Special Path - Liver Basics Flashcards
What are two sources of blood for the liver?
(1) 2/3rd from Portal Vein - drains GI tract
(2) 1/3rd Hepatic artery
* dual blood supply
Blood leaves the liver from what two vessels?
Hepatic Vein and Vena Cava
Functional subunit of the liver is? Provide description
Lobule - hexagonal and 1-2mmwide; central vein is at the center and portal areas are at the periphery
Portal areas contain?
Bile ducts, portal vein, hepatic artery, nerves, and lymph vessels
How are hepatocytes arranged?
Arranged in branching plates which radiate from the central vein and are separated by sinusoids (blood spaces)
Sinusoids are bounded by endothelial cells which are separated from hepatocyte microvilli by….?
Space of disse
What can pass through the space of disse?
RBCs are retained in the sinusoids but large molecules can pass through into hepatocytes
Damage (like fibrosis) in the space of disse does what?
Reduces resorption by hepatocytes and has serious consequences for liver function
Sinusoids contain resident macrophages which have a variety of functions including phagocytosis and release of cytokines. Another name for these resident macropahges is?
Kupffer cells
What is the purpose of hepatic stellate cells and where are they located?
Hepatic stellate cells are located in the space of disse and differentiate into myofibroblasts following injury and are the main source of hepatic fibrosis.
The main source of hepatic fibrosis is from what type of cell?
Hepatic stellate cells
Describe the flow of bile
It flows in the opposite direction to blood.
Bile canaliculi –> centrilobular areas –> bile ducts in portal areas –> gall bladder –> common bile duct
Function of hepatocytes (4):
(1) Synthesis of cholesterol, bile acids, glycogen
(2) metabolism and preparation of substances for excretion via bile (ex. pigments or steroid hormones)
(3) metabolism of fatty acids
(4) synthesis of proteins (albumin, clotting factors, firbinogen, lipoproteins)
Function of bile canaliculus
Transport bile
Function of sinusoids
Kupffer cells phagocytosis of foreign material from blood
Abnormalities of the liver are not usually detected until what?
Majority of hepatic functional mass is lost
All clotting factors except factor ____ are synthesized in the liver.
VIII
List clotting abnormalities of the liver (3):
(1) Decreased synthesis of clotting factors
(2) Decreased clearance of fibrin degradation products, activated coagulation factors and plasminogen
(3) Metabolic changes secondary to liver disease can affect platelet function
Liver dysfunction - What is hypoalbuminemia?
Severe chronic disease (decreased synthesis and increased loss secondary to portal hypertension)
Liver dysfunction - Photosensitization
Hepatic disease or biliary obstruction decreases normal excretion of phylloerythrin (a photodynamic product of chlorophyll produced in herbivores) in bile –> Increased phylloerythrin in serum and concentration in cutaneous tissues –> UV light activates phylloerythrin and results in cutaneous lesions usually in hairless areas
Liver dysfunction - Hepatic Encephalopathy (CNS disturbance caused by abnormal neurotransmission)
Increased concentrations of ammonia derived from amines absorbed in GIT may be responsible.
Occurs when insufficient liver function remains for metabolism (end stage liver in horses and ruminants) or significant portion of blood bypasses the liver (congential portosystemic shunts in dogs and cats).
It can result from shunting of blood within regenerative nodules in end stage liver disease in dogs and cats.
Congenital portosystemic shutns in dogs and cats can lead to?
Hepatic Encephalopathy
Liver dysfunction - Hyperbilirubinemia (icterus) may occur as a result of?
May occur as a result of severe hepatic disease, cholestasis, intravascular or extravascular hemolysis.
Intrahepatic cholestasis is what and occurs as a result of what?
Intrahepatic cholestasis is decreased secretion of bile across hepatocyte membrane. It occurs as a result of disorders of hepatocytes (toxins, bacteria, viruses, ischemia)
Extrahepatic cholestasis is a result of what?
Result of obstruction of bile flow (neoplasia, parasites, inflammation, calculi)
Three responses to liver injury are:
(1) Fibrosis
(2) hepatocellular regeneration
(3) Bile duct proliferation
What is cholestasis?
When bile cannot flow from the liver to the duodenum
The combination of what two things is responsible for the nodularity (coarse or fine) of chronic hepatic disease?
Combination of regeneration and fibrosis
Is advanced fibrosis reversible?
No, it is irreversible, and can be lethal
Hepatic fibrosis is an increase of ____ within lesions and space of Disse.
(1) Fibrillar collagen (type I and III)
(2) Non-fibrillar collagen (type 18)
(3) Extracellular matix (proteoglycans, fibronectin, hyaluronic acid)
Severely fibrotic liver can contain ___x as much collagen and other extracellularm atrix as normal.
6x
Hepatic stellate cells are activated by cytokines to do what following hepatic injury?
Change from lipid storage cells to myofibroblatsic cells which synthesize collagen following hepatic injury.
Can the site of fibrosis within the hepatic lobule be indicative of the type of insult?
Yes, however chronic or severe injury often produces fibrosis affecting most areas of the liver
Centrilobular fibrosis can result from ____
chronic right sided heart failure or toxic injury
Periportal fibrosis can result from ____
chronic inflammation, toxins (some can affect periportal hepatocytes), chornic biliary obstruction
Bridging fibrosis is?
Fibrosis that extends from one portal area to another or from portal areas to centrilobular areas. Associated with impaired hepatic function
Multifocal hepatic fibrosis
Foci of fibrosis randomly scattered throughout the parenchyma
Diffuse hepatic fibrosis
Affects all regions of the lobule and is present throughout the liver
End stage liver disease (cirrhosis) is marked by?
Diffuse fibrosis with formation of regenerative nodules and often bile duct hyperplasia
Can you determine the cause or initial pattern of fibrosis in end stage liver disease?
No
Post necrotic scarring
A single event of widespread necrosis (usually centrilobularo r massive) may be followed by fibrosis and condensation of connective tissue stroma resulting in formation of bands of thick connective tissue.
As much as ___ of the liver can be regenerated in a healthy animal.
2/3rds
In order for regeneration to take place in an orderly fashion, the affected area must have an intact _____.
reticulin framework
In chronic liver disease, hepatocellular regeneration is typically ____.
Nodular
Regenerative nodules restore ___ but not ____. Therefore, normal blood flow cannot be _____.
Regenerative nodules restore mass but not function. Therefore, normal blood flow and bile flow cannot be reestablished.
Regeneration may be the result of proliferation of _____ or ______.
Regeneration may be the result of proliferation of mature hepatocytes (enlargement of existing lobules) or hepatocyte stem cells (oval cells).
Bile duct hyperplasia is proliferation of ____ in portal areas.
Bile duct hyperplasia is proliferation of bile ducts in portal areas. (result of a variety of insults to the liver which are usually chronic).
What is a common cause of bile duct hyperplasia?
cholestasis
Focal (multifocal) necrosis
Random necrosis of clusters of hepatocytes due to many different causes (infectious agents: viral, bacterial, inflammation)
Zonal necrosis
follows the zonal pattern of the simple liver lobule
The three zones of zonal necrosis are:
(1) Periportal (zone 1);
(2) Midzonal (Z2);
(3) Centrilobular (Z3)
Extensive zonal change typically produces what kind of liver?
A liver that has an enhanced lobular pattern on capsule and cut surface (pale, enlarged, friable)
What kind of examination is required to determine the specific type of zonal change?
Microscopic examination
Why is centrilobular a common pattern in zonal necrosis?
Because this area is most susceptible to injury (especially from hepatotoxins and circulatory failure) because it has the highest concentration of enzymes (mixed function oxidases) capable of bioactivating some compounds into toxic forms, and it receives the least oxygenated blood increasing the possibility of hypoxic damage.
Centrilobular necoris can result from what two things?
Severe anemia or right sided heart failure
Zonal necrosis - Paracentral zone invovles necrosis of what?
Cellular degeneration involves only a wedge around the central vein because only the periphery of one acinus is affected.
Paracentral zone may result from what two things?
Hypoxia or toxins
Midzonal pattern of zonal necrosis is unusual but may occur in ____ and ___ with aflatoxicosis.
Pigs and horses
Periportal pattern of zonal necrosis is uncommon but may occur following exposure of what? give example
Toxins that do not require metabolism of mixed function oxidases (ex - phosphorus)
Bridging necrosis is the result of _____ (give two examples)
Result of confluence of areas of necrosis. (centrilobular to centrilobular OR centrlobular to portal)
Massive Necrosis is necrosis of?
All hepatocytes in a lobule or contiguous lobules (not necessarily necrosis of entire liver)
Massive necrosis may develop as a result of:
(1) An extreme degree of zonal (centrolobular) necrosis
(2) An acute vascular accident
(3) Be of nutritional origin (ex hepatosis dietetica)
What is hepatosis dietetica?
A vitamin E/selenium responsive disorder in swine which results in centrilobular to massive necrosis and hemorrhage. The pathogenesis is in part related to generation of free radicals. THe toxic effects of free radicals are normally held in check by free-radical scavengers, such as Vitamin E and Selenium.
Portal hypertension - increased portal venous pressure can have a number of causes, list a few:
Chronic liver disease, obstruction of the portal vein, hepatic vein or post cava, and congestive heart failure
Intrahepatic portal hypertension is increased resistance to blood flow within _____.
sinusoids
What is the most common cause of intrahepatic portal hypertension?
Chronic fibrosis (end stage liver disease or Cirrhosis)
Extrahepatic portal hypertension is post-hepatic and the most common cause is?
Right sided heart failure (thrombosis of vein and neoplasm also possibilities)
Passive congestion of liver is caused by?
Right sided heart failure increases the pressure within the caudal vena cava (extends to the hepatic vein)
Passive congestion - effects on liver
Differ with duration and severity of congestion. Liver swells and protein rich fluid exudes from the capsular surface forming fibrin strands (early) and fibrous capsular plaques (late) - ascites commonly accompanies such lesions
Persistent hypoxia to liver (aka chronic passive congestion) leads to ….. (4) and what is the end result (2)
(1) Degeneration/necrosis of hepatocytes (centrilobular)
(2) fibrosis around central veins
(3) Dilation of sinusoids in centrilobular areas (red)
(4) Lipidosis of hepatocytes in portal areas (yellow)
Result is accentuated lobular pattern and fibrous thickening of capsule
Portosystemic shunts are caused by?
Anomalous development of the portal vein which allows all or part of the portal blood to bypass the liver.
Portosystemic shunts result in?
Liver atrophy (because of lack of hepatotrophic factors; insulin, glucagon, and amino acids), and hepatic encephalopathy
Which hepatocytes are most susceptible to hypoxia?
Hepatocytes in centrilobular area (receive blood last and is less oxygenated)
Effects of severe anemia on the liver
Often results in centrilobular necrosis of hepatocytes, dilation of sinusoids (accentuated lobular pattern)
Infarctions of the liver is the result of?
Infrequent because of dual blood supply, however torsion of lobe results in infarction
What is telangectiasis and what kind of lesions does it create on the liver?
marked by dilations of sinusoids in areas of hepatocyte loss (variable sized, 1-5 mm in diameter) - creates focal red lesions on the liver
Telangectiasis is common in what animal?
Cattle, also occurs in older cats (uncommon in dogs)
What can telangectiasis be confused with in small animals?
Hemangiosarcoma
Congenital cysts can be found in livers of most species. It is common to see multiple in adult ____.
Cats
Potential origins of congenital cysts (2)
Bile ducts or capsule
Congenital polycystic hepatic disease - multiple cysts can be found in what two organs? And what species is it most common in?
Liver and kidneys - most commoni n the dog
What is tension lipidosis and what two species can it be found in?
Pale areas of parenchyma adjacent to serosal attachment of ligament in horses and cattle
Tension lipidosis is caused by?
Decreased blood supply and accumulation of lipid in hepatocytes
Is tenison lipidosis benign or malignant?
Benign
Capsular fibrosis is? and can be caused by?
Fibrous connective tissue on capsule of liver that can be caused by migrating paraiste
What is the function of the liver in relation to lipids?
Lipids are transported to the liver from adipose tissue as FFAs and from the diet as FFAs or chylomicrons (triglycerides, phospholipids, and proteins). FFAs enter the liver cell, and most are esterified to triglycerides which are complexed with apoproteins to form low density lipoproteins which are an energy source for a variety of tissues.
A liver can produce lipids from what two sources except in ruminants?
Amino acids and glucose (except in ruminants)
The presence of excess lipid within the liver (hepatic lipidosis or fatty liver) occurs when?
Rate of triglyceride accumulation within hepatocytes exceeds the rate of metabolic degradation of triglycerides or their release from the liver (as lipoproteins)
Fatty liver is especially common in what type of animals?
(1) animals with high energy demands (pregnancy, lactation)
2) obese animals on restricted diets (low in carbs and proteins or other factors
What happens to the liver as fat accumulates in it?
Hepatomegaly, becomes more friable, greasy and yellow (sections float in formalin)
Common conditions associated with fatty liver (7)
(1) Ketosis and fatty liver syndrome in cattle
(2) Diabetes mellitus in dog and cat
(3) Idiopathic hepatic lipidosis in cats
(4) Equine hyperlipidemia
(5) Dietary excess
(6) Anoxia (sublethal injury)
(7) toxins
Glucose is stored in hepatocytes as?
glycogen
How does glucocorticoid induced hepatocellular degeneration cause glycogen accumulation in the liver?
Glucocorticoids induce glycogen synthetase and enhance hepatic storage of glycogen
Amyloid is proteins composed of?
beta-pleated sheets
Where is amyloid deposited in the liver and what does it impair?
Deposited in space of disse and impairs access of plasma to hepatocytes
Can amyloid deposits produce hepatomegaly?
Yes
Secondary amyloidosis occurs as a consequence of what?
prolonged inflammation
Serum amyloid associated protein which is synthesized by the liver is the precursor to what?
amyloid associated fibrils
Familial amyloidosis occurs in what breeds (2) of cats and what breed of dogs?
Abyssinian and Siamese cats; and Shar-pei dogs
Hepatitis is?
Inflammation of liver
Cholangitis is?
Inflammation of bile ducts (can be intrahepatic or extrahepatic)
Cholangiohepatitis is?
Inflammation that affects bile ducts AND adjacent hepatic parenchyma
Portal hepatitis is?
Inflammation in portal areas
What is the most common route of infection of the liver?
Hematogenous
What are the three routes of infections of liver?
(1) Hematogenous (most common)
(2) ascending via biliary system (less common)
(3) Direct penetration (less common)
Nature and distribution of inflammatory lesions resulting from pathogens is dictated by (3)
Agent, route of entry, predilection for particular cell type
Hematogenous route of infection with viral, bacterial, fungal, or protozoal pathogens usually cause random ____ distributed lesions in the liver.
Multifocal
Ascending route of infection via biliary system are usually caused by what pathogen and cause?
Usually bacterial; cause cholangitis and cholangiohepatitis
Acute hepatitis is often characterized initially by the presence of?
Presence of neutrophils followed by lymphocytes and macrophages
Which pathogens usually stimulate inflammation (including neutrophils)?
Bacterial and protozoal pathogens
Viral infections result in necrosis with ____ inflammation (except macrophages).
Minimal
Toxins cause necrosis with ___ inflammation, except macrophages that remove necrotic cell debris.
minimal
Chronic inflammation of the liver - if pathogen persists, may result in _____ inflammation
Granulomatous
Granulomatous inflammation is characterized by?
Macrophages, neutrophils, lymphocytes, fibrous connective tissue
Common bacterial agents that cause granulomatous inflammation (3)
Salmonella, Mycobacteria, Hitosplasma
Determination of type of inflammation requires _____ examination.
Microscopic
Do focal lesions always alter hepatic function?
No, focal lesions may not alter hepatic function. However, widespread lesions may result in end stage liver.
