Hepatic, Jaundice, Liver anatomy, Functions of liver,

1. LIVER DISEASES – AN OVERVIEWLIVER – A DEEP LOOK!
Dr Rajesh T Eapen

3. INTRODUCTION
• Liver weight 1400 - 1600gm.
• Parenchyma - liver cells (hepatocytes) trabeculae 1 cell thick in adults.
- Kupffer cells in sinusoids are phagocytes.
• - hepatic stellate cells in space of Disse, store vitamin A,
transform into collagen-producing myofibroblasts,
regulate blood flow in sinusoids. -
liver-associated lymphocytes.
• Biliary drainage system - canaliculi (in centre of liver cell plates).
- canals of Hering & cholangioles.
- intra-hepatic bile ducts.
- extra-hepatic bile ducts.
• Vasculature - portal vein supplies 70% of the blood flow.
- hepatic artery supplies 30% of the blood flow.
- sinusoids lined by fenestrated endothelium.
- hepatic venules, hepatic veins drain into the IVC.

6. Functions of Liver

9. • The functional unit of the liver parenchyma is the hepatic acinus with zones 1,2 & 3. Zone 1
is periportal, zone 3 is perivenular, zone 2 intermediate.
• Portal tracts composed of fibrous tissue ramify in the liver and contain 3 structures, portal
vein, hepatic artery, bile duct (portal triad).
• The liver is important for - metabolism of carbohydrate, protein, lipids.
- protein synthesis, albumin, coagulation factors,
complement factors etc.
- storage of iron, copper, vitamins A,D,B12.
- detoxification/drug metabolism.
- bile production.
• Investigation of liver diseases.
Biochemical - enzymes, proteins, bilirubin.
Haematological - coagulation factors among others.
Immunological - antibodies (viruses, autoimmune).
Imaging - ultrasound, CT, MRI, ERCP, MRCP.
Liver biopsy - percutaneous needle biopsy, transjugular biopsy, wedge biopsy at
laparoscopy or open surgery. Useful in providing information as to
the aetiology and severity of the liver disease, ruling out the
presence of other concomitant disease, monitoring response to
therapy. Focal lesions require US or CT guidance.

10. • Morphological patterns of liver injury.
• 1. Degeneration - ballooning degeneration (hydropic change);
- feathery degeneration (bile-induced damage).
Intracellular accumulations - fat (steatosis), iron, copper, bile, Mallory’s hyaline.
• 2. Necrosis - (coagulative or lytic) and apoptosis. Necrosis may be
randomly focal (spotty necrosis), zonal eg zone 3, bridging (bridging hepatic
necrosis, eg portal to venular), involve most or almost all of the liver
(submassive and massive respectively). Zone 3 is most prone to injury as it is farthest
from the blood supply and is the area containing most drug-metabolising enzymes.
• 3. Inflammation - acute, chronic or granulomatous. May be portal, periportal
(interface hepatitis) or acinar (focal, or panacinar).
• 4. Regeneration - hepatocytes have great ability to regenerate. The reserve
compartment is the canal of Hering/bile ductule compartment. Activation is
described as the ductular reaction.
• 5. Fibrosis forms in response to inflammation or direct toxic injury. Can be portal,
perivenular, form bridging fibrosis, finally cirrhosis.
The great variety of liver diseases and the liver’s limited patterns
of response means that close clinicopathological correlation is
required for their diagnosis.

11. JAUNDICE AND CHOLESTASIS
• Jaundice (or icterus) - yellow discolouration of the skin, sclerae and mucous
membranes due to excess plasma bilirubin (hyperbilirubinemia).
• Jaundice appears when plasma bilirubin exceeds 50µmol/l.
(Normal 3 - 17µmol/l)
• Liver disease is not the only cause of jaundice and many patients with significant
liver disease do not have jaundice (are anicteric).
• Cholestasis - arrest of bile flow. A failure of adequate amounts of bile to reach the
duodenum - due to interference anywhere from liver cell microsomes to the
duodenum.

14. MECHANISMS AND CLASSIFICATION OF JAUNDICE
• Mechanisms - Increased bilirubin production.
- Decreased uptake by hepatocytes. -
Impaired conjugation. -
Impaired excretion - intrahepatic
- extrahepatic.
• Classification :
Pre-hepatic - haemolysis most important of several causes.Unconjugated bilirubin
insoluble in water, not excreted in urine. Risk of brain damage in neonates
(kernicterus); pigment gallstones in adults.
Hepatic – e.g. hepatitis, intra-hepatic bile duct damage, congenital
hyperbilirubinemias e.g. Gilbert’s syndrome. Mainly conjugated (except Gilbert’s
syndrome) so soluble in water resulting in dark urine.
Post-hepatic - obstruction to extra-hepatic bile ducts by gallstone, stricture, tumour,
or congenital biliary atresia. Conjugated bilirubin.

15. • In cases of hepatic jaundice, when there is predominantly hepatocyte
damage, the patient is often very symptomatic and raised serum
transaminases are the predominant biochemical finding. This is sometimes
called “hepatocellular jaundice.”
• In cases where there is biliary obstruction, whether intra- or extra-hepatic,
the patient has what is called “cholestatic jaundice” with pruritis, dark urine
and pale stools, and with time may develop skin xanthelasmas and
steatorrhoea. Serum alkaline phosphatase is raised.
• Mixed patterns occur.
• Distinction between intra-hepatic and extra-hepatic obstruction requires
imaging. This should be done urgently and the obstruction relieved where at
all possible.

16. LIVER FAILURE
• Classification. Acute - no pre-existing liver disease.
Chronic - pre-existing liver disease.
• Causes. Acute - viral hepatitis, drugs, toxins, severe fatty change (eg
fatty liver of pregnancy, Reye syndrome), vascular.
Chronic - cirrhosis, chronic hepatitis.
• Morphology. Acute - varying degrees of necrosis up to massive liver
necrosis (zonal to panacinar histologically).
Chronic - that of cirrhosis or chronic hepatitis.
Chronic liver failure is more
common than acute liver failure. Mortality from liver failure without liver
transplantation is 75% to 90%. Drugs and viruses account for about 80% & 15% of
cases of acute liver failure respectively; figures vary according to geographical
area.

17. FEATURES OF LIVER FAILURE
• Hepatic encephalopathy - a neuropsychiatric disturbance leading to coma. The cardinal
feature of acute liver failure, progressing over hours to days. More
insidious in chronic liver failure when it is a sign of worsening liver failure.
• Pathogenesis:- nitrogenous compounds derived from bacterial action in the colon are not
metabolised in the failing liver; in addition shunting of portal blood to systemic circulation by-
passes the liver.
• Compounds involved - ammonia and derivatives of aromatic amino acids (eg mercaptans, a
cause of foetor hepaticus)
• - false neurotransmitters (eg octopamine) -
neuroinhibitors, eg gamma-aminobutyric acid (GABA), endogenous benzodiazepines.
• Morphology of brain - oedema; Alzheimer type 2 astrocytic reaction.

18. • Jaundice - hyperbilirubinaemia; deep jaundice = worse prognosis.
• Haematological - decreased clotting factors (II,VII,IX,X) results in a
bleeding tendency.
• Cardiovascular - hyperkinetic circulation.
• Respiratory - hepatopulmonary syndrome.
• Renal - hepatorenal syndrome.
• Endocrine - in chronic failure - gonadal atrophy, gynaecomastia,
amenorrhoea.
• Skin changes - in chronic failure - spider naevi, palmer erythema.
• Others - impaired metabolism of amino acids, carbohydrates (hypoglycaemia)
and drugs; impaired protein synthesis (low albumin), systemic infections and
endotoxaemia.
• Laboratory investigations - bilirubin (>300umol/l = poor prognosis).
- prothrombin (>50sec.= poor prognosis).
- transaminases.
- albumin.
Possible factors precipitating liver failure in chronic liver disease:-
increase in liver injury due to virus or alcoholic binge,
infection, GIT haemorrhage (which can precipitate
encephalopathy, as can excess dietary protein, constipation,
drugs, uraemia, hypokalaemia).

19. CIRRHOSIS
• Definition. Cirrhosis is a diffuse process in which bridging fibrosis and
regenerative parenchymal nodules result in disruption of the architecture.
Regenerative nodules
surrounded by fibrosis are necessary for the diagnosis. These may be <3mm
(micronodular cirrhosis) or >3mm (macronodular cirrhosis). A micronodular
cirrhosis can transform into a macronodular cirrhosis.
The microvasculature of the liver is markedly altered.
Cirrhosis is the end stage of chronic liver disease.
It is best classified according to aetiology.

24. • Infections. Viral hepatitis.
• Toxins and drugs. Alcohol.
Therapeutic drugs.
• Autoimmune. Hepatitis.
Primary biliary cirrhosis.
• Metabolic. Haemochromatosis.
Wilson disease.
Alpha-1-antitrypsin deficiency.
Glycogen storage disease and many others.
• Biliary obstruction. Congenital atresia.
Sclerosing cholangitis.
• Hepatic outflow obstruction.
• Cryptogenic.
The aetiology of cirrhosis varies throughout the world. In the Western world, alcohol is the most
common factor at 60% and viral hepatitis 10%. Viral hepatitis is the most common factor in Asia and
Africa. Cryptogenic cirrhosis (cause unknown) forms 10%. Once cirrhosis has
developed, it is usually not possible to determine the aetiology by morphology alone and results of
other investigations are required.

25. • Pathogenesis. Liver injury results in chronic inflammation and activation of
Kupffer cell, and other endogenous liver cells with the production of cytokines.
These, together with disruption of the extracellular matrix activates hepatic
stellate cells (HSC). Toxins may activate HSCs.These transform into
myofibroblasts which produce collagen and constrict sinusoids.
• Collagen in the space of Disse leads to “capillarisation” of the sinusoids and loss
of endothelial fenestrations, hindering exchange of solutes.
• New vascular channels in fibrous bands link inflow of blood (venous & arterial)
with outflow (hepatic venules) thus by- passing parenchyma. Existing vascular
channels and biliary channels may be obliterated. The results are internal
vascular shunts and portal hypertension. The hepatocytes in the regenerative
nodules may appear normal microscopically but are unable to adequately fulfill
their functions. Function will be further reduced if there is continuing liver cell
damage.

26. CLINICAL FEATURES
• Cirrhosis may be asymptomatic.
• When symptomatic, the features are nonspecific - weakness, fatigue, weight loss,
anorexia, nausea, gaseous abdominal distension, upper abdominal discomfort.
• The liver may be enlarged, hard and irregular or smaller than normal.
• At this stage the patient is said to have compensated cirrhosis.
• Decompensated cirrhosis manifests as signs of liver failure or complications of
portal hypertension. Deterioration in liver function can be an indication of the
development of hepatocellular carcinoma.
• Death is usually due to one of these 3 conditions.

27. COMPLICATIONS OF CIRRHOSIS
• Liver failure.
• Portal hypertension. Portal venous pressure >10mmHg.
Splenomegaly - hypersplenism leading to thrombocytopenia.
Portal-systemic shunts where portal venous system
anastomoses with the systemic venous system.
• Lower end of oesophagus leading to oesophageal varices and risk of massive GIT
haemorrhage. Periumbilical (“caput medusae”), lower rectum (haemorrhoids),
posterior abdominal wall.
• Ascites, ie excess fluid in the peritoneal cavity. A transudate (<3gm/dL
protein),straw coloured or pale green, a few mononuclear cells. Risk of
spontaneous infection when polymorphs predominate. Is due to aldosterone-
induced retention of Na & water, low oncotic pressure (low albumin), and portal
hypertension. Excess hepatic lymph and intestinal fluid leakage also contributes to
ascites.
• Hepatocellular carcinoma.

30. Fatty Liver
What is it?
• Fatty liver is the collection of excessive
amounts of fat inside liver cells, also called
steatosis.
• Mostly triglycerides.

31. Common type of Fatty Liver
1. Nonalcoholic fatty
liver disease
(NAFLD) - affect
people who drink
little or no alcohol.
•simple fatty liver
(steatosis),
usually causes
no liver damage.

32. 2. Nonalcoholic
steatohepatitis
(NASH), a more
serious type.
Cause by hepatitis
infection,
malnutrition,
obesity, diabetes
mellitus, and Reye's
syndrome .
In some cases, this can
progress either to
cirrhosis, which can
produce progressive,
irreversible liver
scarring, or to liver
cancer.

33. Reye's Syndrome - a deadly disease, attack any child or
adult without warning.
All body organs are affected, with the liver and brain
suffering most seriously.
Cause and cure remain unknown, research has
established a link between Reye's Syndrome and the
use of aspirin and other salicylate-containing
medications.

34. 3. Alcoholic steatosis.
Cause alcohol by
abuse
All body organs are
affected, with the liver
and brain suffering most
seriously.
Cause and cure remain
unknown, research has
established a link between
Reye's Syndrome and the
use of aspirin and other
salicylate-containing
medications.

35. Causes:
1. Nonalcoholic fatty liver - It's unclear exactly
what causes disease.
But many researchers believe the
contributing factors are:
– Obesity
– Hypertension
– Abnormal cholesterol levels

36. 2. It's also unclear exactly how a liver becomes
fatty. The fat may come from other parts of
the body, or the liver may absorb an increased
amount of fat from the intestine.
Another possible explanation is that the liver
loses its ability to change fat into a form that
can be eliminated.

37. What are the symptoms?
• Fatty liver usually produces no symptoms.
• Jaundice
• right-side abdominal pain
• abdominal swelling
• fever.

38. At more advanced stage, liver becomes
cirrhosis
• Cirrhosis refers to scarring of the liver. It
replaces healthy tissue.
• Scar tissue cannot do what healthy liver tissue
does.
• Scar tissue also blocks the normal flow of
blood through the liver.
• Cirrhosis can be life-threatening, but it can
also be controlled if treated early.

39. A fatty liver is enlarged and has a greasy, pale yellow look.

40. How is it diagnosed?
• The liver may be tender when the abdomen is
pressed.
• Blood tests - for liver function.
• Ultrasound or abdominal CT scan.

41. What is the treatment?
• Treatment for fatty liver is aimed at
eliminating or treating the cause of the
condition.
• In some cases, fatty liver is reversible if caught
early in its development.
• Pregnancy-related fatty liver is treated by
delivering the baby, if viable.
• Severe liver damage can occur if fatty liver is
left untreated. In these cases, the patient may
eventually require a liver transplant

42. Now you know how much I care for you.
Please treat me with tender loving care.
Your silent partner and ever-loving
lover….LIVER