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

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

3. 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.

4. 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.

5. The Liver

6. 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

7. 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)

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

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

10. 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.

11. 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.

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

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

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

15. 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

16. 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.

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

18. 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

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

20. Thank You...
Any Questions?