Cirrhosis (mechanism of disease)

This is a mechanism of disease flowchart for cirrhosis, covering the etiology, pathophysiology, and manifestations.
ADDITIONAL TAGS:
Nonalcoholic steatohepatitis
Obesity
Diabetes mellitus
Hyperlipidemia
Primary sclerosing cholangitis
Primary biliary cholangitis
Autoimmune hepatitis
Cell / tissue damage
Signs / symptoms
Labs / tests / imaging results
Cirrhosis
Core concepts
Social determinants of
health / risk factors
Pharmacology / toxicity
Microbial pathogenesis
Biochemistry
Flow gradients
Genetics / hereditary
Inflammation
Pathophysiology
Etiology
Manifestations
Kupffer cells (liver macrophages) destroy hepatocytes → activate hepatic stellate cells → trigger inflammation
Cytokines (PDGF, TGF-B)
Collagen / fibrotic tissue replaces the liver parenchyma (fibrosis)
Excessive connective tissue in periportal and centrilobular zones
Regenerative nodules and fibrous septa compres hepatic sinusoids and venules → loss of fenestrations
Elevated portal vein hydrostatic pressure → intrasinusoidal hypertension → poor blood flow
Impaired substrate exchange
Loss of exocrine and metabolic functions
Stimulate hepatocyte apoptosis
Activate stellate cells → activate myofibroblasts → produce excess collagen / connective tissue
Long-standing alcohol use
Medications (amiodarone, acetaminophen, methotrexate)
Chemicals (pesticides, tetrachloromethane)
Ingestion of aflatoxin, produced by Aspergillus
Hepatotoxicity
Hepatitis
Parasitic infections (schistosomiasis, leishmaniasis, malaria in India, Africa)
Chronic viral infection (Hep C B D)
Thrombosis → occludes hepatic veins (Budd-Chiari syndrome)
Osler-Weber-Rendu (HHT) → vascular dysplasia → high fibrous septa in liver
CHF → congestive hepatopathy (cardiac cirrhosis)
Hemochromatosis
Wilson disease
α1-antitrypsin def
Vitamin deficiency
B12 or folate def
Anemia
Chronic blood loss
↓ vit D3 hydroxylation
Secondary hyperparathyroidism
Portal hypertension
Esophageal varices
Caput medusa
Thrombocytopenia
Splenomegaly
Fatigue / weakness
↓ synthetic function
↓ detoxification
Jaundice
Med / metabolite accumulation
↓ urea synthesis
↑ ammonia
Hepatic encephalopathy
↓ coagulation factors
Bleeding diathesis
+/- petechiae, purpura
↓ bile acids
↓ absorb fat-soluble vitamins
↓ albumin
Ascites +/- peripheral edema
↑ SHBG
↑ estrogen effect (feminization)
Gynecomastia
↓ body hair
↓ libido
Erectile dysfunction
Hypogonadism
Hepatopulm. syndrome
Hepatorenal syndrome
Hepatocellular carcinoma
Spider telangiectasia
Palmar erythema
Hypoxemia
Nail clubbing
Ascites +/- peripheral edema
Amenorrhea
Asterixis

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