation→ stimulated pdn. of TNFα & other cytokines
- Impaired proteasome fn.→ accumulation of large amounts of ubiquitin→ mallory bodies
5. Direct toxicity by forming protein adducts6. Hypoxic damage of centrilobular region7. Reduced levels of ADH & ALDH isozymes8. Abnormal metabolism of methionine9. Malnutrition & vitamin deficiency10. Induction of enzymes
Mechanisms of Fibrosis/Cirrhosis: + Activation of hepatic stellate cells→ produce collagen, lose stored Vit A
Mechanisms of steatosis:
↑ catabolism of fat & ↑ delivery of FFAs to liver
↓
↑ synthesis of FA in liver
↓
↓ oxdn. of FAs by mitochondria
↓
↑ pdn. of TGs
↓
Impaired assembly/secretion/release of lipoproteins
MORPHOLOGY
HEPATIC STEATOSIS Gross
- Massive enlargement
- Soft, yellow, greasy
Microscopy
- Microvesicular steatosis-acinar zone 3
- Macrovesicular steatosis
- Absence of inflammaton of fibrosis
ALCOHOLIC HEPATITIS
Gross
- Enlarged
- Yellow d/t steatosis
- Firm d/t increased fibrosis
Microscopy
4 characteristic features
- Ballooning degeneration of hepatocytes
- Mallory bodies
- Neutrophilic infiltration
- Alcoholic steatofibrosis
ALCOHOLIC CIRRHOSIS Gross
- Early stage
○ Yellow tan, fatty, enlarged and weighs above 2 kg
- Late stage
○ Liver appears brown, non fatty, diffusely nodular, firm
○ Size ↓ progressively to <1kg
○ Capsular surface→ nodular(pig skin appearance), micronodular(hobnail appearance), mixed micro/macronodular pattern
Microscopy
- Loss of architecture
- Regenerating nodules
- Mallory bodies not seen
- Fibrosis
- Vascular reorganisation
CLINICAL FEATURES Hepatic steatosis
- hepatomegaly
- mild elevation of S. BR, ALP, GGTP
- Alc. withdrawal & adequate diet→ liver returns to norma;
Alcoholic hepatitis
- Acute/ following bout of heavy drinking
- Non specific symptoms→ malaise, anorexia, wt. loss, upper abd. discomfort, tender hepatomegaly
- Repeated bouts → cirrhosis within few years
- May be superimposed on cirrhosis
Alcoholic cirrhosis
- Initial phase→ comprensated cirrhosis
- Later phase→ decompensated cirrhosis, portal HTN/ liver dysfn. as complications
- Non specific symptoms
- Hepatic failure pptd. by systemic infecton/ GI hemorrhage
LAB FINDINGS
Alcoholic Steatosis Biochemical findings
- Mod. raised ALT & AST
- ALT: AST >1
- gamma-GT: sensitie test to determine alcohol intake
Liver biopsy : Accumulation of fat in perivenular hepatocytes & later in entire hepatic lobule
Alcoholic Hepatitis Biochemical findings
- ALT & AST ↑ 2-7 times of normal
- ALT:AST ratio>2
- Reason: AST located in mitochondria & alc. damages mitochondria in hepatocytes
- S. br ↑
- S. ALP: mild ↑
- S. albumin: ↓
- Prothrombin time: prolonged
Hematological findings
- Absolute neutrophilic leukocytosis
Urine
- Br & urobilinogen moderately elevated
Alcoholic Cirrhosis LFT
- Hyperilirubinemia
- S. proteins: reversal of AG ratio
- Hypoalbuminemia
- Hyperglobulinemia
- S. transaminases:
AST ↑
ALT ↑ & <300U/dl
AST: ALT ratio> 2 in alc. cirrhosis
Ratio< 2 in cirrhosis coplicating viral hepatitis
- ALP slight ↑
- PT prolonged
Hematological tests
- Anemia & acanthocytosis
- Leukopenia
- Thrombocytopenia
Serological markers: for Hep B&COther biochemical markers
- Blood ammonia : ↑
- HypoNa⁺/K⁺/Mg/phosphate
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