Liver Flashcards
what is the diaphragmatic surface
anterolateral = contains bare area
what is the visceral surface
posteroinferior = covered with peritoneum, except gallbladder/porta hepatis
what is the bare area of the liver
large triangular area on diaphragmatic surface = no peritoneum
what is the falciform ligament
double fold of peritoneum = forms a natural anatomical division of right/left lobe of liver and attaches liver to diaphragm
what is the ligamentum teres
free edge of falciform ligament = remnant of umbilical vein
what are the coronary ligaments
attach the superior surface of liver to posterior diaphragm = anterior/posterior
what are the triangular ligaments
left = union of anterior/posterior layers of coronary ligament at apex of liver = left lobe to diaphragm right = attaches right lobe to diaphragm
what is the functional division of the liver
line down gall bladder/ivc
what is the porta hepatis
point of entry into liver for hepatic arteries and portal vein/exit for hepatic ducts
where is calot’s triangle
at porta hepatis
what are the contents of calot’s triangle
right hepatic artery
cystic artery
lymph node of Lund
lymphatics
what is the liver’s fibroud layer known as
glisson’s capsule
what supplies blood to the liver
25% hepatic artery proper from coeliac trunk to non-parenchymal structures
75% hepatic portal vein
wha tdoes the hepatic portal vein supply the liver with
partially deoxy blood + nutrients from small intestine to liver parenchyma = allows detoxification
what does the portal triad contain
proper hepatic arterioles
hepatic portal venules
bile ducts
what are the structural units of the liver
lobules
what are the functional units of the liver
acini
what are acini
divided into zones according to distance form arteriole blood supply = hepatocytes closest better oxygenated
what is the nerve supply to the liver
parenchyma = hepatic plexus = sympathetic (coeliac plexus) and parasympathetic (vagus)
what is the nerve supply to glisson’s capsule
lower intercostal nerves
with what organs does the pancreas have anatomical relations
stomach duodenum transverse mesocolon common bile duct spleen
what vessels is the pancreas associated with
aorta/IVC posteriorly
superior mesenteric artery behind neck
hepatic portal vein behind neck
splenic artery travels superior border
describe the duct system of the pancreas
acini connected by intercalated ducts = unite into lobules = drain into intralobular collecting ducts = become main pancreatic duct
what forms the hepatopancreatic ampulla of vater
pancreatic duct unites with common bile duct
what is Hartmann’s pouch
mucosal fold in neck of gallbladder = common site for gallstone lodging
what supplies blood to the gallbladder
cystic artery
what is the venous drainage of the gallbladder
cystic veins to portalto portal vein
what structures are found in the porta hepatis
portal vein
r/l hepatic artery
r/l hepatic duct
microscopically = lymphatics/vagus nerve branches/greater splanchnic nerves branches
where is the bare area of the liver
under central tendon of right side of diaphragm
what is the surface marking of the fundus of the gall bladder
tip of 9th costal cartilage
where midclavicular line crosses costal margin
what degenerates to become ligamentum venosum
ductus venosus
what innervates the gall bladder
coeliac plexus = sympathetic and sensory fibres
vagus nerve = parasympathetic innervation
where would disease of gall bladder be felt
rubbing on diaphragm so pain carried by c3,4,5 = right shoulder
where do hepatic veins drain
IVC
which fat soluble vitamins are stored in the liver
KADE
what substances are stored in the liver
iron
glycogen
minerals
fat soluble vitamins
where is iron used
haemoglobin
myoglobin
bone marrow
name 4 sources of iron
meat
liver
egg yolk
shell fish
how much of ingested iron is absorbed in duodenum
about 10% = changes according to needs
what is ferritin
protein-iron complex acting as intracellular store for iron in kupffer cells in liver
how does iron travel in the blood
bound to transferrin
what cells in the liver store iron
kupffer cells
what 2 things occur when body has reached iron capacity
- increased free iron in plasma/intestinal epithelial cells = increased ferritin production = increased iron binding and therefore reduce amount released into blood
- hepatocytes release hepcidin = inhibits ferroportin so reduce amount of iron in blood
what occurs when iron is absorbed
- actively transported into duodenal enterocytes
- then incorporated into ferritin and stored intracellularly
- most bound to ferritin = released back to lumen and excreted in faeces
- absorbed iron not bound to ferritin = released into blood via ferroportin then bind with transferrin
- iron bound to transferrin = to liver
what occurs when iron stores are low
production of intestinal ferritin decreases = decrease amount of iron bound to ferritin = increase free iron released into blood
what is the most abundant plasma protein
albumin
what are the functions of albumin
- binding/transport of large, hydrophobic compounds = bilirubin/FA/hormones/drugs
- maintenance of colloid osmotic pressure
what is colloid osmotic pressure
effective osmotic pressure across blood vessel walls permeable to electrolytes but not large molecules = almost entirely due to plasma proteins
how does albumin maintain the osmotic pressure of the blood
presence in blood = water conc is lower than in interstitial fluid = net flow of wate rout of interstitial fluid into blood plasma
what are the 4 starling forces
- capillary hydrostatic pressure = fluid out of cap
- interstitial hydrostatic pressure = fluid into cap
- osmotic force due to plasma protein conc = fluid into cap
- osmotic force due to interstitial fluid protein conc = fluid out of cap
what occurs to fluid at the arterial end of capillarires
interstitial fluid has high conc of proteins bc fluid loss to lymphatics so has higher osmotic pressure = bulk fluid filtration out of capillaries into interstitial fluid
what occurs to fluid at venous end of capillaries
capillary hydrostatic pressure decrease die to resistance of blood flow but all other starling forces same = bulk fluid absorption into capillaries
what causes a decrease in albumin
decreased synthesis decreased catabolism increased loss = haemorrhage liver failure nephrotic syndrome = albumin filtered into urine burns
what is hypoalbuminaemia
decrease of albumin in blood = caused by liver failure = leads to oedema because decreases capillary oncotic pressure
what are globulins
work as antibodies = alpha/beta made in liver
what is the role of the liver in producing clotting factors
produces all except calcium (IV) and vWF (VIII)
produces bile salts essential for vitamin K absorption
what is the role of vitamin K
essential for synthesis of clotting factors 10, 9, 7 ,2 = 1972
what are complement factors
= plasma protein
sticks to pathogens = mark for neutrophils for killing
what water soluble vitamin is stored in the liver
B12
what are xenobiotics
foreign chemical substance not normally found of produced in body which cannot be used for energy requirements = DRUGS
= absorbed across lungs/skin/ingested
= excreted in bile/urine/sweat/breath
describe pharmacologically active compounds
lipophilic = can pass through memranes
non-ionised at pH 7.4
bound to plasma proteins to be transported in blood
what are microsomal enzymes
enzymes found in small particles consisting of piece of endoplasmic reticulum to which ribosomes are attached
where are microsomal enzymes found
on smooth endoplasmic reticulum mostly in liver hepatocytes
where are non-microsomal enzymes found
cytoplasm/mitochondria of hepatocytes in the liver (+ other tissues)
what processes are microsomal enzymes involved in
oxidative, reductive, hydrolytic
mainly phase 1 reactions = biotransform substances
can be involved in phase 2 = glucuronidation
what are microsomal enzymes induced/inhibited
drugs food age bacteria alcohol
what processes are non-microsomal enzymes involved in
non-specific = can be phase1 or 2
involved in all conjugation reactions
NOT in glucuronidation
what is the aim of liver detoxification
to transform a drug into less toxic/more water soluble so can be excreted
what is the aim of phase 1 reactions
make substance more hydrophilic by adding/exposing a hydroxyl group
give 3 examples of non-synthetic catabolic reactions
oxidation
reduction
hydrolysis
= introduce reactive group to drug ready for conjugation
give 4 examples of oxidation of drugs
hydroxilation = adding OH
dealkylation = remove CH side chains
deamination = remove NH
hydrogen removal
what occurs in hydrolysis
split amide and ester bond
what occurs in reduction
addition of a hydrogen
what is functionalisation
introducing reactive group to drug/adding/exposing oH, SH, NH2, COOH
= occurs mainly in liver catalysed by cytochrome P450 enzyme
what are cytochrome P450 enzymes
microsomal
in phase 1
uses haem group to oxidise substances = products are more water soluble
what is the overall reaction for phase 1 reactions
NADPH + H+ + O2 + RH = NADP+ + H2O + R-OH
give 2 examples of non-microsomal enzymes used in phase 1 reactions
alcohol dehydrogenase
aldehyde dehydrogenase
what are the outcomes of phase 1 reactions (4)
- inactivate drugs
- further activate drug
- activate drug from pro-drug
- make drug into reactive intermediate
what are phase 2 reactions
synthetic anabolic reactions
= conjugation reactions
what is a conjugation reaction
attachment of substituent groups
usually inactive products
catalysed by transferases
= increase hydrophilicity for renal excretion
what is a glucuronidation reaction
adding glucuronic acid to make more hydrophilic
what enzymes are used in glucuronidation reactions
glucuronosyltransferase (UGT) = microsomal
uridine diphospho-glucuronic acid (UDPGA) = coenzyme for conjugation of glucuronic acid
give an example of an active drug to inactive metabolite
phenobarbital to glucuronides
give an example of an active drug to active metabolite
codein to morphine
give an example of an inactive drug to an active metabolite
loratidine to active drug
give an example of an active drug to a reactive intermediate
paracetamol to NAPQI = toxic
how is paracetamol metabolised
predominantly via phase 2 glucuronic acid/sulphate conjugation
how does paracetamol become toxic
low glucuronic acid/sulphate = undergo phase 1 metabolism via oxidation = NAPQI
= removed by glutathione but if low levels glutathione then = toxic!!
what is the equation for alcohol metabolism
ethanol to acetaldehyde by ADH
acetaldehyde to actetate by ALDH
acetate to CO2 + H2O
what is protein turnover and degradation
continuous degradation and resynthesis of all cellular proteins = variable and reflects usage/demand
when is protein turnover increased
tissue damage
pregnancy
starvation
severe burns
what are the 2 primary methods of protein breakdown
lysosomal
ubiquitin-proteosome pathway
where does lysosomal protein breakdown take place
through sinusoidal endothelial cells to Kupffer cells
describe lysosomal protein degradation through
- soluble proteins from blood through sieve plates of sinusoid
- phagocytosed by kupffer cells
- packeaged into lysosomes in kupffer cells
- lysozymes breakdown proteins
where does the ubiquitin-proteasome pathway take place
cytoplasm of cells
describe protein degradation in the ubiquitin-proteasome pathway
- ubiquitin binds to protein = acts as target for proteosomes
- proteosome encases protein and destroys it
- amino acids can be recycled
where does amino acid degradation/catabolism take place
in hepatocytes in liver
what is amino acid catabolism
nitrogen containing amino group removed to produce nitrogen and carbon skeleton
N = excreted/incorporated into other compounds
C = metabolised/krebs
name the 2 main catabolism processes
oxidative deamination
transamination
what is oxidative deamination (in the glucose alanine cycle)
in liver
alanine to pyruvate gives an amine group to alphaketoglutarate to form glutamate
what is the enzyme used in oxidative deamination
glutamate dehydrogenase
what are the implications of oxidative deamination being a reversible reaction
excess ammonia produced = can cross BBB = react with alphaketoglutarate = decrease ATP = dangerous
what is transamination (in the glucose alanine cycle)
transfer of alpha amino group from glutamate to pyruvate to make alanine
glutamate goes to alphaketoglutarate
what is the enzyme for transamination
alanine aminotransferase
where are the enzymes for the urea cycle found
mitochondria/cytosol of hepatocytes
describe the urea cycle in 3 steps
- arginine to ornithine by arginase with generation of urea
- ornithine to citrulline with addition of ammonia and CO2 (carbomyl phosphate)
- citrulline to arginine with addition of ammonia
what is generated from the urea cycle
urea only (= 2 x ammonia)
what occurs if there are enzyme deficiencies of the urea cycle
leads to higher levels of ammonia in blood
no enzymes = no life
why is ammonia associated with neurotoxicity
able to cross BBB
once inside converted to glutamate (glutamate dehydrogenase) = depletion in alpha-ketoglutarate = oxaloacetate reduces = no krebs cycle = cell damage/death
what does 1 cycle of urea cycle consume
3ATP
4PO4-
how is fat stored
most = adipocytes forming adipose tissue some = in hepatocytes
what are lipids
ester of fatty acids and certain alcohol compounds
name 3 functions of a lipid
energy reserves
structural cell membrane
hormone metabolism
what is the role of lipoproteins
transport cholesterol in blood
what is HDL
high density lipoprotein = formed in liver
removes excess cholesterol from blood/tissue then deliver to liver which secretes as bile/convert to bile salts
what is LDL
low density lipoprotein =
produced by hepatic lipase in hepatocytes
main cholesterol carriers = take to tissues for endocytosis
why is LDL bad
high plasma concentrations associated with increase cholesterol deposition in arterial walls
why is LDL needed
essential in supplying cells with cholesterol needed for steroid hormone synth/plasma membranes
what is VLDL
very low density lipoprotein
synthesised in hepatocytes
transport triglycerides from liver to tissues
how much of the energy used by muscle/liver/kidneys is derived from catabolism of fatty acids
under resting conditions = approx half
what is the function of adipocytes
synthesise/store triglycerides during food uptake
release FA/glycerol into blood when food not being absorbed from small intestine
FA/glycerol in blood for uptake in cells = energy for ATP
describe the 4 step process of fat catabolism
- FA across cell membrane
- bind to coenzyme A by acyl CoA synthetase to form acyl CoA
- acyl CoA through mitochondrial membrane by cartinine shuttle
- in mitochondria = Beta oxidation = 2C removed to repeat cycle and acetyl CoA, NADH, FADH formed for Krebs/oxidative phosphorylation
what is the role of lipoprotein lipase
hydrolyses triglycerides in lipoproteins into 3 x FA and 1 x glycerol
what is the role of hepatic lipase
converts intermediate density lipoprotein into LDL = packaging with more triglycerides to be released into body
where is hepatic lipase found
expressed in liver/adrenal glands
where is bile secreted
in liver by hepatocytes continuously
what is the role of bile
emulsify fats
excretory pathway for most steroid hormones/drugs
where is bile stored
in gall bladder = concentrated bc NaCl/water absorbed into blood
what is the space of disse
space separating hepatocytes and sinusoids
what are hepatic lobules
wedge-like arrangements of hepatocytes around 1 to 2 cells deep surrounded by sinusoids = mixed portal/hepatic artery blood
what are the contents of bile
bile salts - mostly cholesterol and waste products lecithin = phospholipid HCO3- bile pigments trace metals
how is bile stored in the gall bladder
bile salts, cholesterol, lecithin = aggregated to mixed micelles
what cells secrete the components of bile
hepatocytes = bile salts, cholesterol, lecithin, bile pigments
epithelial cells lining bile ducts = most of HCO3- rich solution = stimulated by secretin
describe the production and storage of bile
- bile produced in hepatocytes
- transported in micelles through canaliculi
- actin filaments contract around canaliculi to move bile to hepatic ducts
- hepatic duct to cystic duct to gall bladder
what is the enterohepatic circulation
recycling pathway of bile salts
what happens to bile salts during digestion of a fatty meal
most that enter intestinal tract = absorbed by specific Na+ coupled transporters in terminal ileum
what happens to absorbed bile salts
returned via portal vein to liver
uptake to hepatocytes driven by secondary AT coupled to Na+
then secreted into bile
what occurs to lost bile salts
5% lost in faeces
liver synthesises new bile salts from cholesterol
what occurs to bile in the fasted state
bile synthesised/recirculated in liver
sphincter of Oddi shut
bile diverted back to be stored in gall bladder
what occurs to bile in the fed state
fat stimulates release of CCK
CCK relaxes sphincter of Oddi and contracts gall bladder
stored bile shoots into duodenum
what is CCK
cholycystokinin
describe the role of cholesterol in bile
cholesterol extracted from blood = to liver = secreted into bile
solubility achieved by incorporation into micelle
what is ezetimibe
enzyme which blocks protein-mediated transport of cholesterol across membrane of cells of wall of duodenum
what happens to cholesterol in the digestive system
50% absorbed = bile
50% excreted in faeces
what are bile pigments
substances formed from haem portion of haemoglobin when old/damaged erythrocytes break down in spleen/liver
what is bilirubin
predominant bile pigment which is extracted from blood by hepatocytes and actively secreted into bile
what colour is biliverdin
green
what colour is bilirubin
orange/yellow
what colour is stercobilin
gives faeces brown colour
what colour is urobilin
responsible for yellow of urine
what is jaundice
yellow discolouration of skin caused by high serum bilirubin level
what occurs in pre-hepatic jaundice
increased total bilirubin in blood
increased unconjugated bilirubin bc exceed amount liver can conjugate
enlargement of spleen due to haemolysis
what are the clinical signs of pre-hepatic jaundice
normal faeces
normal urine = unconjugated = insoluble so bound to albumin so dont filter into urine
what occurs in hepatic jaundice
problem with liver itself = cannot take up/conjugate/excrete bilirubin
enlargement of spleen = trying to help liver break down RBCs
all levels bilirubin increase = no conjugation + leaky liver
decreased urine urobilinogen
what are the clinical signs of hepatic jaundice
normal faeces
dark urine = raised conjugated bilirubin but decreased urine urobilinogen
what occurs in post hepatic jaundice
= obstruction
high conjugated bilirubin bc liver is fine
no enlarged spleen
increased urine bilirubin
what are the clinical signs of post hepatic jaundice
pale faeces
dark urine = increased urine urobilinogen as hepatic system still working
name 3 causes of prehepatic jaundice
malaria
sickle cell anaemia
thalassaemia
name 3 causes of hepatic jaundice
liver cirrhosis
liver cancer
drugs
name 3 causes of post hepatic jaundice
gallstones
pancreatic cancer
gall bladder cancer
why do gallstones form
if concentration of cholesterol in bile becomes too high compared to phospholipids/bile salts = cholesterol crystallise out of solution
what blood vessel is closely related to the duodenum
superior gastroduodenal artery runs in close proximity to duodenum
what does the pancreas secrete
HCO3-
digestive enzymes
how do secretions leave the pancreas
secretions arise from acinar tissue = secreted into ducts = converge into pancreatic duct = joins common bile duct = enter duodenum
where is the accessory pancreatic duct
emerges above ampulla of vater in duodenum
what does HCO3- do
secreted by epithelial cells lining ducts = duct cells
protect duodenal mucosa from gastric acid
buffers material entering duodenum to pH suitable for enzymes
what is the production of HCO3- from pancreas stimulated/inhibited by
stimulated by release of secretin produced in small intestine in response to acid in duodenum
secretin also stimulates CCK + inhibits acid secretion/gastric motility of stomach
how is HCO3- secreted into the pancreatic duct lumen
by Cl-/HCO3- exchanger
describe the process of HCO3- secretion from pancreatic ducts (5)
- bicarbonate reaction within cell = H+ + HCO3- produced
- H+ out of basolateral to capillary exchanges for Na+ - H+ to portal vein
- Na+/K+ATPase pumps K+ in and Na+ out = provide energy for secretion of HCO3- (K+ out again)
- Cl- in an apical side i exchange for HCO3- out
- Cl- does not accumulate in cell = leaves via cystic fibrosis transmembrane conductance regulator (CFTR channel)
what types of enzymes are secreted by the pancreas
active or precursors secreted by gland cells at pancreatic end of duct system
what does CCK do
stimulates secretion of digestive enzymes
potentiates action of secretin = stimulate bicarb secretion from pancreas
stimulates contraction of gall bladder/relaxes sphincter of oddi
where and why is CCK secreted
produced in small intestine = in response to presence of amino acids/FA in small intestine
give 2 examples of active enzymes secreted by pancreas
alpha amylase = starch to maltose
lipase = triglycerides to monoglycerides and FA
give 3 examples of enzymes precursors secreted by pancreas
zymogen = trypsinogen to trypsin
= mediated by enterokinsases
= trypsin activates other enzymes = chymotrypsin
what is somatostatin
produced in D cells of pancreatic islets/islets of langerhans
= powerful inhibitor of exocrine secretion
what do the isles of langerhans contain
alpha cells
beta cells
D cells
PP cells
what do alpha cells produce
glucagon
what do beta cells produce
insulin/amylin
what do delta/D cells produce
somatostatin
what do PP cells produce
pancreatic polypeptide
what are the phases of pancreatic secretion
cephalic phase
gastric phase
what occurs in the cephalic phase
initiated by sensory experience of eating/smelling food etc
= parasympathetic vagus nerve stimulation of acinar cells
what occurs in the gastric phase
initiates by presence of food in stomach
= parasympathetic vagus nerve stimulation of acinar cells
what has happened by the end of the cephalic and gastric phases
pancreatic ducts filled with inactive zymogens ready for release with HCO3- via sphincter of Oddi
amino acids/FA in duodenum = CCK released = gallbladder contract = sphnicter relax
what is the hepatic diverticulum
cellular expansion of the foregut which gives rise to the parenchyma of the liver
= appear in middle of 3rd week as outgrowth of endodermal epithelium at distal end of foregut
how does the bile duct form embryologically
forms when connection between liver diverticulum and foregut narrows
how are the gallbladder and cystic duct formed embryologically
small ventral outgrowth developing from bile duct
when does bile production begin
12th week - subside during last 2 months
how is the lesser omentum formed
formed due to rotation of liver and stomach
where does the pancreas develop from
endodermal lining of duodenum as 2 buds = dorsal/ventral
when duodenum rotates to become C shaped = fuse together
how is the main pancreatic duct formed
by union of ventral pancreatic duct with distal part of dorsal bud
how are the islets of langerhans formed
develop from pancreas parenchyma at 3rd month
describe the histology of sinusoids
thin discontinuous fenestrated epithelium
no basement membrane
contain scattered kupffer cells but cannot see this on h&e
describe the order of vessels that carry bile
canaliculi
bile ductules
trabecular ducts
bile ducts
describe the histology of hepatocytes
polyhedral epithelial cells
abundant mitochondria = granular cytoplasm
large central spherical nuclei
may be binucleate
what are the 3 layers of the gall bladder wall
- simple columnar epithelium on bm
- specialised mucosa of loose fibrous connective tissue
- thick muscularis propria
describe the histology of the pancreas
poorly defined fibrous capsule
septa divides glands into acini
pacinian corpuscles
do liver cells replicate
yes because binucleate cells so regeneration capable
what are pacinian corpuscles
onion shaped connective tissue built up around nerve endings = reduce mechanical sensitivity of nerve
describe the histology of acinar cells
pyramidal shape
rich rER basally
zymogen granules apically
single nucleus
do liver cells replicate
yes because binucleate cells so regeneration capable
what are ito cells
in sinusoids
fat storing cells
play role in FA regeneration
what cells produce kupffer cells
circulating macrophages derived from monocytes
what is the role of insulin in the liver
liver stores glycogen
insulin promotes conversion of excess glucose to glycogen
glycogen can be broken down and released as glucose in response to glucagon
how is iron stored in the liver
transferrin in hepatocytes
ferritin in kupffer cells
what are the consequences of high fatty acid beta-oxidation
too much acetyl CoA produced = too much for Krebs = increased ketogenesis = results in acetone and hydroxybutyrate
how is high beta oxidation regulated
high levels of glycerol-3-phosphate indicate high levels beta oxidation = insulin released to inhibit (glucagon stimulates beta oxidation)
what 2 ways can ketoacidosis occur
diabetic = not enough insulin alcohol = high glucagon
