Signs and Symptoms of Liver Disease

Liver Disease, Misc

Cirrhosis

WHO definition:

Diffuse liver process where fibrosis has resulted in conversion of the liver architecture into structurally abnormal nodules

Cirrhosis is the final common pathway of any acute or chronic liver disease

scarring and distortion of liver architecture leads to compression of vascular and biliary structures which in turn causes impaired blood and bile flow with impaired delivery of nutrients, O2, and metabolites
Cirrhotic state persists even if original insult is corrected

Histology:

Bands of fibrous tissue that link central and portal areas and form parenchymal nodules

Macronodular 1-5cm separated by broad septa

Micronodular <1cm separated by fine septa

Mixed

Causes of Liver disease by magnitude of ALT elevation:

Chronic ALT>AST (<150U/L or 5x nml)	Chronic AST>ALT (<150U/L or 5x nml)	Severe/Acute ALT>AST (>1000 U/L or >20x nml)	Severe/Acute AST>ALT (>1000 U/L or >20x nml)
A1AT deficiency Chronic HAV,HBV,HCV Hemochromatosis Steatosis, Steatohepatitis AIH Drugs/Toxins Wilson Non-hepatic: -Celiac -Hyperthyroidism	Alcohol related liver injury AST:ALT = 2:1 Cirrhosis Non-Hepatic: Hypothyroidism Macro-AST Myopathy Strenuous exercise	Acute bile duct obstruction Acute Budd-Chiari syndrome Acute viral hepatitis AIH Drugs/Toxins Hepatic artery ligation Ischemic hepatitis Wilson	Meds/Toxins in pt with underlying EtOH liver injury Acute Rhabdomyolysis

Note: almost any liver disease can cause moderate ALT & AST elevations (5-15x nml)

Various Clinical Manifestations of Liver Disease:

Hepatomegaly

Liver exam should include:

consistency
contour
tenderness
presence of masses
bruits
assessment of spleen size
ascites
other sequelae of liver disease

Liver Edge (palpation of the liver edge below the right costal margin in the midclavicular line)

Children: Liver edge > 2cm suggests hepatomegaly

Newborn infant: Liver edge > 3.5cm suggests hepatomegaly

Span of dullness to precussion

1wk of age: 4.5-5cm
12yrs: (Boys) 7-8cm, (Girls) 6.0-6.5cm

Gallbladder

Infants: 1.5-5.5cm (average: 3cm)
Adolescents: 4-8cm
Range for all ages: 0.5-2.5cm

Jaundice

Yellow discoloration of the skin, sclera, and mucous membranes
Indicated for hyperbilirubinemia
Becomes clinically apparent serum biliruin concentration >2-3mg/dL (34-51umol/L)

Neonates might not appear jaundiced until a bilirubin > 5mg/dL (>85umol/L)

Bilirubin

4 forms:

Unconjugated bilirubin - tightly bound to albumin
Free or unbound bilirubin - can cross blood brain barrier --> kernicterus
Conjugated bilirubin - the only form that can appear in the urine
Delta fraction - bilirubin covalently bound to albumin (appears in serum when hepatic excretion of conjugated bilirubin is impaired)

"Direct" is not equal to "Conjugated"

Direct includes both conjugated bilirubin and the delta bilirubin

Pruritis

Itching caused in chronic liver disease usually with cholestasis
Can severely impact quality of life
Generalized or localized (often palms and soles)
Usually worse at night
Exacerbated with stress and heat
Unrelated to degree of hyperbilirubinemia (e.g. deeply jaundiced patients can be asymptomatic)
Relieved by cool temperatures (meds might help)
Pathogenesis unknown
Tx

Cholestyramine
Ursodeoxycholic acid
Opiate antagonists (naloxone)
Antihistamines
SSRI (Sertraline)
Rifampin

Refractory cases Tx - Plasmapheresis, molecular adsorbant recirculating system therapy, surgical diversion of bile

Spider Angiomas

Vascular spider-like lesions, Telangiectasias
Central pulsating arterioles with radiating venules
SVC distribution (Face and chest)
1-10mm
Central clearing with pressure
Due to altered estrogen metabolism assoc w/ hepatic dysfunction

Palmar Erythema

Splotchy erythema over hypothenar and thenar eminances as well as the tips of the fingers
Due to abnormal estradiol levels in the serum and changes in peripheral circulation

Xanthomas

At serum cholesterol levels >500mg/dL, Lipid is deposited in the dermis and subcutaneous tissue
Brown nodules develop pver the extensor surfaces on extremities
Rare: Eyelid xanthelasma

Ascites

Increased hydrostatic and osmotic pressure within the hepatic ad mesenteric capillaries resulting in fluid moving from blood vessels to lymphatics (which become overwhelmed)
Associated with:

Liver disease - portal hypertension (see below)
Nephrotic syndrome
Urinary tract abnormalities
Abnormal renal sodium retention
Metabolic diseases
Congenital or acquired heart disease
Hydrops

Factors that increase risk for intraabdominal fluid:

Decreased albumin (osmotic pressure in blood vessels)
Increased capillary hydrostatic pressure
Increased ascitic colloid osmotic fluid pressure
Decreased ascitic fluid hydrostatic pressure

Gastrointestinal Bleeding

Causes include

Portal hypertensive gastropathy
Gastric antral vascualr ectasia
Varix rupture

Varaceal hemorrhage usually from esophageal origin but may be from gastric, duodenal, peristomal, or rectal origin

Increased pressure within portosystemic collateral system leads to increased wall pressure in varix leading to rupture
Can lead to significant rate of hemorrhage

Portal Hypertension (pHTN)

Increased resistance to portal flow
Normal portal pressure = 1-5mmHg
Portal Hypertension = Portal Pressure > 5mmHg

Clinically significant pHTN occurs when portal pressure > 10-12mmHg
pHTN is the main complication of cirrhosis
pHTN is responsible for:

Ascites
Variceal hemorrhage

Encepahlopathy

Neurological dysfunction which appears in worsening liver disease
Difficult to assess in young children
May appear as:

Deterioration of school performance
Sleep disturbances
Depression
Emotional outbursts

Endocrine abnormalities

Typically associated with hormonal metabolism in the liver
Affected by synthesis, storage, and metabolic functions of liver

Misc findings in liver disease

Anorexia
Abdominal pain or distension from ascites
Spontaneous peritonitis
HSM
Malnutrition
Growth failure
Bleeding (altered synthetic function; coagulation factors)
Altered drug metabolism