Basic Hepatic Physiology Flashcards
Liver Functions (7)
- removes potentially toxic byproducts of certain medications
- metabolizes nutrients from food to produce energy when needed
- helps your body fight infection by removing bacteria from the blood (macrophages)
- produces most of the substances that regulate blood clotting
- produces bile and bile salts, a compound needed to digest fat and to absorb vitamins A, D, E, K
- produces most proteins needed by the body
- prevents shortages of nutrients by storing vitamins, minerals, and sugar
xenobiotic
anything not natural to the body. ex) dust, meds
basic functional unit of liver
lobule
how many lobules in the liver
50,000-100,000
basic structures of a liver lobule (9)
- portal vein
- sinusoids (capillaries)
- central vein
- hepatic artery
- bile canniculi (capillaries that transport bile) and bile duct
- space of dissent and lymphatic duct
- hepatic cellular plates (liver cells)
- kupffer cells (macrophages)
- interlobular septa (holds everything together)
2 things that feed blood to liver
portal vein and hepatic artery
how thick is the hepatic plate
one to two cells thick
sinusoids function
remove bacteria, inside capillaries and move around
what supplies blood pressure to the hepatic artery
aorta to celiac trunk to hepatic artery
what % of O2 comes from portal vein and what % of O2 comes from hepatic artery
50% and 50%
Portal Vein SvO2
85%
Hepatic Artery SaO2
98-100%
normal hepatic BF (and % CO)
1500ml/minute or 25-30% CO
how many ml/min (and %) of blood is supplied via the portal vein
1100ml/min or 75%
how many ml/min (and %) of blood is supplied via the hepatic artery
400ml/min or 25%
average portal vein pressure
9mmHg
what is hepatic portal vein blood flow dependent upon
dependent upon blood flow to the GI tact and spleen
what 3 organs and 1 artery does the celiac artery (branched from the aorta) feed before the blood supply gets to the liver?
artery: hepatic artery branches from celiac artery
organs: stomach, spleen, pancreas
what 3 anatomical landmarks does the superior mesenteric artery (branched from the aorta) feed before the blood supply gets to the portal vein?
pancreas, small intestines, colon
bridging fibrosis
destruction of liver parenchymal cells results in replacement with fibrous tissue that contracts around the vessels. greatly impedes portal vein flow.
“cell plates replaced by fibrosis and chokes sinusoids it surrounds”
fatty liver pathophysiology
fat deposited inside liver cell. starts to crowd intracellular organelles
liver fibrosis pathophysiology
crowded intracellular organelles begins to die. fibrotic tissue replacing dead tissue
cirrhosis pathophysiology
constriction of sinusoids and capillaries. irreversible damage.
stages of alcohol induced liver damage
- fatty liver
- liver fibrosis
- cirrhosis
what constitutes metabolic syndrome
HTN, increased triglycerides, increased BG
3 most common reasons for NAFLD
obesity
DMII
metabolic syndrome
NAFLD
steatotosis
NASH
what NAFLD progresses to, inflammation. progresses to cirrhosis
what type of receptors does the hepatic artery have
alpha receptors (vasoconstriction) beta receptors (vasodilation) dopaminergic receptors (vasodilation) cholinergic receptors (vasodilation)
what type of receptors does the portal vein have
alpha receptors (vasoconstriction) dopaminergic receptors (vasodilation)
normal liver blood volume including what is in hepatic veins and sinusoids
450mL
how much blood can be stored in the hepatic veins and sinusoids
.5-1L (commonly occurs in CHF)
how liver compensates for a hemorrhage
blood shifts from hepatic veins and sinusoids into central circulation (as much as 300mL)
kupffer cells function (3)
- line hepatic venous sinusoids and cleanse blood as it passes through these sinuses. bacterium that passes into these cells is then digested
- also phagocytose cellular debris, viruses, proteins, particulate matter
- release various enzymes, cytokines, other chemical mediators
what system are the kupffer cells a part of
monocyte macrophage system aka reticuloendothelial system
how does fluid and protein get into the spaces of disse
pores in sinusoids are very permeable and therefore permit passage of the fluid and protein into spaces of disse and that is the creation of lymph fluid
a 10-15mmHg increase in hepatic venous pressure does what?
can increase lymph flow to 20x normal, produces “sweating” from the liver surface with large amounts of free fluid entering the abdominal cavity aka ascites
what happens with blockage of the portal vein
produces high pressure in the GI tract with transudation of fluid through the gut into the abdominal cavity which can also cause ascites
metabolic functions of the liver include (5)
- carbohydrate metabolism
- fat metabolism
- protein metabolism
- drug metabolism
- miscellaneous metabolic functions
final products of carbohydrate metabolism
glucose, fructose, galactose. (glucose is final common pathway for most CHO)
specific liver functions associated with CHO metabolism (4)
- conversion of galactose and fructose to glucose
- storage of large amounts of glycogen (glycogenesis)
- gluconeogenesis (used from proteins and fats after you’ve used carbs)
- formation of many chemical compounds from intermediate products of CHO metabolism
chemical formula of glucose, fructose, galactose
C6H12O6
how is most glucose stored after a meal
stored as glycogen
glucose buffer function
storage of glycogen allows liver to remove excess glucose from the blood, store it, and return it to the blood when BG concentration decreases
does glycogen contribute to osmolality
no
2 parts of the body able to store significant amounts of glycogen
liver and muscles
what enhances glycogen storage
insulin
what enhances glycogenolysis
epinephrine and glucagon
how many hours of fasting before hepatic glycogen steers are depleted
24 hours. after that, gluconeogenesis uses fat first to compensate.
the liver and kidney are unique in that they can convert these 4 things to glucose
amino acids
glycerol
pyruvate
lactate
agents that increase gluconeogenesis
glucocorticoids
catecholamines
glucagon
thyroid hormone
agents that decrease gluconeogenesis
insulin
specific liver functions associated with fat metabolism (3)
- oxidation of fatty acids to supply energy for other body functions (beta oxidation)
- synthesis of large amounts of cholesterol, phospholipids, and lipoproteins
- synthesis of fat from CHO and proteins
triglycerides chemical makeup
glycerol and 3 fatty acids
what is the goal of the oxidation of fatty acids
to take out of storage and make glucose aka to derive energy from fat (triglycerides)
how is energy derived 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 coenzyme A
- acetyl coA enters the citric acid cycle and is oxidized to liberate tremendous amounts of energy
where can beta oxidation occur
in all body cells, but occurs especially rapidly in hepatic cells
since the liver cannot use all of the acetyl Co-A it produces, this is what happens
- 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
- the tissues reconvert the acetoacetic acid back into the acetyl Co-A which enters the citric acid cycle and is oxidized to produce energy
- in the way liver is responsible for a major part of fat metabolism
acetyl Co-A is used by the liver to synthesize these 2 things
cholesterol and phospholipids
both cholesterol and phospholipids are used by body cells to form these 3 things
- cell membranes
- intracellular structures
- chemical substances important to cell function ex) hormones
specific liver functions associated with protein metabolism (4)
- deamination of proteins (removal of nitrogen)
- formation of urea for removal of ammonia (NH3) from the body fluids
- formation of plasma proteins
- synthesis of amino acids and synthesis of other compounds from amino acids
3 branch chain amino acids
leucine
isoleucine
valine
deamination
enzymatic process which converts amino acids into their respective keto acids and results in production of ammonia as a byproduct (cleaves off nitrogen and converts back to carbonyl group). liver is principle site
formation of urea from ammonia and purpose
removes ammonia from the body fluids
large amounts of ammonia are formed by deamination process. bacteria in the gut with subsequent absorption into the blood
how can excessive ammonia happen
if the liver does not perform deamination or if there is greatly reduced blood flow
porta caval shunt
shunts portal blood into IVC to bypass liver. increased ammonia and hepatic encephalopathy can develop.
how many plasma proteins (g) can hepatocytes form per day
15-50g/day
most important plasma proteins (quantitatively)
albumin
a1 antitrypsin
what does a1 antitypsin do
trypsin breaks down proteins. ex)emphysema has lack of antitrypsin so lung tissue is degraded
transamination process
a keto acid is formed that has the same chemical composition as the AA to be formed except at the keto oxygen. next an amino radical is transferred from an available AA to the veto acid to take the place of the keto oxygen. this process takes many steps.
phase 1 reaction in the liver
modify substances through CYP450 through oxidation or reduction
oxidation
90% of all reactions
primarily via CYP450 enzymes and secondarily by mixed function oxidases
often generates reactive oxygen species because carboxyl, epoxy, and hydroxyl groups are introduced into the parent compound
reduction
mainly catalyzed by CYP450 enzymes
examples of CYP450 inducers
ethanol
barbiturates
ketamine
benzos
examples of CYP450 inhibitors
ranitidine
amiodarone
ciprofloxacin
drugs with very high rate of hepatic extraction from circulation
lidocaine morphine verapamil labetalol propanolol
drugs that have products of phase 1 reactions that are more active than the parent compound or considered cytotoxic
acetaminophen- glutathione is a free radical scavenger
isoniazid: metabolite that causes cells to activate their programmed cell death
halothane: hepatitis
drugs efficiently extracted from the blood by the liver
(efficiently extracted because fairly lipid soluble at baseline) lidocaine meperidine morphine nortrriptyline pentazocine propoxyphene propanolol labetalol verapamil
drugs poorly extracted from the blood by the liver
acetaminophen clindamycin diazepam digoxin phenytoin theophylline warfarin
phase II drug reactions
may or may not follow a phase 1 reaction, involves conjugation of a substance with a water soluble metabolite
conjugation and most common added proteins
taking something small and adding something large and charged to make it water soluble so it can be excreted in the urine or bile
glucoronide is most common, then sulfate
taurine and glycine can also be utilized by the body
the liver stores large quantities of these fat soluble vitamins
A, B12, D, E, K
iron is stored in the liver as
ferritin
apoferritin
protein produced by hepatic cells, excreted in large amounts to bind to excess iron in body fluids. apoferritin+iron=ferritin which is then stored in hepatocytes until the iron is needed elsewhere in the body
transferrin
binds to iron and carries it in the blood for transport so iron does not travel in its free radical form and oxidize everything
vitamin K is a required co factors for the synthesis of these 4 factors
2 (prothrombin), 7, 9, 10
vitamin K deficiency manifests as a
coagulopathy due to impaired formation of factors 2, 7, 9, 10
2 factors not produced by the liver
factor 8 and vWF
liver is the primary site of degradation for (5)
thyroid hormone insulin steroid hormones including cortisol, aldosterone, estrogen glucagon ADH
hepatocytes continually secrete these 4 things into the bile canniculi
bile salts
cholesterol
phospholipids
conjugated bilirubin
bile ducts from the hepatic lobules eventually form what?
the left and right hepatic ducts
what two ducts form the common bile duct
cystic duct and hepatic duct
flow of bile from common bile duct is controlled by
sphincter of oddi
cholecystokinin
hormone released from intestinal mucosa in response to fat and protein that causes contraction of the gallbladder, relaxation of the sphincter of odd, and ejection of bile into the small intestine. also called the “cystic system”
bilirubin
major end product of hgb degradation. provides valuable tool for diagnosing blood diseases and various types of liver disease
how many days do RBC’s recycle
120 days
Order of events for RBC degradation (5)
- HGB is split into globin and heme
- heme ring is opened and Fe is released and is transported in blood by transferrin
- 4 pyrrole rings of the porphyrin structure are converted to biliverdin
- biliverdin is rapidly converted to free bilirubin and is released from the macrophages
- free bilirubin immediately combines with plasma albumin
how to drive carbon monoxide off of iron
increase in partial pressure O2
what does CO2 combine to
nitrogen
unconjugated or indirect bilirubin
free bilirubin or bilirubin bound to plasma protein. absorbed by hepatocytes, released from albumin, and then conjugated.
conjugated or direct bilirubin
bilirubin conjugated with either glucoronide (80%) or sulfate (20%) then excreted from hepatocytes by an active transport process into bile canaliculi and then into the intestines
urobilinogen
in the intestine, about 1/2 of conjugated bilirubin is then converted by bacteria to urobilinogen which is reabsorbed back into the blood. some of it is excreted into urine, majority is excreted back into intestines and eliminated by feces
jaundice
excess unconjugated OR conjugated bilirubin in the ECF
common 2 causes of jaundice
hemolytic
obstructive
hemolytic jaundice
increased destruction/hemolyzation of RBC’s.
- increased production of bilirubin by macrophages
- increased unconjugated (free/indirect) bilirubin in blood. hepatocytes cannot process or conjugate all of this bilirubin
- so while this results in a primarily increased unconjugated bilirubin, you will aolso see a secondary increased in conjugated bilirubin as well
- rate of urobilinogen in intestine and urinary excretion increases but
- excretory function of liver is not impaired
obstructive jaundice
obstruction of bile ducts or damage to hepatocytes (hepatitis) preventing usual amounts of bilirubin from being excreted into GI tract.
- unconjugated bilirubin enters hepatocytes and is conjugated the usual way. however, now cannot pass from liver into intestine
- conjugated bilirubin enters blood probably either by rupture of cannaliculi or direct emptying of bile into lymph system
- therefore, will see most bilirubin in conjugated form
2 main causes of bile duct obstruction
gallstones, malignancies
total obstruction of bile flow clinical finding
no conjugated bilirubin can reach the intestines to be converted to urobilinogen and therefore no urobilinogen is reabsorbed into the blood and excreted by kidneys. the urobilinogen test is COMPLETELY negative
