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group_5_presentation_2_-_hyperbilirubinemia_jaundice [2017/10/29 15:32] mohamesb [Treatment] |
group_5_presentation_2_-_hyperbilirubinemia_jaundice [2018/01/25 15:18] (current) |
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| + | **LS4M03 ppt link:** [[https://docs.google.com/presentation/d/17I4UVA_GAagsoywBAQvyIQ6UZCuQBjTS8bzAhAupoAA/edit?usp=sharing]] | ||
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| ====== Introduction ====== | ====== Introduction ====== | ||
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| {{::screen_shot_2017-10-12_at_1.23.48_pm.png?500|}} {{::screen_shot_2017-10-12_at_1.44.12_pm.png?480|}} | {{::screen_shot_2017-10-12_at_1.23.48_pm.png?500|}} {{::screen_shot_2017-10-12_at_1.44.12_pm.png?480|}} | ||
| - | **Figure 3:** Excretion of bilirubin (structure on right) by the liver (Marshall, Bangert & Lapsley, 2012; google images) | + | **Figure 3:** Excretion of bilirubin (structure on right) by the liver (Marshall, Bangert & Lapsley, 2012; google images) |
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| - | Interestingly, bilirubin is a strong antioxidant and mild hyperbilirubinemia may have a protective effect against ischemic cardiovascular disease and cancer (Wang, Chowdhury J & Chowdhury N, 2006). In fact, a recent study looking at the history of colorectal cancer done on a large population reported the odds ratios to be reduced to 0.295 in men and 0.186 in women per 1 mg/dl increment in serum bilirubin levels (Wang, Chowdhury J & Chowdhury N, 2006). Furthermore, an inverse relationship between serum bilirubin levels and cancer mortality has also been reported (Wang, Chowdhury J & Chowdhury N, 2006). However, these findings do not suggest a direct cause-and-effect relationship and more research needs to be done in this area. | + | |
| ===== Pathophysiology of Bilirubin Metabolism ===== | ===== Pathophysiology of Bilirubin Metabolism ===== | ||
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| * Improper development of tooth enamel | * Improper development of tooth enamel | ||
| - | ====== Treatment ====== | + | ====== Treatment and Prevention====== |
| - | === Phototherapy === | + | ==== Phototherapy ==== |
| - | Currently, the most popular and effective intervention for neonatal hyperbilirubinemia is phototherapy. Phototherapy is a treatment which exposes a patient to light energy via lamps. The reason this form of therapy is used in jaundice is that it has been shown that when unconjugated bilirubin is exposed to light energy its structure changes to a lighter and less lipophilic stereoisomer, which can be excreted in bile or urine without conjugation. (Lightner & McDonagh, 1984). This process of bilirubin’s structural change through light exposure is called photoisomerization (Lightner & McDonagh, 1984). The bilirubin circulating in the dermal and subcutaneous areas, or the superficial capillaries and interstitial spaces, encounters the light, and photochemical reactions are undergone; structural and configurational isomerization and photo-oxidation transform the unconjugated bilirubin into water-soluble and non-toxic isomers which make them excretable (McDonagh, 2001). {{:phototherapy_mechanism.gif?350 |}} | + | Currently, the most popular and effective intervention for neonatal hyperbilirubinemia is phototherapy. Phototherapy is a treatment which exposes a patient to light energy via lamps. The reason this form of therapy is used in patient's with jaundice is because it has been shown that when unconjugated bilirubin is exposed to light energy, its structure changes to a lighter and less lipophilic stereoisomer which can be excreted in bile or urine without conjugation (Lightner & McDonagh, 1984). This process of bilirubin’s structural change through light exposure is called photoisomerization (Lightner & McDonagh, 1984). The bilirubin circulating in the dermal and subcutaneous areas, or the superficial capillaries and interstitial spaces, encounters the light and photochemical reactions are performed. Moreover, structural and configurational isomerization and photo-oxidation transforms the unconjugated bilirubin into a water-soluble and non-toxic isomer making them excretable (McDonagh, 2001). This form of treatment can be very helpful for individuals with reduced bilirubin-UGT enzyme activity, in which their ability to conjugated is limited {{:phototherapy_mechanism.gif?350 |}} |
| - | **Figure 9:** | + | |
| - | There are four factors that influence the efficacy of phototherapy: the wavelength of light, the irradiance (intensity) of light, the distance between the light source and skin, and the surface area of the body exposed to light. The most effective wavelength of light in degrading bilirubin is in the range of 400-520 nm, with the optimal wavelength being around 460 nm – this is blue light (Vreman, Wong & Stevenson, 2004). Blue light strikes the best balance between penetration of the skin and absorption by the unconjugated bilirubin (Maisels, 2005). Intuitively, there is a strong correlation between the intensity of light used, the surface area of skin exposed to light, short distances between the light source and body, and the rate at which bilirubin levels decline (Tan, 1982). | ||
| - | Phototherapy is mainly used for neonatal jaundice to prevent kernicterus and the potentially irreversible brain damage. When babies are born, their hepatocytes may not be entirely functional yet, which prevents sufficient excretion of bilirubin. Because babies’ blood-brain barriers are still weak, an excess of free unconjugated bilirubin circulating in the blood may pass through and cause neurologic damage to the brain (Kriss, Kollias & Ball, 1995). Phototherapy is not used on adults with jaundice since their hyperbilirubinemia is a result of hemolysis, chronic hepatitis, liver damage through alcohol, and other diseases of the liver; the condition causing jaundice is treated in adults, and not jaundice itself. | + | There are four factors that influence the efficacy of phototherapy: the wavelength of light, the irradiance (intensity) of light, the distance between the light source and skin, and the surface area of the body exposed to light. The most effective wavelength of light in degrading bilirubin is in the range of 400-520 nm, with the optimal wavelength being around 460 nm – which is blue light (Vreman, Wong & Stevenson, 2004). Blue light strikes the best balance between penetration of the skin and absorption by the unconjugated bilirubin (Maisels, 2005). Intuitively, there is a strong correlation between the intensity of light used, the surface area of skin exposed to light, short distances between the light source and body, and the rate at which bilirubin levels decline (Tan, 1982). |
| - | === Exchange Transfusions === | + | Phototherapy is mainly used as a treatment for neonatal jaundice to prevent kernicterus and potentially irreversible brain damage. When babies are born, their hepatocytes may not be entirely functional yet which prevents sufficient excretion of bilirubin. Since the blood-brain barriers of neonates are still weak, an excess of free unconjugated bilirubin circulating in the blood may pass through and cause neurologic damage to the brain (Kriss, Kollias & Ball, 1995). In contrast to babies, phototherapy is not performed on adults with jaundice since their hyperbilirubinemia is usually a result of hemolysis, chronic hepatitis, liver damage through alcohol, and other diseases of the liver. Furthermore, the condition causing the clinical symptoms of jaundice is treated in adults instead of the actual jaundice itself. |
| - | Blood exchange transfusion consists of slowly replacing the recipient’s blood with donor blood, which helps in lowering the bilirubin levels. This once was the main treatment for neonatal jaundice until phototherapy was discovered. Exchange transfusion is rare in developed countries, and it is only used in emergencies of severe hyperbilirubinemia when phototherapy is not proving to be adequately fast (Murki & Kumar, 2011). Prenatal and postnatal care has also significantly improved over time, which has been shown to be a factor in the decline of the frequency of exchange transfusions (Steiner, Bizzarro, Ehrenkranz, et. al, 2007). Exchange transfusion is still common in developing countries (Murki & Kumar, 2011). | + | **Figure 9:** The effect of phototherapy in individuals with deficient UGT activity and decreased ability to conjugate and excrete bilirubin. |
| + | ==== Exchange Transfusions ==== | ||
| - | ====== Prevention ====== | + | Blood exchange transfusion consists of slowly replacing the recipient’s blood with donor blood, which helps to lower the bilirubin levels. This once was the main treatment for neonatal jaundice until phototherapy was discovered. Exchange transfusion is rare in more developed countries, and it is only used in emergencies of severe hyperbilirubinemia when phototherapy is not proving to be adequately fast (Murki & Kumar, 2011). Prenatal and postnatal care has also significantly improved over time, which has been shown to be a factor in the decline of the frequency of exchange transfusions (Steiner, Bizzarro, Ehrenkranz, et. al, 2007). On the other hand, exchange transfusions are still quite common in developing countries that lack sufficient resources for phototherapy (Murki & Kumar, 2011). |
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| + | ==== Prevention ==== | ||
| Studies with rats show fasting increases enterohepatic circulation of bilirubin because of the reduced intestinal motility and increased reuptake of bile pigments into blood circulation (Kotal, Vitek, & Fevery, 1996). Another study, this time with neonates with hyperbilirubinemia undergoing phototherapy, shows that being fed with breast milk along with supplemental formula improved the efficacy of phototherapy more than neonates fed with only formula or only breast milk (Tan, 1998). The above findings imply more frequent feeding of neonates, especially with breast milk and formula supplements, can act as a somewhat preventative measure from severe hyperbilirubinemia and can quicken the treatment process. | Studies with rats show fasting increases enterohepatic circulation of bilirubin because of the reduced intestinal motility and increased reuptake of bile pigments into blood circulation (Kotal, Vitek, & Fevery, 1996). Another study, this time with neonates with hyperbilirubinemia undergoing phototherapy, shows that being fed with breast milk along with supplemental formula improved the efficacy of phototherapy more than neonates fed with only formula or only breast milk (Tan, 1998). The above findings imply more frequent feeding of neonates, especially with breast milk and formula supplements, can act as a somewhat preventative measure from severe hyperbilirubinemia and can quicken the treatment process. | ||
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| ====== Implications & Future Research ====== | ====== Implications & Future Research ====== | ||
| - | === Focus: Stanate (Stannsoporfin) === | + | ====Protective Effects of Mild Hyperbilirubinemia==== |
| + | Interestingly, bilirubin is a strong antioxidant and mild hyperbilirubinemia may have a protective effect against ischemic cardiovascular disease and cancer (Wang, Chowdhury J & Chowdhury N, 2006). In fact, a recent study looking at the history of colorectal cancer done on a large population reported the odds ratios to be reduced to 0.295 in men and 0.186 in women per 1 mg/dl increment in serum bilirubin levels (Wang, Chowdhury J & Chowdhury N, 2006). Furthermore, an inverse relationship between serum bilirubin levels and cancer mortality has also been reported (Wang, Chowdhury J & Chowdhury N, 2006). However, these findings do not suggest a direct cause-and-effect relationship and more research needs to be done in this area. | ||
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| + | ====Focus: Stanate (Stannsoporfin)==== | ||
| Stanate (Stannsoporfin) is in late-stage development at WellSpring pharmaceuticals and is being used for the treatment of neonatal jaundice and prevention of kernicterus (“Compassionate Use of Stanate ™ “, 2013). Stanate’s mechanism of action specifically inhibits the enzyme that blocks the conversion of heme into bilirubin. Since Kernicterus is attributed to high levels of bilirubin, this drug is aimed to stop this excess production. Tin mesoporphyrin IX dichloride is the chemical compound that is being investigated for use in infant jaundice. This drug, given by injections, specifically targets heme oxygenase 1 and 2, which are involved in the cleavage of heme in order to be converted to bilirubin. It is mainly executed when the neonate has very high bilirubin levels and is failing phototherapy. Also, it is used when a family refuses exchange blood transfusion for religious purposes. The results of the clinical trial demonstrated that the use of this drug significantly lowered blood bilirubin levels, and resulted in fewer and shorter uses of phototherapy, compared with placebo (“Compassionate Use of Stanate ™ “, 2013). | Stanate (Stannsoporfin) is in late-stage development at WellSpring pharmaceuticals and is being used for the treatment of neonatal jaundice and prevention of kernicterus (“Compassionate Use of Stanate ™ “, 2013). Stanate’s mechanism of action specifically inhibits the enzyme that blocks the conversion of heme into bilirubin. Since Kernicterus is attributed to high levels of bilirubin, this drug is aimed to stop this excess production. Tin mesoporphyrin IX dichloride is the chemical compound that is being investigated for use in infant jaundice. This drug, given by injections, specifically targets heme oxygenase 1 and 2, which are involved in the cleavage of heme in order to be converted to bilirubin. It is mainly executed when the neonate has very high bilirubin levels and is failing phototherapy. Also, it is used when a family refuses exchange blood transfusion for religious purposes. The results of the clinical trial demonstrated that the use of this drug significantly lowered blood bilirubin levels, and resulted in fewer and shorter uses of phototherapy, compared with placebo (“Compassionate Use of Stanate ™ “, 2013). | ||
| - | === Focus: Glycerin suppositories === | + | ====Focus: Glycerin suppositories==== |
| Glycerin suppositories are a form of laxatives, normally used to relieve constipation. A study using glycerine suppositories was conducted to determine if it would reduce jaundice in premature infants with respect to decreasing exposure to phototherapy (“Glycerin Suppositories to Reduce Jaundice in Premature Infants”, 2012). This randomized, double-blind study incorporated 75 premature babies with physiological hyperbilirubinemia between the ages of 30-35 weeks. This was developed based on previous research showing that delayed meconium (earliest stool of infant) evacuation is a contributing factor to persistent neonatal jaundice. Several studies have been performed, but the results are inconclusive. One study found that a subgroup of male infants with blood group type A displayed a lower mean total serum bilirubin level after induction of earlier meconium with glycerine suppositories. However, in a different study, randomized groups were given glycerine at 12 hours of life, and bilirubin levels were followed for the first 7 days of life. This did not have an effect on serum bilirubin levels in the first 7 days. In the clinical trial through the University of Rochester, total serum bilirubin levels dropped by 0.7 mg/dL when glycerine suppository was employed (“Glycerin Suppositories to Reduce Jaundice in Premature Infants”, 2012). This trial has now been completed, and glycerin being mainly used for constipation, as no concrete evidence fully supports this method in regards to neonatal jaundice. | Glycerin suppositories are a form of laxatives, normally used to relieve constipation. A study using glycerine suppositories was conducted to determine if it would reduce jaundice in premature infants with respect to decreasing exposure to phototherapy (“Glycerin Suppositories to Reduce Jaundice in Premature Infants”, 2012). This randomized, double-blind study incorporated 75 premature babies with physiological hyperbilirubinemia between the ages of 30-35 weeks. This was developed based on previous research showing that delayed meconium (earliest stool of infant) evacuation is a contributing factor to persistent neonatal jaundice. Several studies have been performed, but the results are inconclusive. One study found that a subgroup of male infants with blood group type A displayed a lower mean total serum bilirubin level after induction of earlier meconium with glycerine suppositories. However, in a different study, randomized groups were given glycerine at 12 hours of life, and bilirubin levels were followed for the first 7 days of life. This did not have an effect on serum bilirubin levels in the first 7 days. In the clinical trial through the University of Rochester, total serum bilirubin levels dropped by 0.7 mg/dL when glycerine suppository was employed (“Glycerin Suppositories to Reduce Jaundice in Premature Infants”, 2012). This trial has now been completed, and glycerin being mainly used for constipation, as no concrete evidence fully supports this method in regards to neonatal jaundice. | ||
