Download CIRROSIS BY

CIRRHOSIS
ASSIT.PROF.
TARIK IBRAHIM ZAHER
AMANY MOHAMAD IBRAHIM
Cirrhosis is a condition in which the liver slowly deteriorates
and malfunctions due to chronic injury. Scar tissue replaces
healthy liver tissue, partially blocking the flow of blood
through the liver. Scarring also impairs the liver’s ability to:
1-control infections 
2-remove bacteria and toxins from the blood 
3-prosecc nutrients, hormones, and drugs 
4- make proteins that regulate blood clotting 
5-produce bile to help absorb fats—including cholesterol—
and fat-soluble vitamins


A healthy liver is able to regenerate most of its own cells 
when they become damaged. With end-stage cirrhosis, the
liver can no longer effectively replace damaged cells. A
.healthy liver is necessary for survival
Definition:
Cirrhosis results from the necrosisof
liver cells followed by fibrosis and
nodule formation the liver
architecture is diffusely abnormal
and this interferes with liver blood
flow and function:
1-Portal hypertension
2 - impaird liver function
Causes of cirrhosis
1- HepatitisB & Hepatitis C 
2- Cystic fibrosis 
3-Fat that accumulates in the 
liver (nonalcoholic fatty liver
disease)
4-Hardening and scarring of the
bile ducts (primary sclerosing
cholangitis)
5- Inability to process sugars in
milk (galactosemia)
6-Too much copper accumulated
in the liver (Wilson's disease)



7 -Liver disease caused by your
body's immune system
(autoimmune hepatitis)
8-Poorly formed bile ducts in 
babies (biliary atresia)
9- Iron build up in the body 
(hemochromatosis)
10-Destruction of the bile ducts
(primary
biliary cirrhosis)
ohol
.1
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11-Budd-Chiari syndrome 
12-Veno-occlusive disease 
13-Drugs (methotrexate) 
14-α1-Antitrypsin deficiency 
15-Hepatic venous congesion 
16-Idiopathic (cryptogenic) 
17-Alcohol 
18-Other viruses 
Pathogenesis : Chronic injury to the
liver results in inflammation, necrosis and,
eventually, fibrosis. Fibrosis is initiated by
activation of the stellate cells.Kupffer cells,
damaged hepatocytes and activated also
platelets are probably involved. Stellate
cells are activated by many cytokines and
their receptors, reactive oxygen signals.
In the early stage of activation the stellate
cells become swollen and lose retinoids
with upregulation of receptors for
proliferative and fibrogenic cytokines, such
as platelet-derived growth factor (PDGF),
and transforming growth factor β1 (TGFβ1). TGF-β1 is the most potent fibrogenic
mediator identified.

Inflammatory cells contribute to fibrosis 
via cytokine secretion, in the space of
Disse, the normal matrix is replaced by
collagens, predominantly types 1 and 3,
and fibronectin. Subendothelial fibrosis
leads to loss of the endothelial
fenestrations (ports), and this impairs
liver function. Collagenases (matrix
metalloproteinases, MMPs) are able to
degrade this collagen but are inhibited by
tissue inhibitors of metalloproteinases
(TIMPs), which are increased in human
liver fibrosis. There is accumulating
evidence that in the early stages liver
fibrosis is reversible, particularly when
inflammation is reduced, e.g. by
suppressing or eliminating viruses.
Pathology:The characteristic features
of cirrhosis are regenerating nodules
separated by fibrous septa and loss of the
normal lobular architecture within the
nodules two types of cirrhosis are
present: Micronodular cirrhosis nodules
are usually less than 3 mm in size and the
liver is involved uniformly. This type is
often caused by ongoing alcohol damage
or biliary tract
disease
Macronodular cirrhosis the nodules are
of variable size and normal acini may be
seen within the larger nodules. This type
is often seen following chronic viral
.hepatitis
A mixed picture with small and large 
.nodules is sometimes seen


SYMPTOMS
Patients may be asymptomatic or complain of 
non-specific symptoms, particularly fatigue.
:Specific symptoms include:
-Right hypochondrial pain due to liver distension 
-Abdominal distension due to ascites 
-Ankle swelling due to fluid retention 
-Haematemesis and melaena from 
gastrointestinal haemorrhage
-Pruritus due to cholestasis - this is often an 
early symptom of primary biliary cirrhosis
-Breast swelling (gynaecomastia), loss of libido 
and amenorrhoea due to endocrine dysfunction
-Confusion and drowsiness due to 
neuropsychiatric complications (portosystemic
encephalopathy
-fever-loss of body weight- 
Signs:1-general signs
jaundice-fever-loss of bodyhair-LOSSof body 
weight-pallor-cacheexia
Spider navi :
Vascular
lesions consisting of

a central arteriole surrounded by many smaller vessels
because of an increase in estradiol. These occur in about
1/3 of cases
Palmar erythema:Exaggerations of normal speckled
mottling of the palm, because of altered sex
hormone metabolism.
Ecchymosis(1to 3cm)-purpura(3m to1cm) 
or petechia (<3mm) 
Scratch marks (pruritus):due to bile salt 
deposite in skin
Nail changes : clubbing-terry nail -leuchonychia
Oedema of the lower limb 
Xanthelasmas-parotid enlargement



2- local signs:

Abdominal enlargment –full flankes-umblical
hernia
Dilated viens-divercation of recti 
Venous hum: heard in epigastric region (on

. 
Caput medusa: In portal hypertension, the

examination by stethoscope) because of collateral
connections between portal system and the remnant
of the umbilical vein in portal hypertension
umbilical vein may open. Blood from the portal
venous system may be shunted through the
periumbilical veins into the umbilical vein and
ultimately to the abdominal wall veins, manifesting
.as caput medusa

Splenomegaly increase in size of the

spleen). Caused by congestion of the red pulp as a
result of portal hypertension).
Liver size:enlarged-normal
or

shranked
Neurological signs:
(disorientation-

drowsy-hepatic coma) :
hepatic encephalopathy 
:
Asterixis Bilateral asynchronous flapping of
outstretched, dorsiflexed hands
Fetor hepaticus : Musty odor in breath as a
result of increased dimethyl sulfide


Ascites:
Accumulation of fluid in the peritoneal cavity giving rise to
causes
of ascites according to serum-ascites albumin
gradient :
flank dullness (needs about 1500 mL to detect flank dullness).
High: >1.1g/dl
-Cirrhosis
-Chronic hepatic
congestion
Right sided hart failure
Budd Chiari syndrom
Constrictive
Low<1.1g/dl
Peritoneal carcinomatosis
-Peritonealtuberculosis
- Pancreatic and biliary disease
- Nephrotic syndrome
Nephrotic syndrom
Massive liver
metastases- myxedema
Investigations
These are performed to assess the
severity and type of cirrhosis
Liver function : Serum albumin .
and prothrombin time are the best


indicators of liver function: the outlook is
poor with an albumin level below 28 g/L.
The prothrombin time is prolonged
commensurate with the severity of the
liver disease
Bilirubin

Liver biochemistry : elevation in the serum
Alanine aminotransferase ALP) and serum
Aspartate aminotransferase (AST). In
decompensated cirrhosis all biochemistry is deranged
.Total proteins 
.Alkaline phosphatase

Serum electrolytes: A 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
In addition, serum α-fetoprotein if >200 ng/mL is
strongly suggestive of the presence of a hepatocellular
This can be determined .carcinoma


Lab to detect cause of cirrhosis .
:
1-viral marker 
2-serum autoantibodies
:


-Anti-mitochondrial antibody(primary biliary cirrhosis)
-anti- nuclear,smooth muscle(actin),liver/kidney 
microsomal antibody(AUTOIMMUNA HEPATITIS)
3- serum immunoglobulins:
-IgG

(AUTOIMMUNA HEPATITIS )
-IgM (primary biliary cirrhosis 
4-iron indices


5- copper and caeruloplasmin 
6-alpha 1 antitrypsin 
7- MARKER OF LIVER CIRRHOSIS 
8-Anti-nuclear cytoplasmic antibodies
9-Genetic analyses 


Ultrasound examination
This 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. The patency of the
portal and hepatic veins can be evaluated. It is useful
.in detecting hepatocellular carcinoma-ascites
Elastography is being used in diagnosis and follow-up
to avoid liver biopsy.
CT SCAN
:
hepatosplenomegaly, and dilated
collaterals are seen in chronic liver disease. Arterial
phase-contrast-enhanced scans are useful in the
.detection of hepatocellular carcinoma

Endoscopy is performed for the 
detection and treatment of varices,
and portal hypertensive gastropathy.
Colonoscopy is occasionally
.performed for colopathy
MRI scan: This is useful in the . 
diagnosis of benign tumours such as
haemangiomas. MR angiography can
demonstrate the vascular anatomy
and MR cholangiography the biliary
.tree
Liver biopsy

Scoring system in cirrhosis
(a)Modified Child – Pugh classification
Score
Ascites
Encephalopathy
Bilirubin
)Umol/l)
1
2
None
None
<34
Mild
Mild
34-50
3
Modrate/sever
Marked
>50
Albumin
)g/l)
.>35
28-35
<28
Prothrombin
time seconds over
normal
<4
4-6
>6
Sursurvival % for patient score
above
Child A
)<7)
Child B
(7-9)
Child C
(10+)
1year
82
5year
45
10 year
25
62
20
7
42
20
0
(b)Model 0f end stage- liver
disease (MELD)score
3.8 ×LN (bilirubin in mg/dl)+9.6 ×

LN(creatinine in mg/ dl)+11.2 ×LN (INR)+
6.4
To convert 
bilirubin from μmol/L to mg/dL divide by 
17
creatinine from μmol/L to mg/dL divide by
88.4
LN, natural logarithm; INR, international 
normalized ratio.
MELD scores (with no complications): 1- 
year survival 97% (score <10); 70%

management
Generally, liver damage from cirrhosis 
cannot be reversed, but treatment could
stop or delay further progression and
reduce complications. A healthy diet is
encouraged, as cirrhosis may be an
energy-consuming process. Close followup is often necessary. Antibiotics will be
prescribed for infections, and various
medications can help with itching.
Preventing further liver damage:
Regardless of underlying cause of cirrhosis, there
are drugs known as hepato-toxic effect
(high
dose of paracetamol-alcohol-Halothane-Steroidcontraceptive pills-erythromycin-oral
hypoglycaemics.,etc), avoid this drugs is very
important in hepatic patients.
Vaccination of susceptible patients should be
considered for prevention of chronic liver
.Hepatitis B and Hepatitis A diseases


Treating underlying causes:

. early treatment should be considered 
for Hepatitis C,B (interferon-ribavirinlamivudine)
interferon for viral hepatitis and 
corticosteroids for autoimmune hepatitis.
in ,Wilson's disease Cirrhosis caused by
which copper builds up in organs, is
,.e.g( chelation therapy treated with
to remove the copper )penicillamine
Stop alcohol intake in alcohilic cirrhosis 
Tretment of complications
ascites : Salt restriction-diurietics

Esophageal variceal bleeding: 
propranolol is For portal hypertension 
a commonly used agent to lower blood
pressure over the portal system. In severe
complications from portal transjugular
intrahepatic portosystemic
shunting is occasionally indicated to
relieve pressure on the portal vein. As this
can worsen encephalopathy, it is reserved
for those at low risk of encephalopathy,
and is generally regarded only as a bridge
to liver transplantation or as a palliative
.measure
Hepatic encephalopathy : 
Restriction protien diet-enema-lactulose
Hepatorenal syndrome : 

Is defined as urine sodium <10mmol and serum creatinine >1.5
mg/dl after trial of volume expansion without diuretics treatment
by Terlipressin or noradrenaline with intravenous
albumin improve function in 30% of cases

Spontaneous bacterial peritonitis(SBP):
Symptoms include fevers, chills, nausea, vomiting,

abdominal tenderness and general malaisePatients may
complain of abdominal pain and worsening ascites.Thirteen
percent of patients have no signs or Hepatic encephalopathy
Diagnosis necessitates paracentesis (needle drainage of the
ascitic fluid) and laboratory confirmation of ascitic neutrophils >
250/mm³.[1]
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Treatment of SBP:
Antibiotics


After confirmation of SBP, patients need hospital admission for 
intravenous antibiotics (most often cefotaxime 2g IV Q8-12H for at
least 5 days or ceftriaxone 2g IV Q24H). They will often also
receive intravenous albumin. A repeat paracentesis in 48
hours is sometimes performed to ensure control of infection. Once
patients have recovered from SBP, they require regular
prophylactic antibiotics (e.g. Septra DS 1 tab 5 times/week,
Ciprofloxacin 750 mg PO Q1W, norfloxacin 400 mg Q24H) as long
as they still have ascites.
Intravenous albumin

A randomized controlled trial found that intravenous albumin on
the day of admission and on hospital day 3 can reduce renal
impairment
liver transplantation 

Poor prognostic indicators in
Blood tests

Low albumin (< 28 g/L 
:Low serum sodium(<125mmol/L) 
Prolonged prothrombin time > 6 seconds
Raisedcreatinine >130 um/L 
Clinical:
cirrhosis


Persistent jaundice 
Persistent hypotension 
Haemorrhage from varices, particularly with poor liver function_
Ascites 
Neuropsychiatric complications developing with progressive liver
Small liver 
Aetiology (e.g. alcoholic cirrhosis,if patient continue drinking) 
Failure of response to treatment
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