Laboratory Tests And Diagnostic Procedures in Hepatobiliary Disease

Laboratory Tests And Diagnostic Procedures in Hepatobiliary Disease

Patricia Liu, M.D.

Liver function tests are best utilized in concert with the clinical situation and in conjunction with
serial determinations to ascertain the cause or evolution of the hepatic disorder. In addition, stool
and urine tests, radionuclide imaging, contrast cholangiography (transhepatic cholangiography and
endoscopic retrograde cholangiopancreatography), and histological assessment (liver biopsy) are
often utilized to delineate the nature of the liver disease.

Serum Enzymes (Serum Aminotransferase Transaminases)

Serum glutamic oxaloacetic transaminase, also referred to as aspartate aminotransferase, and
serum glutamic pyruvic transaminase, also called alanine aminotransferase (AST and ALT) are
commonly employed to ascertain liver function. Striking elevations in the serum levels of these
two enzymes are encountered in acute viral hepatitis, acute drug- or toxin-induced liver damage,
and ischemic hepatitis. In addition, levels exceeding 500 IU/L and, on rare occasions, 1,000 IU/L
can also be seen in patients with severe chronic active hepatitis, transiently in patients with
common bile duct stones, and in patients with Budd-Chiari and veno-occlusive disease.

There are a number of important hepatic disorders in which the serum AST and ALT are normal
or minimally elevated . These include idiopathic genetic hemochromatosis, methotrexate-induced
liver injury, liver dysfunction due to amiodarone, the liver disease associated with jejunal ileal
bypass surgery, and patients with chronic hepatitis C virus infection.

The ratio of AST and ALT is also sometimes of value in clinical practice. A ratio greater than 2
with both AST and ALT being less than 300 IU/L is characteristic of alcoholic liver disease.

On rare occasions, if both the AST and ALT are elevated, patients are subjected to a liver biopsy
after a very thorough serologic workup only to find that the liver histology is completely normal.
It is very important to exclude a primary muscle disorder in such patients since not only the AST
but also the ALT can be elevated in patients with muscle disorders.

Serum Alkaline Phosphatase

The sources of serum alkaline phosphatase include liver, bone, small intestine, placenta, and, on
rare occasions, tumors capable of producing alkaline phosphatase.

In general, patients with cholestasis have increased levels. However, the level of serum alkaline
phosphatase is not helpful in distinguishing intrahepatic from extrahepatic cholestasis. Rarely,
patients with hypernephroma and Hodgkin's disease have elevated levels in the absence of liver
involvement. Also, patients with Wilson's disease often have normal values.


On rare occasions, patients with a variety of malignant tumors have elevations in the serum
alkaline phosphatase level that are not caused by liver or bony metastases. This isoenzyme,
referred to as Regan isoenzyme, is biochemically and immunologically indistinguishable from
placental alkaline phosphatase, and in addition to being present in serum, can also be present in
tumor tissue or in malignant effusion fluids.

In normal children with active bone growth, influx of enzyme from osteoid tissue may result in a
threefold elevation above normal in alkaline phosphatase values. In the third trimester of
pregnancy, the serum level may double as a consequence of the contribution of placental alkaline
phosphatase, making interpretation of results of this test difficult during the latter stage of
pregnancy. Also, persons over the age of 50 years may normally have one and a half times normal
values. Subjects with blood groups O and B, who are ABH secretors and Lewis antigen-positive,
may have a significant amount of intestinal alkaline phosphatase in their serum, especially after
ingestion of a fatty meal. Thus, unlike other enzymes in the serum, the activity of alkaline
phosphatase can be noticeably affected by eating; hence, it is recommended that alkaline
phosphatase activity be assayed in the fasting state.

Although an elevation of the serum alkaline phosphatase level may be the first clue to
hepatobiliary disease, the alkaline phosphatase level is normal on rare occasions despite extensive
metastatic hepatic deposits or complete bile duct obstruction.

Patients with stage I or II Hodgkin's disease, hypernephroma, congestive heart failure, myeloid
metaplasia, peritonitis, diabetes, subacute thyroiditis, or uncomplicated gastric ulcer have been
reported to have mild elevations in serum alkaline phosphatase levels that are of probable liver
origin in the absence of overt liver involvement. Recently, twofold to fourfold elevations in serum
alkaline phosphatase levels were reported in several members of a family. No bone or hepatic
disorder was present in this family, who demonstrated the enzyme elevation in a pattern
suggesting autosomal dominant inheritance. In this context, the elevation of the serum alkaline
phosphatase level may be no more specific than that of an elevated sedimentation rate, and the
routine use of automated biochemical tests has indeed increased awareness of this phenomenon.

The most reliable method of determining the tissue origin of an elevated alkaline phosphatase level
is polyacrylamide gel electrophoresis. Since this is not routinely available in most clinical
laboratories and since methods using urea denaturation or heat inactivation are quite unreliable, it
is common practice to measure serum 5'-nucleotidase, or gamma glutamyl transpeptidase, when
dealing with an isolated or disproportionately elevated serum alkaline phosphatase level. In such
instances, elevations of the levels of any of these two enzymes generally imply that the source of
the elevated alkaline phosphatase level is hapatobiliary and not bony. 5'-nucleotidase levels may
increase in normal pregnancy, whereas gamma glutamyl transpeptidase levels do not. However,
commonly used drugs such as barbiturates, phenytoin, and alcohol may cause induction of hepatic
microsomal gamma glutamyl transpeptidase; therefore, an elevated serum level of this enzyme
does not necessarily imply frank liver cell injury. A disproportionately elevated serum gamma
glutamyl transpeptidase level for several days often follows moderate alcohol ingestion. This
finding is used by many physicians to detect alcohol abuse in patients who underestimate or deny
the ingestion of alcohol.


Serum Bilirubin

Most clinical laboratories use spectrophotometry to measure serum bilirubin. The normal value
for total bilirubin is less than 1 mg/dl. Two fractions - a conjugated or direct fraction (normally
less than 0.25 mg/dl) and an unconjugated or indirect fraction are obtained fairly routinely. It is
useful to classify hyperbilirubinemia into conjugated and unconjugated categories. Patients are
considered to have conjugated hyperbilirubinemia if greater than 50 percent of the elevated total
bilirubin level is conjugated, and categorized as having unconjugated hyperbilirubinemia if greater
than 80 percent of the total bilirubin level is unconjugated or indirect-reacting. Mild unconjugated
hyperbilirubinemia (total bilirubin level less than 5 mg/dl) is seen in Gilbert's disease
uncomplicated hemolytic disorders, and congestive heart failure. Mild conjugated
hyperbilirubinemia is a constant finding in the Dubin-Johnson and Rotor syndromes. Conjugated
hyperbilirubinemia of varying intensity is seen in a variety of liver disorders including acute viral,
drug-induced, and toxin-induced hepatitis, shock liver, and metastatic disease to the liver. Even in
fulminant hepatitis, the liver is capable of conjugating the bilirubin.

The height of the serum bilirubin level has no discriminative value in distinguishing intrahepatic
cholestasis from extrahepatic obstruction. Indeed, fairly marked elevations in total serum bilirubin
levels have been reported in patients with non-biliary tract sepsis. Although patients with
fulminant hepatitis may be anicteric, the level of serum bilirubin is of prognostic import in certain
conditions such as alcoholic hepatitis, primary biliary cirrhosis, and halothane hepatitis. In primary
biliary cirrhosis, persistent elevations of greater than 2.0 mg/dl in the serum total bilirubin level
usually occur late in the course of the disease and imply a poor prognosis. Bilirubin levels greater
than 10 mg/dl have been associated with a 60 percent mortality in patients with halothane
hepatitis.

Urine Bilirubin

The presence of bilirubin in the urine implies that it is direct bilirubin that is present, as indirect
bilirubin is tightly bound to albumin and hence not filtered by the normal kidney. This inexpensive
and sensitive test serves several functions: a positive result can rapidly confirm clinically suspected
hyperbilirubinemia; it implies hepatobiliary disease and excludes hemolysis; and it may provide an
early clue to the presence of hepatobiliary dysfunction, as presence of urine bilirubin often
antedates overt icterus.

Urine Urobilinogen

Urobilinogen results from the breakdown of conjugated bilirubin by intestinal bacteria. Normal
excretion in stool averages 100 mg per day. About 10 to 20 percent is absorbed into the portal
circulation, from where most of it undergoes entero-hepatic circulation. A small amount, usually
less than 2 mg per day, is excreted in the urine. Although urinary estimation is dependent upon
several factors including urine pH, rate of urine production, timing of collection (there is a diurnal
variation), and method employed, complete absence of urinary urobilinogen implies absence of
bilirubin in the intestine and strongly suggests complete bile duct obstruction. The passage of
clay-colored stools by the patient is equally meaningful. Increased urinary urobilinogen suggests


hemolysis or hepatic dysfunction.

Serum Lactate Dehydrogenase

Serum lactate dehydrogenase activity may arise from myocardium, liver, skeletal muscle, brain or
kidney tissue, and red blood cells. Therefore, an elevated serum 1actate dehydrogenase value is a
nonspecific finding. The hepatic origin (1aerate dehydrogenase 5) of serum lactate dehydrogenase
can be verified by isoenzyme determination. Increased lactate dehydrogenase levels are seen in
patients with a variety of hepatobiliary disorders including acute viral or drug hepatitis, congestive
heart failure, cirrhosis, and extrahepatic obstruction. Striking elevations in serum lactate
dehydrogenase and alkaline phosphatase levels are highly suggestive of metastatic disease to the
liver.

Serum Albumin and Globulin

Albumin is synthesized exclusively by hepatic parenchymal cells and has a serum half-life of about
20 days. Decreased levels in the serum can occur as a consequence of decreased synthesis or
excessive losses. The former occurs in patients with malnutrition or significant liver disease.
Hypoalbuminemia secondary to excessive loss of albumin is seen in patients with nephrotic
syndrome or protein-losing enteropathy.

A fall in the serum albumin level and a rise in levels of globulins, primarily gamma globulins, are
frequently seen in patients with chronic hepatitis or cirrhosis. Elevations in IgA levels are common
in alcoholic cirrhosis, and elevations in IgG levels are common in chronic active hepatitis.
Elevations in IgM levels are frequently seen in primary biliary cirrhosis; of the immunoglobulins,
only an elevation of the IgM fraction on immunoelectrophoresis has any significant specificity.

Diminished levels of alpha-l-globulins due to deficient alpha-1-antitrypsin activity can be
associated with chronic active hepatitis and cirrhosis in children and adults.

Coagulation Factors

All the clotting factors are synthesized by the liver, with the exception of factor VIII, which is
synthesized by reticuloendothelial cells and vascular endothelial cells. The half-life of these
coagulation factors is short, ranging from six hours for factor VII to five days for fibrinogen.
Therefore, acute liver injury often results in a prolongation of the prothrombin time, which is
dependent upon the activity of factors II, V, VII, and X. Factor VIII levels may be normal or
increased in severe hepatic injury; hence, assessment of factor VIII levels may help distinguish the
coagulopathy of liver disease from that secondary to disseminated intravascular coagulation where
factor VIII levels are generally decreased. Vitamin K-dependent factors include factors II, VII,
IX, and X. A prolongation of the prothrombin time beyond four seconds that of control despite
vitamin K administration (5 to 10 mg parenteral vitamin K; prothrombin time measurement
repeated 24 hours later) signifies fairly advanced liver disease. The prognostic significance of a
markedly elevated prothrombin time is exemplified by the 100 percent mortality reported in a
study of patients with halothane hepatitis who had a prothrombin time greater than 20 seconds.


Other clinically relevant aspects of abnormalities in coagulation include the necessity to correct
these factor deficiencies in patients with significant bleeding and the fact that certain procedures
such as percutaneous liver biopsy are contraindicated in patients with a significant coagulopathy.

Alpha Fetoprotein

Alpha fetoprotein is a unique alpha-l-globulin normally synthesized in large amounts by embryonic
liver cells and in trace amounts by fetal yolk sac cells and the fetal gastrointestinal tract. High
serum concentrations (greater than 500 ng/ml by radioimmunoassay) are present in 70 percent of
patients with primary hepatocellular carcinoma in the United States. Concentrations of this protein
fall dramatically in patients in whom partial curative hepatectomy is carried out. Serial
determinations aid in monitoring the response to therapy or detecting early recurrence.

Patients with yolk sac tumors with germ cell elements may also have high concentrations of alpha
fetoprotein. Modest elevations may be seen occasionally with other tumors, notably
gastrointestinal malignancies metastatic to the liver. Levels up to 500 ng/ml are seen during
pregnancy. High levels indicate multiple pregnancy, significant fetal neural tube defects, fetal
distress, or fetal death.

Serum Ferritin

Serum ferritin levels accurately reflect hepatic and total-body iron stores. However, the serum
ferritin can be elevated in a number of conditions, including idiopathic genetic hemochromatosis,
hepatocellular necrosis of any etiology (alcoholic liver disease, acute and chronic viral hepatitis,
drug-induced liver injury, obesity-related liver dysfunction), Hodgkin's disease, leukemia,
hyperthyroidism, uremia, and rheumatoid arthritis.

Measurement of serum iron concentration, percent transferrin saturation, and serum ferritin level
is the screening regimen currently recommended for idiopathic genetic hemochromatosis.

Serum Ceruloplasmin

Ceruloplasmin, a blue copper-containing glycoprotein is an acute-phase reactant. 95 percent of
patients with Wilson's disease have serum ceruloplasmin concentrations below 20 mg/dl. The
serum ceruloplasmin can be normal in 10 percent of patients with Wilson's and chronic active
hepatitis. It is also low in 10 percent of heterozygotes with Wilson's and low levels can also be
encountered in patients with nephrotic syndrome and protein-losing enteropathy.

Antimitochondrial Antibody

This autoantibody can be detected in the serum by a variety of methods including
immunofluorescence, double immunodiffusion, complement fixation, radioimmunoassay, and
enzyme-linked immunoassay. Mitochondrial antibodies are found in 0.8 to 1.6 percent of the
general population, 6 percent of patients with chronic active hepatitis, and 85 to 90 percent of
patients with primary biliary cirrhosis. Antimitochondrial antibodies are also found in a significant


number of asymptomatic relatives of patients with primary biliary cirrhosis and chronic active
hepatitis. Although the antibody titer has no discriminative value in distinguishing patients with
primary biliary cirrhosis from patients with a variety of other hepatobiliary disorders or
autoimmune conditions, recent studies suggest that the mitochondrial antibodies seen in disorders
other than primary biliary cirrhosis can be differentiated from those that appear to be specific for
primary biliary cirrhosis on the basis of characteristic immunofluorescent patterns that they
mediate in rat and human tissues or the effects of trypsin pretreatment of such tissue sections on
immunofluorescent staining. Mitochondrial antibodies directed against a purported specific
primary biliary cirrhosis antigen are believed to have high diagnostic relevance, and it has been
stated that when such antibodies are not detected in the serum, a diagnosis of primary biliary
cirrhosis should be made with caution and only after a careful period of clinical follow-up.
Mitochondrial antibodies appear to play no part in the pathogenesis of primary biliary cirrhosis
and provide no useful prognostic insight in this disorder.

Bile Acids

Serum levels of bile acids can be measured by sensitive chromatography techniques and
radioimmunoassays. Measurements can be made in the fasting state, two hours postprandially, and
following intravenous isotopic administration (bile acid tolerance test). The cost of the test and
the need for appropriate facilities in the laboratory limit the usefulness of these tests, which
currently appear to be not significantly superior to more routine and readily available tests. In
addition, an abnormal test result does not discriminate between hepatocellular and cholestatic liver
disease.

Blood Ammonia

Ammonia arises from bacterial degradation of nitrogenous contents (dietary protein, blood) in the
intestine. Although the blood and cerebrospinal fluid ammonia levels are elevated in most patients
with hepatic coma, there is a poor correlation between blood ammonia level and the degree of
hepatic encephalopathy. The correlation is better with arterial ammonia as compared with venous
ammonia, which may be increased by muscular exercise, seizure activity, or even clenching the
fist. Serial values of arterial ammonia are occasionally helpful in following individual patients.
Elevations in arterial blood ammonia levels have also been recognized in patients with
portosystemic shunting or inborn disorders of urea metabolism, and in patients following
ureteroileostomy. Blood ammonia measurements are of limited utility in the evaluation of most
patients with known hepatobiliary disease. Its greatest usefulness may be in evaluating patients
with coma or altered mental status of unclear cause. In such patients, an elevated arterial ammonia
concentration would suggest hepatocellular dysfunction as an important contributing factor.

Serum Lipids and Lipoproteins

Patients with cholestatic disorders (both intrahepatic and extrahepatic) frequently have an
elevation in the concentration of serum phospholipids and unesterified cholesterol, skin xanthomas
commonly appear if the total serum cholesterol level exceeds 450 mg/dl for longer than three
months. The major component of unesterified cholesterol is an abnormal low-density lipoprotein


designated lipoprotein X. Contrary to earlier claims, quantitation of serum lipoprotein X levels is
not helpful in distinguishing intrahepatic cholestasis from extrahepatic obstruction. Patients
with cirrhosis or malignant biliary obstruction who are malnourished may have low total serum
cholesterol levels.

Breath Tests

Several radiolabeled compounds have been used to assess hepatic function in humans. Most
studies have employed 14C aminopyrine. The test is inexpensive and entails minimal radioactive
exposure to patients (generally, less than 0.5 µCi per test) but should not be performed in children
or pregnant women. Studies in humans suggest that the aminopyrine test (14CO2 - a metabolic
product of the methyl group of aminopyrine - is measured) is an indirect measure of mixed-
function oxidase mass. Although not yet widely available, breath tests may emerge as excellent
non-invasive screening tests for detecting liver disease or prove useful in the periodic follow-up of
patients in whom liver biopsy is contraindicated.

Hepatic Scintiscanning

Technetium-99m sulfur colloid is taken up selectively by the reticuloendothelial cells and is used
occasionally in clinical practice. It often provides useful information regarding the size and shape
of the liver, although on occasion virtually no hepatic uptake of colloid is present in patients with
severe or far-advanced liver disease. Heterogeneous uptake of colloid by the liver with "shift" of
colloid to the spleen and vertebral bone marrow is characteristic but not specific for cirrhosis of
the liver. Focal defects of the liver are seen in many conditions, including hepatic cysts,
hemangiomas, abscesses, tumors, amyloidosis and "regenerative" cirrhotic nodules, and peliosis
hepatis. Lesions smaller than 2 cm in size and present deep within the hepatic parenchyma may
escape detection on liver scanning.

Hepatic scintiscanning may aid in the distinction between focal nodular hyperplasia and hepatic
adenoma, as scanning usually shows normal findings in the former condition, whereas a cold
defect is usually present in patients with a hepatic adenoma. Avid uptake by an enlarged caudate
lobe is characteristic of Budd-Chiari syndrome. In this condition, there is occlusion of the major
right and left hepatic veins. The caudate lobe has a separate arterial supply and venous drainage
and hence characteristically undergoes compensatory hypertrophy.

Hepatic scintiscanning is also useful in the evaluation of hepatic or splenic trauma (currently CT is
more often employed) and in the detection of remnant or accessory splenic tissue in patients who
have undergone splenectomy.

Hepatobiliary Scanning (Hida Scan)

Agents being used with increasing frequency for biliary scanning are technetium-99m-labeled
acetanilide iminodiacetic acid derivatives (dimethyl, paraisopropyl, and diisopropyl iminodiacetic
acids). These agents are rapidly taken up by functioning hepatocytes and excreted into the bile.
These radiopharmaceuticals are superior to Rose-Bengal as biliary scanners. In a broad sense,


they evaluate hepatic excretory function and the patency of the biliary tree. Adequate visualization
is often obtained in patients with serum bilirubin levels between 5 and 10 mg/dl. Nonvisualization
of the gallbladder within two hours with good visualization of the common bile duct is highly
suggestive of cystic duct obstruction or calculous cholecystitis. Caution in interpretation must be
exercised in those patients with concomitant hepatocellular dysfunction who' exhibit poor hepatic
uptake and concentration of the isotope. Dimethyl iminodiacetic acid scanning is thus most useful
in excluding cystic duct obstruction and acute cholecystitis if the gallbladder is clearly visualized.
Dimethyl iminodiacetic acid scanning has been used to demonstrate the gallbladder as the site of
the defect observed on the inferior border of the liver on technetium-99m sulfur colloid scanning.
Dimethyl iminodiacetic acid can also be used to diagnose choledochal cysts and demonstrate
biliary leaks or assess the patency of biliary-enteric shunts.

Angiography

Selective celiac, superior mesenteric, and hepatic angiography is employed in the evaluation of
selected patients with liver disease. Enlargement of the hepatic arteries, neovascularity,
arteriovenous shunting, and portal vein thrombosis are frequently encountered in patients with
primary hepatocellular carcinoma. However, differentiation from other primary hepatic lesions
such as focal nodular hyperplasia or angiosarcoma and from vascular metastatic tumors such as
hypernephroma, carcinoid, and choriocarcinoma is not always possible. Angiography may be
useful in defining the extent of tumor and delineating the anatomic vascular supply in preparation
for hepatic lobectomy. Angiography has been routinely performed prior to elective shunt surgery
for patients with variceal bleeding in order to define anatomy. Magnetic resonance angiography
may prove to be an adequate option in the future.

Ultrasonography

Ultrasound examination of the abdomen is a useful test in the evaluation of liver disease. It is
available in most hospitals, is inexpensive, and entails no radiation exposure to patients. Thus, it is
particularly applicable in the evaluation of liver and biliary tract disease in children and pregnant
women. Marked obesity and excessive intestinal gas can be limiting factors in obtaining good
resolution of the images. Ultrasound examination of the liver will often identify mass lesions 1 to
2 cm in size in the hepatic parenchyma and do this independent of hepatic function. The nature of
defects seen on technetium-99m sulfur colloid scanning - solid or cystic - can readily be
ascertained and it can facilitate guided aspiration of cysts or biopsy specimens of lesions.
Ultrasonography is an appropriate procedure for detecting gallstones and confirming the presence
of ascites; study in the fasting state is important. It is often used as the first test in the evaluation
of patients with cholestatic jaundice. Dilated bile ducts can be readily seen on ultrasound
examination in patients with mechanical extrahepatic biliary tract obstruction. Dilation of the bile
ducts may not be evident if the obstruction is incomplete or intermittent or if it has been present
for a short duration. Serial ultrasound examinations may provide valuable information in these
circumstances. The common bile duct is frequently dilated following cholecystectomy. Therefore,
an enlarged duct in this situation does not necessarily signify ongoing biliary tract obstruction.


Computed Tomographic Scanning

This modality is useful in detecting mass lesions (cysts, tumors, abscesses) within the liver, and
computed tomographic scanning with contrast enhancement can often accurately predict the
nature of the lesion identified. It has an advantage over ultrasound in obese patients and those
with excessive gas, but its widespread use is limited by the high cost; an additional consideration
is radiation exposure to patients. In patients with cholestatic jaundice, computed tomographic
scanning can distinguish intrahepatic cholestasis from mechanical extrahepatic obstruction with an
accuracy rate of 90 per cent. Computed tomographic scanning after intravenous injection of
iodinated contrast material has been reported to demonstrate hypertrophy of the caudate lobe,
stagnation of contrast material at the periphery of the liver, narrowing of the inferior vena cava in
its intrahepatic section, and failure of opacification of the major hepatic veins in patients with
Budd-Chiari syndrome. This constellation of findings appears to be specific for Budd-Chiari
syndrome, although further confirmatory experience is necessary before this diagnosis can be
confidently made in the absence of liver biopsy or venography.

Hepatic computed tomography has also been used to evaluate iron overload in the liver. It
appears to be moderately sensitive and highly specific for this purpose. However, liver biopsy with
quantitation of liver iron content remains the "gold test" in the diagnosis of hemochromatosis.

Computed tomographic scanning can also be useful in assessing liver fat content. Monoenergetic
computed tomographic scanning has been shown to accurately (good agreement with histologic
and chemical liver fat determination) predict liver fat content in patients with alcoholic liver
disease.

Magnetic Resonance Imaging (MRI)

This modality is useful in evaluating the extent of hepatic metastases. It is also of value in
assessing the patency of hepatic and portal veins and, hence, is a useful test in patients with
suspected Budd-Chiari syndrome and in patients with portal vein thrombosis. Hemangiomas of
the liver also have a characteristic MRI appearance. In patients with iron overload, a characteristic
black or hypointense liver is often encountered.

Percutaneous Transhepatic Cholangiography

Percutaneous transhepatic cholangiography using a "skinny" Chiba needle is performed in most
institutions by skilled radiologists. The success rate with multiple passes approaches 90 to 95
percent in patients with extrahepatic biliary tract obstruction and 70 percent in patients with
intrahepatic cholestasis and normal-sized bile ducts. Percutaneous transhepatic cholangiography
may be preferred over endoscopic retrograde cholangiopancreatography in patients with surgically
distorted gastroduodenal anatomy such as following hemigastrectomy and Billroth II anastomosis.
Marked ascites and irreversible coagulopathy are contraindications to this procedure. Serious
complications occur in about 5 percent of patients and include cholangitis, hemorrhage, bile
peritonitis, pneumothorax, and drug reaction, and are responsible for a 0.5 percent attendant
mortality.


Endoscopic Retrograde Cholangiopancreatography (ERCP)

This procedure is usually performed by a gastroenterologist and has a success rate of 80 to 90
percent in skilled hands. Serious complications occur in about 5 percent of patients and include
pancreatitis, instrumental injury, cholangitis, sepsis, and aspiration pneumonia. Endoscopic
retrograde cholangiopancreatography would appear to be the procedure of choice if
periampullary carcinoma, common duct stone, or postcholecystectomy biliary tract disease is
strongly suspected on clinical grounds. In patients with common duct stones, endoscopic
papillotomy can provide definitive therapeutic benefit.

Needle Biopsy of the Liver

Percutaneous needle biopsy of the liver is a commonly utilized and safe procedure that can be
performed at the bedside. It often provides precise and accurate tissue diagnosis without resorting
to general anesthesia and laparotomy, and most agree that it can be performed as an outpatient
procedure provided facilities are available for short-term observation and hospitalization should
the need arise. Accepted indications for liver biopsy include hepatocellular disease of uncertain
cause, unexplained hepatomegaly and/or splenomegaly, hepatic filling defects demonstrated by
radionuclide scanning, ultrasound examination, or computed tomographic scanning, chronic
hepatitis, fever of unknown origin, and staging of malignant lymphoma. Liver biopsy is often
helpful in the evaluation of patients with clinically suspected alcoholic liver disease to confirm the
diagnosis and ascertain the severity of damage to the liver and in the evaluation of patients with
portal hypertension. Liver biopsy is the single best "liver function test" (the gold standard) in
documenting hemochromatosis, Wilson's disease, certain varieties of glycogen storage disease and
type I Crigler-Najjar syndrome. Liver biopsy is not particularly helpful in distinguishing
intrahepatic from extrahepatic obstruction. Although liver biopsy is not apparently associated
with an excessive risk of complications in patients with extrahepatic obstruction, the
pathognomonic features of extrahepatic obstruction - a bile infarct with feathery degeneration of
surrounding hepatocytes - are not invariably present. Additionally, it provides no information
regarding the site or nature of the obstructing lesion. With the advent of imaging modalities to
visualize the extrahepatic biliary tree, needle biopsy of the liver is rarely performed today when
extrahepatic obstruction is suspected.

Contraindications for percutaneous needle biopsy of the liver include uncooperative or comatose
patients, hydatid cyst disease, hemangioma or angiosarcoma of the liver, right pleural disease or
local infection at the proposed biopsy site, and significant coagulopathy. Arbitrarily employed
contraindications include a prolongation of the prothrombin time greater than four seconds over
control, a partial thromboplastin time greater than 15 seconds over control, and a platelet count
less than 75,000/mm3. A bleeding time should be obtained in patients with borderline clotting
abnormalities or uremia, and in those taking antiplatelet drugs. In patients with a severe
coagulopathy, the transvenous (transjugular) approach may be used. In this technique, a catheter
is placed in the jugular vein and manipulated into a hepatic vein. If bleeding occurs, it occurs
within the vascular system itself.


Percutaneous needle biopsy of the liver is not contraindicated in amyloidosis unless the liver is
massively enlarged or there is an associated bleeding tendency. Tense ascites and severe anemia
are relative contraindications. Complications are numerous but rare and the overall mortality rate
is less than 0.02 percent. The incidence of complications appears to increase significantly if
multiple passes (greater than four using the percutaneous route) are employed. The most common
untoward effect is pain at the biopsy site or right shoulder. Moderate to severe pain with or
without hypotension usually manifests within the first three hours of the procedure. Serious
bleeding occurs in less than 0.3 percent of patients, although asymptomatic subcapsular or
intrahepatic hematomas are probably considerably more common. Extremely rare serious sequelae
include pneumothorax, hemothorax, hemobilia, arteriovenous fistula formation, and perforation of
colon or gallbladder. If suspicion for highly vascular tumors such as carcinoid is high, angiography
or nuclear medicine flow scanning should be performed before percutaneous biopsy. Suspected
primary hepatocellular carcinoma is not a contraindication to biopsy.

Liver biopsy in unsuspected echinococcal cyst disease can be followed by dissemination of
daughter scoleces or fatal anaphylaxis.

Peritoneoscopy and Laparotomy

Peritoneoscopy may be performed using local anesthesia and mild sedation. It permits adequate
visualization of the anterior surface of the liver, gallbladder, and stomach as well as parts of the
small intestine and colon. It has proved useful in the diagnosis by direct visual inspection and
directed needle biopsy of a variety of hepatic disorders including cirrhosis, hepatomegaly, hepatic
malignancy, and portal hypertension. Peritoneoscopy has helped in determining the cause of
ascites and in the staging of Hodgkin's disease. Contraindications include tense ascites, an
uncooperative patient, marked obesity, surgical abdominal scars, and severe coagulopathy.
Serious complications occur in 1 to 2 percent of patients and include air embolism, subcutaneous
emphysema, ascites leak, bowel perforation, and hemorrhage. The overall mortality rate is
approximately 0.03 percent.

Laparotomy is now seldom performed for the express purpose of diagnosing hepatobiliary
disease. On occasion, however, it is necessary to undertake this procedure to obtain biopsy and
culture material and perform operative cholangiography.

The increasing availability of and familiarity with the vast array of both noninvasive (eg,
ultrasonography, computed tomographic scanning, dimethyl iminodiacetic acid scanning, etc.) and
invasive (eg, skinny needle transhepatic cholangiography, endoscopic retrograde
cholangiopancreatography, angiography, liver biopsy, etc.) hepatic tests have resulted in the
infrequent use of peritoneoscopy and laparotomy for the evaluation of hepatobiliary disease.

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Gastroenterology 1978; 74:101-102.
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Rösch J, Lakin PC, Antonovic R, Dotter CT: Transjugular approach to liver biopsy and
transhepatic cholangiography. N Engl J Med 1973; 289:227-231.
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Perrault J, McGill DB, Ott BJ, Taylor WF: Liver biopsy: complications in 1000 inpatients
and outpatients. Gastroenterology 1978; 74:103-106.
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Losowsky MS: Needle biopsy of the liver. A review. J R Soc Med 1982; 75:736-741.
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Kaplan MM: Evaluation of hepatobiliary diseases. In: Stein JH, ed. and chief. Internal
Medicine,4th ed. Mosby-Yearbook, 1994; 544-552.
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Bernardino ME, Galambos JT: Computed tomography and magnetic resonance imaging of
the liver. Sem Liv Dis 1989; 9:32-49.
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Johnson CD: Magnetic resonance imaging of the liver: current clinical applications. Mayo
Clin Proc 1993; 68:147-156.
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Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med
1997;126:137-145.

Non-Neoplastic Disease of the Ovary

1
Non-Neoplastic Disease of the Ovary
David Stanford, M.D.

2
I. Infection
Common bacterial infections occur in association with salpingitis and the form of tubo-ovarian
abscesses. IUD-associated pelvic actinomycosis can involve the ovary.
II. Cysts of Follicular Derivation
A. Follicular cysts occur most commonly soon after menarche or around the time of menopause. May
be incidental findings or palpable masses. Many show disturbances related to increased estrogen
production. Solitary thin-walled cysts up to 8 cm lined by inner layer of granulosa cells and outer
layer of theca cells.
B. Corpus luteum cysts occur in reproductive age group. Rarely may present with rupture and
hemoperitoneum. Solitary cyst containing blood with yellow convoluted wall lined by large
luteinized granulosa cells.
III. Hyperreactio Luteinalis
A. Bilateral multiple luteinized cysts up to 26 cm associated with pregnancy disorders associated with
high HCG such as H. mole, multiple gestations, hydrops fetalis. Incidental finding or symptoms
related to torsion, intra-abdominal bleeding and ascites.
IV. Polycystic Ovaries, Stomal Hyperplasia and Stromal Hyperthecosis
Overlapping syndromes associated with androgen excess, estrogenic manifestations, or both.
A. PCO (Stein-Leventhal): 3rd decade, oligomenorrhea, hirsutism. Bilateral ovarian enlargement.
Thick white cortex with cystic follicles lined by non-luteinized d granulosa cells. No corpora lutea
or albicans.
B. Stromal hyperplasia and hyperthecosis: post-menopausal, estrogenic manifestations
such as endometrial hyperplasia/carcinoma. HAIR-AN syndrome. Bilateral ovarian
enlargement (up to 8 cm) with white to yellow cut surface. Hyperplasia of cortical-
medullary stroma with scattered luteinized cells
V. Massive Edema and Fibromatosis
A. Massive ovarian edema occurs in young women who present with unilateral ovarian enlargement,
abdominal pain, menstrual irregularities and androgen excess. Often have torsion. Ovary enlarged
(5-35 era). Stromal edema surrounding existing follicles. Scattered luteinized cells.
B. Fibromatosis shows similar clinical features but histologically shows acellular proliferation of
spindled cells in a collagenized stroma surrounding existing follicles.
VI. Pregnancy Luteoma
A. 3rd and 4th decade, black multiparous females with bilateral ovarian nodules discovered during
C-section/tubal ligation. 25% of women and up to 2/3 of female newborns show hirsutism. Multiple,
bilateral brown nodules composed of luteinized cells with abundant pink cytoplasm.
B. Nodules regress following pregnancy.

HIV Infection and AIDS

HIV Infection and AIDS


David Kramer, M.D.



I. HIV Transmission Categories

A. Risk Factors in Adults

1. Male sex with male (MSM) 42-45%

2. Injection drug use (IDU) 26-31%

3. Heterosexual 11%

4. Transfusion 1%

a. Less than one in 700,000 units of blood is HIV infected because it is missed by routine screening

5. Hemophilia 1%

6. Undetermined 15%

B. Risk factors in children (<13 years of age)

1. Perinatal 91%

2. Risk unidentified 5%

a. Majority of pediatric cases are caused by perinatal

transmission

3. Transfusion 3%

4. Hemophilia 1%

II. Epidemiology

A. Epidemiology of HIV Infection in Adolescents (13-19 years of age)

1. 15% of adult AIDS cases were acquired during adolescence

2. 25% of heterosexually acquired AIDS cases were infected as teens

3. Serious immune dysfunction at presentation is common

a. Adolescents have a shorter survival time after HIV diagnosis than adults

b. Severity of immune dysfunction suggests long-standing or advanced disease is usually present at

diagnosis

4. Risk factors in adolescents vary by gender

a. Higher proportion of females are infected in the adolescent age group than in any other age group

b. Cause of Infection in Female Teens

(1) Heterosexual contact (54-76%)

(2) Intravenous drug use (16%)

c. Cause of Infection in Male Teens

(1) Received contaminated blood products (46%)

(2) Male sexual contact (33%)

B. Epidemiology of HIV Infection in Women

1. Increasing numbers and percentage of women

2. 20% of 1995 cases were women

3. Third leading cause of death in women of child-bearing age

C. Epidemiology of HIV Infection in Children (<13 years of age)

1. The number of perinatally acquired AIDS cases reported to the CDC declined 27% between 1992 and

1995

2. The cause of the decline was probably more effective antiretroviral therapies and in part because of effect

of perinatal ZDV therapy

3. More than 7,000 children have AIDS

4. >21,000 children have HIV infection

D. Racial and ethnic minority populations

1. AIDS is disproportionately represented among women, children and adolescents with AIDS

2. Reported cases per 100,000 children

a. African-American non-Hispanic - 6.4

b. Hispanic - 2.3

c. White non-Hispanic - 0.4

III. Perinatal Transmission



A. Risk factors in mothers giving birth to HIV-infected children

1. Increasing proportion were infected through heterosexual transmission;

approximately 40%

2. 40% of women have unidentified risk. They probably were infected heterosexually by men unrecognized

to be HIV-infected

3. Transmission because of intravenous drug use decreased to 20%

4. Transfusion-associated infection is extremely rare

B. Timing of Transmission Perinatally Acquired HIV Infection

1. In Utero transmission accounts for 30-50% of perinatally acquired disease. Associated with more rapidly

progressive disease.

2. Intrapartum transmission accounts for 50-70% of perinatally acquired disease. This period affords the

best opportunity for interruption of transmission.

C. Postpartum transmission (breast feeding)

1. The risk of transmission is14%

2. The risk of transmission from a mother who seroconverts while breast feeding is 29%

3. Women with HIV or at risk for HIV living in developed countries should not breast feed

D. Interruption of Vertical Transmission. Administration of AZT therapy during pregnancy, labor and delivery,

and to the infant for the first 6 weeks of life reduces the transmission rate from 25% to 8%.

IV. Immunopathogenesis

A. Constant high-level replication of the virus

1. Approximately one billion viral particles per day are replicated

B. High steady-state level of virus in the blood

C. Immune clearance of virus

1. Production of CD4 cells initially matches viral replication

2. Progressive depletion of CD4 cells occurs

3. Eventual profound immunologic dysfunction intercedes

V. Characteristic Immunologic Disturbances in AIDS

A. Laboratory T-cell abnormalities

1. Decreased number and function of CD4+ T cells

2. Impaired CD8 T-cell cytotoxicity

3. Impaired mitogen and antigen responses

4. Impaired cytokine production (IL-2, (IFN, etc)

B. Clinical T-cell abnormalities

1. Impaired delayed-type hypersensitivity

2. Chronic active viral infections (VZV, CMV, EBV)

3. Opportunistic infections

C. Laboratory B-cell abnormalities

1. Hypergammaglobulinemia

2. Impaired specific antibody responses

a. Primary and secondary

b. T-cell-dependent and independent antigens

D. Clinical B-cell Abnormalities

1. Recurrent bacterial infections

a. Encapsulated organisms most common

(1) S. pneumoniae

(2) H. influenzae

VI. Measurements of Viral Load (VL)

A. Assays Currently Available

1. RNA polymerase chain reaction (RNA-PCR)

2. Branched chain DNA (bDNA)

3. Nucleic acid amplification assay (NASBA)



B. In adults, viral load is predictive of disease progression, independent of CD4 count

1. >100,000 copies/ml--rapid deterioration

2. <10,000 copies/ml--stable course

C. Predictors of Perinatal Transmission. Higher maternal viral loads are associated with increased

transmission. However, even women with undetectable viral loads can transmit infection

D. In children with perinatally-acquired disease, viral loads are much higher than adults (by 1-2 logs)

1. Peak at 1-2 months of age (up to 1,000,000 copies/ml)

2. Slow decline over time (50,000 - >200,000 by age 2 years)

3. Lower viral loads are present in slow progressors as compared to rapid progressors

VII. CDC Classification System for HIV Infection in Children

A. Classifies children on basis of symptoms/disease manifestations and level of immune suppression

1. Clinical categories

a. Category N: not symptomatic

b. Category A: mildly symptomatic

c. Category B: moderately symptomatic

(1) The only AIDS-defining illness in this category is lymphocytic interstitial pneumonitis (LIP)

d. Category C: severely symptomatic

(1) All other AIDS-defining illnesses

2. Immunologic categories (based on CD4 counts and percentage)

a. Category 1: no evidence of suppression

b. Category 2: moderate suppression

c. Category 3: severe suppression

B. Classification provides a comprehensive assessment of child's overall status

C. Classification is used to define progressive disease or clinical endpoints in research trials

VIII. Clinical Presentation of HIV Infection by Symptom Complex

A. Common nonspecific findings (most in CDC category A)

1. In General, most common presenting findings

2. Oral thrush

3. Lymphadenopathy

4. Hepatosplenomegaly

5. Recurrent diarrhea

6. Poor growth

B. Neurologic manifestations (CDC category C)

1. Developmental delay/loss of milestones

2. Progressive symmetrical motor deficits

3. Cerebral atrophy. Infection may present as acquired microcephaly

4. Basal ganglia calcifications

5. Chronic encephalopathy or dementia

C. Lymphocytic interstitial pneumonitis (LIP) (CDC category B)

1. Most common chronic pulmonary process

2. Often associated with parotitis and digital clubbing

3. Insidious development of hypoxemia is common, which is usually reversible with corticosteroids

4. Probably associated with EBV infection

D. Infectious complications

1. Chronic otitis media and sinusitis (CDC category A)

a. Typical pathogens most common

b. S. aureus, coagulase negative staph, and P. aeruginosa are detected in chronic draining ears

2. Recurrent and chronic herpesvirus infections (HSV, VZV). May require prophylaxis or chronic acyclovir

therapy

3. Recurrent serious bacterial infections (CDC category C)

a. Pneumonia. Multiple episodes may lead to bronchiectasis



b. Bacteremia

4. Opportunistic infections (CDC category C)

a. Occur when CD4 count extremely low

b. Pneumocystis carinii pneumonia

c. Cryptosporidiosis

d. Disseminated CMV

e. Disseminated Mycobacterium Avium Complex (MAC)

f. Disseminated fungal infections (Candida sp., Aspergillus sp., rarely Cryptococcus sp.)

E. Neoplasms

1. B-cell lymphoma, CNS lymphoma

2. Kaposi's sarcoma (exceedingly rare)

3. Smooth muscle tumors

F. Other conditions associated with HIV

1. Wasting syndrome

2. Cardiomyopathy

3. Nephropathy

4. Hematologic abnormalities

a. Anemia, thrombocytopenia, neutropenia

b. Absolute lymphopenia

5. Dermatologic diseases

a. Disseminated molluscum contagiosum and flat warts

b. Seborrheic dermatitis

IX. Bimodal Presentation of Pediatric Disease

A. Rapid progressors account for 30% of HIV-infected Patients

1. Onset of symptoms occur in first months of life

a. Failure to thrive

b. Opportunistic infections

c. Encephalopathy

2. Death generally occurs within 3 years

3. High peak viral loads and low CD4 counts

B. Slow progressors account for 70% of HIV-infected Patients

1. These patients are asymptomatic and without physical findings up to several years

2. Life expectancy is >5 years

3. Most common symptom complexes include generalized lymphadenopathy, lymphocytic interstitial

pneumonia, and recurrent bacterial infections

4. Subtle presentations or maternal risk factors may be the only findings in asymptomatic cases

5. Children infected via transfusion or sexual transmission are more likely to have slowly progressive

disease

X. Diagnosis

A. Assays for early diagnosis of perinatally-acquired disease

1. RNA PCR

a. Using NASBA assay, 56% of 36 infected infants had positive test by 14 days of age vs. 33% using

DNA PCR

2. HIV antibody is not definitive because of passive maternal transfer across the placenta

B. Early Diagnostic Evaluation for Perinatally-acquired Disease

1. Perform PCR or culture at birth, 1 month and 3-4 months

a. HIV diagnosis requires 2 positive results that must be at different time points

(1) Definitive diagnosis is usually possible within first 1-3 months of life

(a) Diagnosis is excluded if more than 2 negative results have been obtained, both performed

greater than1 month of age

(b) One performed >4 months of age



2. ICD p24 antigen test

a. If positive, the test may be used to confirm a positive PCR or HIV culture

b. If negative, must repeat PCR or culture

C. Diagnosis of children >18 months of age

1. HIV antibody by western blot

2. Positive results on >two different blood samples

XI. Antiretroviral Therapy

A. Nucleoside Reverse Transcriptase Inhibitors

1. Zidovudine (AZT, ZDV)

a. 120-180 mg/m2/dose po q6-8 hrs

b. Adverse Effects. Anemia and granulocytopenia are the major toxicities. Elevated transaminases are

less common

c. Monotherapy results in 0.5 log decrease in viral load

d. CSF:plasma ratio 60%

2. ddI (didanosine)

a. 90 mg/m2/dose po q12 hrs

b. Major toxicities include pancreatitis and peripheral neuropathy.

c. Monotherapy results in 0.6 log decrease in viral load

3. ddC (zalcitabine)

a. 0.01 mg/kg/dose po TID. Pharmacokinetics suggest this dose may be too low

b. Same toxicities as ddI

4. d4T (stavudine)

a. 1 mg/kg/dose q12 hr

b. Peripheral neuropathy is the major (but rare) toxicity

c. Penetrates CNS

5. 3TC (lamivudine)

a. 4 mg/kg/dose q12 hr

b. Peripheral neuropathy is the primary toxicity (rare)

c. Concurrent use with AZT will suppress HIV resistance to AZT

d. If used as monotherapy, resistance develops rapidly.

B. Non-nucleoside Reverse Transcriptase Inhibitors

1. Nevirapine

a. 120 mg/m2/dose BID

b. Causes 1 log drop in viral load rapidly

c. Penetrates CNS

d. Resistance develops rapidly (especially as monotherapy)

e. Rash is the major (but uncommon) toxicity; may progress to Stevens-Johnson syndrome

2. Delavirdine

a. Similar efficacy as nevirapine

b. Drug-drug interactions with protease inhibitors

c. No published pediatric data

C. Protease Inhibitors (PI's)

1. Overview

a. Interrupts viral assembly and infectivity

b. When combined with nucleosides, they produces a precipitous drop in viral load (1-2 logs) in adults

c. Significant drug-drug interactions

d. Entering clinical trials in children

2. Indinavir (Crixivan)

a. Pediatric formulation is not available (only capsules)

b. The major toxicity is nephrolithiasis (2-5%)



3. Ritonavir (Norvir)

a. First PI available in suspension formulation

b. Side effects

(1) Unpalatable and GI intolerance

(2) Circumoral paraesthesias

(3) Complete inhibition of p450 metabolic pathway leads to a significant increase in levels of drugs

metabolized via this route (rifabutin)

4. Nelfinavir mesylate (Viracept)

a. Available as a powder for suspension

b. Diarrhea (rarely)

5. Saquinavir (Invirase)

a. Pediatric formulation is not yet available

b. Poor bioavailability limits serum drug levels. Last potent of all PI's

c. When used in combination with ritonavir, the levels of saquinavir increase substantially

D. Antiretroviral drug resistance

1. Rapid development of resistance occurs with monotherapy

a. 89% of persons with late-stage disease have ZDV resistance after one year of monotherapy vs 31%

with less advanced disease

2. High viral turnover promotes selection of drug-resistant mutants. Mutants have specific amino acid

substitutions in reverse transcriptase or protease enzyme. Complete suppression of replication decreases

selection of mutants.

E. Goals of Combination Antiretroviral Therapy

1. Complementary drug interactions. Drugs act at different points in replication cycle

2. Reduction or delay in development of drug-resistant mutants

a. Significantly decreasing viral load, fewer drug resistant mutants

b. With multiple drugs, more mutations are necessary to develop resistance

3. Monotherapy is no longer recommended (except for prevention of vertical transmission)

F. General Principles of Combination Therapy

1. Check for drug-drug interactions

2. Monitor laboratory values based on expected drug toxicities

3. Some examples of combination regimens in use

a. 2 nucleosides (eg. ZDV + ddI, ddC or 3TC, d4T + 3TC)

(1) ZDV and d4T are antagonistic in combination

b. 1 nucleoside plus 1 non-nucleoside (eg. ZDV + nevirapine)

c. 2 nucleosides + a protease inhibitor (eg. ZDV + 3TC + ritonavir)

d. 1 nucleoside + a non-nucleoside + a protease inhibitor (eg. ZDV + nevirapine + ritonavir)

G. Initiation of Antiretroviral Therapy

1. Consideration should be given to treating all infants/children at diagnosis

2. Current Recommendations for Antiretroviral Therapy:

a. Significant symptoms

b. Falling CD4 count

c. No consensus on viral load "threshold" of 100,000 copies/ml

d. Some favor highly aggressive therapy (3 drug) to prevent progressive disease ("hit early, hit hard")

XII. Outpatient Management of the HIV-infected child

A. Monitor immunologic function and viral load regularly (Q3-6 Months)

B. Nutritional Assessment every 3 Months

C. Developmental and neuropsychological assessment q3-6 months

1. Physical/occupational therapy

2. Speech therapy

3. Play therapy



D. Provide immunizations with following exceptions:

1. Substitute inactivated enhanced polio vaccine (IPV) for live attenuated polio vaccine

2. Withhold MMR in CDC immunologic category 3

3. Add pneumococcal vaccine

4. Influenza vaccine yearly

5. Varicella vaccine under investigation in this population

E. Prophylaxis against opportunistic infections

XIII. Infection Control in Household Setting, Day Care or School

A. Use "universal precautions" for handling all body fluids containing visible blood

B. Immunize family members of HBsAg positive individuals

C. Siblings of HIV-infected children should receive inactivated polio vaccine and varicella vaccine

Cardiovascular Disorders in Pediatrics

Cardiovascular Disorders in Pediatrics
Congenital heart disease occurs in about 1% of children. Heart murmurs are much more
common, and may be heard in virtually every child if examined carefully.
I. Clinical Evaluation of Cardiovascular Disorders
A. History
1. For neonates, a history of feeding problems, cyanosis, tachypnea, irritability or
grunting respirations may indicate serious cardiac pathology. A history of
feeding less than 2 ounces at each feeding in a term infant may indicate
pathology. A family history of congenital heart disease may be helpful, but the
incidence of congenital heart disease in families where the mother has
congenital heart disease is only 5-10%.
2. For older children, it is unusual for a pathologic murmur to present for the first
time outside of infancy. Two notable exceptions are hypertrophic
cardiomyopathy and murmurs associated with dilated cardiomyopathy.
Symptoms which indicate serious pathology include exercise-induced chest
pain, exercise induced syncope, or cyanosis. Easy fatigability is non specific,
and not helpful in differentiating pathologic from non-pathologic murmurs.
B. Physical Examination
1. Congenital heart disease is more common in infants with congenital anomalies.
a. Trisomy 21. The incidence of heart disease is about 50% in these children.
Anomalies include ventricular septal defects, atrioventricular canal defects,
and patent ductus arteriosus.
b. Trisomy 18. The incidence of heart disease is almost 100%in these
children. Ventricular septal defect is the most common anomaly.
c. Trisomy 13. The incidence of heart disease is about 80%, usually VSD.
d. Turner syndrome (coarctation, hypertension), Marfan syndrome (aortic
aneurysms), and Noonan syndrome (pulmonic stenosis, coarctation) are
other congenital anomalies.
2. Growth parameters may suggest failure to thrive that is caused by
cardiovascular disease. Infants with cardiovascular disease usually have a
normal head circumference, and height may be normal, but the weight is usually
lower than anticipated.
3. Blood pressure determination. All children 3 years of age and older should
have their blood pressure measured on a yearly basis. The blood pressure cuff
should be appropriate for the patient’s size. The width of the cuff should be at
least 2/3 the length of the upper arm, and the bladder should be long enough
to almost encircle the upper arm. Blood pressure levels vary depending on the
age of the child, and hypertension is defined as a blood pressure consistently
greater than the 95th percentile for age.
a. Presenting symptoms of severe hypertension in infants include congestive
heart failure (caused by coarctation), respiratory distress, and failure to
thrive.
b. Symptoms of severe hypertension in older children may include headache,
nausea, vomiting, mental status changes, and epistaxis.
4. Cardiovascular Examination
a. Inspection
(1) Conditions that cause cardiac enlargement (ventricular septal defect,
The recommendations in blood pressure management are from the National
High Blood Pressure Education Project provides tables that will give you
normal data for blood pressure that varies by age, by height of the patient.
Blood pressure should be measured in all children greater than three years of
age. Blood pressure should be measured from the patient's right arm after they
have been sitting in a quiet room for three to five minutes. Blood pressure
should be measured twice and the results averaged, and the blood pressure
should be measured with an appropriate size cuff. The simplest way to
remember that is to try and get the largest cuff you can get on the child's arm.
They recommend that in a pediatric practice you have six cuffs. Three small
cuffs, one adult cuff, a large adult cuff and then a thigh cuff.
For definition of the diastolic blood pressure, the fifth Korotkoff sound is used.
The fifth sound is when the sound totally disappears. There are patients in
whom the fifth Korotkoff sound never occurs. In other words, the sound never
disappears, but then if it goes all the way down to zero, they don't have diastolic
hypertension, which makes sense.
Hypertension is defined as a child that has an average systolic or diastolic
blood pressure greater than the 95th percentile on three separate occasions,
not all done in the same day. So don't rush into the diagnosis of hypertension.
Most children that have modest elevations in blood pressure are overweight
and possibly have a family history of high blood pressure. Those people might
get just a very basic routine screening evaluation which might include a
urinalysis (looking for casts, hematuria, proteinuria), a BUN creatinine, looking
for elevation of creatinine consistent with renal disease, and also a good
cardiac physical exam, feeling femoral pulses. Those people would be treated
with weight reduction, dietary restrictions, and emphasis on physical activity.
Patients should not be restricted from physical activity because of mild
elevations in blood pressure.
People that have significantly elevated blood pressure, and these are the
people in the 99th and above percentile, frequently have underlying disease
that is causing their hypertension. It is not idiopathic or familial hypertension.
The two organ systems that are most commonly implicated are the renal
system and the cardiovascular system. Remember to listen for bruits over the
abdomen because renal artery stenosis is a fairly common cause of significant
hypertension in children, and remember to feel the femoral pulses.
Now, I am going to briefly go over the cardiovascular exam, specifically the
acyanotic category for an atrioseptal defect (ASD). In order to diagnose an
ASD it is not what is outside your ears that is most important. It is what is
between your ears that is most important. You need to know what you are
listening for. If you can do a good ASD exam, then you know how to use your
stethoscope. If you can rule out an ASD every time you listen to a patient, you
will refer many fewer functional murmurs for evaluation, and you will miss many
fewer ASDs.

2D:\FILES\Review Courses\Prep 1\Cardiovascular Disorders.WPD
atrioseptal defect, and a large patent ductus arteriosus) often cause the
left side of the chest to protrude further than the right.
(2) In patients with pectus chest deformities, functional murmurs are often
heard.
b. Palpation
(1) In situations where there is a large left to right shunt (ie VSD, ASD) the
precordial activity is often increased.
(2) Displacement of the apical impulse may be associated with cardiac
enlargement.
(3) Palpation of femoral pulses is critical in diagnosing coarctation of the
aorta.
c. Auscultation
(1) Each sound should be listened to separately.
(2) The first heart sound (S1) is caused by closure of the mitral and
tricuspid valves, and it should be a single sound heard at the lower left
sternal boarder.
(a) The first heart sound may become inaudible at the lower left
sternal border when it is obscured by some pathologic sound. The
most common pathologic sound obscuring S1 is caused by
turbulent flow through a ventricular septal defect (VSD). VSD
murmurs are termed "holosystolic". Other sounds that could
obscure S1 are caused by AV valve regurgitation or by a PDA.
(b) First heart sounds that are "split" or double may be caused by
"clicks", or by some a slight timing difference between the closure
of the mitral and the tricuspid valves.
(c) Aortic valve clicks are heard best at the apex and do not vary with
respiration.
(d) Pulmonary valve clicks are best heard at the upper left sternal
border and do vary with respiration.
(e) Mitral valve prolapse clicks are a not pathological, and should be
ignored unless mitral valve regurgitation is present.
(3) The second heart sound (S2) is caused by the closure of the aortic
and pulmonic valves. The second heart sound should "split" with
respiration.
(a) A "fixed split" second heart sound may indicate the presence of
an ASD, especially if associated with increased precordial activity.
A fixed split S2 may also be seen in patients with complete right
bundle branch block.
(b) A loud single S2 indicates either pulmonary hypertension or the
absence of a closure sound from one semilunar valve. This may
be seen in severe forms of congenital heart disease, such as
truncus arteriosus, tricuspid atresia, tetralogy of Fallot,
transposition of the great vessels, pulmonary atresia, and
hypoplastic left heart syndrome.
(4) Systolic Murmurs
(a) Innocent Systolic Murmurs
i) Peripheral pulmonary flow murmur is heard in most babies
outside of the newborn period.
ii) Still's murmur is often heard for the first time in a 3 to 5 year
old.
The first heart sound at the lower left sternal border, closure of the mitral and
tricuspid valve. It should be a single sound that you hear with your stethoscope.
The second heart sound is heard at the upper left sternal border. It is the
closure sound of the aortic and pulmonic valves. In ordinary people, it should
split and move with respiration. You can't get a two-year-old to take a deep
breath and hold it, but what you listen for is that the second heart sound is not
the same every time. The splitting of the second heart sound is caused by the
patient taking in a breath, augmenting right ventricular filling, and increasing
the time it takes for the right ventricle to eject its contents. In a patient with an
atrial septal defect, the second heart sound is widely split and fixed. The right
ventricle is always filling. It doesn’t matter whether the patient took a deep
breath or not because blood is going from the left atrium through the atrial
septum into the right atrium. So you hear a widely split and fixed second heart
sound. It doesn't vary with respiration.
The systolic murmur heard in someone with an ASD can be very soft and not
easily audible. Many patients with large atrial septal defects have no systolic
murmur. Don't make the diagnosis of an ASD based solely on the presence or
absence of a systolic murmur. The cause of a systolic murmur in someone
with an ASD is flow across the pulmonary valve. It is just a flow murmur, so it
may sound like other innocent, benign flow murmurs. The fourth and final part
of the examination is the presence of a diastolic sound or a diastolic rumble
across the tricuspid valve. The blood that courses from the left atrium through
the ASD into the right atrium and across the tricuspid valve in diastole makes
noise. The classic exam is increased precordial activity, normal first heart
sound, a widely split second heart sound, a systolic ejection murmur at the
upper left sternal border and a diastolic rumble across the tricuspid valve.
To examine the precordial activity, put your hand on the chest. You'll feel this
dilated right ventricle beneath your hand and that should be the first tipoff that
this patient has an ASD and not a functional or innocent murmur. The second
is the wideness of that second heart sound. But if you don't put your
stethoscope at the upper left sternal border and really pay attention to what the
second heart sound is doing, you'll miss it. The last is the diastolic rumble
across the tricuspid valve. It is heard best with the bell of the stethoscope
placed over the tricuspid valve. Push down with the bell of the stethoscope and
make it function like a diaphragm, so then you'll just hear the systolic and high-
frequency sounds. When you let up on the bell of the stethoscope it will begin
to act like a bell and you will start to hear low frequency sounds.

3D:\FILES\Review Courses\Prep 1\Cardiovascular Disorders.WPD
iii) Outflow tract murmurs are often heard in the adolescent and
adult.
(b) Pathologic Systolic Murmurs
i) Ejection-aortic stenosis, pulmonic stenosis, atrial septal
defect.
ii) S1 coincident- VSD, PDA, AV valve regurgitation.
(5) Diastolic murmurs are always pathologic, except venous "hums".
(a) Aortic valve insufficiency
(b) Pulmonic valve insufficiency
(6) Differentiation of Functional Murmurs from Pathologic Murmurs
(a) Serial Exams. Functional murmurs are often louder if the child is
examined during a high output state, such as when febrile or
when anxious.
(b) Functional murmurs change with position. They are often heard
best when the patient is supine. Standing may result in complete
resolution of the murmur.
II. Cyanotic Congenital Heart Disease
A. Transposition of the Great Vessels
1. Because these patients are often quite cyanotic, they commonly present in the
delivery room, or in the nursery when the patent ductus arteriosus begins to
close. Occasionally, very dark skinned infants with transposition may go
unrecognized.
2. Physical Exam. Increased precordial activity, cyanosis, a single second heart
sound, and a systolic "flow" murmur may be apparent.
3. Immediate treatment may include prostaglandin E1 to maintain ductal patency.
The initial dose is usually 0.05 micrograms/kg/min. Apnea is a common and
dangerous side effect.
4. Surgery usually is performed early in life, and it usually consists of an arterial
switch operation.
B. Tetralogy of Fallot. Four primary features consist of ventricular septal defect, right
ventricular outflow tract obstruction, right ventricular hypertrophy, and an
"overriding" aorta. Only the VSD and the right ventricular outflow tract obstruction
are responsible for the physiology.
1. Presentation depends on the amount of pulmonary blood flow. Patients with little
pulmonary blood flow are very cyanotic, and may need prostaglandin E1 to
maintain ductal patency. Patients with less right ventricular outflow tract
obstruction may present with signs of a large left to right shunt, the so-called
"pink-tetralogy".
2. Tetralogy spells should be recognized as a dangerous event that require
surgical intervention (if possible). A tetralogy spell often occurs early in the
morning (upon awakening), is accompanied by intense cyanosis, and usually
occurs when the child is quiet and tachypneic.
3. Treatment of Tetralogy Spells
a. Knee chest position
b. Oxygen
c. Sedation (morphine)
d. Volume expansion
4. Intervention consists of repair in the neonatal period or palliation, followed by
repair at an older age. Survival should exceed 95%.
5. Because of abnormalities of the pulmonary arteries, some patients may be not
As an example of cyanotic heart disease I am using Tetralogy of Fallot.
Cyanosis is caused by the presence of blue blood coming out into the aorta.
So patients with ASDs and VSDs should be acyanotic. They have left to right
shunts. They have too much red blood going into their lungs but they don't
have blue blood going out into their aorta unless they have some additional
problem like pulmonary vascular disease. The four features of Tetralogy of
Fallot are ventricular septal defect, which sits beneath the aortic valve, the aorta
sitting on top of the VSD, a so-called overriding aorta, right ventricular outflow
tract obstruction and right ventricular hypertrophy.
The physiology of Tetralogy of Fallot is based solely on the presence of the
VSD and obstruction between the right ventricle and the pulmonary artery. So
as long as blood finds it easier to get from the right ventricle into the aorta, the
patient will be blue. Exactly when patients get intervened upon, that have
Tetralogy of Fallot, depends upon the severity of their pulmonary stenosis.
Their physical examination, besides the cyanosis, which again is dependent
upon their amount of pulmonary stenosis, will be that of a child with pulmonary
stenosis. You hear only the most distal obstruction. You won't hear the VSD
murmur because there is such a large hole between the left and right ventricles
that the pressure in the two ventricles is identical, so you won't hear a classic
VSD murmur. All that you will hear is a pulmonary stenosis murmur.
Pulmonary stenosis murmurs are unique in that they are associated with clicks.
Clicks sound like split first heart sounds. As the mitral and tricuspid valves
close, the pulmonary valve opens and it clicks as it opens, so the split first
heart sound is the simultaneous closure of the mitral and tricuspid valves
followed shortly thereafter by the clicking open of the pulmonary valve.
Pulmonary ejection clicks vary with respiration. So a click that varies with
respiration, murmur of the pulmonary valves, is a pulmonary ejection click. In
patients with Tetralogy of Fallot, these clicks can be so loud that you can even
palpate and feel the clicks and they will disappear when the patient takes in a
breath. The systolic murmur is caused by the blood rushing across the right
ventricular outflow tract.
Early problems depend upon on the amount of decreased blood flow that the
patient has. Hypercyanotic spells, so-called "Tetrology spells". Frequently that
the mother will call and say that the baby was found in the morning, very
tachypneic and extremely cyanotic. Treatment for that should be knee chest
position, calm down the infant, oxygen. If possible, give morphine once they get
into the Emergency Room. Long term treatment for that should be surgery.
Treatment for patients with Tetralogy of Fallot. Everyone that is operating on
these patients should achieve a mortality rate in the long run that is somewhere
less than 5%, probably in the 1-2% range. Long term complications of
Tetralogy of Fallot repair include arrhythmias, right ventricular failure, and aortic
valve insufficiency, and probably the most common now is right ventricular
failure.

4D:\FILES\Review Courses\Prep 1\Cardiovascular Disorders.WPD
be candidates for surgery. These patients may have long term complications
related to the cyanosis and the polycythemia, including:
a. Headache
b. Altered mental status
c. Stroke
d. Epistaxis
e. Hemoptysis
f. Hyperuricemia and gout
III. Acute Management of Rhythm Disorders
A. A 12 lead ECG should be obtained during and after the tachycardia episode.
B. Narrow QRS complex tachycardia
1. Sinus tachycardia (less than 220 beats/minute) may be caused by exogenous
substances (beta agonist) or hyperthyroidism.
2. If the rate is very rapid and the child is hemodynamically unstable, direct current
cardioversion is recommended with 0.5 watt-seconds/kg, synchronize the
defibrillator.
3. If the child is stable, vagal maneuvers such as an ice bag, abdominal pressure
or rectal stimulation may be successful. If vagal maneuvers are not successful,
adenosine may be given IV. The initial dose is 50 micrograms/kg given iv push.
The dose may be increased up to a dose of 300 micrograms/kg. Adenosine will
only momentarily block AV conduction; therefore, if the patient has recurrent
SVT, adenosine will not help for more than a few seconds, and some other
intervention should be used.
C. Wide QRS Complex Tachycardia
1. If the patient is hemodynamically unstable, DC cardioversion is necessary.
2. If the patient is stable, vagal maneuvers may help differentiate between SVT
with aberrant conduction and ventricular tachycardia.
D. Bradycardia. If the patient is stable hemodynamically the bradycardia may be of
long standing duration. Sinus bradycardia is common in the athletes, or it may
occur with complete heart block. Unstable bradycardia may be palliated with
isoproterenol or
transthoracic pacing. Long term therapy involves placement of a pacemaker.
IV. Rheumatic Fever
A. Diagnosis is based on a modification of the Jones criteria. The criteria are divided
into major and minor categories. Diagnosis requires two major criteria, or one major
and two minor criteria. The patients must have evidence of a preceding
streptococcal infection (should be present in all cases except some patients with
chorea). Evidence of a preceding streptococcal infection includes either a positive
culture, positive ASO titre or recent history of scarlet fever.
Jones Criteria for Rheumatic Fever
Major Criteria Minor Criteria
Long term survival after Tetralogy of Fallot repair should be excellent. After
surgery patients have a 93% 20 year survival rate. In current years, this long
term survival rate should be even higher. So just as a reminder, when you do
a cardiovascular exam, I would implore you to try to do an ASD exam anytime
you are trying to critically evaluate a murmur. If you go through that whole
scenario, precordial activity, first heart sound, second heart sound, systole and
diastole, I think that you will have to refer fewer functional or innocent murmurs
and you won't miss many ASDs.
A pediatric cardiologist referral. Anybody that is symptomatic; If they are
cyanotic, failure to thrive, or if you suspect that they have congestive heart
failure, they should be sent when you suspect it. Also, patients that have
syndromes. All children with Trisomy 21 should be evaluated by a pediatric
cardiologist at least once. There is no other screening test that you run in
medicine that has a 50% true positive rate other than cardiology evaluation of
Down's syndrome because half of them will have significant congenital heart
disease. Asymptomatic patients with pathological murmurs, and I don't mean
the grade 5, PS murmurs, but I'm talking about somebody that you're not sure
if they have a tiny little muscular VSD or not. Or you're not sure if they have
mild pulmonary stenosis. You should not send them until the children are over
two years of age, because many of those VSDs will close spontaneously. Many
of the children that have right ventricular outflow tract murmurs, as the
pulmonary arteries dilate, those murmurs will go away. If they didn't have that
done when they were three-months-old for this outflow tract murmur, frequently
the cardiologist is going to see an ASD and have to see them back to do
another surgery.

1. Carditis 1. Fever
2. Polyarthritis 2. Arthralgia (not when arthritis is used
Inflammatory heart disease. Kawasaki's syndrome consists of fever over
3. Chorea as a major)
4. Subcutaneous nodules 3. Prolonged PR interval on the ECG
101.5ºF for greater than five days, rash, conjunctivitis, swollen hands and feet,
5. Erythema marginatum (not when carditis is used as a
oral mucous membrane changes, and lymphadenopathy. The
major)
lymphadenopathy is the least specific of all the signs, and it is only seen in
between 50-70% of children with diagnosis of Kawasaki's. The rash can be
4. Increased acute phase reactants
anything from a diaper dermatitis looking rash to a rash that looks like scarlet
(ESR, WBC or C-reactive protein)
fever. The conjunctivitis is very helpful. It usually spares the area around the
5.Previous history of rheumatic fever
iris; beet red conjunctivitis but nonpurulent. If they have purulent conjunctivitis
V. Endocarditis you probably need to look for some other diagnosis. The hands can look like
A. Incidence is between 11 and 50 cases per million/year. they were banging them on something hard. They can get swollen and the feet
B. can be so involved that the children cannot walk. The lips, dry, cracked, red. Most common organisms
Also the tongue will have a "strawberry" appearance. Two weeks after the 1. Alpha hemolytic strep
2. Staphylococcus aureus illness, their hands and feet will peel.
3. Staphylococcus epidermidis
4. Enterococci The etiology. In 1996 a paper was published where patients that had
C. Clinical Evaluation Kawasaki's syndrome, had oral, rectal and skin cultures performed. Twelve of
the 16 patients were culture positive for superantigen producing1. Fever, heart murmur, splenomegaly (seen in <50%).
2. Less common features include petechiae, splinter hemorrhages, retinal staphylococcus. The hypothesis is that the Staph produces the superantigen,
hemorrhages (Roth spot), systemic emboli, renal insufficiency. and then it is the immunogenic reaction to that superantigen that causes
3. Positive blood cultures, elevated ESR. Kawasaki's.
4. Echocardiography is indicated if endocarditis is suspected clinically.
Therapy for Kawasaki's. Aspirin is also given concurrent with the gamma 5. Antibiotic Prophylaxis Against Endocarditis
globulin. The current dose of gamma globulin is 2 gm/kg given intravenously. a. Prophylaxis is necessary for all children with high velocity jets in their hearts
(VSD, aortic stenosis, pulmonic stenosis, history of rheumatic fever with It is a one time dose. It is no longer the 400 mg over 5 days. Remember though
valve damage, mitral or tricuspid regurgitation, patent ductus arteriosus, that these patients are under some bit of cardiovascular stress when they're
surgically created shunts) sick and you're giving them a large protein load when you give them the gamma
globulin. So they can get tachypneic or tachycardic while they're getting their b. Prophylaxis is not necessary for atrial septal defect or mitral valve prolapse
gamma globulin. You might have to decrease the rate a little bit and you might without mitral regurgitation because there are no areas of high velocity blood
flow. have to give them diuretics, but the gamma globulin is the cure. Don't stop
c. Endocarditis prophylaxis is given when bacteremia is anticipated, such as giving it just because they appear to be having some problems with the protein.
with dental cleanings, tonsillectomy, or cystoscopy.
d. Complications of Kawasaki's syndrome are coronary artery aneurysms. Around Prophylaxis is not recommended for cardiac catheterization, orthodontic
5% of patients develop coronary artery aneurysms. Patients that do badly and manipulation, or tympanostomy tube placement.
e. SBE prophylaxis usually consists of one dose of amoxicillin, one given require a lot of intensive follow up are those that have so-called giant
before the dental procedure. aneurysms. By giant I mean greater than 8 mm. One of the major problems is
VI. Kawasaki Syndrome that giant aneurysms develop and that is stenosis. You see the left anterior
A. KS is a multisystem probably infectious disease with an uncertain etiology. Recent descending coronary artery stops right there. This patient might benefit from
coronary artery bypass grafting.theories suggest the patients with KS have a high incidence of superantigen
producing staphylococcus aureus or group A beta-hemolytic streptococci.
B. Diagnosis of KS is based on the presence of five of the following: Follow up in patients with Kawasaki's depends on the severity of their coronary
1. Fever lasting five days or longer involvement. People that have no pulmonary involvement or minimal pulmonary
2. Polymorphous exanthem involvement that returns to normal can be released and followed up after
approximately one year and should be treated as normal for the remainder of 3. Redness or induration of the hands and/or feet
their lives.4. Bilateral non purulent conjunctival injection
5. Erythema of the lips or tongue
6. Non-purulent swelling of the cervical lymph nodes Endocarditis. There are between 11 and 50 cases per million population per
C. Complications include coronary artery aneurysms, seen in as many as 20% of year, which comes out to about 4,000 to 8,000 cases of endocarditis across
untreated cases. the United States per year. Most of those people that develop endocarditis, at
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6D:\FILES\Review Courses\Prep 1\Cardiovascular Disorders.WPD
1. Treated cases have a 2% incidence of aneurysms.
2. About 50% of aneurysms resolve spontaneously
D. Treatment of Kawasaki Syndrome
1. High dose aspirin (100 mg/kg) is continued until signs of inflammation have
subsided. This may be based on laboratory (ESR) or clinical grounds.
2. IV gamma globulin (2 grams/kg given over 8 to 12 hours).
a. Most gamma globulin contains high concentrations of antibodies that inhibit
T cell response to staphylococcal superantigens.
b. Patients with clinical failure to IV gamma globulin should be retreated.
3. Long Term Follow-up
a. The vast majority of children with Kawasaki syndrome will have no
aneurysms and will have completed therapy within 6 to 8 weeks.
b. Children with coronary changes that resolve quickly do not require
medication and should have no exercise restrictions.
c. Children with chronic aneurysms require long term follow up, exercise
testing, and exercise restrictions.
least 75% have some underlying cardiovascular etiology - either mitral valve
insufficiency, a ventricular septal defect, an abnormal aortic valve, etc.
Diagnosis is based not on fever and go straight to an echo, but repeated
positive blood cultures with the same organism, possibly associated with
systemic emboli and then go to an echo. But an echo has extremely low
sensitivity and specificity if used as a sort of front line tool to rule out
endocarditis. Prevention of endocarditis. The best we can do is so-called
antibiotic prophylaxis at times of endocarditis risk. What that means is that any
patient that you have that is at risk for developing endocarditis and what that
means is that they have a high velocity jet lesion somewhere in their
cardiovascular system, those people should receive antibiotics prior to
becoming predictably bacteremic. That doesn't mean that the child just fell in
a mud puddle and scraped his knee. You couldn't predict that. So they don't
get antibiotics retrospectively for something like that. But they do get it when
they do to the dentist, if they are going to have cystoscopy, rigid bronchoscopy,
sigmoidoscopy, etc. Procedures that would cause them to become predictably
bacteremic. Even in cases with prosthetic valves, the American Heart
Association recommends that the prophylaxis be performed with amoxicillin.
No longer do you have to admit them and put them on IV antibiotics unless they
have things like antibiotic allergies or other problems.
Just to hammer home the point of the high velocity jets. Patients with VSDs,
for example, where blood is flying through from the left ventricle to the right
ventricle. Those patients should receive antibiotic prophylaxis at time of
endocarditis risk. Patients with mitral valve regurgitation. This echocardiogram
depicts the turbulence of blood as it comes across the mitral valve in systole.
Patients that have mitral valve prolapse clicks, just the click, but no mitral valve
insufficiency, the American Heart Association is very clear that those people
do not require antibiotic prophylaxis at time of endocarditis risk. Six percent of
normal females in your practice should have clicks of mitral valve prolapse
which I would hope you would diagnose as split first heart sounds. Two
percent of males should have those same clicks, but only about 0.2 or 0.4%
should have a click and murmur of mitral valve regurgitation. Those are the
people that have true mitral valve disease that would have an echocardiogram
like this and would be at risk for developing endocarditis.
Children that are not at risk for developing endocarditis are those that have low
velocity shunts within their heart. This is an echocardiogram of a child with an
atrial septal defect. You can see blood coursing through the ASD and it is
laminar, it doesn’t speed up, it doesn't change colors, it doesn't make any
noise. So it doesn't denude the epithelium as blood comes across the atrial
septum, across the tricuspid valve in diastole. Patients with ASD do not require
antibiotic prophylaxis at times of endocarditis risk. Procedures that do not
cause you to become bacteremic are for example tympanostomy tubes. There
are not enough blood vessels in the tympanic membrane to cause you to
become bacteremic when you put the tympanostomy tubes in place.
In summary, when we talk about blood pressure measurement, I would
encourage you to try and get a hold of that article that was in Pediatrics in

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October of 1996. Those tables can be very useful. Don't overcall hypertension.
Somebody has got to be in the 95th percentile on average for three separate
evaluations. Remember how to do the ASD exam and try to do that on every
single patient that you evaluate before referring to a pediatric cardiologist. For
inflammatory heart disease remember the diagnostic criteria for Kawasaki's.