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explain the pathogenesis of Cirrhosis. what are the 3 main morphologic characteristics? central processes? mechanism of fibrosis?
- 3 main morph characteristics:
- bridging fibrous septa--fibrosis (collagen deposition & remodeling)
- parenchymal nodules containing hepatocytes encircled by fibrosis
- disruption of architecture of entire liver
- Central Processes:
- death of hepatocytes
- extracellular matrix deposition
- vascular reorganization
- *collagen deposited in space of Disse --> fibrotic septal tracts --> loss of fenestrations of sinusoidal epithelial cells (apillarization of sinusoids)
- mechanism of fibrosis:
- proliferation of hepatic stellate cells --> activate to fibrogenic cells
- Kupcffer cells & lymphocytes release cytokines & chemokines that modulate expression of stellate cells (TGF-beta, MMP-2)
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what is asterixis? what does it indicate?
- asterixis = hand tremor when trying to extend the wrist
- can indicate hepatic encephalopathy
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describe the virology of HCV infection.
- HCV:
- Hepacivirus
- enveloped, +ssRNA
- infects liver cells & lymphocytes
- Interrupts apoptotic signals via cytokines (TNF-a, IFNa)
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describe the natural hx of HCV
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what is decompensated cirrhosis?
it is the final/later stage of cirrhosis that shows:
- asites
- varices
- encephalopathy
- jaundice
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what factors of cirrosis contribute to creating ascites?
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what is the pathogenesis of SBP?
- protein is LOW (icluding complement proteins), usually <1g/dL is high risk for developing
- poor liver filtration fn can allow spread of microbes
- decreased activity of neutrophils in pt's w/ advanced liver dz
- *poor opsonic activity -->SBP
- *moderate --> CNNA
- *good --> sterile nonneutrocytic ascites
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what dxic tests can be done to evaluate ascites & cirrhosis?
- Ascites:
- look for "shiftin dullness" (air-fluid interface)
- XR - central bowel gas pattern
- US - can schow ascites & fat/fibrosis
- Cirrhosis:
- Serum-Ascites Albumin Gradient >1.1g/dL suggests cirrosis
- MRI - splenomegaly, abnL parenchyma
- cytology to check for cancer
- culture
- biopsy to guide Tx
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what causes SBP? what are the signs and what tests need to be done?
- SBP caused by:
- enteric G- bacteria- E.coli (50%), Kelbsiella (10%), Strep. pneumonia & grp A streps (15-20%) or anaerobic/microaerophilic organisms (55)
- Signs/tests:
- ascites associated w/liver disease
- >250 PMN's/mL of ascites fluid
- usually have fever
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describe the long term management for Cirrhosis
- evaluate for liver transplant, get on waiting list
- while waiting:
- --diuretics: aldosterone blocker b/c we have a 2ndary hyperaldosterone issue (spironolactone), + loop diuretic (furosemide)
- Sodium restricted diet + fresh food, avoid processed
- --Propranolol, metolol (non-selective beta-blockers) b/c might have inadequate venous return (lowBP) b/c of pressure on IVC from ascites
- --therapeutic drainage - no more than 5L & replace w/fluid containing albumin
- --pts w/cirrhosis should get HAV, HBV, pneumococcal & influenza vaccines
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what additional tx may need to be done if having recurrent ascites & varices in liver cirrhosis?
- Transjugular Intrahepatic Portosystemic Shunt (TIPS); appears to be tx of choice for refractory hepatic hydrothorax
- *complications: hepatic encephalopathy b/c can't remove nitrogenous wastes **need to give lactulose to help remove ammonia
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what tx needed for SBP?
- IV cefotaxime (ceftriaxone & amoxicillin-clavulanic acid are alternatives)
- may need supplemental administation of IV albumin
- **in high-risk cirrhotic pt's the risk of peritonitis, hepatorenal syndrome & death may be reduced by prophylactiv norfloxacin, ciprofloxacin, or TMPS**
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what signs indicate hepatorenal syndrome?
- advanced cirrhosis & ascites
- azotemia (serum Cr >1.5mg/dL) in the absence of parenchymal kidney dz or shock & failure of kidney fn to improve
- oliguria
- hyponatremia
- low urinary sodium
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describe pathogenesis of Esophageal Varices
- increased portal venous pressure secondary to cirrhosis
- systemic vasodilation w/decreased vascular resistance and the formation of a hyperdynamic circulation may also contribute
- increased flow is responsible for 40% of increase; resistance to flow is responsible for 60% of increase in portal pressure in cirrhosis
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describe management of esophageal varices.
- they MUST go to ICU
- band ligation **preferred method
- sclerotherapy + Rx
- +prophylatic abiotics
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describe the early treatments of ascites ("dropsy").
- squill bulb (contains cardioactive glycosides similar to digitalis)
- mix of: white chameleon thistle, wall germander, yellow bugle, periwinkle (Pliny only used the first 2)
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what is the pathogenesis of a Mallory-Weiss tear?
vertical mucosal tear of GEJ usually associated w/increased abd pressure
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describe the steps for evaluating an Acute Upper GI bleed.
- Upper endoscopy = test of choice
- early endoscopy is good for management descisions
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what is the management steps for an active UGI bleed?
- **see algorithm
- stabalize: IV fluid, blood if needed
- Vasopressin to vascoconstric @ local site
- admit to ward --> discharge when stable
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