Hepatic Physiology Flashcards
(202 cards)
1
Q
Anesthesia’s goals pertaining to the liver
A
maintain BP and oxygenation, keep the function that the patient does have
2
Q
What does the liver do to drugs? (simplified)
A
makes them water soluble so they can be eliminated by the kidneys
3
Q
What are the basic structures of a liver lobule?
A
portal vein, sinusoids, central vein, hepatic artery, bile canaliculi and bile duct, space of disse, lymphatic duct, hepatic cellular plates, kupffer cells, interlobular septa
4
Q
What makes the structural shape of the liver lobule advantageous?
A
hexagonal shape that shares blood supply and bile ducts in multiple directions with abutting lobules
5
Q
What are the two sources of blood supply to the liver?
A
portal vein
hepatic artery
6
Q
What is the significance of the space of Disse?
A
drains into the lymph
7
Q
What are sinusoids structurally/functionally similar to?
A
capillaries
8
Q
What does the liver cell plate do?
A
collects bile into the bile canaliculi
9
Q
What organ is a huge source of lymph?
A
the liver!
10
Q
Where are the Kupffer cells and what do they do?
A
inside the sinusoids and are macrophages that remove bacteria
11
Q
What is the best source of oxygenation to the liver?
A
the hepatic artery
12
Q
How much of the livers O2 requirement does the portal vein supply?
A
50%
13
Q
Portal vein SvO2
A
85%
14
Q
How much of the livers O2 requirement does the hepatic artery supply?
A
50%
15
Q
Hepatic artery SaO2
A
98-100%
16
Q
The liver has ___ blood flow and ___ vascular resistance
A
high; low
17
Q
normal hepatic blood flow
A
1500mL/minute (25-30% of CO)
18
Q
How much of the hepatic blood flow comes from the portal vein?
A
1100 mL/ minute (75% of total)
19
Q
How much of the hepatic blood flow comes from the hepatic artery?
A
400 mL/ minute (25% of total)
20
Q
What is the average portal vein pressure as blood enters the liver?
A
9 mmHg
21
Q
Pressure in the hepatic vein leaving the liver to the inferior vena cava is about
A
0 mmHg
22
Q
If resistance increases (what can it lead to)
A
portal hypertension
23
Q
Hepatic arterial blood flow is dependent on
A
metabolic demand (autoregulation)
24
Q
Hepatic portal vein blood flow is dependent on
A
blood flow to the GI tract and spleen
25
A decrease in hepatic arterial blood flow produces an ___ portal venous blood flow
increase
26
If arterial pressure is decreased then
decreased pressure through the hepatic artery and the portal vein
27
The superior mesenteric artery supplies blood to ___ (which organs)
colon, small intestines, pancreas
28
The celiac artery supplies blood to ___ (which organs)
stomach, spleen, pancreas
29
The inferior mesenteric artery supplies blood to ___ (which organs)
the colon
30
The blood supply from portal vein comes from (which organs)
stomach, spleen, pancreas, small intestines, and colon
31
Cirrhosis ___ the resistance to blood
greatly increases!
32
Patho of cirrhosis
destruction of liver parenchymal cells = replacement with fibrous tissue that contracts around the blood vessels = impedes portal vein blood flow
33
Most common cause of cirrhosis ___
alcoholism
34
Causes of cirrhosis (besides alcoholism)
viral hepatitis, obstruction of bile ducts, infection in the bile ducts, ingestion of poisons, non-alcoholic fatty liver disease
35
stages of alcohol induced liver damage (3)
1. fatty liver (deposits = liver enlargement) *is recoverable
2. liver fibrosis (scar tissue forms) *recovery possible but with scar tissue
3. cirrhosis (connective tissue destroys liver cells) *irreversible!!
36
micronodular cirrhosis
alcohol abuse can lead directly to cirrhosis from repeated exposure of the cells to toxins causing fibrosis and cirrhosis
37
What medications can cause liver disease?
TPN, amiodarone
38
What are the 3 most common causes of liver disease?
obesity, T2DM, metabolic syndrome
39
Metabolic syndrome
HTN, excess glucose and triglycerides, increased fat
40
NAFLD what does it stand for
non alcoholic fatty liver disease
41
25% of the US population has ___
NAFLD
42
NASH
nonalcoholic steatohepatitis (inflammation)
43
Up to 30% of people with NAFLD will develop
NASH
44
Up to 20% of people with NASH will develop
cirrhosis
45
Which receptors does the hepatic artery have?
alpha 1 (vasoconstriction), beta2 (vasodilation), dopa1 (vasodilation)
46
Which receptors does the portal vein have?
alpha 1, dopa1
47
sympathetic activation results in hepatic artery and mesenteric vessel ____ and ____ hepatic blood flow
vasoconstriction; decreased
48
beta 2 adrenergic stimulation ___ the hepatic artery
vasodilates
49
the liver's normal blood volume including what is in the veins and sinusoids is
about 450mL
50
the liver can expand to hold how much blood (in liters)
up to 1 L
51
when low pressure exists (like in hemorrhage) how much blood can the liver shift into circulation?
as much as 300 mL
52
How is the bacteria in the blood from the portal vein "cleansed"?
Kupffer cells engulfs the bacteria and goes through phagocytosis
53
Pores in the sinusoids are ___
very permeable allowing passage of fluid and protein in to the spaces of disse
54
About how much lymph comes from the liver?
1/2
55
high hepatic vascular pressure causes ____
fluid transudation into the abdominal cavity
56
a _____ increase in hepatic venous pressure can increase lymph flow to 20x normal
10-15 mmHg
57
How does ascites occur?
a high pressure in hepatic venous pressure leads to increase in lymph flow and back up of fluid that leaks through the liver capsule into the abdominal cavity
58
carbohydrates, fats, and proteins all lead to
the citric acid cycle and ATP production
59
list some metabolic functions of the liver
carbohydrate, fat, protein, and drug metabolism
60
carbohydrate metabolism final products
glucose, fructose, and galactose
61
all cells utilize _____ to produce energy in the form of ATP
glucose
62
specific liver functions with carbohydrate metabolism
convert galactose and fructose into glucose, storage of glycogen, gluconeogenesis, formation of chemical compounds
63
What are glucose, fructose, and galactose? What do they have in common?
simple sugars or monosaccharides
| have the same chemical formula (C6H12O6) but structural formulas differ
64
storage of glycogen allows
the liver to remove excess glucose from the blood, store it, and return it to the blood when BG is low (glucose buffer function)
65
Glucose buffer function
removed excess glucose that is stored in the liver and then returned to the blood when BG gets low
66
Does glycogen contribute to intracellular osmolality?
no
67
Structure of glycogen
a branched polymer of glucose (just a bunch hooked together)
68
when glycogen storage capacity is full, glucose is converted to
fat
69
insulin ___ glycogen storage
enhances
70
epinephrine and glucagon ___ glycogen breakdown (aka glycogenolysis)
enhances
71
hepatic glycogen stores are depleted after a ___
24 hours fast
| gluconeogensis kicks in to provide an uninterrupted supply of glucose
72
gluconeogenesis only occurs when
BG concentration falls below normal
73
agents that increase gluconeogenesis
glucocorticoids, catecholamines, glucagon, thyroid hormoen
74
agents that decrease gluconeogenesis
insulin
75
when carbohydrate storage capacity is saturated the liver converts the excess carbs to
fat
76
RBCs and renal medulla can only use ___ for energy
glucose
77
specific liver functions with fat metabolism
oxidation of fatty acids to supply energy, synthesis of large amounts of cholesterol, phospholipids, and lipoproteins, synthesis of fat from carbs and proteins
78
to derive energy from fat (triglycerides)
they must be split into glycerol and fatty acids
fatty acids are then split by beta oxidation into 2 carbon acetyl radicals that form acetyl CoA which enters the citric acid cycle to create a lot of ATP
79
the liver cannot use all of the ___ it produces
acetyl CoA
80
unused Acetyl CoA is
converted to acetoacetic acid which is highly soluble and leaves the hepatocytes enters the blood and absorbed by other tissues which will reconvert into acetyl CoA to be used to produce energy
81
acetyl CoA can also be used to synthesize
cholesterol and phospholipids
82
most of the cholesterol synthesized in the liver is converted to
bile salts and secreted into the bile
83
a small amount of cholesterol is
packaged into lipoproteins and carried to other tissue cells
84
cholesterol and phospholipids can be used to form
cell membranes, intracellular structures, chemical substances important to cell function
85
if protein metabolism doesn't occur
death will occur in a few days
86
specific liver functions associated with protein metabolism include
deamination of proteins, formation of urea for removal of ammonia, formation of plasma proteins, synthesis of amino acids
87
Deamination means
removal of nitrogen
88
essential amino acids have to come from
our diet
89
Deamination of _____ plays a major role in hepatic gluconeogenesis
alanine
90
large amount of ammonia are formed by
deamination process
| bacteria in gut with subsequent absorption into the blood
91
essentially all of the plasma proteins with the exception of ____ are formed by ___
immunoglobulins; hepatocytes
92
the liver can form plasma proteins at the rate of
15-50 g/day
93
if someone loses 1/2 of their plasma proteins the liver can replace them in about
1-2 weeks
94
quantitatively the most important plasma proteins are
albumin and alpha1- antitrypsin
95
albumin is responsible for
maintaining a normal plasma osmotic pressure and is the principal binding and transporting protein
96
qualitatively the most important plasma proteins are
coagulation factors
97
transamination
amino radical is transferred from an available amino acid to the keto acid
98
glycogenesis is
glucose stored as glycogen
99
glycogenolysis
breakdown glycogen to make glucose
100
end products of hepatic biotransformation are either
inactivated or are made more water soluble and excreted in urine or bile
101
phase 1 reactions of hepatic biotransformation
modify substances through cytochrome p450 enzymes and mixed function oxidases
102
oxidation generates
reactive oxygen species because carboxyl, epoxy, and hydroxyl groups are introduced into the parent compound
103
the cytochrome p450 system can be induced by
ethanol, barbiturates, ketamine, benzodiazepines
104
enzyme induction results in an
increase in the production of the enzymes that metabolize these drugs
105
enzyme induction can lead to ___
tolerance of these drugs
106
enzyme induction can promote
tolerance to other drugs metabolized by the same enzymes
107
ranitidine, amiodarone, ciprofloxacin can
prolong the effects of other drugs by inhibiting these enzymes
108
products of phase 1 reactions may be ___
more active than the parent compound or rendered cytotoxic
109
drugs with very high rate of hepatic extraction from the circulation
lidocaine, morphine, verapamil, labetalol, propranolol
110
a decrease in metabolic clearance of drugs that undergo high rate of hepatic extraction is from __
a reduced hepatic blood flow not hepatocyte dysfunction
111
barbiturates and benzodiazepines are inactivated by
phase 1 reactions
112
examples of poorly extracted drugs
tylenol, clindamycin, diazepam, digitoxin, warfarin
113
if someone has liver disease and is given lidocaine what effect will it have on the pharmacokinetics?
the half life is prolonged and the clearance is less so the effect is decreased but stays in the body longer
114
phase 2 reactions of biotransformation involve
conjugation of a substance with a water soluble metabolite
115
water soluble metabolites
glucuronide, sulfate, taurine, glycine
116
conjugated substances can be excreted in
the urine or bile
117
types of phase 1 reactions
oxidation, reduction, hydrolysis, hydration, dehalogenation
118
types of phase 2 reactions
sulfation, glucoronidation, glutathione conjugation, acetylation, amino acid conjugation, methylation
119
the liver is a storage site for
vitamins A, B12, D, E, and K
120
enough vitamin A can be stored for up to
10 months
121
enough vitamin B12 can be stored for up to
1 or more years
122
enough vitamin D can be stored for up to
3-4 months
123
how does the liver store iron?
as ferritin
124
hepatic cells produce and excrete ___ which can bind excess iron in body fluids
apoferritin
125
apoferritin + iron =
ferritin
126
iron is carried in the blood by
transferrin
127
vitamin K is a required cofactor for the synthesis of
factor II, VII, IX, X
128
vitamin k deficiency manifests as
coagulopathy d/t impaired formation of factors 2,7,9,10
129
which factors are not produced by the liver?
factor VIII and vonwillebrand
130
the liver is the primary site of degradation for
thyroid hormone, insulin, steroid hormones, glucagon, ADH
131
hepatocytes continuously secrete ___ into the bile canaliculi
bile salts, cholesterol, phospholipids and conjugated bilirubin
132
flow of bile from the common bile duct is controlled by
the sphincter of oddi
133
gallbladder function
reservoir for bile, concentrates biliary fluid by active transport of Na+ and passive H2O reabsorption
134
Cholecystokinin
is a hormone released from the intestinal mucosa in response to fat and protein that causes contraction of the gallbladder, relaxation of sphincter of oddi and ejection of bile into the small intestine
135
what is the major end product of Hgb degradation?
bilirubin
136
bilirubin provides a valuable tool for diagnosing
hemolytic blood diseases and various types of liver disease
137
after about ___ days RBCs become fragile and their membranes rupture
120
138
how Hgb is broken down
split into globin and heme, heme ring opened and Fe is released and transported by transferrin, the 4 pyrrole rings of the porphyrin structure are converted to biliverdin which is converted to free bilirubin which combines with plasma albumin
139
bilirubin bound to plasma albumin is called
free bilirubin, unconjugated / indirect bilirubin
140
bilirubin is conjugated with
glucuronide* and sulfate
141
in the intestine 1/2 of the ____ is converted by bacteria to ___ which is reabsorbed back into the blood
conjugated bilirubin; urobilinogen
142
What does excess bilirubin in the ECF cause?
jaundice
143
Which kind of bilirubin will cause jaundice?
can be unconjugated or conjugated!
144
Common causes of jaundice
increased destruction of RBCs (hemolytic jaundice), obstruction of the bile ducts or damage to hepatocytes (obstructive jaundice)
145
Which kind of bilirubin is toxic?
conjugated
146
What happens during hemolytic jaundice?
increased production of bilirubin by macrophages and unconjugated bilirubin in the blood
147
When hepatocytes cannot process all of the bilirubin what happens?
primarily an increase in unconjugated bilirubin but also a secondary increase in conjugated bilirubin
148
In hemolytic jaundice excretory function of the liver is
not impaired
149
in hemolytic jaundice the rate of formation of urobilinogen in the intestines ___ and urinary excretion ___
increases; increases
150
What most often causes obstruction of the common bile duct?
gallstones, malignancy but can also be caused by damage to hepatic cells from hepatitis
151
in obstructive jaundice most of the bilirubin in the plasma is in the ____ form
conjugated
152
in hemolytic jaundice majority of the bilirubin in the plasma is in the ____ form
unconjugated
153
when there is total obstruction of bile flow
no conjugated bilirubin can reach the intestines to be converted so no urobilinogen is reabsorbed into the blood and excreted by the kidney
154
with total obstruction of bile flow the test for urobilinogen in the urine is
completely negative
155
serum transaminase measurements reflect
hepatocellular integrity
156
tests that measure the liver's synthetic function include
serum albumin, PT/INR, cholesterol, pseudocholinesterase
157
liver abnormalities are typically divided into
```
parenchymal disorders (hepatocellular dysfunction)
obstructive disorders (biliary excretion)
```
158
normal total bilirubin
< 1.5 mg/dL
159
what does the total bilirubin reflect?
balance between production and biliary excretion
160
a predominately conjugated hyperbilirubinemia is associated with
an increased urobilinogen and reflect intrahepatic cholestasis, extrahepatic biliary obstruction which may lead to hepatocellular dysfunction
161
a primarily unconjugated hyperbilirubinemia may be seen with
hemolysis or with congenital or acquired defects in bilirubin conjugation
162
serum aminotransferases are
enzymes released in the circulation as a result of hepatocellular injury
163
what are two commonly measured serum aminotransferases?
AST/ALT
164
which serum aminotransferase is more specific?
ALT (primarily located in the liver)
165
Alkaline phosphatase is produced by the ____ and excreted into the ___
liver, bone, small bowel, kidneys, and placenta; bile
166
most of the circulating alk phos comes from ___
bone
167
in the presence of biliary obstruction alk phos
is synthesized more and released into the circulation
168
serum albumin has a ___ half life
long half life so its value may initially be normal with acute liver disease
169
low serum albumin levels are indicative of
chronic liver disease, acute stress, malnutrition
170
What can cause hypoalbuminemia?
increased loss in urine (nephrotic syndrome) and in the GI tract (enteropathy with protein loss)
171
increased NH3 in the blood usually reflects disruption of
hepatic urea synthesis
172
PT measures the activity of
fibrinogen, factor II, V, VII, X
173
factor VII has a ____ half life
short half life so PT is useful in evaluating hepatic synthetic function of patients with acute or chronic liver disease
174
if the PT doesn't correct after IV vitamin K
severe liver disease is likely present
175
how much time does it take for vitamin K to correct?
24 hours
176
pre - hepatic classification
bilirubin overload/ increased unconjugated bilirubin
177
causes of pre-hepatic dysfunction
hemolysis, hematoma reabsorption, bilirubin overload from whole blood (massive transfusion)
178
intra-hepatic classification
parenchymal/hepatocellular dysfunction
179
What lab values are affected by intra-hepatic dysfunction?
conjugated bilirubin, aminotransferase enzymes, PT (prolonged), albumin (decreased)
180
what causes intra-hepatic dysfunction?
viruses, drugs, sepsis, arterial hypoxemia, congestive heart failure, cirrhosis
181
post-hepatic classification
cholestasis (obstruction)
182
what lab values are affected by post-hepatic dysfunction?
conjugated bilirubin, alk phos
183
what causes post-hepatic dysfunction?
stones, cancer, sepsis
184
how does general and regional anesthesia affect hepatic blood flow?
decreases it due to direct and indirect effects of anesthetic agents themselves, type of ventilation, and surgical procedure
185
which volatile agent causes the greatest decrease in portal blood flow?
halothane
186
which volatile agent is the agent of choice for hepatic disease?
isoflurane
187
hypoxemia produces
increased SNS stimulation and decrease in hepatic blood flow
188
surgical procedures on or near the liver can
decrease hepatic blood flow by 60% from SNS activation, autoregulation, and direct compression of vessels
189
drugs that decrease hepatic blood flow
beta adrenergic blockers, alpha 1 agonists, vasopressin
190
endocrine stress response secondary to fasting and surgical stress results in
increased circulating levels of catecholamines, glucagon, cortisol
191
the endocrine stress response can be at least partially blunted by
regional anesthesia, deep general anesthesia, pharmacological block of the SNS
192
all opioids can potentially cause
spasm of the sphincter of Oddi and increases biliary pressure
193
which opioids cause the most "spasm" of the sphincter of oddi
the phenylpiperdines - fentanyl, sufentanil, alfentanil, remifentanil
194
IV opioids can induce ___ or result in ____ cholangiograms
biliary colic or result in false positive cholangiograms
195
persistent abnormalities in liver function test may be indicative of
viral hepatitis, sepsis, idiosyncratic drug reaction, surgical complications
196
the most common cause of postoperative jaundice is
over production of bilirubin d/t reabsorption of a large hematoma or RBC breakdown following transfusion
197
hepatitis has been associated with
methoxyflurane, enflurane, isoflurane, halothane
198
potential mechanisms for halothane hepatitis
formation of hepatotoxic metabolites, immune hypersensitivity
199
how much of halothane is metabolized?
20%
200
how much of sevoflurane is metabolized?
1%
201
halothane hepatitis is a diagnosis of
exclusion
202
risk factors associated with halothane hepatitis
middle age, obesity, females, repeat exposure (within 28 days)
