Download The Ageing Liver - Geriatric Medicine

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

Bacterial
infections

Liver Abscess

Primary Biliary
Cirrhosis

Hepatocellular
Carcinoma

Non-Alcoholic Cirrhosis

Obstructive Jaundice
 Choledocholithiasis
 Malignant
Obstruction
Summary… Brief Review of
 Normal Liver
 Morphological changes with ageing
 Vascular changes with ageing
 Metabolic changes with ageing
 Relationship between liver disease and
ageing