1 - Liver I Flashcards
Normal gross appearance of liver
- Red-brown
- Divided into lobes
- Sharp edges
o *if enlarged=rounded (ex. heart failure)
Dual blood supply of liver
- Portal vein: drains blood from spleen, intestines, pancreas
- Hepatic artery
*both drain into hepatic sinusoids
*blood leaves liver via HEPATIC VEIN
Liver composition: ‘layers’
- 1 layer of ‘thick plates’ of hepatocytes
o Between: canaliculi - Hepatic arteriole and portal venule draining into sinusoids
o Sinusoids have holes in them allowing for interaction between liver and blood (Space of Disse)
What do bile canaliculi drain in to?
- Bile canaliculi: no epithelium
- Canals of Hering: partially lined by epithelium
- Bile ducts (portal tracts): completely lined by epithelium
What is the Space of Disse?
- Fluid filled space between endothelial cells and hepatocytes
- Continuous with plasma
- *interface for interaction between liver and blood
- Contains ‘stellate cells’
What do ‘stellate cells’ do?
- Store Vit A (normal)
- Can synthesis collagen and thus cause haptic fibrosis (diseased liver)
o Reduced interaction between liver and circulation
2 models to describe the arrangement of hepatic parenchyma
- Subunit is hepatic lobule
- Subunit is hepatic acinus
Hepatic lobule (hexagonal): centre and periphery
- Centre: hepatic venule or central venule
- Periphery: portal venule, hepatic arteriole bile duct, lymphatic nerves
- *cenrilobular, midlobular, periportal area
Hepatic acinus (diamond shaped) : centre and periphery
- Center: terminal afferent branches of portal venule and hepatic arteriole
- Periphery: hepatic venules
- *zone 1, 2, 3
3 zones compared to different areas (hepatic lobule vs. acinus) and oxygenation
- Zone 1: periportal, most oxygenated
- Zone 2: midlobular
- Zone 3: centrilobular, least oxygenated
Gallbladder
- Absent in horse, rat
- Tubular organ
- Common bile duct empty into INTESTINE
What are the normal liver functions?
- Bilirubin metabolism
- Bile acid metabolism
- CHO metabolism
- Lipid metabolism
- Protein synthesis
- (ammonia metabolism)
What is bilirubin?
- Pigment in body
- If high=jaundice=icterus
*Bilirubin metabolism (know where it comes from, types and enzymes)
- Comes from RBCs (last 120days and die in spleen)
o Hemoglobin phagocytized by macrophages in spleen
o Heme + globin
o *Heme to biliverdin
o *Biliverdin to bilirubin through hemeoxygenase - Bilirubin leaves macrophages in spleen and bind in blood (unconjugated bilirubin)
- *Liver conjugates bilirubin with conjugated acid (conjugated bilirubin)
- Conjugated bilirubin is excreted in bile
What are the 3 types of jaundince?
- Prehepatic
- Hepatic
- Post-hepatic
What causes prehepatic jaundice?
- Increased break down of RBCs
- *liver can’t keep up!
- *lots of unconjugated bilirubin
What causes hepatic jaundice?
- Decreased UPTAKE of bilirubin due to liver DISEASE
- Bilirubin accumulates b/c liver is NOT removing it from blood
What causes post-hepatic jaundice?
- Decreased hepatic excretion of bilirubin with bile (
- *cholestasis: bile obstruction
What kind of jaundice do ruminants get usually?
- Prehepatic
- *can still get other types
When do horses develop physiologic icterus?
- With starvation! (for a couple of days)
o NORMAL - *bilirubin uptake is energy dependant and is decreased during starvation
- **ONLY occurs in horses
- Can also have yellow fat in general (can’t convert keratin to vitamin A)
Where are bile acids synthesized and secreted?
- Synthesized: liver
- Secreted into intestine
o Most reabsorbed by intestine and take up again by liver (very efficient reabsorption and ENTEROHEPATIC CIRCULATION)
What happens with liver disease and bile acids?
- PRODUCTION IS NOT ALTERED
- *usually it is just liver UPTAKE that is reduce?
Liver and CHO metabolism
- Regulate blood glucose metabolism
- Store glucose as glycogen
- Release glucose through glycogenolysis and gluconeogenesis
Liver and lipid metabolism
- Production and degradation of plasma lipids
Liver and protein synthesis
- Synthesizes ~15% of body proteins
o Albumin: if low=edema
o Clotting factors: if low=hemorrhage - Ammonia metabolism
*ammonia metabolism in the liver
- Ammonia is toxic by product of protein catabolism (intestine)
- *converted into urea by liver through UREA CYCLE
What are the different responses of the liver to injury?
- Degeneration, necrosis and apoptosis
- Disturbances of bile flow and icterus
- Regeneration
- Fibrosis
- Bile duct hyperplasia
- End stage liver (cirrhosis)
- Liver failure
What are the 3 different patterns of distribution of degeneration and necrosis in the liver?
- Random
- Zonal (5 types)
- Massive
*can help narrow down the cause
Random necrosis and apoptosis of the liver is due to
- Bacteria
- Viruses
- Protozoa
- *lots of tiny white spots
What are the 5 zonal types of necrosis and apoptosis of the liver?
- Centrilobular
- Paracentral
- Periportal: LEAST COMMON AND LEAST IMPORTANT
- Midzonal
- Bridging necrosis
Centrilobular necrosis
- Most common type
- Hepatocytes are least oxygenated (ex. prone to necrosis)
- Hepatocytes contain greatest concentration of DETOXIFYING ENYMES (ex. mixed function oxidases or cytochrome P450 enzymes)
- *pale around the center (histology)
- Ex. nutmeg liver
What are the common causes of centrilobular necrosis?
- Toxins requiring metabolic activation
- Passive congestion in liver
Paracentral necrosis
- Involves only a WEDGE around the CENTRAL VEIN
o Only ONE acinus is affected - *from severe acute anemia (blood loss)
Periportal necrosis
- Closest to blood supply
- Least common and least important
- Has highest O2 tension
- Affected first by toxins that do NOT require activation
- Have limited mixed function oxidase enzymes (ex. generally, it is affected by toxins that do NOT require activation)
- Uncommon (ex. phosphorus toxicity)
Midzonal necrosis
- Rare
- Not important
Bridging necrosis
- May link centrilobular areas (central bridging) or centrilobular areas to periportal areas
- More of a histological description
Massive necrosis
- Necrosis of ENTIRE HEPATIC LOBULE or CONTIGUOUS LOBULES
What is cholestasis? What are the 2 types of cholestasis?
- Disturbance of bile flow
- *intrahepatic and extrahepatic
Intrahepatic cholestasis
- Affects bile canaliculi or ductulus within the liver
- MAIN CAUSE: liver injury (fibrosis)
o Squeezes them and makes them narrow - *inherited abnormality of bile synthesis and secretion in sheep and goats
- Use histology (yellow lines=dilated bile canaliculi)
Extrahepatic cholestasis
- Affects extrahepatic bile duct
- CAUSES: obstruction to a mass within or outside the lumen
- *will lead to intrahepatic cholestasis
- *if prolonged=leads to fibrosis and bile duct proliferation in liver
- *can tell grossly (squeeze bile duct and look at the bile going to duodenum, if none=cut open bile duct to see disturbance)
- Histologically: lots of fibrosis
Bile duct hyperplasia
- Non-specific reaction to hepatic injury
- Unknow mechanism
- Indicates LONG standing liver injury (chronic)
- *need histology
Regeneration of the liver if small
- Local proliferation of adjacent hepatocytes (unnoticed grossly)
- Especially if basement membranes are intake
Regeneration of liver if extensive (loss of basement membrane)
- Extensive loss of hepatocytes AND LOSS OF EXTRACELLULAR MATRIX SCAFFOLD (RETICULIN) OCCUR
- **see regeneration nodules (GROSSLY)
- *disorganized regeneration: no scaffold
Do regenerative nodules restore hepatic function completely?
- NO
o Blood flow and bile flow is abnormal
o Fibrosis significantly impairs hepatic function
(If nodules on an organ, what are the 2 things you may have?)
- Neoplasia
- Granulomatous inflammation
What are some examples of things that cause fibrosis in the liver: centrilobular area?
- Long standing R-sided heart failure
- Most drugs and toxins
What are some examples of what causes random areas of fibrosis?
- When parasites migrate through hepatic parenchyma
o Loss reticular fibers (basement membranes)
What is bridging fibrosis? (descriptive term from histology)
- Indicates the fibrosis extends from one portal area to another OR to centrilobular area
**What is the gross appearance of fibrosis in the liver?
- *regular surface (still smooth)
- Small
- Firm (difficult to poke)
- Pale white
- Usually has a nodular appearance
**End stage liver (cirrhosis): 3 process that need to be happening at the same time
- Gross pathology term
- Degeneration and necrosis
- Regeneration (ex. regenerative nodules)
- Fibrosis
- *must be present almost DIFFUSELY throughout to call it end stage (cirrhosis)
