non-skeletal mesodermal tissues: adipose tissue, fibrous tissue, muscle, blood vessels and peripheral nerves (despite neuroectodermal origin)
benign, malignant and intermediate (low-grade malignant – locally aggressive, can recur, no metastatic potential)
originate from primitive mesenchymal stem cells
classification according to differentiation lines (e.g. liposarcoma is not a tumor arising from adipose tissue but exhibiting lipoblastic differentiation)
non-skeletal mesodermal tissues: adipose tissue, fibrous tissue, muscle, blood vessels and peripheral nerves (despite neuroectodermal origin)
benign, malignant and intermediate (low-grade malignant – locally aggressive, can recur, no metastatic potential)
originate from primitive mesenchymal stem cells
classification according to differentiation lines (e.g. liposarcoma is not a tumor arising from adipose tissue but exhibiting lipoblastic differentiation)
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues : 2016 U...Ankit Raiyani
This is a complilation of expected changes in the myeloid neoplasms in the upcoming 2016 update of the "WHO classification of tumours of haematopoietic and lymphoid tissues".
Some of the changes may not be incorporated in the actual published book.
This compilation has been prepared from presentations from persons actually concerned with revision of the book. All credits goes to them.
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues : 2016 U...Ankit Raiyani
This is a complilation of expected changes in the myeloid neoplasms in the upcoming 2016 update of the "WHO classification of tumours of haematopoietic and lymphoid tissues".
Some of the changes may not be incorporated in the actual published book.
This compilation has been prepared from presentations from persons actually concerned with revision of the book. All credits goes to them.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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
4. Major Time Spans
Neonatal
first
period
four weeks of life
Infancy
the
Age
first year of life
1 – 4 years (preschool)
Age 5 – 14 years (school age)
5. MORTALITY by TIME SPAN
NEONATE (0-4 WEEKS): CONGENITAL,
PREMATURITY
UNDER ONE YEAR: CONGENITAL,
PREMATURITY/WEIGHT, SIDS
1-4 YEARS: ACCIDENTS, CONGENITAL,
TUMORS
5-14 YEARS: ACCIDENTS, TUMORS,
HOMICIDES
15-24 YEARS: ACCIDENTS, HOMICIDE,
SUICIDE (NONE ARE “NATURAL” CAUSES)
6. Cause of Death Related
with Age
Causes1
Rate 2
Under 1 Year: All
727.4
Causes
1–4 Years: All
32.6
Causes
5–14 Years: All
18.5
Causes
15–24 Years: All
80.7
Causes
Rates are expressed per 100,000 population
Excludes congenital heart disease
1
2
8. • Malformations
– primary errors of morphogenesis, usually multifactorial
– e.g. congenital heart defect
• Disruptions
– secondary disruptions of previously normal organ or body region
– e.g. amniotic bands
• Deformations
– extrinsic disturbance of development by biomechanical forces
– e.g. uterine constraint
• Sequence
– a pattern of cascade anomalies explained by a single localized
initiating event with secondary defects in other organs
– e.g. Oligohydramnios (Or Potter) Sequence, i.e., ABC…
• Syndrome
– a constellation of developmental abnormalities believed to be
pathologically related
– e.g Turner syndrome
14. Organ Specific Anomalies
• Agenesis: complete absence of an organ
• Atresia: absence of an opening (extreme stenosis)
• Hypoplasia: incomplete development or underdevelopment of an organ with decreased numbers
of cells
• Hyperplasia: overdevelopment of an organ
associated with increased numbers of cells
• Hypertrophy: increase in size with no change in
number of cells
• Dysplasia*: in the context of malformations
(versus neoplasia) describes an abnormal
organization of cells
15. Implantation and the Survival of
Early Pregnancy
Only 50-60% of all conceptions advance
beyond 20 weeks
Implantation occurs at day 6-7
75% of loses are implantation failures and
are not recognized
Pregnancy loss after implantation is 2540%
NEJM 2001; 345:1400-1408
16. Approximate Frequency of the More Common Congenital “Malformations” in
the United States
Malformation
Frequency per
10,000 Total
Births
Clubfoot (talipes equinovarus) without central nervous system
anomalies
25.7
Patent ductus arteriosus
16.9
Ventricular septal defect
10.9
Cleft lip with or without cleft palate
9.1
Spina bifida without anencephalus
5.5
Congenital hydrocephalus without anencephalus
4.8
Anencephalus
3.9
Reduction deformity (musculoskeletal)
3.5
Rectal and intestinal atresia
3.4
Adapted from James LM: Maps of birth defects occurrence in the U.S., birth defects monitoring
program (BDMP)/CPHA, 1970–1987. Teratology 48:551, 1993.
18. CAUSES OF ANOMALIES
Genetic
– karyotypic aberrations
– single gene mutations
Environmental
– infection
– maternal disease
– drugs and chemicals
– irradiation
Multifactorial
• Unknown
19. Causes of Congenital Anomalies in Humans
Frequency
Cause
(%)
Genetic
Chromosomal aberrations
10–15
Mendelian inheritance
2–10
Environmental
Maternal/placental infections
Maternal disease states
Drugs and chemicals
Irradiations
Multifactorial (Multiple Genes ?
Environment)
Unknown
2–3
6–8
1
1
20–25
40–60
Adapted from Stevenson RE, et al (eds): Human Malformations and Related Anomalies.
New York, Oxford University Press, 1993, p. 115.
20. Embryonic Development
Embryonic period
weeks 1- 8 of pregnancy
organogenesis occurs in this period
Fetal period
weeks 9 to 38
marked by further growth and maturation
“Perinatal” period
3 months BEFORE1 month AFTER, birth
22. Genetic Causes
Karyotypic abnormalities
80-90% of fetuses with aneuploidy die in utero
trisomy 21 (Down syndrome) most common
karyotypic abnormality (21,18,13)
sex chromosome abnormalities next most
common (Turner and Klinefelter)
autosomal chromosomal deletion usually lethal
karyotyping frequently done with aborted
fetuses with repeated abortions
Single gene mutations
covered in separate chapters
23. Maternal Viral Infection
• Rubella (German measles)
– at risk period first 16 weeks gestation
– defects in lens (cataracts), heart, and CNS
(deafness and mental retardation)
– rubella immune status important part of
prenatal workup
• Cytomegalovirus
– most common fetal infection
– highest at risk period is second trimester
– central nervous system infection
predominates
25. Teratogen Actions
• Proper cell migration to predetermined locations that
influence the development of other structures
• Cell proliferation, which determines the size and form of
embryonic organs
• Cellular interactions among tissues derived from
different structures (e.g., ectoderm, mesoderm), which
affect the differentiation of one or both of these tissues
• Cell-matrix associations, which affect growth and
differentiation
• Programmed cell death (apoptosis), which, as we have
seen, allows orderly organization of tissues and organs
during embryogenesis
• Hormonal influences and mechanical forces, which
affect morphogenesis at many levels
26. Diabetes Mellitus
Fetal Macrosomy (>10 pounds)
maternal hyperglycemia increases insulin
secretion by fetal pancreas, insulin acts
with growth hormone effects
Diabetic Embryopathy
most crucial period is immediately post
fertilization
malformations increased 4-10 fold with
uncontrolled diabetes, involving heart and CNS
Oral agents not approved in pregnancy
Diabetic women attempting to conceive
should be placed on insulin
27. Birth Weight and Gestational Age
Appropriate for gestational age (AGA)
between 10 and 90th percentile for gestational
age
Small for gestational age (SGA) , <10%
Large for gestational age (LGA) , >90%
Preterm
born before 37 weeks (<2500 grams) NL=3000
Post-Term
delivered after 42 weeks
28. Prematurity
Defined as gestational age <
37 weeks
Second most common cause of neonatal
mortality (after congenital anomalies)
Risk factors for prematurity
Preterm Premature Rupture Of fetal
Membranes (PPROM)
Intrauterine infection
Uterine, cervical, and placental abnormalities
Multiple gestation
29.
Fetal Growth Restriction
At least 1/3 of infants born at term are < 2.5kg
Undergrown rather than immature
Commonly underlies SGA (small for gestational
age)
Prenatal diagnosis: ultrasound measurements
Classification
Fetal
Placental
Maternal
30. Fetal FGR
Chromosomal abnormalities
17% of FGR overall
up to 66% of fetuses with ultrasound
malformations
Fetal Infection
Infection: TORCH (Toxoplasmosis, Other,
Rubella, Cytomegalovirus, Herpes)
Characterized by symmetric growth
restriction, i.e., head and trunk
proportionally involved
31. Placental FGR
Vascular
umbilical cord anomalies (single artery,
constrictions, etc)
thrombosis and infarction
multiple gestation
Confined placental mosaicism
mutation in trophoblast
trisomy is common
Placental FGR tends to cause
asymmetric growth with relative
sparing of the head
32. Maternal FGR
Most common cause of FGR by far
Vascular
diseases
preeclampsia
(toxemia of pregnancy)
hypertension
Toxins
ethanol
narcotics
and cocaine
heavy smoking
33. Organ Immaturity
Lungs
alveoli differentiate in 7th month
surfactant deficiency
Kidneys
glomerular differentiation is incomplete
Brain
impaired homeostasis of temperature
vasomotor control unstable
Liver
inability to conjugate and excrete bilirubin
34. APGAR (Appearance, Pulse, Grimace, Activity, Respiration)
Evaluation Of The Newborn Infant
Sign
Heart rate
Respiratory
effort
Muscle tone
0
Absent
Absent
1
Below 100
Slow, irregular
Limp
Response to
catheter in
nostril (tested
after
oropharynx is
clear)
Color
No
response
Some flexion of Active motion
extremities
Grimace
Cough or
sneeze
Blue, pale
2
Over 100
Good, crying
Body pink,
Completely
extremities blue pink
Data from Apgar V: A proposal for a new method of evaluation of the
newborn infant. Anesth Analg 32:260, 1953.
35. Apgar Score and 28 Day Mortality
Score
may be evaluated at 1 and
5 minutes
5 minute scores
0-1,
50% mortality
4,
20% mortality
≥ 7,
0% mortality
36. Perinatal Infection
• Transcervical (ascending)
– inhalation of infected amniotic fluid
• pneumonia, sepsis, meningitis
• commonly occurs with PROM
– passage through infected birth canal
• herpes virus– caesarian section for active herpes
• Transplacental (hematogenous)
– mostly viral and parasitic
• HIV—at delivery with maternal to fetal transfusion
• TORCH
• parvovirus B19 (Fifth), erythema infectiosum
– bacterial
• Listeria monocytogenes
38. Neonatal Respiratory
Distress Syndrome (RDS)
• 60,000 cases / year in USA with 5000
deaths
• Incidence is inversely proportional to
gestational age
• The cause is lung immaturity with decreased
alveolar surfactant
– surfactant decreases surface tension
– first breath is the hardest since lungs must be
expanded
– without surfactant, lungs collapse with each
breath
39. RDS Risk Factors
1)
Prematurity
by far the greatest risk factor
affected infants are nearly always premature
2) Maternal diabetes mellitus
insulin suppresses surfactant secretion
3) Cesarean delivery
normal delivery process stimulates surfactant
secretion
40. RDS Pathology
Gross
solid and airless (no crepitance)
sink in water
appearance is similar to liver tissue*
Microscopic
atelectasis and dilation/collapse of alveoli
hyaline membranes composed of fibrin and
cell debris line alveoli (HMD former name)
minimal inflammation
44. RDS Prevention and Treatment
Delay labor until fetal lung is mature
amniotic fluid phospholipid levels are useful in
assessing fetal lung maturity
Induce fetal lung maturation with antenatal
corticosteriods
Postnatal surfactant replacement therapy
with oxygen and ventilator support
45. Treatment Complications
Oxygen toxicity
Retrolental fibroplasia (Retinopathy.Of.Prematurity)
hypoxia causes ↑ Vascular Endothelial Growth Factor
oxygen derived free radicals damage tissue
(VEGF) and angiogenesis
Oxygen Rx suppresses VEGF and causes endothelial
apoptosis
Bronchopulmonary “dysplasia”
oxygen suppresses lung septation at the saccular
stage
mechanical ventilation
epithelial hyperplasia, squamous metaplasia, and peribronchial
and interstitial fibrosis were seen with old regimens of ventilator
usage and no surfactant use, but are now uncommon
lung septation is still impaired, in hyperoxygenation
46. Necrotizing Enterocolitis
Incidence is directly proportional to
prematurity, like RDS
approaches 10% with severe prematurity
2000 cases yearly in USA
Pathogenesis
not fully understood
intestinal ischemia
inflammatory mediators
breakdown of mucosal barrier
50. Immune Hydrops
Fetus inherits red cell antigens from the
father that are foreign to the mother
Mother forms IgG antibodies which cross
the placenta and destroy fetal RBCs
Fetus develops severe anemia with CHF
and compensatory ↑ hematopoiesis
(frequently extramedullary)
Most cases involve Rh D antigen
mother is Rh Neg and fetus is Rh Pos
ABO and other antigens involved less often
51. Pathogenesis of Sensitization
Fetal RBCs gain access to maternal
circulation largely at delivery or upon
abortion
Since IgM antibodies are involved in primary
response and prior sensitization is
necessary, the first pregnancy is not usually
affected
Maternal sensitization can be prevented in
most cases with Rh immune globulin
(Rhogam) given at time of delivery or
abortion (spontaneous or induced). Rhogam
is anti-D IgG and it coats the fetal cells!
52. Treatment of Immune Hydrops
In utero
identification of at risk infants via blood typing
by amniocentesis, (Chorionic Villi Sampling)
CVS, or fetal blood sampling
fetal transfusions via umbilical cord
early delivery
Live born infant
monitoring of hemoglobin and bilirubin
exchange transfusions
57. PHENYLKETONURIA (PKU)
• Ethnic distribution
– common in persons of Scandinavian descent
– uncommon in persons of African-American and Jewish
descent
• Autosomal recessive
• Phenylalanine hydroxylase deficiency leads to
hyperphenylalaninemia, brain damage*, and
mental retardation*
• Phenylananine metabolites are excreted in the
urine
• Treatment is phenylalanine restriction
• Variant forms exist
58. GALACTOSEMIA
• Autosomal recessive
• Lactose → glucose + galactose
• Galactose-1-phosphate uridyl transferase (GALT)
– GALT is involved in the first step in the transformation of
galactose to glucose
– absence of GALT activity → galactosemia
• Symptoms appear with milk ingestion
– liver (fatty change* and fibrosis), lens of eye
(cataracts*), and brain damage* involved (mechanism
unknown)
• Diagnosis suggested by reducing sugar in urine and
confirmed by GALT assay in tissue
• Treatment is removal of galactose from diet for at
least the two first years of life
60. Cystic Fibrosis (Mucoviscidosis)
Autosomal recessive
Most common lethal genetic disease
affecting Caucasians (1 in 3,200 live
births in the USA)
2-4% of population are carriers
Uncommon in Asians and African-Americans
Widespread disorder in epithelial chloride
transport affecting fluid secretion in
exocrine glands
epithelial lining of the respiratory,
gastrointestinal, and reproductive tracts
Abnormally viscid mucus secretions
61. Cellular Metabolism Of The Cystic Fibrosis
Transmembrane Regulator (CFTR, in red)
Harrison’s Internal Med, 16 th Ed
62. CFTR Gene: Normal
Cystic Fibrosis Transmembrane Conductance
Regulator (CFTR)
CTFR → epithelial chloride channel protein
Sweat gland
agonist induced regulation of the chloride channel
interacts with epithelial sodium channels (ENaC)
CTFR activation increases luminal Cl− resorption
ENaC increases Na+ resorption
sweat is hypotonic
Respiratory and Intestinal epithelium
CTFR activation increases active luminal secretion of
chloride
ENaC is inhibited
63. CFTR Gene: Cystic Fibrosis
Sweat gland
CTFR absence decreases luminal Cl− resorption
ENaC decreases Na+ resorption
sweat is hypertonic
Respiratory and Intestinal epithelium
CTFR absence decreases active luminal secretion of
chloride
lack of inhibition of ENaC is opens sodium channel with
active resorption of luminal sodium
secretions are decreased but isotonic
65. CFTR Gene: Mutational Spectra
More than 800 mutations are known
These are grouped into six classes
mild to severe
Phenotype is correlated with the
combination of these alleles
correlation is best for pancreatic disease
genotype-phenotype correlations are less
consistent with pulmonary disease
Other genes and environment further
modify expression of CFTR
67. Organ Pathology
Plugging of ducts with viscous mucus and loss of
ciliary function of respiratory mucosa
Pancreas
Liver
plugging of bile canaliculi with portal inflamation
biliary cirrhosis may develop
Genitalia
atrophy of exocrine pancreas with fibrosis
islets are not affected
Absence of vas deferens and azoospermia
Sweat glands
normal histology
68.
69.
70. Lung Pathology in CF
• More than 95% of CF patients die of
complications resulting from lung infection
• Viscous bronchial mucus with obstruction
and secondary infection
– S. aureus
– Pseudomonas
– Hemophilus
• Bronchiectasis
– dilatation of bronchial lumina
– scarring of bronchial wall
73. CF Diagnosis
Clinical criteria
sinopulmonary
gastrointestinal
pancreatic
intestinal
salt loss
male genital tract
Sweat chloride analysis
Nasal transepithelial potential difference
DNA Analysis
gene sequencing
74. Clinical Course and Treatment
Highly variable – median life expectance is
30 years
7% of patients in the United States are
diagnosed as adults
Clearing of pulmonary secretions and
treatment of pulmonary infection
Transplantation
lung
liver-pancreas
76. Sudden Infant Death Syndrome
NIH Definition
sudden death of an infant under 1 year of age
which remains unexplained after a thorough
case investigation, including performance of a
complete autopsy, examination of the death
scene, and review of the clinical history
Crib death
another name based on the fact that most die
in their sleep
77. Epidemology of SIDS
Leading cause of death in USA of infants
between 1 month and 1 year of age
90% of deaths occur ≤ 6 months age,
mostly between 2 and 4 months
In USA 2,600 deaths in 1999 (down from
5,000 in 1990)
78. •
•
•
Risk Factors for SIDS
Parental
– Young maternal age (age <20 years)
– Maternal smoking during pregnancy
– Drug abuse in either parent, specifically paternal marijuana and
maternal opiate, cocaine use
– Short intergestational intervals
– Late or no prenatal care
– Low socioeconomic group
– African American and American Indian ethnicity (? socioeconomic
factors)
Infant
– Brain stem abnormalities, associated defective arousal, and
cardiorespiratory control
– Prematurity and/or low birth weight
– Male sex
– Product of a multiple birth
– SIDS in a prior sibling
– Antecedent respiratory infections
Environment
– Prone sleep position
– Sleeping on a soft surface
– Hyperthermia
– Postnatal passive smoking
79. Morphology of SIDS
exclusion
SIDS is a diagnosis of
Non-specific autopsy findings
Multiple petechiae
Pulmonary congestion ± pulmonary edema
These may simply be agonal changes as they
are found in non-SIDS deaths also
Subtle changes in brain stem neurons
Autopsy typically reveals no clear cause of
death
80. Pathogenesis of SIDS
Generally accepted to be multifactorial
Triple risk model
Vulnerable infant
Critical development period in homeostatic
control
Exogenous stressors
Brain stem abnormalities, associated
defective arousal, and cardio-respiratory
control
81. Prevention of SIDS
Maternal factors
attention to risk factors previously mentioned
redress problems in medical care for underprivileged
Environmental
avoid prone sleeping
Avoid sleeping on soft surfaces
back to sleep program: infant should sleep in supine position
no pillows, comforters, quilts, sheepskins, and stuffed toys
Sleeping clothing (such as a sleep sack) may be used in
place of blankets.
Avoid hyperthermia
no excessive blankets
set thermostat to appropriate temperature
avoid space heaters
82. Diagnosis of SIDS
exclusion
SIDS is a diagnosis of
Complete autopsy
Examination of the death scene
Review of the clinical history
Differential diagnosis
child abuse
intentional suffocation
85. Hemangioma
Benign tumor of blood vessels
Are the most common tumor of infancy
Usually on skin, especially face and scalp
Regress spontaneously in many cases
87. Teratomas
Composed of cells derived from more than
one germ layer, usually all three
Sacrococcygeal teratomas
most common childhood teratoma
frequency 1:20,000 to 1:40,000 live births
4 times more common in boys than girls
Aproximately 12% are malignant
often composed of immature tissue
occur in older children
90. TABLE 10-9 -- Common Malignant Neoplasms of Infancy and Childhood
0 to 4 Years
5 to 9 Years
Leukemia
Leukemia
Retinoblastoma
Retinoblastoma
Neuroblastoma
10 to 14 Years
Neuroblastoma
Wilms tumor
Hepatoblastoma
Hepatocarcinoma
Soft tissue sarcoma (especially Soft tissue sarcoma
rhabdomyosarcoma)
Hepatocarcinoma
Soft tissue sarcoma
Teratomas
Central nervous system tumors Central nervous system
tumors
Ewing sarcoma
Lymphoma
Osteogenic sarcoma
Thyroid carcinoma
Hodgkin disease
91. Small
Round Blue Cell Tumors
Frequent in pediatric tumors
Differential diagnosis
Lymphoma
Neuroblastoma
Wilms tumor
Rhabdomyosarcoma
Ewings tumor
Diagnostic procedures
immunoperoxidase stains
electron microscopy
chromosomal analysis and molecular markers
92. Neuroblastomas
Second most common solid malignancy of
childhood (650 cases / year in USA)
Neural crest origin
adrenal gland – 40 %
sympathetic ganglia – 60%
In contrast to retinoblastoma, most are
sporadic but familiar forms do occur
Median age at diagnosis is 22 months
93. Neuorblastoma Morphology
Small round blue cell tumor
neuorpil formation (fibers, i.e., axons
dendrites, mostly unmyelinated)
rosette formation
immunochemistry – neuron specific enolase
EM – secretory granules (catecholamine)
Usual features of anaplasia
high mitotic rate is unfavorable
evidence of Schwann cell or ganglion
differentiation favorable
Other prognostic predictors are used by
pathologists and oncologists
97. Clinical Course and Prognosis
Hematogenous and lymphatic metastases to liver,
lungs and bone
90% produce catecholamines, but hypertension is
uncommon
Age and stage are most important prognostically
Amplification of N-myc oncogene
< 1 year age: good prognosis regardless of stage
present in 25-30% of cases and is unfavorable
up to 300 copies on N-myc has been observed
Risk Stratification
low risk: 90% cure rate
high risk 20% cure rate
98. Wilms Tumor
Most common primary renal tumor of
childhood
Incidence 10 per million children < 15 years
Usually diagnosed between age 2-5
5 – 10 % are multi-focal, i.e., bilateral
synchronous
metachronous
99. Clinical Features
Most children present with a large
abdominal mass
Treatment
nephrectomy and combination chemotherapy
two
year survival up to
90% even with spread
beyond the kidney
100. Pathogenesis of Wilms Tumor
10% of Wilms tumors arise in one of three*
congenital malformation syndromes with
distinct chromosomal loci
Familial disposition for Wilms is rare, and most
of these patients have de novo mutations
Nephrogenic rests of adjacent parenchyma
present in 40% of unilateral tumors, 100% of
bilateral tumors
if found in one kidney, these rests predict an
increased risk for tumor in the contralateral
kidney
101. Pathology of Wilms Tumor
Gross
well circumscribed fleshy tan tumor
areas of hemorrhage and necrosis
Microscopic: triphasic appearance
Blastema: small blue cells
Epithelial elements: tubules & glomeruli
Stromal elements
Anaplasia
correlates with p53 mutation and poor
prognosis and resistance to chemotherapy
Weenies!
Not just the same diseases in smaller people, but DIFFERENT and UNIQUE DISEASES!
Good relative numbers to remember. One of the greatest numbers to measure a country’s quality of medicine, is infant mortality, as well as longevity.
Definitions to know well. Perinatal? Prenatal?
After infancy, surviving that first crucial year, ACCIDENTS are the number one cause of children’s mortality.
What are the common childhood tumors? Leukemia and brain tumors.
The closer to birth, the riskier it is! (until teens, when homicides and suicides enter the picture)
If you took the “unnatural causes” out of the last age group 15-24, it would be even smaller!
Remember: In the classic anatomic classifications of diseases, degenerative, inflammatory, neoplastic, “CONGENITAL ANOMALIES” are the HARDEST to fit in. Embryologic errors is the best short definition.
Know a classic example of each!
Figure 10-1 Malformations. Human malformations can range in severity from the incidental to the lethal. Polydactyly (one or more extra digits) and syndactyly (fusion of digits), both of which are illustrated in A, have little functional consequence when they occur in isolation. Similarly, cleft lip (B), with or without associated cleft palate, is compatible with life when it occurs as an isolated anomaly; in the present case, however, this child had an underlying malformation syndrome (trisomy 13) and expired because of severe cardiac defects. The stillbirth illustrated in C represents a severe and essentially lethal malformation, where the midface structures are fused or ill-formed; in almost all cases, this degree of external dysmorphogenesis is associated with severe internal anomalies such as maldevelopment of the brain and cardiac defects.
Disruption. Disruptions occur in a normally developing organ because of an extrinsic abnormality that interferes with normal morphogenesis. Amniotic bands are a frequent cause of disruptions. In the illustrated example, note the placenta at the right of the diagram and the band of amnion extending from the top portion of the amniotic sac to encircle the leg of the fetus. (Lets click back to our original definition of “Disruption”) Did the hand and foot FORM normally before it was constricted? YES
Note that these differentiations are not always written is stone, e.g., Potter’s Sequence was formerly called Potter’s Syndrome. The term “sequence” implies, one thing leads to another. These events all follow the simple concept of oligohydramnios.
Schematic diagram of the pathogenesis of the oligohydramnios sequence, explaining the LOGIC of the findings.
Amnion nodosum are nodules on the fetal surface of the amnion, and is frequently present in oligohydramnios
Figure 10-4 Infant with oligohydramnios sequence. Note the flattened facial features and deformed right foot (talipes equinovarus), and nodules on the amnion (amnion nodosum)
*NOTE the pediatric definition and examples of dysplasia are DIFFERENT from the pre-neoplastic definitions we learned about many time previously.
Do most losses occur around fertilization/implantation time? YES
Why would the term “WITHOUT CNS deformity” be used?
Which SYSTEM had the highest incidence of congenital anomalies, mostly, minor? Answer: GU
What famous sports figure overcame her club foot to the maximum degree? Ans: Kristi Yamaguchi, gold medal 1992, figure skating
Varus IN, Valgus OUT.
Why is the last item on this list in the BIGGEST font? Ans: Because it is the majority of the cases.
Most genetic studies on stillborns and severe anomalies yield negative results.
More precise figures.
You can’t call a fertilized ovum an embryo until about ONE WEEK post-fertilization.
And after 8 weeks, you have to call it a FETUS.
Figure 10-5 Critical periods of development for various organ systems and the resultant malformations. As you might have guessed, most severe changes take place the earliest, and most changes take place a lot earlier that you think in general.
And the generally accepted significant earliest ones are brain and heart.
1st trimester:Rubella (any ccpp question about a rubella baby would include the buzz wird “cataract”)
2nd trimester CMV
By far the last two do ten times as much damage than the first one.
As long as we opened the door to the term “teratogen” lets talk about how they are known to work. These are NOT just theories!
If you suspect that the 3 usual suspects are also the major teratogens, you are correct.
If you ever asked any physician to give you the differential diagnosis of macrosomy, it is not likely he would ever recall anything beyond diabetes.
Notice these are all MATHEMATICAL definitions.
Is PRETERM the same as PREMATURE? YES, yes strictly a TIME TERM.
Why is “Maternal” in the biggest font? Ans: MOST COMMON, by far.
Is this the same as IMMATURITY? NO
As you can see, FGR is HIGHLY related to malformations (anomalies)
Placental weight correlates with fetal weight ~500g/3000g
What is “pre”-eclampsis (versus eclampsia)? What is the difference? What is the cause? Why is it also called “toxemia”?
Many theories have attempted to explain why preeclampsia arises, and have linked the syndrome to the presence of the following:
endothelial cell injury
immune rejection of the placenta
compromised placental perfusion
altered vascular reactivity
imbalance between prostacyclin and thromboxane
decreased glomerular filtration rate with retention of salt and water
decreased intravascular volume
increased central nervous system irritability
disseminated intravascular coagulation
uterine muscle stretch (ischemia)
dietary factors, including vitamin deficiency
genetic factors
air pollution
What does all this baloney mean? It means they still don’t know!
You can also think of these as being the CHIEF CONCERNS in treating premies.
During childbirth, the infant is exposed to maternal blood and body fluids without the placental barrier intervening and to the maternal genital tract. Because of this, microorganism transmitted by blood (Hepatitis B, HIV), organisms associated with sexually transmitted disease (Neisseria gonorrhoeae and Chlamydia trachomatis), and normal flora of the genito-urinary tract are among those commonly seen in infection of the newborn.
Name the three histologic changes in lung maturation. Ans:
capillaries approaching pneumocytes,
cuboidalsquamous,
higher air/non-air ratio
RDS also previously referred to as HMD (Hyaline Membrane Disease)
Also remember that the term “hepatization” is a term used to describe the “consolidation” or loos of crepitance in the adult lungs during pneumonia also.
“Hyaline “ membranes are proteins, e.g., fibrin, and dead calls
Uneven ventilation results is ventilation/perfusion mismatch. Lung that is perfused but not ventilated results in what amounts to R—>L shunting of unoxygenated blood into the arterial circulation. Physiologically, perfusion is matched to ventilation by arterial constriction due to hypoxia, hypercarbia and acidosis so that nonventilated areas are not perfused. The same mechanism results in generalized pulmonary vasoconstriction in a pathological state with generalized hypoxia, etc. The endothelial and epithelial damage together with the hyaline membranes impair diffusion and result in a vicious cycle. Do you remember ARDS or adult “SHOCK” lung?
Figure 10-12 Necrotizing enterocolitis. A, Postmortem examination in a severe case of NEC shows the entire small bowel is markedly distended with a perilously thin wall (usually this implies impending perforation). B, The congested portion of the ileum corresponds to areas of hemorrhagic infarction and transmural necrosis microscopically. Submucosal gas bubbles (pneumatosis intestinalis) can be seen in several areas (arrows), caused by gas forming bacteria.
Hydrops = Water = Heart failure
Hydrops fetalis. There is generalized accumulation of fluid in the fetus. In B, fluid accumulation is particularly prominent in the soft tissues of the neck, and this condition has been termed cystic hygroma. Cystic hygromas are characteristically seen, but not limited to, constitutional chromosomal anomalies such as 45,X0 karyotypes.
Hemolytic disease of the newborn is another name for this entity and is most often used by non-pathologists.
Name 3 ways that erythropoietic marrow can expand or hyperplase: Cellularity, into appendicular skeleton, extramedullary
Extramedulary hematopoiesis consisting primarily of erythroid precursors in the liver sinusoids. Erythroblastosis fetalis is another term for immune hydrops. Remember that normally there may be some “extramedullary hematopoesis” in a fetal liver at birth, but this rather quickly (weeks?) resolves.
Unconjugated bilirubin is water insoluble and lipophilic. It can cross the blood brain barrier and lead to kernicterus. The basal ganglia and thalamus are particularly susceptible.
As we learned in genetics chapter, almost ALL IEM diseases are autosomal recessive. Recall the differences between AR and AD diseases, from a pedigree and clinical point of view.
*CCPP: Normal at birth but progressive impairment of cognitive function.
Infants affected by galactosemia typically present with symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice.. In the USA now, ALL newborns are screened for galactosemia.
*** CCPP
Cellular metabolism of the cystic fibrosis transmembrane regulator (CFTR) protein conductance (red). In a normal cell (left), CFTR is synthesized in the rough endoplasmic reticulum (RER), is glycosylated in the Golgi apparatus, and functions as a Cl– channel and regulator of other ion channels when located in the plasma membrane. Two possible outcomes of mutations in the CF gene are shown (right). (1) If a mutation disturbs protein folding, e.g., the F508 mutation, CFTR is degraded intracellularly so that no protein is transported to the plasma membrane. (2) With other mutations, the abnormal protein is processed and trafficks to the plasma membrane but functions abnormally at that site.
CF sweat is HYPERTONIC, and in general exocrine secretions are VISCOUS
Chloride channel defect in the sweat duct (top) causes increased chloride and sodium concentration in sweat. In the airway (bottom), cystic fibrosis patients have decreased chloride secretion and increased sodium and water reabsorption leading to dehydration of the mucus layer coating epithelial cells, defective mucociliary action, and mucus plugging of airways. CFTR, Cystic fibrosis transmembrane conductance regulator; EnaC, Epithelial sodium channel.
The many clinical manifestations of mutations in the cystic fibrosis gene, from most severe to asymptomatic. (Redrawn from Wallis C: Diagnosing cystic fibrosis: blood, sweat, and tears. Arch Dis Child 76:85, 1997.)
Pancreas in Cystic Fibrosis. Note that the ducts contain inspisated material and the acini are atrophic and the stroma exhibits fibrosis and chronic inflamation. The islets are preserved.
Normal pancreas for comparison
Figure 10-23 Lungs of a patient dying of cystic fibrosis. There is extensive mucus plugging and dilation of the tracheobronchial tree. The pulmonary parenchyma is consolidated by a combination of both secretions and pneumonia—the green color associated with Pseudomonas infections. (Courtesy of Dr. Eduardo Yunis, Children's Hospital of Pittsburgh, Pittsburgh, PA.)
SIDS remains a basic mystery, still, even after all these years, mostly because it is a diagnosis of exclusion.
If a disease is defined as ABSENCE of etiologies, then it is understandable that it would be ridiculous to ask, “What is the etiology of SIDS?”
Even though the age range for SIDS is 0-1 year, most deaths are much closer to zero.
These are PRIMARILLY STATISTICAL
The are PRIMARILLY THEORETICAL
If a cause for SIDS was found, would it still be called SIDS?
Is it surprising that the top three benign tumors are all CONNECTIVE tissue (i.e., mesenchymal or stromal)?
What is a “birth mark”?
Figure 10-25 Congenital capillary hemangioma at birth (A) and at age 2 years (B) after spontaneous regression. (Courtesy of Dr. Eduardo Yunis, Children's Hospital of Pittsburgh, Pittsburgh, PA.)
Capillary vs. cavernous: Small spaces, small person?
Figure 10-26 Sacrococcygeal teratoma. Note the size of the lesion compared with that of the infant.
The TWO tumors comprise the vast majority of pediatric SOLID (non hematopoetic) malignant tumors.
A word about “SPONTANEOUS REGRESSION” of malignant tumors.
Good general principle: almost all pediatric malignancies are composed of cells which have small round nuclei and minimal cytoplasm (blue), so that is why we make fun of the pediatric pathologists, and say, all the have to look at is SMALL ROUND BLUE cell tumors.
You MUST remember:
What a ROSETTE looks like
The fact that they are CLASSICALLY the hallmarks of neuroblastomas
What are the RED streaks?
Ganglioneuroblastoma: note the typical neuroblastoma features in the lower portion of the picture. Towards the top there is evidence of maturation into ganglion cells, which is a favorable morphologic feature. This is a recurrent principle of the histopathology of tumors, i.e., if the tumor cells actually look like they are “differentiating” into something, this is a more favorable prognostic feature, than if they DO NOT!
A wide variety of expensive genetic and other tests can be done to help put neuroblastoma patients into risk rates.
What does “synchronous” and “metachronous” mean?
Ans: synchronous means “occurring at the same time”, metachronous means NOT occurring at the same time, but one after another.
These 3 syndromes associated with the greatest risk of Wilms tumor are the WAGR(O) syndrome (Wilms tumor-aniridia-genitourinary malformation-retardation), the Denys-Drash Syndrome, and the Beckwith-Wiedemann Syndrome.
Find the blastema, epithelial elements, and stromal elements.
Find the blastema, epithelial elements, and stromal elements.
What do those things look like at the tip of the arrows? (Hint: this is a KIDNEY tumor)
Find the blastema, epithelial elements, and stromal elements.