hepatic diseases Flashcards
1
Q
hepatic blood flow
A
inferior of superior mesenteric vein - portal vein - liver - sinusoidal spaces (space of Disse) - hepatocytes filter blood and blood moved back in the hepatic vein - inferior vena cava
2
Q
normal liver function
A
digestive functions endocrine functions clotting functions plasma proteins organic metabolism cholesterol metabolism excretory/degradative functions
3
Q
drug metabolism
A
phase I - non-synthetic reactions, REDOX* and hydrolysis, may detoxify a substance or make it toxic, typically involves CYP enzymes, may involve alcohol and aldehyde dehydrogenase
phase II - conjugation reactions, typically render a substance non-toxic
4
Q
hematological fxns
A
receives around 25% of cardiac output
removes old or damaged RBCs
synthesizes plasma proteins, transport nutrients and clotting factors
5
Q
AST
A
aspartate aminotransferase
normal values*: 0-50 IU/L
found in: liver, heart, skeletal muscle, kidney, brain, spleen, pancreas and lungs
elevated in: any disease that causes injury/damage to above tissues
6
Q
ALT
A
alanine aminotransferase normal values*: 5-60 IU/L found in liver, heart, muscle and kidney more specific for liver injury than AST elevated in: cirrhosis, obstructive jaundice and hepatitis
7
Q
Alk Phos
A
Alkaline Phosphatase
normal values*: 35-130 IU/L
found in: bone, liver and placenta (cells that line bile duct)
elevates in: obstructive jaundice, liver lesions, cirrhosis, paget’s disease, metastatic bone disease
8
Q
GGT
A
gamma glutamyl transferase
normal values*: 0-85 IU/L (men have higher levels due to prostate)
found in: liver, kidney, prostate and spleen
elevated in: cirrhosis, cholelithiasis, biliary obstruction, chronic alcohol use
9
Q
bilirubin
A
normal value: 0-1.4 mg/dL
direct/conjugated normal value: 0-0.3 mg/dL
both conjugated and unconjugated will elevate in hepatitis and cirrhosis
direct/conjugated - associated with RBC destruction
unconjugated - associated with liver blockage/destruction
10
Q
LDH
A
lactate dehydrogenase
normal range: 90-200 IU/L
found in: liver, kidney, heart, lungs
not specific for liver dysfunction, only tissue breakdown
11
Q
serum albumin
A
normal level: 3.6-5 g/dL
low in liver disease
12
Q
coagulation
A
INR, PT and aPPT
elevated in cirrhosis
13
Q
ammonia
A
NH3
normal values: 15-50 micromol/L
produced from intestinal bacteria
converted to urea in liver
14
Q
BUN
A
blood urea nitrogen
normal values: 10-20 mg/dL
low in cirrhosis
15
Q
cholesterol
A
may be low
16
Q
LFT vs LIT
A
LFT = liver function test -albumin -bilirubin -cholesterol -BUN -INR LIT = liver injury test -AST -ALT -Alk Phos -GGT
17
Q
hepatocellular test magnitude
A
AST/ALT
over 10x normal - hepatitis, drugs, ischemia
under 10x normal - broad diagnosis
18
Q
components of liver disease
A
drugs* chronic alcohol consumption* chronic viral hepatitis* metabolic liver disease immunologic diseases vascular disease
19
Q
hepatitis A
A
acute viral infection
typically self-limiting
transmission - fecal-oral
commonly associated with: poor sanitation and hygiene, overcrowded areas, travel
supportive care, does not lead to chronic infection
vaccination - 2 inactivated vaccines
20
Q
hep A vaccines and doses
A
havrix:
- 1-18: 720 units, 2 doses, 0 and 6-12 mo
- 19+: 1440 units, 2 doses, 1 and 6-12 mo
vaqta:
- 1-18: 25 units, 2 doses, 0 and 6-18 mo
- 19+: 50 units, 2 doses, 0 and 6-18 mo
twinrix (also includes HBV): 18+, 720 units, 3 doses, 0, 1 and 6 mo
21
Q
CDC recommendations for hep A vaccination
A
**all children at 1 year of age
**travelers to countries that have risk of infection
**anticipating close contact with an international adoptee from a country of high endemicity
age 2-18 in communities with high disease incidence, men who have sex with men, illegal drug users, persons with occupational risk for infection, persons who have clotting factor disorders, persons with chronic liver disease
22
Q
hepatitis B
A
not self-limiting - will need treatment
transmission: sexually, parenterally, perinatally
complications: cirrhosis, hepatocellular carcinoma
chronic HBV: detectable serum levels or past 6 months
23
Q
HBV vaccinations
A
engerix-B
- 0-19: 10 mcg at 0, 1 and 6 mo
- 20+: 20 mcg at 0, 1 and 6 mo
-dialysis: 40 mcg at 0, 1, 2 and 6 mo
recombivax HB
- 0-19: 5 mcg at 0, 1 and 6 mo
- 20+: 10 mcg at 0, 1 and 6 mo
-dialysis: 40 mcg at 0, 1, and 6 mo
comvax (+HIB): 6 wk-15 mo, 5 mcg at 2, 4, 12-15 mo
pediarix (+DTaP, IPV): 6 kw-6 yr, 10 mcg at 2, 4 and 6 mo
twinrix (+Hep A): 18+, 20 mcg at 0, 1 and 6 mo
24
Q
HBV vacc. recommendations
A
**infants
**those with a h/o STDs and persons with a h/o multiple sex partners (over 1 partner/6 months)
**healthcare/public safety workers with exposure to blood in the workplace
**chronic dialysis/ESRD patients including predialysis, peritoneal dialysis and home dialysis patients
previously unvaccinated children under 19, adults at risk, adults seeking vaccination, MWHSWM, current or recent inj-drug users, household contracts/partners of persons with HBV infection, clients/staff of institutions for the developmentalyl disabled, international travelers to regions with 2+% prevalence of HBV infection, recipients of clotting factor concentrates, STD clinic patients, HIV patient/HIV testing patient, drug abuse treatment and prevention clinic patients, correctional facilities inmates, persons with chronic liver disease
25
Hep C
most common BBP, transmission: parenteral, sequelae: chronic hepatitis, cirrhosis, hepatocellular cancer
single largest risk factor is injection-drug use
26
screening for Hep C
**anyone born between 1945 and 1965
**current or past use of injection drugs
**patients who have ever been on hemodialysis
coinfection with HIV, received blood transfusions or organ transplantations before 1992, received clotting factors before 1987, patients with unexplained elevated ALT levels or evidence of liver disease, healthcare and public safety workers after a needle-stick or mucosal exposure to HCV-positive blood, children born to HCV positive mothers, sexual partners of HCV positive patients
27
drug induced liver disease
Many drugs are associated with adverse reactions involving the liver
Rare, potentially fatal, largely unpredictable outcome of drug treatment
No specific diagnostic tests for drug-induced liver disease - Important to know the patterns of drug-related pathology
Normal metabolic outcome = decrease the reactivity - However - many causes of drug induced liver disease are a result of bioactivation
28
hepatocellular injury
centrilobular necrosis, steatohepatitis, phospholipidosis, generalized hepatocellular necrosis
significant elevations in the serum aminotransferase
usually precede elevations in total bilibrubin and alkaline phosphatase
most injuries occur within 1 year of initiation
further subdivided based on histology/presentation
29
centrilobular necrosis
AKA direct or metabolite-related hepatotoxicity
damage spreads outward from the middle of a lobe of the liver
mild/early diagnosis - small amount of liver tissue, asymptomatic elevations in aminotransferases, minimal cirrhosis/recovery likely
severe/delayed diagnosis - large amount of tissue affected, NV, upper abdominal pain and jaundice
**EXAMPLE MEDICATION: ACETAMINOPHEN
30
acetaminophen
in overdose, bioactivated to N-Acetyl-p-benzoquinone imine (NAPQI)
NAPQI is very reactive, with a high affinity for sulfhydryl groups
glutathione provides source of available sulfhydrl groups within hepatocyte to detoxify NAPQI
when glutathione stores depleted, reacts directly with hepatocyte
administration of N-acetylcystine early after ingestion of the OD halts this process
31
nonalcoholic steatohepatitis (NASH)
accumulation of fatty acids in the hepatocyte ("supersize me") - can see without drug induced cause in DM and poor diet
Engorgement with fatty acids, eventually disrupts hepatocyte homeostasis
Production of free fatty acids from excess circulating carbs, accelerates this process
May present with abdominal fullness or pain as only complaint
More severe cases: nausea, vomiting, steatorrhea, pruritus, and fatigue.
**EXAMPLE MEDICATIONS: TETRACYCLINE, VALPROATE
32
phospholipidosis
Accumulation of phospholipids instead of fatty acids
Amiodarone is associated with this reaction
Amiodarone and its major metabolite remain in the liver for several months after therapy is stopped
Usually develops in patients treated for more than 1 year
The patient can present with either elevated aminotransferases or hepatomegaly; jaundice is rare
33
generalized hepatocellular necrosis
Mimics the changes associated with viral hepatitis
Drugs causing this reaction generally do so via induction of the innate immune response
Subject to genetic polymorphism.
Wide variation in the sensitivity of the population to hepatic damage
**Example Medication: ISONIAZID
34
isoniazid
Slow acetylators* of the N-acetyltransferase2 (NAT2) genotype are at greater risk
Isoniazid is acetylated to acetylisoniazid, which, in turn, is hydrolyzed to acetylhydrazine.
Acetylhydrazine is toxic to the cellular proteins in the hepatocyte
Rapid acetylators detoxify acetylhydrazine rapidly, converting it to diacetylhydrazine
35
other presentation of drug induced liver injury
toxic cirrhosis
cholestatic injury
liver vascular disorders
36
toxic cirrhosis
Scarring effect of hepatitis leads to the development of cirrhosis
Some drugs tend to cause such a mild case of hepatitis that it may not be detected
Mild hepatitis can be easily mistaken for a more routine generalized viral infection.
If the offending drug or agent is not discontinued, this damage will continue to progress.
**Example Medications: METHOTREXATE (psoriasis and arthritis), VITAMIN A (causes fibrosis when taken for long periods in high doses, accelerated by ethanol)
37
cholestatic injury
Disturbances prevent the movement of bile through the canalicular system
More common in elderly and males
Some may have genetic predisposition
Accumulation of toxic bile acids and excretion products
**EXAMPLE MEDICATIONS: CHLORPROMAZINE, AMOXICILLIN-CLAVULANIC ACID, and CARBAMAZEPINE
38
liver vascular disorders
Peliosis hepatitis is a rare type of hepatic vascular lesion
Development of large, blood-filled lacunae (space or cavity)
Rupture can lead to severe peritoneal hemorrhage
**EXAMPLE MEDS: androgens, estrogens, tamoxifen, azathioprine.
39
assessment of drug-induced liver disease
```
patient history is best and most important technique
assess:
-environmental/occupational exposures
-herbals
-meds (Rx and OTC)
-nutritional status
-recreational drugs
-vitamins/supplements
potential drug reactions should be judges as to the:
-timing of the reaction
-pharmacokinetic considerations
-information from the literature
-inclusion of alternative nondrug causes
-close clinical observation once drug is stopped
```
40
laboratory assessment of liver injury
```
no good clinical test available to determine exact type of liver damage - liver biopsy common
specific patterns of enzyme elevation that have been identified and can be helpful
necrotic:
alkphos: x1
GGT: x1
AST: x3
ALT: x3
LDH: x3
cholestatic:
alkphos: x3
GGT: x3
AST: x1
ALT: x1
LDH: x1
chronic:
alkphos: x1
GGT: x2
AST: x2
ALT: x2
LDH: x1
```
41
alcoholic liver disease
```
most common cause of cirrhosis
responsible for around 44% of cirrhotic deaths
3 main histological phases:
-steatosis/fatty liver
-acute alcoholic hepatitis
-cirrhosis
```
42
pathophysiology - alcohol
alcohol dehydrogenase (ADH) converts EtOH to acetaldehyde
-acetaldehyde has direct toxic effects - damage to hepatocytes, induce fibrosis, couples to proteins
ethanol oxidation increases liver metabolic processes to reduction - increased reactive oxygen species, fatty liver, acidemia, hypertriglyceridemia
43
risk factors for ALD**
women, cumulative EtOH consumption, beer and spirits consumption, binge drinking, drinking between meals, drinking multiple different EtOH beverages
44
fatty liver disease
occurs in around 90-100% of EtOH abuse cases
occurs due to presence of triglycerides in hepatocytes
liver function typically stays normal
reversible with ETOH abstinence
45
acute EtOH hepatitis (AAH)
clinical syndrome of jaundice and liver failure
occurs after decades of heavy drinking
more common in men
typical age presentation 40-60 years old
AAH assessment: CAGE
do you feel you should Cut down on your alcohol consumption?
have people every Annoyed you by critisizing your drinking?
have you felt Guilty about your drinking?
have you ever had a drink first thing in the morning to steady your nerves (Eye-opener)>
clinical pres: rapid onset of jaundice, RUQ pain, encephalopathy
46
AAH assessment labs
```
AST: 2-3x higher than ALT
ALT: elevated, but not much higher than 100 IU/L
INR/PT: elevated
total bili: elevated
albumin: low
```
47
Maddrey's score
```
***(4.6 x (prothrombin time-control prothrombin time)) + serum bilirubin in mg/dL
score over 32:
-poor prognosis
-threshold for starting CSs
-threshold for starting pentoxifylline
```
48
pentoxifylline
MOA: phosphodiesterase inhibitor that also modulates TNF-a
dose: 400 mg TID
showed decreased mortality in hospitalized patients with EtOH hepatitis
decreases the risk of hepato-renal syndrome
49
EtOH withdrawal
signs:
-initial: HA, tremors, sweating, NV, irritability, anorexia,
-worsen between 24-48 hours after EACH cessation
symptom appearance: within a few hours
symptom duration: around 48 hours
50
EtOH withdrawal treatment measures
```
fluid resuscitation
thiamine 100 mg daily during withdrawal period
multivitamins daily
folic acid 1 mg daily for a few weeks
benzodiazepines
```
51
clinical institute of withdrawal assessment (CIWA)
assessment tool used to aid in management
assess patient cognition and agitation
helps nurse decide when and how much benzodiazepine to administer to a patient
52
EtOH withdrawal - delirium tremens
characterized by: severe agitation, tremor, disorientation, persistent hallucinations, elevated HR, elevated breathing rate
appear 72-96 hours post EtHO cessation
typically resolve in 3-5 days
53
delirium tremens treatment
benzos: typically administer a long acting and PRN short acting
haldol - not typically used
clonidine - used for central acting affects for elevated BP and pulse; dose: 0.1-0.2 mg PO q8h during withdrawal period
54
EtOH withdrawal - seizures
present with around 24 hours of EtOH cessation
usually self limiting
usually respond to benzos
chronic treatment NOT indicated
55
cirrhosis
end stage of any chronic liver disease
progression similar regardless of initial insult
complications: portal hypertension, varices, ascites, hepatic encephalopathy and coagulation defects
determination of etiology: past medical/social history, physical presentation, laboratory exam
56
pathophys of cirrhosis
destruction of hepatocytes and increased fibroblasts
replacement of normal hepatic tissue
fibrous scar tissue:
-modify basic architecture of the liver, change in blood flow and liver function
loww of viable hepatocytes:
-altered metabolic breakdown process
-decreased protein synthesis
57
clinical presentation of cirrhosis
```
Jaundice
Scleral icterus
Bruising
Anorexia
Fatigue
Bleeding
Hepatomegaly
Splenomegaly
Spider angiomata
Caput medusae
Gynecomastia
Decreased libido
Testicular atrophy
Pruritis
Dupuytren’s contracture
```
58
labs in cirrhosis
Elevated: AST, ALT, Alk Phos, GGT, LDH, PT, bilirubin
decreased: albumin, total protein, platelets
59
cirrhosis complications
portal hypertension, varices/variceal bleeding
| ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, coagulopathies, hepatorenal syndrome (HRS)
60
treatment goals of cirrhosis
eliminate causes of cirrhosis
prevent further damage/disease progression
educate patients - alcohol cessation, Na restriction
identify and treat acute complications
prevent future complications
61
vicious cycle of portal hypertension
increase in NO, activation of RAAS and SNS, increase in ADH
increase in vasodilation, decrease responsiveness to vasoconstrictors, increase plasma volume
increased blood volume in splanchnic bed
increased resistance (and BP) in portal vein due to fibrosis of sinusoids and formation of scar tissue
cycle continues
62
varices
form when a patient has cirrhosis
portal HTN is so bad that body finds collateral outlets that bypass the liver to relieve this pressure - varices
can form in esophagus, stomach, abdominal wall and rectum
can quickly and dramatically lead to a life-threatening emergency
63
variceal bleeding risk factors
```
poor liver function
large varices
alcoholic etiology
red wale markings
20% of patient will die from first bleed
```
64
signs and symptoms of variceal bleeding
hematemesis - vomiting of blood
melena - dark stick feces, containing partially digested blood
pallor, fatigue, decreased BP, increased HR, altered mental states, decreased Hgb and Hct, NV
65
treatment goals for variceal bleeding
maintain hemodynamic stability, protect airway, correct significant coagulopathies, prevent infectious complications, control acute bleed, prevent rebleed
66
airway protection in variceal bleeding
NG suction
prevent aspiration pneumonia - leading cause of death in active variceal bleed
swalloed blood: high protein load (preceipitate hepatic encephalopathy), nausea, hepatic encephalopathy
67
endoscopic variceal ligation
AKA banding
first line therapy
rubber band ligation system bands active varices, after 48-72 hours the varix will slough off
repeated q 1-2 weeks until entire variceal obliteration
68
octreotide
synthetic somatostatin analogue
MOA: selectively vasoconstricts of splanchnic vasculature, decreased splanchnic/portal blood flow, decreased portal pressure
dosing:
-load: 50-100 mcg IV bolus
-maintenance: 25-50 mcg/hr continuous infusion
treatment duration: continue 24-72 hours post bleeding cessation
69
PPIs for variceal bleeds
esomeprazole or pantoprazole
MOA: decrease stomach acid helps control active GI bleed
dosing:
-initial: 80 mg IV load
-maintenance: 8mg/hr continuous infusion for 72-96 hours; high dose oral PPI x 4 weeks post bleed
70
prophylactic antibiotics for variceal bleeds
treat with prophylactic antibiotics during acute bleed
purpose: prevention of spontaneous bacterial peritonitis
short course of antibiotics: 3rd generation antibiotics, fluoroquinolone
71
nonpharmacological treatment of variceal bleeds
standard therapy fails in 10-20% of cases
other surgical options pursued - balloon tamponade, transjugular intrahepatic portosystemic shunts (TIPS) - increased risk of hepatic encephalopathy
72
treatment algorithm for variceal bleeds
volume resuscitation + PPI + IV octrotide (around 5 days)
+endoscopic therapy (EVL)
+3rd generation cephalosporin (around 7 days)
*recurrent bleed (within 5 days)?
no - initiate secondary prophylaxis
yes - repeat endoscopic therapy - TIPS - recurrent bleed (within 5 days)*?
73
prevention of variceal bleeds
goal: decrease portal pressure
-reduce effects of sympathetic activation
-non selective Bblockers
B1 blockade - decreased cardiac output, decreased splachnic blood flow
B2 blockade - decreased splanchnic blood flow, decreased splanchnic vasodilation, unopposed a-1 stimulation (vasoconstriction)
74
non-selective B blockers
```
propranolol
-starting: 10 mg BID or TID
-titrate to HR and BP tolerance
nadolol
-start: 20 mg daily
-dose adjustments needed with renal failure
CONTINUE INDEFINITELY
```
75
nitrates for variceal bleeds
isosorbide mononitrate
controversial: may be used in combination with Bblockers, decrease rate of first hemorrhage
side effects: increased mortality if used alone, increased ascites development
may be good option in patients unable to undergo EVL
76
variceal bleed prevention
treatment w BBs
primary prevention - large varices (over 5 mm), small varices w increased bleeding risk - child pugh score B or C or red wale marks
secondary prevention - all patient with prior bleed
no benefit in patient without varices OR with small varices and low bleed risk
77
ascites
fluid accumulation in peritoneal space - 15% mortality in 1 year, 44% mortality in 5 years
progressive liver disease
-fluid leaves vascular space and accumulates in peritoneum
-decreased oncotic pressure - low serum albumin
-increased systemic volume - RAAS and sympathetic activated - Na/fluid retention
78
ascites pathophys
1) cirrhosis/portal hypertension
2) decreased protein synthesis, increased capillary permaebility, increased volume overload
3) hypoalbuminemia
4) fluid moved from vascular space to peritoneal space
5) ascites** (big, big belly)
79
s/sxs of ascites
```
abdomen pain
fullness
nausea
SOB
increased abdominal girth
```
80
ascites grading
1 - detected only on ultrasound - requires only salt restriction
2 - moderate abdominal distention
3 - marked ascitic fluid and abdominal distention
4 - AKA tense or refractory distention, unresponsive to diuretics
81
ascites diagnostic paracentesis
for new/worsening ascites
large bore needle inserted into abdomen to remove ascitic fluid
tests: cell count with differential, a total protein count, albumin and bacterial culture
gram stain is ordered but rarely helpful due to low conc of bacteria
82
SAAG (serum ascites albumin gradient
sensitive for etiology
comparison of serum albumin concentration to ascitic albumin concentration
**** calculation: serum Alb - ascites Alb = SAAG
interpretation
1.1+ = ascites due to portal hypertension
under 1.1 = ascites due to other courses
83
alcohol cessation
DRAMATIC improvement in liver function
| may resolve ascites in a few months - makes the ascites more responsive to medical therapy
84
sodium restriction
under 2 grams/day
water restriction unnecessary
usually used in combo w pharmacotherapy
85
diuretics
mainstay of treatment for stable patients
use a combo of diuretics - K sparing and loop
goal: around 0.5 L fluid loss/day
monitor: edema resolution and renal failure (SCr, BUN, electrolytes)
86
spironolactone
MOA: aldosterone antagonist acting in distal tubules; counteracts RAAS activation - decreased ascites
dose: start at 25-100 mg daily, max of 400 mg daily
SE: hyperkalemia, gynecomastia
**must maintain ratio of spironolactone 100:furosemide 40 at all times
87
furosemide
MOA: blocks reabsorption of Na in the loop of henle; helps maintain K levels (w spironolactone)
dose: start 20-40 mg daily, max 160 mg daily
SE: hypokalemia, hyponatremia (d/c at Na uber 120), acute renal failure (SCr over 2.0)
88
amiloride
used for patients experiencing significant and painful gynecomastia with spironolactone (replace)
MOA: blocks reabsorption of Na in the distal tubules, K sparing but NO aldosterone inhibition
dose: start 10 mg daily, max 40 mg dailt
SE: hyperkalemia, hypotension
89
therapeutic paracentesis`
treatment of choice for large volume/refractory ascites
complications: hypotension, hyponatremia, azotemia
must be accompanies by volume expanders - albumin: 8g/L of fluid removed
90
treatment algorithm for ascites
EtOH cessation, avoid NSAIDs, Na restriction
oral diuretics (spironolactone/furosemide) - titrate every 3-5 days - max: 400/160
therapeutic paracentesis with albumin infusion
transjugular intrahepatic portosystemic shunt (TIPS)
liver tranplant
91
spontaneous bacterial peritonitis (SBP)
"spontaneous" infection of perioneal fluid
key mechanism: bacterial translocation
assessment: patient presents w sxs, diagnostic "tap"
predisposing factors: prior SBP, low ascitis fluid total protein, high serum bilirubin
92
assessment of SBP
symptoms of infection: fever, chills, abdominal pain, changes in mental status
ascitic fluid analysis: polmorphonuclear leukocyte count (PMN) greater than or equal to 250 cells/mm^3***, decreased total protein, elevated neutrophil count, positive bacterial culture
PMN = WBC x % neutrophil
93
bacterial etiology in SBP
initiate empiric antibiotic therapy with broad-spectrum anti-infective agent - either PMN over 250 or PMN under 250 + s/sxs of infection
most common bacteria:
-gram negative aerobes: Ecoli, klebsiella pneumoniae
gram positive: streptococcus pneumoniae
94
treatment of SBP
```
ceftriaxone 2 gm IV q24h
cefotaxime 2 gm IV q8h
piperacillin/tazobactrum 3.375 gm IV q6h
ticarcillin/clavulanate 3.1 gm IV q6h
levofloxacin
ciprofloxacin
**treat at least 5 days
```
95
adjuctive albumin for SBP
```
increases likelihood of renal failure
consider 1-1.5 g albumin/kg any of the following during SBP:
-SCr over 1
-BUN over 30
-bilirubin over 4
```
96
antibiotics to prevent SBP
secondary prevention: treat for life
primary prevention: low ascitic protein AND one of the following:
SCr over 1.2
BUN over 25
Na under 130
child-pugh over 9 + bilibruibin over 3
drug options: ciprofloxacin 500-750 mg PO QD, TMP/SMX 1 DS tab PO QD, norfloxacin: 400 mg PO BID
97
pathophys of hepatic encephalopathy (HE)
substances bypass liver - remain in circulation
increased blood ammonia - decreased conversion of NH3 to urea, generated by gut bacteria and is a byproduct of protein catabolism, neurotoxic substance
98
s/sxs of hepatic encephalopathy
```
Mood disturbances
Reversal of sleep/wake cycle
Impaired memory
Short attention span
Asterixis**
Slow monotonous speech
Loss of fine motor skills
EPS-type movement disorders
Hyperventilation
Seizures
Confusion
Coma
```
99
precipitating events of hepatic encephalopathy
increased nitrogen load - GI bleed, excessive protein, constipation, azotemia
drugs: narcotics, benzos, sedatives, diuretics
electrolyte imbalances - hyponatremia, hypokalemia
misc: infection, TIPS
100
diagnosis of hepatic encephalopathy
serum ammonia levels
-normal: under 35 mmol/L
-elevation does not correlate to degree of confusion
-NOT diagnostic
state of confusion or altered mental status + cirrhosis
-diagnosis largely based on clinical suspicion
101
treatment goals for hepatic encephalopathy
```
correct precipitating factors
reverse overt encephalopathy
reduce nitrogen load in gut
avoid recurrence
assess need for long term therapy
```
102
treatment approaches for hepatic encephalopathy
reducing ammonia blood concentrations
-dietary restrictions
-drug therapy to inhibit production or increase removal
inhibition of GABA-benzodiazepine receptors
avoid precipitating factors
103
nutritional management
protein restriction was done in past - small meals or liquid nutritional supplements evenly distributed throughout the day
milk or vegetable sources of protein preferred - increased calorie or nitrogen ratio, increased fiber
branched chain AAs
104
lactulose for HE
MOA: hydrolyzed in colon, osmotically active, lowers colonic pH and binds NH3
dose:
- initiation: 45 ml/hr until catharsis
- maintenance: 15-45 ml/hr q8-12h; titrate to 3-4 soft bowel movements daily; maintain regimen to prevent HE
monitoring: electrolytes, stool frequency/consistency
105
metronidazole for HE
MOA: decreased gut flora = decreased production of NH3
dose: 250 mg PO q6-12h
SE: peripheral neuropathy, disulfram-like reaction, metallic taste
106
neomycin for HE
Oral aminoglycoside
Dose: 3-6 g/daily (divided doses), Max duration = 2 weeks
Side Effects: Irreversible ototoxicity, Reversible nephrotoxicity
**No longer considered 1st line antibiotic
107
rifaximin for HE
Approved in 2005 for HE
Dose: 400 mg q8h x 5-10 days duration (treatment); 550 mg BID (prevention)
SE: headache, flatulence
Costly
108
false NTs for HE
Flumazenil
- No long-term benefit
- Parenteral
- Dose: 0.2 mg up to 15 mg/day
- Not for long term treatment
109
coagulation defects
Liver synthesizes most proteins responsible for hemostasis
Liver damage can cause the following:
-Reduction in synthesis of clotting factors
-Excessive clot breakdown
-Disseminated intravascular coagulation
-Thrombocytopenia
-Platelet dysfunction
110
thrombocytopenia
Occurs in up to 70% of patients
Pathophysiology:
-decreased platelet production (decreased thrombopoetin)
-Splenic sequestration (splenomegaly due to portal HTN)
-Increased PLT destruction
Treatment: Platelet transfusion
111
Vit K for coagulation defects
MOA: Essential factor in production of coagulation proteins
Evaluation:
-increased INR, PT and PTT
-Abnormal bruising, bleeding & skin stigmata
Treatment:
-10 mg vitamin K subcutaneously x 3 days
-Consider FFP to rapidly replete plasma proteins
-DDAVP sometimes used as adjunct
112
hepatorenal syndrome
Development of renal failure in the presence of liver failure - Without alternate explanation
around 8-20% of cirrhotic patients will develop
Mortality:
Type 1 (rapid): median survival = 14 days
Type 2 (slow): median survival = 6 months
113
pathophysiology of hepatorenal syndrome
Increased renal vasoconstriction which leads to decreased renal function
Vasoconstriction due to:
-Renal response to increased cardiac output
-Low arterial pressure
-Increased RAAS and sympathetic nervous system activation
-Increased vasodilatation in splanchnic bed
Eventually – damage to heart (hepatic cardiomyopathy) - Further reduction in renal blood flow
114
hepatorenal syndrome risk factors
```
low urinary Na excretion
low serum Na
low mean arterial pressure
high RAAS activity
high serum K
previous episodes of ascites
absence of hepatomegaly
esophageal varices
poor nutrition
SCr above 1.5 mg /dL
```
115
treatment of hepatorenal syndrome
```
d/c diuretics and treat cause (if known)
1st line:
-albumin + octreotide + midodrine
-albumin dose: 1g/kg on 1st day then 20-40 g/day
-octreotide dose: 100 mcg SQ TID or cont infusion
midodrine dose: 5-7.5 mg PO TID
2nd line:
liver transplant
only definitive cure - prolongs survival
```
116
using common meds in liver impairment
Consider the Following:
-Will the drug will adversely affect the liver ? (uncommon)
-Will the drug’s metabolism will be impaired? (common)
-Will the drug might contribute to a liver disease complication? (common)
General Guidelines:
-Start with a low dose and/or reduced dosing frequency, and titrate slowly.
-Patients with chronic liver impairment may also have renal impairment
117
pain management in liver disease
Cirrhotics may develop pain for a variety of reasons
Choice of appropriate agent tricky
More prone to adverse effects of medications for pain
Balance risk/benefits on individual basis
visceral or musculoskeletal: acetaminophen under 2-3 g/day - tramadol 25 mg q8h - hydromorphone 1 mg q4h, fentayl 12.5 mcg q72h, DC tramadol!!
neuropathic pain - nortripyline 10 mg QHS OR desipramine 10 mg QHS + gabapentin 200 mg QD OR pregabalin 150 mg BID + acetaminophen under 2-3 g/day
118
acetaminophen general considerations
Misperceived as dangerous in cirrhotics
T1/2: 2x healthy controls
Studies in cirrhotics
-Not a lot of data, no evidence-based guidelines
Group of 10 hepatologists published:
-Long term APAP use allowable in cirrhotics at reduced dose of 2-3 g/day
119
NSAID general considerations
in general-AVOID**
Increased serum levels: Metabolism through CYP, Highly protein bound
Renal impairment: Increase Na/H20 retention, Counteracts diuretics, Precipitate HRS
Gastric bleeding: Varices, thrombocytopenia
120
opioids in liver disease
common precipitants of HE/hospitalizations
metabolized in liver (fentanyl and hydromorphone = no active metabolites)
recommend: avoid if possible, use tramadol first, use fentanyl or hydromorphone 2nd line
121
child-pugh disease staging
```
bilirubin (mg/dL):
- 1-2 = 1 point
- 2-3 = 2 points
- over 3 = 3 points
albumin (mg/dL):
- over 3.5 = 1 point
- 2.8-3.5 = 2 points
- under 2.8 = 3 points
ascites:
- none = 1 points
- mild = 2 points
- moderate = 3 points
encephalopathy (grade):
- none = 1 point
- 1 and 2 = 2 points
- 3 and 4 = 3 points
prothrombin time (sec):
- 1-4 = 1 point
- 4-6 = 2 points
- over 6 = 3 points
STAGE
5-6 point = A
7-9 points = B
10-15 points = C
```
122
child-pugh survival rates
A: 1 year = 100%; 2 year = 85%
B: 1 year = 81%; 2 year = 57%
C: 1 year = 45%; 2 year = 35%
123
MELD score`
mayo end-stage liver disease scoring
calculated score: based on SCr, bilirubin, INR and etiology of liver diease
score from 6-40 and used to classify disease severity
used to assess liver transplant
under 15 = survival better with current liver
124
liver transplant contraindications
```
Compliance issues
HIV infection
Lack of social support
Uncontrolled infection
Severe extrahepatic disease
Body Mass Index over 35 kg/m2
Age over 70 years
```
