Concept of metabolism - hepatic A&P 5

Liver - internal anatomy

• Accessory organ of GI tract along with the pancreas and gall bladder

• Vascular organ

• Complex venous, arterial and bile system

Hepatic blood supply

• hepatic artery

• hepatic vein

• hepatic portal vein

Hepatic blood supply - hepatic artery

• branch of aorta; brings oxygenated blood to the liver (goes into liver)

• (400 ml/min)

Heaptic blood supply - hepatic vein

• returns deoxygenated blood from the liver to inferior vena cava (goes away from liver)

which will then move to the superior vena cava, to the right atrium, to the right ventricle

Hepatic blood supply - hepatic portal vein - very important!!!

• ­Union of veins bringing deoxygenated blood from spleen, stomach, esophagus, pancreas, intestines (GI Tract) allll up into the liver

• Rich in dissolved nutrients from these areas (food we consumed)

• Contains toxins and medications - within blood supply of the hepatic portal vein - need to be removed by liver through metabolism!!!

• ­Blood enters liver where the portal vein divides into sinusoids!

  • Specialized capillaries within hepatocytes

Liver functions:

• Removes toxins from bloodstream

• Metabolizes nutrients from food

• Removes bacteria from blood

• Stores sugar, vitamins and minerals

• Regulates blood clotting

• Produces bile to digest fat and absorb vitamins A, D, E, K

• Produces protein (albumin!)

• Conjugates bilirubin

Liver - production of bile/ bile salts

• ­Bile – bitter, yellow/green fluid produced by liver (hepatocytes)

• ­Bile salts – solid salts within bile that aid fat digestion

• ­Needed for digestion of fat and absorption of fat-soluble vitamins A, D, E, and K

Liver - metabolism of drugs

• almost ALL drugs detoxified and metabolized in the liver

• drug induced liver toxicity a concern with many medications

• helps to detoxify and metabolize!!

Liver - metabolism of alcohol

• 80-90% of ingested alcohol metabolized here

• Alcohol can disrupt other functions of the liver

• consumption of alcohol can damage the ability of the liver to have its phagocytic function - important in preventing bacteremia - increase their risk of septicemia

• alcohol use disorder - malnutrition and anorexia

Metabolism and synthesis of glucose

• ­Glucose – main fuel source for brain, muscle and renal tissues

  • ­Liver contributes to the stability of blood glucose

• ­Glycogenolysis – breakdown of glycogen (which is stored in the liver) to glucose

  • ­When more glucose is needed!!

• ­Gluconeogensis – ability of the liver to “make new glucose” from non-carb sources (protein, fat)

• ­Glycogenesis – formation of glycogen from glucose

  • ­When glucose is adequate, and more is available

Metabolism and glucose - glycogenolysis:

• breakdown of glycogen (which is stored in the liver) to glucose

  • ­When more glucose is needed!! - don’t have glucose available

Metabolism and glucose - Gluconeogensis:

• ability of the liver to “make new glucose” from non-carb sources (protein, fat)

Metabolism and glucose - Glycogenesis:

• ­formation of glycogen from glucose

  • When glucose is adequate, and more is available (extra) - stored for later use

Liver - synthesis of nutrients

• Proteins

• Fats

• Vitamins

• Clotting factors

Liver - synthesis of nutrients - proteins

• ­takes amino acids (AA) and turns in to proteins

  • ­Albumin, most globulins, enzymes

Liver - synthesis of nutrients - fats

• ­synthesized from carbohydrates and protein in liver

  • ­Liver can make fat

  • ­Need some fat in body for energy

  • ­Fat absorbed from intestines as triglycerides

  • ­Affects cholesterol levels - pt with liver failure/cirrhosis, will see alterations in their cholesterol levels

Liver - synthesis of nutrients - vitamins

• A, D, E, K

• B 12

Liver - synthesis of nutrients - clotting factors

• ­prothrombin, fibrinogen - controlled by the liver

  • ­Clotting cascade begins here in the liver - not functioning properly, will see alterations in pts ability to clot - won’t have ability to clot quickly - INR will increase (dependent on vit. K)

  • ­Dependent on Vitamin K production and storage!!

Liver - protein metabolism

• ­Within hepatocytes, amino acids (proteins) are converted from ammonia to urea - if liver not functioning properly, lose ability to convert ammonia to urea

• ­Ammonia is very toxic to the central nervous system

  • Especially the brain!

  • ­hepatic encephalopathy!!!!

Liver - removes bacteria from the blood

• Filtration of blood and removal of bacteria and particulate matter

  • The Kupffer cells are phagocytic macrophages

Liver - bilirubin elimination - review

• bilirubin is a component of hemoglobin breakdown

  • Begins with breakdown of RBCs (old or hemolyzed) (in spleen)

  • Hemoglobin broken down into - heme (waste) and globin (protein returned to blood)

• Heme is then converted to biliverdin and then quickly to bilirubin (bilirubin makes the pigment color of bile)

Liver - bilirubin elimination cont. - unconjugated

• bilirubin travels in the bloodstream to the liver: this is called UNCONJUGATED/FREE/INDIRECT bilirubin

• This unconjugated bilirubin travels attached to albumin - its life raft!! - needs this life raft to travel through blood

• Once in liver, the bilirubin is “freed” from the albumin and enters the hepatocytes

Liver - bilirubin elimination - conjugated

•  Bilirubin in the hepatocytes (liver) is then converted to DIRECT/CONJUGATED bilirubin

• ­Conjugated means “united together”

  • ­The bilirubin unites to an enzyme as part of this process

  • ­The conjugated bilirubin is then secreted from the liver as part of bile

• ­Bilirubin gives bile it’s color

• ­Stored in gall bladder

• ­Eventually enters GI Tract

What does it mean for bilirubin to be unconjugated

• this is bilirubin that is traveling in the bloodstream to the liver

• it attaches to albumin

What does it mean for bilirubin to be conjugated:

• conjugated within the liver itself!!

• this is bilirubin that has made its way into the liver, unattached from albumin, enters the hepatocytes

• once in the hepatocytes, the bilirubin unites to an enzyme as part of process

• conjugated bilirubin is then secreted from the liver as bile

Liver - When bilirubin enters intestines, bacteria converts the bilirubin to urobilinogen..

• Urobilinogen is formed in the intestines by bacterial action on bilirubin. About half of the urobilinogen formed is reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidney

• kidneys take important role in the excretion and removal of some of our bilirubin

Liver - Or it converts the bilirubin to stercobilinogen

• Stercobilinogen is formed from the half of the urobilinogen that is not reabsorbed.  Stercobilinogen gives feces its color.  This is then excreted through intestines and is eliminated as feces. - poop!!!

• if bilirubin not eliminated by kidneys, its eliminated by our GI tract

Liver - jaundice

• A symptom, not a disease itself!!!

• Symptom we see due to elevated bilirubin in blood!!!!

  • Visible sign of underlying disease process of the liver or associated organ

• Usually seen when total bilirubin levels in the blood reach 2.5-3 mg/dL

• (Normal = 1.2 mg/dL or less)

• can appear first in the sclera but can appear throughout the pts skin

Jaundice causes: hemolytic or PRE-HEPATIC

Unconjugated bilirubin traveling TO liver!

• Cause of jaundice due to: 

• Hemolytic/Pre-hepatic reasons – “before the liver” – not really liver disease

  • An increased destruction (hemolysis) of RBC’s – “too much” for the liver to handle

Causes:

•Hemolytic Anemia

•Autoimmune or transfusion hemolysis

•Hemolytic processes caused by Sickle Cell Disease or Thalasssemias

•Septicemia - infection throughout body - causes our spleen to enlarge - starts to break down our cells such as RBC at a higher level than it should

•Newborns

Labs: Increased total bilirubin and indirect/unconjugated bilirubin (unconjugated before it gets to the liver so makes sense!!)

Jaundice cause - hepatocellular or INTRAHEPATIC

This is where/when bilirubin becomes conjugated!

• Cause of jaundice Hepatocellular/Intra-hepatic – problem within the liver – liver disease

  • Cirrhosis, hepatitis, cancer, drugs (pharmaceuticals/illicit)

Either liver is unable to:

• Take in the increased bilirubin from the blood - coming in as unconjugated

    OR

• Is unable to conjugate or excrete the bilirubin once it enters the liver

Labs: Increased total bilirubin and either increased indirect/unconugated (if the problem is occurring when the bilirubin is just getting into the liver and has had yet to conjugate) or direct/conjugated bilirubin

Jaundice - obstruction or POST HEPATIC

Bilirubin ready to leave the liver as part of bile

• Obstruction of bile flow/Posthepatic “beyond the liver”

  • Obstructed outflow of bile from the liver

  • Ex:  Cholelithiasis (gall stones), biliary tract tumors, cancer of gall bladder, pancreatitis (comes distal to the gallbladder)

  • Will cause clay/light colored, frothy stools

Bilirubin that was conjugated in the liver cannot leave the liver and accumulates in the liver and enters the blood

Labs: Increased total bilirubin or increased direct/conjugated bilirubin

S&S of jaundice:

The manifestations will depend on the underlying cause

Example:

• Hemolytic anemia

• Cirrhosis

• Gall stones

Collaborative care for Jaundice:

Treat causes and complications

• Hemolytic anemia (pre hepatic)– Administer iron or blood transfusions

• Cirrhosis (intra hepatic)

• Gall Stones (post hepatic) – cholecystectomy

The liver is a large organ..

• also very vascular

• has consistently large volumes of blood flowing through it

• has a right and a left lobe - the right being larger than the left

The liver is surrounded by the:

• Glisson’s capsule

What is the Glisson’s capsule:

• the liver is surrounded by it

• tough capsule that helps to protect it from internal damage and trauma that a pt might sustain

(a laceration to the liver could be life threatening due to it being very vascular - could result in hemorrhagic shock)

What is seated right below the liver?

• the gallbladder

• has bile ducts which flow up into the liver

The gallbladder is responsible for:

• releasing the bile which is initially created in the liver

Blood flow review:

• venous blood flows up into the larger hepatic vein (at the very top of the liver), then dumps into the vena cava

• Aorta delivers the oxygen rich blood down into the liver via the hepatic arteries

Hepatic circulation image:

• aorta sending that oxygen rich blood out to our entire body

  • hepatic artery which branches off of the aorta and goes into the liver again delivering oxygen rich blood

• blood supply from GI tract goes up into the hepatic portal vein - nutrient rich blood

• gallbladder releases bile through bile ducts, goes down into the GI system/GI tract where it works to dissolve and break down fats - metabolism of fats!!

• venous blood goes out of the liver, back to the heart through the hepatic vein - oxygen deprived blood - goes to inferior vena cava, superior vena cava, right atrium, right ventricle, yada yada

Liver lobule:

• within them are sinusoids that have large gaps which allow for nutrients and bacteria to drain within the liver

• Liver lobules are the functional hexagonal units of the liver, consisting of plates of hepatocytes radiating from a central vein toward portal triads. Within these lobules, Kupffer cells (KCs) are specialized

Liver lobules have Kupffer cells:

• phagocytic macrophages

• important in eliminating and cleansing bacteria

• stationary macrophages located in the sinusoidal lumen, serving as the body's largest population of tissue macrophages

At the lobular level and within the sinusoids, our liver…

• metabolizes products

• works to release and produce albumin

• produces bile

Bile (produced by the liver) includes:

• some cholesterol, electrolytes, bile salts

• comes from the hepatocytes themselves

• without bile we wouldn’t be able to dissolve our fats or absorb our fat soluble vitamins A, D, E, K

Once conjugated, bilirubin travels how:

• From the intrahepatic bile ducts, to the gallbladder, to be released into our intestinal tract

Bilirubin metabolism summarized:

• Spleen - responsible for housing many of our blood cells including our old RBCs

• RBCs get broken down or destroyed as they’re old - producing and breaking apart that hemoglobin into heme and globin

• Travels UNCONJUGATED via albumin through our bloodstream into our liver

• As it goes into the liver, starts out unconjugated but then gets conjugated

• CONJUGATED bilirubin is then excreted into the bile duct, into our gallbladder

• Goes out of the gallbladder, secreted into the intestines

• CONJUGATED bilirubin goes into the small intestine, is then converted into stercobilinogen

• Half of that is going to stay within the intestines and half goes back up into the portal vein and then is excreted out through the kidneys (urobilinogen)

Vitamin K deficiency leads to…

• increased INR - takes longer to clot

What does it mean for the liver Kupffer cells to be phagocytic macrophages?

• they filter blood, remove 80-90% of bacteria, toxins and cellular debris, ensuring clearance of pathogens

• so when someone drinks too much and this phagocytic function isn’t as efficient, less bacteria is being removed so they are now at higher risk for septicemia

Why in the post hepatic reasons for jaundice is our stool going to be frothy?

Fat in the stool - wasn’t able to be metabolized and broken down