Liver 1 Flashcards
Hepatic injury, Labs, Cirrhosis
1
Q
Where is the liver located?
A
RUQ of abdomen
-2 lobes made up of thousands of lobules
2
Q
Describe lobules.
A
centered on a branch of the hepatic vein
interconnected by small ducts
contain hepatocytes, separated by sinusoids
“portal triads” at the corners of adjacent lobules
3
Q
What makes up a portal triad?
A
branches of the bile duct, portal vein, hepatic artery
4
Q
What is the role of the hepatic duct?
A
transports bile produced by liver cells to the gallbladder and duodenum
5
Q
What is the only organ in the body that is capable of regenerating its cells?
A
the liver
-70% of the liver tissue can be destroyed before the body is unable to eliminate drugs and toxins via the liver
6
Q
How much of our cardiac output does the liver receive?
A
25%
-the liver has a dual blood supply
7
Q
Describe blood supply to the liver.
A
venous flow in from the portal vein
-from small intestine, pancreatic venous drainage, spleen
arterial flow in from the hepatic artery
-liver oxygenation
venous flow out through the hepatic vein
-blood from both the portal vein and hepatic artery mix together in sinusoids and exits liver
8
Q
What is the role of the gallbladder?
A
stores and concentrates bile
9
Q
What are the major functions of the liver?
A
excretion (bile)
metabolism (bilirubin, drugs, nutrients, hormones)
storage (vitamins/minerals (B12, iron), CHO)
synthesis (plasma proteins like albumin)
10
Q
What are the functions of bile?
A
emulsification: dietary fat, cholesterol, vitamins
elimination of wastes: excess cholesterol, xenobiotics, bilirubin
11
Q
What is enterohepatic recirculation?
A
bile acids reabsorbed into bloodstream, taken up by hepatocytes, deconjugated and then re-secreted into bile
-95% of bile acids reabsorbed
-pool of bile acids largely remains the same
12
Q
What is bilirubin?
A
end product of heme degradation
-from breakdown of RBC in spleen/liver
13
Q
Differentiate between direct and indirect bilirubin.
A
indirect bilirubin=free bilirubin
-insoluble
-bound to albumin for transport to liver
direct bilirubin=conjugated bilirubin
-made by glucuronidation in liver
-excreted in bile
14
Q
When does liver disease become irreversible?
A
when regeneration capacity is overcome
reversible: damage to the functional cells of the liver without destruction of the livers capacity for regeneration
15
Q
What is fulminant liver failure?
A
insufficient residual hepatocytes to maintain minimal essential liver functions
-irreversible
16
Q
Describe the pattern of hepatocellular injury.
A
necrosis–>degeneration–>inflammation
inflammation–>regeneration OR fibrosis
fibrosis–>cirrhosis
17
Q
What are the etiologies of hepatic injury?
A
viruses
drugs
environmental toxins
alcohol
18
Q
What are the two main types of hepatic injury?
A
cholestasis
hepatocellular
19
Q
What is cholestasis?
A
failure of normal amounts of bile to reach the duodenum
leads to accumulation of bile in liver cells and biliary passages (intrahepatic or extrahepatic)
20
Q
What are the causes of cholestasis?
A
cholelithiasis (gall stones)=most common
tumor, viral hepatitis, alcohol-related liver disease, drugs
PBC, PSC
21
Q
What is PBC?
A
primary biliary cholangitis
-slow, immune-mediated destruction of small bile ducts within the liver=impaired excretion of bile
22
Q
What is PSC?
A
primary sclerosing cholangitis
-progressive inflammation and fibrosis affecting any part of the biliary tree
-leads to progressive destruction of bile ducts
23
Q
What are the symptoms of cholestasis?
A
pruritis
jaundice
dark urine
light coloured stools
xanthoma and xanthelasma
steatorrhea
hepatomegaly
24
Q
What is the MOA of ursodiol?
A
MOA unclear: decrease cholesterol saturation
-gall stones are formed from supersaturation of cholesterol
25
What are the uses of ursodiol?
cholelithiasis management
-gradual dissolution of stones in 30-40%
chronic forms of cholelithiasis (PBC or PSC)
-improves serum biochemical tests
-limited efficacy in preventing disease progression in PSC
26
What is a con of ursodiol?
stones often recur after d/c
27
What is an alternative drug that can be used in PBC?
obeticholic acid
28
What is a symptom that is often associated with long standing cholestasis?
pruritis
29
What are the drugs we can use for pruritis due to cholestasis?
cholestyramine (best option)
-will benefit about 90% of pts, must be continued as long as pruritis is present
antihistamines (ex: hydroxyzine)
-no proven benefit, sedative properties may help
naltrexone, rifampin, sertraline
-may be tried if refractory
30
What is hepatocellular damage?
direct damage to hepatocytes
31
What are the causes of hepatocellular damage?
toxic agents: alcohol, drugs, toxins
infections: hepatitis
longstanding cholestasis
ischemic injury: thrombosis
other diseases (autoimmune, iron overload)
32
True or false: hepatocellular damage is chronic
false
can be acute or chronic
33
What does the course of hepatocellular injury depend on?
duration of assault
intensity of assault
-massive: fulminant hepatic failure
-mild to moderate: hepatitis
34
What occurs when hepatocytes are destroyed?
contents of cells are released into the circulation
functional ability of the liver may be compromised
35
What are some conditions which could lead to hepatocellular damage?
autoimmune hepatitis
-chronic inflammation of liver, genetic
hemochromatosis
-excessive absorption of iron
36
What are the two ways to measure liver function?
liver enzyme measurement
-testing for enzymes residing inside hepatocytes
liver function tests (ABC)
-evaluate synthetic capacity of liver
-albumin, bilirubin, clotting
37
Which liver enzymes are released into circulation after injury?
ALP
AST
ALT
GGT
38
How do liver enzymes help us distinguish the type of injury?
they are pretty specific to liver cells
39
Which liver enzymes are elevated with cholestatic injury?
ALP
GGT
40
Where is ALP found?
bile duct > hepatocytes
bone
41
When do we see elevations in GGT?
all liver disorders
-confirms hepatic origin of ALP (doesnt tell you much on its own)
42
Which liver enzymes are elevated with hepatocellular damage?
AST and ALT
43
Describe the aminotransferases.
ALT and ALT
-ALT more specific than AST (L for liver)
-poor correlation with severity, prognosis
-may be minimally elevated in cholestatic syndromes
44
Which liver enzyme is very non-specific and not used?
LDH
45
Describe albumin and the impacts liver diseases poses to normal levels.
most abundant plasma protein in the body
-decreases in liver disease
normal life span is ~ 20 days
-reduced levels after sustained assault
-sx: edema, ascites
-impacts on calcium, highly bound drugs
46
What is the advantage of using pre-albumin level rather than albumin levels?
more sensitive and provides more current information
47
What are the results of bilirubin retention?
deposits in skin and tissues
dark urine, pale stools, jaundice
48
Which coagulation factors are synthesized by the liver?
I, II, V, VII, IX, X
-clotting factors drop with liver disease (moderate to significant damage)
49
What happens to PT if liver is damaged?
increased (longer bleeding times)
50
What are the Big 7 for liver lab tests?
liver enzymes:
-AST (RBC, muscle, liver)
-ALT (liver)
cholestatic enzymes:
-ALP (liver, bone, placenta)
-GGT (liver)
liver function:
-albumin
-bilirubin
-INR/PTT
51
What is cirrhosis?
a chronic diffuse diseases characterized by fibrosis and nodular formation
result of continuous liver injury
-takes a long time to develop (unless its fulminant)
liver becomes hard, shrunken, and nodular
-loss of normal structure and function
-irreversible fibrosis
52
What are the causes of cirrhosis?
alcohol
viral
autoimmune
inherited
drugs/toxins
NAFLD
53
What is MASLD and MASH?
metabolic dysfunction-associated steatotic liver disease
-previously known as NAFLD
metabolic dysfunction associated steatohepatitis
-previously known as NASH
*fat deposited in liver but not related to alcohol intake, related to insulin resistance and metabolic syndrome*
54
What are the 2023 alcohol recommendations?
all lvls of alcohol consumption are associated with some risk
among healthy individuals, there is a continuum of risk:
-negligible/low: < 2 standard drinks/week
-moderate: 3-6 standard drinks/week
-high: > 6 standard drinks/week
55
Which population has potential for greater health risks from alcohol?
women
56
What are the recommendations for alcohol and pregnancy/breastfeeding?
pregnancy: dont drink (pre-conception period as well)
breastfeeding: safest not to drink
57
How much alcohol is needed to cause cirrhosis?
depends:
-how much
-how often
-how long
-pattern of drinking
-body composition, age, drinking experiences, genetics, social factors
58
What are the ways that cirrhosis can be diagnosed?
biochemical markers
-for screening
abdominal ultrasound
-first imaging modality recommended
elastography
-new, non-invasive
liver biopsy
-rarely needed now for diagnosis
59
What does cirrhosis result in?
decreased functioning liver tissue
-impaired function and diminished reserve
-portal HTN
*pts will die ~5-15 years after diagnosis*
60
What is a general overview of the treatment for cirrhosis?
tx of the specific disease
tx of the complications
liver transplant
61
Differentiate compensated and decompensated cirrhosis.
compensated:
-body functions fairly well despite scarring of liver
-may be asymptomatic or non-specific symptoms
-liver enzymes may be abnormal
decompensated:
-severe scarring & disruption of function
-sx: confusion, edema, fatigue, bleeding
-abnormal LFTs
-abnormal exam
62
What are the potential laboratory findings of cirrhosis?
hypoalbuminemia
elevated PT
thrombocytopenia
elevated ALP
elevated AST, ALT, GGT
elevated bilirubin
63
What are the potential signs and symptoms of cirrhosis?
asymptomatic
splenomegaly
jaundice, palmar erythema, spider nevi
ascites and edema
malaise, anorexia, weight loss
encephalopathy
testicular atrophy, loss of body hair, amenorrhea, gynecomastia
64
What are the complications of cirrhosis?
portal HTN
ascites
SBP
hepatorenal syndrome
varices
hepatic encephalopathy
65
True or false: normally the portal system is a high pressure venous system
false
normally a low pressure venous system
66
What occurs if blood flow through the liver is obstructed?
pressure is increased (portal HTN)
-opens "detours" between the portal and systemic circulation
-blood is diverted around the liver rather than filtered through the liver
-portal blood bypasses liver and directly enters systemic circulation (portal-to-systemic shunting)
67
What is portal HTN the result of?
increase in resistance to portal flow and increase in portal venous inflow
-splanchnic dilation
-increase in NO leading to vasodilated state
-RAAS
end up with "back flow" of blood and widening of the venous channels that connect the portal and systemic circulation
68
What can portal HTN cause?
splenomegaly
-uncomfortable/painful to the patient
-sequestration and destruction of RBCs (anemia and thrombocytopenia)
69
What are the consequences of portal-to-systemic shunting?
portal blood bypassing the liver:
-metabolites/toxins in the blood have not been processed by the liver
-increased sensitivity to noxious substances absorbed from GI tract (encephalopathy)
-malabsorption of fat in the stool
-contributes to other complications (ascites, SBP, varices, hepatorenal syndrome)
70
What are ascites?
collection of fluid (up to 20L) in the peritoneal cavity
-can cause massive distention
71
What is the pathogenesis of ascites?
hydrostatic pressure
hypoalbuminemia (reduced oncotic pressure)
-hypovolemia-->aldosterone secretion
renal retention of Na+ and water
72
What should patients with ascites be evaluated for and why?
liver transplant
-poor prognosis
73
What is an essential step in the management of patients with newly diagnosed ascites?
aspiration of ascitic fluid
laboratory analysis: WBC, total protein [ ], albumin
74
What is SAAG?
serum-ascites albumin gradient
=serum albumin - ascitic fluid albumin
if > 11g/L: indicates portal HTN
-likely responsive to diuretics
if < 11g/L likely other causes
-not typically responsive to diuretics
75
What does an elevated total protein concentration tell us in the context of ascites?
> 25g/L associated with a SAAG of > 11g/L
-suggest cardiac dysfunction as etiology of ascites
76
What are the goals of treating ascites?
remove abdominal fluid
prevent symptoms and maintain reasonable QoL
77
What is the management of ascites?
*mainly focused on symptom management*
salt restriction
diuresis
paracentesis
TIPS
liver transplant
78
What should be the salt restriction of a patient with ascites?
< 2g/day
*10-25% will respond*
79
Which diuretics are used for ascites?
spironolactone (of choice) & furosemide
80
What is paracentesis?
aspiration of peritoneal fluid with a needle
-may help decrease discomfort
-fastest for relief
81
What can occur with a large volume aspiration via paracentesis?
fluid steal from the vascular space
82
What is the risk with paracentesis?
abdominal perforation and infection
83
What is TIPS?
transjugular intrahepatic portosystemic shunt
84
What is the only available cure for ascites?
liver transplant
85
Which guidelines are no longer recommended for ascites?
bed rest no longer recommended
fluid restriction no longer recommended unless Na+ < 120-125mEq/L
86
What is the MOA of spironolactone?
inhibits the effects of aldosterone
-weak diuretic and anti-HTN unless aldosterone levels are high
87
What is the onset of spironolactone?
3-5 days
88
What are the safety concerns for spironolactone?
hyperkalemia
dehydration (uncommon if monotherapy)
estrogen-like AEs
DI: drugs affecting K+, may increase digoxin lvl
89
What are the safety concerns for furosemide?
over-diuresis
hypovolemia (potent diuretic)
90
What is the dosing regimen of diuretics for ascites?
spironolactone 100mg
furosemide 40mg
*AM dose (OD)*
91
What is the dosing titration of diuretics for ascites?
100mg:40mg q3-5d
-max 400mg of spironolactone & 160mg furosemide
or start with spironolactone and add on furosemide
92
What are the other diuretics that might be considered for ascites?
metolazone
-refractory ascites to spironolactone and furosemide
amiloride
-intolerant to spironolactone
93
What are the monitoring parameters for diuretics for ascites?
SCr, Na, K
weights and bp
94
What is refractory ascites?
unresponsive to Na-restricted diet and high dose diuretic treatment (400mg spiro and 160mg furosemide)
-recurs rapidly after a therapeutic paracentesis & high-dose diuretics
-poor prognosis
95
Which drugs should be avoided in ascites/cirrhosis in general?
NSAIDs
96
What is the treatment for refractory ascites?
serial therapeutic paracentesis
TIPS
or liver transplant
97
What are the principles of therapy for ascites?
patients should monitor daily weights
-gradual weight loss is the goal
-< 0.5kg/d if no edema, more if edema
-assumes 1kg body weight=1L of fluid
if no response, check urinary sodium
-if low: more diuretic
-if high: non-adherence to low Na diet (counsel)
monitor SCr, Na, K
consider SBP treatment/prophylaxis
98
What is SBP?
spontaneous bacterial peritonitis
-infection in ascitic fluid without obvious cause
-thought to be from bacteria translocation
99
What are the symptoms of SBP?
fever, chills, abdominal pain, etc
-typical symptoms may be absent
100
What should be done as soon as a patient with ascites and cirrhosis is hospitalized and why?
diagnostic paracentesis for SBP
-mortality rates are high and presentation is variable
101
What are the most common pathogens to cause SBP?
E coli
Klebsiella pneumoniae
Streptococcus pneumoniae
102
When do we empirically treat for SBP?
culture +
PMN > 250/uL
high degree of suspicion (dont wait for culture if unavailable)
103
What is the treatment for SBP?
community acquired:
-cefotaxime or ceftriaxone x 5d
nosocomial acquired:
-piperacillin/tazobactam
-meropenem +/- vancomycin
104
When should a second ascitic fluid collection be performed for someone with SBP?
48h after initiation of treatment
-clinical response: decrease in PMN by 25%
105
When do we consider prophylaxis for SBP?
pts having survived an episode of SBP (secondary prophylaxis)
those at high risk (primary prophylaxis)
-high risk: low ascitic fluid total protein ascites or variceal hemorrhage
106
Which antibiotics are used for SBP prophylaxis?
norfloxacin
ciprofloxacin
septra
107
What should occur for the patient after experiencing SBP?
referral for liver transplant
108
What is hepatorenal syndrome?
renal failure in patients with severe liver disease
-characterized by severe vasoconstriction of renal circulation
-no pathologic changes identifiable in kidney
109
Which patients tend to experience hepatorenal syndrome?
patients with massive, tense ascites
-may be precipitated by aggressive diuresis or SBP
110
What is the management of hepatorenal syndrome?
stop diuretics
avoid nephrotoxins (ex: NSAIDs, aminoglycosides)
111
What are varices?
high pressure in portal vein
-creates bypasses/shunts
relatively small veins become engorged with excess blood
112
What are the principles sites of varices?
rectal area
abdominal wall
esophageal
113
What is the poor outcome that can occur with esophageal varices?
rupture causing massive bleeding
-complicated by clotting disorders
-causes massive hematemesis
-very difficult to stop the bleeding
-high risk of recurrent hemorrhage
114
Which type of varices are most common in cirrhosis?
esophageal
115
What are the treatment goals for the acute management of variceal bleed?
adequate blood volume resuscitation
protection of airway from aspiration of blood
prophylaxis against SBP and other infections
control of bleeding
prevention of re-bleeding
preservation of liver function/prevention of hepatic encephalopathy
prevention of AKI
116
What are the treatment strategies for acute variceal bleed?
packed RBCs
-resuscitates blood volume
-goal: HgB 70-90g/L
antibiotic prophylaxis for SBP
-all pts with liver disease with GI bleed should receive
-greater chance of infection with bleed
octreotide or somatostatin IV
-vasoconstrictors which decrease splanchnic blood flow
-stops/slow bleeding
-d/c when free of bleed x 24 hrs
endoscopic therapies
-band ligation or sclerotherapy
TIPS
-if failure despite combined endoscopic and pharmacologic therapy
117
Which patients should receive prophylaxis for variceal bleeding?
patients with small varices + increased risk of bleeding
patients with medium/large varicies
118
Which drugs are used for prophylaxis of variceal bleeding?
nadolol and propranolol
119
What is the MOA of nadolol and propranolol for prevention of variceal bleeding?
decreased portal venous pressure via:
-decreased CO
-alpha vasoconstriction
120
What is the effectiveness of propranolol and nadolol for prevention of variceal bleeding?
reduces bleeding incidence by up to 50%
121
Differentiate nadolol and propranolol.
nadolol:
-initiate 20mg OD, max 240mg/day (120mg with ascites)
-titrate q3-4 days
-minimal CNS effects
-renally excreted
propranolol:
-initial 20mg BID, max 320mg/day (160mg with ascites)
-titrate q3-4 days
-1A2 substrate
*titrate both to 25% decrease in resting HR or pulse 55bpm*
122
Differentiate therapy for primary prophylaxis and secondary prophylaxis of variceal bleeding.
primary prophylaxis:
-NSBB
-EVL (if high risk of bleed, refractory ascites, SBP)
secondary prophylaxis:
-NSBB + EVL
-TIPS for re-bleeding
123
What is hepatic encephalopathy?
CNS dysfunction observed in late-stage cirrhosis
124
What is the cause of hepatic encephalopathy?
not entirely clear MOA:
-accumulation in the bloodstream of neurotoxic substances that are normally removed by the liver
-substances implicated: ammonia, tryptophan, GABA
125
What is the presentation of hepatic encephalopathy?
presentation is variable
-drowsiness, personality changes, confusion
-many sx are reversible with appropriate therapy
126
What are the different severities of hepatic encephalopathy?
grade 1:
-changes in behaviour, mild confusion, slurred speech, disordered sleep
-mild tremor, anxiety, impaired hand writing
grade 2:
-lethargy, moderate confusion
-ataxia, asterixis, personality changes
grade 3:
-marked confusion, incoherent speech, sleeping but arousable
-seizures, muscle twitching, delirium, bizarre behavior
grade 4:
-coma, unresponsive to pain
127
What are the precipitating factors for hepatic encephalopathy?
protein intake or GI bleeding
drugs (diuretics, sedatives/CNS depressants)
surgery
continued alcohol use
constipation
infection/sepsis
renal failure
hypokalemia and/or metabolic acidosis
128
When should treatment for hepatic encephalopathy begin?
ASAP if symptoms appear
129
What is the management of hepatic encephalopathy?
identify and correct precipitant
restrict dietary protein
avoid CNS depressants
therapies aimed at lowering blood ammonia
-lactulose, antibiotics
130
True or false: lactulose is absorbed by the gut
false
131
What is the MOA of lactulose?
degraded by colonic bacteria to formic, acetic, and lactic acids
reduces pH-->reducing ammonia absorption, decreases production of urease-producing bacteria
reduces GI transit time
132
What is the first line therapy for hepatic encephalopathy?
lactulose
133
What is the dosage of lactulose for hepatic encephalopathy?
15-45ml TID-QID
-MD: 2-3 soft formed stools/day
-can decrease dose once mental state improves, often dc within days to weeks
134
What is the onset of lactulose?
12-48 hours
135
What are the adverse effects of lactulose?
nausea, gas, bloating, diarrhea
136
What are the alternatives to lactulose for hepatic encephalopathy?
metronidazole
-sterilizes GIT & inhibits activity of urease-producing bacteria, decreasing ammonia production
-limited use due to adverse effects
rifaximin
-non absorbable derivative of rifampin
-at least as effective as lactluose
-costly
137
Describe the general approach to care for cirrhosis.
discontinue alcohol
avoid ASA/NSAIDs
avoid sedatives/narcotics
adequate nutritional intake (deficiences are common)
138
Which deficiencies are common in liver disease?
protein and micronutrients
-multifactorial: decreased intake, malabsorption/digestion
pts with advanced alcoholic-liver disease or cholestatic disease often have deficiencies in fat-soluble vits (ADEK)
139
Describe thiamine (B1) deficiency due to heavy alcohol use.
ppl with alcohol-related liver disease at risk because:
-inadequate intake, impaired absorption/utilization, increased requirements
deficiency-->Wernickes Encephalopathy
prevention: 200mg/day
140
Describe pyridoxine (B6) and folate deficiency due to heavy alcohol use.
pyridoxine:
-deficiency in 50% of people with AUD
-2mg OD supplementation is suggested
folate:
-deficiency in 2/3 of binge drinkers
-400ug OD supplementation recommended
