2. The Liver
• Largest Gland
– Weighs 1 5 Kg
1.5
– Inf edge is usually
subcostal
– Synthesizes and
detoxifies
By Dave Kotun for NSU Orlando 2
3. OBJECTIVES
• List the tests which aid in the assessment of the
detoxification function of liver
• List tests which aid in the assessment of hepatic injury
and necrosis
• Explain why the gamma-glutamyl-transpeptidase
(GGT) and alkaline phosphatase tests aid in the
assessment of biliary tract obstruction
y
• Recall what effect the liver function has on the y the
prothrombin time and serum albumin
• Compare and contrast the lab findings in the
hepatitises and what impact these conditions have on
individual and community health
• Trace the b ub pa
ace e bilirubin pathway a d the lab findings in
ay and e ab d gs
bilirubin abnormalities and biliary tract obstruction.
• Describe etiologies, lab findings, and complications
associated with the effect of alcohol on the liver
By Dave Kotun for NSU Orlando 3
4. LIVER FUNCTION TESTS
• Tests which can assess the synthetic function of liver
– Prothrombin time
– Serum albumin
– Cholesterol
Ch l t l
• Tests which can assess the detoxification function of liver
– Serum bilirubin: total; direct briefly describe the metabolic pathway of
bilirubin, indicating where unconjugated and conjugated bilirubin exist in the
pathway
– Serum ammonia
• Tests which may be indicative of liver injury
– Aminotransferases
• Aspartate aminotransferase (AST)
• Alanine aminotransferase (ALT)
• Gamma- glutamyl-transpeptidase ( GGT )
• Tests which may be indicative of biliary tract obstruction
– Alkaline h
Alk li phosphatase (ALP)
ht
– Gamma- glutamyl-transpeptidase (GGT)
By Dave Kotun for NSU Orlando 4
5. HEPATOBILIARY DISEASE
• HEPATITIS
• Definition and important causes (viral; alcoholic; drug
induced; toxic or ischemic induced; autoimmune)
– VIRAL HEPATITIS
• Distinguishing between hepatitis A, B, and C in terms
of: mode of transmission; complications; diagnostic
screening
• Liver function test findings
• Clinical presentation
– Why hepatitis C is of particular health concern in the US
today
By Dave Kotun for NSU Orlando 5
6. HEPATOBILIARY DISEASE
• Hepatitis ( cont )
cont.)
– ALCOHOLIC HEPATITIS
– Clinical presentation and diagnostic findings
p g g
– DRUG-INDUCED HEPATITIS
• Examples of drugs which may cause hepatitis
– AUTOIMMUNE HEPATITIS
– Definition
– ACUTE FULMINANT HEPATITIS
CU U S
– Causes and diagnostic findings
By Dave Kotun for NSU Orlando 6
7. HYPERBILIRUBINEMIA
• Causes
– Elevation of unconjugated bilirubin
– Elevation of conjugated bilirubin
• Lab findings associated with biliary tract obstruction
– Complete: early and chronic findings
– Partial or intrahepatic obstruction
• CIRRHOSIS
– Definition
– Major causes
• Lab findings
• Complications
» p
portal hypertension (g
yp (gastroesophageal varices etc.),
pg ),
ascites, spontaneous bacterial peritonitis, hepatic
encephalopathy, hepatorenal syndrome, coagulopathy
By Dave Kotun for NSU Orlando 7
8. OVERVIEW OF LIVER
ANATOMY
• FUNCTIONAL UNIT: liver lobule
– Hexagonal structure with rows of liver cells ( hepatocytes ), a vein in
center (central vein), and “ portal triad “ (hepatic artery and portal
vein branch, bile duct) in each corner
• CIRCULATION
– hepatic artery brings blood rich in O2 to liver; blood flows from
portal triad to central vein
ein
– portal vein drains GI tract and spleen and carries blood rich in
nutrients to liver
• BILIARY TRACT: passageway of bile excretion (bile has bile
acids, bilirubin, and cholesterol)
– Bile is excreted by hepatocytes into adjacent small
passageways (canaliculi ) bile flows to bile duct in portal
triad intrahepatic ducts converge into R and L hepatic ducts
which converge into common hepatic duct cystic duct from
gall bladder joins common hepatic duct common bile duct
enters duodenum at ampulla of Vater
By Dave Kotun for NSU Orlando 8
9. FUNCTIONS OF LIVER
• Liver is the “major metabolic factory and disposal plant
“
– PLASMA PROTEIN SYNTHESIS
• Albumin
– major carrier of substances in blood
– most abundant plasma protein so maintains
plasma oncotic pressure
• most clotting factors
– BILIRUBIN METABOLISM ( figure 1 )
• Metabolic pathway of bilirubin:
• RBC breakdown ( typically in
spleen) heme biliverdin unconjugated bilirubin carried by
albumin to liver liver conjugates bilirubin to glucuronic acid
conjugated bilirubin excreted into small intestine reduced by
bacteria into urobilinogen urobilinogen excreted in feces or
reabsorbed and excreted in urine
By Dave Kotun for NSU Orlando 9
10. FUNCTIONS OF LIVER
• Why must unconjugated bilirubin be conjugated by liver and excreted
from body:
– Bilirubin is toxic if accumulates
– Unconjugated bilirubin is insoluble in water and can’t be excreted
can t
– Conjugated bilirubin is water soluble and can be excreted in bile
• BILE ACID PRODUCTION
– Bile consists of : cholesterol, bile acids, conjugated bilirubin
– Functions of bile:
F ti f bil
– Absorption of fat soluble vitamins ( A, D, E, K )
– Excretion of cholesterol and bilirubin
• DETOXIFICATION
– Converts nitrogenous wastes (ammonia) into urea, and
excretes urea (ammonia is toxic to brain)
– Metabolizes drugs and toxins in microsomes
– Conjugates bilirubin to detoxify and excrete it
• CARBOHYDRATE METABOLISM
– Synthesizes and stores glucose as glycogen
– Releases glucose into blood upon appropriate neural and
g p pp p
hormonal stimulation
By Dave Kotun for NSU Orlando 10
11. FUNCTIONS OF LIVER
• MAJOR SITE OF HORMONAL
BREAKDOWN AND RECYCLYING
– Monitors plasma hormone levels
• Estrogen levels increase in chronic liver failure
and males develop gynecomastia ( to be
discussed )
By Dave Kotun for NSU Orlando 11
12. LIVER FUNCTION TESTS
• INDICATORS OF HEPATIC SYNTHETIC FUNCTION
– Prothrombin time ( nml: 10- 12.5sec)
• Reflects ability to make clotting factors with very short half
lives (several hours) therefore reflects acute changes in
synthetic function (may also reflect chronic changes)
– Albumin ( nml: 3 0 - 5 5gm/dL )
3.0 5.5gm/dL
• Indicative of chronic changes in synthetic function
due to long half life
•SSerum protein electrophoresis can b used t
ti l t h i be d to
evaluate albumin and other proteins made by the
liver
– Cholesterol synthesis
– Gluconeogenesis
By Dave Kotun for NSU Orlando 12
15. Liver Function Tests
• INDICATORS OF HEPATIC DETOXIFICATION FUNCTION
– Ammonia Level
• End product of protein metabolism
– Bacterial action in the intestine with glutamine hydrolysis in the
kidneys
• Most i
M t is removed b th li ’ portal vein circulation and
d by the liver’s t l i i l ti d
converted to urea
• Almost any ammonia (NH3) affects acid-base balance and brain
function
• Uses
– Diagnose Reye’s syndrome
– Evaluate metabolism
– Evaluate progress of liver disease and treatment
– Monitor hyperalimentation patients
• Values
– Adults 15 – 56 μg/dL
– (nml: 12-47umol/L)
• For reference: false increase in ammonia may result from smoking; certain
diuretics; tourniquet on too tight or too long
By Dave Kotun for NSU Orlando 15
16. LIVER FUNCTION TESTS
• INDICATORS OF HEPATIC DETOXIFICATION
FUNCTION
– Bilirubin
• Total ( unconjugated and conjugated bilirubin ): 0.2-1.2
mg/dL
• Direct ( conjugated bilirubin ): 0 – 0.3 mg/dL
• Term “direct” refers to manner of measurement in lab
– Gamma-glutamyl-transpeptidase (GGT )
• Definition: enzyme which catalyzes transfer of glutamic acid
joined at a “gamma” carboxyl group
• Most sensitive indicator of hepatic injury, but nonspecific
for type of injury
• Can be used to monitor alcohol consumption in alcoholics
because is located in microsomes, and alcohol activates
microsomal enzymes
• Males: 15-85 U/L; Dave Kotun for NSU OrlandoU/L
females: 5-55
By 16
17. LIVER FUNCTION TESTS
• TEST WHICH MAY REFLECT HEPATIC INJURY AND
NECROSIS
– Aminotransferases
• Definition: enzymes which catalyze interconversion of amino
acids
– Alanine aminotransferase (ALT): (formerly SGOT)
– 0-48 U/L (U = units ) more specific for liver than AST
(formerly SGPT)
– Aspartate aminotransferase (AST): 0-41 U/L nonspecific
for liver: e.g. increased in MI
• Significant increase in both AST and ALT (>10x)
indicates severe hepatocyte damage
By Dave Kotun for NSU Orlando 17
18. LIVER FUNCTION TESTS
• TEST WHICH WHICH MAY REFLECT HEPATIC
INJURY AND NECROSIS
– ALKALINE PHOSPHATASE ( nml: 30-117 U/L )
• Different forms of ALP in different organs (
isoenzymes ): liver is major source, then bone
• Isoenzyme analysis can help determine source of
elevated ALP
By Dave Kotun for NSU Orlando 18
19. LIVER FUNCTION TESTS
• USE OF LIVER FUNCTION TESTS TO
DIAGNOSE HEPATOBILIARY DISEASE
– HEPATITIS
• Definitions:
– Hepatitis: i fl
titi inflammation and necrosis of li
ti d i f liver cells
ll
H
resulting from different types of injury ( e.g. viruses;
toxins )
– Antigen: biochemical component of a microbial
pathogen or body tissue recognized as foreign by one’s
immune system
– Antibody: protein produced by plasma cells which
forms complex with antigen to destroy microbial
pathogens or body tissue
– Autoimmunity: immune reaction to one’s own tissue
one s
and cells By Dave Kotun for NSU Orlando 19
20. LIVER FUNCTION TESTS
• ACUTE VIRAL HEPATITIS
• Comprise 80-90% of cases of acute hepatitis
• Types: Hepatitis A, B, C, D E
A B C D,
• Mode of transmission; complications; serological screening
• PHASES OF ACUTE VIRAL HEPATITIS
– Incubation period ( weeks: depends on virus )
p
p
– Prodromal phase: variable, systemic symtoms decreased
appetite ( anorexia ); nausea and vomiting; fatigue; arthralgia (
ache in joints ); myalgia ( muscle ache );headache; cough; sore
throat
– Clinical jaundice phase
• occurs 1-2 weeks after onset of prodromal phase
• serum blirubin > 2.5mg/dL to note signs of j
g g jaundice
• many patients do not develop jaundice ( anicteric hepatitis )
• liver enlarged and tender
– Recovery phase: constitutional symptoms disappear but liver
is till l
i still enlarged, and some l b t t are still abnormal
d d lab tests till b l
(aminotransferases )
By Dave Kotun for NSU Orlando 20
21. • LABORATORY FINDINGS IN
ACUTE VIRAL HEPATITIS
C S
– AST (aspartate aminotransferase) and ALT
(alanine aminotransferase) are increased 10 –100 100
x upper limit normal ( 400-4000 U/L )
– AST/ALT ratio < 1 (ALT > AST)
– Increased total bilirubin ( 5-20 mg/dL ) both
conjugated and unconjugated bilirubin increased
(
(necrotic liver cells have decreased ability to both
y
conjugate unconjugated bilirubin and excrete
conjugated bilirubin )
– ALP (alkaline phosphatase): 2x upper limit normal
(ULN)
– GGT (gamma- glutamyl-transpeptidase): 5 x ULN
– Prothrombin ti
P th bi time: not t i ll elevated unless
t typically l td l
acute fulminant hepatitis NSU Orlando discussed)
By Dave Kotun for (to be 21
22. CHRONIC ACTIVE HEPATITIS
(CAH)
• HEPATITIS B ( HBV ): 5% patients develop CAH Criteria- if the
following occur longer than 6 months
– Hepatitis B surface antigen ( HBsAg ) present ALT increased
– HBV resolves when HBsAg disappears and hepatitis B surface
antibody ( anti-HBs ) appears
• HEPATITIS C ( HCV ) 60 80% patients develop CAH
): 60-80% ti t d l
– IS A MAJOR HEALTH CONCERN IN US TODAY
• results in 8,000-13,000 deaths annually in US
• 20-30% patients develop cirrhosis which may progress to
primary liver cancer ( hepatocellular carcinoma )
• 75% patients asymptomatic, so: silenty, over many decades,
HCV destroys liver cells resulting in cirrhosis
• AST and ALT may be normal intermittently making detection
more difficult
• Annual cost related to hepatitis C in US is very high: In 1997
cost was approximately $5.46 billion
By Dave Kotun for NSU Orlando 22
23. CHRONIC ACTIVE HEPATITIS
(CAH)
– MODE OF TRANSMISSON OF HEPATITIS ( for reference )
• Blood:
IV drug addicts sharing needles ( most efficient means of
transmission ) transfusions before 1992; needle stick accidents in
health care professionals (1/2000 infection rate )
• Intranasal cocaine
• Sexual contact
• Tatooing or body piercing: with unsanitary conditions
• Perinatal transmission
• Sharing
Sh i razor or t th b h f
tooth brush from an i f t d person
infected
– DETECTION ( for reference )
• often diagnosed incidentally on routine exam
• screening serology: detection of hepatitis C antibody (enzyme
immunoassay )
• confirmation: recombinant immunoblot assay ( RIBA )
• HCV RNA: confirmation and determination of viral load to monitor
treatment response
– TREATMENT: interferonDave Kotun for NSU Orlando
By alpha and ribavirin ( for reference ) 23
24. CHRONIC ACTIVE HEPATITIS
(CAH)
– ALCOHOLIC HEPATITIS
excessive alcohol intake is the leading cause of liver disease in most
Western countries
– some reasons why alcohol is hepatotoxic: ( for reference )
• alcohol d h d
l h l dehydrogenase ( metabolizes alcohol ) causes f tt change
t b li l hl fatty h
which is initial pathologic change in alcoholic liver disease: fatty
change alcoholic hepatitis ( continuous destruction with acute
episodes of hepatic decompensation ) cirrhosis
p p p
• toxic products of alcohol metabolism: free radicals and
acetaldehyde ( disrupt cell membrane function )
fatty change is reversible, and alcoholic hepatitis is reversible to a
point if patient abstains from alcohol
By Dave Kotun for NSU Orlando 24
25. Alcoholic Hepatitis
• CLINICAL FEATURES OF ACUTE ALCOHOLIC
HEPATITIS
– Variable presentation: mild fatal hepatic
p p
decompensation
– Clinical findings similar to viral hepatitis
anorexia,
anorexia weight loss abdominal pain nausea and
loss, pain,
vomiting, jaundice, fever, tender hepatomegaly (
due to fatty liver and swelling of injured liver cells ),
splenomegaly ( in 1/3 ); ascites in 1/3 due to
transient portal venous obstruction or cirrhosis (
hepatic scarring )
By Dave Kotun for NSU Orlando 25
26. Alcoholic Hepatitis
• LABORATORY FINDINGS IN ALCOHOLIC HEPATITIS
– AST and ALT elevated up to 10 x ULN ( less than viral
hepatitis; AST often < 300 U/L )
– classically AST/ALT ratio > 1 ( or 2 ), but not always
this disproportionate increase in AST ( with
AST/ALT ratio > 2 ) is rarely seen in other forms of
liver disease remember: with viral hepatitis AST/ALT
ratio < 1
– GGT is increased
– MCV > 100 fL
• direct alcohol toxicity
• megaloblastic anemia secondary to folate deficiency (
MCV > 110 fL in diagnostic range; macroovalocytes;
hypersegmented neutrophils )
–HHyperbilirubinemia
bili bi i
By Dave Kotun for NSU Orlando 26
27. DRUG INDUCED HEPATITIS
Drugs:
g
• isoniazid ( anti-tuberculous drug ) – elevated
aminotransferases in 10%; illness like viral
hepatitis i 1% with 10% f t lit rate
h titi in ith fatality t
• Methyldopa
• “ alternative meds “
– some herbal meds ( e.g. senna, mistletoe;
herbal teas with toxic alkaloids; chaparral;
kava kava; comfrey; germander; Jin Bu Huan;
Ma-Huang )
– megadoses of vitamin A
By Dave Kotun for NSU Orlando 27
28. AUTOIMMUNE
HEPATITIS
• Definition: chronic hepatocellular necrosis
and inflammation usually with scarring which
tends to progress to cirrhosis and liver failure
( i th
in those who are untreated or unresponsive
h t td i
to therapy )
• Clinical presentation variable: may
resemble acute viral hepatitis, but patients
may be asymptomatic and diagnosed on
routine exam
• Diagnosis: a diagnosis of exclusion (
exclude other causes of hepatitis ) serologic
p g
testing helps make diagnosis: to be
discussed in By Dave Kotun for NSU Orlando
serology lecture 28
29. Acute Fulmanant Hepatitis
and Liver Failure Causes
• Acetaminophen overdose (suicide; accidental in children)
• Viral h
Vi l hepatitis
ii
• Halothane (anesthetic gas) - may also cause no or mild symptoms
and increase in serum aminotransferases is no longer used in
adults in US, but still in children
,
• Poisonous mushroom (Amanita phalloides)
• Hypotension caused by MI, arrhythmia or sepsis
• Rare: anti-seizure drugs- sodium valproate; phenytoin (may also
cause lless severe abnormalities i li
b liti in liver f
function)
ti )
• Some herbal meds
– Chaparral: native to southwest US; thought to have broad anti-
microbial properties and is used for many conditions such as
veneral skin lesions; popular among patients with HIV
– Jin Bu Huan: used as sedative and analgesic
– Ma- Huang ( has ephedrine ): used for weight loss and to treat
various medical conditions (
i di l diti (e.g. cough; b
h bronchitis; j i t
hiti joint
symptoms)
By Dave Kotun for NSU Orlando 29
30. Acute Fulmanant Hepatitis
and Liver Failure
LAB FINDINGS
• abrupt,
abrupt extreme elevation of ALT and AST: > 100 x ULN (> 4000 units/L)
• prothrombin time significantly prolonged ( > or = 4 sec above
normal)
• elevated serum ammonia may be seen: due to inability of necrotic
hepatocytes to convert ammonia to urea for excretion alterations in
consciousness which may ultimately result in coma can occur: called
hepatic encephalopathy ( to be discussed )
SUMMARY OF KEY LAB FINDINGS IN DIFFERENT FORMS OF HEPATITIS
• FEATURE VIRAL ALCOHOLIC TOXIC/ISCHEMIC
• AST/ALT RATIO <1 > 1 or 2 >1
• PEAK AST 10-100 1-10 > 100 ( x normal )
• nml or inc. usually > 15 sec
PT normal
By Dave Kotun for NSU Orlando 30
31. Hyperbilirubinemia and
Jaundice
J di
• Jaundice, also known as icterus, is noted as
yellowing of sclera and skin, due to increased
serum bilirubin ( > 2.5 mg/dL )
By Dave Kotun for NSU Orlando 31
32. Hyperbilirubinemia and
Jaundice
CAUSES OF UNCONJUGATED HYPERBILIRUBINEMIA
Unconjugated bilirubin is > 80-85% of total bilirubin
U j d bili bi i 80 85% f l bili bi
• BILIRUBIN OVER PRODUCTION
– Hemolytic anemias ( e.g. sickle cell anemia )
– Hemolytic transfusion reaction
– Resorption of major hemorrhages
• DECREASED BILIRUBIN CONJUGATION
– Gilbert s
Gilbert’s syndrome:
• Inherited in 6% population; presents in adolescence or
adulthood with illness, strenuous exercise, fasting, lack of
sleep, stress ( bilirubin rarely > 3-4 mg/dL )
• Significance of Gilbert’s syndrome: recognition avoids
Si ifi f Gilb t’ d iti id
expensive work-up and reassures patient
– Physiologic neonatal jaundice:
Liver too immature to conjugate bilirubin in neonatal period (
especially if neonate is premature )
By Dave Kotun for NSU Orlando 32
33. Hyperbilirubinemia and
Jaundice
J di
CAUSES OF CONJUGATED ( DIRECT ) HYPERBILIRUBINEMIA
OBSTRUCTION TO FLOW OF BILE WITHIN THE BILIARY TREE
Conjugated ( direct ) bilirubin is > 50% of total bilirubin
• GALLSTONES
Cause > 95% biliary tract disease
Types:
– Cholesterol
majority stones in Western countries
• pigmented ( salts of unconjugated bilirubin ) caused by:
– chronic hemolysis ( sickle cell disease )
– parasitic infections in non-Western countries
• TUMORS
– Cancer of head of pancreas
–C Cancer of ampulla of V
f ll f Vater
– Cancer of bile duct
• BILIARY ATRESIA
– destruction or absence of all or part of extrahepatic biliary tree in
infants
– most common cause of death due to liver disease in early childhood
By Dave Kotun for NSU Orlando 33
34. Hyperbilirubinemia and
Jaundice
LAB VALUES IN BILIARY TRACT
OBSTRUCTION
• early, complete obstruction
– increasing conjugated bilirubin ( direct
bilirubin )
– slow i
l increase i ALP ( alkaline
in lk li
phosphatase ) over several days ( < 3-4 x
U
ULN )
– increase in AST ( aspartate
aminotransferase ) and ALT
– ( alanine aminotransferase )
By Dave Kotun for NSU Orlando 34
35. Hyperbilirubinemia and
Jaundice
J di
• Persistent ( chronic ), complete obstruction
– ALP and GGT ( gamma-glutamyl-
transpeptidase) markedly increased:
pp ) y
often 10 –30x ULN
– Progressive increase in total bilirubin
g
• Partial or intrahepatic obstruction
– Progressive increase in ALP a d GG
og ess e c ease and GGT:
often 10-30x ULN
– Minimal increase in direct bilirubin
– Normal AST and ALT
By Dave Kotun for NSU Orlando 35
36. Hyperbilirubinemia and
Jaundice
EXPLANATION OF LAB VALUES FOR CONJUGATED
HYPERBILIRUBINEMIA:
• Complete obstruction to bile flow results in the
following:
– Some bile which is not excreted diffuses back into
the
th serum
– Pressure increases in biliary tract; to overcome
pressure in biliary tract, enzymes found at surface of
smallest bile ducts ( ALP and GGT ) increase
– Toxic waste ( e.g. bilirubin ) builds up in liver cells (
hepatocytes ) due to accumulation of backed up bile in
the cells the liver cells are damaged AST and
ALT increase
• Partial obstruction of biliary tract
– Obstruction is enough to cause pressure in biliary tract
and increase in enzymes ( ALP; GGT ) near small bile
ducts
d cts
– Obstruction is NOT enough to cause significant
By Dave Kotun for NSU Orlando 36
diffusion of bilirubin back into serum
37. Cirrhosis
DEFINITION: diffuse injury and scarring of liver tissue
causing
i
total disruption of liver architecture and function
• CAUSES OF CIRRHOSIS IN WESTERN WORLD:
– ALCOHOLIC LIVER DISEASE 60-70%
– Viral hepatitis 10%
– Biliary disease 5-10%
– Primary hemochromatosis 5%
– Remainder: 10-15%
• Autoimmune h
Ati hepatitis; alpha anti-trypsin
titi lh ti t i
deficiency; Wilson's disease;
– Unknown cause
– Look up the symptoms of Wilson’s disease
By Dave Kotun for NSU Orlando 37
38. Cirrhosis
CONSEQUENCES OF CIRRHOSIS
• PORTAL HYPERTENSION
Definition: increased pressure in portal circulation due to resistance
to portal blood flow in scarred liver
Consequences Of Portal Hypertension:
– Engorgement of veins where systemic and portal circulation
share common capillary beds
• Gastroesophageal varices: in 2/3 patients with advanced
cirrhosis; fatal rupture and hemorrhage occurs in half of patients
with varices
• Hemorrhoids: veins in rectum
• Periumbilical veins: “ caput medusae”
– Congestive splenomegaly
– Ascites
By Dave Kotun for NSU Orlando 38
39. ASCITES
Definition: at least 500 ml of excess fluid in abdominal cavity
Causes:
• Portal hypertension ( hydrostatic pressure driving fluid out of vessel )
• Low serum albumin ( decreased serum oncotic pressure) secondary
to:
– Decreased synthetic ability of cirrhotic liver
– Decreased portal blood flow and supply of amino acids to liver
• Consequence of ascites:
SPONTANEOUS BACTERIAL PERITONITIS abrupt onset of fever,
chills, and generalized abdominal pain without obvious source of
Infection (bacteria can be grown from ascitic fluid )
By Dave Kotun for NSU Orlando 39
40. Coagulopathy
• Definition - increased bleeding tendency
• Causes:
– Decreased ability of liver to make clotting
factors
– Decreased ability of liver to make bile acids
y
to absorb vitamin K from small intestine
(vitamin K needed to make some clotting
factors)
– Decreased platelets because are
sequestered in enlarged spleen (
q g p (due to
portal hypertension)
By Dave Kotun for NSU Orlando 40
41. Hepatic Encephalopathy
• Definition: complex neuropsychiatric syndrome with disturbances in
consciousness, mood,
consciousness mood and behavior along with fluctuating
neurologic signs
• Presentation of hepatic encephalopathy: varies- acute and
reversible vs. chronic and progressive; 4 stages with last stage
being coma which may result in death
• Cause of hepatic encephalopathy: decreased detoxification of
neurotoxic substances ( like ammonia ) by liver ( may occur in
setting of cirrhosis or acute, fulminant liver failure )
• Precipitating factors: ( for reference )
– Increased nitrogen load ( e.g. GI bleeding )
– Electrolyte i b l
El t l t imbalance
– Infection
– Surgery
By Dave Kotun for NSU Orlando 41
42. Hepatorenal Syndrome
• Definition: acute renal failure occurring in
the setting of severe liver disease, in
which there is no structural abnormality of
y
the kidney
• Precipitating factors ( for reference )
p g
– An obvious cause may not be present
– Severe GI bleeding ( e.g. ruptured
gastroesophageal varices )
– Sepsisoverly vigorous attempts to treat
ascites ( present in cirrhotic patients ) with
diuretic agentsDave Kotun for NSU Orlando
or paracentesis (fluid
By 42
drainage)
43. Impaired Estrogen Metabolism
• Symptoms
– In males: breast tissue development ( gynecomastia ),
testicular atrophy
• LAB VALUES IN CIRRHOSIS
– Decreased serum albumin
– Prolonged prothrombin time
– Slight elevation of alkaline phosphatase, GGT and total
bilirubin due to some obstruction to bile flow within liver from
scarring
– AST and ALT nml or slightly elevated due to liver cell injury
Not significantly elevated because significant acute liver cell
necrosis is not occurring, and much liver tissue is already
lost
By Dave Kotun for NSU Orlando 43
44. NORMAL LAB VALUES:
• Serum albumin 3-5.5 gm/dL
• Prothrombin time 10 - 12.5sec
• Total bilirubin 0.2-
1.2mg/dL
1 2mg/dL
• Conjugated ( direct ) bilirubin 0.0-0.3 mg/dL
• Serum ammonia 12- 47 umol/L
• Alanine aminotransferase
• ( ALT ) 0-48units/L
• Aspartate aminotransferase
• ( AST )
S 0 u ts/
0-41units/L
• Alkaline phosphatase 30-117units/L
• Serum amylase 25-125 units/L
• Serum lipase 10-140
units/dL
i /dL
By Dave Kotun for NSU Orlando 44
