Overview of liver structure and

function
&
Assessment of liver function
Lynn Rowbottom
Department of Clinical Biochemistry & Metabolic Medicine
Royal Liverpool & Broadgreen University Hospitals Trust
22g/kg body weight
70kg man=1.5kg
Blood supply to liver
Via hepatic vein
which drains into inferior vena cava
Blood from liver
2/3 from portal vein (i.e from gut =
nutrients/substances for metabolism)
1/3 from hepatic artery (supplies O
2
)
Liver lobule
Liver acini functional unit
Major functions of the liver
Carbohydrate metabolism
Fat metabolism
Protein metabolism
Hormone metabolism
Drug/toxin metabolism & excretion
Storage
Metabolism and excretion of bilirubin
Synthesis of proteins

Carbohydrate metabolism
Glycogenesis
Excess glucose glycogen
Glycogenolysis
Glycogen glucose
Gluconeogenesis
Amino acids/lactate/glycerol glucose
Fat metabolism
Triglyceride oxidation energy
Lipoprotein synthesis
Excess carbohydrate & fat fatty acids &
trigs stored in adipose tissue
Cholesterol (& phospholipid) synthesis &
excretion

Protein metabolism
Deamination and transamination of amino
acids
Non-nitrogenous part glucose or lipid
Nitrogenous part ammonia urea
Hormone metabolism
Insulin-like Growth Factor-1 (IGF-1)
Angiotensinogen
Thrombopoeitin
Hepcidin
Drug/toxin metabolism
Phase I reactions: Intro/unmask functional group
Oxidation (Cytochrome P450)
Reduction
Hydrolysis
Phase II reactions:
Glucuronide/Acetyl/Methyl
Glutathione
Glycine/Sulphate
Usually necessary to achieve renal excretion
Storage
Glycogen
Vitamins A, D & B12
Iron & Copper
Metabolism & Excretion of Bilirubin
Senescent
red cells
(80%)
Haem
Biliverdin
Bilirubin
Bilirubin glucuronide
(H
2
O sol)
Haem proteins
(15%)
Ineffective
erthyropoiesis
(5%)
Renal
excretion
Biliary
excretion
Synthesis of proteins
Plasma protein synthesis
Albumin
Fibrinogen/Prothrombin (& other clotting
factors)
Lipoproteins/Caeruloplasmin/Transferrin/
CRP/1AT/FP/

Synthesis of non-essential amino acids
Assessment of liver function
Clinical assessment
Imaging - level of expertise
Biopsy invasive & level of expertise
Time to prep and stain histology slide
Analysis & interpretation
Biochemical tests
Blood (plasma/serum) & urine

Clinical signs associated with liver
disease
Dupuytrens contracture
Palmar erthyema
Spider Naevi
Male gynaecomastia
Ascites
Jaundice
Clinical signs associated with liver
disease
Oesophageal varices
PALE STOOLS &
DARK URINE
Hepatic encephalopathy
The Liver Function Test (LFT)
Albumin
Total Protein
Bilirubin
Alkaline Phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Gamma glutamyl transferase (GGT)
What does the LFT actual show?
Albumin
Crude indicator of synthetic capacity of liver
Liver synthesises 12g albumin per day
Half-life ~20 days
Maintains plasma oncotic pressure
Binds several hormones, drugs, anions and
fatty acids
Decreases in the acute phase response
(APR)
Total Protein
Very little utility in liver function assessment
Reflects balance between synthesis &
degradation
Often allows calculation of globulin fraction
Globulin = Total Protein - Albumin
Bilirubin
Total Bilirubin
Direct/Conjugated Bilirubin
Differentiate between intra-hepatic and extra
obstruction
Intrahepatic
E.g Liver metastases, Hepatitis
Extrahepatic
E.g Gall stones,
carcinoma of head of pancreas
Alkaline Phosphatase
Maximum activity in pH 9-10.5
Removes phosphate from molecules incl
proteins & nucleic acids
Isoenzymes (Liver, Bone, Intestinal &
Placenta)
Age dependent reference range
Liver: sinusoids & endothelium of central &
periportal veins

Alanine aminotransferase
Catalyses transfer of amino group from
alanine residues
Present in wide range/All tissues
Cytosolic

Aspartate aminotransferase
Catalyses transfer of amino group from
aspartate residues
Present in wide range/All tissues
Cytosolic and mitochondrial
High levels in heart, liver, skeletal muscle,
kidney, lung & red blood cells.
Also found in significant amounts in brain,
gastric mucosa & adipose tissue
Gamma glutamyl transferase
Catalyses transfer of gamma glutamyl group
from peptides to appropriate acceptors
Located in cell membrane of various tissues;
mainly kidney, liver, biliary tract & pancreas
Found in hepatocytes & biliary epithelial cells
Kidney contains largest amount but is not
released into plasma

The LFT
Pattern rather than single analyte result
Abnormal LFT not just in primary hepatic
disorders
Heart failure
Sepsis
Infection/inflammation
Bilirubin
Jaundice
Visible at ~3XULN (50mol/L)
*Unconjugated bilirubin crosses blood-brain barrier
in neonates= brain damage kernicterus*
Conjugated
Bilirubin
Water soluble
Filtered at the glomerulus
Hence reaches the urine=
bilirubinuria
Pathological
Intra or extra hepatic
obstruction

Unconjugated
Bilirubin
Not water soluble=protein bound
Not filtered at the glomerulus
Hence does not reach the urine
Haemolytic states
Gilberts (inherited defect in
UDP glucuronyl transferase)
Mixed: Hepatocellular diseases
Direct:Total
20-40%
>50% <20%
Gilberts, Haemolysis
Hepatocellular Disease
Extrahepatic obstruction
Urobilinogen
When bilirubin reaches the gut
Converted to urobilinogen by gut bacteria
Gets absorbed from the small intestine
Excreted in the urine

If urobilinogen present in urine, shows that
bilirubin is reaching the gut
High plasma bilirubin & No urobilinogen in urine
= bilirubin is not reaching the gut (cholestasis)
Bilirubin & Urobilinogen
ALP
Secreted by cells lining biliary tract
Enhanced synthesis/inducible enzyme
Raised in bone disease (osteoblast
activity)
Raised during growth, pregnancy (different
reference ranges apply)
ALP electrophoresis to determine source
GGT
Indicator of obstruction
(intrahepatic/biliary)
Enhanced synthesis/inducible enzyme
Alcohol & anticonvulsants
Useful in conjunction with ALP
e.g ALP - ?liver/bone/other
ALP & GGT suggests hepatic cause
GGT & N ALP alcohol intake
ALT & AST
Indicators of hepatocellular damage
ALT more specific for liver than AST
AST 80% mitochondrial, 20% cytosolic
High AST also seen in MI, muscle injury & CCF

ALT:AST ratio
ALT:AST <2
ALD
Cirrhosis
Metastatic liver
disease
ALT:AST >2
Viral hepatitis
Infectious hepatitis
Drugs/toxins
NASH
Intra/extrahepatic
obstruction
LFT at RLUH
Analyte Ref range
Albumin 35-50 g/L
Total Protein 60-80 g/L
Globulin 19-35 g/L
Total Bilirubin 2-17 mol/L
ALP 35-125 U/L
ALT <35 U/L
GGT <35 (female)
<50 U/L (male)
AST <45 U/L
Direct Bilirubin 1-6 mol/L by request
Other tests
Prothrombin
Clotting
Alphafetoprotein (AFP)
Raised in liver disease (hep, cirrhosis, biliary tract obstruction, ALD)
Tumour marker (liver, germ cell tumours, pregnancy)
Alpha-1 antitrypsin (1AT)
Protease inhibitor. Deficiency can produce cirrhosis
Raised in APR= may mask deficiency
Caeruloplasmin
Copper transport protein (low in liver disease/Wilsons)
Bile acids
Cholestasis in pregnancy
N-terminal pro-collagen 3 peptide (P3NP)
Marker of fibrosis (esp dermatology patients Rx methotrexate)
Immunoglobulins
IgG : immune hepatitis, IgA : ?alcohol, IgM : PBC
Ferritin
Function tests
BSP clearance
Indocyanine green
14C aminopyrine breath test
Ammonia
Further investigations
Ultrasound/CT/MRI/PET imaging
Endoscopic retrograde
cholangiopancreatography (ERCP)
Percutaneous Transhepatic
Cholangiography (PTC)
Liver biopsy

Coming next time..
Common liver/GI disorders
Presentation & management
Cases
Thank you for listening!
Any questions?