This document discusses the management of hyperbilirubinemia in newborns. It begins by covering bilirubin metabolism, sources of bilirubin, and inherited disorders that can cause jaundice. It then addresses physiological and non-physiological hyperbilirubinemia in newborns. The management section covers evaluation, treatment options like phototherapy and exchange transfusion, and measures to prevent bilirubin toxicity and kernicterus. Key points include the various causes of neonatal jaundice, methods for estimating bilirubin levels, and the mechanisms by which phototherapy works to reduce serum bilirubin.
Hyperbilirubinemia didactics at Neonatal Intensive Care Unit
Source: Nelson's Textbook of Pediatrics 19th edition
Most pictures were taken from Google images
Please find the power point on Phototherapy in jaundice . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Hyperbilirubinemia didactics at Neonatal Intensive Care Unit
Source: Nelson's Textbook of Pediatrics 19th edition
Most pictures were taken from Google images
Please find the power point on Phototherapy in jaundice . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Management of child with neonatal jaundiceNEHA MALIK
Newborn jaundice is a yellowing of a baby's skin and eyes. Newborn jaundice is very common and can occur when babies have a high level of bilirubin, a yellow pigment produced during normal breakdown of red blood cells.
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This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
Management of child with neonatal jaundiceNEHA MALIK
Newborn jaundice is a yellowing of a baby's skin and eyes. Newborn jaundice is very common and can occur when babies have a high level of bilirubin, a yellow pigment produced during normal breakdown of red blood cells.
follow me on my YouTube channel :- medic o mania
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
Neonatal jaundice (hyperbilirubinemia) by Rajiv MavachiRajiv Mavachi
Jaundice is the most common condition that requires medical attention in newborns. The yellow coloration of the skin and sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin.
Dear Viewers,
Greetings from “ Surgical Educator”
Today I have uploaded a video on one of the congenital causes for obstructive jaundice- Biliary Atresia. In this episode, I am discussing about the etiology, types, clinical features, investigations, treatment and surgical outcome of Biliary Atresia. I hope you will enjoy the video. You can watch all my surgical teaching video casts in the following link: surgicaleducator.blogspot.com.
LIVER FUNCTION TESTS BY DR. PREMJEET KAUR, ASSISTANT PROFESSOR BIOCHEMISTRY Premjeet Kaur
BY THE END OF THIS PRESENTATION YOU WILL BE ABLE TO ANSWER WHAT, WHY, WHICH ABOUT LIVER FUNCTION TESTS , WHAT IS JAUNDICE , METABOLISM OF HEME , FORMATION OF BILE PIGMENTS FROM HEME , TRASFER OF LILIRUBIN FROM BLOOD TO BILE , DETERMINATION OF SERUM BILIRUBIN, RETENTION JAUNDICE , REGURGITATION JAUNDICE ,DETERMINATION OF AMMONIA IN BLOOD ,ANTIPYRINE TEST, SERUM ENZYMES IN LIVER DISEASE, ASSESING EXTENT OF LIVER DAMAGE , DIAGNOSIS OF SUBCLINICAL JAUNDICE , BCG TEST , PLASMA PROTEINS , DETOXIFICATION FUNCTION OF LIVER
What is the Difference Between Conjugated and Unconjugated Bilirubin?Sumit Sharma
Bilirubin is a biochemical parameter of your liver function test. Your doctor uses this tool to diagnose liver disease.
In the human body, bilirubin is a waste product of your hemoglobin produced during the red blood cells breakdown in the spleen.
Although bilirubin does not have a specific function, it is generally a component of bile juice. It is also called a bile pigment, which is yellow in color.
There are two forms of bilirubin in our blood.
One is unconjugated bilirubin, which forms during the breakdown of red blood cells, and the other is conjugated, which starts during metabolism in the liver.
The unconjugated bilirubin is a catabolic product of red blood cells. This non-conjugated compound is also known as indirect bilirubin.
Some possible reasons or diseases associated with unconjugated hyperbilirubinemia –
1. Hemolytic anemia
2. Neonatal Jaundice
3. Genetic factors
4. Drug induced unconjugated hyperbilirubinemia
On the other hands, Conjugated bilirubin is generally formed after the glucuronidation of the unconjugated bilirubin.
The conjugation process occurs in your liver and converts your unconjugated bilirubin into conjugated bilirubin. This type of glucuronidation compound is also known as direct bilirubin.
In simple words, direct bilirubin means conjugated bilirubin.
The elevated conjugated bilirubin indicates Conjugated hyperbilirubinemia.
This condition is most commonly seen in cholestatic liver disease.
Cholestatic is a medical condition where the flow of bile juice gets reduced or stopped. You may have this cholestatic liver disease in two forms – Intrahepatic and extrahepatic obstruction.
In this article, we will discuss bilirubin, metabolism of bilirubin, normal range of bilirubin, and its clinical relevance. Further, we will also know the difference between conjugated and unconjugated bilirubin.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
3. PATHOPHYSIOLOGICAL
IMPORTANCE OF BILIRUBIN
METABOLISM
It is the end product of heme degradation.
Serum bilirubin level is an important clinical
marker of hepatobiliary excretory function.
Bilirubin is an endogenous model for plasma
carriage and hepatic throughput of organic
anions.
Hepatic uptake, storage, conjugation and
excretion of bilirubin are finely balanced.
Therefore, enhancement of bilirubin throughput
requires coordinated induction of multiple genes,
which may be mediated by nuclear receptors.
5. Early bilirubin
(15-20%)
0- 3 days
Late bilirubin
(65%)
40- 80 days
Non-Hb
sources (liver)
Increased
erythropoiesis
Erythrocyte
sources
Early and late labeled peaks of radioisotope incorporation into bilirubin
After injection of labeled porphyrin precursor (14
C-glycine)
6. Opening of the heme ring and
Enzyme-catalyzed formation of bilirubin
7. Bilirubin throughput: schema of a hepatocyteBilirubin throughput: schema of a hepatocyte
Sinusoidal
surface
Canalicular
surface
Tight
junction
Liver
sinusoid
Fenestrated
endothelium
8. Bilirubin circulates bound to serum albumin.
BBalb
Albumin-
binding:
Keeps bilirubin
soluble
Prevents
tissue deposi-
tion.
Prevents
renal excretion
Drugs that
displace
bilirubin from
albumin may
precipitate
kernicterus:
Sulfonamides
Coumadin, etc.
9. Bilirubin circulates bound to serum albumin.
At the sinusoidal surface of hepatocytes, it dissociates
from albumin.
BBalb
10. Bilirubin circulates bound to serum albumin.
At the sinusoidal surface of hepatocytes, it dissociates
from albumin.
BBalb
11. Bilirubin circulates bound to serum albumin.
At the sinusoidal surface of hepatocytes, it dissociates
from albumin.
BB
alb
12. Bilirubin circulates bound to serum albumin.
At the sinusoidal surface of hepatocytes, it dissociates
from albumin.
BB
alb
13. Bilirubin enters through the sinusoidal surface, probably by
facilitated diffusion.
Uptake is energy independent and bidirectional.
BB
Bilirubin uptake
is reduced:
In neonates
In cirrhosis
From drug
effect:
novobiocin
In some cases
of Gilbert
syndrome
14. B
Inside the hepatocyte, bilirubin binds to cytosolic proteins
termed ligandins, which are the same as glutathione-S-
transferases (GSTs).
GSTs
B
GST binding
inhibits the
efflux of bilirubin,
thereby increasing
its net uptake
16. B
Conjugation of bilirubin with glucuronic acid is catalyzed
by UGT1A1, which transfers glucuronic acid from
UDP-glucuronic acid to bilirubin
GSTs
UDPUDPGAGA UDPUDP
BB GAGA
UGT1A1
B
Conjugation with
glucuronic acid
makes bilirubin
water-soluble and
non-toxic.
Glucuronidation
is essential for
biliary excretion
of bilirubin.
17. UDP-glucuronosyltransferasesUDP-glucuronosyltransferases
(UGTs)(UGTs)
• UGTs are ER proteins that convert many internal andUGTs are ER proteins that convert many internal and
exogenous toxins to non-toxic metabolites.exogenous toxins to non-toxic metabolites.
• UGT’s are a family of enzymes concentrated in the liver.UGT’s are a family of enzymes concentrated in the liver.
• One UGT isoform, UGT1A1, conjugates bilirubin and isOne UGT isoform, UGT1A1, conjugates bilirubin and is
essential for its excretion.essential for its excretion.
• Inherited UGT1A1 deficiency causes jaundice.Inherited UGT1A1 deficiency causes jaundice.
Substrate
UDPGAUDPGA
•UGTUGT
GlucuronideGlucuronide
UDPUDP
18. Inherited disorders of bilirubin metabolism causingInherited disorders of bilirubin metabolism causing
Unconjugated HyperbilirubinemiaUnconjugated Hyperbilirubinemia
• Crigler-Najjar syndromeCrigler-Najjar syndrome
type 1:type 1:
• Crigler-Najjar syndromeCrigler-Najjar syndrome
type 2:type 2:
• Gilbert syndrome:Gilbert syndrome:
Virtually no UGT1A1 activityVirtually no UGT1A1 activity
UGT1A1 activity below 10%UGT1A1 activity below 10%
UGT1A1 activity ~30%UGT1A1 activity ~30%
19. NEONATAL HYPERBILIRUBINEMIA
• Clinical jaundice appears in newborns when the bilirubin levels is more than
7 mg/dl
• 85% of term newborns and most of the premature infants develop clinical
jaundice
• 6% have bilirubin more than 12.9mg/dl and 35 have bilirubin more than 15
mg/dl.
20. PHYSIOLOGICAL
HYPERBILIRUBINEMIA
• Serum UCB rises to >2mg/dl in first week of life
• Peaks to 6- 8 mg/dl by 3 to 5 days of age
• This normal jaundice is attributed too following conditions:
Increased rbc volume per kg
Increased ineffective erythropoiesis and increased turnover of non heme
proteins
Increased enterohepatic circulation
Decreased uptake of bilirubin from plasma caused by decreased ligandin
Defective conjugation due to decreased UGT activity
Decreased hepatic excretion of bilirubin
21. NON PHYSIOLOGICAL
HYPERBILIRUBINEMIA
• Onset of jaundice is before 24 hours
• Elevation of serum bilirubin that requires phototherapy
• A rise in serum bilirubin levels of >0.2 mg/dl/hour
• Signs of underlying diseases in an infant(vomiting, lethargy, poor feeding,
excessive weight loss
• Jaundice persisting after 8 days in a term infant or after 14 days in a
premature infant.
22. POINTS TO BE NOTED IN HISTORY..
1. A family history of jaundice , anemia, splenectomy or early gallbladder
disease suggests hereditary hemolytic anemia (spherocytosis,
G6PD deficiency)
2. A family history of liver disease may suggest galactosemia, alpha-1 anti
trypsin deficiency, tyrosinosis, hypermethionemia, gilberts syndrome,
criggler najjar syndrome type1 and 2 and cystic fibrosis
3. Sibling with jaundice or anemia may suggest blood group incompatibility
4. Maternal illness during pregnancy may indicate congenital viral infection /
toxoplasmosis
23. • Maternal drugs may interfere with bilirubin metabolism like sulfonamides or
may cause hemolysis in g6pd deficient infants.
• Labour and delivery history may show trauma associated with extravascular
bleeding and hemolysis. Oxytocin use in labour may be associated with
neonatal hyperbilirubinemia
• Infants with HIE , delayed cord clamping.
• Delayed / infrequent stooling
24. BREAST FEEDING JAUNDICE BREAST MILK JAUNDICE
Higher bilirubin levels in infants who are
exclusively breast fed after day 3 of life
Peak level of bilirubin is >12 mg/dl in breast fed
infants
Main factor responsible for breast feeding
jaundice is decreased in take of milk that leads
to slower eliminationof bilirubin and increased
entero hepatic circulation
Late onset of more than 4 days after life
Bilirubin continues to rise and may reach upto
20 to 30 mg/dl by 14 days.
Mechanism thought to be due to unidentified
factors in the milk interfering with the bilirubin
metabolismand due to increased beta
glucorinidase in breast milk causing increased
enterohepatic circulation.
25. POINTS TO BE NOTED IN THE
PHYSICAL EXAMINATION• Prematurity
• SGA ----------- polycythemia and in-utero infection
• Microcephaly ---------- in-utero infection
• Extra vascular blood bruising , cephalhematoma
• Pallor ---------------- hemolytic anemia or extra vascular blood loss
• Petechiae associated withcongenital infection, sepsis or erythroblastosis
• HSM --------- hemolytic anemia, congenital infection/ liver disease
• Omphalitis
• Chorioretinitis ------------- congenital infection
• Evidence of hypothyroidism
26.
27.
28.
29.
30. METHODS OF BILIRUBIN
ESTIMATION
• Visual inspection is not a reliable method of bilirubin estimation
• Screening of total serum bilirubin (TSB) collected predischarge from the baby
and plotted on an hour specific normogram helps to identify the infants at
risk.
• Trans cutaneous bilirubin measurement using multiple wavelength analysis
can reliably estimate serum bilirubin levels
31. TRANSCUTANEOUS BILIRUBIN ESTIMATION
ADVANTAGES DISADVANTAGES
• Reliably estimates irrespective of skin
pigmentation post natal age and weight of
infant
• Reduce the number of invasive blood tests
performed
• Reduce the health care costs
• It’s a screening tool and needs to confirm
the value with total serum bilirubin levels
when
1. TcB is > 70 th percentile for the
phototherapy value
2. When TcB exceeds more than 75th
percentile in bhutani’s normogram
3. At follow up if TcB is more than 13 mg/dl.
• TcB monitoring is unreliable after
phototherapy has begun due to bleaching
of skin.
32. • End tidal corbon monoxide (ETCOc)
o Offers insight into the underlying pathological process contributing to
hyperbilirubinemia
o Only parameter that provide direct information on the rate of bilirubin
production
o Can differentiate between infants with increased production, decreased
elimination or decreased conjugation if the test is used in combination with total
serum bilirubin levels
33. OTHER CLINICAL TESTS TO BE
DONE..
1. Blood type , Rh and antibody screen of the mother
2. Blood test, Rh and antibody screen if the infant
• Routinely recommended if the mother is Rh negative
• Peripheral smear for RBC morphology and reticulocyte count
• Hematocrit
• Identification of antibody on infants RBC if result of direct Coomb’s test is
positive
• Direct bilirubin
• A G6PD screen in male infants
34. • In cases of prolonged jaundice
Measure the direct component
Test for liver disease
Congenital infection
Sepsis, metabolic defects
Hypothyroidism
TPN is an important cause for prolonged hyperbilirubinemia
35. BILIRUBIN TOXICITY
• Bilirubin enters the brain as free unbound bilirubin or bilirubin bind to albumin
in case of disrupted blood-brain barrier.
• FFAs and some drugs interfere with the binding of bilirubin to albumin
• The blood brain barrier is disrupted in cases of hyperosmolarity, asphyxia and
hypercarbia.
• More permeable in premature infants.
36. KERNICTERUS
• Pathological diagnosis
• Yellow staining of brain with bilirubin and evidence of neuronal injury
• Most commonly in basal ganglia, various cranial nuclei, brainstem nuclei,
cerebellar nuclei, hippocampus, anterior horn cells of spinal cord.
• Microscopically there is necrosis, neuronal loss and gliois.
• Clinically characterized by athetosis, auditory neuropathy, upward gaze
limitation, dental dysplasia and intellectual defects.
37. ACUTE BILIRUBIN
ENCEPHALOPATHY
3 phases :
1.Early phase : hypotonia, lethargy, high-pithced cry and poor suck
2.Intermediate phase : hypertonia of extensor muscles, irritability, fever and
seizures. Mostly fatal. If infants survive this phase then chronic bilirubin
encephalopathy (clinical diagnosis of kernicterus is made).
3.Advanced phase : pronounced ophisthotonus, shrill cry, apnoea, seozures,
coma and death.
38. MANAGEMENT OF UNCONJUGATED
HYPERBILIRUBINEMIA
• GENERAL PRINCIPLES
• PREVENTIVE MEASURES AND EARLY IDENTIFICATION OF CAUSE IMPORTANT
• ANY MEDICATION THAT INTERFERE WITH BILIRUBIN METABOLISM/ INTEGRITY OF
BLOOD-BRAIN BARRIER SHOULD BE DISCONTINUED
• CORRECT INADEQUATE FEEDING OF INFANTS AND EVACUATION OF MECONIUM
• ASPIRATION OF CEPHALHEMATOMA
• TREATMENT OF SEPSIS AND HEPATITIS
• CORREECT HYPOTHYROIDISM IF PRESENT
39. • ROLE OF PHENOBARBITONE:
• Barbiturates shown to improve the maturation of microsomal enzymes,
ligandin and gludoronyl transferace thus improving the uptake conjugation
and maturation of bilirubin
• Lag period of 48 to 72 hours exists before enzyme activity is induced by
phenobarbitone so is administered within 72 hours of life even administered
prenatally
• Indicated in infants with
i. Cord bili >2.5 mg/dl
ii. Early onset jaundice due to any cause
iii. Difficult or instrumental / oxytocin induced delivery
iv. G6PD deficiency and type ii crigler najjar syndrome
• Added benefit of phenobarbitone is that it protects fetal brain against
hypoxic damage and may reduce the incidence of intraventricular
hemorrhage.
40. • Clofibrate is another drug which is a potent enhancer of glucoronyl
transferace than phenobarbital .
• 100% increase in hepatic metabiolism in one study in one week
• But it is slow in action and takes several days for its action .
42. PHOTOTHERAPY
• Relatively safe and effective method for treatment of neonatal
hyperbilirubinemia
• Bilirubin absorbs light maximally at 425- 475nm
• 3 photochemical reactions occur when bilirubin is exposed to light:
A. Structural isomerization
B. Photoisomerization
C. Photo- oxidation
43. • STRUCTURAL ISOMERIZATION
• Intramolecular cyclization of bilirubin to lumirubin.
• Lumirubin is rapidly excreted in bile and urine without conjugation
• The conversion is irreversible
• Most important pathway in the lowering of serum bilirubin
• Strongly related to the dose of phototherapy used in the range of 6 to 12 micro
watts/cm^2/ nm
44. N
H
M
V
O
N
H
M CH2
OH
CH2
N
H
N
H
CH2
CH2
C
OOH M M
V
O
CH2
C
O
Internal hydrogen bonds are disrupted
transiently upon exposure of bilirubin to light.
C
C
The dipyrrole carbon bridges switch direction.
49. Phototherapy changes the
configuration of bilirubin making
it transiently water soluble
• Photo isomerization
• Occurs in extravascular spaces of skin
• The natural isomer of UCB is converted to less toxic polar isomer and it diffuses
into blood and is excreted in to bile without conjugation
• But it’s a reversible reaction and the UCB thus formed again will be reabsorbed
from the gut
• Not the major pathway of bilirubin is excretion after starting phototherapy
• Photo – oxidation
• Converts bilirubin to small polar compounds that are excreted in urine
• Least important reaction for lowering of bilirubin
50. INDICATIONS OF PHOTOTHERAPY
• Levels of bilirubin are hazardous to the infant although it has not reached
the levels requiring exchange transfusion
51. • Prophylactic phototherapy is indicated in
• ELBW infant and Severely bruised infants where bilirubin is anticipated to
increase rapidly
• In hemolytic disease of newborn when rise in serum bilirubin is plotted
• phototherapy is contraindicated in
• Infants with direct hyperbilirubinemia caused by liver disease or obstructive
jaundice, and phototherapy may lead to bronze baby syndrome
52. TECHNIQUE OF PHOTOTHERAPY
• Effective phototherapy depends on :
• Light spectrum
• Irradiance
• Distance from the infant
• Extent of skin exposure
• Conventional phototherapy delivers spectral irradiance at infants level of 8
to 10 micro watts/cm^2/nm, 430 to 490 nm when positioned at 20cm above
the infant
• Intensive phototherapy delivers atleast 30micro watt/cm^2/nm
53. • Methods to increase the efficacy of phototherapy:
• Reducing the efficacy of phototherapy unit and infant to 15 to 20 cm
• Using compact fluorescent tubes
• Providing double surface phototherapy
• Using slings/ cloth of white colout to reflect light on to the baby
• Using high intensity gallium nitride light emitting diodes
54. PRECAUTIONS TO BE TAKEN IN
PHOTOTHERAPY
• Eye patches and genital shield to be ensured
• Infants are turned every 2 hours
• Eye patches should not occlude the nares as asphyxia and apnoea can
result
• Infant temperature should be properly maintained and servo controlled
• Infants should be weighed daily
• Skin colour is NOT a guide to bilirubin level so bilirubin has to repeated every
10 to 12 hours
55. SIDE EFFECTS OF PHOTOTHERAPY
1. Insensible water loss – especially those under radiant warmers. Term infants
40% and pre term infants 80% - 190%, servo controlled warmers decrease
this water loss
2. Redistributuin of blood flow -
• in term infants the cerebral and pulmonary velocity increases and the left
ventricular and renal velocity decreases. Returns to normal after discontinuation
of phototherapy
• In preterm infants the cerebral blood flow velocity increases and the renal bood
flow decreases. Also the usual post prandial increase in superior mesenteric
artery blood flow is blunted
56. 4. Watery diarrhea and increased fecal loss. The diarrhea is due to
increased bile salts and UCB in the bowel.
5. Low calcium levels seen in preterm infants receiving phototherapy
6. Retinal damage
7. Tanning of skin
8. Bronze baby syndrome
9. Mutations, sister chromatid exchange and DNA strand breakage
10. Tryptophans are reduced. Also methionine and histidine.
57. EXCHANGE TRANSFUSION
• Removes the partially hemolysed and antibody coated RBCs as well as
unattached antibodies and replaces it with donor RBCs lacking the
sensitizing antigen
• Within in half an hour of exchange bilirubin levels decrease to 60% of its
value
• Furthur increase in post exchange bilirubin is due to the antibody coated
RBCs sequestrated in bone marrow and spleen.
58. INDICATIONS OF EXCHANGE
TRANSFUSION
• When phototherapy fails to prevent a rise in bilirubin to toxic levels
• To correct anemia and heart failure in hydropic infants with hemolytic
disease
• To stop hemolysis and bilirubin production by removing antibody and
sensitized RBCs
• In hemolytic disease immediate exchange is usually indicated if:
• Cord bilirubin level is more than 4.5 mg/dl and cord Hb level is under 11
mg/dl.
• Bilirubin level is rising more than 1mg/dl/hour despite phototherapy or more
than 0.5 mg/dl/hour if Hb is between 11 and 13 mg/dl
• Progression of anemia despite adequate control of bilirubin levels
59.
60. BLOOD FOR EXCHANGE
TRANSFUSION• We use fresh (< 7 days old), irradiated and reconstituted whole blood(PCV
45%-50%) made from PRBCs and FFP collected in CPD.
• In Rh hemolytic disease blood should be type Rh negative cross
mathched against the mother
• In ABO incompatibility blood should be type O Rh negative or Rh
compatible with the mother and infant, be cross mathched against the
mother and the infant and have low titre of naturally occurring anti –a or
anti- b antibodies. Usually type O cells with AB plasma used
• In other isoimmune hemolytic diseases, blood should not contain
sensitizing antigen cross matched against the mother.
• Double the volume of infants blood is used for exchange
transfusion(160ml/kg)
61. TECHNIQUE OF EXCHANGE
TRANSFUSION
Infant under servo controlled radiant warmer and cardiac, blood pressure,
and oxygen saturation monitor in place
An assistant should be assigned to the infant to record volume of blood,
observe the infant and check vital signs
Measurement of potassium and pH of the blood may be indicated if the
blood is > 7 days old or if metabolic abnormalities are noted following
exchange transfusion
62. • Blood should be warmed to 37 c⁰
• Sterile technique to be used. Old,dried umbilical cord can be softened with
saline soaked gauze to facilitate loading the vein and inserting the catheter.
• Exchange is done by push-pull technique through the umbilical vein inserted
only as far as to permit free flow of bood. Catheter in heart can lead to
arrhythmia.
63. • Isovolumetric exchange transfusion involves simultaneously pulling blood out
of umbilical artery and pushing new blood into the umbilical vein. Better
tolerated in small sick or hydropic infants
• If not possible to insert catheter in umbilical vein, exchange transfusion can
accomplished through a central venous catheter placed in the anterior
cubital fossa or into the femoral vein through the saphenous vein
64. • In push pull technique blood is removed in aliquots that are tolerated by
infants:
• 5ml for <1500 g
• 10 ml for 1500-2500g
• 15 ml for 2500-3500g
• 20 ml for >3500g
• Blood in the pint should be gently mixed after every deci litre of clood
transfused to prevent settling of RBCs.
• After exchange transfusion bilirubin levels are measured every 4 hourly**
65. COMPLICATIONS OF EXCHANGE
TRANSFISION1. Hypocalcemia and hypomagnesemia
• Due to citrate in the blood
1. Hypoglycemia
• Glucose conc of CPD is about 300mg/dl and may stimulate insulin secretion and
hypoglycemia
1. Acid – base balance disturbance
• Citrate is metabolized to alkali and if not metabolized as the baby is ill will cause
acidosis
1. Hyperkalemia
• Potassium levels are greatly elevated in stored PRBCS, but washing before before
reconstitution removes the excess potassium
1. Cardiovascular complications
• Perforation of vessels, embolization, vasospasm, thrombosis, infarction
66. 5. Bleeding
• Due to thrombocytopenia and deficient factors
6. Infections
• Bacteremia, hepatitis, cytomegalovirus, HIV etc
7. Hemolysis
• Hemoglobinemia, hemoglobinuria and hyperkalemia caused by overheating
of the blood
8. Graft- versus host diseases
• Transient maculopapular rash, eosinophilia, lymphopenia and
thrombocytopenia
• Can be prevented by using irradiated blood.
9. Miscellaneous ( hypothermia, hyperthermia)
67. IV IMMUNOGLOBULINS
• Adjunctive treatment for hyperbilirubinemia due to hemolytic disease
• Recommended when serum bilirubin is approaching exchange levels
despite maximal interventions including phototherapy
• IVIg (0.5-1 g/kg/dose; repeated in 12 hours) has been shown to reduce the
need for exchange transfusion in both ABO and Rh incompatibility
• Presumably by reducing hemolysis
68. METALLOPORPHYRINS
• Proposed mechanism is competitive enzymatic inhibition of rate-limiting
conversion of heme-protein to biliverdin by heme- oxygenase
• A single intramuscular dose of metalloporphyrins reduce the need for
subsequent phototherapy.
• Particularly useful when jaundice is anticipated like ABO incompatibility/
G6PD deficiency
• Complications include transient erythema if the infant is receiving
phototherapy
• Data on efficacy, toxicity and long term benefits are being evaluated.
69. CONJUGATED
HYPERBILIRUBINEMIA
• Failure to excrete conjugated bilirubin from the hepatocyte in the
duodenum
• Manifested by a CB level of >2mg/dl or CB level >15% of total bilirubin
• a/w hepatomegaly, splenomegaly and pale stools
70. DIFFERENTIAL DIAGNOSIS
1. Liver cell injury(normal bile ducts)
a) Prologed use of parentral nutrition . Sepsis and ischemic necrosis also cause
cholestasis
b) Infection : viral , bacterial, parasitic
c) Metabolic : alpha 1 antitrypsin deficiency, cyctic fibrosis, galactosemia,
tyrosinemia, hypermethionemia,storage disorders, etc.
2. Excessive bilirubin load(insipissated bile duct syndrome) :
• seen in any hemolytic condition especially in infants with erythroblastosis fetalis
• Also in infants supported on ECMO
71. 3. Bile flow obstruction
• Extra hepatic : isolated, a/w choledochal cyst, trisomy 13 or 18 or polysplenia
• Intrahepatic : allagille syndrome , choledochal cyst, bile duct stenosis, rupture of
bile duct, lymph node enlargement
• In the NICU the most common cause of unconjugated hyperbilirubinemia
in decreasing order are :
• Parentral nutrition
• Idiopathic hepatitis
• Biliary atresia
• Alpha 1 anti trypsin deficiency
• Intra uterine infection > choledochal cyst > galactosemia > hemolytic disorders
72. DIAGNOSTIC TESTS AND
MANAGEMENT
• Evaluate for hepatomegaly, splenomegaly, petechiae, chorioretiitis and
microcephaly
• Evaluate liver damage by assessing liver function by SGOT, SGPT, PT, APTT,
and serum albumin levels
• Establish enteral feeds so that PN can be stopped
• Test for bacterial, viral and intra uterine infections
• Serum analysis of alpha 1 antitrypsin deficiency
• Serum and urine amino acid determination
• Urinalysis for glucose and reducing substances
73. • If known causes are ruled out we have to differentiate idiopathic neonatal
hepatitis from bile duct abnormalities
• Investigations done for the same are:
o abdominal usg for choledochal cyst or mass
o Hepatobiliary scan with Tc
o Nasoduodenal tube to be passed for duodenal fluid collection
74. • Most cholestasis in NICU is due to prolonged parenteral nutrition. After ruling
out other causes(sepsis, metabolic disorders, choledochal cyst and
presence of gallbladder) the following management is done :
Enteral feedings even @volumes of 10ml/kg/day is initiated safely
Once enteral feedings are restarted , infants should receive fat soluble vitamin
supplements of A,D,E and K
patients on parenteral nutrition should have there LFTs regularly checked.
decrease the mineral content ( like copper and manganese)
Phenobarbital should not be used to treat cholestasis in this population