Term
Physiologic anatomy (review)
- liver
- biliary system
- hepatic vein
- hepatic artery
- portal vein
- GI tract veins |
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Definition
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Term
Lymph flow/ascites
*2 causes of ascites* |
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Definition
Ascites = high hepatic vascular pressures -> fluid transudation into the abdominal cavity from the liver and portal capillaries
if pressure in the hepatic veins/vena cava rises 3-7 mmHg above normal, excessive fluid transudates into the lymph, leaks through the outer surface of the liver capsule directly into the abdominal cavity.
- fluid is almost pure plasma, containing 80-90% as much protein as normal plasma.
At vena caval pressures of 10-15 mm Hg (CHF):
- hepatic lymph flow increases to as much as 20 times normal
- "sweating" from the surface of the liver can be so great that it causes large amounts of free fluid in the abdominal cavity (ascites)
Blockage of portal flow through the liver:
- high capillary pressures in the entire portal vascular system -> edema of the gut wall and transudation of fluid through the serosa of the gut into the abdominal cavity -> ascites.
large clots in portal vein -> portal HTN
high hepatic vascular pressures -> ascites |
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Term
Metabolism of CHO
- 4 functions
- glucose buffer |
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Definition
1. Storage of large amounts of glycogen
2. Conversion of galactose and fructose to glucose
3. Gluconeogenesis
- also concerned with maintaining a normal blood glucose concentration, because gluconeogenesis occurs to a significant extent only when the glucose concentration falls below normal -> large amounts of amino acids and glycerol from the triglycerides are converted into glucose, thereby helping to maintain a relatively normal blood glucose concentration.
4. Formation of many chemical compounds from intermediate products of carbohydrate metabolism
Storage of glycogen allows the liver to remove excess glucose from the blood, store it, and then return it to the blood when the blood glucose concentration begins to fall too low.
- In a person with poor liver function, blood glucose concentration after a meal rich in carbohydrates may rise two to three times as much as in a person with normal liver function. |
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Term
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Definition
Fats are emulsified by acid, pepsin in stomach; minimal digestion by lingual or gastric lipase
Requirement for bile salts:
- emulsification in SI
- digestion by pancreatic lipases
- bile salt micelles transport fats to surface of epithelial cells
- fats diffuse into epithelial cells (bile salt stays in lumen)
- bile salts travel down to terminal ileum, where they're reabsorbed by Na+ co-transported |
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Term
Metabolism of proteins, amino acids
- 4 functions |
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Definition
Liver is indispensable for protein metabolism
1. Deamination of amino acids
- required before AA's can be used for energy or before they can be converted into carbohydrates or fats
- A small amount of deamination can occur in the other tissues of the body, esp in the kidneys
2. Formation of urea for removal of ammonia from the body fluids
- Large amounts of ammonia are formed by the deamination process, and still additional amounts are continually formed in the gut by bacteria and are then absorbed into the blood.
- w/o this function of the liver to form urea, the plasma ammonia concentration rises rapidly -> hepatic coma and death.
- greatly d/c blood flow through the liver – e.g. when a shunt develops between the portal vein and the vena cava - can cause excessive ammonia in the blood, an exceedingly toxic condition.
3. Formation of plasma proteins
- 90% of all the plasma proteins
- The liver can form plasma proteins at a max rate of 15 to 50 g/day.
- plasma protein depletion -> rapid mitosis of the hepatic cells and growth of the liver to a larger size + rapid output of plasma proteins until the plasma concentration returns to normal.
- chronic liver disease (e.g., cirrhosis), plasma proteins, such as albumin, may fall to very low levels -> plasma oncotic pressure d/c -> edema, ascites.
4. lnterconversions of the various amino acids and synthesis of other compounds from amino acids
- nonessential amino acids can all be synthesized in the liver
- a keto acid having the same chemical composition as that of the AA to be formed is first synthesized. Then an amino radical is transferred through several stages of transamination from an available amino acid to the keto acid to take the place of the keto oxygen. |
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Term
Storage of bile in gallbladder
- How can a patient w/o a GB still absorb fats? |
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Definition
- The liver produces 900 ml of bile per day, but the GB can only hold 60 ml
- bile concentrated 12-20x by active absorption of Na+ (with Cl- and H2O)
- interdigestive: sphincter of Oddi is constricted, bile secreted by liver flows into the gallbladder
- on eating, hormonal (e.g. CCK) and neural stimuli cause contraction of the gallbladder, relaxation of sphincter of Oddi -> bile flows into the bowel
- bile secretion from the liver increases as bile acids are returned via the enterohepatic circulation
- Common bile duct as a the site of bile storage. Usually have to reduce fat intake |
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Term
| Synthesis of blood substances |
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Definition
Albumin (major blood pr: 50%)
- transports FA, steroid hormones, fat-soluble vitamins & drugs, Ca++, lipophilic substances
Glycoprotein transport proteins
- transcortin, thyroid-binding globulin, sex hormone-binding globulin, transferrin
Acute phase proteins (of the inflammatory response)
- ceruloplasmin, alpha-1 antitrypsin, alpha1-acid gycoprotein, alpha2-macroglobulin |
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Term
| Removal/excretion of drugs, hormones |
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Definition
detoxify/excrete
- into bile -> feces
- into sinusoidal blood -> urine
many drugs (sulfonamides, penicillin, ampicillin, erythromycin) - detoxified or secreted into bile
major routes for excreting Ca++(-> bile -> gut -> feces)
via oxidation, reduction, or hydrolysis
most imp enzyme is cytochrome P450 - removal/clearance of circulating hormones (and drugs)
- insulin
- glucagon
- growth hormone
- GI hormones
- thyroxine
- steroid hormones (estrogen, cortisol, aldosterone)
- Liver damage -> excess accumulation of hormones in the body fluids -> overactivity of the hormonal systems |
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Term
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Definition
can lead to development of collateral blood vessels to surrounding tissue in order to bypass a blockage and reconnect to systemic circulation
*Esophageal varices* - when collateral vessels connect to esophagus
- vulnerable to erosion, rupture, especially if pressure gets too high -> medical emergency |
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Term
BILE
-functions
-synthesis
-stimulus for release |
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Definition
Fat digestion, absorption
- detergent action: emulsification
- micelle transport of lipids to intestinal mucosa for absorption
Gastric acid buffer
Excretion of waste products from blood
- bilirubin
- excesses of cholesterol (ONLY means the body has of getting rid of cholesterol)
- toxic substances (drugs, hormones)
cholesterol -> primary bile acids -> secreted by liver into SI -> bacteria convert to secondary bile acids
bile acids conjugated to bile salts (ionized)
Regulation
- synthesis by liver is continual (increases with depletion of bile pool or resection of ileum)
- secretion by liver: portal blood bile salts/acids concentration (positive feedback); secretin (water, electrolytes)
- gallbladder contraction: *CCK*, secretin, vagus
- reciprocal relationship b/t bile synthesis and secretion:
- return of bile to liver inhibits synthesis, but increases secretion!
- removal of distal ileum decreases rate of return in portal blood --> increased synthesis |
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Term
The enterohepatic circulation of bile salts and its physiologic significance
- How much bile is synthesized de novo by the liver?
- size of bile pool?
- how many cycles of circulation?
- biliary secretion |
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Definition
Bile acids are actively secreted by the liver
Once in the intestine they help in digestion & absorption of lipids
As they move toward the distal SI, some of the primary acids --> secondary acids
The more hydrophobic bile acids are absorbed passively throughout the intestine. The more hydrophilic acids are absorbed by a Na+-co-transport process in the *ileum*
A minor fraction of bile acids is propelled into the colon
The absorbed bile acids are transported via the portal circulation to the liver, where they're extracted from the blood and re-secreted
Synthesis of new primary acids from cholesterol occurs at a rate to compensate for the acids lost from the bowel
Normally there are 1-2 g of bile salts in the enterohepatic circulation, and normally only about .5 g is lost daily
- 0.2-0.6 g/day
- 3 g
- 4-12 p/day
- bile pool X # of cycles = 12-36 g/day |
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Term
| Which nutrients are stored in the liver |
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Definition
Vitamin A - 10 mo supply
Vitamin D - 3-4 mo
Vitamin K - 1 year
Vitamin B12 - 1 year
Folate - 3-4 mo
Storage, homeostasis of iron (3-4 mo)
- in the form of ferritin (iron bound to apoferritin) - when iron is available in the body fluids in extra quantities, it combines with the apoferritin to form ferritin and is stored in this form in the hepatic cells until needed elsewhere
- released when needed by the body - When the iron in the circulating body fluids reaches a low level, the ferritin releases the iron
- Thus, the apoferritin-ferritin system of the liver acts as a blood iron buffer as well as an iron storage medium.
Removal of duodenum -> only place in SI we can absorb iron and folate
- Iron and folate used by RBC
- Deficiency in these two --> microcytic anemia
- Malabsorption problem: you'll first see microcytic anemia, takes a little longer to see macrocytic (pernicious) anemia |
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Term
Bile secretion
- how much per day?
- Bile-dependent fraction
- Bile-independent fraction |
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Definition
- 600-1,200 ml/day
- liver synthesis = fecal excretion = 0.2-0.6 g/day
- biliary secretion = (bile pool)(# cycles) = 12-36 g/day
- bile pool = 3 g
Hepatocytes secrete the bile-dependent fraction; not under direct neural or hormonal control; hepatocytes are always secreting bile
- bile acids, primary or secondary, are the major component actively secreted by the hepatocytes. As anions, their secretion is accompanied by the passive movement of cations into the canaliculus --> osmotic gradient down which water moves
Bile ducts secrete water/electrolyte or bile-independent fraction; stimulated by secretin and high HCO3- concentration
- Active transport of Na+ by hepatocytes
- HCO3- is actively secreted by epithelial cells that line the ducts
- secretion & absorption of Na+, Cl-, and water => bile becomes more alkaline, and its Cl- content decreases
- secretory activity of the epithelial cells of the bile ducts is under hormonal control
- secretin stimulates production of bile that's relatively low in bile salt and high in HCO3- by increasing the active transport of Na+ and HCO3- from the epithelial cells into the bile |
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Term
Enterohepatic circulation: image. Think about where the following play roles in this circulation:
- cholesterol
- primary, secondary bile acids
- drugs/hormones/bilirubin |
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Definition
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Term
Enterohepatic circulation: image
CCK causes contraction of GB, secretion of bile in response to fat ingestion
Liver hepatocyte takes up bile, re-secretes it
Some bile is lost in fecal and urinary secretion (<.5 mg/day in urine, .2-.6 g in feces)
The terminal ileum is the only place where bile salts are absorbed. In a patient who's had their terminal ileum removed. If a pt has this removed, bile salts go into colon, bile pool decreases, nothing's being reabsorbed, liver increases the rate of synthesis of bile
Conc of bile in portal vein coming back to liver = *secretagogue* - stimulates liver to i/c bile production!! One of the strongest secretagogues
When bile conc goes down, CCK not secreted, no contraction of GB -> sphincter of Oddi contracts, bile stored in GB -> conc of bile in ileum d/c -> bile conc in portal circulation d/c -> rate of secretion by liver d/c
Positive feedback - more blood coming back to liver by portal vein, more blood is secreted (not produced) |
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Definition
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Term
| Bile acids & mixed micelles |
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Definition
Bile acids are amphipathic
At low concentrations of bile acids, there's little interaction of their molecules
Higher concencrations: aggregation of molecules (micelle formation) takes place) such that hydrophobic regions interact with one another, and hydrophilic regions interact with H2O
This is key to how bile acids emulsify lipids and form mixed micelles with products of lipid digestion
emulsion droplet + long-chain FA + bile salt => mixed micelle in an alkaline environment
Mixed micelle diffuses into acidic environment, releases lipid into epithelial cell
Bile salt micelle diffuses back out to the alkaline environment |
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Term
| Absorption of bile acids in terminal ileum |
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Definition
Mechanism of bile salt absorption: Na+ co-transport in terminal ileum
CONJUGATED bile acids are absorbed via Na+ co-transporter
UNCONJUGATED bile acids are absorbed via simple diffusion
--> may bind to cellular component --> portal blood (BA bound to proteins, esp. albumin --> liver |
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Term
| Clinical Implications of bile problems: watery diarrhea vs. steatorrhea |
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Definition
Bile needed (not GB) for proper digestion of fats
Decreased bile or bile acid pool -> malabsorption of fats -> steatorrhea
Bile salts in colon -> irritation, inhibition of water and Na+ absorption -> stimulate cells in colon to increase secretions -> watery diarrhea |
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Term
| Characteristics (anatomy, physiology) contributing to the very high lymph flow in the liver |
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Definition
- the pores in the hepatic sinusoids are very permeable, allow ready passage of both fluid and proteins into the spaces of Disse
- the lymph draining from the liver usually has a protein concentration of about 6 g/dl, (only slightly less than plasma).
- the extreme permeability of the liver sinusoid epithelium allows large quantities of lymph to form (15-20% of total body lymph)
- Small proteins leak across space of Disse - removed by way of lymph flow |
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Term
Blood flow in liver: high flow, low vascular resistance
- Hepatic artery
- Hepatic portal vein |
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Definition
total: about 1350 ml/min (27% of resting CO)
"Blood flow buffer"
HA: 350 ml/min - 20-30% of blood supply
- oxygenated; high pressure (~90)
- branches to form arterioles, capillaries, which drain into sinusoids
HPV: 1 L/min - 70-80% of blood supply
- poorly oxygenated; low pressure (9 mmHg)
- clot => backup of blood into splanchnic organs -> i/c hydrostatic pressure in capillary beds -> ascites
hepatic vein from liver into vena cava = 0 mmHg
- clot => i/c filtration out of capillary vein -> edema
- this small pressure gradient of 9 mmHg means that there is low resistance to flow
- branches to form small venules
- empty into sinusoids
If HPV flow drops, hepatic artery blood flow increases in order to keep total blood to liver constant, and vice versa
*sinusoids -> hepatic veins -> vena cava* |
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Term
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Definition
Because the liver is an expandable organ, large quantities of blood can be stored in its blood vessels.
- normal blood volume (in hepatic veins and sinuses) = 450 ml (almost 10% of total BV).
- high pressure in the right atrium -> back pressure in the liver -> liver expands, 0.5 - 1 L of extra blood can be stored in the hepatic veins and sinuses
- occurs especially in cardiac failure with peripheral congestion
- the liver is a large, expandable, venous organ capable of acting as a valuable blood reservoir in times of excess blood volume and capable of supplying extra blood in times of diminished blood volume.
Hypovolemia/hypotension - liver can contract and expel blood into systemic circulation in an attempt to i/c BP/volume
Under normal conditions, contains about 10% of blood volume |
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Term
Hepatic macrophage system
Kupffer cells |
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Definition
Blood-cleansing function - portal blood has higher bacteria count than hepatic venous blood - cleans up 99% (Kupffer cells)
Kupffer cells = phagocytic macrophages, line the hepatic venous sinuses, in direct contact with hepatic blood flow
- major role in host defense
- cleanses blood as it passes through sinuses
- phagocytosis of blood elements, pathogens, dead liver cells
- become enlarged & proliferate in response to liver insult mediated through the blood stream |
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Term
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Definition
fat storage cells
space of Disse
storage of fat soluble vitamins (A, D, K)
synthesis of collagen following liver injury
? regulation of sinusoidal resistance and endothelial permeability |
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Term
Lipid metabolism
- 3 functions
- cholesterol & bile |
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Definition
1. Oxidation of fatty acids to supply energy for other body functions
- production of ketone bodies
2. Synthesis of large quantities of cholesterol, phospholipids, and most lipoproteins
- proteins, CHO --> lipoproteins (VLDL, LDL, HDL, cholesterol, phospholipids)
- catabolism of lipoproteins
3. Synthesis of fat from proteins and carbohydrates
- glucose, AA's --> fatty acids
Bile synthesis from cholesterol = only way to remove cholesterol from blood |
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Term
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Definition
Modify or amplify hormone action
- Vit D - imp for Ca++ absorption
Removal/clearance of circulating hormones via cytochrome P-450 enzymes
- insulin
- glucagon
- growth hormone
- GI hormones
- thyroxine
- all steroid hormones (estrogen, cortisol, aldosterone) |
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