09: Cirrhosis & Portal Hypertension Flashcards
What is cirrhosis?
- End-stage chronic liver disease
- Characterized by regenerative nodules surrounded by fibrous septa, disruption of architecture
What are common etiologies of cirrhosis?
- Alcohol
- Viral hepatitis
- Non-alcoholic fatty liver disease
- Genetic/metabolic
NB: All these etiologies have same cirrhotic presentation.
Trace the pathway to cirrhosis.
- Injury
- Inflammation
- Fibrosis
- Resolution (if intervene at stage 0-3 fibrosis)
- Cirrhosis –> HCC
NB: Average time from injury to cirrhosis = 20yrs.
Describe the pathogenesis of cirrhosis.
- Inflammation, cytokines and/or toxins stimulate stellate (ito) cells
- Stellate cell transforms into myofibroblast and deposits **type I & II collagen **in all portions of lobule
- Architecture and vasculature disrupted; diffusion of solutes impaired
What are the complications of cirrhosis?
- Portal hypertension
- Varices
- Ascites
- Hepato-renal syndrome
- Loss of synthetic function
- Hepatic encephalopathy
- Protein loss
- Coagulopathy
- Decreased muscle mass
- Infection (2/2 loss of complement)
List the causes of portal hypertension.
- Pre-hepatic:
- Portal vein thrombosis
- Splenic vein thrombosis
- Intra-hepatic:
- Pre-sinusoidal: schistosomiasis
- Sinusoidal: cirrhosis
- Post-sinusoidal: veno-occlusive disease
- Post-hepatic:
- Budd-Chiari syndrome (occlusion of vena cava of hepatic vein)
Describe blood flow through the liver.
- High flow (mesenteric vessels)
- Low pressure (vast network of sinusoids)
What are the efffects on blood flow of portal hypertension?
- Fibrosis restricts blood flow –> ↑portal vein pressure
- Collaterals acquire ↑pressure –> varices of spleen, esophagus & stomach; gastropathy (mucosal friability)
- Ascites due to fluid shift into peritoneum
- ↓toxin metabolism due to shunting –> peritonitis
What pressure defines portal hypertension?
- Measure the portal vein-hepatic vein pressure gradient
- **Free HV pressure **= catheter w/ deflated balloon in hepatic vein
- **Wedged PV pressure **= inflated ballon in hepatic vein
- PV-HV pressure > 10 mmHg = significant pHTN (nl = <7 mmHg)
Describe the pathophysiology of portal hypertension.
- ↑resistance to inflow/outlow due to fixed scarring of liver
- ↑flow to portal system
- ↑splanchnic flow (vasodilation/NO), due to:
- ↑eNOS activity in splachnic bed
- shear stress releasing VEGF & TNF –> ↑NO production
- ↑heme oxygenase activity & CO production
- ↑cardiac output
- low SVR
- ↑blood volume
- ↑splanchnic flow (vasodilation/NO), due to:
What are esophageal varices and how are they treated?
- Extremely dilated sub-mucosal veins in the lower third of the esophagus
- Risk of bleeding; death from bleed >20%
- Acute therapy:
- Stabilize hemodynamics
- Decrease portal pressure (**octreotide **or somatostatin)
- Endoscopy (banding)
-
Transjugular Intrahepatic Porto-Systemic Shunt (TIPS)
- Produces connection between portal and hepatic veins
- Surgical shunt; limited indications:
- Cirrhosis of children
- Budd-Chiari syndrome
- Non-cirrhotic pHTN
- Chronic therapy: beta-blockers (propranalol or nadolol) or banding ablation
What are ascites?
Accumulation of fluid in the abdomen
What can cause ascites?
- Portal hypertension
- Cirrhosis
- Hepatic (or portal vein) occlusion
- Heart failure
- Peritoneal inflammation
- TB peritonitis
- Carcinomatosis
- Ovarian cancer
- Nephrogenic ascites
- Pancreatic ascites
- Other (schistosomiasis, non–cirhotic portal HTN, polycystic liver disease)
Trace the pathway of ascites in portal HTN.
- Cirrhosis –> portal hypertension
- Splanchnic arterial vasodilation –> ↓systemic vascular resistance
- Arterial underfilling –> sensed “hypovolemic” state
- Stimulation of systemic vasoconstrictors
- Renal vasoconstriction (to retain Na & H2O)
- Early stages of cirrhosis
- ↑systemic & local vasodilators
- preserved renal perfusion
- Late stages of cirrhosis
- ↓local vasodilators, ↑local vasoconstrictors
- Hepatorenal syndrome
Describe the pathophysiology of ascites.
- ↓albumin due to hepatic synthetic dysfunction –> ↓oncotic pressure –> fluid leaking out of vascular space
- ↑sinusoidal hydrostatic pressure –> ↑fluid movement from sinusoids to space of Disse –> ↑hepatic, thoracic duct lymph flow
- ↑lymph production exceeds capacity of lymphatics to return it to circulation –> XS lymph spills into peritoneal cavity
- initially reabsorbed by peritoneal surface of diaphragm (communicates with supradiaphragmatic lymphatics)
- when ascites formation > reabsorption, clinically evident ascites occurs
- Hypovolemia activates RAAS pathway & sympathetic nerve activity –> renal Na & H2O retention
- ADH secretion increases w/ more profound vasodilation –> water retention & hyponatremia
How is ascites due to portal hypertension diagnosed?
- Serum-ascites albumin gradient (SAG) > 1.1 g/dL
- WBC < 50 cc/mm; mostly mononuclear
- Normal ascitic fluid amylase
What is the treatment for ascites?
- Bedrest
- Na+ restriction (1.5-2 g/day)
- Fluid restriction (1.5L if Na+ <120)
- Diuretics (maximum dose)
- **Spironolactone **(aldosterone inhibitor)
- **Furosemide **(loop diuretic)
- Amiloride, HCTZ, Metolazone, Zaroxyln
- Large-volume paracentesis
- TIPS (for refractory ascites)
- Surgery (Leveen/Denver shunt; transplantation)
What is a hepatic hydrothorax and how is it treated?
- Ascites leak through rents (<1cm holes in diaphragm)
- Dx by fluid characterstics (similar to ascites)
- TIPS is treatment of choice if refractory
- Liver transplant may be necessary
- Avoid chest tubes; surgical repair not usually effective
What is spontaneous bacterial peritonitis?
Infection of ascitic fluid independent of another intra-abdominal source (e.g., perforation); monomicrobial; source: a) enteric flora enters portal circulation, not cleared or b) translocation of bacteria from gut
How is spontaneous bacterial peritonitis diagnosed?
Ascites WBC > 500 or 250 w/ greater than 50% PMNs
What risks contribute to spontaneous bacterial peritonitis?
- GI bleeding/hypotension
- Advanced liver disease
- Previous history of SBP
How is spontaneous bacterial peritonitis prevented?
- Early treatment of other infections
- Prophylactic antibiotics to GI bleeders
- Oral quinolones, bactrim can prevent recurrence when given chronically
What are the most common organisms in spontaneous bacterial peritonitis, and how is it treated?
- E. coli, Klebsiella, Pneumococcus, Enterococcus
- Broad spectrum abx and then narrow spectrum abx if culture results known
- Re-tap after 48 hours to confirm therapy response
- Volume expand with albumin (reduce hepato-renal syndrome)
NB: SBP does not have same presentation as acute peritonitis (no abdominal pain or fever; pts often p/w hepatic encephalopathy and/or fatigue).
