Liver Flashcards
What are the liver’s functions?
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Regulation of protein, carbohydrate, and lipid metabolism
- “taking good stuff and saying, what do I need to do with this”
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Regulation of cholesterol production and excretion
- liver makes cholesterol
- some people have increased cholesterol level despite diet d/t HMG CoA making cholesterol working overtime
- liver makes cholesterol
-
B-oxidation of fatty acids
- alternative energy source when bile not present
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Bile acid production
- necessary for effiicent lipid absorption
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Degradation of hormones
- produce and secrete hormones into blood including insulin-like growth factor, angiotensinogen, cytokines
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Detoxification and excretion of drugs and toxins
- via Kupffer cells
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vitamin storage
- store B12, iron
What is source of blood flow to liver? Blood flow rate? % C.O?
- Liver is provided blood flow via hepatic artery and portal vein
- Blood flow 450 mL/min in hepatic artery
- this is arterial source for hepatocytes
- Portal vein= 1L/min
- portal vein varries venous blood from intestine
- nutrients, bacteria and foreign bodies processed here
- causes “first pass” effect
- 30% CO into liver
Normal liver will have very ___ capillary and venous pressure
low
What is portal HTN?
- Increase in pressure somewhere along portal tract
- prehepatic-
- portal V, thrombosis, congestion, atresia (biliary ducts aren’t formed, creating extra pressure before liver)
- intrahepatic
- cirrhosis, fibrosis, wilson’s disease
- post-hepatic
- any obstruction b/w liver and Right heart
- hepatic vein thrombosis, CHF, Pericarditis
- any obstruction b/w liver and Right heart
- prehepatic-
The blood from hepatic artery and portal vein ____ in liver
mix
What are kuppfer cells (littoral cells)?
- Attached to sinusoidal membrane present throughout liver
- Scoop up waste and present to liver cells
- phagocytose bacteria and damaged RBC
What is the space of disse?
Interstitial space of liver
Hepatcocytes are major producers of ____ which is secreted into space of Disse.
lymph
Eventually absorbed into lymphatic vessels–> thoracic duct
What are 3 symptoms that can occur with any obstruction of blood flow?
Ascites
Hepatomegaly
Jaundice
What is ascites?
- Ascites is fluid formation in peritoneal space
- Increased hepatic vein pressure (increased right vena cava pressure, increased portal venous pressure causes…
- increased pooling of blood in capillaries causes…
- increased hydrostatic pressure in capillaries
- exudation of fluid from plasma and space of disse into peritoneal cavity of abdomen
- causes ascites (contains both fluids and proteins)
Is ascites a part of the ECF?
No, outside of ECF
What is hepatomegaly?
- Increase in liver size due to fluid retention
- can also enlarge from excess fat
- Liver normally has 400mL of blood and can increase to 1L in pathological condition
- this can affect CV system since it will have to keep BP up with 0.5 L circulating elsewhere
- can happen along with ascites
- can detect on physical exam by palpation
What is bilirubin
- End-product of RBC degradation, incorporated into bile and excreted in feces (metabolite also secreted by kidneys)
What is obstructive jaundice?
- Obsturciton of bile ducts (cirrhosis, gallstones, biliary atresia, CA)
- bile not secreted so nothing to get rid of bilirubin, bilirubin absorbed into blood causing yellowing
What is hepatic jaundice?
Results from acute or chronic hepatitis, drug hepatotoxiicty and cirrhosis
- Reduces ability of cells to metabolize bilirubin
What is hemolytic jaundice
nothing to do with liver itself!!
- Results from anything that increases hymolysis of RBC (malaria, sickle cell, genetic disease)
- this causes an increase in bilirubin production faster than the bile can excrete it
What is neonatal jaundice?
- Uusally not pathologic
- results from metabolic changes as liver and GI function aren’t perfect after birth
- not able to secrete enough bile just yet to get rid of bilirubin
- Can resolve by UV light
- UV light turns bilirubin to make it more hydrophilic, get through kidney, make urobilin and be excreted
- sometimes will find it’s a problem with the biliary tree–> this will have to be treated sx
What is cirrhosis?
Destruction of liver by scarring
In what ways does liver affect carbohydrate metabolism?
“blood glucose monitor”
- Glycogen storage and glycolysis
- Gluconeogenesis
- Conversion of monosaccharides to glucose
- formation of chemical compounds
- pyruvic acid, lactic acid, succinic acid, acetyl coA that can be used in other metabolic pathways
What is glycogen storage and glycolysis in liver?
- excess monosaccharaides not used is polymerized and stored as glycogen
- glucokinase convertes glucose to glycogen
- stored hepatic glycogen can provide glucose for 12-17 hours during fasting
- when blood glucose levels low, glucagon and other hyperglycemic hormones (such as epinephrine and growth hormone) stimulate glycolysis to break down glycogen and release glucose into blood
- through phosphorylase
- If glycogen not used, converted to triglycerides and transported to adipose tissue for storage
What is gluconeogenesis?
- Amino acids and glycerol (from TG) are converted to glucose by gluconeogenesis
- provides alternate energy soruce during fasting and starvation
What are GLUT2 transporters?
Transporters in liver that are insulin independent for glucose
- This allows high capacity transport
- also found in brain, pancras, kidneys, and basolateral side of enterocytes
The liver converts _____ to glucose
Monosaccharides
- Conversion of monosaccaharides to glucose
- ATP allows galactose and fructose to enter glycolytic pathway and be stored as glycogen , or undergo glycolysis
What role does liver play in lipid metabolism?
Building blocks, cholesterol regulation, energy
- High rate of beta oxidation of fatty acids
- Forms most lipoproteins
- VLDL
- LDL
- HDL
- Synthesizes lots of cholesterol and phospholipids
- converts unused glycogen to TG
How do lipids first come into liver?
Via systemic circulation (NOT portal, like most other nutrients)
What is b-oxidation of fatty acids?
TG are hydrolyzed to fattyacids and glycerol–> mitochondira–> b-oxidation–> acetyl CoA–> citric acid cycle
- provides energy when you need it
- in cases of fasting/used up glycogen store
- happens while gluconeogenesis happens
What are the various lipoproteins formed by liver?
- Purpose- carrier proteins that shuttle lipid to other parts of body
- VLDL- high triglycerides, some cholesterol and phospholipids
- take triglycerides to adipose tissue
- LDL: high cholesterol, phospholipids, little TG (theses are the bad guys)
- implcated in CV disease
- HDL: 50% protein, less chol and phospholipids (good guys)
- transport lipid from tissue to liver
- beneficial in terms of CV health
How does liver synthesize cholesterol and phospholipids?
HMG CoA Reductase
- Acetyl CoA molecules combine to form sterol nucelus–> side chains added–> cholesterol
- HMG CoA reductase catalyzes the reaction and is the target of statin drugs
How does liver convert unused carbs to triglycerides?
- Glucose–> glycolysis–> acetyl CoA–> TG polymers made using malonyl coa and nadph–> packed into VLDL–> adipose tissue
Role of liver in protein metabolism?
- Deamination of amino acids
- production of urea
- synthesis of plasma proteins
- intervoncersion of amino acids
What is the deamination of amino acids?
First step in removal of excess amino acids; aminotransferases remove amino group form amino acids creating ammonia
- Ammonia can be transferred again, or released as ammonia
- excess ammonia can be removed by production of urea
How does the liver produces urea?
NH3 combines with CO2 to form urea
Critical process to get rid of toxic NH3
Role of liver in synthesis of plasma proteins?
- 90% of plasma proteins are made by liver (albumin, globulins, fibrinogen)
What is role of liver in interconversion of amino acids?
Transamination cna convert certain amino acids to others that may be needed
What are other metabolic function of the liver?
- VItamin storage
- formation of blood coagulation products
- iron storage
- drug, hormone, waste removal
