2. The liver and its diseases
Emyr Wyn Benbow
University of Manchester

3. LIVER DISEASE By the end of this talk, you should know about
Normal anatomy and physiology of the liver
Common diseases affecting the liver
Viral hepatitis
Causes of chronic hepatitis
Alcoholic liver disease
Causes of cirrhosis
Clinical consequences of liver disease

4. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION
right upper quadrant of abdomen
g in adult
peritoneal covering
4 anatomical lobes (right-left-caudate-quadrate)

5. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION
2 functional lobes (right-left) in 8 segments
related to
afferent blood
supply

6. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION
hepatic artery from coeliac axis
portal vein from gut
venous outflow via hepatic veins to inferior vena cava

7. LIVER DISEASE
Functional unit is the ACINUS

8. LIVER DISEASE

9. LIVER DISEASE NORMAL METABOLIC ACTIVITIES CARBOHYDRATES
forms and stores glycogen
released under hormonal control

10. LIVER DISEASE NORMAL METABOLIC ACTIVITIES PROTEINS
deamination of amino acids
formation of urea
synthesis of albumin, α-1-antitrypsin, clotting factors

11. LIVER DISEASE NORMAL METABOLIC ACTIVITIES LIPIDS fatty acid oxidation
triglyceride and cholesterol synthesis
bile salt metabolism
cholesterol + amino acid
allow micelle formation in gut

12. LIVER DISEASE NORMAL METABOLIC ACTIVITIES VITAMINS
fat soluble vitamins require bile salts for absorption
A, D, K, B12 stored in the liver
vitamin K needed for hepatic production of prothrombin (factor II)
25-hydroxylation of vitamin D takes place in liver

13. LIVER DISEASE NORMAL METABOLIC ACTIVITIES INACTIVATION OF HORMONES
oestrogens/steroids conjugated to glucuronic acid
may inactivate insulin and thyroxine

14. LIVER DISEASE NORMAL METABOLIC ACTIVITIES DRUG DETOXIFICATION
microsomal enzymes on endoplasmic reticulum (cytochrome p450 systems)
enzyme induction may occur

15. LIVER DISEASE NORMAL METABOLIC ACTIVITIES BILIARY EXCRETION
bilirubin is unconjugated (fat soluble) before liver cell membrane, transported across, conjugated to glucuronic acid (water soluble), secreted in bile
bile acids and cholesterol metabolism are important in gall stone formation

16. LIVER DISEASE HEPATITIS Inflammation of the liver Causes viruses
alcohol
drugs
autoimmune disease

17. LIVER DISEASE
VIRAL HEPATITIS
Hepatitis A
infectious
epidemic
oral-faecal transmission
2-6 weeks incubation period

18. LIVER DISEASE VIRAL HEPATITIS Hepatitis B serum sporadic
blood-borne orsexual transmission
6 weeks to 6 months incubation period

19. LIVER DISEASE
VIRAL HEPATITIS
Hepatitis C
transfusion related
blood-borne transmission
2 weeks to 6 months incubation period

20. LIVER DISEASE VIRAL HEPATITIS Hepatitis D delta agent Hepatitis E
needs hepatitis B for disease
Hepatitis E
very similar to HAV
Epstein-Barr Virus
infectious mononucleosis
Cytomegalovirus
immunosuppressed patients

21. LIVER DISEASE
VIRAL HEPATITIS
asymptomatic subclinical disease
acute clinical jaundice
acute massive necrosis (< 2%)
chronic hepatitis

22. LIVER DISEASE VIRAL HEPATITIS chronic hepatitis > 6 months
(especially hepatitis B and C)
grade of disease = portal and lobular inflammation, interface hepatitis
stage of disease = fibrosis (portal, bridging, nodules) and cirrhosis
may lead to cirrhosis and ultimately hepatocellular carcinoma

23. LIVER DISEASE ALCOHOL 1 unit of alcohol = 10ml or 8g pure ethanol
equivalent to half pint of beer, glass of wine, half measure of spirits

24. LIVER DISEASE ALCOHOL calculate by Beck’s: 275ml x 5.0%ABV
= units
recommended ‘safe’ limits:
14 units/week for women
21 units/week for men

25. LIVER DISEASE ALCOHOL 1 unit of alcohol = 10ml or 8g
calculate by white wine
125ml x 12%ABV = 1.5 units
175ml x 12%ABV = 2.1units
250ml x 12%ABV = 3 units

26. LIVER DISEASE
ALCOHOL
alcohol absorbed from upper small intestine, then via portal vein to liver
some metabolism in stomach by alcohol dehydrogenase
alcohol converted to acetaldehyde and excreted by conversion to carbon dioxide in citric acid cycle
cytochrome p4502E1 involved

27. LIVER DISEASE

28. LIVER DISEASE
ALCOHOL
variations related to weight, gender and body fat
rate of metabolism variable
can be induced, tolerance increases
roughly equivalent to 1 unit per hour

29. LIVER DISEASE

30. LIVER DISEASE ALCOHOL fatty change reversible
alcoholic hepatitis reversible Mallory’s hyaline
fibrosis reversible
pericellular
cirrhosis irreversible

31. LIVER DISEASE ALCOHOLIC LIVER DISEASE fatty change - reversible
alcoholic hepatitis
- Mallory’s hyaline
pericellular fibrosis
cirrhosis
- irreversible
H&E
Oil Red O

32. LIVER DISEASE ALCOHOLIC LIVER DISEASE fatty change - reversible
alcoholic hepatitis
- reversible
Mallory’s hyaline
pericellular fibrosis
cirrhosis – irreversible
Mallory’s hyaline

33. LIVER DISEASE ALCOHOLIC LIVER DISEASE fatty change - reversible
alcoholic hepatitis - reversible Mallory’s hyaline
pericellular fibrosis
- reversible
cirrhosis – irreversible

34. LIVER DISEASE ALCOHOLIC LIVER DISEASE fatty change - reversible
alcoholic hepatitis - reversible Mallory’s hyaline
pericellular fibrosis
- reversible
cirrhosis - irreversible

35. Alcohols: ethanol llegal intoxication is 0.08 g/dL
0.2 g/dL is drunk, 0.3 is smashed, 0.4 is out cold
lethal toxicity
> 0.4g/dL in alcohol naïve
> 0.5g/dL in anyone
but very variable

36. Alcohols: ethanol
but some have survived far higher levels than these potentially fatal values, up to 1.3g/dL
death due to respiratory depression
synergy with other respiratory depressants

37. Alcohols: ethanol Elimination average elimination rate 0.015 g/dL/hr
from legal intoxication to undetectable takes about 5 hours
alcoholics may eliminate up to 0.05 g/dL/hr
post mortem production of alcohol up to 0.05g/dL

38. LIVER DISEASE NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) fatty change
non-alcoholic steatohepatitis (NASH)
fibrosis
cirrhosis
changes identical to alcohol
associated with obesity, diabetes, hyperlipidaemia, some drugs

39. LIVER DISEASE
CIRRHOSIS - disease of all of the liver with parenchymal nodules and surrounding fibrosis
CAUSES
alcohol
viruses
metabolic diseases
autoimmune

40. LIVER DISEASE CIRRHOSIS - CAUSES alcohol viruses
especially HBV and HCV
metabolic diseases
autoimmune
Orcein- HBsAg
IHC-HBsAg

41. LIVER DISEASE CIRRHOSIS - CAUSES alcohol viruses metabolic diseases
iron, copper, glycogen storage disease, lipid disorders, -1 antitrypsin deficiency
autoimmune
Perls’
-1ATD,
DPAS
-1ATD,IHC

42. LIVER DISEASE CIRRHOSIS - CAUSES alcohol viruses metabolic diseases
autoimmune
“lupoid”, young women: anti-nuclear and anti-smooth muscle antibodies
primary biliary cirrhosis: middle aged women, anti-mitochondrial antibodies
AiCH

43. LIVER DISEASE CIRRHOSIS – EFFECTS Liver failure
protein synthesis: low albumin
coagulation factors: bleeding
jaundice
encephalopathy: confusion
Portal hypertension
Hepatocellular carcinoma

44. LIVER DISEASE Cirrhosis – effects Liver failure Portal hypertension
ascites
varices
splenomegaly
Hepatocellular
carcinoma

45. LIVER DISEASE CIRRHOSIS – EFFECTS LIVER FAILURE PORTAL HYPERTENSION
HEPATOCELLULAR CARCINOMA
very common carcinoma where HBV endemic (SE Asia, Africa)
very poor prognosis, about 6-9 months
Raised serum alpha-fetoprotein levels
AFP
HCC

46. LIVER DISEASE Summary Be aware of drug metabolism
risks of viral hepatitis
bleeding tendency in chronic liver disease
increased risk of alcoholism in medical profession