Hepatic week 1 Flashcards
(152 cards)
1
Q
What are the functions of the liver?
A
stores vitamins, minerals, and sugar preventing shortage of nutrients
regulates blood clotting
produces proteins
produces bile needed to digest fat and absorb fat soluble vitamins
helps to fight infection by removing bacteria from the blood
removes toxic byproducts of medications
metabolizes nutrients from food to make energy
2
Q
The basic functional unit of the liver is
A
the lobule
3
Q
How many lobules are in the liver?
A
50,000-100,000
4
Q
The largest organ in the body is
A
the liver
5
Q
Basic structures of a liver lobule include
A
portal vein, sinusoids (like capillaries), central vein, hepatic artery, bile canaliculi and bile duct (transport & storage), space of Disse and lymphatic duct, hepatic cellular plates, Kuppfer cells, & interlobular septa
6
Q
The portal vein and hepatic artery empty into the
A
central vein
7
Q
The Space of Disse is where
A
the lymph fluid flows across and empties into the lymphatic duct
8
Q
The bile canaculi produces
A
bile that drains down into the bile duct
9
Q
The liver receives its blood supply from the
A
portal vein and hepatic artery
10
Q
The portal vein supplies _____ of the livers O2 requirement
A
50%
11
Q
The portal vein SvO2 is
A
85%
12
Q
The hepatic artery supplies ______ of the livers O2 requirement
A
50%
13
Q
Describe the blood flow and the resistance in the liver.
A
The liver has high blood flow and low vascular resistance
14
Q
Normal hepatic blood flow in the liver is
A
1500 mL/minute (25-30% of CO)
15
Q
Describe the blood flow of the portal vein.
A
1100 mL/min or 75% of total
16
Q
Describe the blood flow of the hepatic artery.
A
400 mL/min or 25% of total
17
Q
Portal vein pressure as blood enters the liver averages
A
9 mmHg
18
Q
Pressure in the hepatic vein leaving the liver
A
enters the vena cava and the pressure is 0 mmHg here
19
Q
The pressure difference between the portal vein and the hepatic vein demonstrates
A
resistance to flow in the hepatic sinusoids is very low
20
Q
Describe the overall blood flow to the liver.
A
Aorta branches into the celiac artery which shunts blood to the hepatic artery, stomach, spleen, & pancreas before going to the portal vein
The superior mesenteric artery shunts blood to the pancreas, small intestines and colon before going to the portal vein
The inferior mesenteric artery brings blood to the colon then becoming the portal vein
The portal vein and the hepatic artery feed into the liver which then feeds the hepatic veins and ultimately the inferior vena cava
21
Q
Cirrhosis greatly increases the
A
resistance to blood flow
22
Q
The most common cause of cirrhosis is
A
alcoholism
23
Q
Other causes (besides alcoholism) of cirrhosis include
A
viral hepatitis obstruction of bile ducts infection in the bile ducts ingestion of poisons (carbon tetrachloride) non-alcoholic fatty liver disease
24
Q
Describe how cirrhosis impedes portal vein blood flow.
A
destruction of liver parenchymal cells results in replacement with fibrous tissue that contracts around the blood vessels (bridging fibrosis)
greatly impedes portal vein blood flow
25
Stages of alcohol induced liver damage includes
fatty liver
liver fibrosis
cirrhosis
26
Describe the fatty liver stage.
deposits of fat causes liver enlargement
| strict abstinence can lead to a full recovery
27
Describe the liver fibrosis stage.
scar tissue forms
| recovery is possible but scar tissue remains
28
Describe the cirrhosis stage of alcohol induced liver damage.
growth of connective tissue destroys liver cells
| the damage is irreversible!
29
Repeated exposure of hepatocytes to toxins can lead directly to
fibrosis and cirrhosis, most frequently, micronodular cirrhosis
30
The most common causes of non-alcoholic fatty liver disease are
obesity, DMII, & metabolic syndrome
| -less common but possible are nutrition (patients on TPN) & medication (amiodarone)
31
Describe the adrenergic receptors located in the hepatic artery.
alpha 1- produces vasoconstriction
| beta 2, dopaminergic 1 & cholinergic receptors- produce vasodilation
32
Describe the adrenergic receptors located in the portal vein.
alpha 1- produces vasoconstriction
| dopaminergic 1- produces vasodilation
33
Sympathetic activation results in
hepatic artery and mesenteric vessel vasoconstriction and decreased hepatic blood flow
-beta 2 adrenergic stimulation vasodilates the hepatic artery
34
The liver is known as an
expandable organ- large blood reservoir
35
The livers normal blood volume is
450 mL- includes what is found in the hepatic veins + sinusoids
36
When high pressure occurs in the right atrium, it produces
back pressure causing the liver to expand
| 0.5-1 L of blood can be stored in the hepatic veins & sinusoids
37
When low pressure occurs in the body such as during hemorrhage,
the blood shifts from the hepatic veins and sinusoids into the central circulation (as much as 300 mL)
38
Hepatic macrophages serve a
blood cleansing function
39
Blood from the intestinal capillaries that enters the portal vein contains
many bacteria
- blood from the portal vein almost always grows bacilli when cultured but it is extremely rare to grow bacilli from a systemic blood smaple
40
Kupffer cells that line the hepatic venous sinusoids
cleanse the blood as it passes through the sinuses
-takes 0.01 second for a bacterium to pass into a Kupffer cell after coming into contact with the cell
the bacterium is then digested (phagocytosis)
41
Additional Kupffer cell roles include
phagocytose cellular debris, viruses, proteins, and particulate matter
release various enzymes, cytokines, and other chemical mediators
42
Kupffer cells are a part of the
monocyte-macrophage system AKA the reticuloendothelial system
43
The liver has very high
lymph flow
44
Pores in the sinusoids are very
permeable and allow easy passage of fluid and protein into the spaces of Disse
this permits large amounts of lymph with a protein concentration similar to plasma to form
45
About _____ of all lymph in the body comes from the liver
half
46
High hepatic vascular pressure causes
fluid transudation into the abdominal cavity
47
When above normal pressures occur in the hepatic vein, this results in
excessive amounts of lymph fluid
| -can leak through the outer surface of the liver capsule into the abdominal cavity
48
A 10 to 15 mmHg increase in hepatic venous pressure can increase lymph flow
to 20x normal
produces 'sweating' from the liver surface with large amounts of free fluid entering the abdominal cavity resulting in ascites
49
Blockage of the portal vein produces high
pressure in the GI tract with transudation of fluid through the gut and into the abdominal cavity resulting in ascites
50
The liver is a large, chemically reactant pool of cells that:
have a high rate of metabolism
share substrates and energy from one system to another
process and synthesize multiple substances that are transported throughout the body (numerous enzymatic pathways)
51
The final products of carbohydrate metabolism are
glucose, fructose, and galactose
| the liver ends up converting galactose and fructose into glucose for a common final pathway
52
Glucose is important because
all cells utilize glucose to produce energy in the form of ATP
53
Describe the 4 steps of carbohydrate metabolism.
Conversion of galactose and fructose to glucose
storage of large amounts of glycogen
gluconeogenesis
Formation of many chemical compounds from intermediate products of carbohydrate metabolism
54
Glucose, fructose, and galactose are called
simple sugars or monosaccharides
55
Most of the glucose absorbed following a meal is
normally stored as glycogen
56
Storage of glycogen allows the liver to
remove excess glucose from the blood, store it, and return it to the blood when BG concentration decrease: glucose buffer function
57
Glycogen is a readily available source of
glucose that does not contribute to intracellular osmolality
58
Glucose concentration in the blood after a carbohydrate rich meal can rise
2 to 3 times as much in a person with poor liver function as compared to a person with normal liver function
59
glycogen is a branched polymer of
glucose
60
When glycogen storage capacity is exceeded, the excess glucose is
converted to fat
61
The only organs capable of storing significant amounts of glycogen are
liver and muscle
62
Insulin enhances
glycogen storage
63
Epinephrine and glucagon enhance
glycogen breakdown (glycogenolysis)
64
Hepatic glycogen stores are depleted after
a 24 hour fast;
| after this period gluconeogenesis is necessary to provide an uninterrupted supply of glucose
65
Gluconeogenesis occurs only when
BG concentration falls below normal
| vital in maintenance of normal BG concentration
66
The liver (and kidney) are unique in their ability to
convert amino acids, glycerol, pyruvate, and lactate to glucose
67
Agents that increase gluconeogenesis:
glucocorticosteroids, catecholamines, glucagon, thyroid hormone
68
Agents that decrease gluconeogenesis are
insulin
69
When carbohydrate storage capacity is saturated the liver converts excess carbohydrates to
fat
70
Excess carbs that are converted to fat are fatty acids that are used for
fuel or stored in the adipose tissue and liver for later use
71
Most cells can directly use fatty acids as
an energy source
RBCs and the renal medulla can only use glucose
neurons normally use only glucose but can use ketone bodies produced in the liver by the breakdown of FAs following a few days of starvation
72
Specific liver functions associated with fat metabolism are
oxidation of FAs to supply energy for other body function (known as beta oxidation)
synthesis of large amounts of cholesterol, phospholipids, and lipoproteins
synthesis of fate from carbs & proteins
73
In order to derive energy from fat (triglycerides)
they must be split into glycerol & FAs
74
After fatty acids are split into glycerol and FAs, FAs are then split by
beta oxidation into 2- Carbon acetyl radicals that form acetyl coenzyme A (acetyl Co-A)
75
Acetyl Co-A then enters the
citric acid cycle and is oxidized to liberate tremendous amounts of energy
76
Beta oxidation can occur in all body cells but occurs especially rapidly in
hepatic cells
77
The liver CANNOT use all of the acetyl Co-A it produces, it is
converted to acetoacetic acid (combination of 2 acetyl Co-A molecules)
acetoacetic acid is highly soluble and leaves the hepatocytes, enters the blood, and is absorbed by other tissues
tissues reconvert the acetoacetic acid back into acetyl Co-A which enters the citric acid cycle and is oxidized to produce energy
in this way, the liver is responsible for a major part of fat metabolism
78
Acetyl Co-A is used by the liver to synthesize
cholesterol and phospholipids
79
About 80% of the cholesterol synthesized in the liver is converted to
bile salts and secreted into the bile
| -the remaining cholesterol is packaged in lipoproteins and carried by the blood to all tissue cells in the body
80
Both cholesterol and phospholipids are used by body cells to form:
```
cell membranes
intracellular structures
chemical substances (hormones) important to cell function
```
81
____ are also synthesized in the liver and transported predominately in lipoprotiens
phospholipids
82
Fat metabolism is the
synthesis of fat from proteins & carbs which occurs primarily in the liver
83
After fat is synthesized, it is transported in
lipoproteins to the adipose tissue to be stored
84
Protein metabolism is a
critical liver function
| -without this function death will occur in a few days
85
Specific liver functions associated with protein metabolism:
1. deamination of proteins
2. formation of urea for removal of ammonia from the body fluids
3. formation of plasma proteins
4. synthesis of amino acids and synthesis of other compounds from amino acids
86
Essential proteins are those
that cannot be made and must be eaten via the diet
87
Deamination of the amino acids in proteins is required before
they can be used for energy or before they can be converted to CHO or fats
88
Deamination is an
enzymatic process which converts AAs into their respective keto acids and results in production of ammonia as a byproduct
89
The primary site of deamination is
the liver
90
Deamination of alanine plays a major role in
hepatic gluconeogenesis
| minor deamination of glutamine in the kidney
91
The liver normally deaminates most of the AAs derived from dietary protein consumption, the branched chain AAs are metabolized by
skeletal muscle
92
Urea forms from
ammonia
| urea removes ammonia from the body fluids
93
Large amounts of ammonia are formed by
deamination process
| bacteria in the gut with subsequent absorption into the blood
94
Urea readily diffuses out of
the liver and is excreted by the kidneys
| this is due to its water solubility
95
If the liver does not perform the function of formation of urea,
ammonia concentration rises rapidly and results in hepatic coma and death
96
A greatly reduced blood flow through the liver can cause
excessive ammonia in the blood and toxicity
- a porta-caval shunt may be performed in patients with portal vein hypertension but then it can cause an increase in ammonia in the blood sense it bypasses the liver
97
All of the plasma proteins with the exception of the
immunoglobulins are formed by hepatocytes
98
The liver can form plasma proteins a the rate of
15 to 50 g/day
99
After the loss of as much as 1/2 of the plasma proteins, the liver
can replace them in about 1 to 2 weeks
100
Quantitatively the most important plasma proteins are
albumin which is responsible for maintaining a normal plasma osmotic pressure and the principal binding and transport protein for FAs, hormones, and drugs
alpha 1 antitrypsin
101
Qualitatively the most important plasma proteins are:
coagulation factors
102
The synthesis of AAs and other compounds from AAs are among the
most important functions of the liver
103
The so-called "non-essential" AAs can be synthesized in the
liver by interconversion of one AA to another
104
A keto acid is formed that has the same chemical composition as the AA to be formed
except at the keto oxygen
105
An amino radical is transferred from an
available AA to the keto acid to take the place of the keto oxygen
process takes many steps and is called transamination
106
Many exogenous substances including
drugs undergo hepatic biotransformation
| -end products are inactivated or are made more water soluble and can be excreted in the urine or bile
107
Biotransformation involves
2 types of reactions
108
Phase 1 reactions modify substances through
CYP450 enzymes and mixed function oxidases
109
Reduction is
mainly catalyzed by the P450 enzymes
| electron added to make it more water solbule
110
Oxidation is
90% of all reactions
often generates reactive oxygen species because carboxyl, epoxy, and hydroxyl groups are introduced into the parent compound
111
The CYP450 enzyme system can be induced by
ethanol, barbiturates, ketamine, and benzodiazepines
112
Enzyme induction results in an increase in
the production of the enzymes that metabolize these drugs
113
Enzyme induction can lead to
tolerance of these drugs
114
Enzyme induction can promote
tolerance to other drugs metabolized by the same enzymes; this is known as cross-tolerance
115
CYP450 inhibitors include _______ and can_______
ranitidine, amiodarone, & ciprofloxacin
| prolong the effects of other drugs by inhibiting these enzymes
116
Products of phase 1 reactions may be more
active than the parent compound or may be rendered cytotoxic
-think acetaminophen, isoniazid, halothane
117
Some drugs have a very high rate of hepatic extraction from the circulation meaning that
a decrease in their metabolic clearance is usually a product of reduced hepatic blood flow now hepatocyte dysfunction
drugs include lidocaine, morphine, verapamil, labetalol, & propranolol
118
Barbiturates and benzodiazepines are inactived by
phase 1 reactions
119
Drugs that are poorly extracted include
acetaminophen, diazepam, digitoxin, and warfarin
120
Compare the half-life volume of distribution and clearance of a normal liver versus liver disease.
liver disease patients have higher half-life & volume of distribution with a lower clearance
121
Phase II reactions which may or may not follow a phase I reaction involve
conjugation of a substance with a water metabolite
| glucuronide (most common), sulfate, taurine, & glycine
122
Conjugated substances can be excreted
in the urine or bile
123
Vitamin K is a required cofactor for the synthesis of
Factors II (prothrombin), 7, 9, & 10
124
Vitamin K deficiency is manifested as a
coagulopathy due to impaired formation of factors 2, 7, 9, and 10
125
Factor VIII and von willebrand's factor are
not produced by the liver
126
the liver is the primary site for degradation for
thyroid hormone, insulin, glucagon, ADH, and steroid hormones (cortisol, aldosterone, and estrogen)
127
Hepatocytes continuously secrete
bile salts, cholesterol, phospholipids, & conjugated bilirubin into the bile canaliculi
128
Bile ducts from hepatic lobules eventually form the
left and right hepatic ducts
| these ducts combine to form the hepatic duct which with the cystic duct from the gallbladder forms the common bile duct
129
Flow of bile from the common bile duct is controlled by
Sphincter of Oddi
130
The Gallbladder serves as
reservoir for bile. through active transport of Na+ and passive H2O reabsorption the gallbladder concentrates biliary fluid
131
Cholecystokinin is a
hormone released from the intestinal mucosa in response to fat & protein that causes contraction of the gallbladder, relaxation of the Sphincter of Oddi and ejection of bile into the small intestine
132
Phase I reactions include
oxidation, reduction, hydrolysis, hydration, & dehalogeation
133
Phase II reactions include
sulfation, glucoronidation, gluthaione conjugation, acetylation, amino acid conjugation, and methylation
134
The liver is a storage site for vitamins and stores large quantities of
Vitamins A, B12, D, E, and K
enough A can be stored to prevent deficiency for 10 months
enough B12 can be stored for 1 or more years
enough D can be stored for 3 to 4 months
135
The liver stores iron as
ferritin
136
Hepatic cells produce and excrete large amounts of a protein called
apoferritin which can bind excess iron in body fluids
137
Apoferritin + iron equals
ferritin which is then stored in hepatocytes until the iron is needed elsewhere in the body
138
During low levels of iron in the circulation,
ferritin release iron
139
Iron is carried in the blood by
transferrin
140
The apoferritin-ferritin system acts as
an iron storage and buffer system
141
The major end product of hemoglobin degradation is
bilirubin
142
Bilirubin is excreted in
the bile and eliminated in the feces
143
Bilirubin is a valuable tool for diagnosing
hemolytic blood disease and various types of liver disease
144
After ___ days, RBCs become fragile and their cell membranes rupture
120
145
The released hemoglobin that is fractured is
phagocytized by tissue macrophages
146
Describe the process of hemoglobin breakdown.
The hemoglobin is split into globin & heme
the heme ring is opened and the Fe is release and is transported in the blood by Transferrin
The 4 pyrrole rings of the porphyrin structure are converted to biliverdin
biliverdin is rapidly converted to free bilirubin and released from the macrophages
the free bilirubin immediately combines with plasma albumin
147
The simplistic version of the hemoglobin breakdown is:
hemoglobin--> globin + heme--> Fe + pyrrole rings--> biliverdin--> free bilirubin--> bilirubin + albumin
148
Bilirubin bound to plasma albumin is called
"free bilirubin", unconjugated or indirect bilirubin
149
Free bilirubin is absorbed by
hepatocytes and released from albumin
150
Bilirubin is then conjugated with
glucoronide
| sulfate
151
Conjugated bilirubin (direct bilirubin) is excreted from the
hepatocytes by an active transport process into the bile canaliculi and then into the intestines
152
In the intestine about 1/2 of the conjugated bilirubin is converted by
bacteria to urobilinogen which is reabsorbed back into the blood
-some of this is then excreted in the urine
majority of this is re-excreted by the liver back into the intestines and eliminated in the feces
