Liver Gallbladder, Pancreas, Spleen

What is the anatomy of the liver?

The liver is in the RUQ - inferior to the diaphragm

• Neonate- 5% of body weight

• Hepatocytes represent 80% of the cytoplasmic mass within the liver

Liver = 4 lobes - each lobe has a ton of hepatocytes

Blood flows past hepatocytes via sinusoids from branches of the portal vein and hepatic artery to a central vein

Central veins join form hepatic veins -which drain into the inferior vena cava 

Hepatocytes

Each hepatocyte is located adjacent to bile canaliculi, which coalesce to form the common hepatic duct

The duct and the cystic duct form the gallbladder joins to form the bile duct, which enters the duodenum at a site surrounded by the sphincter of Oddi

What are Kupffer cells

Kupffer cells: macrophages located in the liver that play roles in maintaining liver homeostasis and defending against pathogens

• Immune surveillance: cells engulf bacteria, viruses, and other foreign particles, protecting the liver from infections

• inflammation regulation: produce inflammatory response mediators such as cytokines and chemokines to respond to infections and tissue damage

• lipid metabolism: help regulate lipid metabolism by clearing cholesterol and fatty acids from the liver

• fibrosis control: contributes to repair of liver fibrosis by producing collagen and other extracellular matrix components

• iron metabolism: they store and release iron maintain iron balance in liver

What are the factors that affect hepatic blood flow??

What are the functions of the liver?

Detoxification

Metabolism 

Immune system 

Production of Bile 

Storage of micronutrients 

production of cholesterol

Blood sugar balance

What is the Bile formation of the liver??

• What is its function 

• produced by??

• Secreted by??

Bile helps excrete material not excreted by the kidneys and aids in the absorption and digestion of lipids via the secretion of bile salts and acids

Bile is produced by hepatocytes and is mainly composed of water, electrolytes, bile salts, bile acids, cholesterol, bile pigment, bilirubin, and phospholipids.

Secreted by hepaptocytes into bile canaliculi

Functions of the liver, fat soluble vitamin storage and metabolism

• what vitamins

Fat-soluble vitamins that reach the liver via chylomicrons or VLDL are stored or metabolized in the liver

• these vitamins are A, D, E, K

  • Vit A: stored in hepatic stellate cells

  • Vit D:  25-hydroxylation by the hepatic CYP-450 system 

  • Vit E: converts Vit E into active form or excretes it 

  • Vit K: not stored or metabolized in the liver but required for the function of coagulation factors made by the liver

Function of the liver in Drug metabolism

• what are the phases 

Liver metabolizes a wide range of drugs the end result of which is to produce water-soluble compounds that can be excreted in bile

• Phase 1 - mediated by Cytochrome P450 via oxidation, reduction, and hydrolysis

• Phase 2 - conjugation of the drug or metabolic byproducts to highly polar ligands 

• Phase 3 - movement of drug into the bile or bloodstream

Function of the liver: cytochrome P450

Large group of enzymes that metabolize a vast majority of substances in the body

• inhibitors: block CYP450 enzyme can lead to decreased drug metabolism, causing a buildup of the drug in the body and increasing the risk of toxicity

• Inducers: substances that speed up the CYP450 enzyme can lead to faster drug metabolism, which mat result in a sub-therapeutic effect and treatment failure for the drug being broken down more quickly 

Functions of the liver: bilirubin metabolism

• production of what

• what does it transport

• what is the coagulation process

• what are the excreations

production: RBC - broken down in spleen liver and bone marrow - hemoglobin converted to heme then further converted into bilirubin

Transport: unconjugated bilirubin binds to albumin and is then transported to the liver

Conjugation: bilurbuin is conjugated with glucuronic acid, making it water-soluble

Excreation: conjugated travels into the intestines - converted into urobilinogen and excreted by the feces as stercobilin small amount is reabsorbed into the blood and excreted in the urine as urobilin

Functions of the liver concerning metabolism 

• What is glycogenisis

• What is glucogensiis

• What is glycolysis

• what s fatty acid oxidation

Glycogenesis: stored glycogen for breakdown during fasting to release into blood stream to maintain stable blood sugar levels

Glucogenesis: new glucose synthesis - synthesized from non-carbohydrates to produce blood sugar occurs during prolog fasting and requires lots of energy

Glycolysis: glucose breakdown for ATP - liver takes up excess glucose and breaks it down to produce pyruvate to produce atp energy for the liver - happens in a fed state 

Fatty acid oxidation and ketogenesis: during fasting or porlonged exercise - fatty acid are broken to produce energy for livers activities and to produce ketones - released into the bloodstream

Function of the liver involving protein metabolism

• what is the role of the liver

• deamination of amino acids 

• formation of urea for the removal of ammonia 

• formation of all plasma proteins except gamma globulin 

• inter-conversions of the various amino acids and synthesis of other compounds from amino acids

Functions of the liver: metabolism

• How is formation of the urea taking place 

• What is lactulose

Formation of urea: 

• Ammonia formed from decomposition is highlytoxic to tissue 

• increased ammonia due to liver dx= hepatic coma 

• 2 molecules of ammonia = urea 

Lactulose = a drug used to bind to ammonia in the gut

• ammonia will buind to only ammonia formed in the gut and allow the body to ecrete through the bowels 

Functions of the liver metabolism

Liver

• plays a role in thyroid hormone function as the side of deiodination of T3 and T4 → converts it to the active form 

• synthesis every plasma protein - protein C and S brakes for the clotting cascade 

• synthesis of intrinsic and extrinsic clotting factors 

• production of TPO - this si the main stimulator of platelet production

How do we measure liver function?

• tests 

AST, ALT, Alkaline phosphate, Total bilirubin, D. Bilirubin 

Coagulations test: PT, PTT, INR

LDH

Platlet count 

glucose levesl 

What are ALT tests:

What are AST tests:

What are ALP tests:

ALT: Alt enzymes found in the liver that convert proteins for energy - if the liver is damdged, their will be ALT found in the blood

AST: Enzyme that helps the body break down amino acids - increase AST levels in the blood = liver damage, liver dx, or muscle damage 

ALP: Enzyme found in the liver and one that breaks proteins - higher in blood = liver damage or dx - blockade bile duct or certain bone dx - bone enzyme too

How do we measure liver function using the cogulations test

• elevated PT or INR

• Thromboelstography(TEG)

will be elevated in extensive liver damage 

• pts with liver dx inc risk for clotting despite having elevated PT and INR 

TEG real time measurement of cogulability reliable test with someone who has liver dx

How we mesure liver function based on LDH, Glucose, ammonia?

LDH: can be elevated if the liver dx but also because of other organs used to measure liver dx

Glucose: sudden drop in glucose in a setting of liver function can indicate acute liver failure - a marker for acute liver failure and carries a very high mortality rate 

ammonia: normal byproduct of protein metaboilism but in liver dysfunction cannot be excreted properly

What are the stages of liver function

• inflammation 

• fibrosis 

• cirrhosis 

• end-stage liver failure 

Inflammation- the liver becomes inflated due to factors such as viral infection, alcohol abuse or autoimmune disorder 

• sx: pain, tenderness and swelling 

Fibrosis: scar tissue formation - blocks blood flow and damages healthy liver cells 

• sx: fatigue, jaundice, ascities 

Cirrhoisis: advanced fibrosis where ther is sever scaring and unable to function properly 

• sx: advanced jaundice, hepatic encephalopathy, bleeding 

End-stage liver failure: loss function 

• sx: jaundice, coma, organ failure

The gallbladder 

• what is the gallbladder 

RUQ

stores bile produced by the liver for emulsion of fats 

Stimulated by CCK = release into common bile duct 

Bile stored in the gallbladder becomes concentrated 3-10 fold 

Gallbladder Pathologies 

• what are gallstones

• What is cholecystsis

• What is choledpocholitis

gallstones: form in the gallbladder because of high cholesterol or bilirubin- typically no symptoms will pass - cholelithiasis

Cholecystitis: inflamed and thickened - caused by a blockade of the cystic duct by a gallstone or infection - when it is not caused by obstruction = acalculous cholecystitis

Choledocholithiasis: common bile duct obstruction - depends on the site, obstruction can lead to pancreatitis 

• sx: RUQ. jaundice, elevated LFT, an elevated lipase 

Gallbladder removal

Pancreas 

• contain??

Contains: the in between number of lobes between called ACINI

In between ACINI, there are groups of endocrine cells called the islet of Langerhans

Small ducts emerge from these lobules and unite and reunite to form pancreatic duct

What does the pancreas secrete

• Exocrine and endocrine secretions 

Exocrine: 

• digestive in function it is conveyed to duodenum through pancreatic duct, pancreatic juice contains enzymes:

  • Lipase: fat fatty acids and glycerol

  • Amylase: starcth maltose

  • Trypsin: peprones amino acids

Endocrine:

• secreted by the islets of Langerhans ad directly poured into circulation - this secretion has 2 different hormones, which are secreted by 2 different cells of islets of Langerhans 

• Glucogen : secreted by alpha cells 

• Insulin : secreted by beta ce;ls 

Enzymes: Amylase and lipase are secreted in their active form; ither enzymes need to be activated or else they will auto digets the pancreas itself 

• symogens or proenzymes are precursors too the activetd enzymes responsible for digesting proteins 

Enteroopeptides: Enzyme produced y the duodenum - the first part of the small intestine - critical firs step - it cleaves and activates trypsinogen and trypsin 

Trypsin: once activated, this enzyme starts the domino effect activating other pancreatic enzymes 

Pancreatitis:

• what is it 

• hows it caused 

• Sx

Can be acute or chronic - caused by an infection, diet related - alcohol, obstructive, or elevated Calcium

Sx: recurring abdominal pain, weight loss, diarrhea and oily foul- foul-smelling stools due to inability to properly digest food- can lead to the development of diabetes 

Necoritizing pancreatitis:

• what is it

• What can it cause 

Pancreatic tissue dies Leads to:

• infection

• hemorrhage 

• abdominal compartment syndrome 

• multisystem organ failure 

  • AKI

Pancratic cancer

• What is it caused by

• What are the Sx

• What is the prognosis

The majority is from Adenocarcinomas, small percentage is from neuroendocrine tumors that arise from hormone-producing cell 

Sx: not present until very late in stages - later diagnosis and higher mortality 

• jaundice, abdominal pain, weight loss, nausea and voimmiiting, dark urine, light-colored stools, fatigue, new-onset diabetes 

Prognosis: very poor prognosis 5 5-year - 12% live

Spleen: 

• Where 

• Functions??

LUQ - can live without spleen

Filtering blood: remove old 

immune function: Contains WBC that help fight infections, stores macrophages 
Blood storage: stores and release in an emergency such as bleeding 

Regulation of blood cell production: spleen monitors the numebr of RBC in the body and tells the bone marrow to make more 

lymphatic drainge: spleen helps drain lymph fluid from abdominal area 

What is the Spleens recycling process?

RBC age they become less efficient at carrying oxygen

The spleen detects the old cells and tears them in its red pulp

Macrophages WBC spleen engulf and break down the old red blood cells 

iron and other components from are recycled and used to produce new rbc 

RBC -breakdown sent to liver and the body - bilirubin and iron 

Spleen injuries can be minimal to severe

• splenectomy 

• splenic embolization

Splenectomy: surgical removal of the spleen

Splenic embolization: minimally invasive procedure used to block blood flow in the spleen’s artery using coils or other materials - it is used to treat conditions like tramua, blood disorders, and splenic aneurysms