simple about cirrhosis by medical students UniSZA. lets learn together

1. MED STUDENT OF UniSZA
CIRRHOSIS
Nurfarhana binti Lazim
Nazihah bt Mohamad
Siti Aisyah binti Mat Jusoh
Noor Azira binti Sharif
Siti Hamidah binti Mahbud

3. LIVER
• the second largest organ and the largest gland
• predominantly occupies the right
hypochondrium but the left lobe extends to
the epigastrium
• shape: prism or wedge
• is pinkish brown in color, with a soft
consistency, and is highly vascular and easily
friable

5. • covered by peritoneum with the exception
of the ‘bare area’.
• the upper surface of the liver is percussed
at the level of the fifth intercostal space
• the anterior surface is separated from the
inferior (visceral) surface by a sharp
anterior (inferior) border that is clinically
palpable.

6. Segmental
Division
Anatomical
division
Physiological
division
divided by
Falciform
ligament (ant)
Ligamentum
venosum
(post)
Fossa for gall
bladder
Fossa for IVC

7. • The liver has a unique dual blood supply
(about 1500 mL/min) both from the proper
hepatic artery (20-40%) and from the portal
vein (60-80%)

12. • formed of hexagonal lobules with a central
vein in the center and portal triad at the
corners.
• plates are separated by blood sinusoids
lined by endothelium and contain VonKupffor cells.
• hepatocytes at the periphery of the lobules
facing portal tracts are called the limiting
plates.

16. Portosystemic
anastomosis
Gastroesophageal
junction
Left
gastric
vein
Around
umbilicus
Anal
area
Paraumbilical
vein
Azygos
vein
Superior
rectal
vein
Middle &
inferior
rectal
vein
Veins of
anterior
abdominal
wall

17. Physiology of the liver
FUNCTIONS OF THE LIVER

18. PROTEIN METABOLISM
synthesis and storage
• the liver is the principal site of synthesis of all circullating protein apart
from γ-globulin which are produced in the reticulo endothelial system.
• the liver receives amino acid from the intestine and muscles and, by
controlling the rate of gluconeogenesis and transamination, regulate
levels in the plasma.
•Plasma cotains 60-80 g/L of protein, mainly in the form of albumin,
globulin and fibrinogen

19. • albumin has a half life of 16-24 days, and 10-12 g are synthetized daily.
• its main function are:
- to maintain the intravascular oncotic ( colloid osmotic) pressure
- to transport water- insoluble substances such as
*bilirubin,
*hormones
*fatty acid
*drugs
• reduced synthesis of albumin over prolonged periods
 hypoalbuminaemia ( in chronic liver disease and
malnutrition)
•Hypoalbuminaemia also found in :
- hypercatabolic states ( trauma with sepsis)
- diseases where there is an excessive loss ( nephrotic syndrome,
protein losing enteropathy )

20. • transport or carrier proteins such as transferrin and caeruloplasmin, acute
phase and other proteins such as:
- α1- antitrypsin
- α- fetoprotein
are also produced in liver.
• the liver also synthesized all factors involved in coagulation ( apart from
one-third of factor VII ) that is :
- fibrinogen
- prothrombin
- factors V,VII,IX,X and XII
- protein C and S
- antithrombin
- complement system
• the liver stores:
- large amounts of vitamins, particularly A, D and B12
- lesser amounts of others vitamin K and folate
- also minerals ( iron in ferritinhaemosiderin and copper

21. Degradation (nitrogen excretion)
This is the
major pathway
for the
elimination of
nitrogenous
waste
Failure of this
process occurs in
severe liver
disease

22. CARBOHYDRATE METABOLISM
Major function of the liver :
- Glucose homeostasis
- Maintenance of blood sugar
Liver stores – 80 g of glycogen
Immediate fasting state
Prolonged starvation
• blood glucose mantained by
glycogenolysis or by gluconeogenesis
Ketone bodies and fatty acids
• source of gluconeogenesis
- lactate
- pyruvate
- amino acids from muscle (mainly
alanine and glutamine)
- glycerol from lipolysis of fat stores

23. LIPID METABOLISM
Fats are insoluble in water and are transported in the plasma as
protein lipid complexes ( lipo proteins)
The liver has a major role in the metabolism of lipoproteins
It synthesizes :
•VLDLs
•HDLs
•LCAT
• IDLs
• LDLs
• triglycerides ( mainly of dietary origin)
• Cholesterol ( dietary origin )

24. FORMATION OF BILE
• Bile secretion and bile acid metabolism
bile consist of water , electrolytesbile acids, cholesterol,phospholipids and
conjugated bilirubin
• bilirubin metabolism
Bilirubin is produced mainly from the breakdown of mature red cells in the
kuffer cells of the liner and in the reticuloendothelial system

25. HORMONE AND DRUG INACTIVATION
•The liver catabolizes hormones such as:
- insulin
- glucagon
- oestrogens
- growth hormone
- glucocorticoids
- parathyroid homones
• it is the major site for the metabolism of drugs and alcohol

26. IMMUNOLOGICAL FUNCTION
The liver act as ‘sieve’ for the bacterial and other antigens carried to it via
the portal tract from the gastrointestinal tract
- kuffer cell ( macrophage, sp. Memb. Receptor for
degrade without ab )
- the reticulo endothelial sys.  tissue repair
- T and B lymphocyte interaction
- cytotoxic activity in disease processes
ligands ag

27. Liver Cirrhosis
BY: SITI AISYAH MAT JUSOH

28. cirrhosis
• Consequence of chronic liver disease
characterized by replacement of liver tissue by
diffuse hepatic fibrosis, scar tissue and
regenerative nodules
• The liver architecture is diffusely abnormal and
this interferes with liver blood flow and function
• Occur at any age, has significant morbidity and is
an important cause of hepatic death

30. Epidemiology
• According to World Health Organization (WHO) every year 34 million people are infected by Hepatitis C. About 150 million
people are chronically infected and at risk of developing liver
cirrhosis and/or liver cancer. And more than 350,000 people
die every year from Hepatitis C-related liver disease.
• In Malaysia, according to the Malaysian Liver Foundation
(MLF), an estimated 2.5 million people suffer from chronic
Hepatitis, and this doesn’t include other serious liver afflicted
diseases such as Jaundice, Alcoholic liver disease (ALD),
Non-Alcoholic fatty liver disease (NAFLD) and Liver Cirrhosis
brought about by toxins from everyday products and alcohol
consumption.

31. • Indian had a high prevalence of alcoholassociated chronic liver disease
• Hepatitis B was the predominant etiology
in Malay and Chinese compared to Indians
• Hepatitis C cirrhosis was highest in Malay
University of Malaya Medical Centre(2006)

32. pathogenesis
• Cardinal features of cirrhosis:
– an increase in fibrous tissue
– progressive and widespread death of liver cells
– inflammation leading to loss of the normal liver
architecture

34. • Following liver injury, stellate cells in space of
Disse are activated by cytokines and their
receptors, reactive oxygen intermediates and
other paracrine and autocrine signals produced
by Kupffer cell, activated platelets and
hepatocytes
• This transform stellate cell into myofibroblast-like
cell, capable of producing collagen, proinflammatory cytokines and other mediators
which promote hepatocyte damage and cause
tissue fibrosis
• The progression of liver injury to cirrhosis may
occur over weeks to years

35. • Destruction of liver architecture causes
distortion and loss of normal hepatic
vasculature with the development of
portosystemic vascular shunts and the
formation of nodules
• It evolves slowly over years to decades and
normally continues to progress even after
removal of the aetiological agent

36. • Can be classified histologically into two
types:
– Micronodular cirrhosis
– Macronodular cirrhosis

37. Micronodular cirrhosis
characterised by small nodules about <3mm in diameter and seen in
alcoholic or biliary tract disease

38. Macronodular cirrhosis
characterised by larger nodules of various sizes and normal acini may be seen
within larger nodules, areas of previous collapse of the liver architecture are
evidenced by larger fibrous scars. This types often seen following chronic viral
hepatitis

39. Etiology
Common
Others
•
•
•
•
• Biliary cirrhosis: primary or
secondary
• Autoimmune hepatitis
• Hereditary Haemochromatosis
• Hepatic venous congestion
• Budd Chiari Syndrome
• Wilson’s Disease
• Drugs
• Alpha 1 Antitrypsin deficiency
• Cystic Fibrosis
• Galactosemia
• Glycogen storage disease
• Veno-occlusive disease
• Idiopathic (Cryptogenic)
Alcohol
Hepatitis B
Hepatitis C
Non-alcoholic fatty liver disease

40.  Long-term heavy drinking of alcohol
– Estimated that the development of cirrhosis requires, on
average, the ingestion of 80 grams of ethanol daily for 10
to 20 years
– This corresponds to approximately one liter of wine,
eight standard sized beers, or one half pint of hard liquor
each day
– Chronic consumption of alcohol  secretion of proinflammatory cytokines (TNF-alpha, IL6 and IL8),
oxidative stress, lipid peroxidation, and acetaldehyde
toxicity  inflammation, apoptosis and eventually
fibrosis of liver cells
– females are twice as susceptible to alcohol-related liver
disease, with shorter durations and doses of chronic
consumption

41. Chronic viral hepatitis type B, C
and D
o Infection with the hepatitis C virus causes
inflammation of the liver and a variable
grade of damage to the organ that over
several decades can lead to cirrhosis  the
most common reason for liver transplant
– Hepatitis D is dependent on the presence of
hepatitis B and accelerates cirrhosis in coinfection

42. • Non-alcoholic steatohepatitis
– fat builds up in the liver and eventually causes scar
tissue
– associated with diabetes, protein malnutrition,
obesity, coronary artery disease, and treatment with
corticosteroid medications
• Primary biliary cirrhosis
– more common in women
– an autoimmune disease of the liver
– slow progressive destruction of the small bile ducts of
the liver, with the intralobular ducts (Canals of
Hering) affected early in the disease. When these
ducts are damaged, bile builds up in the liver
(cholestasis) and over time damages the tissue

43. • Autoimmune chronic active hepatitis
– uncommon condition that results in the body's
immune system attacking and destroying liver
cells.
– abnormal immune response results in
inflammation of the liver
• Haemochromatosis
– too much iron is absorbed by the body and the
excess is deposited in the liver and cause liver to
enlarge and becomes damaged,
– Causes: hereditary haemochromatosis(HHC), a
genetic disorder, and transfusional iron overload,
which can result from repeated blood transfusion.

44. • Wilson’s disease
– an autosomal recessive genetic disorder in which
copper accumulates in tissues; this manifests as
neurological or psychiatric symptoms and liver
disease
– When the amount of copper in the liver
overwhelms the proteins that normally bind it, it
causes oxidative damage through a process
known as Fenton chemistry; this damage
eventually leads to chronic active
hepatitis, fibrosis (deposition of connective tissue)
and cirrhosis

45. • Alpha-1 antitrypsin deficiency
– Alpha-1 antitrypsin (A1AT) is a protein produced by the
liver that protects the lungs
– a genetic disorder that causes defective production
of alpha 1-antitrypsin(A1AT), leading to decreased A1AT
activity in the blood and lungs, and deposition of
excessive abnormal A1AT protein in liver cells.
– Because A1AT is expressed in the liver, certain mutations
in the gene encoding the protein can cause misfolding
and impaired secretion, which can lead to liver cirrhosis
• Galactosaemia
– the enzymes needed for further metabolism of galactose
are severely diminished or missing entirely, leading to
toxic levels of galactose 1-phosphate in various tissues
resulting in hepatomegaly and cirrhosis

46. Symptom of liver disease
Signs of chronic liver disease
Complication of cirrhosis

48. Symptoms Acute
liver disease
•
•
•
•
Malaise
Anorexia
Fever
Jaundice

49. Symptoms chronic liver disease
•
•
•
•
•
•
right hypochondrial pain
abdominal distension
ankle swelling
haematemesis and melaena
pruritus
breast swelling (gynaecomastia), loss of libido and
amenorrhoea
• confusion and drowsiness

50. Signs of chronic liver disease

51. INVESTIGATION OF CIRRHOSIS
Siti hamidah bt mahbud

52. To assess severity
Liver function test.
Serum albumin and prothrombin time
(marker for synthetic function of liver)
•the outlook is poor with an albumin level below
28 g/L.
•prothrombin time ^ = ^ severity of the liver
disease

54. Liver biochemistry.
Aminotransferases (ALT and AST) – present in
hepatocytes and leak to blood when cell damage.
• AST(mitochondrial enzyme: present in heart
,muscle ,kidney & brain)= ^ in hepatic necrosis, MI,
muscle injury, congestive cardiac failure.
• ALT (cytosomal enzyme: present in liver) = ^ in
lever disease.
Alkaline phosphate (ALP) –present in canalicular &
sinusoidal membranes of the liver, bone, intestine,
placenta.
• ^ in cholestasis, may also ^ in metastases to liver
and cirrhosis

55. can be normal, depending on the severity of
cirrhosis. In most cases there is at least a slight
elevation in the serum ALP and serum
aminotransferases.
Bilirubin = ^ in liver disease

56. Serum electrolytes.
low sodium indicates severe liver disease due
to a defect in free water clearance or to excess
diuretic therapy.
Serum creatinine.
An elevated concentration > 130 μmol/L is a
marker of worse prognosis.

57. Type of cirrhosis
This can be determined by:
■ viral markers
■ serum autoantibodies
Anti-mitochondrial antibody (AMA) = primary
biliary cirrhosis
■ serum immunoglobulins
^ igM = primary biliary cirrhosis.

58. ■ iron indices and ferritin
■ copper & α1-antitrypsin
Serum copper and serum α1-antitrypsin
should always be measured in young
cirrhotics.
 Total iron-binding capacity (TIBC) and
ferritin should be measured to exclude
hereditary haemochromatosis; genetic
markers are also available

59. Imaging
Ultrasound examination.
can demonstrate changes in size and shape of
the liver. Fatty change and fibrosis produce a
diffuse increased echogenicity. In established
cirrhosis there may be marginal nodularity of
the liver surface and distortion of the arterial
vascular architecture.

60. CT scan
CT scan showing an
irregular lobulated
liver. There
is splenomegaly and
enlargement of
collateral vessels
beneath the anterior
abdominal wall
(arrows) as a result of
portal hypertension.

61. Endoscopy
performed for the detection and Treatment of
varices, and portal hypertensive gastropathy..
MRI scan.
This is useful in the diagnosis of benign tumours
such as haemangiomas.
Liver biopsy
necessary to confirm the severity and type of
liver disease.

62. Complication & effect of cirrhosis
• Portal hypertension and
gastrointestinal
haemorrhage
• Ascites
• Portosystemic
encephalopathy
• Hepatorenal syndrome
• Hepatocellular
carcinoma
• Bacteraemias,
infections
• Malnutrition

63. Portal hypertension
•
Elevation of hepatic venous pressure
gradient to > 5mm Hg.
• It is caused by combination of 2
simultaneously occuring hemodynamic
processes :
1. Increased intrahepatic resistance to passage
of blood flow through liver
2. Increased splanchnic blood flow secondary
to vasodilation

64. Portal hypertension

66. Ascitis
• Accumulation of fluid within the peritoneal
cavity
• Most common complication of cirrhosis
• Two-year survival of patients with ascites is
approximately 50 percent

67. Ascitis
• Assessment of ascites
– Grading
• Grade 1 — mild;
Detectable only by US
• Grade 2 — moderate;
Moderate symmetrical
distension of the
abdomen
• Grade 3 — large or gross
asites with marked
abdominal distension
• Therapy: diuretics
paracentesis

68. Portosystemic encephalopathy
• Toxic substances (ammonia) bypass the liver
via collaterals and gain access to the brain
• Symptoms: lethargy
mild confusion
anorexia
reversal of sleep pattern
disorientation
coma

69. Hapatorenal syndrome
• acute renal failure coupled with advanced hepatic
disease (due to cirrhosis or less often metastatic tumor or
severe alcoholic hepatitis)
• characterized by:
–
–
–
–
Oliguria
benign urine sediment
very low rate of sodium excretion
progressive rise in the plasma creatinine concentration

70. Hepatorenal syndrome
• Reduction in GFR often clinically masked
• Prognosis is poor unless hepatic function
improves
• Nephrotoxic agents and overdiuresis can
precipitate HRS

71. Management of cirrhosis

72. • Treatment options for cirrhosis depend on the
cause and the level of liver damage. The goals
of treatment are to prevent further liver
damage and reduce complications.
• When cirrhosis cannot be treated, the liver
will not be able to work and a liver transplant
may be needed

74. way to manage cirrhosis
• Maintain a healthy lifestyle (eat a healthy diet
and exercise regularly)
• Limit salt in your diet to prevent or reduce fluid
build up
• Avoid raw shellfish
• Stop drinking alcohol
• Talk to your doctor about hepatitis A and
hepatitis B vaccinations
• Do not share needles, razors, toothbrushes or
other personal items with others

75. REFERENCES
BOOK
• Kumar & Clarks; Clinical Medicine; 7th Edition
WEB
1. Cirrhosis: Diagnosis, Management, and
Prevention ; American family physician
By : S. PAUL STARR, MD, and DANIEL RAINES, MD, Louisiana State University
Health Sciences Center School of Medicine at New Orleans, New Orleans,
Louisiana
2. Cirrhosis ; American liver foundation