Liver Metabolic Function

Question 1

describe the functional unit of the liver

Answer 1

liver lobule
hexagonal shape with portal triads at corners
central vein in middle
hepatocytes and sinusoid endothelial cells fill most space

Question 2

what are hepatic acinus zones?

Answer 2

3 liver regions varying based on arterial supply
(1 = most, 3 = least)

Question 3

what are the functions of the acinus zones?

Answer 3

1 (periportal zone) - respiaratory chain, TCA cycle, gluconeogenesis, urea synthesis, bile production/excretion
2 - ammonia detox
3 (perivenular zone) - glycolysis, glutamine synthesis, xenobiotic metabolism

Question 4

describe glycolysis

Answer 4

glucose -> pyruvate or lactate
free energy forms high energy ATP and NADH
10 steps (enzyme catalysed)
pyruvate becomes intermediate in TCA cycle (or converted to acetyl CoA)
stimulated by insulin

Question 5

describe gluconeogenesis

Answer 5

hepatocytes synthesise glucose from non carbohydrate sources (lactate/glycerol,AAs)
stimulated during fasting by hormones (glucagon, GH, cortisol)

Question 6

describe glycogen storage and breakdown

Answer 6

high glucose levels stimulate insulin secretion (beta-cells of pancreas)
promotes glucose uptake by hepatocyes and stored as glycogen
a fall in glucose levels stimulates glucagon to release glycogen from hepatocytes
(exercise = adrenaline stimulated glycogenolysis)

Question 7

describe glycogenolysis

Answer 7

breakdown of glycogen to glucose-1-phosphate + glycogen
glycogen removed by phosphorolysis (glycogen phosphorylase)
G1P converted to G6P by phosphoglucomutase
G6P can enter glycolysis

Question 8

describe lipogenesis

Answer 8

hepatocytes synthesise lipids (triglycerides) from glucose/AAs
excess carbs/protein/fat converted to triglycerides and stores in adipose

Question 9

describe lipolysis

Answer 9

fatty acids derived from triglycerides to produce ATP (split into glycerol and fatty acids)
lipolysis catalysed by lipases
enhanced by adrenaline/noradrenaline during increased sympathetic tone (exercise)
inhibited by insulin

Question 10

what is the result of lipolysis?

Answer 10

glycerol and fatty acids
glycerol - glycolysis/gluconeogenesis pathway or glucose/pyruvate depending on ATP
fatty acids - beta oxidation producing acetyl CoA (then TCA cycle)

Question 11

describe lipoproteins

Answer 11

most lipids are non polar
made water soluble combining them with proteins
(transport vehicle for cell services)

Question 12

describe ketogenesis

Answer 12

in starvation, liver converts fatty acid to ketone bodies (acetoacetate/b-hydroxybutyrate)
they’re released into blood for CNS/muscle utilisation
switch regulated by malonyl CoA (high in conc. after a meal, low in starvation)

Question 13

describe protein metabolism

Answer 13

all cells of body
catalysed by proteases
liver important (stores most protein, rapid synthesis/degredation of tissues and AAs, 90% of protein production)

Question 14

explain protein digestion

Answer 14

proteins -> peptides -> AAs
not stored for future use
AAs oxidised for ATP or used by body for growth/repair
excess AAsconverted to glucose (gluconeogenesis) or lipids (lipogenesis)

Question 15

explain protein anabolism

Answer 15

complete protein - contains adequate amounts of all essential AAs
non-essential AAs produced through transamination

Question 16

explain protein catabolism

Answer 16

proteins from worn out cells (RBCs) broken down into AAs
hepatocytes convert AAs into fatty acids, ketone bodies or glucose
AAs oxidised to produce ATP (after deamination/amine group removal)

Question 17

explain AA deamination

Answer 17

occurs in hepatocytes
produces nitrogen containing amine groups (NH2)
ammonia = highly toxic and alters plasma acid-base balance (converted to urea by liver)

Question 18

what are the contents of bile?

Answer 18

bile salts (processes fat in SI)
bile pigments
cholesterol
lecithin
mucus

Question 19

what do ductal epithelial cells do?

Answer 19

add watery, bicarbonate rich fluid to bile

Question 20

explain the secretion of bile

Answer 20

bile salts transported to liver in enterohepatic circulation and enters via Na-dependent organic anion transporter
transported into bile calaliculi by active bile salt export pump
bile canaliculi epithelium transport Na and bicarb into lumen (with water)
stimulated by secretin, glucagon, gastrin

Question 21

explain bile acid independent secretion

Answer 21

secretion of water/electrolytes by hepatocytes/ductal epithelial cells
Na/bicarb actively secreted into bile ducts (passive water/chloride movement)

Question 22

explain bile salt recycling

Answer 22

95% recycled
reabsorbed into portal circulation in terminal ileum
many unaltered/reused
some unconjugated and require reconjugation
remainder - secondary bile salts (excreted in faeces)

Question 23

explain bile secretion regulation

Answer 23

main regulator - enterohepatic circulation
increased return increases bile production following meal
fluid protection by ductal epithelial cells enhanced by secretin (gastrin/glucagon slightly)

Question 24

explain the excretory role of bile

Answer 24

bile pigments - haem excretory products (0.2% of bile composition)
main component is bilirubin
excretes some drugs (morphine/rifampicin)
excess cholesterol excreted in bile

Question 25

what can liver metabolic reactions be disturbed by?

Answer 25

congenital enzyme deficiency
nutritional deficiency/excess
toxic/chemical damage to organelles
hypoxic/ischaemic insult
secondary to metabolic disease effects

Question 26

describe the inherited diseases of metabolic dysfunction

Answer 26

essential product deficit (G6P)

precursor accumulation (OTC deficiency, inadequate protein metabolism) = hyperammonaemia

alternative pathway activation (amino-acidopathy)

Question 27

how can mitochondrial damage lead to metabolic dysfunction?

Answer 27

b-oxidation of fatty acids inhibition (micro0vesicular steatosis)
oxidative phosphorylation interference (insufficient ATP)
resp chain impairment (excess ROS, lipid peroxidation)
increase in permeability transition (apoptosis)

Question 28

what kinds of toxic damage can the liver get?

Answer 28

mitochondrial damage (antibacterial/viral drugs)
endothelial damage to hepatic veins (cytotoxic drugs)
glutathione depletion/cell death (paracetamol, hypoxic ischaemia)

Question 29

what are the pathological manifestations of metabolic liver disease?

Answer 29

no structural abnormality, severe functional disturbance
hepatocyte injury (apoptosis, necrosis, cirrhosis, tumours)
lipid/glycogen storage manifesting as hepatomegaly

Question 30

what are the common symptoms of metabolic disease in the liver?

Answer 30

newborn acute metabolic crisis (mimics sepsis)
severe vomiting
failure to thrive
recurrent encephalopathy (acidosis)
progressive seizures/disability (hepatomegaly)

Question 31

explain reye-like syndrome

Answer 31

usually neonatal - age 3
26 possible inherited metabolic disorders
episodic vomiting since neonate, growth issues, family history of metabolic disease
caused by stress (infection/fasting)
present with progressive encephalopathy, multisystem failure, acidosis
caused by mitochondrial dysfunction