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Terms in this set (86)
What are some causes of cirrhosis?
-Chronic alcohol consumption
-Hepatitis B and C
-Metabolic liver disease
Under normal conditions, hepatic stellate cells function to store _________ and help to maintain the normal matrix in the sinusoidal space
During chronic liver disease, stellate cells undergo an "activation process". What does this do?
Causes stellate cells to lose vitamin A and become highly proliferative and synthesize fibrotic scar tissue
______ ______ is characterized by hypervolemia, increased cardiac index, hypotension, and decreased systemic vascular resistance.
What is the main component in the patho of acites and renal dysfunction?
Activation of neurohumoral vasoactive factors
What is the activation of neurohumoral vasoactive factors?
A response that occurs in an effort to maintain the arterial blood pressure within normal limits
How is cirrhosis usually Dx?
Ct and MRI
Liver biopsy (if failed non-invasive attempts)
What elements are part of the Child-Pugh Grading?
Child-Pugh Grade 1`
Total Bili <2
Prothrombin time <4
Child-Pugh Grade 2
Total Bili 2-3
Encephalopathy 1 and 2
Prothrombin time 4-6
Child-Pugh Grade 3
Total Bili >3
Encephalopathy 3 and 4
Prothrombin time >6
What grading system is used to prioritize transplant recipients and helps to estimate prognosis for pts with ESLD?
What 3 lab values are used to determine a MELD score?
MELD Scoring range
0-40; higher numbers indicate a greater risk of death within 3 months (and thus a greater likelihood to get a transplant)
_______ is an accumlation of excessive amount of fluid within the peritoneal cavity
What is the most common complication of cirrhosis?
nearly half of patients with ascites will die
How does ascites form?
It is a results of the development of sinusoidal hypertension and portal hypertension
Portal hypertension activates the release of overproduction nitric oxide which leads to splanchnic and peripheral arteriolar vasodilation which will lead to a drop in ______ _______
What two things are released in response to arterial hypotension?
RAAS activation and ADH (sodium and water retention)
Due to persistent renal sodium and water retention along with increase splanchnic vascular permeability promotes leakage into the ____ ____
What is SAAG and what is it used for?
Serum-Ascites Albumin Gradient
it is used for interpreting ascitic fluid and determining if ascites is a result of portal HTN or another process
What is the SAAG formula?
SAAG = serum albumin -ascitic albumin
A SAAG greater than or equal to ___ indicates portal hypertension
Tx goals for Ascites
Control ascites, prevent or relieve ascites-related symptoms
Does Tx have a great effect on survival?
When should tx be initiated?
in stable patients
What drugs should be avoided in ascites?
Those that decrease renal perfusion: ACE, ARB, BB, NSAIDS
When using diuretics for ascites, what is the ratio of spironolactone:furosemide? Why is this ratio used?
It is used because it usually maintains normokalemia
MOA of Aldactone
K-sparing aldosterone antagonist diuretic
MAX dose of Aldactone?
Why is Aldactone usually not used as monotherapy? What is it combined with?
Pts commonly become hyperkalemic
Combined with loop diuretic
Can Lasix be used as monotherapy for the tx of Ascites?
Max dose of Lasix
What is the goal of Duiretic therapy in ascites?
increase urinary excretion of sodium to >78mmol/day
When should diuretics be stopped?
-If pts develop uncontrolled or recurrent encephalopathy
-Serum Na <120 mEq/L despite fluid restriction
-SCr >2.0 mg/dL
What do you give if you pull off too much fluid?
Give albumin post-paracentesis for extraction volumes >5L
Portal hypertension is the presence of a gradient of ____ mmHg between the protal and central venous pressures
Esophageal and gastric varices and variceal bleeing may arise after an HVPG of ___ is reached
What is the 1st line primary prophylaxis for portal vein hypertension?
MOA of BB in portal vein hypertension
Reduces portal pressure by reducing portal venous inflow by decreasing cardiac output via beta-1 and decrease splanchnic blood flow through beta-2 blockade
What should the HR of BB be when treating for portal vein hypertension
What is a mechanical prophylaxis therapy that places rubber bands around varices until the varices are obliterated?
EVL (endoscopic variceal ligation)
What are some treatments for an acute variceal hemorrhage?
What is a natural occurring hormone that is more effective for controlling acute hemorrhae from esophageal varices?
What is a somatostatin analogue that selectively induces splanchnic vasocontriction? It also inhibits growth hormone, glucagon, and insulin more effectively than somatostatin
Antidiuretic hormone that is a non-selective vasoconstrictor. It acts on V1 receptors which causes smooth muscle contraction and V2 receptors and causes antidiurtic effects
Why is vasopressin not used as much as octreotide?
There are more systemic effects with vasopressin
Long-acting selective alpha 1 that causes vasoconstriction, and is a pordrug that is rapidly hydrolyzed to active metabolite, rapid onset, lacks CNS penetration, minimal cardiac effects
Midodrine (Proamatine, Orvaten)
What is an infection of ascitic fluid that occurs in the absence of any evidence of an intra-abdominal, surgically treatable source of infection?
Spontaneous Bacterial Peritonitis (SBP)
What is the key mechanism by which SBP occurs?
3 most common pathogens with SBP
Clinical presentation of SBP
Dx of SBP
Absolue polymorphonuclear counts of >250
S/S of SBP infection regardless of count
Tx of SBP
Cefotaxime 2g q8hr (or a similar 3rd gen Cef)
Duration of Tx for SBP
Alternative tx for SBP
Ofloxacin or IV Cipro
Prophylaxis of SBP
Bactrim DS or norfloxacin
When should pts receive long term prophylaxis?
Those who survived an episode of SBP
According to Dipro, what else can be used for prophylaxis? (3)
7 days of Norfloxacin or IV Cipro or IV Ceftriaxone
What is the main cause of Hepatic Encephalopathy (HE)?
Patho of HE
Accumulation of gut-derived nitrogenous substances that are in systemic circulation----> they enter in the CNS and alter neurotransmission and can affect consciousness and behaviour
What are the tx goals of HE?
lower blood ammonia levels and avoid precipitating factors
Nutritional support when treating for HE?
Protein withdrawal during acute episodes
What are some pharm treatments for HE?
Lactulose is converted to _____ and ____ by gut flora
acetic acid and lactic acid
How does lactulose decrease ammonia levels (3)
-Laxative effect that reduces the time period available for ammonia absorption
-Leaching of ammonia from circulation into the colon by increased bacterial uptake
-Reducing production of ammonia by interfering directly with the uptake of glutamine by the intestinal wall and its subsequent metabolism to ammonia
How are Neomycin and Metronidazole useful for lowering ammonia?
Inhibits the activity of urease-producing bacteria and ultimately decrease production of ammonia
Neomycin also inhibits ___ further reducing ammonia production
Why is Rifaximin preferred over Neomycin and metronidazole?
Why is Flumazenil used in HE?
It enhances GABAergic tone and increases amounts of endogenous BZDs which may contribute to HE
When is Bromocriptine indicated for HE?
Chronic HE in pts who are unresponsive to other therapies
What two procoagulant factors are elevated in chronic liver disease?
Factor VIII and von Willebrand factor
End stage chronic liver disease is associated with decreased synthetic capability of the liver which leads to decreased levels of _______ factors
The rebalanced homeostasis is seen in chronic liver disease and can be tipped toward either thrombosis of clinically significant bleeding at any time
What is used for treatment of bleeding?
______ is functional renal failure that occurs in the setting of cirrhosis; represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury
Patho of HRS
Extreme systemic vasodilation causes intense renal vasoconstriction, which reduces blood supply to the kidneys and causes extreme sodium retention and oliguria.
Treatment for HRS
-Expand intravascular volume with IV albumin
What do you use to bridge pts about to get a liver transplant with HRS? What about critically ill pts with HRS?
NE IV continuous (MAP >10) + albumin for 2 days
Midodrine + octreotide +albumin
For HRS what is the only therapy shown to prolong survival?
What is the median survival for type 1? Type 2?
Patho of Hepatopulomary syndrome?
defect in arterial oxygenation, which is caused by the pulmonary vascular dilation that occurs in the presence of liver disease
How can you treat HPS?
You can't; just a liver transplant can fix it; supportive care is only thing you can do
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