The increase in direct bilirubin immediately rules out the rest of the options where the increase in total bilirubin would be at the expense of indirect bilirubin. Bile duct atresia is the main indication for infant liver transplantation.

The increase in direct bilirubin immediately [HIDDEN] where the increase in total bilirubin would be at the expense of indirect bilirubin. Bile duct atresia is the main indication for infant liver transplantation.

A 1-month-old infant comes to the hospital emergency department referred by his pediatrician for jaundice. He reports jaundice for 10 days and it has been increasing. The blood test showed a total bilirubin of 7mg/dl with an indirect bilirubin of 1.5mg/dl. The most probable cause, among the following, of this jaundice is:

Jaundice

Causes The most common cause of jaundice in infants is normal physiologic jaundice. Pathologic causes of neonatal jaundice include: Breastmilk jaundice Formula jaundice Hereditary spherocytosis Glucose-6-phosphate dehydrogenase deficiency Pyruvate kinase deficiency ABO/Rh blood type autoantibodies Alpha 1-antitrypsin deficiency Alagille syndrome (genetic defect resulting in hypoplastic intrahepatic bile ducts) Progressive familial intrahepatic cholestasis Pyknocytosis (due to vitamin deficiency) Cretinism (congenital hypothyroidism) Sepsis or other infectious causes Pathophysiology Transient neonatal jaundice is one of the most common conditions occurring in newborns (children under 28 days of age) with more than eighty percent affected during their first week of life. Jaundice in infants, like adults, is characterized by increased bilirubin levels (total serum bilirubin greater than 5 mg/dL).

Clinical rounds in the well-baby nursery: treating jaundiced newborns.

Ten pearls (and pitfalls) in the management of the jaundiced newborn: Remember to take a history. Ask about jaundice in previous siblings and check family ethnicity. Don't ignore jaundice in the first 24 hours--it is considered pathologic until proven otherwise. Some normal infants may appear jaundiced and have a bilirubin level of 5 mg/dL at 23 hours and 59 minutes. On the other hand, a bilirubin level of 5 mg/dL at 10 hours is almost certainly pathologic. Use your judgment. Don't treat 35 to 37 week gestation infants as if they were full-term infants. Although these babies are cared for in well-baby nurseries and are generally treated like full-term infants, they are not full term. They are not as vigorous and do not nurse as well as full-term infants. Infants at 37 weeks gestation are four times more likely to have a serum bilirubin level greater than 13 mg/dL than those at 40 weeks gestation. Don't send 35-week gestation infants home before 48 hours. Document your assessment, particularly if the infant is being discharged early. Document the presence or absence of jaundice and its severity. A late rising bilirubin is typical of G6PD deficiency. Think about the ethnic background: G6PD deficiency is much more likely to occur in families from Greece, Turkey, Sardinia, and Nigeria, and particularly in Sephardic Jews from Iraq, Iran, Syria, and Kurdistan. Your practice may not contain many such families but remember in today's world of travel and intermarriage, etc, these genes are ubiquitous and the diagnosis of G6PD deficiency should always be considered in a newborn child with a significant elevation of bilirubin, particularly if it is a male and the rise in bilirubin is of late onset. Don't use homeopathic doses of phototherapy. As with any drug, phototherapy should be provided in a therapeutic dose (see above), but with the light sources commonly used, it is impossible to overdose the patient. Don't ignore a failure of response to phototherapy. If the bilirubin rises despite adequate phototherapy, there must be a reason. Consider the possibility of an unrecognized hemolytic process. Provide timely follow-up. Infants discharged (as most are) before 48 hours should be seen by a health-care professional within 2 to 3 days of discharge. Don't ignore prolonged jaundice. About one in three normal breast-fed infants still will be clinically jaundiced when they are 2 weeks old (two thirds will be biochemically jaundiced). These infants all have indirect hyperbilirubinemia. Occasionally, however, an infant with prolonged jaundice has direct hyperbilirubinemia. In these infants, the diagnosis of biliary atresia or some other cause of cholestatic jaundice must be considered. If the infant is clinically jaundiced beyond age 2 weeks, you should: 1) check the newborn record to make sure that the metabolic screen for hypothyroidism is normal (congenital hypothyroidism is a cause of indirect hyperbilirubinemia), and 2) ask the mother about the color of the urine and stool. If the baby's stools are pale or the urine is dark yellow, you must get a direct bilirubin to rule out cholestasis. If there is direct hyperbilirubinemia, a urine dipstick will identify the presence of bile (bilirubin). If the color of the urine and stool are normal (by history), it is reasonable to follow the child for another week. However, any infant who is still jaundiced beyond age 3 weeks must have a measurement of direct bilirubin. Don't ignore severe jaundice. If the bilirubin is sufficiently elevated, kernicterus can occur in a healthy, breast-fed infant.

Excessive bilirubin elevation in a patient with hereditary spherocytosis and intrahepatic cholestasis.

Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.

Extreme hyperbilirubinemia in a patient with hereditary spherocytosis, Gilbert's syndrome, and obstructive jaundice.

Hyperbilirubinemia may be of several etiologies in the individual patient. An 18-year-old man presented with extreme hyperbilirubinemia (direct bilirubin 23.0 mg/dl, total bilirubin 60.0 mg/dl), hepatosplenomegaly, and anemia. Hematologic studies prelaparotomy documented the presence of hereditary spherocytosis. Intraoperative liver biopsy revealed moderately reduced levels of glucuronyl transferase activity (Gilbert's syndrome). Common bile duct obstruction secondary to choledocholithiasis was found, and a cholecystectomy and splenectomy were performed. This case stresses the potential confusion among several diseases which may present with hyperbilirubinemia.

Neonatal jaundice

Pathological jaundice Any of the following features suggests pathological jaundice: Clinical jaundice appearing in the first 24 hours or greater than 14 days of life. Increases in the level of total bilirubin by more than 8.5 μmol/l (0.5 mg/dL) per hour or (85 μmol/l) 5 mg/dL per 24 hours. Total bilirubin more than 331.5 μmol/l (19.5 mg/dL) (hyperbilirubinemia). Direct bilirubin more than 34 μmol/l (2.0 mg/dL).

Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach.

Standard recommendations for evaluating and treating jaundice in term babies include following all babies closely for jaundice, obtaining several laboratory tests in those with early jaundice or bilirubin levels more than 12 to 13 mg/dL (205 to 222 mumol/L), using phototherapy to try to keep bilirubin levels below 20 mg/dL (342 mumol/L), and doing exchange transfusions if phototherapy fails, regardless of the cause of the jaundice. These recommendations are likely to lead to unnecessary testing and treatment of many jaundiced term infants. Because most jaundiced infants have no underlying illness, and the generally recommended laboratory tests lack sensitivity and specificity, they are seldom useful. In most babies, the only blood tests needed to evaluate jaundice are the blood type and group (of baby and mother) and a direct Coombs' test. A determination of direct bilirubin level should be added if jaundice is prolonged (greater than 2 to 4 weeks) or the baby has other signs of illness. Bilirubin toxicity is rare in term babies without hemolysis. In this low-risk group, the risks and cost of identifying and treating high bilirubin levels may exceed the benefits. Such infants need not be closely followed for jaundice. If significant jaundice is nonetheless found, treatment should be deferred to relatively high levels of serum bilirubin, with a goal of keeping bilirubin levels below 400 to 500 mumol/L (23.4 to 29.2 mg/dL). Babies with hemolytic disease should be followed more closely, and their bilirubin levels kept below 300 to 400 mumol/L (17.5 to 23.4 mg/dL). These recommendations should be reevaluated as new data become available. In the meantime, currently available data justify an approach to the jaundiced term infant that is less aggressive than previously recommended.

Liver function tests

The measurement of bilirubin levels in the newborns is done through the use of bilimeter or transcutanoeus bilirubinometer instead of performing LFTs. When the total serum bilirubin increases over 95th percentile for age during the first week of life for high risk babies, it is known as hyperbilirubinemia of the newborn (neonatal jaundice) and requires light therapy to reduce the amount of bilirubin in the blood. Pathological jaundice in newborns should be suspected when the serum bilirubin level rises by more than 5 mg/dL per day, serum bilirubin more than the physiological range, clinical jaundice more than 2 weeks, and conjugated bilirubin (dark urine staining clothes). Haemolytic jaundice is the commonest cause of pathological jaundice. Those babies with Rh hemolytic disease, ABO incompatibility with the mother, Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and minor blood group incompatibility are at increased risk of getting haemolytic jaundice.

Coexistence of gilbert syndrome and hereditary spherocytosis in a child presenting with extreme jaundice.

Gilbert syndrome is the most common inherited disorder of bilirubin glucuronidation. It is characterized by intermittent episodes of jaundice in the absence of hepatocellular disease or hemolysis. Hereditary spherocytosis is the most common inherited hemolytic anemia and is characterized by spherical, osmotically fragile erythrocytes that are selectively trapped by the spleen. The patients have variable degrees of anemia, jaundice, and splenomegaly. Hereditary spherocytosis usually leads to mild-to-moderate elevation of serum bilirubin levels. Severe hyperbilirubinemia compared with the degree of hemolysis should be lead to suspicion of additional clinical conditions such as Gilbert syndrome or thalassemia. We present the case of a 12-year-old boy with extreme jaundice and nausea. The diagnosis of hereditary spherocytosis was confirmed by osmotic fragility test results and that of Gilbert syndrome by genetic analysis findings.

Hereditary spherocytosis in neonates with hyperbilirubinemia.

Hereditary spherocytosis (HS) is the most common inherited hemolytic disease among people of Northern European decent. Neonates with HS can develop significant hyperbilirubinemia, but we suspect that HS is underrecognized as a cause of neonatal jaundice. We used electronic record repositories of Intermountain Healthcare to identify all neonates with a diagnosis of HS in a recent 5-year period. We compared these with the number of new HS cases anticipated on the basis of national prevalence and also with the number who had elevations in mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), and bilirubin. We compared MCHC and RDW values of neonates who had direct antiglobulin test-positive (DAT[+]) and DAT(-) results and jaundice with values of neonates who had HS. Eight neonates received a diagnosis of HS; however, we may have failed to diagnose 90% of cases. To assess whether some with a missed diagnosis of HS developed significant hyperbilirubinemia, we examined records of all 670 with a bilirubin level of >or=20 mg/dL. Records of the 20 with the highest MCHC and RDW values suggested that HS was present but unrecognized in at least 7. Follow-up revealed a subsequent diagnosis of HS in 5; the other 2 are no longer in our health system. MCHC and RDW values were highest in those with HS, intermediate in the DAT(+) group, and lowest in the DAT(-) group. An MCHC of >or=36.0 g/dL had 82% sensitivity and 98% specificity for identifying HS. We speculate that HS is underrecognized as a cause of neonatal hyperbilirubinemia. We speculate further that an MCHC of >or=36.0 g/dL can alert caregivers to the possibility of HS.

Jaundice

Jaundice, also known as icterus', is a yellowish or greenish pigmentation of the skin and whites of the eyes due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine. Normal levels of bilirubin in blood are below 1.0 mg/dl (17 μmol/L), while levels over 2–3 mg/dl (34-51 μmol/L) typically result in jaundice. High blood bilirubin is divided into two types - unconjugated and conjugated bilirubin.

Severe neonatal hyperbilirubinemia secondary to combined RhC hemolytic disease, congenital hypothyroidism and large adrenal hematoma: a case report.

ABO blood group incompatibility, neonatal sepsis, G-6-PD deficiency, thyroid dysfunction, and hereditary spherocytosis are all probable causes of neonatal hyperbilirubinemia. However, the etiology of some hyperbilirubinemia is extremely complicated, which may be caused by multiple factors, resulting in severe jaundice. We report a case of severe jaundice due to three causes, showing the significance for the investigation of the etiology of neonatal hyperbilirubinemia. At 96 h of life, a full-term and vaginal delivery male infant with yellowish discoloration of body was transferred to our hospital. When he entered neonatal intensive care unit on the fourth day after birth, he developed jaundice and the transcutaneous bilirubin was 28 mg/dl. Total bilirubin was 540.2 μmol/L, while the indirect bilirubin was 516.7 μmol/L. Both parents and the baby's blood types were O Rh(D +), and direct coomb's test was negative. But mother's indirect coomb's test was positive. Investigating for minor blood group revealed that the father's blood type of Rh was CCDee, the mather's was ccDEE, and CcDEe for the baby. After intensive phototherapy and double volume exchange transfusion, the total bilirubin remained at 303 μmol/L. At day 10, the bilirubin level was 303.5 μmol/L, intensive phototherapy was continued, and intravenous immunoglobulin was used again. The test for thyroid hormones at day 10, the TSH was 13.334mIU/L. And the screening for congenital hypothyroidism showed the TSH was 33mIU/L. Because of the palpable abdominal mass, ultrasound and MRI was done, showed a huge mass in the right adrenal gland. Brainstem auditory evoked potential was performed at day 7, which indicated hearing impairment (65db for left ear and 70db for the right). Euthyrox and intermittent phototherapy were given as following treatment. The jaundice did not subside until the 12th day. Even if their parents' ABO blood group and Rh (d) are consistent, a Coomb test is required for newborns with hyperbilirubinemia since they may have minor blood group incompatibilities. When bilirubin rises rapidly or the clinical treatment effect is inadequate, additional causes should be aggressively screened. Adrenal ultrasound should be performed on newborns with palpable abdominal mass, anemia and jaundice to determine whether there is adrenal hemorrhage.

Neonatal jaundice

Physiological jaundice Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods. Phase one Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 μmol/l (12 mg/dL). Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255 μmol/l (15 mg/dL). Phase two - bilirubin levels decline to about 34 μmol/l (2 mg/dL) for two weeks, eventually mimicking adult values. Preterm infants - phase two can last more than one month. Exclusively breastfed infants - phase two can last more than one month.

Neonatal jaundice

If the neonatal jaundice is not resolved with simple phototherapy, other causes such as biliary atresia, Progressive familial intrahepatic cholestasis, bile duct paucity, Alagille syndrome, alpha 1-antitrypsin deficiency, and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests. Prolonged neonatal jaundice is serious and should be followed up promptly. Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below). These should be detected or excluded as part of the differential diagnosis to prevent the development of complications. They can be grouped into the following categories: Unconjugated Hemolytic

Breastfeeding

Breast milk jaundice is jaundice that persists despite appropriate weight gain. This type of jaundice may start as breastfeeding jaundice and persist, or may not appear until after the baby has begun to gain weight, typically around 4–5 days old. It often persists beyond the second and third weeks of life. There is no single cause of breast milk jaundice; rather, the causes are multifactorial and frequently debated in the literature. The causes of breast milk jaundice include variations in bilirubin metabolism, genetic variations, and variations in breastmilk, including the harmless and helpful germs found naturally on the surface of the skin and in the breastmilk. Breast milk jaundice is usually not a reason to stop nursing. It is important to consult with a physician to determine when it may be necessary to test for other causes of jaundice that may require additional treatment, such as enzyme deficiencies or problems with the red blood cells (i.e., elliptocytosis, spherocytosis,

Jaundice

A much less common sign of jaundice specifically during childhood is yellowish or greenish teeth. In developing children, hyperbilirubinemia may cause a yellow or green discoloration of teeth due to bilirubin deposition during the process of tooth calcification. While this may occur in children with hyperbilirubinemia, tooth discoloration due to hyperbilirubinemia is not observed in individuals with adult-onset liver disease. Disorders associated with a rise in serum levels of conjugated bilirubin during early development can also cause dental hypoplasia. Causes Jaundice is a sign indicating the presence of an underlying diseases involving abnormal bilirubin metabolism, liver dysfunction, or biliary-tract obstruction. In general, jaundice is present when blood levels of bilirubin exceed 3 mg/dl. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are:

Investigation of prolonged neonatal jaundice.

Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7,139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1,000 live births. Diagnoses included: giant cell hepatitis (n = 1), hepatoblastoma (n = 1), trisomy 9p (n = 1), urinary tract infections (n = 2), glucose-6-phosphate dehydrogenase deficiency (n = 3) and failure to regain birthweight (n = 1). In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process.

InternalMed_Harrison

Hemolytic disorders that cause excessive heme production may be either inherited or acquired. Inherited disorders include spherocytosis, sickle cell anemia, thalassemia, and deficiency of red cell enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase. In these conditions, the serum bilirubin level rarely exceeds 86 μmol/L (5 mg/dL). Higher levels may occur when there is coexistent renal or hepatocellular dysfunction or in acute hemolysis, such as a sickle cell crisis. In evaluating jaundice in patients with chronic hemolysis, it is important to remember the high incidence of pigmented (calcium bilirubinate) gallstones found in these CAuSES of iSoLATED HyPERBiLiRuBinEMiA PART 2 Cardinal Manifestations and Presentation of Diseases I. Indirect hyperbilirubinemia A. Hemolytic disorders 1. Inherited a. Spherocytosis, elliptocytosis, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies b. 2. Acquired a. b. c. d. e. B. 1.

Pediatrics_Nelson

The clinical pattern of physiologic jaundice in term infantsincludes a peak indirect-reacting bilirubin level of no morethan 12 mg/dL on day 3 of life. In premature infants, the peakis higher (15 mg/dL) and occurs later (fifth day). The peak levelof indirect bilirubin during physiologic jaundice may be higherin breast milk–fed infants than in formula-fed infants (15 to17 mg/dL versus 12 mg/dL). This higher level may be partly aresult of the decreased fluid intake of infants fed breast milk. Jaundice is unphysiologic or pathologic if it is clinically evidenton the first day of life, if the bilirubin level increases more than 0.5 mg/dL/hr, if the peak bilirubin is greater than 13 mg/dLin term infants, if the direct bilirubin fraction is greater than 1.5 mg/dL, or if hepatosplenomegaly and anemia are present.

Jaundice

Prehepatic causes Prehepatic jaundice is most commonly caused by a pathological increased rate of red blood cell (erythrocyte) hemolysis. The increased breakdown of erythrocytes → increased unconjugated serum bilirubin → increased deposition of unconjugated bilirubin into mucosal tissue. These diseases may cause jaundice due to increased erythrocyte hemolysis: Sickle-cell anemia Spherocytosis Thalassemia Pyruvate kinase deficiency Glucose-6-phosphate dehydrogenase deficiency Microangiopathic hemolytic anemia Hemolytic-uremic syndrome Severe malaria (in endemic countries) Hepatic causes

Pediatrics_Nelson

Physical evidence of jaundice is observed in infants when bilirubin levels reach 5 to 10 mg/dL (versus 2 to 3 mg/dL in adults). When jaundice is observed, the laboratory evaluation for hyperbilirubinemia should include a total bilirubin measurement to determine the magnitude of hyperbilirubinemia. Bilirubin levels greater than 5 mg/dL on the first day of life or greater than 13 mg/dL thereafter in term infants should be evaluated further with measurement of indirect and direct bilirubin levels, blood typing, Coombs test, complete blood count, blood smear, and reticulocyte count. These tests must be performed before treatment of hyperbilirubinemia with phototherapy or exchange transfusion. In the absence of hemolysis or evidence for either the common or the rare causes of nonhemolytic indirect hyperbilirubinemia, the diagnosis is either physiologic or breast milk jaundice. Jaundice present after 2 weeks of age is pathologic and suggests a direct-reacting hyperbilirubinemia.

Bilirubin

Jaundice Hemoglobin acts to transport oxygen your body receives to all body tissue via blood vessels. Over time, when red blood cells need to be replenished, the hemoglobin is broken down in the spleen; it breaks down into two parts: heme group consisting of iron and bile and protein fraction. While protein and iron are utilized to renew red blood cells, pigments that make up the red color in blood are deposited into the bile to form bilirubin. Jaundice leads to raised bilirubin levels that in turn negatively remove elastin-rich tissues. Jaundice may be noticeable in the sclera of the eyes at levels of about 2 to 3 mg/dl (34 to 51 μmol/l), and in the skin at higher levels. Jaundice is classified, depending upon whether the bilirubin is free or conjugated to glucuronic acid, into conjugated jaundice or unconjugated jaundice..

Jaundice

Laboratory findings depend on the cause of jaundice: Urine: conjugated bilirubin present, urobilinogen > 2 units but variable (except in children) Plasma proteins show characteristic changes. Plasma albumin level is low, but plasma globulins are raised due to an increased formation of antibodies. Unconjugated bilirubin is hydrophobic, so cannot be excreted in urine. Thus, the finding of increased urobilinogen in the urine without the presence of bilirubin in the urine (due to its unconjugated state) suggests hemolytic jaundice as the underlying disease process. Urobilinogen will be greater than 2 units (i.e., hemolytic anemia causes increased heme metabolism; exception: infants where gut flora has not developed). Conversely, conjugated bilirubin is hydrophilic and thus can be detected as present in the urine — bilirubinuria — in contrast to unconjugated bilirubin which is absent in the urine.

Bilirubin glucuronide

At birth, infants don't develop enough ability to conjugate bilirubin. Up to 8% to 11% neonates will develop hyperbilirubinemia in the first week of their lives. Hemolytic jaundice In jaundice owing to hemolysis (Prehepatic (or hemolytic) jaundice), the pathophysiology is that overproduction of bilirubin from the extravascular or intravascular hemolysis overwhelms the capacity of the liver to excrete it. The bilirubin present in the plasma is largely unconjugated in this setting as they haven't been taken up and conjugated by the liver. In this case, total serum bilirubin increases while the ratio of direct bilirubin to indirect bilirubin remains 96 to 4 as up to 96%-99% of bilirubin in the bile are conjugated mentioned above. Brain damage

Neonatal cholestasis

Neonatal cholestasis defines persisting conjugated hyperbilirubinemia in the newborn with conjugated bilirubin levels exceeding 15% (5.0 mg/dL) of total bilirubin level. The disease is either due to defects in bile excretion from hepatocytes or impaired bile flow. General presentations in neonates include abdominal pain and general gastrointestinal upset. Physical examination may show palpable liver and enlarged spleen. Differential diagnosis typically presents with a host of possibilities, many of them not treatable. Histopathology shows dilated bile duct system at all levels and bile duct proliferation in response to back pressure. The incidence has been found to be about 1 in 2,500 live births. See also Neonatal jaundice References Neonatology

Neonatal jaundice

A bilirubin level more than 34 μmol/l (2 mg/dL) may be visible. For the feet to be affected level generally must be over 255 μmol/l (15 mg/dL). Complications Prolonged hyperbilirubinemia (severe jaundice) can result in chronic bilirubin encephalopathy (kernicterus). Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus. Infants with kernicterus may have a fever or seizures. High pitched crying is an effect of kernicterus. Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment. Causes In newborns, jaundice tends to develop because of two factors—the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the relatively immature metabolic pathways of the liver, which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice.

Breast Milk Jaundice -- Evaluation

The evaluation of a patient presenting with hyperbilirubinemia must include a work-up to rule out pathological causes of hyperbilirubinemia before making the breast milk jaundice diagnosis. First, both unconjugated and conjugated bilirubin levels must be measured. Conjugated bilirubin levels higher than 1 mg/dL or 20% of the total bilirubin level indicate conjugated hyperbilirubinemia (also known as cholestasis or direct hyperbilirubinemia). Once cholestasis is suspected, disorders such as biliary atresia, neonatal hepatitis, and other bilirubin excretion disorders. Both breast milk jaundice and hemolytic anemias cause elevated unconjugated bilirubin levels. Hemolytic causes for hyperbilirubinemia include ABO incompatibility, G6PD deficiency, hereditary spherocytosis, and other antibody-mediated hemolysis. Hemolysis assessment should consist of direct Coombs’ testing, measurement of hemoglobin, hematocrit, and reticulocyte count, a peripheral blood smear, and genetic testing.

Jaundice

Posthepatic pathophysiology Posthepatic jaundice (obstructive jaundice) is due to a blockage of bile excretion from the biliary tract → increased conjugated bilirubin and bile salts. In complete obstruction of the bile duct, conjugated bilirubin cannot access the intestinal tract → no further bilirubin conversion to urobilinogen → no stercobilin or urobilin. Instead, excess conjugated bilirubin is filtered into the urine without urobilinogen in obstructive jaundice. Conjugated bilirubin in urine (bilirubinuria) gives urine an abnormally dark brown color. Thus, the presence of pale stool (stercobilin absent from feces) and dark urine (conjugated bilirubin present in urine) suggest an obstructive cause of jaundice. Because these associated signs are also positive in many hepatic jaundice conditions, they cannot be a reliable clinical feature to distinguish obstruction versus hepatocellular jaundice causes. Diagnosis

Neonatal jaundice

Post-liver Biliary atresia or bile duct obstruction Alagille syndrome Choledochal cyst Non-organic causes Breastfeeding jaundice "Breastfeeding jaundice" (or "lack of breastfeeding jaundice") is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.

Jaundice

Treatment of jaundice is typically determined by the underlying cause. If a bile duct blockage is present, surgery is typically required; otherwise, management is medical. Medical management may involve treating infectious causes and stopping medication that could be contributing to the jaundice. Jaundice in newborns may be treated with phototherapy or exchanged transfusion depending on age and prematurity when the bilirubin is greater than 4–21 mg/dl (68-360 μmol/L). The itchiness may be helped by draining the gallbladder, ursodeoxycholic acid, or opioid antagonists such as naltrexone. The word "jaundice" is from the French jaunisse, meaning "yellow disease". Signs and symptoms

Bilirubin

Very high levels of bilirubin may be caused by: Neonatal hyperbilirubinemia, where the newborn's liver is not able to properly process the bilirubin causing jaundice Unusually large bile duct obstruction, e.g. stone in common bile duct, tumour obstructing common bile duct etc. Severe liver failure with cirrhosis (e.g. primary biliary cirrhosis) Crigler–Najjar syndrome Dubin–Johnson syndrome Choledocholithiasis (chronic or acute). Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis. To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests (especially the enzymes alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase), blood film examination (hemolysis, etc.) or evidence of infective hepatitis (e.g., hepatitis A, B, C, delta, E, etc.). Jaundice

Hemolytic jaundice

As one of the three categories of jaundice, the most obvious sign of hemolytic jaundice is the discolouration or yellowing of the sclera and the skin of the patient, but additional symptoms may be observed depending on the underlying causes of hemolysis. Hemolytic causes associated with bilirubin overproduction are diverse and include disorders such as sickle cell anemia, hereditary spherocytosis, thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemolysis secondary to drug toxicity, thalassemia minor, and congenital dyserythropoietic anemias. Pathophysiology of hemolytic jaundice directly involves the metabolism of bilirubin, where overproduction of bilirubin due to hemolysis exceeds the liver's ability to conjugate bilirubin to glucuronic acid.

Neonatal jaundice

Breast milk jaundice Whereas breastfeeding jaundice is a mechanical problem, breast milk jaundice is a biochemical occurrence and the higher bilirubin possibly acts as an antioxidant. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one third of healthy breastfed infants.


Very easy question. They are describing the "portrait" of a degenerative aortic stenosis... Elderly patient with clinical dyspnea and syncope, and systolic murmur radiating to carotids and tip, all typical of this disease.

An 81-year-old patient consults for an episode of syncope. He reports dyspnea on exertion for a year. On cardiac auscultation there is a 3/6 systolic murmur on the left sternal border radiating to the carotids and tip. Which pathology seems most likely?

First_Aid_Step1

Auscultation of the heart (eg, physiologic murmur) Aortic valve sclerosis Where to listen: APT M 111234567777777 Left sternal border: Aortic regurgitation Pulmonic regurgitation cardiomyopathy PA M T Aortic area: Systolic murmur Pulmonic area: Tricuspid area: Mitral area (apex): Crescendo-decrescendo systolic ejection murmur and soft S2 (ejection click may be present). LV >> aortic pressure during systole. Loudest at heart base; radiates to carotids. “Pulsus parvus et tardus”—pulses are weak with a delayed peak. Can lead to Syncope, Angina, and Dyspnea on exertion (SAD). Most commonly due to age-related calcification in older patients (> 60 years old) or in younger patients with early-onset calcification of bicuspid aortic valve.

[Mitral valve prolapse as an initial clinical feature of dilated cardiomyopathy: report of two cases].

Two cases with mitral valve prolapse (MVP), without any other cardiac abnormalities at the initial evaluation, developed the clinical features mimic to dilated cardiomyopathy (DCM) during follow-up period. Case 1. A 40-year-old man visited our hospital in May 1982 to evaluate a heart murmur. A standard 12-lead electrocardiogram (ECG) showed an abnormal Q wave in lead III. Echocardiography revealed MVP, but neither dilatation nor wall motion abnormality of the left ventricle (LV) were observed. Thallium-201 scintigraphy revealed an abnormal thallium uptake at the apex and inferior wall. He had no episode of acute myocardial infarction or myocarditis, but complete right bundle branch block developed, thus, he was hospitalized in October 1984. He had no coronary artery lesions, and had only mild mitral regurgitation on left ventriculography. The motion of the interventricular septum and apex was reduced on echocardiogram and a persistent perfusion defect was observed at the inferior wall and the interventricular septum on Tl-201 scintigrams. In December 1985, he experienced an Adams-Stokes attack due to complete atrioventricular block. Echocardiographically, the left ventricle enlarged, and the wall motion abnormalities and a perfusion defect on Tl-201 scintigrams were relatively severe. Case 2. A 46-year-old woman occasionally experienced palpitation of short duration and chest oppression since 1977. She was admitted to our hospital because of cardiac symptoms in 1982. A heart murmur of Levine II was heard and a standard 12-lead ECG showed single supraventricular extrasystole and T wave inversion in lead III and aVF. Echocardiography revealed MVP and mild mitral regurgitation, but neither dilatation nor wall motion abnormality of the LV was observed. During 6-year follow-up period, permanent atrial fibrillation developed and LV developed dilatation and wall motion abnormalities progressed. Thus, during follow-up periods, DCM-like features developed in two cases who had had MVP as a sole echocardiographic abnormality with systolic murmur and non-specific ECG changes. We consider that these two may be important cases who may show a relation between cardiomyopathic process and MVP.

Valvular heart disease

Medical signs of aortic stenosis include pulsus parvus et tardus, that is, diminished and delayed carotid pulse, fourth heart sound, decreased A2 sound, sustained apex beat, precordial thrill. Auscultation may reveal a systolic murmur of a harsh crescendo-decrescendo type, heard in 2nd right intercostal space and radiating to the carotid arteries. Aortic regurgitation Patients with aortic regurgitation may experience heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea, palpitations, and angina pectoris. In acute cases patients may experience cyanosis and circulatory shock.

[beta-Blocking therapy in obstructive hypertrophic cardiomyopathy. Long term results (author's transl)].

34 patients have been controlled after beta-blocking therapy, for a mean period of 5 years. Symptoms and evolution: syncope disappeared, angoy passed from 47% to 23%, dyspnea from 65% to 47%, dizziness from 70% to 54%, weakness from 30% to 37%. A systolic murmur was present in 75% of the cases. Two patients died by heart failure. Phonocardiogram: the systolic murmur was unchanged, like the carotid pulse. Paradoxical splitting of the 2 degrees sound was more frequent, atrial sound unimodified, isometric contraction shortened (60%) and the Q-1 degree sound interval prolonged (90%). Electrocardiogram: 1 degree A/V block appeared in 24% of the cases, complete A/V block in 9%, atrial fibrillation in 3%. Left atrial enlargement was more frequent; left ventricular hypertrophy unchanged. Heart catheterization (10 cases, after a mean period of 5.5 years): left ventricular pressure gradient passed from 80% to 90%; a low cardiac index from 20% to 30%; telediastolic pressure of left ventricle was unmmodified in 10% of cases, more elevated in 50%, less elevated in 40%. Chest X ray: cardiac size was unchanged in 65% of cases, enlarged in 32%; smaller in 3%. In conclusion, symptoms improved in most of the patients; no case of sudden death was observed. Some data however show that the evolution of the myocardiopathy goes on to congestive heart failure and arise doubts on the real usefullness of beta-blocking drugs in the disease.

[Various etiologies of systolic murmurs radiating from the apex of the heart to the neck].

The authors studied systolic murmurs in 89 cases, 50 of aortic stenosis, 14 cases of obstructive cardiomyopathy and 20 cases of mitral incompetence. This systolic murmur is characterised by its exceptional intensity, its raspy character at the base, becoming softer at the apex and in the axilla, the presence of a thrill and irradiation into the neck in 50 to 75% of cases. The etiological diagnosis was ensured precisely by 1) pharmaco-dynamic tests: amyl nitrite accentuates the systolic ejection murmurs and attenuates murmurs due to mitral regurgitation. 2) careful analysis of diastole: a systolic murmur extending into early diastole, a third sound or an opening snap and a low-pitched diastolic murmur, suggest mitral incompetence. A high-pitched diastolic murmur is in favour of aortic stenosis. 3) the carotid arteriogram and catheterisation show the characteristic abnormalities of the carotid arteriogram found in aortic valve disease and the existence of a trans-aortic or intra-ventricular pressure gradient, when there is an obstruction to left ventricular jection. The F wave of the apex cardiogram or left atrial reflux of the contrast medium during cineangiocardiography, confirm mitral incompetence. The main phono-hemodynamic and phono-anatomical correlations have been emphasized: 1. The intensity of the systolic murmur is directly proportional to the degree of obstructive cardiomyopathy or mitral incompetence, but does not parallel the degree of the sub-valvular apparatus. 3. The maximum intensity of the murmur occurs all the later when the stenosis is tight, whilst it is earlier in severe obstructive cardio-myopathy. 4. The lozange shape of the murmur of mitral incompetence on phono-cardiography is, above all, due to those cases with lesions of the sub-valvular apparatus. Finally, a study of the sound recorded by the Allard-Laurens micromanometer permitted us to determine the mechanism of this irradiating systolic murmur.

[Clinical features of five patients with delayed third degree atrioventricular block after ethanol septal ablation for hypertrophic obstructive cardiomyopathy].

To analyze the clinical features of patients with delayed third degree atrioventricular block after ethanol septal ablation for hypertrophic obstructive cardiomyopathy. The clinical data of cases with delayed third degree atrioventricular block after septal ablation for hypertrophic obstructive cardiomyopathy at our hospital from 2000 to 2011 were collected. Five out of 235 patients (2.1%) developed delayed third degree atrioventricular block. Delayed third atrioventricular block occurred at 32 h post ablation (28 - 120 h). Their average age is 46 (33 - 64) years old, there are 4 males and 1 female. Left ventricular outflow gradient before ablation was 70 - 100 mm Hg (1 mm Hg = 0.133 kPa). Intraprocedural third degree atrioventricular block occurred in 4 patients. The average injected dose of Ethanol was 1.8 (1.4 - 4.3) ml. Syncope occurred in 3 patients. Temporary pacemaker was reimplanted to all 5 patients and removed after an average of 8 d (3 - 18 d). All 5 patients were in normal sinus rhythms at discharge without the need of implanting permanent pacemaker. There was no syncope in these 5 patients after discharge during the telephone follow up for an average of 9 (1 - 72) months. The incidence of delayed third degree atrioventricular block after septal ablation is rare. Prolonged electrocardiography monitoring and prophylactic temporary pacemaker backup post ablation are necessary to detect this event and to prevent syncope related to delayed third degree atrioventricular block after septal ablation.

[Echographic diagnosis of systolic murmur among 280 young French militaries. Implications for the expertise in military medicine].

Clinically discovering a systolic murmur is frequent among the young military population. When this murmur does not sound benign, a transthoracic echocardiography (TTE) is made to detect any cardiopathy, which could cause sudden cardiac death. The aim of this study was to evaluate the interest of systematic TTE in the assessment of any cardiac systolic murmur (CSM) among militaries. We ran a retrospective monocentric study in the "Clermont-Tonnerre" military hospital in Brest. We included all patients sent for TEE, aged 15 to 30 years old, from the 1st January 2010 until the 31st July 2013. Two hundred and eighty TTES assessing CSM were performed. We found 28/280 (10%) echocardiographic abnormalities: 13 were bicuspid aortic valves (4.6%), 6 were ventricular septal defects (2.15%), 3 were atrial septal defects (1.07%), 4 were mild mitral regurgitations (1.43%), one mild pulmonary stenosis (0.35%) and one aortic stenosis (0.35%). No hypertrophic cardiomyopathy was found. Concerning military expertise, 11 (3.92%) patients among these 28 with abnormal TEE were considered unfit for work or "fit for work with limitations". Assessing a cardiac systolic murmur with TEE lead to the diagnosis of a cardiomyopathy in 10% of the case. This study enhances the importance of systematic TEE when a CSM is detected in the young military, in order to determine if those soldiers can still fulfill their military duty.

[Aortic valve stenosis].

Aortic valve stenosis is the most frequent reason for prosthetic valve replacement in adults. Its incidence increases with age. Development of the most frequent form, degenerative-calcific aortic stenosis, is related to atherosclerotic risk factors. The narrowing of the aortic valve orifice leads to creation of a systolic pressure drop, the gradient, between left ventricle and ascending aorta. The pressure overload from aortic stenosis causes concentric left ventricular hypertrophy and later heart failure. Typical symptoms of severe aortic stenosis include dyspnea, angina, and dizziness or syncope. On auscultation, a loud systolic murmur over the base of the heart is apparent, which is transmitted to the carotids. The ECG often shows left ventricular hypertrophy. The most important diagnostic technique is echocardiography, which allows to measure the gradient and to calculate the orifice area, which determine the degree of severity. The development of symptoms or impaired left ventricular function in severe aortic stenosis should prompt surgical treatment by valve replacement. Truly asymptomatic patients with preserved left ventricular function should be followed conservatively.

Aortic stenosis

An easily heard systolic, crescendo-decrescendo (i.e., 'ejection') murmur is heard loudest at the upper right sternal border, at the 2nd right intercostal space, and radiates to the carotid arteries bilaterally. The murmur increases with squatting and decreases with standing and isometric muscular contraction such as the Valsalva maneuver, which helps distinguish it from hypertrophic obstructive cardiomyopathy (HOCM). The murmur is louder during expiration but is also easily heard during inspiration. The more severe the degree of the stenosis, the later the peak occurs in the crescendo-decrescendo of the murmur.

[Regression of mitral valve prolapse to a state masquerading as dilated cardiomyopathy: a case report].

A 40-year-old man was admitted to our hospital in May 1982 for evaluation of a heart murmur. A standard 12-lead electrocardiogram (ECG) showed an abnormal Q wave in lead III. Echocardiography revealed prolapse of the anterior mitral valve leaflet (MVP), but neither dilatation nor wall motion abnormalities of the left ventricle (LV) were observed. Thallium-201 scintigraphy revealed an abnormal thallium uptake at the apex and inferior wall. He had no episode of acute myocardial infarction or myocarditis, but complete right bundle branch block suddenly appeared, and he was hospitalized in October 1984. He had no coronary artery lesions, and only mild mitral regurgitation on left ventriculography. The motion of the interventricular septum and apex was reduced on echocardiography and a persistent perfusion defect was observed at the inferior wall and the interventricular septum on T1-201 scintigraphy. In December 1985, he experienced an Adams-Stokes attack due to complete atrioventricular block. Echocardiographically, the left ventricle became enlarged and the wall motion abnormality and a perfusion defect on T1-201 scintigrams were of relatively severe degree. Thus, left ventricular dilatation and wall motion abnormality may progress in some cases of MVP as it did in this one. We consider this case a very interesting one in speculating on the relationship between MVP and DCM.

Heart murmur

Anatomic sources Systolic Aortic valve stenosis typically is a crescendo/decrescendo systolic murmur best heard at the right upper sternal border sometimes with radiation to the carotid arteries. In mild aortic stenosis, the crescendo-decrescendo is early peaking whereas in severe aortic stenosis, the crescendo is late-peaking, and the S2 heart sound may be obliterated. Stenosis of Bicuspid aortic valve is similar to the aortic valve stenosis heart murmur, but a systolic ejection click may be heard after S1 in calcified bicuspid aortic valves. Symptoms tend to present between 40 and 70 years of age.

Valvular heart disease

Medical signs of aortic regurgitation include increased pulse pressure by increased systolic and decreased diastolic blood pressure, but these findings may not be significant if acute. The patient may have a diastolic decrescendo murmur best heard at left sternal border, water hammer pulse, Austin Flint murmur, and a displaced apex beat down and to the left. A third heart sound may be present Mitral stenosis Patients with mitral stenosis may present with heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea, palpitations, chest pain, hemoptysis, thromboembolism, or ascites and edema (if right-sided heart failure develops). Symptoms of mitral stenosis increase with exercise and pregnancy

[Mitral valve prolapse with myocardial disarrangement and familial hypertrophic cardiomyopathy: a case report].

This is a report of a patient with mitral valve prolapse (MVP) and myocardial abnormalities on endomyocardial biopsy in whose relatives hypertrophic cardiomyopathy (HCM) was identified. A 19-year-old woman was admitted to our hospital for evaluation of a heart murmur. A systolic ejection murmur was audible in the third intercostal space at the left sternal border, and a standard 12-lead electrocardiogram showed ST-T wave changes in leads II, III and aVF. Echocardiography revealed prolapse of the anterior leaflet of the mitral valve, but no left ventricular hypertrophy. Endomyocardial biopsy disclosed mild hypertrophy and disarrangement of the myocardium. The family study revealed asymmetrical septal hypertrophy in her mother, who had no history of hypertension. Her younger sister had mild hypertrophy of the interventricular septum on echocardiography, and her histopathological findings suggested a diagnosis of HCM. This case was clinically regarded as MVP, but development of left ventricular hypertrophy as noted in her mother may occur in the future.

[Mitral valve prolapse syndrome].

Within one and a half year 24 patients with arrhythmias or chest pain were investigated to detect a mitral valve prolapse syndrome which was found in 9 cases by echocardiography. Within this group 6 patients complained of fatigue, dizziness, dyspnea or syncope, 6 had chest pain, 7 paroxysmal tachycardia and 2 patients premature beats. Auscultation revealed in 3 cases a systolic click, in 1 case a systolic click with late systolic murmur and in 5 cases a systolic murmur only. The ECG showed premature ventricular contractions in 2 patients, ST-T abnormalities in 6 patients. Echocardiography showed a late systolic prolapse in 6 and a pansystolic prolapse in 3 patients. In 3 cases also an angiography was performed and in this way a mitral valve prolapse detected; hemodynamics and coronary arteries were normal in all 3 cases but in one case a mitral insufficiency and in one case an asynergy of the anterior wall was found. Pathophysiology, clinical symptoms and phonocardiographic, echocardiographic and angiographic findings in mitral valve prolapse syndrome are discussed.

Revelation of an obstructive hypertrophic cardiomyopathy in an elderly patient.

Hypertrophic cardiomyopathy (HCM) is classified as a primary cardiomyopathy. HCM is a clinically heterogeneous but relatively common autosomal dominant genetic heart disease that probably is the most frequently occurring cardiomyopathy. HCM is characterized morphologically and defined by a hypertrophied, nondilated left ventriculum (LV) in the absence of another systemic or cardiac disease that is capable of producing the magnitude of wall thickening evident (e.g., systemic hypertension, aortic valve stenosis). Most HCM patients have the propensity to develop dynamic obstruction to LV outflow under resting or physiologically provocable conditions, produced by systolic anterior motion of the mitral valve with ventricular septal contact. The phenotypic features of HCM may develop at any age from infancy to adulthood, and are characterized by a great heterogeneity in the extent, magnitude, and distribution of left ventricular hypertrophy. Hypertrophic obstructive cardiomyopathy (HOCM) often leads to heart failure, severe ischemia, severe symptoms and death. Determination of the exact site of the hypertrophy and of the obstruction of the left ventricular outflow tract, in asymmetric septal hypertrophy, establishes which is the best treatment strategy. In the treatment of HOCM, drug therapy with negatively inotropic drugs, percutaneous transluminal septal myocardial ablation by alcohol-induced septal branch occlusion, surgical myectomy and DDD pacemaker therapy are considered the therapeutical options. We present a case of an obstructive hypertrophic cardiomyopathy in an 84-year-old Italian woman with a left ventricular outflow tract (LVOT) peak gradient with the Valsalva maneuver of 188 mm Hg and with a history of first episode of syncope.

First_Aid_Step2

Systolic murmurs: Aortic stenosis: Harsh systolic ejection murmur; radiation to carotids. Mitral regurgitation: Holosystolic murmur; radiation to axillae or to carotids. Mitral valve prolapse: Midsystolic or late-systolic click. Flow murmur: Very common, and does not imply cardiac disease. Diastolic murmurs: Always abnormal. Aortic regurgitation: Early decrescendo murmur. Mitral stenosis: Midto late, low-pitched murmur. Heart auscultation locations from the upper right sternal border, upper left sternal border, lower left sternal border, and apex: All (Aortic) People (Pulmonic) Try (Tricuspid) McDonald’s (Mitral). Causes of CHF— Hypertension Endocrine Anemia Rheumatic heart disease Toxins Failure to take meds Arrhythmia Infection Lung (pulmonary Gallops: S3 gallop: Dilated cardiomyopathy (ﬂoppy ventricle), mitral valve disease; often normal in younger patients and in high-output states (e.g., pregnancy).

InternalMed_Harrison

Figure 271e-12 A 70-year-old patient with known cardiac murmur and progressive shortness of breath and a recent episode of syncope. Echocardiography shows severe calcific aortic stenosis. A heavily calcified aortic valve (arrow) is shown in the parasternal long-axis views (top panels) and short-axis view (bottom left). Doppler interrogation shows a peak transaortic velocity of 5.2 m/s consistent with a peak instantaneous gradient of 109 mmHg and a mean gradient of 66 mmHg, and a corresponding aortic valve area of <0.6 cm2 (lower right). Ao, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle. (See Videos 271e-8, 271e-9, and 271e-10.)

[Progression from hypertrophic obstructive cardiomyopathy to dilated cardiomyopathy. Apropos of 4 cases].

Four cases of hypertrophic obstructive cardiomyopathy diagnosed on clinical, phonomechanographic, echocardiographic and haemodynamic criteria progressing to dilated cardiomyopathy are reported. This evolution was observed over a number of years (up to 20 years) and was accompanied by a clinical aggravation in all cases with 2 deaths and atrial fibrillation in 3 of the 4 cases. The signs of intraventricular obstruction [systolic murmur, bulge on the carotid pulse tracing, systolic anterior motion of the mitral valve (SAM) and intraventricular pressure gradient] disappeared as the left heart chambers dilated with a reduction in ventricular wall motion and parietal thinning but no change in myocardial mass.

InternalMed_Harrison

Figure 271e-15 A 34-year-old woman with known cardiac murmur and syncope with a family history of sudden cardiac death. Echocardiogram shows classic findings of hypertrophic cardiomyopathy, including marked left ventricular wall thickness, particularly in the interventricular septum, notable in the parasternal long-axis view (upper left) and apical view (upper right). Note reverse septal curvature in the apical view (upper left). There is substantial flow acceleration through the left ventricular outflow tract (lower left) with evidence of a late peaking systolic gradient (arrow, lower right) caused by outflow tract obstruction. Ao, aorta; IVS, interventricular septum; LA, left atrium; LV, left ventricle; PW, posterior wall; RV, right ventricle. (See Videos 271e-13, 271e-14, and 271e-15.)

Syncope (medicine)

Typically, tachycardic-generated syncope is caused by a cessation of beats following a tachycardic episode. This condition, called tachycardia-bradycardia syndrome, is usually caused by sinoatrial node dysfunction or block or atrioventricular block. Obstructive cardiac lesion Blockages in major vessels or within the heart can also impede blood flow to the brain. Aortic stenosis and mitral stenosis are the most common examples. Major valves of the heart become stiffened and reduce the efficiency of the hearts pumping action. This may not cause symptoms at rest but with exertion, the heart is unable to keep up with increased demands leading to syncope. Aortic stenosis presents with repeated episodes of syncope. Rarely, cardiac tumors such as atrial myxomas can also lead to syncope.

Mitral valve prolapse.

Mitral valve prolapse is a condition that is being recognized with increased frequency. It is not known whether its incidence is increasing, or whether we are better able to diagnose it today. In the idiopathic or familial variety, the mitral valve pathology is almost always that of myxomatous degeneration. Some authors have suggested the presence of a cardiomyopathy because of significant left ventricular dysfunction in many cases. Idiopathic prolapse occurs predominantly in females, often at a young age, and may be associated with chest pain, dyspnea, fatigue, presyncope, syncope, and/or sudden death. The clinical findings are variable and typically consist of a nonejection click and/or late systolic murmur, heard best at the cardiac apex. Diagnosis can be confirmed by echocardiography and/or ventricular cineangiography, the latter permitting accurate recognition of the anatomy of the prolapsed leaflets. The complications of infective endocarditis, severe mitral insufficiency, and life-threatening ventricular arrhythmias represent the major problems of management. It is important to distinguish the idiopathic form of mitral valve prolapse from that due to coronary artery disease and to realize that mitral valve prolapse may occur in Marfan's syndrome, Turner's syndrome, or in association with secundum atrial septal defect or ruptured chordae tendineae. Typical clicks and/or murmurs have also been described in patients with a history of rheumatic fever and in hypertrophic cardiomyopathy. Although much descriptive knowledge has accumulated over the past 15 years, many unanswered questions remain regarding the idiopathic type of prolapse. What is the nature and cause(s) of myxomatous degeneration? What is the relation of the valve pathology to the left ventricular dysfunction? What is the relation of both of these factors to disabling chest pain, electrocardiographic changes, and life-threatening arrhythmias? Hopefully, answers to these and other important questions regarding mitral valve prolapse will be forthcoming.

Valvular heart disease

Minor tricuspid insufficiency is common in healthy individuals. In more severe cases it is a consequence of dilation of the right ventricle, leading to displacement of the papillary muscles which control the valve's ability to close. Dilation of the right ventricle occurs secondary to ventricular septal defects, right to left shunting of blood, eisenmenger syndrome, hyperthyroidism, and pulmonary stenosis. Tricuspid insufficiency may also be the result of congenital defects of the tricuspid valve, such as Ebstein's anomaly. Signs and symptoms Aortic stenosis Symptoms of aortic stenosis may include heart failure symptoms, such as dyspnea on exertion (most frequent symptom), orthopnea and paroxysmal nocturnal dyspnea, angina pectoris, and syncope, usually exertional.

Mitral valve replacement

Mitral stenosis and regurgitation The most common cause of mitral stenosis is rheumatic fever, seen mostly in the developing world. Other causes are mitral degenerative disease, severe calcification (elderly), congenital deformities, malignant carcinoid syndrome, neoplasm, left atrial appendage thrombus, endocarditic vegetations, certain inherited metabolic diseases, or complications of previous procedures at the aortic valve. Mitral stenosis causes left atrial pressure to increase, which, if left untreated, can lead to ventricular dilation, hypertrophy, atrial fibrillation, and thrombus creation. Symptoms include shortness of breath (dyspnea) on exertion, when lying flat (orthopnea) or during the night (paroxysmal nocturnal dyspnea), and fatigue.

InternalMed_Harrison

DIASTOLIC HeART MuRMuRS early Diastolic Murmurs (Fig. 51e-1E) Chronic AR results in a high-pitched, blowing, decrescendo, early to mid-diastolic murmur that begins after the aortic component of S2 (A2) and is best heard at the second right interspace (Fig. 51e-6). The murmur may be soft and difficult to hear unless auscultation is performed with the patient leaning forward at end expiration. This maneuver brings the aortic root closer to the anterior chest wall. Radiation of the murmur may provide a clue to the cause of the AR. With primary valve disease, such as that due to congenital bicuspid disease, prolapse, or endocarditis, the diastolic murmur tends to radiate along the left sternal border, where it is often louder than appreciated in the second right interspace. When AR is caused by aortic root disease, the diastolic murmur may radiate along the right sternal border. Diseases of the aortic root cause dilation or distortion of the aortic annulus and failure of leaflet

List of MeSH codes (C14)

– heart failure, congestive – cardiomyopathy, dilated – dyspnea, paroxysmal – edema, cardiac – heart neoplasms – heart rupture – heart rupture, post-infarction – ventricular septal rupture – heart valve diseases – aortic valve insufficiency – aortic valve stenosis – aortic stenosis, supravalvular – williams syndrome – aortic stenosis, subvalvular – cardiomyopathy, hypertrophic – discrete subaortic stenosis – heart murmurs – heart valve prolapse – aortic valve prolapse – mitral valve prolapse – tricuspid valve prolapse – mitral valve insufficiency – mitral valve stenosis – pulmonary atresia – pulmonary valve insufficiency – pulmonary valve stenosis – leopard syndrome – pulmonary subvalvular stenosis – tricuspid atresia – tricuspid valve insufficiency – tricuspid valve stenosis

Palpitations

Positive orthostatic vital signs may indicate dehydration or an electrolyte abnormality. A mid-systolic click and heart murmur may indicate mitral valve prolapse. A harsh holo-systolic murmur best heard at the left sternal border which increases with Valsalva may indicate hypertrophic obstructive cardiomyopathy. An irregular rhythm indicates atrial fibrillation or atrial flutter. Evidence of cardiomegaly and peripheral edema may indicate heart failure and ischemia or a valvular abnormality. Blood tests, particularly tests of thyroid gland function, are also important baseline investigations (an overactive thyroid gland is a potential cause for palpitations; the treatment, in that case, is to treat the thyroid gland over-activity).

InternalMed_Harrison

Death in patients with severe AS occurs most commonly in the seventh and eighth decades. Based on data obtained at postmortem examination in patients before surgical treatment became widely available, the average time to death after the onset of various symptoms was as follows: angina pectoris, 3 years; syncope, 3 years; dyspnea, 2 years; congestive heart failure, 1.5–2 years. Moreover, in >80% of patients who died with AS, symptoms had existed for <4 years. Among adults dying with valvular AS, sudden death, which presumably resulted from an arrhythmia, occurred in 10–20%; however, most sudden deaths occurred in patients who had previously been symptomatic. Sudden death as the first manifestation of severe AS is very uncommon (<1% per year) in asymptomatic adult patients. Calcific AS is a progressive disease, with an annual reduction in valve area averaging 0.1 cm2 and annual increases in the peak jet velocity and mean valve gradient averaging 0.3 meters/s and 7 mmHg, respectively

Does this patient have an abnormal systolic murmur?

Our objective was to review the available evidence of the precision and accuracy of the clinical examination for abnormal systolic murmurs. We conducted a MEDLINE search, manually reviewed all reference lists, and contacted authors of published studies. Each study was independently reviewed by 2 observers and graded for methodologic quality. We found that most studies were conducted using cardiologist examiners. In the clinical setting, the reliability of detecting systolic murmurs was fair (kappa, 0.30-0.48). The most useful findings for ruling in aortic stenosis are a slow rate of rise of the carotid pulse (positive likelihood ratio, 2.8-130), mid to late peak intensity of the murmur (positive likelihood ratio, 8.0-101), and decreased intensity of the second heart sound (positive likelihood ratio, 3.1-50). The most useful finding for ruling out aortic stenosis is the absence of murmur radiation to the right carotid artery (negative likelihood ratio, 0.05-0.10). Smaller, lower-quality studies indicate that cardiologists can accurately rule in and rule out mitral regurgitation, tricuspid regurgitation, hypertrophic cardiomyopathy, and echocardiographic mitral valve prolapse. We conclude that the clinical examination by cardiologists is accurate for detecting various causes of abnormal systolic murmurs. Studies of the clinical examination by noncardiologists are needed.

[Clinical characteristics of cardiac syncope in children].

To explore the clinical characteristics of cardiac syncope (CS) in children, and understand their significance in predicting the cardiac syncope. Twenty-three patients were referred to our department for evaluation of syncope. The diagnosis of the above cases was cardiac syncope. Each patient was interviewed using a standard questionnaire. The clinical histories and standard baseline electrocardiogram were analyzed to identify the variables contributing to the diagnosis of CS in children. A cardiac cause was identified in 23 syncopal patients presenting to the Department of Pediatrics, Peking University First Hospital: sick sinus syndrome in 7, congenital long QT syndrome in 4, third degree atrioventricular block in 2, supraventricular tachycardia in 2, ventricular tachycardia in 1, atrial fibrillation in 1, pacemaker dysfunction in 1, idiopathic pulmonary hypertension in 3, hypertrophic cardiomyopathy in 1, and dilated cardiomyopathy in 1. The average age of CS patients was 9 years. In totally 23 patients, exertion related syncope spells were found in 14 cases (60.9%), syncope spells at various position 7/23 (30.4%), absence of prodromes in 12/23 (52.2%), syncope spells with incontinence in 4/23 (17.4%), history of heart disease in 4/23 (17.4%). Abnormal standard baseline electrocardiogram was found in 21 cases (91.7%). The children with cardiac syncope have overt clinical features, especially abnormal findings in electrocardiogram and exertion related syncope spells are the most common clinical features.

Heart murmur

Tricuspid valve regurgitation presents as a holosystolic (pansystolic) murmur at the left lower sternal border with radiation to the left upper sternal border. Prominent v and c waves may be seen in the JVP (jugular venous pressure). The murmur will increase with inspiration. Hypertrophic obstructive cardiomyopathy (or hypertrophic subaortic stenosis) will be a systolic crescendo-decrescendo murmur best heard at the left lower sternal border. Valsalva maneuver will increase the intensity of the murmur, as will changing positions from squatting to standing. Atrial septal defect will present with a systolic crescendo-decrescendo murmur best heard at the left upper sternal border due to increased volume going through the pulmonary valve, and is associated with a fixed, split S2 and a right ventricular heave.

Aortic Coarctation Associated With Hypertrophic Cardiomyopathy in a Woman With Hypertension and Syncope: A Case Report With 8-Year Follow-Up.

Coarctation of the aorta (CoA) is a common congenital cardiovascular malformation with aortic narrowing in the region of the ligamentum arteriosum. Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy that is characterized by left ventricular wall thickening and likely left ventricular outflow tract (LVOT) obstruction. They are two irrelevant diseases, and their coexistence has not been reported before. Here, we described a young female patient who concurrently has CoA and HCM. The patient has had hypertension since 18-years old and complained of chest discomfort on effort and fatigue thereafter. Initially, she was diagnosed as having hypertrophic cardiomyopathy and primary hypertension. The presence of CoA was not found until she was 35 years old when she had an onset of paroxysmal supraventricular tachycardia (PSVT) and presented with syncope. Failure of the ablation procedure <ivia</i the femoral artery revealed the possibility of CoA and PDA that was confirmed by aortic CTA and angiography. CoA was then treated successfully with a covered stent, and the symptoms of the patient improved remarkably. Additionally, the patient had typical imaging features of HCM, and two novel HCM-causing heterozygous mutations were identified by genetic testing, DSP-encoding desmoplakin, and MYBPC3-encoding myosin-binding protein C. The HCM was suspected to be contributing to the clinical presentations of the patient and challenged the timely diagnosis of CoA. The 8-year follow-up on aortic CTA and angiography revealed no stent graft-related complications. Moreover, no changes in HCM-related imaging features were found in the follow-up echocardiography 8 years after the correction of aortic coarctation, which strengthened the diagnosis of HCM. Here, we reported the diagnostic challenges, management, and 8-yeasr follow-up findings in a rare case of CoA combined with HCM. The case highlighted the importance for physicians to exclude CoA in young hypertensive patients, and proved the efficacy of stent repair in treating CoA in older patients.

Pulsus bisferiens

Pulsus bisferiens, also known as biphasic pulse, is an aortic waveform with two peaks per cardiac cycle, a small one followed by a strong and broad one. It is a sign of problems with the aorta, including aortic stenosis and aortic regurgitation, as well as hypertrophic cardiomyopathy causing subaortic stenosis. Pathogenesis In hypertrophic cardiomyopathy, there is narrowing of the left ventricular outflow tract (LVOT) due to hypertrophy of the interventricular septum. During systole, the narrowing of the LVOT creates a more negative pressure due to the Venturi effect and sucks in the anterior mitral valve leaflet. This creates a transient occlusion of the LVOT, causing a midsystolic dip in the aortic waveform. Towards the end of systole, the ventricle is able to overcome the obstruction to cause the second rise in the aortic waveform.