Liver Cirrhosis

Liver Cirrhosis

By Group#5: Kate Bratcher, Tamara Campbell, Tim Pittman and
Jennifer Southard
What is the liver?

The largest organ in the abdomen.

It is comprised of four lobes, two major blood vessels,
and hepatocytes.
It is the only human organ capable of regenerating
tissue.
What are the functions of the liver?
There are three main
functions of the liver:
1)Vascular functions
2)Metabolic functions
3)Secretory and
excretory functions
1)Vascular functions

Formation of lymph
Neutralizing toxins,
most medicines and
hemoglobin
2)Metabolic functions

In carbohydrate metabolism: Gluconeogenesis,

Glycogenolysis, Glycogenesis, the breakdown of
insulin and other hormones
In protein metabolism: Deamination and
transamination of amino acids, removal of
ammonia by synthesis of urea, synthesis of non-
essential amino acids, synthesis of plasma
proteins, and synthesis of coagulation factors I, III,
V, VII, IX, and XI
2)Metabolic functions

In lipid metabolism: Cholesterol synthesis,

production of triglycerides, oxidizing triglycerides
to produce energy
In other areas: In the first trimester fetus, the liver
produces red blood cells and by week forty-two of
gestation, the bone marrow does this task
3)Secretory and excretory functions
Produces and excretes bile for food digestion
Stores glycogen, vitamin B12, iron, and copper
Only cells with the enzyme needed to convert
glucose-6-phosphate to glucose which enters the
blood stream
Cirrhosis

Damaged and dead

liver cells are then
replaced by fibrous
tissue which leads to
scarring
This scaring causes
liver cells to regenerate
in an abnormal pattern
which will lead to
decreased blood flow to
and through the liver.
It will also led to blood
back up in the portal
veins
What is Liver Cirrhosis?
Diffuse fibrosis of the liver with
nodule formation
Abnormal response of the liver to
any chronic injury

The Effect of The Liver Nodule

The serious and

sometimes deadly
complications of
cirrhosis are
because of the
decreased blood
flow to the liver and
blood back up in
the portal veins
Anatomy of the portal venous system
Mechanism of Portal HTN

Cirrhosis
Resistance portal flow
Mechanical Dynamic
Nodules Nitric oxide
Causes of Cirrhosis

Alcoholic Liver Disease

Hepatitis C and B
Chronic Autoimmune Hepatitis
Inherited Metabolic Diseases
Primary Biliary Cirrhosis
Nonalcoholic Steatohepatitis
Other causes
Alcoholic Liver Disease (ALD)

Usually develops after

decades of heavy
drinking.
Most common form of
cirrhosis in U.S.
The more you drink
the greater the risk of
developing ALD.
Hepatitis C and B

Second major cause of cirrhosis and chronic liver

disease in the United States.
Causes inflammation along with low grade
damage that after several decades leads to
cirrhosis.
Hepatitis B is the most common worldwide and
acts on the liver in the same way.
Chronic Autoimmune Hepatitis

Condition in which the persons own immune

system attacks the liver causing inflammation and
liver cell death.
Symptoms include jaundice, fever, and sometimes
hepatic dysfunction.
Serum protein electrophoresis and detection of
auto antibodies can help diagnose autoimmune
hepatitis.
Inherited Metabolic Disease

Hemocromatosis is a genetic disease can alter the

bodys ability to regulate iron absorption.
A faulty mechanism causes the body to absorb too
much iron and over time the excess is deposited
into the liver causing cirrhosis.
The gene that causes hemochromatosis was
identified on Chromosome 6 in 1996.
Primary Biliary Cirrhosis

Classified as a chronic bile duct disease, it causes

slow destruction of the bile ducts.
Bile then builds up in the liver which can lead to
cirrhosis and even complete liver failure.
The cause is unknown but may be related to
immune system problems.
Ursodiol may be beneficial but it does not cure the
disease, a liver transplant may be necessary.
Nonalcoholic Steatohepatitis (NASH)

Inflammation due to accumulation of fat in the liver

Many times patients do not know they have NASH
because it has no symptoms, and there is no
specific treatment.
Losing weight along with maintaining control of
diabetes and elevated lipid levels are essential.
Low fat diet and avoiding alcohol completely are
also recommended.
Other causes of Cirrhosis

Wilsons Disease is a genetic disorder that causes

excessive copper accumulation in the liver.
Glycogen storage diseases can interfere with the
way the liver produces and stores enzymes and
proteins the body needs to function properly.
Long term exposure to environmental toxins and
severe reactions to prescription drugs.
Schistosomiasis is a disease caused by parasitic
worms, not found in the United States but infects
about two million people worldwide.
Pathophysiology

Irreversible chronic injury of the hepatic

parenchyma
Extensive fibrosis - distortion of the
hepatic architecture
Formation of regenerative nodules

Clinical Manifestations

Spider angiomas
Palmar erythema
Nail changes
Muehrcke's nails
Terrys nails
Gynecomastia
Testicular atrophy




Clinical Manifestations

Muehrcke's nails Terrys nails

Clinical Manifestations

Fetor hepaticus Cruveilhier-

Jaundice Baumgarten murmur
Asterixis Hepatomegaly
Pigment gallstones Splenomegaly
Parotid gland Caput medusa
enlargement

Laboratory Studies

most common measured laboratory test classified

as LFTs include
the enzyme tests (principally the serum
aminotransferases, alkaline phosphatase, and gamma
glutamyl transpeptidase), the serum bilirubin
tests of synthetic function (principally the serum
albumin concentration and prothrombin time)
Radiologic Modalities

Can occasionally suggest the presence of

cirrhosis, they are not adequately sensitive or
specific for use as a primary diagnostic modality
Major utility of radiography in the evaluation of the
cirrhotic patient is in its ability to detect
complications of cirrhosis
Diagnosis

Liver biopsy
Obtained by either a percutaneous, transjugular,
laparoscopic, or radiographically-guided fine-needle
approach
Sensitivity of a liver biopsy for cirrhosis is in the range of
80 to 100 percent depending upon the method used, and
the size and number of specimens obtained
not necessary if the clinical, laboratory, and radiologic
data strongly suggest the presence of cirrhosis
liver biopsy can reveal the underlying cause of cirrhosis
Histopathology
Histopathology
Morphologic Classification

Micronodular cirrhosis
Nodules less than 3 mm in diameter
Believed to be caused by alcohol,
hemochromatosis, cholestatic causes of cirrhosis,
and hepatic venous outflow obstruction
Morphologic Classification

Macronodular
cirrhosis

Nodules larger than 3
mm
Believed to be
secondary to chronic
viral hepatitis
Morphologic Classification

Relatively nonspecific with regard to etiology

The morphologic appearance of the liver may change as
the liver disease progresses
micronodular cirrhosis usually progresses to macronodular cirrhosis
Serological markers available today are more specific than
morphological appearance of the liver for determining the
etiology of cirrhosis
Accurate assessment of liver morphology may only be
achieved at surgery, laparoscopy, or autopsy
Evaluation of Cirrhosis
Complications

Other Pulmonary syndromes

Hepatic hydrothorax
Portopulmonary HTN
Hepatic Encephalopathy
Hepatocellular carcinoma
Ascites

Accumulation of fluid within the peritoneal cavity

Most common complication of cirrhosis
Two-year survival of patients with ascites is
approximately 50 percent
Mechanism of Ascites
Ascites

Definition: fluid in the

peritonial cavity
Ascites

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
Older system -subjective
1+ minimal, barely detectable
2+ moderate
3+ massive, not tense
4+massive and tense



Ascites

Imaging studies for confirmation of ascites

Ultrasound is probably the most cost-effective modality
Ascites

The most successful therapeutic regimen is the

combination of single morning oral doses of
Spironolactone and Furosemide, beginning with
100 mg and 40 mg
Two major concerns with diuretic therapy for
cirrhotic ascites:
Overly rapid removal of fluid
Progressive electrolyte imbalance
Who gets a belly tap?
What do I want to order ?
Ascites

Treatment aimed at the underlying cause of the

hepatic disease and at the ascitic fluid itself
Dietary sodium restriction
Limiting sodium intake to 88 meq (2000 mg) per day

Complications

Ascites
Spontaneous Bacterial Peritonitis
Hepatorenal syndrome
Variceal hemorrhage
Hepatopulmonary syndrome
Spontaneous Bacterial Peritonitis

Infection of ascitic fluid

Almost always seen in the setting of end-stage
liver disease
The diagnosis is established by
A positive ascitic fluid bacterial culture
Elevated ascitic fluid absolute polymorphonuclear
leukocyte (PMN) count ( >250 cells/mm3)

Spontaneous Bacterial Peritonitis

Clinical manifestations:
Fever
Abdominal pain
Abdominal tenderness
Altered mental status
Hepatorenal 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
Hepatorenal Syndrome

Reduction in GFR often clinically masked

Prognosis is poor unless hepatic function improves
Nephrotoxic agents and overdiuresis can
precipitate HRS
Assessing kidney function in pts with
cirrhosis
Cr assays are subject to interference by chromogens,
bilirubin being the major one
There is decreased hepatic production of creatine
The edematous state that complicates end-stage liver
disease leads to large distribution of Cr in the body
and lower serum Cr concentration
Complications such as variceal bleeding, spontaneous
bacterial peritonitis or sepsis lead to increased Cr
tubular excretion

Proulx et al. Nephrology Dialysis Transplantation 2005

 HRS is a form of acute or subacute renal failure
characterized by severe renal vasoconstriction, which
develops in decompensated cirrhosis or ALF
Nearly half of patients die within 2 weeks of this
diagnosis
The annual incidence of HRS ranges between 8% and
40% in cirrhosis depending on the MELD score
The frequency of HRS in severe acute alcoholic
hepatitis and in fulminant liver failure is about 30% and
55%, respectively

Munoz S. Medical Clinics of North America July 2008

Munoz S. Medical Clinics of North America July 2008
Classification of the hepatorenal syndrome

Type 1: cirrhosis with rapidly progressive acute renal
failure
Type 2: cirrhosis with subacute renal failure
Type 3: cirrhosis with types 1 or 2 HRS superimposed
on chronic kidney disease or acute renal injury
Type 4: fulminant liver failure with HRS

Munoz S. Medical Clinics of North America July 2008

Causes of AKI in pts with cirrhosis

Acute tubular necrosis (41.7%)

Pre-renal failure (38%)

Hepatorenal syndrome (20%)

Post-renal failure (0.3%)

Moreau et al. Hepatology 2003

Major diagnostic criteria for hepatorenal
syndrome

Cirrhosis with ascites

Serum creatinine > 1.5 mg/dL
No improvement in serum creatinine (decrease to a level of
<1.5 mg/dL) after at least 2 days with diuretic withdrawal and
volume expansion with albumin. The recommended dose of
albumin is 1 g/kg of body weight per day up to a maximum of
100 g/day
Absence of shock
No current or recent treatment with nephrotoxic drugs
Absence of parenchymal kidney disease as indicated by
proteinuria >500 mg/day, microhematuria (<50 RBC/high
power field) and/or abnormal renal ultrasonography

Angeli et al. Journal of Hepatology February 2008

Minor diagnostic criteria for hepatorenal
syndrome
Urine volume < 500 mL/24 h
Urine sodium <10 mEq/L
Urine osmolality greater than plasma osmolality
Urine red blood cells < 50 per high power field
Serum sodium <130 mEq/L

Angeli et al. Journal of Hepatology February 2008

Type 1 hepatorenal syndrome

The serum creatinine level doubles to greater than 2.5

mg/dL within 2 weeks
It is characterized by its rapid progression and high
mortality, with a median survival of only 1 to 2 weeks
It can be precipitated by spontaneous bacterial
peritonitis and variceal hemorrhage
In some cases acute hepatic injury, superimposed on
cirrhosis, may lead to liver failure and HRS

Munoz S. Medical Clinics of North America July 2008

Type 2 hepatorenal syndrome

Serum creatinine increases slowly and gradually

during several weeks or months
Many patients with type 2 HRS eventually
progress to type 1 HRS because of a precipitating
factor
The median survival of type 2 HRS is about 6
months

Munoz S. Medical Clinics of North America July 2008

Type 3 hepatorenal syndrome

85% of end-stage cirrhotics have intrinsic renal

disease on renal biopsy
Patients with long-standing diabetic nephropathy,
obstructive renal disease, or chronic
glomerulonephritis can develop HRS from a
precipitating event or worsening liver failure

Munoz S. Medical Clinics of North America July 2008

Type 4 hepatorenal syndrome

More than half of patients with ALF develop HRS,

although the frequency varies depending on the
ALF etiology
The pathophysiology of HRS in ALF is believed to
be similar to that postulated for HRS occurring in
cirrhosis

Munoz S. Medical Clinics of North America July 2008

Munoz S. Medical Clinics of North America July 2008
Pathogenesis

Portal hypertension leads to arterial vasodilatation and pooling of blood

in the splanchnic bed, with a decrease in systemic vascular resistance
The modulation of cardiac output is relatively unable to prevent the
severe reduction of effective circulating volume due to the splanchnic
arterial vasodilation
Activation of the renin-angiotensin-aldosterone system and the
sympathetic nervous system and stimulation of antidiuretic hormone
release become necessary to maintain arterial blood pressure
As the liver disease worsens these circulatory changes gradually
increase until systemic hemodynamic stability depends on
vasoconstriction of the extrasplanchnic vascular beds

Munoz S. Medical Clinics of North America July 2008

Nitric oxide

Nitric oxide (NO) is a potent vasodilator that is

elevated in the peripheral circulation of patients with
cirrhosis
The imbalance between NO and vasoconstrictors such
as endothelin-1 in the renal microcirculation has been
proposed to be responsible for the progressive
deterioration in kidney function in these patients

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

 Nitric oxide has a very short half-life; therefore,
measurement of the NO metabolites, nitrite and nitrate
(NOx), are commonly used to estimate NO levels in
the circulation
Because both metabolites are excreted predominantly
by the kidney, decreased renal clearance rather than
overproduction could account for the elevated level of
NOx in decompensated cirrhosis

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

 L-Arginine (L-Arg), a nonessential amino acid, is the
precursor for NO production by nitric oxide synthase
The liver is the major site for arginine metabolism,
where arginine generated in the urea cycle is rapidly
converted to urea and ornithine by arginase-1
NOS and arginase-1 compete for available arginine
and it is possible that the overproduction of NO results
from an excess availability of substrate

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

 Patients with either compensated cirrhosis,
cirrhotic patients with ascites, refractory ascites
(RA) or chronic hepatorenal syndrome (HRS) type
II were included in the sudy
Normal healthy volunteers, organ donors and
chronic renal failure (CRF) patients without liver
disease were included as controls

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

 After adjusting for all demographics and variables, HRS was the
only disease state predicting high levels of NOx in the peripheral
circulation (P < 0.001)
Multivariate analysis also revealed that HRS was an independent
factor predicting high levels of L-Arg (P = 0.03)
Chronic renal failure and stages of progressive renal dysfunction in
decompensated cirrhosis were not independently associated with
peripheral levels of NOx or L-Arg
Peripheral levels of NOx reliably reflect NOx levels in the
splanchnic circulation, suggesting that peripheral levels of NOx can
be used diagnostically as a marker for disease state

Kayali et al. Journal of Gastroenterology and Hepatology February 2009

Varices
Esophagus
Gastric
Colo-rectal
Portal
hypertensive
gastropathy
Varices Diagnosis

History : Hematemases, melena

Physical examination
Ultrasound abdomen
Endoscopy
Variceal hemorrhage

Occurs in 25 to 40 percent of patients with

cirrhosis
Prophylactic measures
Screening EGD recommended for all cirrhotic
patients
Treatment

TIPS
Significant suppression of the endogenous
vasoconstrictor systems
Decrease in creatinine levels
More easily controllable ascites

Angeli et al. Journal of Hepatology February 2008

Varices
Management-General

ABC
2 IV Lines
Type and cross match
Resuscitation
IVF
Blood
Platelet transfusion (platelet <75,000)
Fresh frozen plasma (Correct Pt)


Varices
Management-Specific

IV vasoconstrictors (Octreotide)
Endoscopic therapy
Banding
Sclerotherapy
Shunting
Surgical
TIPS

Variceal Banding
 Types of Shunts

Surgical shunt

TIPS (Transjugular intrahepatic

portosystemic shunt)
Varices Prevention

Treat underlying disease

Endoscopic banding protocol
B-blockers
Shunt surgery (only if no cirrhosis)
Liver transplantation
Hepatopulmonary syndrome

Hepatopulmonary syndrome
Liver disease
Increased alveolar-arterial gradient while breathing room
air
Evidence for intrapulmonary vascular abnormalities,
referred to as intrapulmonary vascular dilatations (IPVDs)
Hepatic Hydrothorax

Pleural effusion in a patient with cirrhosis and no

evidence of underlying cardiopulmonary disease
Movement of ascitic fluid into the pleural space
through defects in the diaphragm, and is usually
right-sided
Diagnosis -pleural fluid analysis
reveals a transudative fluid
serum to fluid albumin gradient greater than 1.1
Hepatic hydrothorax

Confirmatory study:
Scintigraphic studies demonstrate tracer in the chest
cavity after injection into the peritoneal cavity
Treatment options:
diuretic therapy
periodic thoracentesis
TIPS
Portopulmonary HTN

Refers to the presence of pulmonary hypertension

in the coexistent portal hypertension
Prevalence in cirrhotic patients is approximately 2
percent
Diagnosis:
Suggested by echocardiography
Confirmed by right heart catheterization
Hepatic Encephalopathy

Spectrum of potentially
reversible neuropsychiatric
abnormalities seen in patients
with liver dysfunction
Diurnal sleep pattern pertubation
Asterixis
Hyperactive deep tendon reflexes
Transient decerebrate posturing
 Hepatic Encephalopathy
Clinical features

Reversal of sleep
pattern
Disturbed
consciousness
Personality changes
Intellectual deterioration
Fetor hepaticus
Astrexis
Fluctuating

Flapping Tremor

Drawing Tests
Hepatic Encephalopathy

Monitoring for events likely to precipitate HE [i.E.-

variceal bleeding, infection (such as SBP), the
administration of sedatives, hypokalemia, and
hyponatremia]
Reduction of ammoniagenic substrates
Lactulose / lactitol
Dietary restriction of protein
Zinc and melatonin
Hepatocellular Carcinoma

Patients with cirrhosis have a markedly increased

risk of developing hepatocellular carcinoma
Incidence in well compensated cirrhosis is
approximately 3 percent per year

Hepatocellular Carcinoma

Symptoms are largely due to mass effect from the

tumor
Pain, early satiety, obstructive jaundice, and a palpable
mass
Serum AFP greater than 500 micrograms/l in a
patient with cirrhosis are virtually diagnostic
Median survival following diagnosis is
approximately 6 to 20 months
Prognostic Tools

MELD (model for end-stage liver disease)

Identify patients whose predicted survival post-procedure
would be three months or less

MELD = 3.8[serum bilirubin (mg/dL)] + 11.2[INR] +
9.6[serum creatinine (mg/dL)] + 6.4
Prognostic Tools

Child-Turcotte-Pugh (CTP) score

initially designed to stratify the risk of portacaval shunt
surgery in cirrhotic patients
based upon five parameters: serum bilirubin, serum
albumin, prothrombin time, ascites and encephalopathy
good predictor of outcome in patients with complications
of portal hypertension
 Prognostic Tools

APACHE III (acute physiology and chronic

health evaluation system)
Designed to predict an individual's risk of dying in the
hospital

Treatment Options

The major goals of treating the cirrhotic patient

include:
Slowing or reversing the progression of liver disease
Preventing superimposed insults to the liver
Preventing and treating the complications
Determining the appropriateness and optimal timing for
liver transplantation
Liver Transplantation

Liver transplantation is the definitive treatment for

patients with decompensated cirrhosis
Depends upon the severity of disease, quality of
life and the absence of contraindications
Liver Transplantation

Minimal criteria for listing cirrhotic patients on the

liver transplantation list include
A child-Pugh score 7
Less than 90 percent chance of surviving one year
without a transplant
An episode of gastrointestinal hemorrhage related to
portal hypertension
An episode of spontaneous bacterial peritonitis
Vaccinations

Hepatitis A and B
Pneumococcal vaccine
Influenza vaccination
Surveillance

Screening recommendations:
serum AFP determinations and ultrasonography every six
months
Avoidance of Superimposed Insults

Avoidance of:
Alcohol
Acetaminophen
Herbal medications

References

Up to Date
Harrisons
New England Journal
http://www.openclinical.org/aisp_apache.html
Nail abnormalities: clues to systemic disease,
American Family Physician, March 15, 2004 Robert
Fawcett