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Pathophys II > Hepatic week 1 > Flashcards

Hepatic week 1 Flashcards

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

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2
Q

The basic functional unit of the liver is

A

the lobule

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3
Q

How many lobules are in the liver?

A

50,000-100,000

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4
Q

The largest organ in the body is

A

the liver

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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

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6
Q

The portal vein and hepatic artery empty into the

A

central vein

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7
Q

The Space of Disse is where

A

the lymph fluid flows across and empties into the lymphatic duct

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8
Q

The bile canaculi produces

A

bile that drains down into the bile duct

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9
Q

The liver receives its blood supply from the

A

portal vein and hepatic artery

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10
Q

The portal vein supplies _____ of the livers O2 requirement

A

50%

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11
Q

The portal vein SvO2 is

A

85%

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12
Q

The hepatic artery supplies ______ of the livers O2 requirement

A

50%

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13
Q

Describe the blood flow and the resistance in the liver.

A

The liver has high blood flow and low vascular resistance

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14
Q

Normal hepatic blood flow in the liver is

A

1500 mL/minute (25-30% of CO)

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15
Q

Describe the blood flow of the portal vein.

A

1100 mL/min or 75% of total

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16
Q

Describe the blood flow of the hepatic artery.

A

400 mL/min or 25% of total

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17
Q

Portal vein pressure as blood enters the liver averages

A

9 mmHg

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18
Q

Pressure in the hepatic vein leaving the liver

A

enters the vena cava and the pressure is 0 mmHg here

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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

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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

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21
Q

Cirrhosis greatly increases the

A

resistance to blood flow

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22
Q

The most common cause of cirrhosis is

A

alcoholism

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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
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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

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25
Q

Stages of alcohol induced liver damage includes

A

fatty liver
liver fibrosis
cirrhosis

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26
Q

Describe the fatty liver stage.

A

deposits of fat causes liver enlargement

strict abstinence can lead to a full recovery

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27
Q

Describe the liver fibrosis stage.

A

scar tissue forms

recovery is possible but scar tissue remains

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28
Q

Describe the cirrhosis stage of alcohol induced liver damage.

A

growth of connective tissue destroys liver cells

the damage is irreversible!

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29
Q

Repeated exposure of hepatocytes to toxins can lead directly to

A

fibrosis and cirrhosis, most frequently, micronodular cirrhosis

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30
Q

The most common causes of non-alcoholic fatty liver disease are

A

obesity, DMII, & metabolic syndrome

-less common but possible are nutrition (patients on TPN) & medication (amiodarone)

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31
Q

Describe the adrenergic receptors located in the hepatic artery.

A

alpha 1- produces vasoconstriction

beta 2, dopaminergic 1 & cholinergic receptors- produce vasodilation

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32
Q

Describe the adrenergic receptors located in the portal vein.

A

alpha 1- produces vasoconstriction

dopaminergic 1- produces vasodilation

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33
Q

Sympathetic activation results in

A

hepatic artery and mesenteric vessel vasoconstriction and decreased hepatic blood flow
-beta 2 adrenergic stimulation vasodilates the hepatic artery

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34
Q

The liver is known as an

A

expandable organ- large blood reservoir

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35
Q

The livers normal blood volume is

A

450 mL- includes what is found in the hepatic veins + sinusoids

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36
Q

When high pressure occurs in the right atrium, it produces

A

back pressure causing the liver to expand

0.5-1 L of blood can be stored in the hepatic veins & sinusoids

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37
Q

When low pressure occurs in the body such as during hemorrhage,

A

the blood shifts from the hepatic veins and sinusoids into the central circulation (as much as 300 mL)

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38
Q

Hepatic macrophages serve a

A

blood cleansing function

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39
Q

Blood from the intestinal capillaries that enters the portal vein contains

A

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

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40
Q

Kupffer cells that line the hepatic venous sinusoids

A

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)

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41
Q

Additional Kupffer cell roles include

A

phagocytose cellular debris, viruses, proteins, and particulate matter
release various enzymes, cytokines, and other chemical mediators

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42
Q

Kupffer cells are a part of the

A

monocyte-macrophage system AKA the reticuloendothelial system

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43
Q

The liver has very high

A

lymph flow

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44
Q

Pores in the sinusoids are very

A

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

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45
Q

About _____ of all lymph in the body comes from the liver

A

half

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46
Q

High hepatic vascular pressure causes

A

fluid transudation into the abdominal cavity

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47
Q

When above normal pressures occur in the hepatic vein, this results in

A

excessive amounts of lymph fluid

-can leak through the outer surface of the liver capsule into the abdominal cavity

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48
Q

A 10 to 15 mmHg increase in hepatic venous pressure can increase lymph flow

A

to 20x normal
produces ‘sweating’ from the liver surface with large amounts of free fluid entering the abdominal cavity resulting in ascites

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49
Q

Blockage of the portal vein produces high

A

pressure in the GI tract with transudation of fluid through the gut and into the abdominal cavity resulting in ascites

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50
Q

The liver is a large, chemically reactant pool of cells that:

A

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)

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51
Q

The final products of carbohydrate metabolism are

A

glucose, fructose, and galactose

the liver ends up converting galactose and fructose into glucose for a common final pathway

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52
Q

Glucose is important because

A

all cells utilize glucose to produce energy in the form of ATP

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53
Q

Describe the 4 steps of carbohydrate metabolism.

A

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

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54
Q

Glucose, fructose, and galactose are called

A

simple sugars or monosaccharides

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55
Q

Most of the glucose absorbed following a meal is

A

normally stored as glycogen

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56
Q

Storage of glycogen allows the liver to

A

remove excess glucose from the blood, store it, and return it to the blood when BG concentration decrease: glucose buffer function

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57
Q

Glycogen is a readily available source of

A

glucose that does not contribute to intracellular osmolality

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58
Q

Glucose concentration in the blood after a carbohydrate rich meal can rise

A

2 to 3 times as much in a person with poor liver function as compared to a person with normal liver function

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59
Q

glycogen is a branched polymer of

A

glucose

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60
Q

When glycogen storage capacity is exceeded, the excess glucose is

A

converted to fat

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61
Q

The only organs capable of storing significant amounts of glycogen are

A

liver and muscle

62
Q

Insulin enhances

A

glycogen storage

63
Q

Epinephrine and glucagon enhance

A

glycogen breakdown (glycogenolysis)

64
Q

Hepatic glycogen stores are depleted after

A

a 24 hour fast;

after this period gluconeogenesis is necessary to provide an uninterrupted supply of glucose

65
Q

Gluconeogenesis occurs only when

A

BG concentration falls below normal

vital in maintenance of normal BG concentration

66
Q

The liver (and kidney) are unique in their ability to

A

convert amino acids, glycerol, pyruvate, and lactate to glucose

67
Q

Agents that increase gluconeogenesis:

A

glucocorticosteroids, catecholamines, glucagon, thyroid hormone

68
Q

Agents that decrease gluconeogenesis are

A

insulin

69
Q

When carbohydrate storage capacity is saturated the liver converts excess carbohydrates to

A

fat

70
Q

Excess carbs that are converted to fat are fatty acids that are used for

A

fuel or stored in the adipose tissue and liver for later use

71
Q

Most cells can directly use fatty acids as

A

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
Q

Specific liver functions associated with fat metabolism are

A

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
Q

In order to derive energy from fat (triglycerides)

A

they must be split into glycerol & FAs

74
Q

After fatty acids are split into glycerol and FAs, FAs are then split by

A

beta oxidation into 2- Carbon acetyl radicals that form acetyl coenzyme A (acetyl Co-A)

75
Q

Acetyl Co-A then enters the

A

citric acid cycle and is oxidized to liberate tremendous amounts of energy

76
Q

Beta oxidation can occur in all body cells but occurs especially rapidly in

A

hepatic cells

77
Q

The liver CANNOT use all of the acetyl Co-A it produces, it is

A

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
Q

Acetyl Co-A is used by the liver to synthesize

A

cholesterol and phospholipids

79
Q

About 80% of the cholesterol synthesized in the liver is converted to

A

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
Q

Both cholesterol and phospholipids are used by body cells to form:

A 
cell membranes
intracellular structures
chemical substances (hormones) important to cell function
81
Q

____ are also synthesized in the liver and transported predominately in lipoprotiens

A

phospholipids

82
Q

Fat metabolism is the

A

synthesis of fat from proteins & carbs which occurs primarily in the liver

83
Q

After fat is synthesized, it is transported in

A

lipoproteins to the adipose tissue to be stored

84
Q

Protein metabolism is a

A

critical liver function

-without this function death will occur in a few days

85
Q

Specific liver functions associated with protein metabolism:

A
  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
Q

Essential proteins are those

A

that cannot be made and must be eaten via the diet

87
Q

Deamination of the amino acids in proteins is required before

A

they can be used for energy or before they can be converted to CHO or fats

88
Q

Deamination is an

A

enzymatic process which converts AAs into their respective keto acids and results in production of ammonia as a byproduct

89
Q

The primary site of deamination is

A

the liver

90
Q

Deamination of alanine plays a major role in

A

hepatic gluconeogenesis

minor deamination of glutamine in the kidney

91
Q

The liver normally deaminates most of the AAs derived from dietary protein consumption, the branched chain AAs are metabolized by

A

skeletal muscle

92
Q

Urea forms from

A

ammonia

urea removes ammonia from the body fluids

93
Q

Large amounts of ammonia are formed by

A

deamination process

bacteria in the gut with subsequent absorption into the blood

94
Q

Urea readily diffuses out of

A

the liver and is excreted by the kidneys

this is due to its water solubility

95
Q

If the liver does not perform the function of formation of urea,

A

ammonia concentration rises rapidly and results in hepatic coma and death

96
Q

A greatly reduced blood flow through the liver can cause

A

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
Q

All of the plasma proteins with the exception of the

A

immunoglobulins are formed by hepatocytes

98
Q

The liver can form plasma proteins a the rate of

A

15 to 50 g/day

99
Q

After the loss of as much as 1/2 of the plasma proteins, the liver

A

can replace them in about 1 to 2 weeks

100
Q

Quantitatively the most important plasma proteins are

A

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
Q

Qualitatively the most important plasma proteins are:

A

coagulation factors

102
Q

The synthesis of AAs and other compounds from AAs are among the

A

most important functions of the liver

103
Q

The so-called “non-essential” AAs can be synthesized in the

A

liver by interconversion of one AA to another

104
Q

A keto acid is formed that has the same chemical composition as the AA to be formed

A

except at the keto oxygen

105
Q

An amino radical is transferred from an

A

available AA to the keto acid to take the place of the keto oxygen
process takes many steps and is called transamination

106
Q

Many exogenous substances including

A

drugs undergo hepatic biotransformation

-end products are inactivated or are made more water soluble and can be excreted in the urine or bile

107
Q

Biotransformation involves

A

2 types of reactions

108
Q

Phase 1 reactions modify substances through

A

CYP450 enzymes and mixed function oxidases

109
Q

Reduction is

A

mainly catalyzed by the P450 enzymes

electron added to make it more water solbule

110
Q

Oxidation is

A

90% of all reactions
often generates reactive oxygen species because carboxyl, epoxy, and hydroxyl groups are introduced into the parent compound

111
Q

The CYP450 enzyme system can be induced by

A

ethanol, barbiturates, ketamine, and benzodiazepines

112
Q

Enzyme induction results in an increase in

A

the production of the enzymes that metabolize these drugs

113
Q

Enzyme induction can lead to

A

tolerance of these drugs

114
Q

Enzyme induction can promote

A

tolerance to other drugs metabolized by the same enzymes; this is known as cross-tolerance

115
Q

CYP450 inhibitors include _______ and can_______

A

ranitidine, amiodarone, & ciprofloxacin

prolong the effects of other drugs by inhibiting these enzymes

116
Q

Products of phase 1 reactions may be more

A

active than the parent compound or may be rendered cytotoxic
-think acetaminophen, isoniazid, halothane

117
Q

Some drugs have a very high rate of hepatic extraction from the circulation meaning that

A

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
Q

Barbiturates and benzodiazepines are inactived by

A

phase 1 reactions

119
Q

Drugs that are poorly extracted include

A

acetaminophen, diazepam, digitoxin, and warfarin

120
Q

Compare the half-life volume of distribution and clearance of a normal liver versus liver disease.

A

liver disease patients have higher half-life & volume of distribution with a lower clearance

121
Q

Phase II reactions which may or may not follow a phase I reaction involve

A

conjugation of a substance with a water metabolite

glucuronide (most common), sulfate, taurine, & glycine

122
Q

Conjugated substances can be excreted

A

in the urine or bile

123
Q

Vitamin K is a required cofactor for the synthesis of

A

Factors II (prothrombin), 7, 9, & 10

124
Q

Vitamin K deficiency is manifested as a

A

coagulopathy due to impaired formation of factors 2, 7, 9, and 10

125
Q

Factor VIII and von willebrand’s factor are

A

not produced by the liver

126
Q

the liver is the primary site for degradation for

A

thyroid hormone, insulin, glucagon, ADH, and steroid hormones (cortisol, aldosterone, and estrogen)

127
Q

Hepatocytes continuously secrete

A

bile salts, cholesterol, phospholipids, & conjugated bilirubin into the bile canaliculi

128
Q

Bile ducts from hepatic lobules eventually form the

A

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
Q

Flow of bile from the common bile duct is controlled by

A

Sphincter of Oddi

130
Q

The Gallbladder serves as

A

reservoir for bile. through active transport of Na+ and passive H2O reabsorption the gallbladder concentrates biliary fluid

131
Q

Cholecystokinin is a

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
Q

Phase I reactions include

A

oxidation, reduction, hydrolysis, hydration, & dehalogeation

133
Q

Phase II reactions include

A

sulfation, glucoronidation, gluthaione conjugation, acetylation, amino acid conjugation, and methylation

134
Q

The liver is a storage site for vitamins and stores large quantities of

A

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
Q

The liver stores iron as

A

ferritin

136
Q

Hepatic cells produce and excrete large amounts of a protein called

A

apoferritin which can bind excess iron in body fluids

137
Q

Apoferritin + iron equals

A

ferritin which is then stored in hepatocytes until the iron is needed elsewhere in the body

138
Q

During low levels of iron in the circulation,

A

ferritin release iron

139
Q

Iron is carried in the blood by

A

transferrin

140
Q

The apoferritin-ferritin system acts as

A

an iron storage and buffer system

141
Q

The major end product of hemoglobin degradation is

A

bilirubin

142
Q

Bilirubin is excreted in

A

the bile and eliminated in the feces

143
Q

Bilirubin is a valuable tool for diagnosing

A

hemolytic blood disease and various types of liver disease

144
Q

After ___ days, RBCs become fragile and their cell membranes rupture

A

120

145
Q

The released hemoglobin that is fractured is

A

phagocytized by tissue macrophages

146
Q

Describe the process of hemoglobin breakdown.

A

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
Q

The simplistic version of the hemoglobin breakdown is:

A

hemoglobin–> globin + heme–> Fe + pyrrole rings–> biliverdin–> free bilirubin–> bilirubin + albumin

148
Q

Bilirubin bound to plasma albumin is called

A

“free bilirubin”, unconjugated or indirect bilirubin

149
Q

Free bilirubin is absorbed by

A

hepatocytes and released from albumin

150
Q

Bilirubin is then conjugated with

A

glucoronide

sulfate

151
Q

Conjugated bilirubin (direct bilirubin) is excreted from the

A

hepatocytes by an active transport process into the bile canaliculi and then into the intestines

152
Q

In the intestine about 1/2 of the conjugated bilirubin is converted by

A

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

Pathophys II (43 decks)

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