Liver
Northland Community and Technical College

Instructor Terry Wiseth

FUNCTIONS OF THE LIVER

A) digestion

B) detoxification

C) biosynthesis

D) energy metabolism

E) other functions

DIGESTION

the digestive function is the secretion of bile

the liver produces bile which is made up of:

bile salts

bile acids

lecithin

cholesterol

BILE

functions to emulsify fats so they can be absorbed

recirculation of bile salts

essential for lipid digestion

bile is secreted continuously but between meals it passes from the liver to the gallbladder where it is stored and concentrated

during digestion
contractions of the
gallbladder expel
bile to the duodenum

constituents of bile:

1) bile salts which emulsify fats

2) cholesterol from dietary sources and liver synthesis

3) bilirubin which is the main bile pigment

HEPATIC PORTAL CIRCULATION

blood that has passed through capillaries of:

stomach

large intestine

spleen

pancreas

is carried by the
hepatic portal vein
to the liver

75% of the blood to the liver is from the GI system by way of the hepatic portal vein

25% of blood to the liver is from systemic circulation by way of the hepatic artery

brings O2 to the liver

blood leaves the liver by the hepatic vein

the hepatic portal system allows the liver first access to amino acids and glucose absorbed by the intestines

the liver has a central role in regulating blood levels of glucose, amino acids and fatty acids

during absorption of nutrients from a meal the liver stores glucose as glycogen and coverts amino acids to fatty acids

Liver Cells

Glycogen storage in liver cells

DETOXIFICATION

produces urea, detoxifies drugs and inactivates hormones

functions by adding a polar group to drugs, hormones and metabolites so they can be excreted as less toxic substances

BIOSYNTHESIS

synthesizes plasma proteins and lipoproteins

functions to synthesize all plasma proteins (except immunoglobulins)

also synthesizes protein carriers for cholesterol and fatty acids

ENERGY METABOLISM

metabolizes glucose, fatty acids and ketones

functions to:

store glucose as glycogen

convert amino acids to fatty acids and glucose

synthesize and degrade lipids

regulate blood levels of glucose, amino acids and fatty acids

OTHER FUNCTIONS

convert and contain iron, heme molecules and transferrin

functions to destroy aging or damaged RBC

hemoglobin released serves as the major source of bilirubin

heme groups are converted into bilirubin by spleen, liver and bone marrow

LIVER ANATOMY

structures of function are the hepatocytes (liver cells)

lobules are sheets of hepatocytes organized around a central vein

capillaries (sinusoids) run between the sheets of liver cells

sinusoids receive blood enriched by absorbed nutrients from branches of hepatic portal vein

MICROSCOPIC LIVER ANATOMY

blood received by the sinusoids has a low O2 content but the sinusoids also receive blood from branches of the hepatic artery

high O2 content

bile secreted by the hepatocytes into a network of microscopic tubules

bile canaliculi are located within each lobule of the liver

bile canaliculi converge into larger tubules that eventually all join to form the bile duct

MICROSCOPIC LIVER LOBULE

BIOCHEMISTRY OF THE LIVER

the liver converts some substances to a more water soluble form that can be eliminated by the kidney

ex: a substance handled by adding a polar compound is bilirubin

BILIRUBIN

bilirubin is a by product of hemoglobin degradation

conjugated substances may be excreted in the bile and then eventually in the feces

80% of bilirubin is excreted with feces

remaining 20% is reabsorbed by the plasma and recycled by the liver or excreted by the kidneys

bilirubin circulates in the plasma and is taken up by hepatic cells

hepatic cells pass bilirubin to canaliculi, bile ducts and the gallbladder

the gallbladder releases bile to the duodenum

changing color of a bruise is visible evidence of heme converted to bilirubin

BIOCHEMISTRY OF DETOXIFICATION

liver also converts some substances to less toxic forms

ex: ammonia is converted to urea

enzymes in the liver degrade some hormones as well as convert certain drugs and toxins to inactive forms (detoxification)

DETOXIFICATION

some drugs or toxins are actually made more toxic by liver metabolism

ex: ethylene glycol (auto antifreeze) is converted by the liver to oxalic acid

oxalic acid is highly toxic

ethanol can be used as an antidote

LIVER METABOLISM

the ability to metabolize drugs decreases with age

drug dosages appropriate for young adults may produce toxic side effects in the elderly

SYNTHESIS BY THE LIVER

liver also synthesizes plasma proteins except for globulins

albumin (plasma osmotic pressure)

protein carriers (for cholesterol and triglycerides)

clotting factors

angiotensinogen

complement proteins
(immune response)

LIVER AND BILE

fat digestion requires bile

Other components of bile:

1) bile acids

2) cholesterol

3) bilirubin (bile pigment)

4) licithin (phospholipid)

5) detoxified chemicals

6) NaHCO3

BILE ACIDS

synthesized from cholesterol (0.5 gram/day)

before secretion they are combined with amino acids or taurine

forms a water soluble form called a bile salt

BILE

total bile acid and bile salt content of the body is 3 - 4 grams

bile acid content of the body re-circulates 10 times per day

some bile salts are lost in the intestines (app. 0.5 g/day)

RECYCLING OF BILE SALTS

bacteria in the intestines

are able to break bile salts

down into bile acids

bile acids are absorbed in

the small intestine and
returned to the liver by the
hepatic portal system

liver converts reabsorbed bile acids into bile salts and secretes them along with newly synthesized bile acids

BILE AND THE GALLBLADDER

bile is continuously secreted by the liver

between meals bile is stored in the gall bladder

sphincter of common bile duct is normally closed

this forces bile up the cystic duct into the gall bladder

the gall bladder actively absorbs Na+ and H2O thus concentrating bile up to 20 times

gall bladder capacity of 30 - 40 ml

effectively stores the equivalent of 200 - 800 ml of bile

DUODENUM INFLUENCE ON BILE SECRETION

duodenal hormone cholecystokinin

stimulates relaxation of the sphincter common bile duct

stimulates contraction of gall bladder

result is the release of bile to the duodenum

CHOLESTEROL SECRETION

normally the cholesterol secreted in bile is kept in solution by the detergent action of lecithin

excessive secretion of cholesterol by the liver or over concentration of bile in the gall bladder can cause precipitation of cholesterol from solution

precipitated cholesterol can form aggregates called gallstones

GALL STONES

if the stones block the hepatopancreatic ampulla digestion is impaired along with severe discomfort

a blocked ampulla can cause abnormally high concentrations of trypsin in the pancreas

PANCREATITIS

results in pancreatolysis and the pancreas begins to digest itself

pancreatic enzymes attack the pancreatic tissues

normally enzymes are not activated until released into the intestines

CHOLELITHIASIS

disease characterized by the formation of gallstones

predisposing factors for gallstone formation:

1) stasis of bile flow

2) high cholesterol level in the bile

3) infection (cholecystitis)

stones are formed from
calcium or cholesterol

GALL BLADDER SURGERY

1) sphincterotomy

an endoscope is passed through the mouth to the duodenum

bile duct is opened and widened to allow removal or passage of stones

2) cholecystectomy

removal of the gall bladder by surgery

the digestive system works almost as well without a gall bladder because bile can simply flow directly from the liver to the duodenum

some dietary adjustments may be necessary

3) lithotripsy

focused ultrasound waves are used to disrupt gallstones or kidney stones

90% of all patients are able to have this procedure done on an out-patient basis

4) urosidiol (actigall)

a naturally occurring bile acid which acts as a detergent gradually dissolving cholesterol based gallstones

UROSIDIOL

urosidiol also inhibits intestinal absorption of cholesterol and decreases the synthesis of cholesterol by the liver

may be a possible candidate for lowering plasma cholesterol levels

thus reducing the incidence of coronary artery disease

JAUNDICE

abnormal yellow color of the skin and sclera

caused by increased levels of bilirubin in the blood

may be accompanied by dark urine

CAUSES OF INCREASED BILIRUBIN

1) abnormal metabolism of bilirubin

overproduction of bilirubin due to hemolysis

ex: incompatible blood transfusion

2) hepatic cell (liver) disease

impaired uptake of bilirubin by the liver cells

ex: hepatitis and cirrhosis

3) obstruction to outflow of bilirubin

liver damage (scarred bile ducts)

gallstones, inflammation of bile ducts

KERNICTERUS

in infants an extreme elevation of bilirubin (20 mg/dl)

gray matter of CNS may take up bilirubin and cause death

treated by photo therapy (strong white or blue light)

causes bilirubin to be converted to an excretable form

DIETARY FIBER AND PLASMA CHOLESTEROL

polysaccharide content of plants is unavailable for absorption and utilization by the human intestine

amylases secreted by the salivary glands and pancreas are effective against glycogen and starch but not against cellulose, lignin and pectin

DIETARY FIBER

indigestible polysaccharides are called dietary fiber

dietary fiber passes intact through the small intestine but can be partly metabolized to methane, CO2 and fatty acids by microbes in the large intestine

CONSTIPATION

fiber is not an essential nutrient , but it is important in preventing constipation

bulk stretches the intestinal wall, stimulating motility and reducing gut transit time

DIETARY FIBER AND DISEASE

recent studies recommend increased fiber content in the diet to prevent or relieve:

constipation

hemorrhoids

inflammatory diseases of the colon

colon and rectal cancer

heart disease

DIETARY FIBER

all conditions but heart disease are caused or promoted by mechanical or chemical effects of feces on the large intestine and rectum

reducing the time that feces spends in the colon will reduce the incidence of these diseases

DIETARY FIBER AND HEART DISEASE

the beneficial effects of dietary fiber in heart disease arises from the fact that fiber traps bile acids and increases their excretion in feces

bile acids are derived from cholesterol and are normally recycled effectively

if increased amounts of bile acids are lost with feces the liver must replace the lost bile salts by:

using cholesterol from the body’s store

synthesizing cholesterol using acetyl - CoA from fatty acids

ARTIFICIAL FIBER

resins that bind bile acids and are not absorbed by the intestine

colestipol and cholestyramine

increase the loss of bile acids to the feces

imitate the effect of dietary fiber and are the safest treatment of elevated cholesterol and fatty acids

CIRRHOSIS

condition in which necrosis of the liver leads to a proliferation of fibrous connective tissue (fibrosis)

can be caused by alcoholism, hepatitis infection, obstructed bile flow and back pressure from elevated hepatic vein pressure

blood ammonia levels are frequently elevated

ammonia is a by-product of protein metabolism

normally ammonia is converted to urea by the liver

HEPATITIS

inflammation of the liver

may be caused by viral or toxic factors

viral hepatitis produced by 3 known viral agents

known as hepatitis A,B and C

VIRAL HEPATITIS

Hepatitis A

transmitted by fecal-oral route

recovery in 1-2 months

Hepatitis B and Hepatitis C are transmitted by blood and possibly body fluids

recovery in 3-4 months

50% of hepatitis C infections progress to chronic hepatitis

VIRAL HEPATITIS

no treatment exists to cure viral hepatitis

symptoms may be treated by injections of interferon

vaccines are available for hepatitis A and hepatitis B

LIVER PATHOLOGY

the following slides show the liver cells under the microscope

notice differences in the:

cell size

integrity of the cell membranes

irregularities of the shapes of the nucleus

triangular or cuboidal shaped nuclei may indicate cancerous cells

ROLES OF THE LIVER IN THE ABSORPTIVE STATE

about 75% of glucose and amino acids in the plasma are taken up by the liver after absorption into the blood from the intestines

role of the liver during the absorptive stage is to transform nutrients into more complex forms for storage

ex: glucose is converted to glycogen

UPTAKE OF GLUCOSE

most cells require the presence of insulin for the uptake of glucose

liver cell do not require insulin for amino acid or glucose uptake

insulin does have an effect on carbohydrate metabolism

G-6-P

stimulates conversion of glucose to glucose-6-phosphate

G-6-P is not able to leave the cell

conversion effectively stores glucose in the cells when insulin levels are high

TRANSPORT AND STORAGE OF LIPIDS

most of the nutrients entering the liver follow metabolic pathways to lipids rather than glycogen

ex: glucose----> acetyl CoA---> triglycerides

triglycerides can be stored in the liver or released into the plasma to travel to adipose tissue

lipids travel in the bloodstream in the form of lipoproteins

complexes of triglycerol, phospholipid, cholesterol or complex proteins

CLASSIFYING LIPOPROTEINS

lipoproteins are categorized based on their density

protein components of lipoproteins serve as shipping labels that target lipids for different sites in the body

VLDL

liver releases lipids in the form of Very Low Density Lipoproteins (VLDL)

VLDL average about 3 hours in the circulatory system

VLDL deliver their lighter elements to cells

VLDL then become Low Density Lipoproteins (LDL)

ultimately they return to the liver

LDL

LDL have an important health implication

cholesterol that they contain may be taken up by a variety of cells

including those of arterial walls

CHYLOMICRONS

blood rich with lipids following a meal

chylomicrons from lymph and lipids manufactured in the liver

chylomicrons have a relatively short life span in the blood stream

about 8 minutes

LIPOPROTEIN LIPASE

lipoprotein lipase is present in the walls of the capillaries that supply adipose tissue

capillary cells liberate free fatty acids allowing lipoproteins to enter cells

insulin stimulates lipoprotein lipase activity

the presence of this enzyme determines which tissues receive the lipids

HDL

High Density Lipoproteins (HDL) are also important for lipid uptake

HDL are synthesized primarily by the liver

HDL facilitates the uptake of lipids and activation of lipoprotein lipase

HDL particles collect liberated cholesterol in the blood and carry it back to the liver for excretion as bile acids or recycled as bile

HDL VS LDL

LDL can distribute cholesterol to the blood vessel wall

low ratio of HDL to LDL is likely to result in blood vessel disease

a high ratio of HDL to LDL may carry a reduced risk of disease even if plasma lipids are above normal

exercise and consumption of omega oils from cold water fish (tuna) promotes high ratios of HDL to LDL

END
LIVER

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