Structure and Function of the Liver Flashcards
What is the Blood Supply for Liver?
Dual blood supply:
- 2/3 from Portal Vein which drains from the gut. Everything from the gut comes straight to the liver
- Remainder from the Hepatic Artery
What makes up the vessels in the Liver Structure?
Portal Triad
- Hepatic Artery
- Portal vein
- Biliary Duct
Central Vein
What is the function of the Liver?
- Carbohydrate metabolism
- Fat Metabolism
- Protein Metabolism
- Hormone Metabolism
- Toxin/Drug: Metabolism and Excretion
- Storage: Glycogen, Vitamin A/B12, Iron
- Bilirubin: Metabolism and Excretion
How does the liver perform Carbohydrate metabolism?
Gluconeogenesis
- Amino acids/lactate/glycerol → glucose
Glycogen synthesis (glycogenesis)
- Excess glucose → glycogen
Glycogen Metabolism (Glycogenolysis)
- Glycogen → glucose
How does the Liver perform Fat Metabolism?
Catabolism
- Triglyceride oxidation → energy (ketogenesis)
Anabolism
- Lipoprotein synthesis
- Excess carbohydrate & fat → Fatty acid synthesis→ fatty acids & triglycerides → stored in adipose tissue
- Cholesterol (& phospholipid) synthesis & excretion
- Bile Acid synthesis
How does the Liver perform Protein Metabolism?
-
Deamination and transamination of amino acids. Urea synthesis and nitrogen removal
- Non-nitrogenous part → glucose or lipid
- Nitrogenous part → ammonia → urea
-
Plasma Protein Synthesis
- Albumin
- Fibrinogen/Prothrombin (& other clotting factors)
- Lipoproteins/Caeruloplasmin/Transferrin/
- CRP/α1AT/αFP
- Synthesis of non-essential amino acids
Which hormones are metabolised by the liver?
- Insulin-like Growth Factor-1 (IGF-1)
- Angiotensinogen
- Thrombopoeitin
- Hepcidin
How does drug/toxin metabolism occur?
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
Describe how Bilirubin is metabolised and excreted?
- Haem catalysed by haem oxygenase to Bilverdin
- Bilverdin catalysed by Bilverdin Reductase to Unconjugated Bilirubin
- Unconjugated Bilirubin catalysed by UDP-Glucoronyl Transferase to Conjugated Bilirubin (dissolvable in solvent to be excreted in urine and faeces)
How is Liver function Assessed?
- Clinical assessment
- Imaging
- Biopsy (Time, Analysis & interpretation)
- Biochemical tests (Blood (plasma/serum) & urine)
What are some clinical signs of Liver Disease?
- Dupuytren’s Contracture
- Palmar Erythema
- Ascites
- Jaundice
- Spider Naevi
- Male gynaecomastia
What can liver disease lead to?
- Cirrhosis
- Oesophageal Varices
- Hepatic Encephalopathy
What are the uses of Liver Function tests?
- Screening for the presence of Liver disease
- Assessing Prognosis
- Measuring the efficacy of treatments for Liver Disease
- Monitoring disease progression
- Assessing severity, especially in patients with cirrhosis
- Stratifying the differentials between hepatic and cholestatic disease
What are some Liver Functions tests?
LFTs allow differentiation of patterns of liver disease between hepatocellular injury and cholestasis
- Serum bilirubin
- AST or ALT (indicators of hepatocellular damage)
- ALP (indicate a cholestatic picture)
- Serum albumin (determine chronicity of disease and synthetic function)
- PT or INR (determine synthetic function and identify severity of disease)
How can abnormal LFTs present outside of primary hepatic disorders?
- Heart failure
- Sepsis
- Infection/inflammation
What is the function of Albumin in the LFTs?
- Crude indicator of synthetic capacity of liver. Half-life ~20 days so may not present initially
- Maintains plasma oncotic pressure
- Binds several hormones, drugs, anions and fatty acids
- Decreases in the acute phase response (APR)
How is Bilirubin used in the LFTs?
- Total Bilirubin
- Direct/Conjugated Bilirubin
- Differentiate between intra-hepatic (liver mets, hepatitis) and extrahepatic obstruction (gallstones, carcinoma of head of pancreas)
When is Jaundice visible?
Visible when bilirubin >50 µmol/L
What is Kernicterus?
Unconjugated bilirubin crossing blood brain barrier in neonates
Describe the features of Unconjugated Bilirubin
- Not water soluble=protein bound
- Not filtered at the glomerulus hence does not reach the urine
What are the pathological states that lead to increased Unconjugated Bilirubin?
- Haemolytic states
- Gilbert’s (inherited defect in UDP glucuronyltransferase)
Describe the features with conjugated Bilirubin?
- Water soluble
- Filtered at the glomerulus hence reaches the urine = bilirubinuria
Which pathological states lead to increased Conjugated Bilirubin?
Intra or extra hepatic obstruction
How is Urobilinogen produced and excreted?
- When bilirubin reaches the gut, it is converted to urobilinogen by gut bacteria
- It gets absorbed from the distal small intestine
- It is then excreted in the urine
How is Urobilinogen pathologically significant?
- 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)
What is ALP and when is it raised?
- Secreted by cells lining biliary tract
- Enhanced synthesis/inducible enzyme
- Raised in bone disease (↑osteoblast activity)
- Raised during growth, pregnancy (different reference ranges apply)
What is ALT and its use?
Alanine aminotransferase (ALT)
- Catalyses transfer of amino group from alanine residues
- Cytosolic and present in wide range/All tissues
What is AST and its use?
Aspartate aminotransferase (AST)
- Catalyses transfer of amino group from aspartate residues
- Cytosolic (20%) and mitochondrial (80%). It is present in wide range/all tissues.
- There are high levels in heart, liver, skeletal muscle, kidney, lung & red blood cells. Also found in significant amounts in brain, gastric mucosa & adipose tissue
What are the uses of Transaminases?
- Indicators of hepatocellular damage
- ALT more specific for liver than AST
- ALT:AST ratio often used
High AST also seen in MI, muscle injury & CCF
What is GGT?
- Located in cell membrane of various tissues; mainly kidney, liver, biliary tract & pancreas. Found in hepatocytes & biliary epithelial cells
- Catalyses transfer of gamma glutamyl group from peptides to appropriate acceptors
- Kidney contains largest amount but is not released into plasma
How is GGT used clinically?
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
What is Liver Fibrosis?
- Continuous inflammation can lead to fibrosis due to altered remodelling of the extracellular matrix. Complex and dynamic process
- In healthy tissue, ECM remodelling is tightly controlled and synthesis of ECM proteins is relatively slow
- Chronic wound healing causes immune cells to infiltrate the interstitial matrix resulting in a pro-fibrogenesis environment
What is Liver Cirrhosis?
- Slow deterioration of the liver until unable to function normally
- Scar tissue replaces normal rissue and partiall blocks blood flow
- There are 2 forms of liver cirrhosis: Compensated and Decompensated
- Insidious involvement
- Liver may in theory be able to regenrate to some extent
