Cirrhosis of Liver
Introduction
• The term cirrhosis was first used by Rene
Laennec (1781-1826) to describe the
abnormal liver color of individuals with
alcohol induced liver disease.
• Derived from Greek word Kirrhos means
Yellowish brown color.
Definition:
• Cirrhosis is a chronic progressive disease of the
liver characterized by extensive degeneration
and destruction of the liver parenchymal cells.
• The liver cells attempt to regenerate, but the
regenerative process is disorganized, resulting
in abnormal blood vessels and bile duct
architecture.
Contd.
• 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.
Contd.
• Scarring also impairs the liver's ability to:
control infections
remove bacteria and toxins from the blood
process nutrients, hormones, and drugs
make proteins that regulate blood clotting
produce bile to help absorb fats—including
cholesterol—and fat-soluble vitamins
Incidence :
• The overall incidence of cirrhosis in the US is
approximately 360 per 100,000 population
• It is the 10th leading cause of death in the US, with
mortality rate of 9.2 deaths per 100,000
populations.
• Of those deaths, 45% were alcohol related. Men
are more likely than women to have alcoholic
cirrhosis.
• Worldwide, post necrotic cirrhosis is the most
common in women. Mortality is higher from all
types of cirrhosis in men and non whites.
Etiology:
1. Not clearly defined
2. Alcohol.
• Heavy alcohol for several years can cause chronic
injury to the liver and damages.
• For women, consuming two to three drinks—
including beer and wine per day and for men,
three to four drinks per day, can lead to liver
damage and cirrhosis.
• A common problem in alcoholic is protein
malnutrition.
Cont..
3. Obesity: WHO ,2008, estimated that more than
200 million men and close to 300 million women
were obese, obesity is a common cause of chronic
liver disease , 17% of liver cirrhosis is attributable
to excess body weight.
4. Chronic hepatitis C. Chronic hepatitis C causes
inflammation and damage to the liver over time
that can lead to cirrhosis and approximately 20%
patient will develop cirrhosis.
Cont..
• Chronic hepatitis B and D. Hepatitis B and D is virus
that infects the liver and can lead to cirrhosis, but it
occurs only in people who already have hepatitis B.
approximate 10%- 20% will develop cirrhosis.
• Nonalcoholic fatty liver disease (NAFLD). This is
associated with obesity, diabetes, protein
malnutrition, coronary artery disease, and
corticosteroid medications.
Cont..
• Autoimmune hepatitis. It is caused by the body's
immune system attacking liver cells and causing
inflammation, damage, and eventually cirrhosis.
• genetic factors -About 70 percent of those with
autoimmune hepatitis are female.
• Diseases that damage or destroy bile ducts.
Several different diseases( cholangitis) can
damage or destroy the ducts that carry bile from
the liver, causing bile to back up in the liver and
leading to cirrhosis.
Cont….
• Inherited diseases. Cystic fibrosis, alpha-1
antitrypsin deficiency, hemochromatosis, Wilson
disease, galactosemia, and glycogen storage
diseases are inherited diseases that interfere the
liver function properly, cirrhosis can result.
• Drugs, toxins, and infections. drug reactions(
Acetaminophen, isonazide, methotrexate)
prolonged exposure to toxic chemicals, parasitic
infections, and repeated bouts of heart failure with
liver congestion.
Types of cirrhosis :
• Alcoholic (historically called Laennec’s cirrhosis)
cirrhosis:
• also called micro nodular or portal cirrhosis and
usually associated with alcohol abuse.
• The first change in the liver from excessive intake is
an accumulation of fat in the liver cells;
uncomplicated fatty changes in the liver are
potentially reversible if the person stops drinking
alcohol.
• If the alcohol abuse continues, widespread scar
formation occurs throughout the liver.
Cont..
• Post necrotic cirrhosis( macro nodular):most
common world wide, massive loss of liver cells
with irregular patterns of regenerating cells due to
complication of viral, toxic or idiopathic
(autoimmune) hepatitis.
• Billiary cirrhosis: is associated with chronic billiary
obstruction and infection. There is diffuse fibrosis
of the liver with jaundice.
• Cardiac cirrhosis: chronic liver disease results from
long-standing, severe right side heart failure with
corpulmonale, constrictive pericarditis, and
tricuspid insufficiency.
Pathophsiology :
Liver insult due to alcohol ingestion, viral hepatitis,
exposure to toxin
Hepatocyte damage
Liver inflammation - ↑WBCs, nausea, vomiting, pain,
fever, anorexia, fatigue
Alteration in blood and lymph flow
Cont..
Liver necrosis →liver fibrosis and scarring → portal
hypertension
- Ascities, edema,
- Spleenomegaly ( thrombocytopenia,
leucopenia)
- Varices (esophageal varices,
hemorrhoids, anemia)
↓ billirubin metabolism – hyperbilirubinemia,
jaundice
Cont..
•
•
•
•
↓ bile in gastrointestinal tract – light colored stool
↑ urobilinogen – Dark Urine
↓ vit K absorption- bleeding tendency
↓ metabolism of protein, carbohydrate, fats→
hypoglycemia,
• ↓ plasma protein- ascites and edema
• ↓androgen and estrogen detoxification(↓
hormone metabolism)- ↑ estrogen and androgens
hormone – Gynecomastia, loss of body hair,
menstrual dysfunction, spider angioma, palmer
erythema, testicular atrophy
Cont..
• ↓ Aldesterone metabolism so ↑ levels – sodium
and water retention-- edema
• Biochemical alteration - ↑ AST, ALT levels, ↑
bilirubin, low serum albumin, prolong prothombin
time, elevated alkaline phosphatase.
• Liver failure
• Hepatic encephalopathy
• Hepatic coma
• Death
Clinical manifestations
•
•
•
•
Early manifestations
No symptoms
GI disturbances: anorexia, dyspepsia,
flatulence, weakness, fatigue, nausea,
vomiting, weight loss, abdominal pain,
bloating, diarrhea, constipation
Abdominal pain, dull and heavy feeling
Fever, lassitude, weight loss, enlargement of
liver and spleen.
Cont…
•
•
•
•
•
Later manifestations:
Results from liver failure and portal
hypertension
Jaundice
Peripheral edema
Ascites
Others: Skin lesion, hematological disorders,
endocrine disturbances, and peripheral
neuropathy
Advanced stage: small and nodular liver
Jaundice
It results from the functional derangement of liver
cells and compression of bile duct by connective
tissue overgrowth
• Jaundice occurs as a result of decreased ability to
conjugate and excrete bilirubin
• If obstruction of the biliary tract occurs,
obstructive jaundice may also occur and usually
accompanied by pruritus
Skin lesion
Spider angioma ( telangiectasia or spidernavi)
are small dilated blood vessels with a bright red
center point and spider like branches occurs in
nose, cheeks, upper trunk, neck and shoulders.
• Palmer erythema, a red area that blanches
with pressure, is located on the palm of the
hand.
• Both lesions are due to increase estrogen in
blood as a result of the damaged liver’s
inability to metabolized steroid hormone.
Hematologic problem
Thrombocytopenia, leucopenia, anemia, due to
spleenomegaly (back flow of blood from portal
vein into the spleen.)
• Anemia due to inadequate RBC production and
survival, and due to poor diet, poor absorption
and bleeding from varices.
• Coagulation problems result from the liver’s
inability to produce prothrombin and blood
clotting and manifested by hemorrhagic
phenomena or bleeding tendencies e.g. epistaxis,
purpura, gingival bleeding, heavy menstrual flow.
Endocrine problem
In men: Gynecomastia, loss of axillary and pubic
hair, testicular atrophy and impotence with loss of
libido due to increased estrogen level.
• In younger female, amenorrhea may occur and in
older, bleeding may occur.
• ↑aldosterone hormone may cause sodium water
retention and potassium loss.
Peripheral neuropathy: probably due to dietary
deficiency of thiamine, folic acid and cobalamin.
Clinical Manifestations
Complication
Portal hypertension
• The nodules and scar tissue can compress
hepatic veins within the liver.
• This causes the blood pressure within the liver to
be high, a condition known as portal
hypertension.
• Portal venous pressure is more than 15mmHg or
20 cm of water (normal 5-10mm Hg)
Cont…
• Is characterized by ↑venous pressure in the
portal circulation, spleenomegaly, large collateral
vein, ascites, systemic hypertension, and
esophageal varices.
• The common area to form collateral channels are
in the lower esophagus( the anastomosis of the
left gastric vein and azygos vein), the parietal
peritoneum, rectum.
• High pressures within blood vessels of the liver
occur in 60% of people who have cirrhosis.
Cont..
Esophageal Varices:
• Esophageal Varices are a complex of tortuous
veins at the lower end of the esophageal
enlarged and swollen as a result of portal
hypertension.
• 10-30% of UGI bleeding due to rupture of
varices.
• 80% bleeding due to esophageal Varices.
• 20% due to gastric varices.
Cont..
•
•
•
•
Peripheral edema and Ascites:
Edema results from decreased colloidal oncotic
pressure from impaired liver synthesis of albumin
(hypoalbuminia)
Ascites is the accumulation of serous fluid in the
peritoneal cavity.
Protein move from the blood vessels via the larger
pore of sinusoids into the lymph space.
When the lymphatic system is unable to carry off
the excess protein and water, they leak through
the liver capsule into the peritoneal cavity.
Cont..
Hepatic encephalopathy/Coma:
• Hepatic encephalopathy is a neuropsychiatric
manifestation of liver damage.
• It can occur in any condition in which liver
damage causes ammonia to enter the systemic
circulation without liver detoxification.
• Liver is unable to convert ammonia to urea. The
ammonia crosses the blood brain barrier and
produces neurologic toxic manifestations.
Stages of Hepatic Encephalopathy
Stages
Clinical Symptoms
Clinical Signs
1
Normal level of
consciousness with
periods
of lethargy and euphoria;
reversal of
day–night sleep patterns
Asterixis; impaired
writing and ability
to draw
line figures.
2
Increased drowsiness;
disorientation;
inappropriate behavior;
mood swings; agitation
Asterixis; fetor
hepaticus.
Stages Contd.
Stages
Clinical Symptoms
Clinical Signs
3
Stuporous; difficult to
rouse; sleeps most
of time; marked
confusion; incoherent
speech
Asterixis; increased
deep tendon reflexes;
rigidity
of extremities.
4
Comatose; may not
respond to painful
stimuli.
Absence of asterixis;
absence of deep
tendon
reflexes; flaccidity of
extremities.
Contd.
• Serum ammonia is decreased: by less protein
diet and by antibiotic agents e.g. neomycin
sulfate, it reduces the number of intestinal
bacteria capable of converting urea to
ammonia
• Susceptible patients: excessive diuresis,
dehydration, infections, surgery, fever, and
some medications (sedative agents,
tranquilizers, analgesic agents, and diuretic
medications that cause potassium loss)
Cont..
• Lactulose: to reduce serum ammonia level
• Low-protein diet: 1.0 and 1.5 g/kg or up to
0.5g/kg
• Intravenous administration of glucose to
minimize protein breakdown
• Administration of vitamins to correct deficiencies
• Correction of electrolyte imbalances (especially
potassium with potclor)
• Neurologic status is assessed frequently
Contd.
• Fluid intake and output and body weight are
recorded each day.
• Vital signs are measured and recorded every 4
hours.
• Serum ammonia level is monitored daily.
• Protein intake is restricted in patients who are
comatose or refractory encephalopathy
Contd.
• Electrolyte status is monitored and corrected
if abnormal.
• Sedatives, tranquilizers, and analgesic
medications are discontinued
Cont..
Hepatorenal syndrome:
• Hepatorenal syndrome is a serious complication
of cirrhosis characterized by functional renal
failure with advancing azotemia, oliguria, and
ascites.
Diagnosis
• Liver function test : ↑alkaline phosphate, ALT,AST
and y – glutamyl transpeptidase ( GGT)
• Blood test: ↓ total protein, ↓ albumin, ↑ serum
bilirubin and globulin, ↑serum ammonia
• Prothombin time is prolonged (normal: 10-14sec)
• Liver cell biopsy to identify liver cell changes
• Ascites fluid test
• Liver ultrasound
• CT Scan: enlarged or atrophied, characteristics
• Stool for occult blood
• Endoscopy
Management
Medical management
• Dietary modification: table salt, salted butter,
margarine, ordinary can and frozen foods
should be avoided.
• The diet should be adequate calories and
protein (75- 100 gm/day) unless hepatic
encephalopathy is present, in which case
protein is limited.
• Restrict fluid
Contd.
• Diuretics:
spironolactone,
aldosterone
blocking agents.
• Vitamins B and fat soluble vitamins (A, D, E, K).
• Corticosteroids drugs to improve liver function
in post necrotic cirrhosis.
• Daily weight loss should not exceed 1 to 2 kg
(2.2 to 4.4 lb) in patients with ascites and
peripheral edema or 0.5 to 0.75 kg (1.1 to 1.65
lb) in patients without edema.
Management contd.
• Bed Rest: useful therapy
– upright position activation of the reninangiotensin-aldosterone system and
sympathetic nervous systemresults in
reduced renal glomerular filtration and
sodium excretion and a decreased response
to loop diureticsavoid
Contd.
• Paracentesis: removal of fluid (ascites) from
the peritoneal cavity through a small surgical
incision or puncture made through the
abdominal wall under sterile conditions (upto
5-6l removal is safe)
• Insertion of a peritoneovenous shunt to
redirect ascitic fluid
Parencentesis
Management Contd.
• Replace Fluid and Electrolytes: intravenous
fluids with electrolytes and volume expanders
are provided to restore fluid volume and
replace electrolytes
• Transfusion of blood components also may be
required
• An indwelling urinary catheter to monitor
urine output
Contd.
• Pharcological therapy:
– Vasopressin (↓portal pressure)
– Vasopressin +Nitroglycerine (↓ portal pressure)
– Somatostatin and octreotide (↓ bleeding)
• Balloon Temponade: used for controlling
hemorrhage
– Use of double ballon teamponade Isengstaken
Blakemore tube)
Contd.
– Used to to exert pressure on the cardia (upper
orifice of the stomach) and against the bleeding
varices
– The balloon in the stomach is inflated with 100 to
200 mL of air.
– An x-ray is done to confirm proper positioning of
the gastric balloon
Sengstaken
Blakemore
Tube
Management Contd.
Sclerotherapy:
• In endoscopic sclerotherapy , a sclerosing
agent is injected through a fiberoptic
endoscope into the bleeding esophageal
varices to promote thrombosis and eventual
sclerosis.
• The procedure has been used successfully to
treat acute GI hemorrhage
Sclerotherapy
Contd.
• Esophageal banding therapy (variceal band
ligation)
• a modified endoscope loaded with an elastic
rubber band is passed through an overtube
directly onto the varix (or varices) to be
banded.
• After suctioning the bleeding, the rubber band
is slipped over the tissue, causing necrosis,
ulceration, and eventual sloughing of the
varix.
Esophageal Banding
Contd.
Transjugular intrahepatic portosystemic
shunting (TIPS)
• Method of treating esophageal varices in
which a cannula is threaded into the portal
vein by the transjugular route.
• An expandable stent is inserted and serves as
an intrahepatic shunt between the portal
circulation and the hepatic vein reducing
portal hypertension.
Stenting
cont,..
Surgical management
• Liver transplantation
• Removing the liver and replacing it with a
healthy donor organ is another way to
treat liver cancer or liver cirrhosis
• About 80-90 percent of people who
undergo liver transplantation, survive.
Contd.
• Direct surgical ligation of varices
– splenorenal, mesocaval, and portacaval
venous shunts
Shunt
Cont..
• Treat underlying cause: if cirrhosis is from
heavy alcohol use, the treatment is to
completely stop drinking alcohol.
• If cirrhosis is caused by hepatitis C, then
treatment of hepatitis C
• Avoidance of hepatotoxic substances.
Nursing Management
Assessment
• History taking: past and present health history
(alcohol intake, medication, infection etc)
chief complain sign and symptoms of disease
• Physical examination
• Psychosocial assessment
Nursing Diagnosis
(1) Ineffective tissue perfusion related to
bleeding tendencies and varices that may
hemorrhage
Goal
• ‘Hemorrhage will be prevented as evidenced
by absence of bleeding, normal vital sign and
urine output of at least 0.5 ml/kg.’
Cont..
• Interventions :
• Assess patient’s condition
• Monitor for bleeding from gums, melena, hematuria,
hematemasis
• Assess vital sign for sign of shock
• Monitor urine output
• Protect patient from physical trauma to prevent
hemorrhage
• Avoid unnecessary injection and apply gentle pressure after
injection
• Instruct the client to avoid vigorous nose blowing, straining
with bowel movement.
• Provide stool softener to prevent straining with rupture of
varices
• Advice to use soft tooth brush to prevent gum bleeding
(2) Activity intolerance related to bed rest, fatigue, lack of
energy, and altered respiratory function secondary to
ascites.
Goal: ‘The patient will maintain a balance between rest and
activity as evidenced by the absence of fatigue’
Interventions:
• Assess level of activity tolerance and degree of fatigue,
lethargy, and malaise when performing routine ADLs.
• Assist with activities and hygiene when fatigued.
• Encourage rest when fatigued or when abdominal pain or
discomfort occurs.
• Assist with selection and pacing of desired activities and
exercise.
• Provide diet high in carbohydrates with protein intake
consistent with liver function.
• Administer supplemental vitamins (A, B complex, C, and K).
(3) Impaired skin integrity related to pruritus from
jaundice and edema
Goal: ‘Decrease potential for pressure
development; breaks in skin integrity’
ulcer
Interventions:
• Assess degree of discomfort related to pruritus
and edema.
• Note and record degree of jaundice and extent of
edema.
• Keep patient’s fingernails short and smooth.
• Provide frequent skin care; avoid use of soaps and
alcohol-based lotions.
Cont…
• Massage every 2 hours with emollients; turn
every 2 hours
• Initiate use of alternating-pressure mattress or
low air loss bed.
• Recommend avoiding use of harsh detergents.
• Assess skin integrity every 4–8 hours. Instruct
patient and family in this activity.
• Restrict sodium as prescribed.
• Perform range of motion exercises every 4 hours;
elevate edematous extremities whenever
possible.
(4) High risk for injury related to altered clotting
mechanisms and altered level of consciousness
Goal: Patient is conscious, no hemetemesis, melena.
Intervention
• Assess level of consciousness and cognitive level.
• Provide safe environment (pad side rails, remove
obstacles in room, prevent falls).
• Provide frequent surveillance to orient patient and
avoid use of restraints.
• Replace sharp objects (razors) with safer terms.
Cont..
• Observe each stool for color, consistency, and
amount.
• Be alert for symptoms of anxiety, epigastric
fullness, weakness, and restlessness.
• Test each stool and emesis for occult blood.
• Observe
for
hemorrhagic
manifestations:
ecchymosis, epistaxis petechiae, and bleeding
gums.
• Record vital signs at frequent intervals, depending
on patient acuity (every 1–4 hours).
• Keep patient quiet and limit activity.
(5) Disturbed body image related to changes in
appearance, and role function.
Goal: ‘Patient verbalizes feelings consistent with
improvement of body image and self-esteem’
Intervention:
• Assess changes in appearance and the meaning
these changes have for patient and family.
• Encourage patient to verbalize reactions and
feelings about these changes.
• Assess patient’s and family’s previous coping
strategies.
Cont…
• Assist patient in identifying short-term goals.
• Encourage and assist patient in decision
making about care.
• Identify with patient resources to provide
additional support (counselor, spiritual
advisor).
• Assist patient in identifying previous practices
that may have been harmful to self (alcohol
and drug abuse).
Nsg diagnosis cont….
(6) Fluid volume excess related to portal
hypertension and hyperaldesteronism as
evidenced by weight gain, depended edema,
ascites
(7) Dysfunctional family processes, alcoholism
related to abuse of alcohol and inadequate
coping ability as evidenced by deteoriation in
family relationship, family denial, neglected
obligation.
References
• Brunner And Siddhartha's (2004).MedicalSurgical Nursing (12th Ed)
• Chintamani .Lewis’s Medical Surgical Nursing,
Mosby .2011
• Cirrhosis of Liver, emedicine, Available from:
www.emedicinehealth.com/cirrhosis/page8_e
m.htm
• M. Joycee Black, Hokanson Jane Hawks.
Medical –Surgical Nursing. Clinical
management for positive outcomes. 7th ed.
2005.
Thank You
Liver cirrhosis case
• Mrs MW, 59 years old, is divorced and
unemployed. She was admitted to an
acute medical ward at the hospital
presenting with general malaise, a
grosslydistended abdomen, swollen
ankles and jaundice. It was also noted
that she smelt of alcohol and was
showing signs of alcohol withdrawal
• 1 What is cirrhosis of the liver?
• 2 List possible causes of cirrhosis.
• 3 What other clinical signs and
symptoms may Mrs MW present with?
• 4 What drug treatment, including dose,
would you recommend for Mrs MW’s
• alcohol withdrawal? What
recommendations would you make if
the patient was
• unable to take the medication orally?
What is cirrhosis of the liver?
• Cirrhosis is defined as the histological
development of regenerative nodules
surrounded by fibrous bands in response
to chronic liver injury.
• It is an advanced stage of liver fibrosis
that is accompanied by distortion of the
hepatic vasculature.
List possible causes of cirrhosis
• Causes of cirrhosis can usually be identified by the patient’s history combined
• with serological and histological investigation.
• . Alcoholic liver disease and hepatitis C and B are the most common causes of
cirrhosis
• The association of excessive alcohol consumption with liver disease has been
recognised for centuries.
• After the identification of the hepatitis C virus and of non-alcoholic steatohepatitis
in obese patients with diabetes, the diagnosis of cirrhosis without an apparent
cause (cryptogenic cirrhosis) is rarely made.
• Genetic causes of cirrhosis include haemochromatosis and Wilson’s disease.
• Epidemiological studies have identified a number of factors that contribute to the
risk of developing cirrhosis.
• Regular (moderate) alcohol consumption, age older than 50 years, and male gender
are examples that increase cirrhosis risk in chronic hepatitis C infection, and older
age, obesity, insulin resistance or type 2 diabetes, hypertension and
hyperlipidaemia in non-alcoholic steatohepatitis.
What other clinical signs and symptoms may
Mrs MW present with?
• Cirrhosis is often asymptomatic until complications
of liver disease are present.
• Mrs MW may present with itching, jaundice, dark
urine, pale fatty stools,
• abdominal pain, nausea, fatigue, bleeding – such as
nose bleeds, hepatic encephalopathy, hepatomegaly,
ascites, distended abdominal veins, spider
angiomata, palmar erythema and asterixis. She may
also present with the signs and symptoms of alcohol
withdrawal, which include irritability, anxiety,
tachycardia, tremor, sweating, confusion and
hallucinations.
•
•
•
•
•
What drug treatment, including dose, would you recommend for Mrs MW’s
alcohol withdrawal? What recommendations would you make if the patient
was unable to take the medication orally?
Long-acting benzodiazepines (e.g. diazepam and chlordiazepoxide) are used to
attenuate alcohol withdrawal symptoms but they also have a dependence
potential.
To minimise the risk of dependence, administration should be for a limited
period only (e.g. chlordiazepoxide 20 mg 4 times daily, gradually reducing to
zero over 7–14 days).
Mild alcohol withdrawal symptoms may be treated with a lower starting dose,
such as 15 mg four times a day.
In all cases, the patient should be counselled about the proposed length of the
treatment course.
Benzodiazepines should not be prescribed if the patient is likely to continue
drinking alcohol. In patients unable to take medication by the oral route,
diazepam may be administered by intramuscular or slow intravenous injection
(into a large vein, at a rate of not more than 5 mg/min), at a dose of 10 mg,
repeated if necessar after not less than 4 hours. Alternatively, diazepam may be
administered via the rectal route as a rectal solution or suppository. The
intramuscular route should only be used when both the oral and intravenous
routes are not possible.
• Mrs MW weighs 61 kg (with the ascites) and her laboratory data are as
follows:
• Total protein 49 g/L (63–80 g/L)
• Albumin 20 g/L (32–50 g/L)
• Total bilirubin 114 micromol/L (<17 micromol/L)
• ALP 382 IU/L (100–300 IU/L)
• ALT 88 IU/L (5–42 IU/L)
• INR 1.6
• GGT 306 IU/L (<50 IU/L)
• Diagnosis of alcoholic cirrhosis of the liver was made based on Mrs MW’s
clinical
• features, liver function tests, abdominal ultrasound, CT scan and liver
biopsy.
• Describe how Mrs MW’s laboratory results relate to
her diagnosis.
• 2 What treatment would you recommend to reduce
her risk of bleeding?
• 3 What medications would you advise Mrs MW to
avoid in view of her bleeding risk?
• 4 What treatment options are available to help Mrs
MW abstain from alcohol in the future?
Describe how Mrs MW’s laboratory
results relate to her diagnosis.
• Albumin is synthesised in the liver and has a long half-life of
around 20 days.
• Mrs MW’s low serum albumin is indicative of chronic liver
disease.
• Albumin synthesis is also depressed in states of poor
nutrition.
• Bilirubin is carried within the plasma by albumin to the liver,
where it is conjugated by glucuronidation.
• Subsequently, low circulating albumin levels and/or damage
to the liver cells result in reduced conjugation of the bilirubin.
• Blockage of the biliary tract (e.g. cholestasis) will result in increased
levels of conjugated bilirubin.
• Bilirubin levels of more than 35 micromol/L can result in visual signs
of jaundice.
• The concentration of both the unconjugated and conjugated bilirubin
are likely to be raised in Mrs MW. However, only total bilirubin was
measured in this case.
• Alkaline phosphatase (ALP) is present in high concentrations in the
cells lining the biliary tract and an ALP level exceeding 300 IU/L,
together with a raised bilirubin as in the case of Mrs MW, is indicative
of cholestasis. Jaundicebecomes progressively more severe in
unrelieved cholestasis.
• Alanine aminotransferase (ALT) is present in high concentrations in
the liver and the enzyme is released during hepatocellular damage
and a modestly raised level like Mrs MW’s is indicative of chronic liver
disease.
• The increased susceptibility to bleeding observed in
patients with liver failure (raised INR) results from
depressed fibrinogen levels and the reduced synthesis of
clotting factors by the cirrhotic liver.
• In addition, the absorption of fat-soluble vitamin K is
impaired in cholestasis and subsequently the synthesis of
vitamin K-dependent clotting factors is reduced.
• Gamma-glutamyl transferase (GGT) is found in the liver, but
this test is relatively non-specific. It is released following
tissue damage and is raised in cholestasis in parallel with
ALP. GGT release is stimulated by alcohol and some drugs
(such as phenytoin and carbamazepine), and therefore the
GGT level can be used to assess abstinence in alcoholics,
like Mrs MW.
What treatment would you recommend to reduce her
risk of bleeding?
• Mrs MW has a raised INR value of 1.6 and is therefore at increased
risk of bleeding.
• Vitamin K can be given to correct the vitamin deficiency, either as an
intravenous injection or orally. Konakion MM is phytomenadione (10
mg/mL) in amixed micelles vehicle.
• Konakion MM may be administered by slow intravenous injection or
by infusion in glucose 5%.
• For oral administration, the water-soluble preparation menadiol
sodium phosphate, is used in patients with hepatic disease, especially
biliary obstruction.
• The usual dose is 10 mg daily. Alternatively, phytomenadione tablets
may be used in those patients who do not have impaired fat
absorption.
• If vitamin K is ineffective in controlling the clotting times (monitored
via the INR result) then fresh frozen plasma may be required.
What medications would you advise Mrs
MW to avoid in view of her bleeding risk?
• Medications known to increase the risk of
bleeding in cirrhotic patients include
• aspirin, clopidogrel, dipyridamole,
corticosteroids, NSAIDs, heparin and warfarin.
• Mrs MW would need to be counselled about
the risks associated with these medications
and advised to always check with the
pharmacist before buyingany medications
over the counter
What treatment options are available to help
Mrs MW abstain from alcohol in the future?
• Disulfiram is an aversive therapy that works by inhibiting acetaldehyde dehydrogenase.
•
•
•
Interactions between disulfiram and alcohol can result in potentially severe reactions,
such as myocardial infarction, congestive heart failure, respiratorydepression and death.
Patients taking disulfiram should be warned of the possible presence of alcohol in liquid
medicines, tonics, foods and even in toiletries and mouthwashes.
Patient adherence to disulfiram is poor and there is a lack of strong evidence for its
effectiveness, thus it is not routinely recommended.
• Acamprosate is indicated for the maintenance of abstinence in alcohol dependent adults.
•
•
•
•
It appears to decrease brain hyper excitability during alcohol withdrawal, which may reduce
alcohol consumption.
Treatment should be initiated as soon as possible after the alcohol-withdrawal period is
complete.
The recommended period of treatment with acamprosate is one year and treatment should
be combined with counselling.
The GGT level can be monitored as a marker of abstinence from alcohol.
• Mrs MW, 59 years old, is divorced and
unemployed. She was admitted to an acute
medical ward at the hospital presenting with
general malaise, a grossly
• distended abdomen, swollen ankles and
jaundice. It was also noted that she smelt of
alcohol and was showing signs of alcohol
withdrawal.
• On examination, Mrs MW was found to be
encephalopathic. The doctors decided to treat
her encephalopathy and ascites.
• What is hepatic encephalopathy? What are the clinical
signs and symptoms?
• 2 What factors may precipitate hepatic
encephalopathy?
• 3 List two treatment options for the management of
Mrs MW’s hepatic encephalopathy. Describe the
mechanism of action for one of these.
• 4 What factors are likely to have contributed to the
development of ascites in Mrs MW?
• 5 Name two treatment options for the management of
Mrs MW’s ascites. Describe the pharmacology of these
therapies, including any potential side-effects. What
would you monitor in order to determine whether the
therapy was effective?
What is hepatic encephalopathy? What are
the clinical signs and symptoms?
• Hepatic encephalopathy is a neuropsychiatric
syndrome which may complicate almost all types of
liver disease.
• It may occur intermittently and be reversible or
may occur acutely, with rapid progression to coma
and death.
• Mrs MW presented with signs of hepatic
encephalopathy including flapping tremor of the
hands, intellectual deterioration, slurred speech,
confusion, drowsiness and irritability.
2 What factors may precipitate hepatic
encephalopathy?
• Factors that may precipitate hepatic encephalopathy
include:
• hypokalaemia and/or profound diuresis caused by a
brisk response to a potent diuretic,
• diarrhoea and vomiting, because of the resulting
fluid and electrolyte imbalance, constipation,
• a large protein meal or gastrointestinal haemorrhage,
infection, especially peritonitis,
• and CNS depressant drugs, such as opioids or
benzodiazepines.
List two treatment options for the management of Mrs MW’s
hepatic encephalopathy. Describe the mechanism of action for
one of these.
• Treatment goals for hepatic
encephalopathy include provision of
supportive care, identification and
removal of precipitating factors,
reduction in the nitrogenous load from
the gut and optimisation of long-term
therapy.
• Therapy should be directed toward improving mental status
via bowel cleansing with lactulose or with enemas. The
dose of lactulose should be titrated to give two soft stools
per day without diarrhoea.
• Lactulose is metabolised in the colon to lactic, acetic and
formic acids, causing the pH of the colon to drop from 7 to
5.
• Colonic acidification with lactulose alters the bacterial
population and favours the growth of weak ammoniaproducing bacteria rather than proteolytic ammonia
producers such as E. coli.
• In addition, the drop in colon pH leads to ionisation of
nitrogenous products with a subsequent reduction in their
absorption from the gastrointestinal tract into the blood.
• Third, the osmotic laxative effect speeds the intestinal transit,
thereby decreasing the time available for the absorption of
potentially toxic nitrogen compounds. It is imperative to
monitor
• Mrs MW’s bowel frequency while treating with lactulose since
fluid and electrolyte
• imbalances secondary to diarrhoea may precipitate hepatic
encephalopathy.
• Mrs MW’s mental test score should also be repeated to assess
benefit.
• Neomycin (4 g daily in divided doses) is a non-absorbable
antibiotic which may be used to reduce the number of
bacteria in the bowel that normally break down protein.
• Neomycin therapy is usually limited to one week’s therapy
because some absorption may occur with a risk of
nephrotoxicity and ototoxicity.
What factors are likely to have contributed to
the development of ascites in Mrs MW?
• Mrs MW presented with a swollen abdomen,
swollen ankles, pitting oedema and
breathlessness. There are two key factors
involved in the pathogenesis of ascites
formation, namely, sodium and wate retention
and portal hypertension.
• The development of renal
vasoconstriction in cirrhosis is partly a
homeostatic response involving
increased renal sympathetic activity and
activation of the renin–angiotensin
system to maintain blood pressure during
systemic vasodilatation.
• Decreased renal blood flow decreases
glomerular filtration rate and thus the
delivery and fractional excretion of
sodium.
• Cirrhosis is associated with enhanced reabsorption of
sodium both at the proximal tubule and at the distal
tubule. Increased reabsorption of sodium in the
distal tubule is due to the increased circulating
concentrations of aldosterone, occurring secondary
to the reduced hepatic metabolism of aldosterone.
• However, some patients with ascites have normal
plasma concentrations of aldosterone, leading to the
suggestion that sodium reabsorption in the distal
tubule may be related to enhanced renal sensitivity
to aldosterone.
• In compensated cirrhosis, sodium retention can
occur in the absence of vasodilatation and effective
hypovolaemia. Sinusoidal portal hypertension can
reduce renal blood flow even in the absence of
haemodynamic changes in the systemic circulation,
suggesting the existence of a hepatorenal reflex.
• Portal hypertension increases the hydrostatic
pressure within the hepatic sinusoids and favours
transudation of fluid into the peritoneal cavity.
Systemic vasodilatation, the severity of liver disease
and portal pressure contribute to the abnormalities
of sodium handling in cirrhosis.
Name two treatment options for the management of Mrs MW’s ascites.
Describe the pharmacology of these therapies, including any potential sideeffects. What would you monitor in order to determine whether the therapy
was effective?
• Management of ascites aims to mobilise
ascitic fluid, relieve abdominal discomfort
• and breathlessness and to exclude infection.
Diuretics have been the mainstay
• of treatment of ascites since the 1940s when
they first became available.
• Spironolactone, an aldosterone antagonist, is the drug of
choice since
• secondary hyperaldosteronism often coexists in patients with
hepatic ascites.
• Aldosterone is usually metabolised by the liver and is highly
protein bound, therefore the free aldosterone levels are
raised in cirrhosis. Spironolactone competes with aldosterone
for receptor sites in the distal tubule, resulting in potassium
retention and sodium and water loss.
• The initial dose of spironolactone is 100–200 mg and can be
slowly increased according to response. There is a lag of 3–5
days between the beginning of spironolactone treatment and
the onset of the natriuretic effect.
• The aim is to remove the fluid gradually with a maximum weight loss
of
• 0.5 kg/day in the absence of peripheral oedema, or 1.0 kg/day if
peripheral
• oedema is present. Too rapid a diuresis will result in intravascular
fluid loss rather than the peripheral oedema.
• The diuretic should be stopped if the serum sodium falls below 120
mmol/L or if there is a rising serum creatinine. Urinary electrolytes
should be monitored to ensure that the spironolactone therapy is
effective.
• The aim is to reverse the sodium/potassium ratio in the urine so that
• more sodium than potassium is excreted. Most frequent side-effects
of spironolactone are those related to its anti-androgenic activity,
such as decreased libido, impotence and gynaecomastia in men and
menstrual irregularities in women.
• Other side-effects include hyperkalaemia, uraemia, hyponatraemia
and nausea.
• In addition to spironolactone, ascites can be managed by
paracentesis.
• That is the removal (‘tapping’) of ascitic fluid from the
peritoneal cavity under aseptic conditions.
• A colloid (human albumin solution (20%)) is infused (40 Ml (8
g of albumin) per litre of ascites drained) intravenously during
paracentesis, in order to prevent intravascular volume
depletion and the onset of renal failure.
• Following paracentesis, ascites recurs in the majority (93%) if
diuretic therapy is not reinstituted, but recurs in only 18% of
patients treated with spironolactone.
• Cirrhotic ascites can become infected and if peritonitis occurs
• survival depends on early, vigorous antibiotic therapy. The
patient should be monitored for signs of infection