Respiratory System Blood Tests Reveal Liver Damage
1. MD-2204 (Respiratory System)
MD-2204 (Respiratory System)
PREPARED BY: MUHAMMAD ARIFF B. MAHDZUB
BACHELOR MEDICINE AND SURGERY (MBBS)
UNIVERSITY COLLEGE SHAHPUTRA, KUANTAN
DR. MISHAL
MD-2204 (DIGESTIVE SYSTEM)
PROBLEM BASED LEARNING (PBL)
Hepatitis C virus
2. LEARNING ISSUES
• PATIENT HISTORY, SIGNS AND SYMPTOMES
• ANATOMY OF THE LIVER (GROSS ANATOMY)
• HISTOLOGY OF THE LIVER
• BLOOD TEST AND NORMAL VALUES
• PHYSIOLOGY OF LIVER
• HEPATITIS
• TRANSFUSION-TRANSMITTED DISEASES (TTD)
• LIVER BIOPSY
• DIFFERENTIAL DIAGNOSIS
• TREATMENT & MANAGEMENT
4. TRIGGER 2 (FOLLOW-UP VISIT)
• DENIED ALCOHOL/DRUG
• NO JAUNDICE HISTORY
• WIDOWER (3 MONTH), NOT ADMIT EXTRA SEX
• AGE 40, HAVE BLEEDING STOMACH ULCER
• NEED SURGERY, AND TRANSFUSION 4 UNITS OF BLOOD
5. TRIGGERS 3 (NEXT VISIT)
• NO JAUDICE, NO HEPATOSPLENOMEGALY, NO PORTAL
HYPERTENSION
• RT-PCR FOR HCV IS DONE, GENOTYPE OF HCV IS
DETERMINED, LIVER BIOPSY
• DIAGNOSE : INFECTIOS ETIOLOGY OF TTD
6. CLARIFY DIFFICULT WORD
• TTD : virus, parasite, or other potential pathogen that can be
transmitted through a transfusion to a recipient
• RT PTC: spesific type of technology in molecular biology used
to amplify a single copy or a few copies of a piece of RNA
7. CLINICAL SIGNIFICANCE OF RT-PCR
• To identifies the presence of viral RNA and the actual
virus
• Detection and confirmation of chronic HCV infection
• very sensitive to low viremia
• so, usefull for person who was infected with HCV
very recently, called acute infection, as not develop
antibodies yet
8.
9. • Largest visceral organ
• Triangular organ
• Upper part abdominal cavity
just beneath diaphragm
• Occupies :
-right hypochondrium
-epigastrium
-left hypochondrium
• Lobes :
-right , left, caudate, quadrate
10. • LOBES
-liver is divided into a larger
right lobe and a smaller left
lobe by the falciform
ligament
• RIGHT LOBES
-Largest lobe
- Quadrate lobe and caudate lobe.
- Divided into anterior and
posterior sections by the right
hepatic vein
11. • QUADRATE LOBE
-Inferior surface of Rt.lobe
-Boundaries :
Ant. – Inf. border of liver
Sup. – porta hepatis
Rt. – fossa for gallbladder
Lt. – fissure for ligamentum teres
• CAUDATE LOBE
-Posterior surface of Rt. Lobe
-Boundaries :
Inf. – porta hepatis
Rt. – groove for inf. vena cava
Lt. – fossa for lig. venosum
12. • LEFT LOBES
-smaller and more flattened than
the right
-Divided into lateral and medial
segments by the left hepatic vein
• COUINAUD CLASSIFICATION
-Right hepatic vein divides Rt.
lobe into ant. and post. segments.
-Middle hepatic vein divides liver
into Rt. and Lt. lobe
-Left hepatic vein divides Lt. lobe
into a medial and lateral part.
-Portal vein divides liver into
upper and lower segments
13. • BLOOD SUPPLY OF LIVER
1. Right & Left hepatic arteries
2. Portal vein
3. Hepatic veins
17. INFLOW TO THE LIVER
- Hepatic Artey (O2
blood)
- Portal Vein (nutrients
and compound
absorbed from GIT)
OUTFLOW FROM LIVER
- Hepatic Vein (drain
into vena cava)
- Common hepatic
duct
19. - Portal Triad consist of portal vein, hepatic artery and bile duct
- Central vein Sublobular vein Collecting vein Hepatic vein Vena cava
- Sinusoid : Capillary-like vessel lined by fenestrated discontinous epithelium
20. - Space of Disse: A space between hepatocyte and sinusoidal
epithelial cell which a space for exchange between hepatocyte
and blood
• Kupffer cells :
I. Interspersed among endothelial cell.
II. Fixed macrophage within hepatic tissue
III. Enter sinusoidal lumen to function like other macrophage
IV. Breakdown damaged RBC hemoglobin
21.
22. HEPATIC LOBULE
• Structural unit of liver
• Roughly hexagonal in shape
• Centered on a terminal hepatic
venule (central vein)
• Portal tract (portal triad) situated
at the angle of hexagon
HEPATIC ACINUS
- Roughly berry-shaped unit of liver
parenchyma
- Have 3 zone
i) Zone 1 : near to portal tract (receive
most oxygenated blood
ii) Zone 2
iii) Zone 3 : far from portal tract (receive
least oxygenated blood)
23. Acute viral hepatitis
Characterized by:
• diffuse cell injury with swelling
• Spotty necrosis
• Process mediated by lymphocyte : alter the cell membrane antigen destroy the hepatocytes
• At the same time of damage , compensatory hypertrophy and replication of hepatocytes happen
• Finally, inflammation reaction most intense around portal tracts and also diffuse through sinusoid
• Most case resolve , but type B and C disease can become chronic.
Lobular disarray and spotty necrosis
24. Chronic Viral Hepatitis
1. Characterized by :
• hepatic necroinflammation (chronic inflammatory infiltrate and necrosis of
hepatocyte)
• Fibrosis
2. According to necroinflammatory activity , chronic hepatitis might be mild,
moderate and severe
2. Mild Chronic Viral hepatitis :
• dense lymphocytic portal
reaction. However, there
is very little spillage of
these lymphoid cells into
the lobules
• In addition, there is
spotty necrosis, but
necrotic cells are quite
rare
• no evidence of diffuse
liver cell injury.
Figure: This low-power hematoxylin and eosin-stained
liver biopsy demonstrates a periportal mononuclear
infiltrate and mild periportal fibrosis
25. • Moderately chronic
hepatitis was
characterized by:
dense portal and
periportal inflammation
and extensive piecemeal
necrosis,
affecting 50% of the
circumference of almost
all the portal tracts,
and lobular necrosis and
inflammation were
significant, with damage
of 1/3-2/3 the lobe.
The liver parenchyma showed
moderate lymphocytic infiltrate in
the portal tracts and portal fibrosis.
Intralobular moderate inflammatory
infiltrate was present.
26. Severe Chronic Viral Hepatitis:
• destruction of large chunks of
parenchyma, even tracts or bridges,
• beginnings of scars.
• lymphoid infiltrate with prominent
extension into the periphery of the
lobule and further extension deeper
into the parenchyma.
• associated with considerable spotty
necrosis and occasionally with
confluent necrosis as well, which may
bridge between central and portal
zones.
• Liver cells may be trapped within these
zones of confluent necrosis, a degree
and pattern of necrosis that is a
potential precursor of cirrhosis.
27.
28. BLOOD TEST AND NORMAL VALUES
NOTED
“BASE ON THE TRIGGER 1, BLOOD TEST WAS ORDERED
WHICH SHOW THE ELEVATION OF LIVER ENZYMES
APPROXIMATELY 3 TIMES THE UPPER LIMITS OF
NORMAL AND ALSO RAISED GLOBULIN FRACTION”
29. WHAT IS BLOOD TEST???
• A blood test is a laboratory analysis performed on a blood sample
that is usually extracted from a vein in the arm using a needle, or
via fingerprick. Multiple tests for specific blood components (such
as a glucose test or a cholesterol test) are often grouped together
into one test panel called a blood panel or blood work.
• Blood testsare often used in health care to determine physiological
and biochemical states, such as disease, mineral content,
pharmaceutical drug effectiveness, and organ function. Typical
clinical blood panels include a basic metabolic panel or a complete
blood count. Blood tests are also used in drug tests to detect drug
abuse.
31. Continue...
• A basic metabolic panel measures sodium, potassium, chloride, bicarbonate, blood urea nitrogen
(BUN), magnesium, creatinine, glucose, and sometimes includes calcium. Blood tests focusing on
cholesterol levels can determine LDL and HDL cholesterol levels, as well as triglyceride levels.
• Some blood tests, such as those that measure glucose or a lipid profile, require fasting (or no food
consumption) eight to twelve hours prior to the drawing of the blood sample.
• For the majority of blood tests, blood is usually obtained from the patient's vein. However, other
specialized blood tests, such as the arterial blood gas, require blood extracted from an artery.
Blood gas analysis of arterial blood is primarily used to monitor carbon dioxide and oxygen levels
related to pulmonary function, but it is also used to measure blood pH and bicarbonate levels for
certain metabolic conditions.
• While the regular glucose test is taken at a certain point in time, the glucose tolerance test involves
repeated testing to determine the rate at which glucose is processed by the body.
37. Digestion
• production of bile
• mixture of water, bile salts, cholesterol, and the pigment
bilirubin
• stored in the gallbladder
• cholecystokinin stimulates the gallbladder to release bile.
• emulsifies large masses of fat
• easier for the body to digest.
38. Metabolism
• metabolizing carbohydrate, lipids, and proteins
• Hepatocytes absorb much of glucose and store it as the
macromolecule glycogen
• absorption and release of glucose by the hepatocytes
helps to maintain homeostasis
• Fatty acids are absorbed by hepatocytes and
metabolized to produce energy in the form of ATP.
• Glycerol is converted into glucose by hepatocytes
through gluconeogenesis
• Hepatocytes first remove the amine groups of the
amino acids and convert them into ammonia and
eventually urea.
• amino acids can be broken down into ATP or converted
into new glucose molecules through gluconeogenesis.
39. Detoxification
• hepatocytes of the liver monitor the contents of the blood and
remove many potentially toxic substances before they can
reach the rest of the body.
• metabolize alcohol and drugs into their inactive metabolites
40. Storage
• storage of many essential nutrients, vitamins, and minerals
• Glucose is transported into hepatocytes under the influence of
the hormone insulin and stored as the polysaccharide
glycogen.
• absorb and store fatty acids from digested triglycerides
• stores vitamins and minerals - such as vitamins A, D, E, K, and
B12, and the minerals iron and copper
41. Production
• production of several vital protein components of blood
plasma: prothrombin, fibrinogen, and albumins.
42. Immunity
• function of the Kupffer cells that line the
sinusoids.
• capturing and digesting bacteria, fungi,
parasites, worn-out blood cells, and cellular
debris
• large volume of blood passing through the
hepatic portal system and the liver allows
Kupffer cells to clean large volumes of blood
very quickly.
46. • Bilirubin consists of an open chain of four pyrrole-like
rings (tetrapyrrole). In heme, these four rings are
connected into a larger ring, called a porphyrin ring.
• Bilirubin can be conjugated and unconjugated.
47. Unconjugated
• Erythrocytes generated in the bone marrow are
disposed of in the spleen when they get old or
damaged.
• This releases hemoglobin, which is broken down
to heme as the globin parts are turned into amino
acids.
• The heme is then turned into unconjugated bilirubin
in the monocyte macrophages system of the spleen.
This unconjugated bilirubin is not soluble in water,
due to intramolecular hydrogen bonding. It is then
bound to albumin and sent to the liver.
48. • In the liver, bilirubin is conjugated with glucuronic
acid by the enzyme glucuronyltransferase, making it
soluble in water: the conjugated version is also often
called "direct" bilirubin.
• Much of it goes into the bile and thus out into the
small intestine.
• Though most bile acid is resorbed in the terminal
ileum to participate in enterohepatic circulation,
conjugated bilirubin is not absorbed and instead
passes into the colon.
Conjugated
49. • There, colonic bacteria deconjugate and metabolize the bilirubin into
colorless urobilinogen, which can be oxidized to form urobilin and stercobilin: these
give stool its characteristic brown color.
52. Introductions of Hepatitis B
Infectious disease
caused by HBV
Affects the liver
Humans are the
only natural hosts
No animal
reservoir
Can cause both
acute & chronic
infections
Many people are
asymptomatic
during the initial
infection
It may take 30-180
days for symptoms
to begin
53. Morphology of the virus
• 3 forms:
1. Spherical particles measuring 22nm in diameter
2. Tubular or filamentous forms
I. same diameter but may be over 200nm long
II. result from overproduction of HBs Ag
3. Larger 42nm (Dane particles) containing partially ds circular DNA
• The outer surface contains
1. HBsAg
2. Surrounds an inner nucleocapsid core that contains HBcAg
• DNA polymerase is associated with the core
• Genome: partially double stranded circular DNA
54. Signs & symptoms
Acute
infection
Associated with acute viral hepatitis
General ill health (few weeks and then gradually improves)
Loss of appetite, nausea & vomiting
Body aches
Mild fever
Dark urine
Jaundice
Severe liver disease --> die
May be entirely asymptomatic
Chronic
infections
Asymptomatic
Associated with chronic hepatitis cirrhosis in several years
↑ incidence of liver cancer
55. Mode of Transmission
– Vertical transmission
– Sexual intercourse
– Parenteral
– High risk groups:
• Blood transfusion & transfusion with other human blood product
• Dialysis
• Health care personnel
• Living with infected person
– Contact with non-intact skin or mucous membrane with secretions or saliva
containing HBV
• Travel in countries where the infection rate is high
• Tattooing & acupuncture (less common with improved sterility)
• Re-use of contaminated needles & syringes (IVDU)
• Exposure to infectious blood or body fluids containing blood
56. Pathogenesis of Hepatitis B
Interferes with the
functions of liver
replicating in the
hepatocytes
The virions bind to the
host cell via the preS
domain of the viral
surface antigen
internalized by
endocytosis
HBV-preS-specific
receptors are
expressed on
hepatocytes
Host immune response
causes hepatocellular
damage and viral
clearance
Cytotoxic T
lymphocytes eliminate
HBV infection
by killing infected cells
& producing antiviral
cytokines
contribute to most of
the liver injury
Antigen nonspecific
inflammatory cells can
worsen the induced
immunopathology
Platelets activated at
the site of infection
may facilitate the
accumulation of CTL in
the liver
57. Diagnosis
• Detection of Dane particles in blood by electron microscopy
• Immunoassays
– for detection of hepatitis B virus infection
– involve serum or blood tests that detect either viral antigens
(proteins produced by the virus) or antibodies produced by the
host
• Hepatitis B surface antigen (HBsAg)
– Used to screen the presence of infections
– May not present in early infection
– May be undetectable later in the infection as it is being cleared by
the host
– Shortly after the appearance of the HBsAg, another antigen called
58. Prevention
Vaccination that
contains HBsAg as
the immunogen
Education of
chronic carrier
regarding
precautions
Screening of blood,
ovum, sperms &
organ donors
Adequate
sterilization
61. HEPATITIS A
Cause hepatitis A
(infectious
hepatitis)
Piconavirus
1 serotype
Short IP
3-4 weeks
Children most
frequently
infected
Sporadic@
epidemic
Mild ,very low
mortality
No carrier state
Outbreaks-
camps,
boarding school
Recover within 3-
6 months
low risk of
death,but higher
in
elderly@chronic
liver disease
62. ROUTE OF TRANSMISSION
Fecal route transmission
• Eat and drink food that come in contact with feces;
• houseflies
• poor cleaning after handling feces
• homosexsual,bisexual
Blood transfusion
• Rarely transmitted,low level viremia,low chronic infection
63. RISK FACTORS
• Travellers-asia,south africa,central America
• Iv drugs user
• Living in nursing home center
• Working in food,health care,sewage industry
70. HEPATITIS G
Flavivirus
Cause chronic
infection lasting for
decades
Transmitted via
sexual
intercouse&blood
Patient with
HIV&HGV has low
mortality rate,less
virus in blood than
HIV alone
HGV may interfere
with replication of
HIV
71.
72. Viral agents
• Human immunodeficiency virus (HIV)
• Hepatitis viruses
• West Nile virus (WNV)
• Cytomegalovirus (CMV)
• Human T-cell lymphotrophic viruses (HTLVs)
• Parvovirus B19
73. 1. HIV : a member of the Lentivirus family of retroviruses, is the causative
agent of acquired immunodeficiency syndrome (AIDS).
2. WNV : a flavivirus, is transmitted by mosquito bite.
The organism has the potential of being transmitted through blood.
3. CMV : belongs to the herpes group of viruses. The organism's
transmission is prevented by transfusing leukocyte-depleted blood
products, which is consistent with the fact that CMV is a leukocyte-
associated pathogen.
4. Human T-cell lymphotrophic virus–1 (HTLV-1) and HTLV-2 have been
shown to be transmitted by blood transfusion.
Infection with these retroviruses may result in HTLV-related
myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell
leukemia/lymphoma.
5. Parvovirus : a nonenveloped virus that is usually transmitted by
– vertically from mother to child
– blood products.Transmission by blood products is common because the
virus does not have a lipid envelope, rendering inactivation methods
74. Hepatitis C virus
• The hepatitis C virus (HCV) is a :
– Spherical
– Enveloped
– single-stranded RNA virus
– Flaviviridae family
• HCV is predominantly transmitted by means of :
– percutaneous exposure to infected blood.
• In developed countries, most new HCV infections are related to :
– intravenous (IV) drug abuse
• The use of the polymerase chain reaction (PCR) assay has reduced the risk
of acquiring HCV from blood transfusions to 1 in 230,000 donations.
75. Bacterial Infections
• Bacteria that potentially evades the sterility of the
transfusion loop can come from :
– donor's blood
– skin
– contaminated environment.
• The incidence of bacterial transmission depends on :
– blood product
– definition of the cases.
• The estimated residual risk of contamination of blood
products with bacterial agents is :
– 1 in 5,000 for platelets
– 1 in 30,000 for red blood cells.
76. Microbiologic spectrum of bacterial contamination
• A multitude of microorganisms have been isolated from
contaminated blood products.
• Some of these organisms and species include the following:
– Yersinia
– Proteus
– Pseudomonas
– Escherichia
– Klebsiella
– Acinetobacter
– Serratia
– Staphylococcus, Bacillus, and Enterococcus
78. DEFINITION
• Is a procedure in which tissue samples from the liver are
removed for examination under a microscope to look for signs
of damage or disease.
• During a liver biopsy, a special needle is used to determine if
cancer or other abnormal cells are present, or to determine
how well the liver is working.
79. 3 types of liver biopsies
1. Percutaneous or needle biopsy (common)
2. Laparoscopic or open biopsy
3. Transvenous biopsy
80.
81.
82.
83. Your doctor may recommend a liver
biopsy if you have:
• Abnormal liver test results that cannot be explained
• A mass (tumor) or other abnormalities on your liver as seen on
imaging tests
• Ongoing, unexplained fevers
84. INDICATION OF LIVER BIOPSY
Liver biopsy has three major indications:
• for diagnosis
• for assessment of prognosis
• to assist in the management of patient with known liver
disease.
85. WHY IT IS DONE ?
• Find the cause of abnormal blood test results from aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) tests.
• See how much the liver is inflamed or scarred by hepatitis or other liver diseases
• See whether other liver conditions, such as hemochromatosis and Wilson's disease,
are present.
• Check the response to treatment for liver disease.
• Check the function of a transplanted liver
86. RISKS
• Pain-most common complication after a liver biopsy. If
pain makes you uncomfortable, you may be given
a narcotic pain medication, such as
acetaminophen with codeine (Tylenol with
Codeine).
• Bleeding-Excessive bleeding may require you to be
hospitalized for a blood transfusion or surgery to
stop the bleeding.
• Infection - Rarely, bacteria may enter the abdominal
cavity or bloodstream.
• Accidental injury to a nearby organ-In rare
instances, the needle may stick another internal
organ, such as the gallbladder or a lung, during a
liver biopsy.
87. • If you have a transjugular liver biopsy, other
infrequent risks include:
– Collection of blood (hematoma) in the neck. Blood
may pool around the site where the catheter was
inserted, potentially causing pain and swelling.
– Temporary problems with the facial nerves.can injure
nerves and affect the face and eyes, causing short-
term problems, such as a drooping eyelid.
– Temporary voice problems. You may be hoarse, have a
weak voice or lose your voice for a short time.
– Puncture of the lung. If the needle accidentally sticks
your lung, the result may be a collapsed lung
(pneumothorax).
88. CONTRAINDICATIONS
• Liver biopsies should not usually be performed when there is biliary
obstruction and cholangitis.
• Abnormal coagulation indices:
– A percutaneous biopsy will not usually be undertaken if the INR is greater than
1.3.
– Thrombocytopenia : if the platelet count is >60 x 109/L then the biopsy can be
safely performed. If the platelet count is 40-60 x 109/L then platelet transfusion
may increase the count enough for the biopsy to be performed safely
– Drugs that affect platelet function (such as aspirin or clopidogrel) should
bediscontinued (where possible) 5-10 days before biopsy.
– Warfarin must be stopped and the INR monitored until it falls to 1.3 or less
before the biopsy is undertaken.
92. 1. Fatty liver, or steatosis, is a broad term that describes the buildup of
fats in the liver
2. Cirrhosis is a slowly progressing disease in which healthy liver tissue is
replaced with scar tissue, eventually preventing the liver from
functioning properly
3. Typhoid fever is an infection that causes diarrhea and a rash. It is most
commonly due to a type of bacterium called Salmonella typhi (S. typhi).
4. Hepatitis C is an infection of the liver. It's caused by the hepatitis C
virus
96. Conclusion
• Based on the table :
– Although liver cirrhosis have major of the sign n symptom
– But the most likely disease is hepatitis C
• Sign & symptom for the disease is same as patient’s complaint and
investigation
98. TREATMENT
Treatment for hepatitis C, depending on:
• How damaged the liver is.
• Other health conditions have.
• How much hepatitis C virus contain in body.
• type (genotype) of hepatitis C
Treatment isn't always an option because
• have serious side effects,
• are expensive,
• don't work for everyone.
100. Chronic Hepatitis C
• common for people to live with hepatitis C for years because it is
asymptomatic
• most people diagnosed with hepatitis C find out that they already
have chronic infection.
• If no damage to your liver, no treatment needed
• routine blood tests needed to determine liver function
• The medicines usually used to treat hepatitis C are interferons
combined with ribavirin plus a protease inhibitor e.g boceprevir or
telaprevir. Used for 6 months to a year and help get rid of the virus.
101. Management
• Patient must get vaccinated to protect from Hepatitis A and B
virus
• Patient must have enough sleep
• Careful with drugs and alcohol
• Relax and avoid depression and anxiety
Editor's Notes
Dane particles capable of infecting hepatocytes
The spherical & filamentous forms are incomplete viral coat proteins & are not infectious