Chronic Liver Disease Flashcards
1
Q
- Vascular Disease (pericentral): Hepatic venous outflow obstruction; Ischemic necrosis
- Steatophepatitis (pericentral)
- Chronic Hepatitis (periportal)
- Chronic Cholestatic Syndromes (bile duct injury)
A
Classifications of Chronic Liver Disease
2
Q
- a histological diagnosis of severe fibrous scarring encircling regenerative nodules of hepatocytes
- Micronodules (3cm): assoc w/ chronic hepatitis
- Results in loss of collagen type III architectural framework between hepatocytes
- associated with clinical liver dysfunction (decreased detoxification and decreased protein synthesis) and portal hypertension
A
Cirrhosis
3
Q
- hepatitis C now predominates in U.S. (approximately 26%)
- Alcohol (21%)
- Alcohol + HCV (15%)
- Cryptogenic (18%)
- hepatitis B (15%)
- other causes (5%)
A
Most common etiologies of cirrhosis
4
Q
- reside in space of disse between hepatocytes and sinusoidal epithelium
- normally quiescent
- activated during liver injury –> flatten and behave as fibroblasts; release collagen
A
Stellate Cells
5
Q
- Jaundice: inadequate metabolism and excretion of bilirubin; a late sign of chronic liver disease
- Palmar Erythema
- Telangiectasia / Spider Angiomata
- Testicular atrophy & gynecomastia: due to failure of the liver to clear circulating estrogenic precursors
- Dupuytren’s contractures: contractures of the palmar fascia; of unknown cause
A
Stigmata of Chronic Liver Disease
6
Q
- Portosystemic shunts / Varices
- Ascities
- Congestive splenometgaly/hypersplenism
A
Consequences of Portal hypertension (due to cirrhosis)
7
Q
- dilated veins resulting from obstruction to portal blood flow
- especially gastric, esophageal, periumbilical (“caput medusa”) and peri-rectal veins (hemorrhoids)
- high risk of hemorrhage after erosion & coagulopathy
- stasis in the portal circulation is predisposing to thrombosis
- endoscopy (EGD) for diagnosis and treatment
A
Varices
8
Q
Normal: HVWP - IVC < 4 mmHg
Cirrhosis: HVWP = IVC > 4mmHg; > 12 mmHg is clinically signficant
A
Hepatic Venous Wedge Pressure
9
Q
- Beta blocker (propranolol)
- EGD to band larger varicose
A
Prophylaxis for Variceal bleeding
10
Q
- Engorgement and congestion of the spleen related to portal hypertension.
- Complications can include significant sequestration/consumption of RBCs and platelets (thrombocytopenia)
A
Slpenomegaly
11
Q
Coagulopathy due to impaired synthesis of:
- coagulation factors (2, 5, 7, 9, 10): increased PT
- epoxide reductase (diminished vit K activtaion)
Hypoalbuminemia with edema: decreases oncotic pressure of the blood
A
Consequences of decreased protein synthesis
12
Q
- fluid accumulation in peritoneal space
Pathogenesis:
- New hypothesis: systemic arterial vasodilation: increases in nitroc oxide with increased blood volume in splanchnic circulation
- “overflow hypothesis”: primary renal sodium & water retention; expanded intravascular volume is displaced to the peritoneal space by effects of cirrhosis and portal hypertension
- “compensatory hypothesis” ascites accumulates as a result of cirrhosis and portal hypertension, causing decreased intravascular volume; induces renal retention of sodium and water
A
Ascites
13
Q
- Diuretics: Spironolactone or furosemide
- limit salt intake (
A
Ascites Management
14
Q
- Renal failure in setting of ascites and cirrhosis
- Marked sodium retention is unresponsive to volume expansion and diuresis
- Kidneys show no tissue pathology
- poor prognosis
- tx: possible TIPS shunt or liver transplant
A
Hepatorenal Syndrome
15
Q
- New onset ascites must be tapped
- clear transudate in common causes of uncomplicated cirrhosis
- Serum-ascites albumin gradient: SAAG >1.1 is consistent with portal hypertension; if
A
Diagnostic Paracentesis
16
Q
- Infection in the ascites
- translocation of bacteria from gut or seeding from circulation is not cleared due to low opsonins and complement, most commonly due to E. coli, Klebsiella, or Strep. pn.
- Systemic presentation: low-grade fever, abdominal tenderness, encephalopathy, ascites, renal failure
- Labs - high WBC, acidosis; WBC > 500 mm3, polys > 250 mm3
- if clinical evidence, treat empirically with I.V. cefotaxime (broad spectrum)
A
Spontaneous Bacterial Peritonitis
17
Q
- a neuro-psychiatric syndrome with signs of mental confusion and neurological instability; early hyper-reflexia and asterixis (flapping tremor) progressing to coma
- due to decreased hepatic clearance
- EEG: triphasic slow waves
- Fetor: odor of mercaptans
- Constructional apraxia: slow to remake the shape with sticks
Dx: measure NH3 ammonia
Tx: reduce the amount of protein in the gut; avoid constipation (prescribe lactulose)
A
Hepatic Encephalopathy
18
Q
The clinical parameters include:
(1) low albumin (normal 3.5-5.0 g/ dl)
(2) jaundice (bil. greater than 2.5-3.0 mg/ dl)
(3) ascites
(4) encephalopathy
(5) state of nutrition, or prothrombin time (prolonged > 3”)
A
Child’s Criteria
19
Q
Indications: evidence of end-stage liver disease
- expected survival 1.8 INR , Bil > 3
- Mayo End-stage Liver Disease model (MELD)
Contraindications:
- systemic infection or AIDS
- severe cardiopulmonary disease
- metastatic malignancy
A
Indications for Liver transplant
20
Q
- significant complication of cirrhosis
clinical profile/risk factors:
- cirrhosis of several years
- Hepatitis B and Hepatitis C
- Aspergillus induce p53 mutations)
Diagnosis:
- LFTs may show deterioration, especially AlkP (obstruction by mass-effect)
- CT or sonogram (mass)
- alpha-fetoprotein (↑)
Increased risk for Budd-Chiari Syndrome
A
Hepatocellular Carcinoma
21
Q
- a venous thrombosis of the hepatic vein
- usually associated with a hypercoagulopathy (oral contraceptives, polycythemia, or inherited hypercoagulable states (anti-thrombin III deficiency); occasionally due to hepatocellular carcinoma
- May result in liver infarction
- Presents with painful hepatomegaly and ascites
Liver function tests:
- Acute disease: high AST,ALT ~5X norm
- Subacute: normal LFTs
A
Budd-Chiari Syndrome
22
Q
- multiple sublobular hepatic venous thrombosis and sclerosis (smaller veins)
- most commonly associated with chemotherapy (azathioprine, 6MP) or graft-vs-host disease (50% incidence with 20-40% mortality).
A
Veno-Occlusive Disease
23
Q
- Fatty Change
- Centrilobular Neutrophilic Infiltrate (vs. lymphocyte/monocyte)
- Hepatocyte balloon degeneration
- Mallory bodies
Alcohol-related:
- AST > ALT (alcohol is a mitochondrial poison)
Non-alcohol related:
- Associated with obesity
- diagnosis of exclusion: ALT > AST
A
Chronic Steatohepatitis
24
Q
- AST & ALT > 1.5x normal
- 4-6 months duration
- periportal mononuclear (lymphocytes & monocytes) infiltrate
- Viral
- Autoimmune
- Drug related (methyldopa, isoniazid)
- Granulomatous: TB, sarcoidosis
- Metabolic
A
Chronic Hepatitis
25
- Pathogenesis - damage to hepatocytes associated with presence of auto-antibodies
- Type 1 (ANA and SMA antibodies) is most common
- predominately young females (
Autoimmune Hepatitis
26
- Drugs commonly cited as causes of chronic hepatitis include: α-methyldopa, nitrofurantoin, oxyphenacetin, and isoniazid.
- Pathogenesis - chronic hepatitis tends to occur as a result of drug-induced immune-mediated hypersensitivity
- Treatment and prognosis - discontinue the drug
Drug-Induced Hepatitis
27
- Iron overload, leading to deposition in tissues and organs
- autosomal recessive, strongly associated genetic marker (C282Y)
- Tissue damage due to generation of free radicals
Extrahepatic organ involvement:
- skin → bronze color (“bronze diabetes”)
- pancreas → diabetes
- heart → failure
- joints → chondrocalcinosis, pain/ arthiritis
Labs:
- increased ferritin (storage)
- decreased TIBC
- increased serum iron
- increased % transferrin saturation
- Use prussian blue stain to distinguish iron (blue) from lipofuscin (brown)
Hemochromatosis
28
- Autosomal recessive defect in ATP7B gene, decreasing hepatocyte copper excretion into bile, leading to copper accumulation
Presents with:
- cirrhosis
- cornea → Kaiser-Fleischer ring
- basal ganglia → ataxia, dysarthria, chorea, and Parkinsonian symptoms
- RBC → hemolysis
- Renal tubules → renal tubular acidosis
Dx:
- measure ceruloplasmin (key molecule that carries copper in blood; decreases in WD)
- Rhodanine: stain for copper
Wilson's Disease
29
- Auto-codominant inherited disorder of the protease inhibitor, αAT (PiZZ phenotype),
resulting in accumulation of αAT in hepatocytes (trapped) and relative serum deficiency
- results in unchecked protease activity, which is tissue-toxic in liver (cirrhosis) and lung (pan-lobular emphysema)
Diagnostic tests
- decreased serum αAT
- alpha-AT eiosinophilic globules in hepatocytes
- PAS-D positive
α-Antitrypsin deficiency
30
- inability for bile/cholesterol to exit via canaliculi, resulting in increase in serum cholesterol and bile acids
- causes steatorrhea and deficiency of fat-soluble vitamins (ADEK)
Clinical presentation:
- Pruritis
- Xanthomas: cholesterol deposits in skin
- Xanthelasma: Cholesterol deposits around eyes and eyelids
Chronic Cholestasis
31
- Chronic inflammation of extrahepatic bile ducts with few neutrophils
- commonly caused by a stone, stricture, or tumor mass that narrows the common bile duct and impedes bile flow
- Lab: increase in alkaline phosphatase, GGT and bilirubin
Complication:
- Ascending Cholangitis: Bile duct necrosis, with neutrophils
- Chronic Cholangitis: Ductopenia
Chronic Extrahepatic Obstruction (EHO)
32
- Autoimmune granulomatous destruction of intrahepatic bile ducts
- classically in women ~40 y.o.
- florid bile duct lesion
Labs:
- increased alk phos, GGT and bilirubin
- AMA (antimitochondrial antibody) positive
- increase in IgM globulin
Dx: requires liver biopsy
Primary Biliary Cirrhosis (PBC)
33
- inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
- Periductal fibrosis with onion-skin appearance
- predominantly in males
- associated with ulcerative colitis
- increased risk for cholangiocarcinoma
Labs:
- increase in alk phos, GGT and bilirubin
- p-ANCA positive
Diagnosis: requires imaging
Primary Sclerosing Cholangitis
34
1. Amount of periportal lymphocytic infiltrate
2. Amount of lobular necrosis ("acidophilic bodies")
3. Amount of portal tract necrosis: Erosion of limiting plate/piecemeal necrosis/interface hepatitis
Grade/Activity/Severity of Inflammation of Chronic Hepatitis
35
- degree of fibrosis
1. Mild: expansion of portal tracts
2. Moderate: bridges of fibrosis between portal tracts to hepatic veins
3. Severe: Cirrhosis, encircling nodules
Stage of Hepatitis
36
Ground-glass hepatocytes: Pale cells with fine, pink cytoplasm
- virtually pathopneumonic of HBV
Hepatitis B
37
- common, discrete small tumors (< 3cm)
- form vascular lakes
- if large, can cause heart failure, thrombocytopenia
Hemangioma
38
- Discrete vascular mass w/ fibrous capsule
- affects mostly females
- growth can bes stimulated by estrogen/birth control
- normal hepatocytes, but not portal tracts/central veins
- risk of rupture
Hepatic Adenoma
39
- Discrete mass
- females 2:1
- Similar to hepatic adneoma, but with central scar and fibrous arms
Focal Nodular Hyperplasia
40
- Malignant tumor of hepatocytes
Dx: increase in alpha-fetoprotein
Risk factors:
- Chronic Hep B +/- cirrhosis
- Cirrhosis
- Aspergillus
Complication:
- increased risk for Budd-Chiari syndrome: presents with painful hepatomegaly and ascites
Hepatocellular Carcinoma
41
- dense collagen stroma in healthy young adults w/o cirrhosis
- better prognosis
Fibrolamellar Variant of Hepatocellular Carcinoma
42
- an adenomcarcinoma from bile duct epithelium (intrahepatic or extrahepatic)
- positive stain for Mucin and CEA
Cholangiocarcinoma
43
- from colon, pancreas, lung or breast
- multiple nodules
- detected as hepatomegaly
Metastases to liver
