liver structure and function Flashcards
what is the largest gland in the body
liver
what percent of blood flow does the liver recieve
metabolically active
28%
what percent of O2 does the liver extract
~20% of O2 used by body
highly aerobic
what are the two blood supplies of the liver
- hepatic artery (25%, oxygenatied, nutrient poor)
- portal vein (75%, deoxygenated, nutrient rich)
how does blood exit the liver (through which vessel)
hepatic vein
all blood from GI tract and spleen flow through the liver by which vessel
portal vein
what are congenital portosystemic shunts
- some blood from portal vein bypasses liver
- intrahepatic shunt
- extrahepatic shunt
what occurs in animals that have congenital liver shunts
- not be able to efficiently metabolize nutrients from the gut
- small in stature, and/or poor growth
- otherwise healthy ot have V/D or PU/PD
- develop hepatic encephalopathy due to high ammonia levels w/ ammonium urate stones in urinary tract
- slow to metabolize and recover from drugs
what do hepatocytes do
- ~80% liver vol.
- synthesis of proteins, carbs, lipids, metabolism and detox
- produce bile that drains into small bile canaliculi between adjacent hepatocytes
what are the other cell types of the liver
6% of liver cells
- endothelial cells
- Kupffer cells
- Stellate cells
what are kupffer cells
- resident macrophages inside sinusoids
- remove particulates from blood
- part of reticuloendothelial system
what are stellate cells
- located in perivascular space (space of disse)
- contain large lipid droplets
- play key role in VA storage
- capable of forming proliferative myofibroblasts (fibrogenic)
what is the functional unit of the liver
lobule (hexagonal)
what is a lobule
- cords of hepatocytes surrounded by sinusoidal capillaries
- portal tract
- central collecting vein
what makes up the portal tract
- hepatic artery
- portal vein
- bile duct
(lymphatic vessel also here)
what is the main cell type in the liver lobule
hepatocyte
what is the exocrine function of the liver
produce bile, which drains into small bile canaliculi adjacent to the hepatociles
what do bile canaliculi collect into and then drain into
collect into larger collecting bile ducts, drain into the common bile duct empyting into the duodenum
how does blood leave the lobule and leave the liver
blood leaves lobule through central collecting veins, and ultimately leaves liver through the hepatic vein
what is the purpse of the microvilli on the hepatocytes
- project into the space between the hepatocyte and the hepatic sinusoid
- help absorb substances from the blood and aid in the secretion of plasma proteins
the liver is a key…
frontline immune tissue
what do kupffer cells play a role in
pathogenesis of chronic and acute alcohol-related liver disease ALD
what can activated kupffer cells produce
large amount of ROS, pro-inflammatory cytokines, chemokines (may contribute to liver injury)
in a healthy liver, hepatic stellate cells are considered to be:
quiescent
what do hepatic stellate cells contain
numerous VA lipid droplets, contituting the larges reservoir of VA in the body
what happens during liver injury to stellate cells
they transform into activated myofibroblast-like cells to generate scar tissue
what happens in chronic liver disease/prolonged activated of hepatic stellate cells
prolonged activation of hepatic stellate cells causes liver fibrosis as characterized by widespread scar formation
what is cirrhosis
scarring damage is irreversible
liver regeneration
- remarkable regenerative capacity
- healthy liver: partial hepatectomy (70%) of a leads to compensatory regenerative growth
- restoration of organ size in a mater of days
bile production is
one of the main functions of the liver
what is bile produced by and secreted into and stored
hepatocytes, bile canaliculi, gallbladder
what is bile comprised of
- bile acids
- cholesterol
- elecrolytes
- bilirubin and biliverdin
- glibulins
- water
- lecithin, amino acids, drugs, heavy metals, vitamins, also some hormones, proteins and peptides
what is the function of bile in digestion
emulsification of fat/oils - aids in digestion/absorption
what is the functionof bile in absorption of fat and fat-soluble vitamins
biliary tract pathology may result in a decrease in the absorption of fat and fat soluble vitamins
what is the function of bile in elimination (mostly via feces)
- excess cholesterol
- lipid-soluble metabolites, drugs
- heavy metals
- bilirubin
- other toxicants
what does enterohepatic recycling influence
elimination times of some drugs and metabolites
what increases solubility of molecules
hydroxylation modifications
what does amphipathic mean
molecule is both hydrophobic and hydrophilic (aids in bile acids ability to emulsify fats)
what do bile acid conjugation reactions do
with glycine and taurine
they are within hepatocytes and increase bile acid solubility in water and enhances their ability to emulsify lipids
what are bile salts
bile acids associated with Na+ or K+ ions
what do bile acids and salts facilitate
the absorption and/or elimination of lipophilic/hydrophobic molecules (such as cholesterol)
bile salt pathologies
due to lack of bile salts or other bile ingredients
gall stones
bile salts keep the cholesterol in a soluble form in the gallbladder, which prevents the formation of gallstones
vitamin deficiencies
bile helps in the digestion of fats and oils, this are essential for hormone production, storage of the fat-soluble vitamins A, D, E, K, cellular membrane homeostasis
GI issues
bile salts help promote intestinal motility, which allows defecation
bile malabsorption pathologies
- when bile salts cannot be reasorbed in the intestine
- as bile salts attract water molecules, the first symptom is watery diarrhea
- can be an acute or chronic condition, and is often associated with irritable bowel syndrom, crohn’s disease, and celiac disease
bilirubin production via:
reticuloendothelial system
old or damaged RBC are removed by:
macrophages in the spleen, liver (kupffer cells) and bone marrow
what is the filtration function of kupffer cells
- remove particulates from blood
- eliminates senescent blood cells and foreign bodies
how is bilirubin produced and eliminated
- RBCs accumulate oxidative injury, which exposes antigens recognized by macrophages
- macrophages convert hemoglobin into biliverdin and then to unconjugated bilirubin
- macrophages export the unconjugated bilirubin into blood, where it binds to serum albumin
- small amounts of bilirubin also come from metabolism of other heme-containing proteins - myoglobin
bilirubin elimination via:
hepatocytes and bile
unconjugated bilirubin is transported within the hepatocyte by ligand or Z protein and conjugated to ____ to form ____ to increase ____
glucuronic acid; conjugated bilirumin (BG); water solubility
~10% urobilinogen undergoes ____ via portal vein
enterohepatic recirculation
icterus
excess amounts of bilirubin in the bloodstream causes icterus - the yellow discoloration of the skin and mucous membranes that can occur with liver disease
if bilirubin excretion is compromised….
there will also be lightly colored stool
cholestasis
any condition in which the flow of bile from the liver to duodenum stops or slows
what can cholestasis be caused by
- gallbladder obstriction, gall stones
- bile duct obstruction, narrowing of bile ducts, bile duct tumor
- liver infection
- cancer
- genetic defects affecting bile acid synthesis
- liver dysfunction: defective phase II enzymes, such as glucuronyl transferase
what are symptoms of cholestasis
itching, dark urine, light colored bowel movements
what are the blood related functions of the liver
- removes old or damaged RBC from the circulation
- breaks down hemoglobin
- iron storage
- synthesizes many serum proteins
- synthesizes blood coagulation proteins
most of the iron that enters the liver is derived from plasma and is bound to:
tansferrin
what is iron taken up by
hepatocytes via transferrin receptors 1 and 2
iron is stored in liver cells in
ferritin
hepatocytes release iron via the plasma membrane iron exporter:
ferroportin 1 (FPN)
what inhibits iron release through its interaction with the iron export ferroportin
hepcidin (produced in liver)
dietary iron is absorbed by duodenal enterocytes and exported to blood via
ferroportin (FPN) iron exporter
iron from senescent erythrocytes is:
recycled by macrophages and liver kupffer cells and exported into plasma via FPN exporters
mobilization of iron is negatively regulated by the
liver hormone hepcidin
what is hepcidin
liver peptide hormone
what do high serum iron levels promote
hepatocyte hepcidin expression and release
what does chronic liver disease cause
anemia
what is the main protein produced by the liver
albumin
what are the functions of albumin
- maintenance of fluid pressure in arteries and veins
- carry the other compounds through the bloodstream
fluid leaked from vessels is called ____ when it occurs in the abdominal cavity
ascities
fluid leaked from vessels is called ____ when it occurs in the thoracic cavity
pleural effusion
what is the “pulling power” called
oncotic pressure
what is hypoproteinemia
decreased plasma protein concentration - common cause of edema
what are the causes of hypoproteinemia
- decreased rate of plasma protein production by the liver - during liver failure or malnutrition; abdomen is grossly distended by edema and ascities
hepatocytes synthesize most blood coagulation factors:
prothrombin, fibrinogen, factor V, VII, IX, XI, XII, protein C and S, and antithrombin
liver sinusoidal endothelial cells:
factor VIII and von Willebrand factor
vitamin K
- important for clottin factor synthesis
- bile salts important for VK absorption
- stored in hepatocytes
- anti-coagulation rat poinsons interfere with VK function - causing bleeding
- liver failure can cause severe bleeding problems
what vitamins are stored in the liver
- lipid-soluble vitamins (A, D, E, K)
- vitamin B12
vitamin A is stored in
hepatic stellate cells lipid droplets as retinyl ester
what is active retinol converted to
retinyl ester by lecithin: retinol acyltransferase
what are the functions of VA
- formation of the photoreceptor rhodopsin
- signaling molecule within gene transcription
- normal function of the immune system
- mobilization of iron stores for RBC production
what is cholecalciferol
VD produced in the body
what does the liver store
glycogen, lipid, vitamin, minerals, and other sever as buffers to prevent the adverse consequences of insufficient or excessive dietary intake
what is glycogenesis
hepatocytes convert excess glucose into glycogen
what is glycogenolysis
stored glycogen is converted back into glucose and relesed into the body to supply energy
where also can the liver manufacture glucose from
protein or fats
in liver disease, the body can have a difficult time regulating blood glucose levels, usually leading to ____
hypoglycemia
how are triglycerides created
from excess glucose when carbohydrate intake exceeds the normal glycogen storage
what is fatty liver syndrome (lipidosis)
consequence of anorexia; fat is broken down rapidly tp supply energy and nutrients - FA’s overwhelm liver’s ability to process them
what is hepatic steatosis (fatty liver)
infection, inflammation, obestity, poor dietary habits, drug toxicity, alcohol liver disease, fatty liver syndrome, food additives
what are fatty acids oxidized into
acetyl-CoA
what can fatty acids in cells be esterified into
triglycerides that are excreted from the liver
