Liver! Flashcards
Major Components of the liver:
Structural framework
connective tissue capsule, trabeculae and reticular network forms the framework for hepatic architecture
Sinusoids and hepatic cords
biliary tree
Major components of the liver
Cells of the liver
hepatocytes
Kupffer cells
Stellate cells
Endothelial cells
Biliary epithelium
liver architecture
Hepatic Architecture
Hepatic Lobule
an anatomic unit with the central vein at the center of the lobule and portal triads at the periphery
Hepatic Acinus
a functional unit with the central axis bridging between portal areas, with the outer part of the acinus around the central vein
Hepatocytes
- Account for approximately 80% of total liver mass
- Arranged in branching, single-cell plates between sinusoids
- Numerous microvilli on the surface facing the sinusoid
- Responsible for most of the synthetic, secretory, storage, detoxification and metabolic functions of the liver
- Contain numerous intracellular organelles
- Produce and secrete bile into bile canaliculi
Kupffer cells
- member fo the mononuclear phagocyte system
- mobile macrophages located within the sinusoids
- Phagocytose immune complexes and particulate matter in the sinusoids
- produce pro-inflammatory and anti-inflammatory cytokines to contribute to innate immunity
- Pro-inflammatory products can activate hepatic stellate cells to create collagen
Hepatic Stellate Cells
Located in the space of disse
normal function is storage of Vitamin A
During hepatic injury they convert to a myofibroblast phenotype and produce collagen and other ECM components to promote hepatic fibrosis
Sinusoidal Endothelium
- Second most common cell in the liver
- 15-20% of all cells
- 3% of liver mass
- Contain numerous fenestrae
- They lack a well organized basement membrane
- Discontinuous capillary allows intimate contact with blood components and hepatocytes
- Facilitate exchanges between plasma and hepatocytes
Blood Vessels
liver has dual blood supply
Hepatic artery
Protal vein
Blood flow is from portal triad to central vein
Discontinuous capillary with fenestrated endothelium allows intimate contact with blood components and hepatocytes
Lymphatic Vessels
- Fluid from the hepatic interstitium flows into the space of disse then to the portal interstitum to the portal lymphatics
- fluid is derived form the blood as well as products of hepatocytes, hepatic stellate cells and kupffer cells
- Liver accounts for 50% of the lymph that enters the thoracic duct
- Role of lymphatics in disease is poorly understood
- obesity, lipidosis, hypercholesterolemia, lipoprotien associated disease
Biliary System
- Bile is transported form the hepatocyte through a progressively enlarging duct system for secretion into the small intestine
- bile canaliculi
- Intrahepatic bile ductules
- Interlobular bile ducts
- interlobar ducts
- Lobar ducts
- Extrahepatic bile duct
Comparative Hepatic Anatomy:
How many lobes?
Dogs and Cats
6
left lateral, left medial, quadrate, right medial, right lateral, cuadate
Comparative Hepatic Anatomy:
How many lobes?
Mice and Rats
4
right, caudate, left, middle
Comparative Hepatic Anatomy:
How many lobes?
Horse
5
Right, Quadrate, left medial, left lateral, caudate
Comparative Hepatic Anatomy:
How many lobes?
Bovine
4
right, caudate, left, quadrate
Comparative Hepatic Anatomy:
How many lobes?
Elephant and Chicken / Avian
2
Left, right
Comparative Hepatic Anatomy:
How many lobes?
Pig
5
left medial, left lateral, right medial, right lateral, cuadate
Comparative Hepatic Anatomy:
How many lobes?
Humans
4
left, right, quadrate, cuadate
Who doesn’t have a gallbladder?
- Equines
- horses, mules, etc.
- Cervids
- white-tailed deer, elk, moose, etc
- Camels
- Rats
- Elephants
- Giraffes
- but often present in neonates, involuting with age
- Rhinoceroses
- Doves, pigeons, ostriches, and some psittacines
- but most avian species have gall bladder
- Among others
Liver Function
- The liver plays a central role in metabolism
- synthesis and metabolism of proteins, lipids, and carbohydrates
- Storage of nutrients
- conjugation and detoxification reactions
- Immune functions
- Waste product excretion
- Bile synthesis and secretion
Nutrient synthesis, storage, and metabolism
Glucose metabolism
Degradation of plasma lipids and synthesis / storage / oxidation of fatty acids
Production of most plasma proteins
Production of cholesterol and lipoproteins
Nutrient storage
Conjugation and Detoxification
Xenobiotic biotransformation and excretion
- Phase 1 reactions:
- Convert toxins into less (sometimes more) harmful intermediate compounds
- Cytochrome P-450
- Convert toxins into less (sometimes more) harmful intermediate compounds
- Phase 2 reactions
- convert phase 1 products into water soluble products for excretion
- conjugation reactions
- glucuronidation
- Sulfation
- Glutathione and amino acids conjugations
- conjugation reactions
- convert phase 1 products into water soluble products for excretion
Immune Functions
Removal of foreign material from blood
Kupffer cells
Hepatocytes protein synthesis
Inflammation and innate immunity are signaling pathways
Bile Synthesis and Secretion
- Bile
- bile = water + bile salts + bilirubin + cholesterol + fatty acids + lecinthin
- Bilirubin is derived form hemoglobin and other heme proteins
- is taken up by hepatocytes, conjugated to glucuronic acid to become water soluble and less toxic, and excreted through the biliary system
- Bile acids are produced by hepatocytes and efficiently recycled by the enterohepatic circulation
- bile acids are essential for digestion and absorption of lipids and fat-soluble vitamins
- Excretion of wast products and metabolites
Liver - Dysfunction
liver has a large functional reserve capacity
Clinical evidence of disease may initially be absent
There are a wide variety of clinical assays to use to evaluate liver function
- Liver enzymes
- gamma-glutamyl transpeptidase (GGT)
- Alkaline phosphatase (ALP)
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Bilirubin, bile products, albumin, total protein
- Prothrombin TIme
Liver - Dysfunction
Clinical Signs
icterus
photosensitization
Encephalopathy
Hemorrhage
Edema
Gastrointestinal distrubances
Unthriftiness
Icterus
- Excess bilirubin results in yellow discoloration of tissue
- causes of hyperbilirubinemia
- over productions
- hemolysis or excessive RBC degradation
- Hepatocyte injury
- decreased uptake, conjugation or secretion of bilirubin
- Decreased bile flow
- intrahepatic (bile canaliculi)
- Extrahepatic (Bile ducts / gallbladder)
- over productions
- causes of hyperbilirubinemia
Photosensitization
- Activation of pigments by UV light causes erythema, hair loss, and dermal necrosis
- Type 1:
- increased ingestion of photodynamic pigments
- Type 2
- abnormal metabolism of photodynamic pigments
- Type 3
- decreased secretion of photodynamic pigments
- Type 1:
Encephalopathy
Accumulation of ammonia, toxic products and neurotransmitter-like substances cause neurologic dysfunction
These substances are normally excreted by the liver
Accumulation can be due to decreased metabolism by the liver or vascular shunting past the liver
Sings ranged form depression to convulsions
Hemorrhage
all clotting factors are produced by the liver
Factor V!!! is one possibele exception
With severe hepatic injury, decreased production can result in defective secondary hemostasis
Edema
albumin, produced mainly by the liver, regulates plasma osmotic pressure
Hypoalbuminemia results in fluid imbalance and edema
Gastrointestinal Disturbances
decreased bile excretion will disrupt digestion
decreased bile acids decrease fate and fat-soluble vitamin absorption
Unthriftiness
chronic liver dysfunction resutls in weight oss and poor conditions
Hypoabluminemia
Altered fat and protein metabolism
Altered digestion
Liver - Dysfunciton
Acute Hepatic Disease
icterus and Gastrointestinal abnormalities
Liver dysfunction:
Chronic Hepatic Disease
weight loss and unthriftiness
