Liver histopathology Flashcards
What structures do hepatic portal triads contain?
hepatic artery
portal vein
bile duct
(+ lymphatics + nerves)
Why do hepatic artery branches run close to the bile ducts in the portal triads?
They become a capillary network
which provide nutrients and O2
which nourish the ducts, terminal hepatic venules and sinusoids
What is the function of the hepatic veins?
They carry away blood which contains proteins such as albumin, clotting factors, lipoproteins
These are secreted into the blood by the liver
What do the portal veins provide?
They bring blood in from the capillary beds in the small intestine, where newly absorbed nutrients have entered the blood stream
This blood is cleaned by Kupffer cells, which remove any debris or bacteria by phagocytosis
What do bile ducts carry and to where?
They carry bile out of the liver into the gut via the Ampulla of Vater
Bile contains bile salts and cholesterol, and is used for fat emulsification and absorption in the gut
Bile salts are reabsorbed in the ileum and enter enterohepatic circulation
What connective tissue structures encase the portal triad?
A sheath known as the LIMITING PLATE encases the portal triads
This separates the triads from the liver parenchyma
And provides support to the enclosed structure
What kind of damage is the liver parenchyma susceptible to?
Inflammation: can be caused by either infective (e.g. viral hepatitis) or non-infective toxic agents (e.g. alcohol)
Fat accumulation: either in alcoholics or obesity +/- metabolic syndrome and NAFLD etc
Other direct or indirect injury to the liver parenchyma
What damage is the portal vein susceptible to?
Sepsis at the liver hilum
Thrombosis
Cirrhosis and fibrosis can cause obstructions
What kind of damage can occur at the hepatic arteries?
vasculitis
thrombosis
these can both impair nutrition of the bile ducts and surrounding structures
What kind of damage can occur at the sinusoids?
Cirrhosis can cause obstruction
RBC sickling can cause obstruction or thrombosis
swelling from toxins such as chemo
What damage are the hepatic veins susceptible to?
cardiac failure can cause back pressure into the IVC and hepatic veins
this can cause damage and hepatomegaly
What damage are the bile ducts susceptible to?
obstruction: by gallstones liable to secondary infection e.g. cholangitis Liver flukes (found in SE asia) may ascend into bile ducts from the gut
What are the 2 main ways of looking at the functional units of the liver?
Acinar concept: liver in terms of blood flow. More abstract concept but more relevant for histopath
Classical liver lobule: hepatic venule in the middle of a liver lobule which drains several portal tracts. Similar to how liver looks down microscope
What is the ‘classical liver lobule’ concept of liver structure?
hexagon structure (=lobule) with a portal triad/tract at each corner of the shape
The centre of the lobule contains the terminal hepatic venule
Sinusoids carrying blood and canniculi carrying bile lie adjacently and join the centre of the hexagon/lobule with the portal triad periphery
Blood travels from the portal tract to the terminal venule
Bile however travels in the retrograde direction from the terminal venule to the bile duct in the portal triad
What is the space of Disse?
It is the space between the sinusoids and the liver cells/parenchyma
This space contains Ito cells
What is the function of Ito cells?
Also known as hepatic stellate cells or perisinusoidal cells
Normally the cells are in a quiescent state
they become activated when the liver is damaged
They then proliferate and make ECM. They then also secrete collagen used in scar formation following injury
Where are the bile canniculae in the liver located?
Located between adjacent hepatocytes
These then drain into the canal of Hering
Which then drain into bile ducts
What is the ultrastructure of the lobule sinusoid?
carries blood between hepatic venule and portal triads
lined by fenestrated epithelium: allows plasma flow from the portal blood. Between the sinusoid and space of Disse
This means that the hepatocytes are bathed in nutrient rich plasma
Plasma collecting in space of Disse will flow back into the portal tracts and then go on to form the body’s lymph fluid
Kupffer cells are also located in the sinusoid
What is the function of the Kupffer cells?
Tissue fixed macrophages = APCs
Located in the sinusoids
They phagocytose bacteria and debris
Especially in portal blood coming from the small intestine
Also secretion of inflammatory and immune mediators
What is the Acinar concept of the liver lobule?
More abstract, looks at liver in terms of blood flow
blood enters: hepatic artery + portal vein
Liver acinus: zone 1 (most oxygenated cells), zone 2, zone 3 (least oxygenated, closest to the hepatic venule)
Deoxygenated blood leaves via the hepatic venule which becomes the hepatic vein (drains into IVC)
Which zone of the liver acinus is most susceptible to damage?
Zone 3 as it is closest to the terminal venule and is in the most deoxygenated zone
In addition, any back pressures in the hepatic vein (e.g. from cardiac failure) will affect zone 3 structures first
May also be damaged by drug toxicity or fat accumulation
Why are zone 3 cells in the liver acinus most susceptible to drug toxicity?
Zone 3 hepatocytes perform the detoxification of many drugs and metabolites
Hence there is a high [CYP] enzyme in these cells
The secondary by-products of these reactions are therefore at their highest amounts in zone 3 and can cause most damage here
e.g NAPQI from paracetamol metabolism
What is the limiting plate in a lobule?
This is the connective tissue structure that contains the portal triad
It provides structure, support and separation from the liver parenchyma
