3 liver cell all

8/11/2019 3 Liver Cell All

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LIVER CELL FAILURE

DONE BY :Fatima S. Bajari

Ohood Al Bajri

Malath Al Shereef


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OBJECTIVES

Liver Anatomy

Physiology Liver Cirrhosis


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hati adalah kelenjar yangterbesar tubuh.

hati terbagi menjadi lobuskanan dan kiri dengan

menandai eksternalligamentum falciform.

Liver Anatomy


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The Right Lobe The Left Lobe

VIII

V

IV

IV

III

II

VII

VI

Liver Segments

terdiri dari 4 lobus(kiri, kanan,

caudatus,quadrate) dandibagi menjadisegmen 8


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Portal v. 70%

Hepatic a. 30%


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The most common anatomy of the hepatic artery


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The anatomy of the portal vein


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The anatomy of the Bile duct


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Liver Physiology

the liver performs several important functionsincluding:

Protein metabolism (Synthesis and storage)

Carbohydrate metabolism

Lipid metabolism

Formation of bile (Bile secretion and bile acid metabolism)

Hormone and drug inactivation Immunological function


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Protein metabolism (Synthesis and storage)

The liver is the principal site of synthesis of all circulating proteins, which areproduced in the reticuloendothelial system.

Plasma contains 6080 g/L of protein, mainly in the form of albumin, globulin andfibrinogen .

Albumin main functions are first to maintain the intravascular oncotic (colloidosmotic) pressure, and second to transport water-insoluble substances such asbilirubin,hormones, fatty acids and drugs.

Transport or carrier proteins such as transferrin and caeruloplasmin.

The liver also synthesizes all factors involved in coagulation ( fibrinogen,prothrombin, factors V, VII, IX, X and XIII, proteins C and S and antithrombin aswell as components of the complement system)

The liver stores large amounts of vitamins, particularly A, D and B12, vitamin K andfolate), and also minerals iron in ferritin and haemosiderin and copper.

As The liver receives amino acids degraded by transamination and oxidative

deamination ammonia, converted to urea excreted by kidneys.

L

iver

Physio

logy

Cont


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Formation of bile (Bile secretion and bile acid metabolism)

- RBCs >> heme Oxidized into >> bileverdine >> reduction to (indirect bilirubin).

1- Uptake of indirect bilirubin through Y and Z receptors in the liver.

2- Conjugation and Secretion:

- Conjugationoccurs in the liver by glucouronyl transferease and the conjugatedbilirubin is secreted with the bileinto the small intestine in the form ofstercobilinogenwhich passing into three directions:

Part of it enters the enterohepaticcirculation.

Another part escapes to the systemic circulationreaching the kidneyandsecreted in urine (urobilinogen).

The last part passes to the large intestineto be transformed into stercobilin.

L

iver

Physio

logy

Cont


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Hormone and drug inactivation

The liver catabolizes hormones such as insulin, glucagon, estrogens,growth hormone, glucocorticoids and parathyroid hormone.

It is also the prime target organ for many hormones (e.g. insulin). It isthe major site for the metabolism of drugs and alcohol .

Fat-soluble drugs are convertedto water-soluble substances thatfacilitate their excretion in the bile or urine.

Cholecalciferolis converted to 25-hydroxycholecalciferol.Liver

Physio

logy

Cont


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Immunological function

The reticuloendothelial system of the liver contains manyimmunologically active cells.

The liver acts as a sieve for the bacterial and other antigens carried to

it through the portal vein from G.I.T., they are phagocytosedbyKupffer cells, these cells secrete interleukinsand tumour necrosisfactor (TNF).

The reticuloendothelial system plays a role in tissue repair, T and Blymphocyte interaction, and cytotoxic activity in disease processes.

L

iver

Physio

logy

Cont


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Liver Cirrhosis

Definition:

It is a chronicliver disease results from necrosisof

hepatocytes followed by fibrous tissue deposition andformation of regenerating nodules with loss of hepaticarchitecture.

This derangement eventually produces portalhypertension and liver cell failure.


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Pathogenesis

Long standing injury to the liver lead toinflammation, necrosis and eventually fibrosis(initiated by activation of stellate cells).

These liver injuries e.g. (virus, alcohol, .... )stimulate kupffer cells release of cytokinesstimulate into (stellate) cells excessiverelease and deposition of collagen fibres loss

of hepatic architecture (cirrhosis).

P h l


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PathologyThe characteristic features of cirrhosis are regenerating nodules separated

by fibrous septa and loss of the normal lobular architecture within thenodules .

Two types of cirrhosis have been described which give clues to the underlyingcause:

Micronodular cirrhosis:

Regenerating nodules are usually less than 3 mm in size and the liver isinvolved uniformly.

This type is often caused by ongoing alcohol damage or biliary tract disease.

Macronodular cirrhosis.:

The nodulesare of variable size

and normal acini may be seen within the larger nodules. This type is oftenseen following chronic viral hepatitis.

A mixed picture with small and large nodules is sometimes seen.


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Investigations

These are performed to assess the severity andtype of liver disease.

1- SeverityLiver function:

Serum albumin and prothrombin time are the best indicators of liver function

Liver biochemistry:

This can be normal, depending on

the severity of cirrhosis. In most cases there is at least a slight elevation in theserum ALP and serum aminotransferases.

Serum electrolytes:

A low sodium indicates severe liver diseasedue to a defect in free water clearanceor to

excess diuretic therapy.

Serum creatinine:An elevated concentration > 130 mol/L is a marker of worse prognosis. In addition,serum -fetoprotein if > 200 ng/mL is strongly suggestive of the presence of ahepatocellular carcinoma.


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Cont. Investigations2- Type This can be determined by:

viral markers

serum autoantibodiesserum immunoglobulins

iron indices and ferritin (Total iron-binding capacity

(TIBC) and ferritin should be measured to exclude hereditary

Haemochromatosis)

copper, caeruloplasmin (Serum copper and serum 1-antitrypsin should always be

measured in young cirrhotics. )1-antitrypsin

Ultrasound examination:

This can demonstrate changes in size and shape of the liver. Fatty change

and fibrosis produce a diffuse increased echogenicity. The patency of the portal andhepatic veins can be evaluated. It is useful in detecting hepatocellular carcinoma

CT scan

Endoscopy is performed for the detection and treatment of varices, and portalhypertensive

Biopsy:

This is usually necessary to confirm the severity and typeof liver disease.


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Management

Patients should have 6-monthly ultrasound to detect the earlydevelopment of a hepatocellular carcinoma.

Treatment of the underlying cause may arrest or occasionallyreverse the cirrhotic changes .

Patients with compensated cirrhosis should lead a normal life.

The only dietary restriction is to reduce salt intake.

Aspirin and NSAIDs should be avoided.

Alcohol should be avoided ??


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LIVER TRANSPLANTATIONWhat are the Indications?

- Acute liver disease:

Patients with fulminant hepatic failure of any cause, including acute viral hepatitis maybe considered.

- Chronic liver disease:

The indications for transplantation are usually for complications of cirrhosis, no longerresponsive to therapy.

- All patients with end-stage (Childs grade C) cirrhosis.

. In addition specific extrahepatic complications of cirrhosis, even with preserved liverfunction, such as hepatopulmonary syndrome (shunting in the lung leading to hypoxia)and porto-pulmonary hypertension,can be reversed by liver transplantation.

- Primary biliary cirrhosis: Patients with this disease should be transplanted when theirserum bilirubin is persistently > 100 mol/L or symptoms such as itching are intolerable.

- Chronic hepatitis B if HBV DNA negative or levels falling under therapy. Following

transplantation, recurrence of hepatitis is prevented by hepatitis B immunoglobulin


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- Chronic hepatitis C is the most common indication.

- Autoimmune hepatitis. In patients who have failed to respond to medical treatmentor have major side-effects of corticosteroid therapy.

- Alcoholic liver disease !!

- Primary metabolic disorders. Examples are Wilsons disease, hereditaryhaemochromatosisand 1- antitrypsin deficiency.

- Other conditions, such as sclerosing cholangitis

LIVER TRANSPLANTATION Cont..


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Contraindications:

Absolute contraindications:

- active sepsis outside the hepatobiliary tree

- malignancy outside the liver,

- liver metastases

- If the patient is not psychologically committed.

Relative contraindications:- mainly anatomical considerations that would make surgery more difficult, such as

extensive splanchnic venous thrombosis.

With exceptions, patientsaged 65 years or over are not usually transplanted.

In hepatocellular carcinoma the recurrence rate is high unless there are fewer

than three small (< 3 cm) lesions, or a solitary nodule of < 5 cm.

LIVER TRANSPLANTATION Cont..

P i


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Prognosis


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COMPLICATIONS AND EFFECTS OFCIRRHOSIS


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Portal hypertension

Variceal haemorrhage

Ascites

Portosystemic encephalopathy (PSE)

Renal failure (hepatorenal syndrome)

Hepatopulmonary syndrome

Porto-pulmonary hypertension

Primary hepatocellular carcinoma

COMPLICATIONS AND EFFECTS OF CIRRHOSIS


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Cont.com

plicationsandeffects

ofcirrhosis:1-Portalhypertension

The portal vein is formed by the union of the superior mesenteric and splenic

veins.

The pressure within it is normally 58 mmHg with only a small gradient across

the liver to the hepatic vein in which blood is returned to the heart via the inferior

vena cava.

Portal hypertension can be classified according to the site of obstruction:

prehepaticdue to blockage of the portal vein before the liver

intrahepaticdue to distortion of the liver architecture, which can be

presinusoidal (e.g. in schistosomiasis) or postsinusoidal (e.g. in cirrhosis)

posthepaticdue to venous blockage outside the liver(rare).

Portal hypertension


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As portal pressure rises above 1012 mmHg the compliant venous system

dilates and collaterals occur within the systemic venous system.

The main sites of the collaterals are at the gastro-oesophageal junction, the

rectum, theleft renal vein, thediaphragm, theretroperitoneumand the anterior

abdominal wall via the umbilical vein.

The collaterals at the gastro-oesophageal junction (varices)

Rectal varices are found frequently (30%)

gut becomes congested giving rise to portal hypertensive gastropathy andcolopathy, in which there is punctate erythema sometimes erosions, which can

bleed.

Portal hypertension

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ofcirrhosis:1-Portalhypertension

P th h i l


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Pathophysio logy

Portal vascular resistance is increased in chronic liver disease.

During liver injury: stellate cells are activated and transform into myofibroblasts.

expression of the specific smooth muscle protein -actin under the influence of

endothelin, nitricoxide or prostaglandins.

the contraction of these activated cells contributes to abnormal blood flow

patterns and increased resistance to blood flow.

the balance of fibrogenic and fibrolytic factors is shifted towards fibrogenesis.

leads to portal hypertension and opening of portosystemic anastomoses in both

precirrhotic and cirrhotic livers. Neoangiogenesis also occurs.

Patients with cirrhosis have a hyperdynamic circulation due to the release of

nitric oxide and glucagon, which leads to peripheral and splanchnic

vasodilatation.

This effect is followed by plasma volume expansion due to sodium retention

and this has a significant effect in maintaining portal hypertension.

Cont.com


ofcirrhosis:1-Portal

hypertension


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Causes

Intrahepatic causes

Posthepatic causes

Prehepatic causes

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hypertension


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Prehepatic causes


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Extrahepatic blockage is due to portal vein thrombosis.

The cause is often unidentified, but some cases are due to portal vein occlusion

secondary to congenital portal venous abnormalities or neonatal sepsis of the

umbilical vein.

Many are due to inherited defects causing prothrombotic conditions, e.g. factor V

Leiden.

Patients usually present with bleeding, often at a young age.

They have normal liver function and, prognosis excellent.

The portal vein blockage can be identified by ultrasoundwith Doppler imaging; CT

and MR angiography.

Treatment is repeated endoscopic therapy ornonselective beta-blockade.

Splenectomy is only performed if there is isolated splenic vein thrombosis.

Anticoagulation prevents further thrombosis and does not increase the risk

of bleeding; used when there is a high risk of recurrent thrombosis.

Prehepatic causes

Cont.com



hypertension

Intrahepatic causes


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cirrhosis is the most common intrahepatic cause of portal hypertension

other causes:

Non-cirrhotic portal hypertension.portal hypertension and variceal bleeding without cirrhosis.

Histologically, the liver shows mild portal tract fibrosis.

The aetiology is unknown, but arsenic, vinyl chloride, antiretroviral therapy and

other toxic agents have been implicated.

A similar disease is found frequently in India.

liver lesion does not progress and the prognosis is therefore good.

Schistosomiasis with extensive fibrosis is the commonest cause,

endemic areas such as Egypt and Brazil.

often there may be concomitant liver disease such as HCV infection

.

Other causes include congenital hepatic fibrosis, nodular regenerativehyperplasiaand partial nodular transformation(rare).

The common features of hyperplastic liver cell growth in the form of nodulesbut in

contrast to cirrhosis, fibrosis is typically absent.

A wedge liver biopsy is usually required to establish the diagnosis.

hormones are none implicated in aetiology or progression.

Intrahepatic causes

Cont.com



hypertension


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Posthepat ic causes

Prolonged severe heart failure with tricuspid incompetence

constrictive pericarditis

both lead to portal hypertension.

Cont.com



hypertension


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Clinical features

Patients with portal hypertension are often asymptomaticand the only clinical

evidence of portal hypertension is splenomegaly.

Clinical features of chronic liver disease are usually present.

Presenting features may include:

haematemesis or melaena from rupture of gastro-oesophageal varices orportal hypertensive gastropathy

ascites

encephalopathy

breathlessness due to porto-pulmonary hypertension or

hepatopulmonary syndrome (rare).Cont.com



hypertension


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Variceal haemorrhage

Approximately 90% of patients with cirrhosis will develop gastro-oesophageal

varices, over 10 years, only onethird of these will bleed from them.

Bleeding is likely to occur with large varices, red signs on varices (diagnosed

at endoscopy) and in severe liver disease.

Cont.com


ofcirrhosis:2-Varicea

lhaemorrhage


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Management

Management can be divided into the active bleeding episode,the

prevention of rebleeding, and prophylactic measures to prevent the first

haemorrhage.

the prognosis depends on the severity of the underlying liver disease, with

an overall mortality from variceal haemorrhage of 25%, reaching50% in

Childs grade C.

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lhaemorrhage


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In i t ia l management of acute var iceal bleeding

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lhaemorrhage

Resusci tat ion


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Resusci tat ion

Assess the general condition of the patientpulse and blood pressure.

Insert an intravenous line and obtain blood for grouping and crossmatching,haemoglobin, PT/INR, urea, electrolytes, creatinine, liver biochemistry and blood

cultures.

Restore blood volume with plasma expanders or blood transfusion.

Prompt correction of hypovolaemia is necessary in patients with cirrhosis as theirbaroreceptor reflexes are diminished.

Ascitic tap.

Monitor for alcohol withdrawal. Give thiamine i.v.

Start prophylactic antibioticsthird generation cephalosporins, e.g. cefotaxime.

These treat and prevent infection and early rebleeding and reduce mortality.

Cont.com



lhaemorrhage

Urgent endos copy


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Urgent endos copy

toconfirm the diagnosis of varices.

excludes bleeding from other sites (e.g. gastric ulceration) or portal

hypertensive (or congestive) gastropathy.

injected with a sclerosing agent that may arrest bleeding by producing vessel

thrombosis

Cont.com



lhaemorrhage

Balloon tamponade is used mainly to control bleeding if endoscopictherapy or vasoconstrictor therapy has failed

Transjugular intrahepatic portocaval shunt (TIPS)

is used when bleeding cannot be stopped after two

sessions of endoscopic therapy within 5 days.

Emergency surgery

This is used when other measures fail or if TIPS is not

available

and, particularly, if the rebleeding is from gastric fundal

varices.


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Lon g-term measu res

Oral propranolol in a dose sufficient to reduce resting pulse rate by 25% has been

shown to decrease portal pressure.

Portal inflow is reduced by two mechanisms:

1. decrease in cardiac output (1),

2. blockade of 2 vasodilator receptors on the splanchnic arteries, leaving an

unopposed vasoconstrictor effect.

Cont.com



lhaemorrhage

Ascites


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The pathogenesis of ascites in liver disease is secondary to renal sodium and

water retention.

Several factors are involved:

Sodium and water retention results from peripheral arterial vasodilatation andconsequent reduction in the effective blood volume.

Portal hypertension exerts a local hydrostatic pressure and leads to increased

hepatic and splanchnic production of lymph and transudation of fluid into the

peritoneal cavity.

Low serum albumin (a consequence of poor synthetic liver function) may further

contribute by a reduction in plasma oncotic pressure.

Co

nt.complicationsand

effectsofcirrhosis:3-Ascites


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Co

nt.complicationsand

effectsofcirrhosis:3-

Ascites

M t


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Management

The aim is to reduce sodium intake and increase renal excretion of sodium,

Check serum electrolytes and creatinine at the start and every other day; weigh

patient and measure urinary output daily.

Bed rest alone will lead to a diuresis in a small proportion of people by

improving renal perfusion, but in practice is not helpful.

By dietary sodium restriction it is possible to reduce sodium intake to 40 mmol

in 24 hours and still maintain an adequate protein and calorie intake with a

palatable diet.

Drugs: many contain significant amounts of sodium (up to 50 mmol daily).

include antacids, antibiotics(particularly the penicillins and cephalosporins) and

effervescent tablets. Sodium-retaining drugs (nonsteroidals, corticosteroids)

should be avoided.

Co

nt.complicationsand


Ascites

Cont Management


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Cont. Management

Fluid restriction is probably not necessary unless the serum sodium

is under 128 mmol/L.

The diuretic of first choice is the aldosterone antagonist

spironolactone

Paracentesis This is used to relieve symptomatic tense ascites.

Shunts a transjugular intrahepatic portosystemic shunt (TIPS) is used for

resistant ascites providing there is no spontaneous portosystemic

encephalopathy and minimal disturbance of renal function.Co

nt.complicationsand


Ascites

Spontaneous bacterial peritonitis (SBP)


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Spontaneous bacterial peritonitis (SBP)

A serious complication of ascites with cirrhosis.

occurs in approximately8%. The infecting.

Organisms access to the peritoneum by haematogenous spread

most are Escherichia coli, Klebsiella or enterococci.

The condition should be suspected in any patient with ascites who clinically

deteriorates.

A raised neutrophil count in ascites is alone sufficientevidence to start treatment

immediately.

A third-generation cephalosporin (cefotaxime or ceftazidime) is used and is

modified on the basis of culture results.

Mortality is 1015%.

Recurrenceis common (70% within a year) and an oral quinolone

SBP is an indication to refer to a liver transplant centre.

Co

nt.complicationsand


Ascites


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Portosystemic encephalopathy (PSE)

This is a chronic neuropsychiatric syndrome secondary to cirrhosis.

Acute encephalopathy can occur in acute hepatic Failure.

can occur in portal hypertensive patients due to spontaneous shunting or in

those with surgical or TIPS shunts.

Encephalopathy is potentially reversible.

Co

nt.complicationsand


Ascites

Pathogenesis


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Pathogenesis

The mechanism is unknown but several factors are involved.

In cirrhosis portal blood bypasses the liver via the collaterals and the toxic

metabolites pass directly to the brain to produce the encephalopathy.

Many toxic substances may be causative factors including ammonia, free fatty

acids, mercaptans andaccumulation of false neurotransmitters (octopamine) or

activation of the -aminobutyric acid (GABA) inhibitory neurotransmitter

system.

Increased blood levels of aromatic amino acids (tyrosine and phenylalanine) and

reduced branched-chain amino acids (valine, leucine and isoleucine) also occur.

Ammonia has a major role ammonia-induced alteration of brain

neurotransmitter balanceespecially at the astrocyteneurone interfaceis

the leading pathophysiological mechanism.

Ammonia is produced by intestinal bacteria breaking down protein.

Co

nt.complicationsand


Ascites

Clinic al features


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Clinic al features

drowsy and comatose

Chronically:disorder of personality, mood and intellect, reversal of normal sleep rhythm.

irritable, confused, disorientated and has slow slurred speech.

General features include nausea, vomiting and weakness.

Coma occurs as the encephalopathy becomes more marked, there is always

hyperreflexia and increased tone.

Signs include:

fetor hepaticus (a sweet smell to the breath)a coarse flapping tremor

decreased mental function

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nt.complicationsand


Ascites


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Add i t ional invest igat ions

Electroencephalography (EEG) shows a decrease in the frequency of the

normal -waves

Visual evoked responses also detect subclinical encephalopathy.

Co

nt.complicationsand


Ascites

Management


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Management

Identify and remove the possible precipitating cause.

Give purgation and enemas to empty the bowels of nitrogenous

substances.

Maintain nutrition with adequate calories if necessary via a fine-bore

nasogastric tube, do not restrict protein for more than 48 hours.

Give antibiotics. Rifaximin is mainly unabsorbed and well tolerated long

term. Metronidazole (200 mg four times daily) is also effective in the acute

situation.

Neomycin should be avoided.

Stop or reduce diuretic therapy.

Give intravenous fluids as necessary (beware of too much sodium).

Treat any infection.

Increase protein in the diet to the limit of tolerance as the encephalopathy

improves.

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nt.complicationsand


Ascites


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Course and progno s is

Acute encephalopathy in acute liver failure has a very poor prognosis with high

mortality.

In cirrhosis chronic PSE is very variableand adversely affects prognosis.

Very rarely with chronic portosystemic shunting an organic syndrome with

cerebellar signs or choreoathetosis can develop

myelopathy leading to a spastic paraparesis due to demyelination.

Patients should be referred to a liver transplant centre.Cont.complicationsand


Ascites

Renal failure (hepatorenal syndrome) occurs in a patient with advanced cirrhosis portal hypertension with jaundice and)


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occurs in a patient with advanced cirrhosis, portal hypertension with jaundice and

ascites.

The urine output is low with a low urinary sodium concentration

The renal failure is described as functional sometimes precipitated by diuretic,

NSAIDs, diarrhoea or paracentesis, and infection, particularly spontaneous

bacterial peritonitis.

The initiating factor is thought to be extreme peripheral vasodilatation possibly

due to nitric oxide leading to an extreme decrease in the effective blood volumeand hypotension.

This activates the homeostatic mechanisms, causing a rise in plasma renin,

aldosterone, norepinephrine and vasopressin leading to vasoconstriction of the

renal vasculature.

There is an increased preglomerular vascular resistance causing the blood flow to

be directed away from the renal cortex.

This leads to a reduced glomerular filtration rate and plasma renin remains high.

Salt and water retention occur with reabsorption of sodium from the

renal tubules.Cont.complicationsan

deffectsofcirrhosis:4

-Renalfailure(hepato

renalsyndrome)

Cont. Renal failure (hepatorenal syndrome))


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Other mediators have been incriminated in the pathogenesis of the

hepatorenal syndrome, in particular the eicosanoids.

This has been supported by the precipitation of the syndrome by inhibitors of

prostaglandin synthase such as non-steroidal anti-inflammatory drugs

(NSAIDs).

Diuretic therapy should be stopped and intravascular hypovolaemia

corrected, preferably with albumin.

Terlipressin or noradrenaline with intravenous albumin improves renal

function in one-third of patients.

Liver transplantation is the best option.

Cont. Renal failure (hepatorenal syndrome)

C

ont.complicationsan

deffectsofcirrhosis:4-Renalfailure(hepato

renalsyndrome)



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This is defined as a hypoxaemia occurring in patients with advanced liver

disease.

It is due to intrapulmonary vascular dilatation with no evidence of primarypulmonary disease.

The patients have features of cirrhosis with spider naevi and clubbing as well

as cyanosis.

Most patients have no respiratory symptoms, but with more severe disease,

patients are breathless on standing.

Transthoracic ECHO shows intrapulmonary shunting, and arterial blood

gases confirm the arterial oxygen desaturation.

These changes are improved with liver transplantation.

Cont.complication

sandeffectsofcirrhosis:5-Hepatopulmonar

ysyndrome


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Porto-pulmonary hypertension

there is pulmonary hypertension.

It occurs in 12%of patients with cirrhosis related to portal hypertension.

It may respond to medical therapy.

Severe pulmonary hypertension is a contraindication for liver transplantation.

Cont.complicationsandeffectsof

6-Porto-pulmonaryhypertension

Primary hepatocellular carcinoma

H t ll l i (HCC) i th fifth t ld id


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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide.

Aet io logy

Carriers of HBV and HCV have an extremely high risk of developing HCC.

In areas where HBV is prevalent 90% of patients with this cancer are positive for

the hepatitis B virus.

Cirrhosis is present in approximately 80% of these patients.

The development of HCC is related to the integration of viral HBV DNA into the

genome of the host hepatocyte and the degree of viral replication (> 10 000

copies/mL).

The risk of HCC in HCV is higher than in HBV (even higher with both HBV and

HCV) despite no viral integration.

Unlike HBV infection, cirrhosis is always present.

Primary liver cancer is also associated with other forms of cirrhosis, such as

alcoholic cirrhosis and haemochromatosis.

Cont.complic

ationsandeffectsof7

-Primaryhepatocellularcarcinoma

Cont. Primary hepatocellular carcinoma


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Non-alcoholic fatty liver disease is associated with HCC probably secondary to

the presence of cirrhosis.

Males are affected more than females.

Other aetiological factors are aflatoxin (a metabolite of a fungus found in

groundnuts) and androgenic steroids, and there is a weak association with the

contraceptive pill.

Cont.complic

ationsandeffectsof7-Primaryhepatocellularcarcinoma

Pathology


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Pathology

The tumour is either single or occurs as multiple nodules throughout the liver.

Histologically it consists of cells resembling hepatocytes.

It can metastasize via the hepatic or portal veins to the lymph nodes, bones and

lungs.

Clinic al features

The clinical features include weight loss, anorexia, fever, an ache in the right

hypochondrium and ascites.

The rapid development of these features in a cirrhotic patient is suggestive

of HCC.

On examination an enlarged irregular tender liver may be felt.

Increasingly due to surveillance HCC is found without symptoms in cirrhotics.Cont.complic


Invest igat ions


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Serum -fetoprotein may be raised.

Ultrasound scans show filling defects.

Enhanced CT scans identify HCC but it is difficult to confirm the diagnosis in

lesions < 2 cm.

MRI can further help to delineate lesions.

Tumour biopsy, particularly under ultrasonic guidance.

Cont.complic



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Treatment and pro gno s is

Surgical resection is occasionally possible.

Conventional chemotherapy and radiotherapy.

Radiofrequency ablation is also effective.

Antiangiogenic compounds are being evaluated: sorafenib prolongs survival

in patients with non-resectable tumours.

Liver transplantation is curative in patients with smaller tumours (< 3 nodules

< 3 cm diameter or a single tumour < 5 cm).

In advanced cases survival is seldom more than 6 months.Cont.complicationsandeffectsof7-Primaryhepatocellul

arcarcinoma


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Types of cirrhosis

Type of cirrhosis


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Common

Alcohol

Less common

Metabolic

Wilsons disease

Alpha -1antitrypsindeficiency

hemochromatosis

Biliary obstruction

biliary cirrhosis

Hepaticcongestion

Budd- chiarisyndrome


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Alcoholic cirrhosis

acetaldehyde

responsible for liver cell damaged

Alcohol( ethanol )

metabolized in the liver

Oxidation


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Alcoholic cirrhosis


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Alcoholic cirrhosis Signs of chronic liver

diseases :1. Drowsiness2. Hyperventilation

3. Flapping tremor

4. Jaundice5. Ascites

6. Leukonychia

7. Peripheral Oedema

8. Bruising

9. Dupuytren's contracture

Alcoholic cirrhosis
http://upload.wikimedia.org/wikipedia/commons/2/21/Dupuytren's2010.JPG


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coho c c rrhos s

Usually the patient present with one of the Complications of

cirrhosis :1. Portal Hypertension

Ascites

Hypersplenism (with or without splenomegaly)

Varices (lower oesophageal and rectal)

2. Synthetic Dysfunction

Hypoalbuminaemia

Coagulopathy

3. Hepatopulmonary Syndrome

4. Hepatorenal Syndrome5. Encephalopathy

6. Hepatocellular Carcinoma


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Investigations

CBC :

1. Macrocytosisin the absence ofanemia .

2. Leukocytosis or leukopenia.3. Thrombocytopenia.

LFTs :

All LFTs are high.

Liver biopsy :

It is diagnosticand shows mallorybodies

( alcoholic hyaline )

Eosinophilic Mallory bodies areseen in hepatocytes, which aresurrounded by fibrous tissue


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Management

General measures :1. Stop drinking alcohol .

2. Nutritional support toimprove malnutrition

especially vitamine B1thiamine.

3. Alcoholic cirrhosis

Management as cirrhosis.


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Management

Be carful

if patient need glucose

administration increasethiamine requirement andprecipitate wernicke korsakoff syndrome

therefore thiamine shouldbe given IV before glucoseinfusion .


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Biliary cirrhosis

Biliary cirrhosis results fromprolongedbiliary obstructionanywhere between the smallinterlobular bile duct and papilla of

vater . Types of biliary cirrhosis :

1. Primary

2. Secondary


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Primary biliary cirrhosis

Primary biliary cirrhosis is a chronic diseaseof liver in which small interlobular bile ductsof liver become progressively damagedand

leading to cirrhosisand cholestasis.

Etiology is unknown antimitochondrialantibodies are found in almost all patients.


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I i i


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Investigations

1) Liver function test : ALK ( veryhigh)2) Atimitochondrial antibodies (AMA) >

95 % of cases.3) Serum cholesterolis high.

4) SerumIgM may be very high.5) Ultrasound : diffusealteration inliver architecture.

6) Liver biopsy show chareacteristicfeatures such as :

A. Infiltration of portal tract by lymphocyteand plasma cells .

B. Loss of small bile ductsC. Portal tract fibrosis

D. Periductal epithelioid granulomata about40% of cases.


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Management1. Ursodeoxycholic acid (Ursodiol) is the most frequently

used treatment. This helps reduce the cholestasis andimproves liver function tests

2. Pruritus :

A. Cholestyramine.

B. Rifampicin .C. Opioid antaonists .

3. Malabsorption:

A. Monthly inject vit K.

B. Vit D and calcium supplentsC. Reducing fat intake to 40 g/d.

D. Bisphosphonate for osteoporosis.

4. Statins for hypercholesterolemia.


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Secondary biliary cirrhosis

This develops afterprolonged large bile ductobstruction due to :

1) Gall stones2) Bile duct stricture.

Sing and symptoms are same asthat of PBC.

Diagnosis is based onultrasound which commonbile duct dilated .

Hemochromatosis


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Hemochromatosis is a condition in which the amount

of total body iron is increase that damaged theorgans . It may be primary or secondary.

primary Hemochromatosis :

is inherited autosomal recessive disease characterizedbyexcess iron deposition in various organs in form ofhemosiderin leading to fibrosis and functional organsfailure.

i H h t i


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primary Hemochromatosis

Mostly organs affected are :1)Liver 2) pancreas 3)heart

4) adrenals 5) testes 6)kidneys7) Pituitary

Clinical features


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Clinical features

Mostly affecting men.1. Hepatic cirrhosis.

2. DM.

3. Cardiomegaly with or without heartfailure & conduction disturbance.

4. Bronze pigmentation.

5. Loss of libido , impotence & testicular

atrophy.6. Arthritis.

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Investatigations

1. Serum ferritin is increased.2. Serum iron concentration

increased.

3. Serum iron binding capacity isreduced.

4. Liver biopsy : shows heavy irondeposition and hepatic fibrosis .

T t t


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Treatment

1. Avoid food rich by in ironsuch as red meat , vitaminC , alcohol.

2. venesection of 500ml

(250 mg iron ) weeklyuntil the serum iron isnormal .

3. Chelating agent

deferoxaminesubcutaneous injection. Ifthe dose not toleratevenesection .

S d H h t i


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Secondary Hemochromatosis

Secondry causes of ironoverload are hemolyticanemia such as thalassemiain which multipletransfusions are required .

Treatment: chelatingtherapy with deferoxamine

is usually required.

Wilson's disease


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autosomal recessivegenetic disorder in which copper

accumulates in tissues. Increase copper content is due to increase absorption from

small intestine and decrease excretion in bile .

The most affected organs are:

1) Liver 2)basal ganglia ( brain) 3)eyes

4) Kidneys 5) Skeleton

Clinical features


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HormonesHypoparathyroidism

Heart andkidney

EyesNeuropsychiatricsymptoms

Liver disease

Pain in the face,legs, and feet

cardiacarrhythmias

KayserFleischer

rings

behavioralchanges,

depression,anxiety andpsychosis

fatigue

Abdominal paincardiomyopathyResting tremorconfusion

Convulsions(seizures)

renal tubularacidosis

Dystopia of bulbarmuscle such asdysarthria and

dysphagia

Bruising

Muscle crampsTetanic contractions

portalhypertension:1. Upper GI

bleeding2. Abdominal

distension

investigations
http://upload.wikimedia.org/wikipedia/commons/0/00/Kayser-Fleischer_ring.jpg


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investigations

1. serum copper:

Is reduce but it may be normal.

2. Serum Ceruloplasmin :

abnormally low (100-1000 g/24h .

4. liver function tests :

Are high .

5. Liver biopsy :May show acute or chronic hepatitis or cirrhosis.

Treatment


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Treatment

1. Pencillamine: is the drug of choice thatchelates and excretes copper throughkidney in urine. Pyrodoxine50mg /week should be added, since

pencillamine is an antimetabolite ofthis vitamin and causes deficiency. Thedose can be reduced once the diseaseis controlled, but treatment mustcontinue for life. Side effects are skinrashes, leukopenia, and renal damage.

2. Trientine dihydrochoride: if patientdevelops side effects of pencillamine

Continue Treatment


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ont nu r atm nt

3. Zinc acetate: Oral zinc acetate

daily promotes fecal excretion ofcopper and used as maintenancetherapy after chelation withpencillamine or as a first-linetherapy in presymptomaticor

pregnantpatients.4. Ammonium tetrathiomolybdate:is an initial therapy forneurologic Wilsons disease.

5. Liver transplantation: indicated

for fulminant hepatic failure, endstage liver disease and selectedcases of severe neurologicaldisease.


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1-Antitrypsin Deficiency


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yp y The genetic variants of 1-AT are characterized by

their electrophoreticmobilities as medium (M), slow(S) or very slow (Z).

The normalgeneotype is protease inhibitor MM thehomozygotefor Z is PiZZ, and the heterozygotesarePiMZ and PiSZ.

This results in decreased synthesis and secretionofthe protein by the liver.

Causes liver disease is uncertain.

The failure of secretion of the abnormal proteinleads to an accumulation in the liver, causing liverdamage.

Clinical features


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The majority of patients with clinical

disease are homozygoteswith a PiZZphenotype.

Some may present in childhoodand a

few require transplantation.

10 -15% of adult patients will developcirrhosis, usually over the age of 50

years, and 75% will have respiratoryproblems.

Cli i l f t s


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Clinical features

Approximately 5% ofpatients die of theirliver disease.

Heterozygotesmaydevelop liverdisease, but the riskis small.


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Treatment

No specific treatment is available otherthan management of complications of liverdisease. Liver transplantation may beadvised for advanced liver disease.

On physical examination


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On physical examination

Sign of ChronicLiver

Disease+DupuytrensContracture

+Peripheral

Neuropathy+

Cerebellar Signs

Alcohol


Disease

+Young+

Kayser-FleisherRings

+

Cerebellar Signs

Wilson's


Disease

+

Increasedpigmentation of

the skin

Haemochromatosis

Sign of

Chronic LiverDisease

+

Tattoos

Hepatitis C


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Reference


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Thank You

3 liver cell all

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