This document discusses pediatric clinical chemistry and provides definitions related to different pediatric age groups. It summarizes reference intervals and clinical conditions evaluated in pediatrics, including fetal maturity and lung development. Key tests discussed include the L/S ratio test to evaluate fetal lung surfactant maturity, tests to diagnose premature rupture of membranes, and evaluation of blood gases, electrolytes, liver function, and other important analytes in pediatrics. Sampling considerations and point-of-care testing in pediatrics are also summarized.
Test for pancreatic and intestinal functions are very important for clinical evaluation gastro intestinal disorders . So it will e useful for medical and allied professional students and practitioners.
introduction for renal system
nephron
protein & urine
definition of microalbuminuria
causes
atherosclerosis role
DM role (micro¯ovascular changes due to atherosclerosis )
Hypertension role
possible sign and symptoms associated with microalbuminuria
enjoooooooooy ....... :)
Liver function tests and interpretation is a very important topic for students of medical and allied fields. It is essential for efficient practice of clinical and laboratory medicine.
Serum Protein and Albumin-Globulin RatioASHIKH SEETHY
For MBBS Biochemistry Practical. Explains various methods of protein estimation and estimation of AG ratio, conditions leading to alterations in AG ratio etc.
Test for pancreatic and intestinal functions are very important for clinical evaluation gastro intestinal disorders . So it will e useful for medical and allied professional students and practitioners.
introduction for renal system
nephron
protein & urine
definition of microalbuminuria
causes
atherosclerosis role
DM role (micro¯ovascular changes due to atherosclerosis )
Hypertension role
possible sign and symptoms associated with microalbuminuria
enjoooooooooy ....... :)
Liver function tests and interpretation is a very important topic for students of medical and allied fields. It is essential for efficient practice of clinical and laboratory medicine.
Serum Protein and Albumin-Globulin RatioASHIKH SEETHY
For MBBS Biochemistry Practical. Explains various methods of protein estimation and estimation of AG ratio, conditions leading to alterations in AG ratio etc.
GGT is one of a large group of enzymes “Peptidases”.
A membrane bound enzyme whose active site faces the external side of cell.
Hepatobiliary tract enzyme.
They are water soluble substances.
2. They are synthesized at a relatively low rate in well nourished individuals.
3. Plasma level of ketone bodies < 1mg/dl.
4. Urinary level of ketone bodies <3 mg/24 hour urine.
A research including most disorders concerned with the inborn (neonates) including:
Malnutrition / Nutrition disorders
Congenital renal disorders
Inborn metabolic errors
congenital liver disorders (Cigler Najar syndrome - Rotor syndrome - Dubin johnson syndrome) and others ...
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
Laboratory diagnosis of H. Pylori infection, Ola ElgaddarOla Elgaddar
A short presentation for the different laboratory techniques used in diagnosing Helicobacter Pylori infection. A special focus is given for the diagnostic performance of every test.
GGT is one of a large group of enzymes “Peptidases”.
A membrane bound enzyme whose active site faces the external side of cell.
Hepatobiliary tract enzyme.
They are water soluble substances.
2. They are synthesized at a relatively low rate in well nourished individuals.
3. Plasma level of ketone bodies < 1mg/dl.
4. Urinary level of ketone bodies <3 mg/24 hour urine.
A research including most disorders concerned with the inborn (neonates) including:
Malnutrition / Nutrition disorders
Congenital renal disorders
Inborn metabolic errors
congenital liver disorders (Cigler Najar syndrome - Rotor syndrome - Dubin johnson syndrome) and others ...
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
Laboratory diagnosis of H. Pylori infection, Ola ElgaddarOla Elgaddar
A short presentation for the different laboratory techniques used in diagnosing Helicobacter Pylori infection. A special focus is given for the diagnostic performance of every test.
Created by ArtsmartB6 for Worcester East Middle School's PBIS program. Included is how PBIS has positively effected our school's overall climate, suspension rates and academics.
This is the first one of a series of lectures about the "Cell". I am here introducing some basic principles about the cell structure, types, histology and biochemistry
It describes the analysis of amniotic fluid fin the laboratory and its Significance. Prepared by Sintayehu Ambachew Wondemagegn
at University of Gondar
* These are Dr Gebresilassie's Amazing Notes.
* If you have feedback, contact me on https://t.me/Hanybal2021
* For further OBGYN notes - join us on telegram https://t.me/OBGYN_Note_Book
Pathological analysis of body fluids with lab investigations,
Including Amniotic fluid, Semen analysis, Synovial fluid, Gastric fluid
Other body fluids: Sweat,saliva,tear
To perform his experiments, how did Mendel prevent pea flowers from self-pollinating and control their cross-pollination?
He cut away the pollen-bearing male parts of a flower and dusted that flower with pollen from another plant.
Enhancing Laboratory Leadership through Financial Management Skills.pptxOla Elgaddar
In our recent presentation titled 'Strengthening Lab Leadership through Financial Management,' we explored how financial skills can enhance lab management. Attendees discovered practical ways to leverage financial tools for more effective resource allocation and sustainable growth. The session showcased how mastering financial management can streamline lab operations and improve overall leadership performance.
Harmonization of Laboratory Indicators, 09 03-2017Ola Elgaddar
Most of Medical labs are having KPIs to monitor their performance and enhance process improvement. This presentation discusses in short the IFCC attempts to reach a consensus and harmonize medical labs quality indicators.
Strategic planning, Ola Elgaddar, 12 12-2016Ola Elgaddar
A simple introduction to the basic concepts of strategic planning addressing anyone who works in any organization, aiming at elucidating some vague terms like strategy, environmental scanning, mission, vision,......!!
It is very important to every employee, who is a bit away from decision makers in his organization, to know the basic concepts at least.
ELISA is one of the commonly used laboratory techniques. As it is a multi-step manual technique, every step should be carefully monitored. Here is a short presentation on the common things that should be considered when using ELISA.
Are we using the correct quality goals?Ola Elgaddar
Setting quality goals / specifications is a debatable issue since 1999. I am trying here to show the options and the continuos trials from several professional bodies to reach a consensus in this matter.
This was an oral presentation in the first international conference of the Chemical Pathology Department, Medical Research Institute, Alexandria University - February 2016
What do clinicians need to know about lab tests?Ola Elgaddar
A presentation in the Annual meeting of the Egyptian American Scholars (AEAS) in Cairo 2015.
I am trying here to describe, in short, from my point of view as a laboratorian, the points that we need to discuss with clinicians. Both groups should share some terms and definitions and should see things from the same perspective!
The forth lecture about the "Cell".
Here, I am discussing the several signaling pathways.....It is highly dependent on the 3rd lecture; Receptors.
Enjoy :)
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
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
3. Definitions
Child:
• Legal definition: A human being below the age
of 18 years unless under the law applicable to
the child, majority is attained earlier.
• Biological definition: Anyone in the
developmental stage of childhood, between
infancy and adulthood.
4. - Neonate: newborn up to first 28 days of life
- Infant: comprises neonatal period up to 12
months
- Toddler: 1-3 years
- Pre-school: 3-5 years
- School-age: 6-10 years
- Adolescent: 11-14 years
15. - Laboratory evaluation starts from the
prenatal period.
- The most important clinical conditions are:
1) Evaluation of maturity.
2) Diagnosis of congenital abnormalities
16. Intrauterine Growth Retardation
(IUGR)
AGA (Appropriate for Gestational Age):
Birth weight is between 10th and 90th percentile for
infant’s gestational age (GA).
SGA (Small for Gestational Age):
Birth weight <10th percentile for GA.
IUGR (Intra Uterine Growth Retardation):
Deviation and reduction in expected fetal growth
pattern.
Not all IUGR infants are SGA
17. ASYMMETRIC vs. SYMMETRIC
GROWTH RETARDATION
- Most growth retarded infants have
asymmetric growth restriction. First there is
restriction of weight and then length, with a
relative “head sparing” effect.
- This asymmetric growth is more commonly due
to extrinsic influences that affect the fetus
later in gestation, such as preeclampsia,
chronic hypertension, and uterine anomalies.
18. - In the human brain, most neurons develop
prior to the 18th week of gestation. Early
gestational growth retardation would be
expected to affect the fetus in a symmetric
manner.
- Examples of etiologies for symmetric growth
retardation include genetic or chromosomal
causes,
early
gestational
intrauterine
infections (TORCH) and maternal alcohol use.
19. CAUSES:
A. Maternal
• Low pre-pregnancy weight
• Recent pregnancy and/or high parity
• Chronic illness - such as malabsorption,
diabetes, renal disease
• Inadequate or poorly balanced dietary intake
• Decreased O2 availability to fetus (e.g., high
altitude, severe maternal anemia)
20. B. Uterine and placental factors:
Inadequate placental growth, uterine
malformations, decreased utero-placental blood
flow (e.g., toxemias of pregnancy, diabetic
vasculopathy) and multiple gestations
C. Fetal causes:
Include Chromosomal abnormalities and
intrauterine infections (i.e., TORCH)
21.
22. The most important organ we are after for
maturity is the lung
Assessment of Fetal Lung Maturity:
-Fetal lung maturation is marked by production
of a detergent-like material, surfactant, which
forms a film on the alveolar surfaces.
23.
24. -Prior to 35th week of gestation, the major
component of surfactant is α-palmitic β-myristic
lecithin.
- After
that
time,
dipalmitic
lecithin
predominates and phosphatidyl glycerol (PG)
appears about a week later.
- Minor phospholipid components of surfactant
include phosphatidyl inositol, phosphatidyl
ethanolamine, phosphatidyl serine, and
sphingomyelins.
25. -Since sphingomyelin (S) concentration in AF is
constant during the third trimester, it serves as a
reference material against which surfactant
lecithin (L) can be compared.
- Measurement of L/S ratio avoids problems
associated with variability in chemical extraction
and inaccuracy in estimates of absolute
concentration per AF volume
26. 1) Quantification of Pulmonary Surfactant: L/S
Ratio (Lecithin / sphingomyelin):
-It is the most valuable assay for the assessment
of fetal pulmonary maturity.
-At 32 weeks the L/S ratio reaches 1. Lecithin
then rises rapidly, and an L/S ratio of 2.0 is
observed at 35 weeks.
- A ratio of 2.0 or greater has repeatedly been
associated with pulmonary maturity.
27. -A mature L/S ratio predicted the absence of RDS in
98 percent of neonates. With a ratio of 1.5 to 1.9,
approximately 50 percent of infants will develop RDS.
Below 1.5, the risk of subsequent RDS increases to 73
percent.
Other tests to evaluate surfactant:
- Evaluation of Amniotic Fluid Turbidity visually
- Shake Test
- Foam Stability Index
- Tap Test
28. 2) Test for PG: Amniostat-FLM:
-A rapid immunologic semiquantitative
agglutination test that can be used to determine
the presence of Phosphatidylglycerol (PG)
- Results are reported as:
Negative
Low- positive (PG 0.5-2ug/ml)
High -positive (PG ≥2ug/ml)
- RDS rarely develops if PG is ≥2ug/ml
29. 3) Fluorescent Polarization FLM Tests:
- The TDx analyzer is an automated fluorescence
polarimeter that determines surfactant albumin
ratio.
- The test requires 1 ml of uncentrifuged amniotic
fluid and can be run in less than 1 hour.
- The surfactant albumin ratio (SAR) is determined
with amniotic fluid albumin used as an internal
reference.
-A ratio of 50 to 70 mg surfactant per gram of
albumin is considered mature.
- Correlates with L/S and has a better precision.
30.
31. 4) Lamellar Body Counts:
- Lamellar bodies are the storage form of
surfactant.
- They scatter light & can be counted directly
using the platelet channel of most cell counters
- A lamellar body count >30,000/μl
uncentrifuged AF is highly predictive of
pulmonary maturity, while a count <10,000/μl
suggests a risk for RDS.
- Neither meconium nor lysed blood has an
effect on the lamellar body count.
32. Assessment of Premature Rupture of
Membranes
- Pre mature rupture of the membranes is the most
common cause for pre maturity.
- Diagnosing premature rupture of membranes is
done by:
1) PH assessment of vaginal discharge:
Unlike vaginal secretions whose pH is acidic, AF is
alkaline. The vaginal pool aspirate of a gravida with
watery discharge can be tested with nitrazine
paper to estimate pH visually.
33. 2) An aliquot of the aspirated fluid can also be
applied to a glass microscope slide, dried for 5
minutes and examined microscopically for a
‘fern' pattern, which indicates the presence of
AF in the vaginal fluid pool.
34.
35.
36. 3) Fetal fibronectin in maternal plasma or AF:
- Fetal fibronectin is a chorionic trophoblast
protein.
- If fetal fibronectin is increased in maternal
plasma or AF or cervicovaginal secretions
between 22-34 weeks gestation, it denotes loss
of integrity of the fetal membranes.
- A POC device is available at the obstetrician
office for measuring fetal fibronectin.
- It has a high predictive value for impending
early delivery of the baby & RDS
38. Sampling in pediatrics
Pre analytical considerations:
- Difficult sampling (Capillary; heal, thumb):
needs an expert
- Small patient’s size, number of times for blood
to be drawn for repeat analysis.
- Different sizes of tubes.
43. Choice of the analyzer:
- Dead volume? The smaller, the better
- Clot detector
- Sample cubs & primary tubes
44. Point of care analysis:
•
•
•
•
•
•
Portable testing devices that are easy to use
Small sample volume
No sample preparation is required
Provide rapid bed side results
Can be connected to the hospital LIS
Mainly used for: bilirubin, glucose, Hb, electrolytes
& blood gases
45. Point of care analysis:
• High cost, so its use should be rationalized for tests
that needs short TAT
• Neither their performance nor their dynamic ranges
are as good as the tradition lab equipments.
• Should be properly validated using appropriate
quality assurance procedures
• Very low or very high results should be checked in
the main laboratory
46. The most important items that need
evaluation in pediatrics are:
1. Regulation of blood gases & pH.
2. Kidney function with regulation of water &
electrolytes
3. Liver function: physiologic jaundice & energy
metabolism
4. Calcium and bone metabolism
5. Endocrine functions
6. Genetic diseases & neonatal screening
47. 1) REGULATION OF BLOOD GASES &PH
-Requires fully mature lungs & kidneys after
birth.
- Immature lungs or surfactant may result in
respiratory distress syndrome (RDS), where
there is failure in excreting CO2 resulting in
respiratory acidosis. (Plasma bicarbonate is not
affected early, before renal compensation takes
place)
-
48. - The trauma & relative anoxia during delivery
causes an increase in lactic acid production &
accordingly, metabolic acidosis. (Reduced
bicarbonate level, supplying bicarbonate
reverses the condition)
-Persistent acidosis that is not corrected by
bicarbonate administration is an indication for
possible inborn errors of metabolism.
49. -Alkalosis is uncommon in pediatric patients,
most common causes:
1) Hyperammonemia: Secondary to
diseases & inborn errors of metabolism
2) Pyloric stenosis & loss of gastric acids
3) Hypokalemia
liver
50. 2) KIDNEY FUNCTION
- From the 35th week of gestation, rapid kidney
development takes place in preparation for extra
uterine life
GFR:
- At birth, GFR is about 25 % of its value in older
children.
51. - Tubular function shows a similar pattern,
where the concentrating power of the kidney
in the early months of life is only about 78 %
of its value in the adult kidney.
- This gradual process of renal development
results in serum electrolytes level shift seen in
the neonatal period.
52. - The kidney primarily maintains water
homeostasis
- Other causes of water loss in the neonatal
period:
1) Insensible water loss through the skin
2) The use of radiant heaters (radiated heat) to
maintain body temperature.
3) Insensible water loss from the lungs in RDS
54. 3) Liver function
Physiologic Jaundice:
- The processing of many normal metabolic
pathways and the metabolism of exogenous
compounds proceed slower in neonates.
- The most striking effect of an immature liver, even
in a full term baby, is the failure to adequately
metabolize bilirubin.
55. - Fetal blood is produced first by the embryonic
yolk sac, then by the liver, and finally by the fetal
bone marrow.
- With the switch of erythropoiesis to the fetal liver,
fetal hemoglobin production begins.
- HbF consists of two α- and two γ-chains.
- As the fetal bone marrow begins red cell
production, HbA production increases.
- At birth fetal blood contains 75% HbF and 25%
HbA. HbF production rapidly diminishes during the
first year of postnatal life. In normal adults, less
than 1% of hemoglobin is HbF.
56. -HbF has a higher affinity for oxygen than does
HbA. Thus in the placenta, oxygen is released from
the maternal HbA, diffuses into the chorionic villi,
and binds to the fetal HbF.
-Bilirubin accumulates as fetal hemoglobin is
rapidly destroyed and replaced by adult
hemoglobin.
- At birth, UDP - glucuronoyltransferase, the
enzyme responsible for conjugating bilirubin, is
immature. This results in the accumulation of
unconjugated bilirubin and the development of
physiologic jaundice.
57. -A normal baby may have a serum bilirubin up to
15 mg / dl, most of it unconjugated. This level
should fall to the base line by the age of 10 days.
-If severe and passes the immature BBB, it might
lead to kernicterus (Bilirubin encephalopathy).
- Complete absence of the bilirubin conjugating
enzyme results in severe persistent jaundice
(Crigler – Najjar syndrome)
58.
59. Carbohydrate metabolism:
-At birth, a full term baby has sufficient glycogen
stores to provide glucose as an energy source.
-If the delivery is stressful, these energy reserves
may become depleted prematurely.
- At that time, the normal physiologic rule of the
gluconeogenesis pathway becomes essential
where there is conversion of alanine into
glucose.
60. -The later pathway is not always mature at birth
which may result in what is termed “physiologic
hypoglycemia”.
- This condition usually corrects quickly as the
enzyme system matures.
61. -Persistent and severe hypoglycemia should
alert the physician towards a possible inborn
error of metabolism, such a galactosemia.
- Galactosemia is due to failure of conversion of
galactose to glucose as a result of genetic
deficiency in any of the following enzymes:
galactose-1-phosphate uridyltransferase (GALT),
galactokinase (GALK) or uridine diphosphate
galactose-4-epimerase (GALE)
62. Nitrogen metabolism:
-The liver is involved in the metabolic inter
conversions of amino acids and in the synthesis
of non-essential amino acids.
- The liver synthesis most of the plasma proteins
including albumin, transferrin, complements and
coagulation factors.
63. -Important in nitrogen metabolism through the
Urea cycle.
-Owing to the immaturity of urea cycle enzymes
early in life, the level of ammonia in the plasma
of neonates is highly elevated than its level in a
one year old child.
- Persistently elevated ammonia level, should
alert the investigator to possible liver damage.
64. 4) CALCIUM AND BONE METABOLISM
- Normal bone growth requires integration of
calcium, phosphate and magnesium metabolism
with endocrine regulation from vitamin D,
parathyroid hormone & calcitonin.
-The active metabolite of vitamin D is 1,25
dihydroxy vitamin D.
-Hydroxylation of Vitamin D from diet takes
place in liver and kidneys and requires normal
functioning of these organs.
65. - Absorption of vitamin D from the
gastrointestinal tract, conversion to its active
form in the kidney, and incorporation of
calcium and phosphate into the growing bone
requires normally active PTH.
- Secretion of PTH is in turn modulated by serum
calcium & magnesium levels, where low level
of both divalent cations inhibits PTH secretion.
66. - Rapid bone growth occurring in infancy and
puberty requires optimal coordination of
mineral absorption, transport and endocrinecontrolled incorporation of the minerals into
growing bone.
- Approximately 98% of total body calcium is
present in bone and less than 2 % is
measurable in blood.
67. Hypocalcemia:
- Hypocalcemia is defined as total serum calcium
below 7.0 mg / dl or ionized calcium below 3.0
mg / dl.
- In the newborn, particularly immature, these
levels may be commonly encountered with
few symptoms. However, hypocalcemia can
result in irritability, twitching and seizers.
Serum calcium is usually measured in children
with seizers of unknown etiology.
- Prolonged hypocalcemia can result in reduced
bone growth and rickets.
69. Rickets:
- Disease caused by a
mineralization defect during
bone formation resulting in
increase in osteoid, the
unmineralized organic matrix
Of bone.
70. Causes:
1. Vitamin D deficiency: inadequate exposure to
sun, poor vitamin D diet, malabsorption
2. End organ resistance to vitamin D
3. Phosphate depletion: e.g. Fanconi syndrome
Biochemical findings:
1. Low serum calcium & phosphates
2. High serum ALP (Due to increased osteoblastic
activity)
3. 25 (OH) D: to assess vitamin D status.
71. N.B:
- Vitamin D-dependent rickets type I is an
inherited defect in 25(OH) D-1α hydroxylase
causing impaired formation of 1, 25(OH)
vitamin D.
- Vitamin D-dependent rickets type II is an
inherited disorder characterized by very high
serum concentration of 1, 25(OH) vitamin D.
This syndrome is due to resistance to 1,
25(OH) vitamin D, secondary to defects in the
1,25(OH) vitamin D receptor.
72. Hypercalcemia:
- Defined as total serum calcium > 11.0 mg / dl.
- This is unusual in pediatrics, but has
potentially severe clinical implications.
- Patients with hypercalcemia have poor muscle
tone, constipation, failure to thrive and may
develop kidney stones leading to renal failure.
73.
74. 5) ENDOCRINE FUNCTION
Hypothalamic – pituitary – thyroid axis:
Primary hypothyroidism
(Congenital hypothyroidism):
- Results from any defect that causes failure of the
thyroid gland to synthesize and secrete thyroid
hormones.
- Incidence: 1/4000 births
- Untreated patients with this condition have severe
mental retardation with unusual facial features.
75.
76. - Treatment by thyroid replacement therapy is
usually successful when diagnosis is
established.
- The best diagnostic test is to measure serum
TSH level which is high as a result of failure of
the long feedback loop (between pituitary &
thyroid gland). Thyroid hormone levels in
untreated patients are very low.
- The only neonatal screening program in Egypt.
77. Secondary hypothyroidism:
- It is a result of pituitary failure to secrete TSH
which results in lack of thyroid gland
stimulation and subsequent production of
thyroid hormones.
- Diagnosed by low TSH.
- It is important to study the other pituitary
pathways to determine whether this is an
isolated TSH defect or panhypopituitarism.
78. Neonatal Graves‘ disease:
-The fetal thyroid-pituitary axis functions
independently from the mother's axis in most
cases.
-However, if the mother has preexisting Graves'
disease, her auto antibodies can cross the
placenta and stimulate the fetal thyroid gland.
Thus the fetus can develop hyperthyroidism.
- Measurement of thyrotropin-binding inhibitory
immunoglobulins is useful for assessing risk of
fetal or neonatal Graves' disease.
79.
80. Hypothalamic – pituitary – adrenal cortex axis:
- The most important disorder is congenital
adrenal hyperplasia (CAH)
- CAH: Congenital absence of one or more of the
synthetic enzymes that lead to cortisol and
aldosterone biosynthesis. This leads to
compensatory increase in ACTH leading to
stimulation of steroids biosynthesis till the block
point causing:
81. 1. Hyperplasia of the adrenal cortex
2. Accumulation of intermediate compounds
proximal to the block
3. Shunting of the substrate towards the
adrenal androgen pathway
- The most common disorder is 21-Hydroxylase
deficiency (1 / 5000 births)
82.
83.
84. Growth factors:
- G.H deficiency results in poor growth and
stunted growth.
- When G.H acts on its receptors on the liver,
the liver secretes IGF-1 & its binding protein
IGF-BP3
- Due to the diurnal and pulsatile pattern of G.H
secretion, a single measurement is not
sufficient to diagnose its deficiency.
85. - Insulin induced hypoglycemia & clonidine
induced hypotension are common stimulatory
tests used to detect G.H deficiency.
- Measuring IGF-1 & IGF-BP3 is considered an
effective tool for assessing G.H deficiency
because:
1. Their basal levels do not have the great
variation that occurs for G.H
2. Infants with defects in IGF-1 & IGF-BP3
synthesis and secretion are unlikely to respond
to G.H replacement.
87. Screening for diseases in pediatrics:
I) Pre natal:
- Maternal screening
- Fetal screening:
amniocentesis, chorionic villi sampling & pre
implantation genetic diagnosis
II) Post natal
88. MATERNAL SERUM SCREENING FOR FETAL
DEFECTS:
Multiple of the median (MoM):
- The MoM is now universally used as a common
currency for converting analyte values into an
interpretative unit and is also the starting
point for calculating risks for neural tube
defects, Down syndrome, and trisomy 18.
89. - For each analyte, each lab should develop a
set of median values for each week (or day) of
gestation using the laboratory’s own assay
values measured on the population to be
screened.
- Individual test results are then expressed as
MoM by dividing each individual test result by
the median for the relevant gestational week.
90.
91. Screening for Down syndrome (trisomy 21) &
trisomy 18:
First trimester screening (Double test) –
[11th- 14th gestational weeks]
- Combining two serum markers (free beta HCG,
PAPP-A), with ultrasound nuchal translucency
(NT)
- PAPP-A is lower in pregnancies complicated
with Down syndrome than in normal ones.
- HCG is higher & NT is thicker in Down
syndrome pregnancies.
92. Second trimester screening (Triple test)[15th – 18th gestational weeks]
A method combining measurements of 3
analytes, with maternal age into a single risk
estimate.
• AFP (alpha fetoprotein )
• uE3 (unconjugated estriol )
• HCG (Human chorionic gonadotrophin)
93.
94. In Down syndrome:
- AFP & uE3 are 25% lower than expected
- HCG is two folds higher than expected
- A 4th analyte, Dimeric Inhibin A (DIA), that is
elevated in cases of Down syndrome is added
and the test is called Quadruple test
95.
96. Fetal trisomy 18:
- AFP and uE3 concentrations are low
- HCG concentrations are also very low
- No role for DIA
Women who test positive (or those who test
negative but aged above 35) should be offered
amniocentesis to obtain fetal cells for
karyotyping or other DNA based techniques;
the only way to confirm Down or trisomy 18
syndromes diagnosis.
97. Screening for Neural tube Defects (NTD):
- Optimal screening is between 16 and 18 weeks
of gestation.
- The most commonly used AFP MoM cutoffs are
between 2.0 and 2.5 MoM.
- A second sample is needed for moderately
elevated results (2.0 to 3.0 MoM)
- If the result for the second AFP test is not
elevated, the woman is considered to be
screen-negative.
98. - If the result is still elevated:
• 4-D U/S is used to verify gestational age
• Identify other possible reasons for the
increased AFP (ex: multiple pregnancy,
abdominal hernias into the umbilical cord)
- Patients still having an unexplained ↑↑ AFP
test results amniocentesis for measurement
of amniotic fluid AFP and acetylcholinesterase.
99.
100. - Ultrasound
diagnosis of open
neural tube defects
is now so reliable
that it is often used
for diagnosis in
women with
elevated maternal
serum AFP without
waiting for amniotic
fluid measurements.
101. FETAL SCREENING:
I) Amniocentesis:
- Removal of amniotic fluid containing fetal cells,
via a needle puncture from the uterus.
- Any genetic analysis can be performed on
these cells.
- Performed 14-20th week of gestation.
102. FETAL SCREENING:
I) Amniocentesis:
- Removal of amniotic
fluid containing fetal cells,
via a needle puncture
from the uterus.
- Any genetic analysis can
be performed on these
cells.
- Performed 14-20th week
of gestation.
103. Amniotic fluid testing is done for:
• Diagnosis of NTD (Confirming a screen positive
mother)
• Diagnosis of congenital diseases
• Diagnosis of Isoimmunisation disease
• Assessment of fetal lung maturity
104. 1) Diagnosis of NTD:
AFP:
- Patients with unexplained high maternal serum
AFP levels and normal ultrasonography should
be offered amniotic fluid testing
- AFP values greater than or equal to 2.0 MoM
are considered elevated.
- A frequent interference is contamination of the
fluid with fetal blood. Elevated amniotic fluid
AFP should be tested for fetal hemoglobin, a
sensitive marker of fetal blood contamination.
105. Acetylcholine Estrase (AChE):
- AChE is a neural enzyme present in cerebrospinal fluid
and fetal blood.
- It is not present in maternal blood and is not normally
detectable in amniotic fluid.
- The abnormal presence of acetylcholinesterase in
amniotic fluid is suggestive of an open fetal defect.
- When AChE is detected, the ratio of AChE to
pseudocholinesterase
(PChE),
a
non-specific
cholinesterase normally found in amniotic fluid, may
help distinguish open neural tube defects from fetal
blood contaminated fluid.
106. 2) Tests for isoimmunization disease:
- Isoimmunization disease is a fetal haemolytic
disorder caused by maternal antibodies
directed against antigens on fetal
erythrocytes.
- The amount of bilirubin in the amniotic fluid is
useful for determining the severity of the
condition.
- The most common cause of severe disease is
sensitization of Rh-negative woman to the D
antigen of the Rh system.
107. - An association exists between gestational age,
severity of the disease, and bilirubin
concentration.
- The concentration of bilirubin is too low to be
measured by standard photometric
techniques (up to 0.03mgldL) but the
determination can be done by absorption
spectrophotometry.
- The maximal absorbance of bilirubin is at 450
nm.
108. - In the absence of significant amounts
of bilirubin, the absorbance spectrum for
the amniotic fluid between 365 and 550
nm is nearly exponential.
109. -When plotted on a semi log scale (linear
curve), the degree to which the curve
deviates from a straight line at 450 nm is
linearly proportional to the concentration of
bilirubin (∆A 450)
110. - Results of (∆A 450) are established into
3 classification zones based on
gestational age “ Liley's zones”
111. II) CVS:
- Chorionic villi are
precursors of the placenta
and a good source of fetal
tissue.
- CVS can be performed
safely by 10th week both
transabdominally and
transvaginally
- Used for:
•Cell culture &
karyotyping
•Enzyme assays
•Direct gene analysis
112. III) Pre implantation
genetic diagnosis (PGD):
- For couples undergoing
IVF.
- Fertilized eggs are checked
for the gene mutation and
only the unaffected embryos
are introduced into the
uterus in the hope of a
successful implantation.
- Cells are isolated from the
blastocyst (16 – 20 cells
embryo), where DNA is
extracted and tested for
common or expected genetic
mutations.
113. POST NATAL NEW BORN SCREENING:
- NBS is a process of early identification of health
conditions followed by their subsequent timely
treatment before the onset of disease processes
thereby minimizing the risk of long-term
sequelae.
- Key issues considered for NBS:
• What are the effects of each genetic disorder?
• What treatment is currently available for each
genetic disorder, and at what age does treatment
begin?
114. • Based on demographics, how many people
are likely to be affected by each genetic
disorder?
• Should all newborn infants receive the same
screening tests? Why or why not?
• Can a test in question be performed on a large
scale in laboratories? Why or why not?
• What is the cost per test and the total for
screening?
• Will early identification of persons with the
genetic disorder lead to cost savings in
treatment or care? Why or why not?
115. Alpha-1-antitrypsin Deficiency:
Clinical description:
- Alpha-1-antitrypsin deficiency can lead to early
onset of emphysema and/or liver failure.
- These symptoms usually appear when a person
is in their 30’s or 40’s.
- Symptoms are more severe in smokers than in
nonsmokers.
116. Genetics:
- This disorder is caused by a mutation in the
proteinase inhibitor (PI) gene on chromosome 14.
- The normal protein coded for by this gene is
involved in tissue repair.
- Disorder symptoms depend on which type of
mutation an individual has in the PI gene.
- There are more than 70 different alleles of the PI
gene.
- The M allele is the wild variant. The mutant alleles
S and Z are the most common disease causing
variants.
117. Inheritance:
Autosomal recessive
Testing:
- This disorder can be detected by testing the
levels of alpha-1-antitrypsin in blood. If they are
abnormally low, the next step is to identify the
exact alpha-1-antitrypsin protein variants the
person carries.
- Abnormal forms of the alpha-1-antitrypsin
protein can be detected using dried blood as a
sample for gel electrophoresis.
118. Cystic Fibrosis:
- Cystic fibrosis is caused by mutations in the
cystic fibrosis transmembrane regulator (CFTR)
gene on chromosome 7 which codes for the
protein that controls ion transfer across cell
membranes.
- Disruption of salt transfer results in abnormal
gland secretions and dehydration due to
increased loss of salt and water during sweating.
- CF affects almost all of the glands in the body
that secrete fluid, resulting in a variety of
symptoms.
119. - Secretions may be thick and cause blockage in
the pancreas, intestines and lungs.
- Mucus blockage also provides places for
bacteria to multiply, increasing the probability
of infection.
- CF children show poor digestion, dehydration,
coughing and vomiting.
Molecular
analysis
has
identified
approximately 100 mutations in the CFTR
gene. Different mutations determine the
severity of symptoms seen in CF patients.
120. Testing:
- Mutation in the CFTR gene results in an
increase in an enzyme called trypsinogen. The
initial newborn screen tests for this enzyme
using a dried blood sample.
- There are hundreds of mutations in the
population, the most common is ∆F508.
- Testing all mutations is very difficult unless a
clinically accepted microchip technology is
available.
121. - Measurement of chloride content in sweat
collected after pilocarpine iontophoresis, is
still the gold standard test for diagnosing CF
Cystic Fibrosis Foundation Sweat Test2.flv
122. Huntington’s disease:
- Huntington’s disease is characterized by the
progressive death of certain neurons in the brain.
- Symptoms generally appear between the ages of 3540 years and include depression, mood swings,
amnesia, involuntary twitching and lack of
coordination.
- As the disease progresses, involuntary movements
increase, memory declines, and walking, speaking
and swallowing ability gradually diminish.
- Death soon follows from choking, infections or heart
failure.
123. Genetics:
- Huntington’s is caused by excessive repeating of
the DNA bases CAG (trinucleotide repeats) in
the huntingtin gene on chromosome 4.
- The normal number of repeats is 10 – 35,
Huntington’s disease patients have 36 - 121
repeats.
Inheritance
Autosomal dominant
Testing
The huntingtin gene is analyzed in a blood sample
to determine the number of CAG repeats.
124. Maple Syrup Urine Disease (MSUD)
- Individuals with maple syrup urine disease
(MSUD) are unable to properly metabolize
three amino acids: leucine, isoleucine and
valine.
- The enzymes required to process these three
amino acids are absent, inactive or only
partially active.
- Because these amino acids do not get broken
down completely, high levels accumulate in
the blood, urine and sweat.
125. -The by-product of isoleucine has a
characteristic sweet smell which gives the
disorder its name.
- The three amino acids and their derivatives can
be toxic at high levels and can lead to brain
injury, mental retardation, seizures, vomiting,
coma and even death.
Genetics:
The most common type is classic MSUD which is
caused by a defect in the BCKDHA gene on
chromosome 19.
126. Inheritance
Autosomal recessive
Testing
- Newborn screening programs that test for
MSUD use the same blood sample collected
for PKU and galactosemia tests.
- Generally, blood is analyzed for elevated levels
of leucin
127.
128. Phenylketonuria (PKU)
- PKU is caused by the lack of phenylalanine
hydroxylase , an enzyme that processes the
amino acid phenylalanine.
- Phenylalanine is not broken down and
accumulates in the blood & it is toxic to the
brain.
- Untreated individuals with PKU show
progressive developmental delay in the first
year of life, mental retardation, seizures,
autistic-like behavior and a peculiar body odor.
129. Genetics
- In PKU individuals, the phenylalanine
hydroxylase gene on chromosome 12 is
disrupted.
Inheritance
Autosomal recessive
130. Testing
- The blood phenylalanine level can be measured
using a spot of dried blood.
- The PKU test (the Guthrie test) was the first
genetic screening test developed.
- Automated tests (MS / MS) are now used in some
screening programs.
- The timing of the test is important; the test should
be completed after the first day and before the
seventh day of life. If done too soon, low levels in
the newborn can be masked by the presence of
maternal phenylalanine.
131. Sickle Cell Disease:
- A group of inherited disorders of RBCs
- If the gene encoding hemoglobin is mutated, it
causes a change in the shape of the molecule.
- When the mutated hemoglobin delivers
oxygen to the tissues, the red blood cell
collapses, resulting in a long, flat sickle-shaped
cell. These cells clog blood flow, resulting in a
variety of symptoms including pain, increased
infections, lung blockage, kidney damage,
delayed growth and anemia
132.
133. Genetics
- The gene encoding the beta chain of the
hemoglobin
molecule,
located
on
chromosome 11, can be mutated in a variety
of ways that result in different types of sickle
cell disease.
- Some mutations are more common than
others. The three most common types of
sickle cell disease are hemoglobin SS (Hb SS),
hemoglobin SC (Hb SC), and hemoglobin sickle
beta thalassemia (HbS beta-thalassemia).
134. Inheritance
Autosomal recessive
Testing:
- Most screening programs utilize thin-layer
isoelectric focusing (IEF) or high performance
liquid chromatography (HPLC) techniques
performed on capillary blood collected from a
heel stick and absorbed onto filter paper.