Download hepatitis , cirrhosis

Hepatitis
And
Liver Cirrhosis
The liver
-The liver is the largest organ in the body, occupying The
entire upper right quadrant of the abdomen.
- Performs over 500 vital function.
- It processes all nutrients the body requires
- The liver manufactures bile,
- One of the liver's major contribution is to criminate the
toxic substance
Old red blood cells are removed from the blood by the liver and spleen
- Damage to the liver can impair these and many
other fractures
The liver lined with two types of cells :
Acini cell : it is the functional unit of liver .
Kupffer's cell, monocytes, lymphocytes:
It is apart of reticular endothelial system
[ monocytes macrophage], its phagocytic cells that are
capable of removing old and defective blood cells ,
bacteria, and other foreign material from portal blood ,
This phagocyte action remove the enteric bacilli and
other harmful substances that filter into the blood from
the intestine .
Hepatitis
.Hepatitis is inflammation of the liver that can be caused by
viruses ( e.g., hepatitis B or hepatitis C ) , medications ( e.g
.,methydopa or isoniazid ) , or immunologic abnormalities (
e.g., autommune hepatitis)
.Hepatitis can occur as acute or chronic disease
. Chronic disease generally is defined as that persisting for 6
months or longer .
Viral Hepatitis
.symptoms and time course alone cannot be used for
differentiating between the virus types
.Therefore, viralserologies are needed to distinguish between
infections caused by each of the viruses.
Hepatitis viruses
Virus
Other name
Family
type
Usual route of
transmission
Hepatitis A
Infectious
hepatitis
Picornavirus
RNA
Oral - fecal
Hepatitis B
Serum
hepatitis
hepadnavirida
e
DNA
Blood or
sexual
Hepatitis c
Non-A ,NonB
flaviviridae
RNA
blood
Hepatitis D
Delta
hepatitis
Delta viridae
RNA
Blood or
sexual
RNA
Oral - fecal
Hepatitis E
Hepatitis F
Hepatitis G
Oral - fecal
flaviviridae
blood
Hepatitis A
It is most common type of viral hepatitis occurring world-wide
symptoms , of infection with HAV are usually acute in onset
and infection occur primarily in children and young adult
Character of virus:
In small RNA virus that can be detected in the liver , feces and
blood during the late incubation periods and preicteric
phase of illness .
Epidemiology:
From the time of infection to the development of hepatitis
symptoms such as jaundice, malaise and right upper
quadrant pain.
The contagious period for hepatitis A appears to start 1 to 2
weeks before onset symptoms and end strongly (10 to 15
days) thereafter. Because high concentrations of hepatitis A
are found in the stool of infected patients, usually mode of
transmission is by directed fecal- oral contact or fecal
contamination of food or water, there is no carrier state for
hepatitis A.
Sings and symptom:
Hepatitis A is associated with:
-Fever (in 50% of patients)
- anorexia
- abdominal discomfort
jaundice . -
- nausea
- malaise
- dark urine
PathoPhysiology:
Hepatitis A infections are asymptomatic in approximately
one third of patient, and other third develop mild
nonspecific symptoms, and last develop more sever
symptom including jaundice.
Patient with more sever symptom have an increase in their
serum aspartate aminotransferase (AST), alanine
aminotransferase (ALT), and bilirubin, which resolve over
4 or 6 months.
Diagnosis:
- can not be made on clinical symptoms alone.
- diagnosis is based on measurement of immunoglobulin
M ( IgM) antibodies to hepatitis A in the serum .
(IgG) antibodies to hepatitis A appear in the serum and
against reinfection.
Serological test :
With the onset of jaundice, antibody to HAV (anti-HAV)
Become measurement in the serum.
1- Level of anti- HAVantibody of immunoglobulin M (IgM)
Class risen sharply
Indicate acute infection
( IgM : Onset of jaundice – short half life)
2- then after acute illness , anti – HAV antibody of the
immunoglobulin G (IgG) class predominate and remain
indefinitely
Indicate past stage of HVA infection.
( IgG: last stage – long half life-chronic, recovery stage )
Hepatitis B VIRUS
Hepatitis (B)
(( serum hepatitis ))
By DNA virus
Etiology :
B can be transmitted by blood or sexual exposure.
through the infected blood exposurecontaminated fluid splashes
in an eye or when sterile techniques are not used with:
Intravenous needles.. tattooing .. body piercing ...
Two type of circulating antigen are present in
the majority of patient :
Hepatitis B surface antigen .. HBsAg
The outer coat of the hepatitis B virus
Hepatitis B core antigen .. HBcAg
The core of hepatitis B virus that is produced and replicates in the
hepatocyte nucleus<< cause tissue damage
HBeAg appearance in the serum of the patient during the
incubation period
If the test are positive for hepatitis B E antigen the patient have
high dgree of infectivity.
Incubation period : 17 -98 day
Pathophysiolgy:
Cute hepatitis B associated wih high elevation in AST and
ALT Also in bilirubin
In chronic hepatitis is association with mild elevation in AST
and ALT
With normal alkaline phosphatase and #-glutamyl
transpeptdase .
Platelet and RBC remain normal.
Sign and symptom:
If it is acute Malasia, Anorexia, Nause, Vomiting, Jaundice
Dark yellow urine ,Weakness Flu like symptom << before
appearance of jaundice and dark yellow color
If it is chronic fatigue , weakness and malasia is the sign
Diagnosis:
After infection with hepatitis B:
HBsAg can be measured in the serum 30 to 60 days after
exposure to hepatitis B
So, antibodies against HBsAg developed and provide longterm immunity.
IgM antibodies against HBcAg develop and persist for about
6 months
So. HBcAg antibodies and IgM antibodies can use as markers
for hepatitis B.
HBeAg is a marker of rapid viral replication.
The develop HBeAg antibodies correlast with loss of
replication virus and decrease infectivity of the virus.
Present of HBeAg, HBDNA indicate replication.
Hepatitis C
(( NON-A , NON-B ))
By RNA virus
Etiology:
infected blood exposures such as blood transfusions,
needlesticks or tattooing .
Also by sexual transmission and perinatal (mother or infant )
transmission.
Incubation period :15 to 160 days
Pathophysiology :
Serum ALT, AST and bilirubin increase but not high as in
hepatitis B
Sign and symptom : The same as hepatitis B
Diagnosis :
Hepatitis C can be diagnosis by detection of antibodies
against the hepatitis virus or hepatitis C viral RNA in
the patient Serum
It can be measured within 1week of infection.
Antibodies against hepatitis C can be measured 6 to 9
week after infection.
If the patient test positive for antibodies against hepatitis
C and negative for hepatitis C viral RNA << mean the
patient have resolved infection.
Differential features of viral hepatitiS
Hepatitis A
Hepatitis B
Hepatitis C
Synonyms
Infectious disease
Serum hepatitis
Test for hepatitis
antigens and antibody
-ve
+ve
Incubation period
28 to 94 day's
17 to 98 day's
Age groups
Most common in
young children
All age group
affected
All age
Transmission
Usually fecal to oral
route
Transfusion of blood
and blood products
Blood and body fluid
Clinical feature
Flu, Fatigue, Anoxia,
Fever, Abdominal,
discomfort,
Anthologies,
Skin rashes,
Enlarge ,tender liver,
Light stool ,
Dark urine,
Jaundice
Tend to be more
several and
sometimes requires
hepatalization for
extended periods
Similar change in
hepatitis B
Similar to hepatitis A
-ve
and B
Hepatitis D
((delta))
the virus is an incomplete or detective RNA ..
nucleocapside core is thought to be coated with HBsAg
so, hepatitis D infection can only occur as coinfection or
superinfection with hepatitis B .
Etiology :
It can transmission by serum or I.V drugs users
Diagnosis:
Anti-delta IgM is detected during cute infection
HDAg and anti-HDAg disappear from serum when HBsAg
is cleared
HD need HB in replication, HBsAg
Incubation 1-2 month
Hepatitis E
Is the waterborne pathogen of C hepatitis
The virus is RNA virus
Etiology:
It can transmission by fecal-oral rout or by contact with
contaminated food or water.
Incubation period:1 to 2 month
Symptom :
Jaundice
Fatigue
Loss of appetite
Diarrhea
Nausea
Fever
Abdominal pain
Occurs for Young to middle age adults
Hepatitis F
Little is known about the virus , suggesting the need for
further research
Hepatitis G
(HGV)
The virus is RNA
Etiology:
Transmission by sexual , blood transfusion, injection drug
user ,
or by hemdialysis patient , accidental needle stick exposure
blood-born means
Pathogenesis
Liver appears normal in size and color but some time
slightly edematous, enlarge and tender edged to
palpation
.The characteristic picture is a combination of hepatocyte
necrosis and regeneration , a diffuse mononuclear cell in
filtration , hyperplasia of kupffer cells , and varying
degree of bile stasis . the mononuclear cells are primarily
lymphocytes , with some oesinophils noted .
. Labular disarray is apparent , probably due to the
presence of ballooned hepatic plates, which obliterate the
sinusids , smudging of hepatocyte cell membranes , and
the presence of inflammatory cell.
. Large hepatocytes with a .. ground glass.. appearance of
the cytoplasm due to the presence of HBsAg are
characteristic in chronic hepatitis B but are not seen in
acute hepatitis B
. Although the liver cell plates may be disrupted leading to
focal disruption of the reticulin network , this framework
is generally preserved , since the necrosis tend to be
limited to single of adjacent group cell.
. In severe cases of hepatitis , this framework is destroyed
leading to the characteristic pattern of bridging necrosisi
and a poorer prognosis
. In severe cases of hepatitis , this framework is generally
preserved , since the necrosis tend to be limited to single or
adjacent group cells.
Investigation:
1-liver biochemistry:
a) Elevation of aspirate amino transferase (AST) > 500 UI/L
and alanine aminotransferase (ALTA)
b) Elevation of lactate dehydrogenises (LDH)
c) Alkaline phosphates: is usually normal or mildly elevation
<300UI/L
d) Bilirubin (in blood): is expected to be elevated and too wear
as disease regress. ) Urinary bilirubin: persist through out the
disease.
2-hematological test:
Prothrombin time (PT): is prolonged in sever cases
Erythrocyte sedimentation rate is raised due to cytokine.
3-viral markers test (anti-body to HAV)
Present of anti-HAV IgM indicate an acute infection.
4- Differential diagnosis:
Clinically it is from all other causes of jaundice but
in particular from after type of viral hepatitis
Clinical feature :
Varies from fulminant hepatic failure to sub clinical from off to begin
asymptomatic..
1) Prodromal phase:
– occur in all patients and may be present 1or 2 weeks before one set of
jaundice (not all patient develop jaundice)
- main feature at this time are malaise , lassitude , anorexia , headache,
low-grad fever , and for smokers the less of desire to smoke . patient
may have discomfort in the right upper guardant .
- Many patient experience arthrolgia , arthritis ,urticaria ,and transient
skin rashes ..
2) Icteric phase:
The onset of jaundice usually lasts 4 – 6 week in addition to that urine
become dark and stool pale where the fever subside and appetite
normalize and feel well , the liver become moderately enlarge and
tender in addition may have spleenomegaly or tender
lymphadenopathy .
3) Recovery phase:
If uncomplicated recovery begins 1 -2 weeks from jaundice and last 2 – 6
weeks. Easy fatigue ability is common .stool color normalize, jaundice
lessens. Urine color lightens, speenomegaly take several weeks , lab take
3-6 months.
Complication:
* a few patient show rapid clinical deterioration following
the acute jaundice due to fuliminant hepatitis and
massive liver necrosis. Is frequently associated with acute
renal failure
The most common complication of viral hepatitis is called
chronic persistent hepatitis .
* following acute viral hepatitis a few patient may
develop chronic active or aggressive hepatitis in which
there is piecemeal destruction of liver and development
of cirrhosis
Cirrhosis
Definition:
Cirrhosis is characterized by a diffuse increase in the fibrous
connective tissue of the liver, with areas of necroses and
regeneration of parenchymal cells, imparting a nodular
texture histologically. In its later stages, cirrhosis leads to
such deformity of the liver that it interferes with
hepatobiliary function and the circulation of blood to and
from the liver
Cirrhosis Pathophysiology:
-Primary event is injury to hepatocellular
elements
-Initiates inflammatory response with cytokine release->toxic
substances
-Destruction of hepatocytes, bile duct cells, vascular
endothelial cells
-Repair thru cellular proliferation an regeneration
-Formation of fibrous scar
-Primary cell responsible for fibrosis is
stellate cell
-Become activated in response to injury and
lead to ed expression of fibril-forming collagen
-Above process is influenced by Kupffer cells which activate
stellate cells by eliciting production of cytokines
-Initially, fibrosis may be reversible if inciting events are
removed
-With sustained injury, process of fibrosis becomes irreversible
and leads to cirrhosis
Forms of cirrhoses
Etiology, pathology, pathogenesis
A-LAENNEC'S CIRRHOSIS:
-The 1st change in the liver caused by alcohol is the gradual
accumulation of fat within the liver cells (fatty
infiltration).
-The accumulation of fat reflects a number of metabolic
disturbances, including excess formation of triglycerides,
their decreased utilization in the formation of
lipoproteins, and decreased oxidation of fatty acids.
-The primary cause of liver damage is believed to the
direct effect of alcohol on the liver cell, which is increased
by malnutrition
-Grossly the liver is enlarged, fragile, and greasy in the
appearance and may be functionally deficient because
of the large accumulation of fat
-In far-advanced cases of Laennec's cirrhosis, thick fibrous
band formed at the periphery of many lobules,
partitioning the parenchyma into fine nodules.
-In the final stages the liver is shrunken, hard, and almost
devoid of normal parenchyma, resulting in portal
hypertension and hepatic failure.
B-POSTNECROTIC CIRRHOSIS:
Postnectotic cirrhosis presumably follow patchy necrosis of
liver tissue, resulting in large and small degenerative
nodules surrounded and partitioned by scar and
interspersed with normal liver parenchyma.
-About 75% of cases tend to progress and result in death
within 1-5 years.
-It is account for about 25% of the cases have a prior history
of viral hepatitis
-Many patients have positive test results for HBAg,
indicating that chronic active hepatitis may be an
essential event.
-A small percentage of cases stem from documented
intoxication with industrial chemicals, poisons, or
drugs(phosphorus, chloroform, carbon tetrachloride)
-A peculiar feature of postnecrotic cirrhosis is that it appears
to predispose the patient to the occurrence of a primary
hepatic neoplasm of liver (hepatoma).
C- BILIARY CIRRHOSIS
Liver cell destruction that begins around the bile ducts gives
rise to a pattern of cirrhosis known as biliary cirrhosis.
-The most common cause of biliary cirrhosis is posthepatic
biliary obstruction.
-Stasis of bile causes its accumulation within the liver
substance with destruction of liver cells.
- Fibrous bands begin forming around the periphery of the
lobule.
-The liver is enlarged, firm, finely granular, and has a
green hue.
-Jaundice is always an early and primary part of the
syndrome, as are pruritis, malabsorption, and
steatorrhea.
-The cause of this condition associated with lesions of the
intrahepatic bile ductules is unknown
-bile capillaries and ductules contain bile plugs, and the
liver cells frequently contain a green pigment.
-The extrahepatic biliary tract is not involved.
-Portal hypertension as a complication is rare.
Clinical manifestations
cirrhosis is insidious in its development
Early symptoms:
-are vague and nonspecific and include lassitude,
anorexia, dyspepsia, flatulence, a change in
bowel habits (either constipation or diarrhea),
and slight weight loss. Nausea and vomiting,
especially in the morning, are common.
-In most cases the liver is hard and palpable
regardless of whether it is enlarged or atrophied.
The major and late manifestation
Develops as a result of two types of disordered
physiology:
A-Manifestation of hepatocellular failure:
-jaundice occurs when there is active inflammation of the
liver bile ductules (cholangitis)
-Endocrine disturbances .
- spider angiomas, testicular atrophy, gynecomastia,
pectoral and axillary's alopecia , palmar erythema are
all considered to be caused by an excess of circulating
estrogen
-increased pigmentation of the skin is result from excessive
activity of melanin stimulating hormone.
-hematological disorder
-(Nose bleeding, gingival bleeding, menstrual bleeding)
result of decreased hepatic production of the clotting
factor
-anemia, leucopenia, thrombocytopenia are result from
hyper slenism
-folate, vitamin b12 , iron deficiency secondary to blood loss,
increase hemolysis of RBCs , patient more susceptible to
infection
-peripheral edema
-hypoalbuminemia abnormal salt and water retention
result from failure of the liver to inactivate aldosterone
and ant diuretic hormone
-sweetish odor
May be result from inability to metabolize methionine
-encephalopathy
Abnormalities in metabolism of ammonia
B-PORTAL HYPERTENSION MANIFESTATION :
-Portal hypertension is defined as a sustained elevation of
pressure in the portal vein above the normal level.
The primary mechanism for inducing portal hypertension,
regardless of the disease, is increased resistance to blood
flow through the liver.
-Increase in splanchnic arterial flow.
-decreased outflow through the hepatic vein and increase
inflow combine to overload the portal circuit.
-The back pressure in the portal system causes
splenomegaly and is partly responsible for the
accumulation of ascites.
-the important collateral channels which develop as a
result of cirrhosis and portal hypertension are found in
lower esophagus , the shunting of the blood through this
circuit to venae cavae cause dilatation of these veins
(esophageal varices)
-collateral circulation also involves the superficial to
dilated veins around the umpilicus (caput medusae)
-dilatation of anastomoses between the branches of the
inferior mesenteric vein and rectal vein lead to develop
of internal hemorrhoids
Complications:
Ascites
Accumulation of protein-rich fluid in the peritoneal cavity
Complaints associated with ascites:
-abdominal and back pain
-gastroesophageal reflux
-shortness of breath (secondary to impaired diaphragm
movement)
-large protuberant abdomen and an umbilical hernia
(Ascetic fluid is a good culture medium for bacterial
growth, and infections can occur spontaneously)
*Hepatic Encephalopathy:
The ultimate result of advance cirrhosis or severe hepatitis
is liver failure and hepatic coma (hepatic
encephalopathy)
Characterized by:
-increasing drowsiness
-personality changes
-mental confusion(flapping tremor of fingers or hands )
-Eventually, deepening coma and death follow.
Neurological complications (in coordinating, tremor, nystagmus, incontinence)
-As the disease progresses , a characteristic sweet pungent
odor may be present in patients breath (may be related
to exhalation of mercaptans)
*Gastrointestinal Bleedin:
-the major cause of GI Bleeding is shunting of
blood away from the high-pressure portal
system to low-pressure systemic collateral in the
esophagus (esophageal varices), rectum
(hemorrhoid)and other part of GI tract
-these veins become enlarged and tortuous and
can rupture easily
-Bleeding may be increased by deficiencies in the
vitamin k-dependant clotting factors
The pathogenesis of hepatic encephalopathy may be
related in part to increased in arterial and CNS
ammonium levels
-ammonia is produced in the lower GI tract when these
proteins and urea are metabolized by bacterial action
-the ammonia is then absorbed into the blood stream and
converted into ammonium ion
-Normally, liver converts ammonium into urea for
excretion by the kidney but when the liver is
malfunctioning as in cirrhosis , serum ammonium level
increase and encephalopathy enues.
-the carbotoxicity of ammonia result from inhibition of
oxidative metabolism by the citric acid cycle in the
brain
-alpha ketoglutarate combines with ammonia to produce
high CNS level of glutamine while robbing the citric acid
cycle of the alpha ketoglutarate needed for production
of highly
energy ATP.
Alanod AL Turki
Sara ALGeelani
Leena ALGhamdi
Hailah ALMogherah
Amal arafah
Ghadah AL-Yosef