The Ageing Liver Dr ‘Yinka Ogundipe SpR in Geriatric Medicine Royal Infirmary of Edinburgh Dec 12th 2006

Outline Normal Liver Morphological changes with ageing Vascular changes with ageing Metabolic changes with ageing Relationship between liver disease and ageing

The Normal Liver…in brief Largest gland & ‘solid’ organ. Up to 1.5kg in men & 1.3kg in women. Holds up to 13% blood volume (~one pint). 2 lobes; right 2/3rd > left 1/3rd Thousands of lobules.

The Normal Liver…in brief 2 distinct blood supplies Arterial – Hepatic arteries Venous – Portal vein Venous drainage – Hepatic veins 2/3rd of liver is parenchymal; 1/3 is biliary tract. Average lifespan of a hepatocyte is ~ 150 days.

The Liver

The Liver…Functions in health - manufacture, break down & regulation of many hormones - making enzymes & proteins e.g albumin, clotting factors - manufacturing bile  - storing iron, vitamins & other essential chemicals - processing digested food from the intestine - controlling levels of fats, amino acids & glucose in blood - clearing blood of particles & some bacterial infections - neutralising and destroying drugs & toxins

Morphological Changes of Ageing…1 ↓ Number of hepatocytes ↓ Liver size / volume Up to 1/3 to 1/2 reduction btw 3rd – 10th decade Generally < 60 yrs - process appears slower > 60 yrs - process is more rapid. Female > Male (in non-invasive cross-sectional studies)

Morphological Changes…2 ↑ Lifespan of hepatocytes ↑ Nuclei size & polyploidy ↑ Mitochondrial volume

Morphological Changes…3 ↑ Intracellular protein ↑ Inter-hepatocyte space - (↑ collagen) ↑ Lipofuscin deposition - (↓ intracellular proteinolysis)

Vascular Changes… ↓ Liver blood flow (by ≤ 35%) [Normal = ~1.5L/min] ↓ Liver perfusion (≤ 10%) i.e. blood flow per unit vol. of liver tissue The above are of uncertain significance but may be closely linked to changes in liver function with ageing.

Metabolic Changes…1 No clinically significant to LFTs But minor & transient changes E.g. in acute illness, heart failure In particular, ↑ Alkaline Phosphatase ?? Acute phase protein response, if transient rise But if persistent, could indicate possible liver dx.

Metabolic Changes…2 Minimal change to Blood Urea Nitrogen But peak urea synthesis is inversely related to age

Metabolic Changes…3 ↓ Liver cholesterol synthesis ↓ Bile acid synthesis ↑ Secretion of cholesterol into bile ?? Latter two as possible cause for ↑ gallstones with ageing

Metabolic Changes…4 ↓ Liver Enzyme Function Not due to ↓ enzyme deficiency Due to ↓ Liver blood flow Affects both Oxidative & Conjugative metabolism

Metabolic Changes…5 Consequent ↓ drug clearance Up to 50% for some drugs Age alone might account for 10 – 30% Other influences Diet / Nutrition Smoking Gender

Age Related Liver Diseases… ↑ Prevalence of drug-induced injury ↑ Morbidity and ↑ Mortality Older pts are more likely to present: with more severe liver dx and/or chronic phase dx.

Specific Liver Diseases…1 Prevalence unchanged (with age) But more severe Alcoholic hepatitis Viral hepatitis

Specific Liver Diseases…2 Prevalence mildly ↑ with age Non-Alcoholic Cirrhosis Obstructive Jaundice Choledocholithiasis Malignant Obstruction Bacterial infections Liver Abscess Primary Biliary Cirrhosis Hepatocellular Carcinoma

Summary… Brief Review of Normal Liver Morphological changes with ageing Vascular changes with ageing Metabolic changes with ageing Relationship between liver disease and ageing

Thank You... Any Questions?