liver: patho and pharm Flashcards
prevention: vax - hep A
2 doses 6 mo apart
rec: all children beginning at 12 mo, special high risk pops (health care, traveling, handle food, not requirement)
prevention: vax - hep B
3 doses at least 4 mo apart
rec: all infants beginning as newborns, titer for healthcare
classes for chronic HBV
different strains, mutate, some more resistant so we use 2 classes - usually combo
interferons
nucleoside analogs
hbv treatment
only for high risk pt - evidence that liver is suffering:
elevated AST, hepatic inflam (US or CT), advanced fibrosis
lots of drugs, changes constantly
hbv treatment: disadvantages
prolonged therapy
costs and adverse effects - interfere with a lot of drugs and each other and SE
high relapse - develop back into having an acute attack, treatment not great
hcv treatment
only recommended for chronic - however this is changing with newer and more effective drugs (treat anyone with detectable viral loads)
now easily treatable and eliminated in most
treat with direct acting antiviral therapy and interferon based regiments (some also need nucleoside analogue)
cost! but beneficial bc work well
note!: can take acetaminophen but <2g/day! (avoid NSAIDS all together if in liver fail), help with fatigue and malaise
pharm for cirrhosis/liver disease
lactulose
rifaximin
lactulose
hyperosmotic laxative
I: reduce ammonia abd in hepatic encephalopathy, also constipation
moa: creates acidic env to reduce blood ammonia levels by converting ammonia to ammonium (water sol and trapped in intestines = not abs)
PO or enema/rectal
lactulose: nc
can be given to titrate by # of stools (2-3/day) or by ammonia levels - not just given for high ammonia levels though - must have s/s of encephalopathy
make sure pt is NOT hypoK - increases renal ammonia production (monitor levels)
can take at home to treat LOC changes
rifaximin
2nd line if lactulose isnt working, so for hepatic encephalopathy
moa: inhibit bacterial rna synthesis by binding to bacterial DNA (initially used as an abx for GI)
sometimes preventative - hcp pref
PO
rifaximin: SE
peripheral edema, n, ascites, dizzy, fatigue, pruritis, skin rash, abd pain, anemia
has been associated with increased risk of c diff - monitor
liver function
met and/or storage of: fat, CHO, P, vits and min
blood volume reservoir: distend (compress to alter circulating BV)
blood filter: purify blood -> remove billy (hgb breakdown)
blood clotting factors -> proT and fibrinogen
drug metabolism and detox
liver anatomy
lobes = funcitonal units, made of hepatocytes, arranges around central vein, can regrow/generate
kupfer cells line inner liver caps/sinusoids, remove bacteria and toxins from blood
liver: portal circulation
blood into liver from stomach, intestines, spleen, pancreas (rich in nutrients), enters via portal vein
absorbed products of digestion come directly to liver and sent to lobules -> 1st pass effect
LFT: ALT, AST, alk phos
enzymes
not great indicator of disease severity
abn is elevated
LFT: billy
total, conjugated, direct, unconjugated (indirect)
abn is elevated
LFT: serum ammonia
liver breaks down
abn is elevated
LFT: serum P
liver makes
abn is decreased
LFT: serum albumin
abn is decreased
LFT: proT time
abn is elevated
jaundice
icterus
sclera! palms and soles, mucus membranes
caused by elevates billy in blood -> usually causes problems and is noticeable with total billy >2-2.5, look at conjugated v unconjugated to determine cause
yellowish discoloration of skin and deep tissues
3 classifications
jaundice: hemolytic
increased breakdown of RBCs
bleeding or polycythemic
jaundice: hepatocellular
liver unable to take buildup of billy from blood or unable to conjugate
liver not doing its job
jaundice: obstructive
decreased or obstructed flow of bile (billy cant get out)
r/t gallstones
bilirubin
by product of heme breakdown - mainly hbg
direct = conjugated
indirect = unconjugated
elevations of indirect billy = billy overP or impaired liver F
elevations of direct = liver working out cant get out -> bile obstruction, gallstone
jaundice: cm
urine = darker
liver E = elevated
stools = normal or clay colored (infection or obstruction)
pruritus = billy buildup - general or [] in palms and soles
hepatitis
viral
systemic, mainly affects liver -> inflamm
various strains cause different types -> A, B, C, can also be caused by epstein barr virus and cytomegalovirus (just inflam, not infection)
hepatitis (just inflam, not infection), can also occur from OH abuse, drugs, chm, bacteria
E is v dangerous for preg
hepatitis: patho
viral infection -> immune inflam mediators -> lysis of infected cells -> edema and tissues swelling -> tissue hypoxia -> hepatocyte death
hepatitis: cm
similar btw all types
many cases of all types are asymptomatic -> but can range from none, mild, liver fail
cause abn elevated LFTs -> non consistent with cellular liver damage
prodromal -> icteric -> recovery
hepatitis: cm - prodromal
2 weeks after exposure
fatigue, anorexia, malaise, n/v, HA, hyperalgesia, cough, low grade fever
HIGHLY transmissible
hepatitis: cm - icteric
begins with jaundice
jaundice, dark urine, clay colored stools
liver enlarges and may be painful with palpation
fatigue abd pain persists or increases in severity
recovery
resolution of jaundice
6-8 wks after exposure, S diminish
liver remains enlarged/tender
hepatitis: complications
most recover w/o
higher mortality in elderly and comorbidities
chronic hep, liver cirrhosis, liver cancer, fulminant ural hep-acute liver fail
hep A
feral -> oral, parental (drugs), sexual
acute onset with fever, mild severity, no chronic hep, usually children and adults, HH, vax -> high risk and travel with low sanitation
hep B
parental, sexual
insidious onset (60-180 days), severe - can be prolonged or develop chronic, any age group, HBV vax (kids and hc workers), safe sex, hygeine
hep C
parental, sexual, mom -> fetus
insidious onset, mild-severe S, can develop to chronic, any age, screen blood, hygiene, no vax, leads to hepatocellular carcinoma (new treatments and more widely avail), liver transplant
cirrhosis
can progress from hep, cirhosis is scarring and irreversible but hep is not
irreversible, inflam, fibrotic liver disease -> higher death rate
structural change from injury (OH/viruses) and fibrosis -> infiltration of leukocytes and active inflam
chaotic fibrosis leads to obstructive biliary channels and BF -> jaundice and portal htn
regeneration disrupted by hypoxia, necrosis, atrophy, liver fail -> this is why it is irreversible
severity and rate of progression depend on cause
cirrhosis: common causes
hep B+C, accessive OH, idiopathic, non OH fatty liver disease, autoimmune, hereditary metabolism
cirrhosis: common causes - alcoholism and liver disease
OH -> acetylhide (excessive amounts alter hepatocyte F and activate hepatic stelocyte cells -> fibrosis
acetylehide inhibits export of P and alters met of vits and mins -> malN
OH cirrhosis most common but still onyl 25%
various stages/spectrum: fatty liver -> steatohepatits -> cirrhosis
kuffer cells attract neutrophils -> inflam -> toxins accumulate from gut bacteria -> cell mediated immunity
OH and liver disease: fatty liver
mildest, asymp
reversible
fat deposits increase lipogenesis
OH and liver disease: steatohepatitis
precursor to cirrhosis, inflam, degen of hepatocytes
increased hepatic fat storage, stim irreversible fibrosis
anorexia, n, jaundice, edema
OH and liver disease: cirrhosis
fibrosis and scaring alter liver structure
immune issues
cirrhosis: patho
liver cells destroyed -> try to regen -> disorganized process -> abn growth -> poor blood flow and scar tissue -> hypoxia -> liver fail
cirrhosis: cm - early
insidious
GI: n/v, anorexia, flatulence, change in bowel habits
fever, weight loss, palpable liver
cirrhosis: cm - late
jaundice, peripheral edema bc low albumin and loss of pulling power (3rd spacing), low PT (protein), ascites (3rd spacing and portal htn), skin lesions (spider angiomata vascular), hematologic problems (anemia, bleed -> CF; portal htn = veins burst)
endocrine issues: small testes, amenorrhea, impotence, infertile
esophageal and anorectal varices: distended veins, portal htn, burst -> bleed, mortality
encephalopathy: toxins -> confusion, coma, death
cirrhosis: cm - portal htn
resistant portal BF: varices and ascites, all blood has to go through liver, fibrosis blocks free flow and causes buildup
cause: sustemic hypoT, vascular underfilling, stim of vasoconstrictive S (RAAS), plasma V expansion, increased CO -> ascites
asymp until complications: variceal hemorrhage, ascites, peritonitis (gut bacteria), hepatorenal S (liver and kidney fail), cardiomyopathy (HF)
tm: liver transplant, reversible, treat s and complications
cirrhosis: cm - hepatic encephalopathy
LOC primary diagnosis
grade by severity
correlated with liver labs -> mainly ammonia (primary chem driver of LOC changes)
hepatic encephalopathy: minimal
abn results on psychometric or neurophysical testing without cm
hepatic encephalopathy: grade 1
changes in behavior, mild confusion, slurred speech, disordered sleep
hepatic encephalopathy: grade 2
lethargy, mod confusion
hepatic encephalopathy: grade 3
marked confusion (stupor), incoherent speech, sleeping but arousable
hepatic encephalopathy: grade 4
coma, unresponsive to pain
acute liver fail
fulminent liver fail
separate liver failure not caused by cirrhosis or other liver disease
most common cause -> acetaminophen OD, treat with acetylcysteine
patho: edematous hepatocytes and patchy areas of necrosis and inflam cell infiltrates and disrupts liver tissues
6-8 wks after viral hep or met liver disease -> rapid onset, 5 days -> 8 wks after acetaminophen OD
s similar to cirrhosis, just without cellular changes
tm: not much, liver transplant
