Approach to Patient with

Hepatic Disorders
 Liver Structure and Function
 largest organ in the body;
 weighs about 1-1.5kg
 Located in the RUQ of the abdomen
under the right lower rib age against
the diaphragm
 Blood Supply
a. 20% from Hepatic Artery (oxygen-
rich)
b. 80% from Portal Vein (nutrient-rich)

A mixture of venous and arterial blood

bathes the liver cells
Hepatic Portal Vein
Artery

Liver
Common capillary bed/
sinusoids of liver

Central Veins
of each Lobule

Hepatic Vein

Inferior Vena Cava

 Liver Cells
 Hepatocytes – 2/3 of liver mass and
does most of the liver functions
 Kupffer cells – engulf particulate
matter (bacteria) that enter the liver
through portal blood
 Ito cells – fat-storing cells
Functions of Liver
 Glucose Metabolism
I.
Meal Glucose absorption in Portal Circulation Liver
intestines

Glucose converted Stored in

to glycogen hepatocytes

II.
Exercise Protein/Fat Liver creates glucose
breakdown
(gluconeogenesis)
 Ammonia Conversion
Ammonia from: use of amino acids Ammonia from: production
from protein for gluconeogenesis of intestinal flora/ from diet

Portal Circulation

Liver: converts ammonia to urea

Systemic circulation

Excreted in the kidneys

(urine)
 Protein Metabolism
 Synthesizes plasma protein
(albumin, alpha and beta globulin)
 Clotting factors (prothrombin)
- liver needs Vit. K to synthesize prothrombin
 Fat Metabolism
 Fatty
acids are degraded into ketone
bodies for energy during
hypoglycemic state, starvation and
uncontrolled DM.
 Vitamin and Iron Storage
 Large amounts of Vit. A, B, and D and
several B-complex vitamins are
stored in the liver
 Iron and copper are also stored in the
liver
 Drug Metabolism
First-pass Effect

Oral meds pass the Portal Liver (metabolized)

G.I.T. circulation

Decreased
bioavailability

Bioavailability – fraction of drug that reaches the systemic

circulation
 Bile Formation
 Formed by the hepatocytes
 Primary bile acids are cholic acid and
chenodeoxycholic acid (CDCA)
 Major components: water(82%), bile
acids(12%), lecithin &other
phospholipids (4%) and unesterified
cholesterol (0.7%)
 Bilirubin Excretion
Degradation of
Senescent RBC’s in
the spleen

Release of
Hemoglobin

Heme oxygenase Biliverdin reductase

Heme
CO & biliverdin bilirubin
molecule
 Enterohepatic Circulation

Bile
(conjugated bilirubin)

Bile ducts

duodenum

Ileum and colon Reabsorbed into Liver:

(converted into urobilinogen) portal circulation reexcreted into bile

Excreted in feces Systemic circulation

(stercobilin) kidney

Excreted in urine
Clinical History
 Symptoms of Liver Disease
 Nature of Disease
 Pattern of Onset
 Disease Progression
 Potential Risk Factors
 Symptoms of Liver Disease
A. Fatigue - most common
characteristic of liver
disease
e.g. lethargy, weakness,
restlessness
B. Nausea/Vomiting – provoked by
odor of food or fatty food
intake
C. RUQ pain/discomfort – arises from
stretching/irritation of
Glisson’s capsule w/c
D. Pruritus/Itching – related to
accumulation of bile
salts in the dermis
E. Jaundice – hallmark of liver disease
and most reliable marker
of severity
- accompanied by acholic
tools/ tea-colored urine?
e.g. jaundice without dark urine indicates
unconjugated hyperbilirubinuria
 Nature of Disease
Hepatocellular injury vs.
Cholestatic injury
Hepatocellular: ALT/AST elevated out
of proportion to alkaline phosphatase
Cholestatic: Alkaline phosphatase out
of proportion to ALT/AST
Viralvs Bacterial
( Viral Hepatitis/ Liver
abscess)
 Pattern of Disease (Staging)
 Course of disease (acute vs. chronic)
 Early vs. late
 Pre-cirrhotic, cirrhotic, end stage
 Disease Progression
(Grading)
 Severity and activity of disease
 Active vs. inactive; mild moderate,
severe
 Potential Risk Factors

A. Alcohol consumption
 for women: 2 drinks(22-30g/day)
for men: 3 drinks (33-45g/day)

 Assess presence of abuse or

dependence
Alcoholism – defined on behavioral
patterns and consequences of alcohol
intake not on the basis fo amount of
consumption.
Abuse – repetitive pattern of drinking alcohol
that has adverse effects on social, family,
occupational and health status
Dependence – alcohol-seeking behavior despite
its adverse effects

C Have you ever felt you ought to Cut

down on drinking?
A Have people Annoyed you by
criticizing your drinking?
G Have you ever felt Guilty or bad
about your drinking?
E Have you ever had a drink first
thing in the morning to steady your
nerves and get rid of hangover?
Eye-opener
B. Medications
 Currently taking meds? on maintenance
drugs? Herbal medicines? Birth control
pills? Self-medication? Illicit drug use?

C. Lifestyle
 Personal habits/hygiene
 Eating habits/food preference
 Sexual activity/preference
 Recent travel
 Environment/sanitation/occupation
 Tattoe, piercing, needle-stick injury
 Exposure/contact with patients with liver
disease
D. Past Medical History
 Previous hospitalizations
 Previously acquired diseases
 Recent surgery
 Blood transfusions

E. Family History
 Related familial diseases of the liver
Physical Examination
 A. Icterus

 Assess for these areas:

sclerae (under natural light)
skin ( for fair-skinned individuals)
oral-mucosa ( for dark-skinned
individuals)
• Clinically evident when serum bilirubin
exceeds 2.5mg/dL
 Types of Jaundice
A. Hemolytic - increased destruction of red
blood cells
e.g. transfusion reactions, Hemophilia
B. Hepatocellular – inability of damaged liver
cells to clear normal amounts of bilirubin from the
blood
e.g. viral hepatitis, cirrhosis
C. Obstructive – occlusion of bile duct by
gallstone, inflammatory process, tumor or
enlarged organ (extrahepatic)
- obstruction of small bile ducts within
the liver (intrahepatic)
 B. Spider Angiomata

 superficial tortous arterioles

typically fill from center outwards
usually seen on arms, face and upper
torso.

C. Palmar Erythema
 D. Hepatomegaly/Splenomegaly

 liver size varies; not a reliable sign

of liver disease
 Palpation: assess liver edge for
unusual firmness, irregularity and
nodules.

E. Hepatic Tenderness
 Most reliable P.E. finding
 Discomfort/pain on touching/pressing
 F. Ascites

 accumulation of excess fluid within

the peritoneal cavity
 Percussion: shifting dullness

(+) abdominal fluid wave

 G. Hepatic Encephalopathy
 Accumulation of ammonia due to damaged
liver cells fot to brain dysfunction
 P.E. : a. changes in personality, sleep
patterns, irritability, mental
dullness
(not due to meds, F&E imbalance,
etc.)
b. asterixis/flapping tremors of body
and tongue
c. Fetor hepaticus – sweet ammonial
odor, fruity- odor of
breath

* Trail-making test – N=15-30secs

 H. Others

• Umbilical Hernia – due to ascites

• Caput Medusa – collateral veins seen
radiating from umbilicus
• Hyperpigmentation/Xanthelasma- tendon
xanthomata due to increased lipids and
cholesterol
• Kayser-Fleischer rings- golden brown
copper pigment deposited at periphery of
cornea.
• Hepatic Bruit – sound produced in lung
CA.
Diagnostic Procedure
 i. Lab Tests/Liver Function
Tests
a. Pigment studies
b. Protein Studies
c. PT
d. Serum Aminotransferases
e. GGT,LDH
f. Cholesterol Studies
 a. Pigment Studies
Measures the ability of the liver
to conjugate and excrete
bilirubin

Serum bilirubin (direct) 0-0.3mg/dL

(total) 0-0.9mg/dL
Urine bilirubin 0(0)
Urine urobilinogen 0.05-2.5mg/24hr
Fecal urobilinogen 40-200mg/24hr
 b. Protein Studies
Albumin: cirrrhosis
chronic hepatitis
edema, ascites
Globulin: cirrhosis
liver disease
chronic obstructive jaundice
viral hepatitis
A/G ratio is reversed in chronic liver
disease
 c. Prothrombin
 Normal 100% or 12-16secs
 Prolonged in liver disease
 d. Serum Aminotransferases
A. ALT (SGOT) 10-40units
- to monitor coure of
hepatitis/cirrhosis and effects of
treatments that may be toxic to liver
- Increased : liver disorder
b. AST (SGPT) 5-35 units
- present n tissues high in
metabolic activity (heart, liver,
skeletal muscle)
- increase with damaged tissues
 e. GGT/ LDH
 Elevated in alcohol abuse
 Marker for biliary cholestasis
 f. Cholesterol Studies
 Elevated in damaged liver
Normal values:
HDL M: 35-70mg/dL
F: 35-85mg/dL
LDL <130µg/dL
ii. Diagnostic Imaging
 a. US/CT scan
 Firstoption for suspected obstructive
jaundice
 Can also detect fatty liver
 b. ERCP
 Both diagnostic (biliary tree
visualization) and therapeutic ( stone
extraction, stents)
 Extrahepatic cholestasis: dilated
ducts
 Intrahepatic cholestasis: ducts not
dilated
 c. Doppler US/MRI

 Asses
hepatic vasculature and
dynamics
iii. Liver Biopsy
 Goldstandard in evaluation of liver
disease
Alcoholic Liver
Disease
  due to chronic, excessive
alcohol ingestion
a. Fatty liver
b. Alcoholic hepatitis
c. Cirrhosis
 Alcoholic Cirrhosis (Laennec’s)
 An irreversible chronic injury of the
hepatic parenchyma and extensive
fibrosis in association of regenerative
nodules
 ii. Clinical Manifestations
 Anorexia, malnutrition, wt. loss
 Sx of hepatocellular dysfunction: jaundice, portal
hypertension, bleeding varices, ascites,
encephalopathy
 Hormonal disturbances:
Men: gynecomastia, testicular atrophy
Women: virilization, menstrual problem
 iii. Lab Findings
 Anemia – due to G.I. blood loss
- coexistent nutritional deficiency (folic &
B12)
 Elevated transaminases
 Prolonged PTT – reduced synthesis of clotting
proteins; Vit. K
 Decreased serum albumin – impaired protein
synthesis
 Increased ammonia levels – may lead to
encephalopathy
 iv. Prognosis
 Abstinence to alcohol consumption decreases
morbidity/mortality and delays/prevents
complications
Major Complications
 a. Portal Hypertension
 Normal pressure in portal vein
( 5-10mmHg); PH is > 10mmHg
 Damaged liver structures leads to
increased resistance to portal blood
flow (presinusoidal, postsinusoidal &
sinusoidal venous compartments)
 In Cirrhosis, resistance is usually at
sinusoidal area
 portal venous system has no valves

facilitates retrograde blood flow from high

pressure portal venous system to a lower
pressure systemic circulation

Cardioesophageal Rectum Retroperitoneal Falciform

junction space ligament of liver

Esophagogastric hemorrhoids ascites Periumbilical/abdominal

varices wall collaterals
(caput medusa)
 b. Esophageal Varices
i. Factors to Bleeding:
 Muscular exertion from lifting heavy
objects; straining at stool, sneezing,
coughing or vomiting.
 Esophagitis
 Irritation of vessels by poorly chewed
foods or irritating fluids; reflux of
stomach contents
 salicylates
ii. Treatment:
 Life- threatening EMERGENCY!!!
- replacement of blood loss to maintain
intravascular volume BEFORE Dx studies
and interventions to stop bleeding
(hemostasis)
*** excessive fluid administration would
increase portal pressure leading to further
bleeding
 Close monitoring of CVP, urine output,
mental status
 Only when hemodynamically stable should
we proceed to Dx procedure and
hemostasis
iii. Medical Management:

c. Vasoconstrictors:
• Vasopressin – generalized
vasoconstriction leading to decreased
blood flow to portal venous system
• Somatostatin/Octreotide – direct
splanchnic vasoconstriction
b. Balloon Tamponade
- tube introduced to the
stomach, gastric balloon inflated and
pulled back into the stomach cardia.
- done if bleeding is too
vigorous and endoscopy is not
available

e.g. triple lumen (Sengstaken-

Blakemore)
c. Endoscopic Intervention
– first line of treatment to control
bleeding acutely.
c.i. Endoscopic Sclerosis – varices
injected with sclerosing agents via a
needle- tip catheter passed through
the endoscope
c.ii. Endoscopic Band Ligation –
varices are ligated with
endoscopically placed small elastic
O-rings
d. non-selective beta adrenergic
blocker – causes hypotension and
eventually causes hypovolemia.
iv. Surgical Management
b. Portal-systemic shunt – to permit
decompression of the portal system

Non-selective – decompresses entire

portal system
Selective – decompresses only the
varices while maintaining blood flow
to the liver.
 c. Ascites
Accumulation of fluid in the
peritoneal space
Signs and Symptoms:
 Increased abdominal girth/ rapid weight
gain
 Short of breath – due to enlarged
abdomen
 Striae/distended veins
 Fluid and electrolyte imbalance
*** assessment based on the s/sx to assess
progression of the disease
 Cirrhosis
Continued arterial
with portal
underfilling
hypertension

Splanchnic Persistent activation of systems for

arterial retention of sodium and water;
vasodilation ascites and edema formation

Decreased in
circulating arterial hypervolemia
blood volume

Activation of
renin- Kidney retains
angiotensin and sodium and water
SNS and ADH
Management:
b. Dietary Modification
- low sodium diet (2g/d NaCl)
- to create a (-) Na balance leading to
diuresis
e. Diuretics
• Spironolactone (Aldactone) first line of
treatment for ascites from cirrhosis
• Furosemide – may produce hyponatremia
with prolonged use
• Ammonium Chloride/Acetazolamide –
contraindicated (precipitates hepatic
coma)
 *** daily wt. loss should not exceed:
1-2kg in patients with
ascites/edema
0.5-0.75kg in patients without
edema
*** fluid restriction is not attempted
unless Na is very low
Complications:
 Fluid and electrolyte imbalance
 Encephalopathy – due to
hypovolemia and dehydration
 Decrease potassium = increased
ammonia in systemic circulation
c. Bed Rest
- upright posture promotes activation
of RAAS system leading to decreased
GFR, Na excretion and decreased
response to loop diuretics

d. Paracentesis
 d. Hepatic Encephalopathy
A complex neuropsychiatric
syndrome characterized by these 4
major factors:
• Hepatocellular disease/portal systemic
collateral shunts
• Disturbances of awareness and mentation
• Shifting combinations of neurologic signs:
asterixis,rigidity,hyperreflexia
• A characteristic symmetric high voltage
triphasic slow wave pattern on ECG
Hepatocellular
dysfunction

Shunting of
Metabolic
portal
abnormalities in the
venous bood
CNS
into systemic
circulation

Liver is Toxic substances Accumulation

bypassed not detoxified by in systemic
liver circulation

*** Ammonia not converted to urea

 Common Precipitants

 Increased Nitrogen  Electrolyte and

Load Metabolic
- Gastrointestinal imbalance
bleeding - Hypokalemia
- Excess dietary protein - Alkalosis
- Azotemia - Hypoxia
- Constipation
- Hyponatremia
- hypovolemia
 Drugs  Miscellaneous
- Narcotics - Infection
- Tranquilizers - Surgery
- Sedatives - Superimposed
- diuretics acute liver disease
- Progressive liver
disease
- Portal-systemic
shunts
 Asterixi
Stag Mental Status s
EEG
e
I Euphoria or depression, +/- Triphasic
mild confusion, slurred waves
speech, disordered sleep

II Lethargy, moderate + Triphasic

confusion waves

III Marked confusion, + Triphasic

incoherent speech, waves
sleeping but
IV arousable
Coma; initially - Delta
responsive to noxious waves
stimuli, later
 Treatment:
 Elimination or treatment of
precipitating factors
 Lowering of blood ammonia levels by
decreasing the absorption of protein
and nitrogenous products from the
intestine