Cirrhosis & PHTN Flashcards
Phase 1 vs. 2 of liver drug metabolism
Phase 1: changes lipophilic molecules into water soluble ones via Cytochrome
Phase 2: attachment of large molecules to improve water solubility (glucuronidate, methyl, acetic acid, etc.)
In liver injury, _____________ cell activation lead to the accumulation of scar (fibril-forming) matrix
Stellate
In liver injury, ____________ cell (macrophage) activation leads to activation of Stellate cells
Kupffer
Potential etiologies of Cirrhosis
Viral (Hep B and C) Toxic (Alcohol, drugs) Metabolic (fatty liver) Biliary (PCS and PBC) Genetic (Hemachromatosis, Wilson's Disease, Alpha-1 Antitrypsin) Cystic Fibrosis
What are some pathophysiologic changes that occur during cirrhosis
Unable to process bile (distributes to skin and eyes/scleral icterus) Coagulopathy Less albumin (ascites/edema) Hypoglycemia Portal HTN Longer drug half-lives
consequence of liver cirrhosis; root cause of many complications of cirrhosis; increased pressure in the portal system
Portal HTN
Portal HTN will cause a backup of blood through what veins?
Left gastric vein (esophageal varices) Rectal vein (hemorrhoids) Umbilical vein (caput medusae) Splenic vein (splenomegaly)
Once a patient develops complications (below )of cirrhosis, they have________
Variceal hemorrhage Ascites Spontaneous Bacterial Peritonitis HRS HPS Portopulmonary HTN Hepatocellular carcinoma Hepatic encephalopathy
Decompensated Cirrhosis
MOST devastating complication of cirrhosis and portal HTN; prevention includes endoscopy, non-selective b-blockers and band ligation
Variceal Hemorrhage
Prevention/treatments for Variceal Hemorrhage
Upper Endoscopy
Non-slective b-blockers
Band ligation
The most common cause of ascites is…
cirrhosis
most common complication of cirrhosis;
Ascites
used to help determine the cause of ascites
SAAG
A SAAG score of >1.1 g/dL is indicative of…
Cirrhosis, liver disease
Treatment for Ascites
Low sodium diet
Diuretics
Surgical Shunt (Denver shunt/TIPS)
LVP (Large Volume Paracentesis)
When using diuretics for ascites, you need to carefully monitor the levels of…
sodium (hyponatremia)
complication of cirrhosis; peritoneal fluid >250 neutrophils; due to bacterial translocation from gut (E. coli)
Spontaneous Bacterial Peritonitis (SBP)
With Spontaneous Bacterial Peritonitis, which gut microbe is usually the etiologic agent?
E. coli
complication of cirrhosis; development of acute renal failure due to blood stagnating in mesenteric system instead of the systemic circulation; presents with oliguria, low urine sodium and systemic hypotension
Hepatorenal Syndrome
Oliguria, low urine Na+, and systemic hypotension are clinical presentation of
Hepatorenal Syndrome (HRS)
What are the diagnostic criteria for Hepatorenal Syndrome
- Cirrhosis w/ ascites
- Increased Serum creatinine >1.5 mg/dl
Hepatorenal Syndrome Type (1 or 2) is defined as being RAPIDLY FATAL, 50% reduction of clearance (or doubling of serum creatinine) in <2 weeks
Type 1
Hepatorenal Syndrome Type (1 or 2) is defined as less severe, slower and characterized by diuretic refractory ascities
Type 2
Liver transplant, in the setting of Hepatorenal Syndrome, will result in an improvement of renal function (True or False)
True
The most common causes of Hepatocellular Carcinoma (worldwide vs. Western)
- Worldwide: HBV (Hep. B)
- Western:
1. HCV (Hep. C)
2. Non-alcoholic fatty liver disease
3. Alcohol
How can you potentially diagnose Hepatocellular Carcinoma w/o biopsy
MRI
- AFP can be helpful
Although not sensitive or specific, but if AFP (Alpha Feto Protein) is >200, _______ highly suscipicious
HCC
procedure done for cirrhotic liver; shunt is placed between hepatic and portal veins with the goal of reducing portal HTN; used for varices and ascites; complications include hepatic encephalopathy and hepatic failure (toxins bypass liver into systemic circulation)
TIPS
complication of cirrhosis, and possibly TIPS; disturbance of CNS function due to hepatic insufficiency and toxic buildup (ammonia); patients will present with AMS (altered mental status)
Hepatic Encephalopathy
What neurotoxin can accumulate and cross BBB causing hepatic encphalopathy?
Ammonia
How to diagnose Hepatic Encephalopathy
- Diagnosis of exclusion
- Elevated ammonia (helpful, but not sensitive/specific)
Live-saving intervention for decompensated cirrhosis; shows ~90% 5 year survival
Liver Transplant
The most common cause of acute liver failure is…
Drugs
Drug-induced liver injury can be caused by either…
1) toxic reaction to drug/metabolite
2) immune-mediated inflammatory reaction to the drug
What are the two patterns of hepatotoxicity due to drugs
Intrinsic: predictable, dose-depending injury (higher dose= more injury)
Idiosyncratic: injury not predictable (not dose-dependent)
Acetaminophen is metabolized in the liver via what three pathways?
1) Glucoronidation*
2) Sulfation*
3) Cytochrome P-450 (phase 1; produces toxic NAPQI)
- are the main metabolizers (phase II) and produce non-toxic products
Which drug is the single most common cause of Acute Liver Failure, usually due to overdosing
Acetaminophen
Examples of etiologies for Chronic Liver Failure
Hep B and C (both are viral etiologies –> cirrhosis –> CLF)
Cirrhosis requires that what two anatomic alterations take place?
1) thick fibrosis of septa
2) Regenerative nodules
Fibrosis stage is _______ but cirrhosis is not _______
reversible
What will a cirrhotic liver look like on CT?
Shrunken liver
Bumpy/nodular texture
Why might the spleen be enlarged with liver cirrhosis?
Portal HTN causes back-pressure of blood into the celiac trunk and into the splenic vein
The repetitive injury and repair that leads to cirrhosis can make someone more prone to…
HCC
What will hepatocellular carcinoma look like on a slice of liver tissue?
Nodular
Darker and more bile-stained (Greenish)
If you wanted to see the severe fibrosis in liver cirrhosis, which stain would you use on a tissue sample?
Trichrome stain
What aspects of the “healing process” in the liver contributes to the development of cirrhosis?
- Loss of vessel fenestrations
- Deposition of basement membrane
- Fibrosis (collagen deposition) in Space of Disse
How can cirrhosis result is hematemesis?
Cirrhosis—> Portal HTN—> Esophageal/gastric varices—> Rupture with massive bleeding
Also note that cirrhosis can cause diminished clotting factors, further worsening bleeding
What is prehepatic cause of PHTN in non-cirrhotic CLF?
Portal Vein Thrombosis
- Normal liver tissue and functions (until severe) b/c patient don’t have cirrhosis, and their liver is provided adequate blood flow by proper hepatic artery.
What is intra-hepatic cause of PHTN in non-cirrhotic CLF?
Amyloidosis (accumulation of abnormal proteins)
- Congo red stain + (amyloid appears orange-red color)
- Apple-green under polarized light
What is post-hepatic cause of PHTN in non-cirrhotic CLF?
Budd-Chiari Syndrome
*Thrombotic occlusion of the hepatic vein causing venous back pressure to damage liver
What is the histologic hallmarks of Budd-Chiari Syndrome?
Hepatocytes are congested with RBCs
- looks bloody
Why might the caudate lobe not be effected by a Budd-Chiari Syndrome clot?
Caudate lobe is drained by small veins that directly enter IVC (bypasses thrombosed hepatic vein); compensatory hypertrophy (caudate hypertrophy) occurs
