liver (W4) Flashcards
what does the liver do?
so much stuff!
1. metabolism/storage
2. blood volume reservoir
3. blood filter
4. blood clotting factors
5. drug metabolism and detoxification
liver metabolism
fat, cholesterol, protein, vitamins, minerals
blood reservoir
distends and compresses to alter circulating blood volume
blood filter
helps purify blood
blood clotting factors
includes prothrombin and fibrinogen
drug metabolism and detoxification
metabolizes drugs and removes toxins
when liver isn’t working…
effects all of these things:
1. metabolism/storage
2. blood volume reservoir
3. blood filter
4. blood clotting factors
5. drug metabolism and detoxification
portal circulation
brings blood to liver, stomach, intestine, spleen, pancreas
where does blood enter the liver?
portal vein
where are absorbed products of digestion sent?
directly to liver and sent to lobules
first pass effect
liver responsible for first past effect, oral drugs have hight mg, liver takes a portion
what is a LFT
liver function test
AST
ALT
Alk phos
not a great indicator of disease severity
LFT
LFE, increase
bilirubin
serum ammonia, increase
serum protein, decrease
serum albumin, decrease
PT, increase
jaundice AKA icterus
increase levels of bilirubin in blood
visible at 2-2.5
yellow
classifications of jaundice
- hemolytic, increased breakdown of RBC
- hepatocellular, liver unable to take up bilirubin from blood or unable to conjugate it
- obstructive, decreased/obstructed flow of bile
bilirubin
by productive of heme breakdown
unconjugated versus conjugated
conjugated/direct bilirubin
30%
the liver isn’t working, bilirubin can’t get out
obstruction/gallstones
unconjugated/indirect bilirubin
70%
elevations when overproduction or impaired liver function
where to look for jaundice
sclera of eyes
palms/soles of feet
mucus membranes
jaundice manifestations
darker urine
liver enzymes, elevated
stools, normal/clay-colored
pruritis
viral hepatitis
systemic virus
liver
inflammation
A/B/C
other types of viruses that can cause inflammation of liver: epsetin barr/cytomegalovirus
inflammation of the liver can occur from: ETOH abuse, certain drugs, bacteria, chemicals
most common types of hepatitis
a and b
hepatitis e
very dangerous in pregnancy
pathogenesis of hepatitis
viral infection
immune response: inflammatory mediators
lysis of infected cells
edema/swelling
tissue hypoxia
hepatocyte death- can lead to LT liver failure
clinical manifestations of hepatitis
similar between all types
many times asymptomatic
can range from none, mild, liver failure
causes abnormal LFTs but not consistent with cellular damage within the liver- trend data
3 stages of hepatitis a/b/c
prodromal, icteric, recovery
prodromal
2 weeks after exposure
fatique, anorexia, malaise, nausea, vommitting, HA, hyperalgesia, cough, low grade fever
HIGHLY TRANSMISSIBLE
icteric (active)
begins with jaundice
jaundice, dark urine, clay-colored stools
enlarged liver, painful upon palpation
fatigue, abdominal pain persists or increases in severeity
recovery
resolution of jaundice
6-8 weeks after exposure
symptoms diminish
liver remains enlarged/tender
viral hepatitis complaints
most require with no complications
higher mortality in older/comorbidities
complications include: chronic hepatitis, liver cirrhosis, liver cancer, fulminant viral hepatitis (acute liver failure)
hepatitis a
foodborne illness
transmissible via fecal oral, parental, sexual
acute onset with fever
usually mild severity
does not lead to chronic hepatitis
affects children/adults
prevent with: hand hygiene, vaccine (get if high risk, traveling to areas with poor sanitation)
hepatitis b
iv drug use, sexual contact
dirty needles/unsafe sex
insidious
reallllyyyyy long incubation period
can lead to chronic
any age group
vaccine
hepatitis c
iv drug use/sexual contact/mother to fetal/medical mishaps
insidious
mild to severe symptoms
80% converts to chronic hepatitis
any age is affected
sceening blood, hygiene
no vaccine
leads to hepatocellular carcinoma- transplant
new treatment available! can be cured
which hepatitis conditions have vaccines?
a and b
hep a series
2 doses, 6 months apart
recommended for all children beginning at 12 months
special high risk population
hep b series
3 doses, 4 months apart
recommended for all infants as newborns
hep c series
kidding! no vaccine
HBV pharm considerations
chronic disease
- interferons
- nucleoside analogs
treatment only for high risk patients:
increased AST levels
hepatic inflammation
advanced fibrosis
disadvantages:
prolonged therapy
costly
AE- drug interactions/etc.
high relapse
HCV pharm considerations
treatment only recommended for chronic disease
treatable and eliminated in most patients
treated with direct anti-viral therapy and interferon based regiments
some require treatment along with nucleoside analogue medication as well
hepatitis and tylenol
2 gram max, avoid if serious advanced liver disease
cirrhosis
irriversible inflammatory fibrotic liver disease
what happens to the liver during cirrhosis
structural changes from injury, either alcohol or virus, and fibrosis
what is chaotic fibrosis?
leads to obstructive biliary channels and blood flow, causes jaundice and portal hypertension
what disrupts the regeneration of liver during cirrhosis?
hypoxia, necrosis, atrophy, and liver failure
removal of toxin
can stop porgression, not reversible
cirrhosis common cause
hepatitis B and C
excessive alcohol intake
idiopathic
NASH
most common type of cirrhosis
alcoholic cirrhosis
stages of alcoholic liver disease
alcohol fatty liver- mildest asymp (reversible)
alcoholic steatohepatitis- the precursor to cirrhosis, inflammation, degeneration of hepatocytes
alcoholic cirrhosis- fibrosis and scarring alter the liver structure
pathogenesis of cirrhosis
liver cells destroyed
cells try to regenerate
disorganized process
abnormal growth
poor blood flow and scar tissue
hypoxia
liver failure
stages of liver damage
healthy liver
fatty liver- deposits of fat lead to liver enlargement
liver fibrosis- scar tissue forms
cirrhosis- growth of connective tissue destroys liver cells
early manifestations of cirrhosis
slow, insidious process
GI disturbances
fever, weight loss
palpable liver
late manifestation of cirrhosis
jaundice
peripheral edema
decreased albumin and protein
ascites
skin lesions
hematologic problems
endocrine problems- amenorrhea
esophageal and anorectal varices
encephalopathy
portal hypertension
resistant portal blood flow, leads to varices and ascites
what causes portal hypertension
systemic hypotension, vascular underfilling, stimulation of RASS system, plasma volume expansion, increased CO- all lead to ascites
portal hypertension is asymp until
complications occur- variceal hemmorhage, ascites, peritonitis, heptorenal syndrome, cardiomyopathy
portal hypertension is asymp until
complications occur- variceal hemorrhage, ascites, peritonitis, hepatorenal syndrome, cardiomyopathy
fibrosis of the liver
irreversible, prevent/treat complications
and wait for liver transplant
vascular lesions
common in end-stage liver failure
hepatic encephalopathy
LOC is primary driver of diagnosis
encephalopathy is graded by severity
minimal to grade 4
liver not filtering out toxins, toxins enter the brain, impact LOC- confusion (abnormal psychometric test) to coma (unresponsive)
encephalopathy
encephalopathy
high ammonia levels, neurotoxin, crosses BBB
never diagnose encephalopathy based on
ammonia level
acute liver failure- fulminant liver failure
separate liver failure, not caused by cirrhosis of liver
most common cause of acute liver failure
acetaminophen OD
patho of acute liver failure
edematous heptocytes and patchy areas of necrosis and inflammatory cell infiltrates and disrupts the liver tissue
when does acute liver failure occur
6-8 weeks after viral hepatitis or metabolic liver disease
5-8 weeks after acetaminophen OD
s/s of acute liver failure
similar to cirrhosis
treatment for acute liver failure
not much, liver transplant
lactulose
hepatic encephalopathy
hyperosmotic
indication: reduce ammonia absorption in hepatic encephalopathy
MOA: reduces blood ammonia levels by converting ammonia to ammonium
given PO/enema aka recetal
can be given to titrate by number of stools or by ammonia levels
not just given for high ammonia levels- must have s/s of encephalopathy
make sure patient is not hypokalemic
rifaximin
hepatic encephalopathy
second line if lactulose isn’t working
moa: inhibits bacterial RNA synthesis by binding to bacterial DNA (usually used as an AB for GI infections)
can be given preventative- HCP preference
given PO
SE: peripheral edema, nausea, ascites, dizziness, fatigue, pruritis, skin rash, abdominal pain, anemia
associated with increased risk of c diff
