Pbd - Week 4

Front 1

What are the normal temperature ranges in children:
- rectal
- ear
- oral
- axillary

Back 1

Children's temperatures
- rectal: 36.6 - 38
- ear: 35.8 - 38
- oral: 35.5 - 37.5
- axillary: 34.7 - 37.3

Front 2

What is the average temperature for adults when taken via the following routes:
- rectal
- ear
- oral
- axillary

Back 2

Temperatures in adults:
- rectal: 37.5
- ear: 37.3
- oral: 37.0
- axillary: 37.0

Front 3

When is a person's temperature the lowest? Highest?

Back 3

Lowest in the early morning and highest in the evening.

Front 4

What is the site of neural control of thermoregulatory responses

Back 4

The pre-optic region of the anterior hypothalamus.

Front 5

Microbes, inflamatory agents & some cytokines induce the synthesis and release of pyrogenic cytokines from certain cells (monocytes, PMNs, Lcytes, etc). List 2-3 examples of these cytokines and what is there destination. What do they cause this tissue to secrete? What is the effect of this secretion and how does this effect cause fever?

Back 5

Pyrogenic cytokines:
IL-3, TNF, IFN, IL-6
When they reach the endothelial cells of the hypothalamic vascular organs they stimulate it to release PGE2. Elevated PGE2 causes an increase in cAMP, monoamines and Ca+ in the thermoregularoty centre of the ant Hothalamus = vconstriction and increased heat production

Front 6

What are 6 diseases that can accompany a fever?

Back 6

1. Infections
2. Inflammatory or thrombotic
3. Neoplastic
4. Immune
5. Endocrine or metabolic
6. Non-infectious inflammation (like crohn's)

Front 7

What are 7 cardinal symptoms of a fever?

Back 7

1. chills
2. rigor
3. sweats
4. Tachypnea
5. Tachycardia
6. changes in mental status
7. blister of fever (ie cold sores d/t reactivation of herpes)

Front 8

What is the mechanism of antipyretic medications?
When should they be given?

Back 8

They inhibit COX2 which interferes with the synthsis of PGE2 in the hypothalamus (PGE2 causes increase cAMP & Ca+ = increase set-point = heat generation & vconst)
Antipyretics should only be given for hyperthermia (>49.6C) with anhidrosis, or for hyperpyrexia (>41C)

Antipyretics DO NOT prevent febrile seizures in children!

Front 9

What is a minor anomalie?

What is a major anomalie?

Back 9

Minor anomalie: unusual anatomical featurs of no serious medical/cosmetic consequence.

Major anomalie: primary - malformation
secondary - disruption & deformation

Front 10

When should you suspect "covert anomalies" or a syndromic diagnoses

Back 10

In the presence of 3 or more minor anomalies.

Front 11

How is "malformation" defined?

Back 11

Malformation = a morphological defect resulting from an intrinsically abnormal developmental process. (ie problem with the substrate)

Front 12

How is a "disruption" defined?

Back 12

Disruption = a morphological defect resulting from the extrinsic breakdown of, or interference with an originally normal developmental process.
E.g. an amniotic band tha

Front 13

How is a "disruption" defined?

Back 13

Disruption = a morphological defect resulting from the extrinsic breakdown of, or interference with an originally normal developmental process.
E.g. an amniotic band that amputates some toes

Front 14

How is a deformation defined?
E.g.?

Back 14

Deformation: an abnormal form, shape or position of part of the body caused by MECHANICAL forces
E.g. Potter sequence cause by oligohydramnios

Front 15

How is a dysplasia defined?

Back 15

Dysplasia: an abnormal organization of cells into tissue and its morphological results. The process and consequence of dishistiogenesis.
E.g. Achondroplasia

Front 16

What is a "sequence" birth defect?

Back 16

Sequence = pattern of multiple anomalies derived from a single known (or presumed) prior anomaly or mechanical factor. E.g Potter's where the prior anomaly was the lack of kidneys or amniotic leak.

Front 17

What is an association birth defect?

Back 17

Association = non-random concurrence of independent malformation whose etiology (single or multiple) is unknown.
E.g. VACTERL

Front 18

What are the anomalies seen in the association birth defect VACTERL?

Back 18

Vertebral anomalies
Anal atresia
Cardiovascular anomalies
Tracheoesophageal anomalies
Esophageal atresia
Renal anomalies
L - preaxial Limb anomalies

Front 19

What is a birth defect syndrome?

Back 19

Syndrome = a recognized pattern of developmentally independent malformation having one etiology.
E.g Down's, Marfan etc

Front 20

Autosomal dominant "vertical" inheritance:
- which gender(s) are affected and which transmit?
- does the affected person have to have an affected parent?

Back 20

Autosomal dominant:
- BOTH transmit and BOTH can be affected
- Each affected individual has an affected parent unless it is a de novo mutation

Front 21

In an autosomal dom condition, disease occurs despite the normal gene (& normal gene product)... why? (4 reasons)

Back 21

1. Haploinsufficiency - having only a single functional copy of a gene (other copy inactivated by mutation) and the single functional copy can't produce enough gene product to bring about a wild-type condition
2. Dominant neg effect - synthesis of an abnormal protein that interferes with normal one
3. Mutation enhances the function of the protein (overactivity = bad)
4. Inheriting a mutant copy of one gene may predispose to cancer where is there is a high chance of random loss/mutation of the other copy

Front 22

Define the term penetrance?

Back 22

Penetrance = the proportion of individuals carrying a particular variation of a gene (an allele or genotype) that also express an associated trait. May be explained in part by modifier genes in different individuals

Front 23

Define variable expressivity.
How can this phenomena be explained (3 ways)

Back 23

Variable Expressivity - the different degrees of severity of the manifestations of a disease in different individuals with mutations in the same gene.
May be explained by:
genotype - phenotype effects
presence of modifier genes
environmental factors

Front 24

Familal hypercholesteremia presents in early to late adulthood. What are the 3 phenotypic features?

What is the etiology?

Back 24

1. increased serum cholesterol
2. premature atherosclerotic plaques
3. myocardial infarctions

Etiology: mutations in the LDL receptor that leads to accumulation of LDL in the serum

Front 25

How is familial Hcholesteremia diagnosed (2) and managed (2)?

Back 25

Dx: quantification of the LDL-receptor function in skin Fblasts.
DNA analysis to find mutation

Management:
- low fat high carb diet
- medication (statins)

Front 26

What are the 4 major phenotypic features of achondroplasia?

What is the etiology (ie gene product that is affected and the impact of the mutation of gene product functioning)

Back 26

1. prenatal (3rd trimester) onset
2. proximal short stature
3. megalencephaly (large head)
4. narrow foramen magnum

Etiology:
mutation in fibroblast growth receptor 3 (normally binds Fblas growth factor to slow formation of bone - mutation = gain of function = inappropriate inhibition of chondrocytes in growth plate = inhibited growth)

Front 27

How is achondroplasia diagnosed?

How is it managed in childhood? Early adulthood?

Back 27

Dx: confimation of clinical features by radiology or DNA analysis.

Management: goal tx complications
- childhood - monitor for chronic otitis media, Hcephalus, brain-stem compression
- early adult - spinal stenosis (check reflexes), obesity, dental complications

Front 28

CF is a progressive pulmonary diseases with an onset in neonatal to adulthood. What are 5 cardinal features of CF? (1 is specific to babies)

Back 28

1. high sweat Cl-
2. azoospermia
3. exocrine pancreatic insuff
4. growth failure
5. meconium ileus

Front 29

What is the etiology of CF?

Back 29

Mutations in the CFTR (a Cl- channel protein that maintains the hydration of secretions) cause thick, dehydrated secretions.
Esp common in ppl of northern European decent.

Front 30

How is CF diagnosed (3)?

How is CF managed?

Back 30

CF is dx:
1. Clinical criteria
2. sweat Cl- test
3. molecular testing to look for mutation (>1500 have been ID'd)

Management: symptomatic tx to clear lung secretions, prevent & tx infections and proper nutrition (mean survival age is now 37yrs)

Front 31

What is the inheritance pattern of CF?

Back 31

"Horizontal" aka autosomal recessive - the disease "skips a generation, and parents of an affected child are usually normal (but heterozygous for mutant allele)

Front 32

Sickle cell anemia usually occurs in childhood. What are the 4 phenotypic features of the disease?

What is the etiology of the disease?
(how does it cause anemia?)

Back 32

Phenotype:
1. FTT
2. anemia
3. functional asplenia
4. infarction

Etiology: a missence mutation (Glu --> Val) in the B subunit of Hgb. In low O2 blood the mutant hgb molecules aggregate into fibers = sickeling. Sickeled cells are removed from the blood faster than they can be replaced = hemolytic anemia

Front 33

How is sickle cell anemia Dx?

How is sickle cell anemia managed? What form of Tx is currently being developed?

Back 33

Dx: significant quantities of sickeled Hgb. Can use DNA analysis to confirm.

Management is base on support & prevention for complications (fever, resp symptoms, splenomegaly & neuro changes).
Stem cell T-plant is being developed but has ++ risks

Front 34

What are the symptoms of being heterozygot for the sickle cell trait?

Back 34

Ppl with sickle cell trait are asymptomatic unless under conditions of severe anoxia in which case they may be sickeling.
Advantageous b/c confers resistance to malaria.

Front 35

Duchene muscular dystrophy usually presents during childhood. What are the 4 phenotypic features of the disease?

H

Back 35

1. muscle weakness
2. Calf hypertrophy
3. ? intellectual compromise (? r/t lack of motor skills and not actual intelligence)
4. elevated serum CK

Front 36

What is the etiology of duchene muscular dystrophy:
- implicated gene & gene-product/function)

What is the name of the milder form of the disease?

Back 36

- DMD gene encodes dystrophin (intracellular protein that maintaines muscle membran integrity & assembly of the synaptic junction)

- if the mutation allows for some production of dystrophin then the clinical features are much milder & called Becker Muscular Dystrophy.

Front 37

How is Duchene Muscular Dystrophy diagnosed? (3)

How is it managed? (mean age of death?)

Back 37

Dx: family Hx, muscle biopsy (to test for immunoreactivity of dystrophin), serum CK, and DNA analysis

Management - NO cure!
symptomatic: anti-congestive meds for cardiomyopathy
- prednisone to improve strength & function
Mean age of death is 40.

Front 38

For duchenne's, what is the pattern of inheritance?
How do 1/3 of all cases occur? What about the remaining 2/3?

Back 38

X-linked recessive.
1/3 are new mutations and 2/3 of cases have carrier mothers (each of their sons have 50% risk of disease and dtrs have 50% risk of carrier status)

Front 39

Some females express an X-linked recessive trait/disease in spite of having 2 X chromosomes.... why?

Back 39

1. Turner's syndrome (only inherited one X xsome)
2. X-inactivation: in all female cells, only 1 X is 'active' and the other is randomly 'inactivated'. If, by chance, the mutant X is active and the normal X is inactive then the female will have clinical manifestations of the disease.

Front 40

Hemophilia A can occur in infancy --> adulthood. What are the 3 phenotypic features of the disease?

Mutations in what gene cause the disease? What is the effect of the mutation?

Back 40

1. Bleeding diathesis
2. Hemarthroses - bleeding into the joints
3. hematomas

Mutations in the F8C gene that encoder clotting factor 8. (occurs in 1/7500 males). Without F8 the normal clotting cascade is blocked.
** 1/3 of all mutations are de novo! **

Front 41

How is hemophilia A diagnosed (2ways)

How is it managed?

Back 41

Dx: measure F8 activity levels (this predicts clinical severity), DNA analusis of the F8 gene

Management: IV replacement of F8
(this has increased life expectancy from 1.4 years to ~65yrs)

Front 42

Multifactorial diseases show much less heritability and do not have a single causative factor. In Alzheimer's disease, which gene has been implicated as the "susceptibility locus?"

Back 42

Susceptibility locus: APOE gene. (linkage analysis & association studies have found that APOE e4 form is increase in frequency in ppl with AD)

Front 43

What is the difference between developmental age and gestational age?

Back 43

Developmental age is from the date of fertilization, to the date of birth or intrauterine death. Gestational age however starts at the date of the mother's LMP.

Front 44

How long is the embryonal period? How about the fetal period? Perinatal period?

Back 44

Embryonal period: conception to 8th week
Fetal period: 9th week to birth
Perinatal period: birth to end of 1st week of life.

Front 45

What is the difference between a still birth and a spontaneous abortion?

Back 45

A stillbirth is the death of a fetus (>20wks gestational or > 500g) before the complete expulsion or removal of the fetus. Whereas a spontaneous abortion is loss of a fetus/embryo that is < 20wks.

Front 46

What is fetal maceration and when/why does it occur?

Back 46

Maceration = softening & degenerative changes of fetal tissues that occurs after the death & retention of fetus in utero. Occurs d/t digestive action of fetal autogenous enzymes.

Front 47

What (broadly speaking) tends to be the cause of an early (embryonic period) vs. a late (fetal period) spontaneous abortion?

Back 47

Early abortions: often d/t genetic abnormalities of the embryo characterized by growth disorganization ranging from an emby placental chorionic sac (GD1) to a ++ maalformed embryo (GD4). Late abortions relfect more diverse maternal, placental & fetal conditions (ie genes + env).

Front 48

Stillbirths after 28wk (>1000g) account for 55% of perinatal deaths. ~9% of stillbirths occur during L&D ("fresh" stillbirth). While a clear cause is NOT id'd in up to 50% of stillbirths, what do most of these babies show signs of? What is the most common recognized cause of SB's?

Back 48

Most stillbirth babies have sign of suffering from acute intrauterine asphyxia.
Of the recognized causes of SB, maternal antepartum hemorrhage (abruptio placentae) is the most common. Lots of other factors are associated but not causes!

Front 49

What is the correct definition of asphyxia?
Asphyxiation is a mechanism of injury and death and has many causes. What are 2 examples of causes of asphyxiation?

Back 49

a decrease in the amount of O2 and an increase in the amount of CO2 in the body d/t interference w/respiration.
E.g.
Umbilical cord compression & placental abruption

Front 50

What are 4 signs of intrauterine asphyxiation? (M, EA, P, C&H)

Back 50

1. Meconium d/c (when in the amniotic fluid it is a response to actue physiologic stress such as asphyxia)
2. Excessive aspiration of amniotic debris (fetus takes large gulps in response to stress)
3. Thoracic visceral petechiae (++ small hemorrhages over the pleura, epicardium & thymus)
4. Pulmonary congestion & hemorrhage - as the fetus dies from asphyxia, lungs become engorged e/blood & may have extensive bleeding into alveoli or lobular septa. ** NOT specific to that mechanism of death**

Front 51

Some intrauterine infections result from hematogenous spread from the mother. What are the most important agents of blood borne infections? (ie TORCH)

Back 51

T - toxoplamosis
O - Other (syphilis, various viruses)
R - Rubella (causes growth restriction, microceph, cataract, myocarditis, deafness & heart disease)
C - Cytomegalovirus (causes tissue necrosis & destruction esp in liver, brain & lungs) greatest risk in 2nd trimester
H - Herpes Simplex virus (infection occurs during passage thru birth canal = viremia w/massive necrosis of liver & encephalitis)

Front 52

Hydrops fetalis is the accumulation of extavascular fluid leading to what 4 signs?

Back 52

- ++SQ edema
- pleural effusion
- percardial effusion
- ascities
Fully developed Hydrops is usually fatal for the fetus or neonate (latter usually dies b/c lungs not fully developed)

Front 53

What are the immune and non-immune causes (name 3/6) of hydrops fetalis?

Back 53

immune: RH incompatibility. Only if mom is Rh -ve and fetal blood enters her circulation. She will develop anti-Rh+ IgG Ab's that cross the placenta and cause hemolysis. (In ABO incompatibility mom develops IgM Ab's that can't cross the placenta.
non-immune causes: LOTS! congenital heart malformation, xsomal abnormalitis, anemia, Hgbnopathies, metabolic storage diorders, TORCH infections, etc.

Front 54

What tissues tend to be infected by ascending genital tract infections vs maternal blood borne infections?

What do ascending infections most commonly cause? Why/how?

Back 54

Ascending infections - infect placental surface tissues (ie chorioamnionitis).
Blood borne - infect placental cillus tissue (chronic villitis)

Ascending infections proliferate in amniotic fluid and are swallowed by the fetus. Most commonly cause premature labor by causing the release of inflamatory cells which stimulat contraction (~25% of all preterm births are associated with chorioamnionitis)

Front 55

Describe the pathway of the blood flow in the fetus while it is in utero. How does this change with birth?

Back 55

O2 rich blood flows into the R atria, thru the foramen ovale into the L atria (to the general circulation). It also bypasses the pulmonary circulation by shunting from the pulmonary artery through the ductus arteriosis to the thoracic aorta.

Front 56

What causes the fetal holes in the heart to close?

Back 56

1. F.ovale: closes d/t elevated L atrial BP
2. Ductus arteriosis closes d/t reduction of the pulmonary vascular bed resistance

Front 57

What are the 5 criteria for apgar's?

Back 57

1. HR (absent, <100, >100)
2. RR (absent, slow/irreg, good)
3. Muscle tone (limp, some flexion, active)
4. Response to catheter in nose (none, grimace, cough/sneeze)
5. Color (blue/pale, pink body/blue limbs, fully pink)
** take at 1min and at 5min. If <7 at 5min repeat at 10min

Front 58

Birth trauma's are usually associated with that?
What are the common injuries (4)?

Back 58

Most commonly associated with intrument delivery (forceps/vacuum).
Injuries:
- Skull / clavicle #
- intracranial hemorrhage
- visceral damage (liver lacerations)
- nerve palsies (esp. brachial plexus)

Front 59

What is the gestational age of babies which are:
-premature
-mature
-postmature

Back 59

-premature: < 37wks
-mature: 37-42wks
-postmature: >42wks

Front 60

When is the neonatal period?
What does it mean to be small for gestational age? What about large?

Back 60

Neonatal = Birth to 4wks.
Small for GA = <10th percentile
Large for GA = > 90th percentile

Front 61

What are the 6 causes of prematurity?

Back 61

(<37wks!)
1. PROM = rupture 2hrs before the onset of labour; occurs in 30-40% of premies, is a risk factor for fetal sepsis
2. Chorioamnionitis - intrauterine infection +- PROM
3. Placenta previa - placental implantation over the uterine outlet
4. Impaired uteroplacental perfusion (materna HTN, CVas disease or lupus)
5. Cervical incompetence
6. multiple gestations

Front 62

What causes Hyalin Membrane disease (Neonatal Resp Distress Syndrome - NRD) (~5steps)

Back 62

Hyaline Membrane disease (NRD)
Cause: deficiency of surfactant = ↑ surface tension requiring high inspiratory pressures to inflate alveoli which collapse btwn breaths. Hypoxia and ↑CO2 result causing pulmonary Vcon & hypoperfusion. This leads to necrosis, desquamation of debris & leakage of fluid.
** surfactant is from Type 2 pneumocytes & appears after 35 weeks.

Front 63

What are the 3 stages of Hyalin Membrane Disease (a consequence of prematurity)?
(E, R, Fp)

Back 63

1. Exudative (0-4days) - necrosis, exudation of fluid & formation of membranes
2. Reparative (4-10days) - regen of T2 pneumocytes, prolif of septal mesenchymal & removal of membranes & debris.
3. Fibro-proliferative (10-20days) - fibrosis, squamous metaplasia and remodeling of alveoli. Can become chronic (>1mo) = bronchopulmonary dysplasia

Front 64

What is the main Tx for Hyalin membrane Disease?

Back 64

Exogenous surfactant by inhalation therapy
Prolonging pregnancies
Giving mothers exogenous C-steroids to induce fetal surfactant production

Front 65

Necrotizing Enterocolitis (NEC) is a multifactorial complication of prematurity. It involves bacterial colonization and immature host defenses. When does it develop and what is an example of predisposer?
Pathogenesis?
What happens as it heals?

Back 65

NEC develops as soon as oral feeding starts. Heart disease predispose babies to NEC.
Ischemic necrosis of the bowel mucosa --> full thickness. Mucosa sloughs off w/some bleeding. (may cause ileus). Bacteria invades (can get gas producers). Full thickness necrosis can = perfs & perontonitis.
Healing occurs with adhesions & scarring = stenosis or obstruction (40% require Sx resection)

Front 66

Germinal Matrix Hemorrhage:
- where is this?
- when/why does hemorrhage occur?
- consequnces?

Back 66

Germinal matrix is a highly vascular area in the fetal cerebral hemispheres that produces neruons & glial cells.
- It involutes by ~32wks, but is prone to hemorrhage d/t hypoxic insults. Bleeding can extend into the intraventricular cavity & adjacent tissue.
- Affects 40% of very low birth wt babies, & consequences will depend on extant of tissue destruction from the bleed (as well additional damage from original hypoxic insult)

Front 67

What is meant by arteriole "onion skinning?" and what is the cause?

Back 67

Sustained HTN (whatever the cause) causes irreversible hypertrophy in the arterioles that only causes further HTN

Front 68

Describe each of the following vaculitis:
1. Giant cell - location & inflam type
2. Takayasu's - age & inflam type
3. Polyarteritis nodules - inflam type, effect?
4. Kawasaki's - age & location
5. Wegner's - inflam type, location/effect
6. Churg-Strauss - inflam type

Back 68

1. Giant cell = most common, granulomatous inflammation of temporal artery
2. Takayasu's = women <40yrs, granulomatous

3.Polyarteritis nodules: (HepB) necrotizing inflam, ischemia d/t thrombosis (symptoms depend on vessel)
4. Kawasaki - babies' coronary arteries Japanese >>>> US

5. Wegners - granulomatous, in lungs causes GNephritis
6. Churg-Strauss - granulomatous, allergy

Front 69

If a thrumbus forms in the L artia it can only embolise to where?

What is Phlegmasia cerulea dolens?

Back 69

A thrombus from the L atria can only embolize into the arterial side b/c can't cross capillaries!

PCD = throbosis at the ileo-femoral veins causing a blue, swollen & painful leg

Front 70

What causes varicose veins?

What are the 3 components of Virchow's triad?

Back 70

Incompetent valves

Virchow: hypercoagulability, hemostasis & endothelial damage

Front 71

Rheumatic fever occurs in 3% of ppl who have had an acute stept group A (B-hemolytic infection). What is the hypothesized mechanism?

Back 71

Cross reactivity between bacterial Ag's and those on the heat, joints and tissues (it is NOT d/t direct bacterial infection!)

Front 72

Aschoff bodies are pathognomonic (diagnostic) of what disease? What are they?

Back 72

Aschoff bodies are areas of focal fibrinoid nevrosis surrounded by inflam cells that later resolve into firbous scar tissue. They are diagnostic of R - fever

Front 73

What valves are most commonly affected by R-fever?

Back 73

Mitral regurgitation and aortic stenosis is common whereas tricuspid involvement is less common.

Front 74

In order to get infective endocarditis you need to have:
Conditions that favor infection of the endoth (2) and,
Implantation of the organism on teh endocardial surface

Back 74

Conditions that favor infection: 1. endothelial surface injury
2. throbums formation at the site of injury

Implantation of organisms:
1. bacterial entry into the circulation
2. bacterial adherence to the endocardial surface

Front 75

When endothelim gets damaged a plt-fibrin thrombus formed. How does this help bacteria? (2ways)

Back 75

1. Provides a surface for adherence
2. fibrin then covers the bugs and protects them from host defences

Front 76

What advantage do G+ve and streps have that helps them cause infective endocarditis?

Back 76

G+ve bacteria are well suited to cause IE b/c they can evade complement.
Steptoccoci are good at causing IE b/c the dextran on their cell wall helps them adhere

Front 77

What are 6 findings on P/E indicative of Infective Endocarditis?
M R. JOSP

Back 77

1. Osler's Nodes= pea-sized red nodules on the fingers & toes
2. Petechiae (d/t vasculitis)
3. Splinter hemorrhages under the nail
4. Janeway lesions = painless nodular discolorations on palms & soles
5. Roth spots = emboli to retina
6. Murmur (either d/t underlying predisposing pathology or to IE itself)

Front 78

What is the karyotype for Klinefelter's?
What is the phenotype and when does it appear?

Back 78

1/1000 males, 47XXY
Normal until puberty --> tall, thin, Hogonads, infertile, gynecomastia and increased learning difficulties

Front 79

What is the phenotype for 47, X Y Y
-height, intelligence, ferility, dysmorphisms

Back 79

Tall, increased risk of educational or behavioural problems, normal intelligence, nondysmorphic & fertile

Front 80

47 XXX (Trisomy X)
- height, intelligence & fertility

Back 80

47 X X X
Above average stature, fertile & some learning & behaviour problems

Front 81

What are the indications for invasive prenatal testing? (6)

Back 81

1. Late maternal age
2. previous child with T 21
3. Carrier (of balanced Xsome)
4. MSS +ve at 16weeks
5. Integrated prenatal screen +ve (1st & 2nd trimester)
6. abnormal USS

Front 82

What are 6 indications for Xsomal analysis?

Back 82

1. known or suspected xsomal abnormalities
2. multiple congenital abnormalities
3. disorder of sex differentiation
4. Undiagnosed mental retardation
5. Multiple miscarriages / infertility
6. Select malignancies (solid or hemat)

Front 83

3 wyas can a balanced zxsomal defect lead to phenotypic abnormalities?

Back 83

1. Break w/in a gene
2. Position effect (closer or further to a promoter)
3. Cryptic deletion or duplication near the breakpoints

Front 84

What are the 6 pathogenetic mechanisms that account for the large majority of heart malformations?
(Tm, bf, a, e, tg, s/l)

Back 84

1. Interruption of normal tissue migration
2. Abnormal intracardiac blood flow
3. Abnormal cardiac apoptosis
4. Abnormal cardiac ECM
5. Abnormal targeted tissue growth
6. Abnormal situs and looping of the heart

Front 85

In a L --> R shunt most of the blood goes to where? This causes __x__. What is the effect of x on the heart?

What is the effect of x on the shunt? What in turn does this cause?

Back 85

Most of the blood goes to the pulmonary circulation. This increased blood flow causes structural changes in the pulmonary arteries that increase vascular resistance. The R ventricle dilates & hypertrophies in response to these high pressures (Cor pulmonale with possible heart failure)

If the resistance gets high enough the shunt REVERSES and baby can become cyanotic.

Front 86

In a R --> L shunt blood bypasses the lungs. What 3 things does this cause?

On what 2 things does survival depend?

Back 86

1. R ventricular Htrophy - d/t excessive demand on the R ventricle
2. Systemic hypoxia (b/c blood inadequately oxygenated)
3. Heart failure

Survival depends on:
1. Some pulmonary perfusion
2. some mixing of the blood (ie presence of a shunt!)

Front 87

What are 4 common L ---> R shunts?

What are 4 common R ---> L shunts?

Back 87

Common L --> R shunts:
1. ASD
2. VSD
3. patent ductus arteriosus
4. AVSD

Common R --> L shunts:
1. Tetralogy of Fallot
2. Transposition of great arteries
3. Tricuspid atresia
4. anomalous pulmonary venous connection

Front 88

What are the symptoms of a coarctation of the aorta that has a patent vs. closed ductus arteriosus?

Back 88

L-sided obstructions
Patent DA : differential cyanosis of the body (blue bottom)
Closed DA: differential Bp's in upper/lower or R/L.

Front 89

What is an early life presentation of a L-sided obstruction?

What is the effect on the heart of an aortic valve stenosis or atresia?

Back 89

systemic underperfusion & metabolic acidosis.

L ventricular hypoplasia

Front 90

What are the consequences of a R-sided heart obstruction? (4)

Back 90

1. R ventricular hypertorphy or hypoplasia
2. Cyanosis (requires a R-->L shunt)
3. R heart failure
4. Pulmonary hypoperfusion

Front 91

Define the following terms:
- infant:
- postneonatal infant:
- Sudden Unexpected Natural Death
- Sudden Unexpected Infant Death:

Back 91

- infant: < 1 yrs old
- postneonatal infant: 28days - 1yr
- Sudden Unexpected Natural Death: death that occurs instantaneously or w/in 24hrs of onset of acute S & S
- Sudden Unexpected Infant Death: sudden & unexpected death occurring in a child < 12months

Front 92

What is the most common cause of post-neonatal infant death in industrialized countries?

What is the most common cause of death in childhood?

Back 92

SIDS!

Unintentional injury (MVC & drowning)

Front 93

What are the 9 risk factors for SIDS? (4 are to do with the mother)

Back 93

1. Prone sleeping position
2. Soft bedding +- plush toys
3. Overheating
4. low SES
5. Maternal smoking during pregnancy
6. Maternal age < 20
7. late or no prenatal care
8. preterm +- male babies

Front 94

It is unclear whether SIDS is a single disease entity or an end result of several disease processes. Given this what is the most widely accepted hypothesis for the pathogenesis of SIDS? (triple risk model)

Back 94

SIDS results from delayed development of arousal and Card/resp control:
- precipitated by an environmental trigger
- acts on a genetically/developmentally vulnerable infant
- occurs during a period when maturation of critical homeostatic controls is happening

Front 95

What are the gross and microscopic findings of SIDS?
1. petechiae in 3 places
2. respiratory system
3. brain

Back 95

1. Petechiae on thymus, pleura & epicardium
2. Resp tract inflammation with pulmonary congestion & edema
3.Brain swelling with increased wt & gliosis

Front 96

What are the top 4 causes of early cholestasis?

Back 96

1. Biliary atresia
2. Idiopathic neonatal hepatitis
3. a1-antitrypsin deficiency
4. Other causes of hepatitis
(Alagille syndrome, choledochal cyst)

Front 97

What is biliary atresia?

Back 97

Biliary atresia is a progressive necrotizing inflammatory process causing loss of patency in the extra-hepatic biliary system.
Occurs in 1/10 00 births and is the most common cause of infantile jaundice for which Sx is indicated

Front 98

What are the 2 clinical groups associated with biliary atresia?
1 - onset? cause?

2 - onset? cause?

Back 98

Perinatal form (80% of all cases)
- jaundice at 4-8wks
- progressive destruction of ducts beginning after birth
- cause unknown ? viruses / genetics

Fetal form (20%)
- persistent jaundice from birth caused by presumed abnormal development of biliary system (associated w/ other anomalies)

Front 99

With regard to location of the fibrosis, what are the 3 types of biliary atresia?

Which types are operable?

Back 99

Type I: common bile duct
Type II: hepatic duct below porta hepatis
Type III: bile ducts at porta hepatis

Only types I and II are operable.
* Cirrhosis will develop w/in 3-6 months

Front 100

What are the 2 main criteria for diagnosing biliary atresia?
How are these criteria met (2 investigations)?

Back 100

Must confirm biliary obstruction and exclude all other causes by:
1. Imaging - USS, HIDA scintigraphy or intraoperative cholangiogram
2. Biopsy - live changes associated with large bile duct obstruction & to exclude other causes

Front 101

Optimal treatment of biliary atresia requires what?

What are the 3 surgical treatment options?

Back 101

Optimal tx of biliary atresia requires diagnosing it before cirrhosis. (BA will cause death w/in 2years without Tx).

1. In types I & II, resection of the affected ducts.
2. In types III (the majority of cases) - "Kasai" or Portoenterostomy; affected ducts are removed and a loop of small bowel is anastamosed to the porta hepatis to drain the bile (BUT get ++ ascending infections)
3. Liver transplant (80% 5-yr survival rate)

Front 102

What are 3 or 4 of the common S&S of an inborn error in metabolism?

Back 102

1. acute or chronic encephalopathy
2. Myopathy
3. metabolic acidosis
4. Hoglycemia
5. hepatic syndromes
6. cardiomyopathy
7. dysmorphic features

Front 103

PKU (incidence 1/12-16,000; carriers 1/50), is an inborn error of aa metabolism. What are the S&S if untreated?

What is one rare cause of PKU?

Back 103

- impaired brain development & microcephaly (mental retardation)
- Sz's
- behaviour problems
- musty body odor
- eczema
- decrease skin and hair pigmentation (blonde & blue eyes)

Rare cause: Cofactor (BH4) deficiency - will present the same way

Front 104

If a neonate has significantly raise Phe levels (>>120) then how is PKU dx confirmed?

Back 104

PKU enzyme works in the liver therefore must do biopsy to confirm disorder.

Front 105

PKU has genetic heterogeneity. What are the 4 types of PKU listed in lecture?
1. Classical (enz activity? tx?)
2. Type II / atypical (severity?)
3. Type III (enz activity? tx?)
4. Type IV (cause? prognosis?)

Back 105

1. Classic: < 1% residual enzyme activity = strict diet for life
2. Atypical or Type II - milder & can tolerate some Phe
3. Type III: 5% enzyme activity no diet needed
4. Type IV: BH4 cofactor defect, need NT replacement therapy - poor outcome
4

Front 106

In order to do newborn screening what are the criteria for:
- the disease (2)
- the test (5)
- the management (2)

Back 106

Disease: must be common and medically significant

Test: sensitive, specific, cost-effective, easy, & must have confirmatory test available

Management: access to supports, must be benefits to early dx

Front 107

What is the current recommendation for the Tx of PKU?

Back 107

People used to think it was only important to be on the diet during certain years but new studies show that going off the diet in adulthood will have consequences.