Path: Liver 1 - Structure, Function, Dysfunction (i)

Liver disease

increasing reason for morbidity/mortality

less common than heart disease, cancer, stroke

managed by gastroenterologists (some specialised as hepatologists)

surgeons

gall stones

pancreatitis

sometimes extra hepatic billiary tract disease

GPs: abnormal LFTs

different patterns depending on where in world you are

cirrhosis

alcohol

chronic viral disease (HBV)

tumour

liver mets

pancreatic cancer

primary HCC

Causes of liver damage

alcohol

NAFLD: a/w metabolic syndome (type 2 insulin resistant DM, obesity, etc)

viruses (acute +/- chronic in some) Hep A,B,C,D,E

Drugs (e.g. MTX)

inherited metabolic disorders

HFE hereditary haemochromatosis

Wilson's

A1AT deficieny

vasc

congestion

ischaemia

chronic biliary disease (injury to liver from retained bile salts)

different causes of injury may interact

Structure

1.5 kg

large functional reserve

can take a lot of damage

up to 1/2 can regenerate after acute damage

stable cell pop

capable of regeneration, but usually don't unless damaged

limited repertoire of response/patterns to acute + chronic injury

dual blood supply

1/4 from hep art

3/4 from hep portal vein

GIT -> spleen -> liver for detoxification

blood flows into sinusoids (blood spaces between hepatocytes)

lined by fenestrated epithelium (allows hepatocytes to efficiently detoxify blood) + macrophages (Kupffer cells)

Space of Disse between hepatocytes + sinusoids contains hepatic stellate cells (aka perisinusoidal or Ito cells, in quiescent state, inactive, involved in fibrosis/scar tissue formation)

venous drainage: portal tracts (triads of smallest branches of hep artery, bile duct + portal vein) -> sinusoids -> central venules -> hep vein -> IVC -> right ventricle

sharp interface between portal tract + surrounding parenchyma

importance of hx, exam (least helpful with liver) + tests

Bile drainage

formed by hepatocytes

secreted into bile canaliculi (tubes) between hepatocytes

small ductules form from canaliculi, which join to for small ducts in portal tracts

left + right hep duct = common hep duct

common hep duct joined by cystic duct (from gallbladder) = CBD

in 75%, pancreatic duct joins CBD @ ampulla of vater (entrance to SI)

if blockage occurs can also cause acute pancreatitis

GB stores bile only + releases it in response to hormones (can survive without it)

Acinus

functional unit of liver

zone 1: encircled portal tracts (oxgenated blood from hep arts)

zone 2: between 1 and 3

zone 3: around central veins (poor oxygenation)

zones explain patterns of damage/fibrosis (e.g. ischaemic/toxic injury most severe in zone 3)

under microscopy: light parts = sinusoids, dark parts = parenchyma

Liver function

synthesis of most plasma proteins

albumin

clotting factors

bile formation

bilirubin excretion

bile salt digestion

fat-soluble vits ADEK needed

detoxification of endogenous/exogenous compounds

intermediary metabolism

alteration +/or storage of vits, mins, glycogen (+ abnormally copper, iron, fat)

immune

detect, capture + clear bacteria, viruses, macromolecules

large collection of phagocytic cells

buffer between gut + rest of body

haematopoiesis in foetal infant, before BM takes over