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What are the parts of the blastocyst and what do they become?
Inner cell mass: becomes fetus
Outer trophoblast: develops important endocrine fxns as well as contributing to formation of placenta
What are the functions of the placenta?
Circulatory, respiratory, digestive, renal, some endocrine
How does the size of the mom's pituitary change during pregnancy?
Increases its size by 1/3 to 1/2 during pregnancy. Mostly due to hyperplasia of the lactotrope's increased production of PRL
What does PRL couple with during gestation to stimulate the formation of the mammary glands?
Estrogen and Progesterone
What are the concentrations of the following after pregnancy:
GH, ACTH, FSH, TSH, LH
GH: stays about same or decreases
ACTH/TSH: increase some
FSH and LH: fall to low levels
Because of hormones produced by the placenta, what might a pregnant woman have signs/symptoms of?
Hyperthyroidism (hCT has some TSH-like activity), Cushing's, DM
What effect do estrogen and progesterone have on the isthmus?
Estrogen constricts the isthmus
Progesterone relaxes the isthmus
During which phase does estrogen stimulate regrowth of endometrium following menstruation?
During follicular phase
What does estrogen do to the cervical mucus?
Thins and alkalinizes it (facilitates conception).
After ovulation, how long does estrogen enhance sm m contractility causing isthmus of tubes to contract for?
3 days
How does PG in semen aid in transport of sperm?
Stimulates backward contractions in uterus.
Which female hormone is produced by W in sexual stimulation and also helps propel sperm?
OT, stimulates contractions to propel sperm up
What stimulates production of glandular (secretory) endometrium?
Progesterone
What is responsible for hCG's long 1/2 life of 24 hours in the B-subunit of Glycoprotein hormones?
The fact that it is ~10% sialic acid
What synthesizes hCG?
Syncytiotrophoblast
What is the function of the hCG?
Maintains corpus luteum; Stimulates Leydig cells in male fetus.
How does the concentration of hCG change throughout pregnancy?
Doubles in ~1d (it doubles every 48 hours during 1st 6 wks). Peaks about 10-12 weeks and then drops rapidly before declining slowly throughout rest of pregnancy.
At its peak [ ], what is hCG compared with LH level?
200x more what teh LH level was during the LH-ovulatory surge.
How soon is hCG detected?
8d after fertilization (~1-2 days after blastocyst has undergone implantation). Detected in urine after 14 days.
Low levels of hCG during pregnancy are signals for what?
Ectopic pregnancy, threatening abortion
Which hormone is believed to serve as maternal GH of pregnancy, stimulate nitrogen, calcium and potassium retention, stimulate maternal lipolysis, exert anti-insulin action
hCS
How is glucose moved from maternal blood to fetal side?
By facilitated transport
Is fetal blood glucose more or less than mom's?
Less than mom's
Is there more hCS in maternal or fetal circulation?
Maternal
Low levels of hCS are a sign of what?
Placental insufficiency
How does the activity of E & P change during pregnancy?
Increases
What produces E & P during 1st two months of pregnancy?
Corpus luteum (essential for 1st 7-8 weeks of gestation
What is required to maintain pregnancy?
Progesterone.
What does the placenta make from cholesterol?
Synthesizes pregnenolone and progesterone from cholesterol
What does conjugation of DHEA w/ sulfate do?
Decreases its androgenic potency which is especially important when the fetus is female
What is the principle E formed during pregnancy?
Estriol
What makes up the fetoplacental unit?
Placenta + fetal adrenal
What does the fetoplacental unit produce?
Three different estrogens: estriol, estradiol, estrone
Is estriol more or less potent than estradiol and estrone?
Estriol is about 1/80 the potency of estradiol and about 1/7 that of estrone
This stimulates growth/production of female external genitalia, uterus (enlarged from 50 to 1100 gms), ducts in breast, hormone binding proteins:
Estrogen
Some of this substance enters fetal circulation and becomes substrate for synthesis of cortisol and corticosterone by fetal adrenals, while the rest serves to increase mom's plasma level. Also forms and maintains decidua in uterus, maintains endometrium:
Progesterone
Polypeptide hormone produced by corpus luteum, placenta and other tissues. Role not clear: may help w/ implantation and inhibit uterine contractions early in pregnancy. Helps soften pubic symphysis and ripens cervix before labor:
Relaxin
Increases transport of Ca from maternal to the fetal circulation:
Parathyroid Hormone-Related Peptide (PTH-rP)
When does increase in oxytocin secretion begin?
Once labor is initiated. Estrogen has stimulated an increase in oxytocin receptors and distention of uterus may also serve to increase # of oxytocin receptors
What is the positive feedback loop that enhances delivery?
Once contractions begin, they reflexively stimulate stronger contractions
What do estrogens and progesterone do to lactation?
They block lactation
How long can a nursing mom experience lactational amenorrhea?
25-30 weeks
What is the thick yellow fluid produced by mammary glands the first days after delivering. Source of important nutrients and vitamins. Essential for infant's initial well-being, immune system and growth:
Colostrum
What does the mom pass to her baby through her milk?
Antibodies and other factors resulting in healthier babies. Some pediatric specialists recommend that babies are almost exclusively breastfed for the first 6 mos.
How are water, many electrolytes and respiratory gases transferred across placenta?
Simple diffusion
How is glucose transported across the placenta?
Facilitated Diffusion
How are amino acids and inorganic phosphate transported across the placenta?
Secondary Active Transport
How is Calcium transported across the placenta?
Active transport (CaATPase)
Why do moms need extra iron during pregnancy?
W/ pregnancy, mom needs an additional 1 gm of iron to produce RBCs (Hb/RBC production increases). Need 600mg for maternal RBC production. 400mg for fetus and placenta RBC production. Need 60mg/day of elemental iron which can be supplied by 300mg of ferrous sulfate.
How does cardiac output change in pregnancy?
Increases ~30-40%. Stroke volume increaes initially, HR increases next.
Which heart murmurs are common and benign in pregnancy?
Late systolic and ejection (due to decrease in viscoscity of the mom's blood and increase in stroke volume).
What is a serious and perhaps pathologic murmur during pregnancy?
One during diastole
Difference between changes of stystolic P and Diastolic P?
Systolic P dec is small.
Diastolic P dec is modest, then returns towards pre-preg levels
Are BP values greater than pre prego normal or abnormal?
Abnormal
What are the consequences of iron deficiency in a pregnancy?
Iron depleted mother may experience iron deficient anemia, preterm labor, late-spontaneous abortion
What are the calcium levels like in the fetal blood vs the maternal?
Both total and ionized calcium levels usually higher in fetal than maternal blood.
How much milk does a mom produce at height of lactation?
1.5L/day of milk or more if nursing twins
What are the consequences of maternal calcium deficiency?
Ca in mom's milk will come from either mom's dietary Ca intake or from mom's bones
How does total ventilation change during pregnancy?
Increases 30-40%
How does PCO2 change from pre-prego?
Decreases: because ventilation increases more than metabolic rate.
What is PO2 in placental venous blood compared to maternal arterial blood?
PO2 in placental venous blood is ~30 mmHg while the maternal arterial blood is ~100mmHg. This PO2 is adequate for the fetus because high fetal blood flow and high affinity that fetal Hb has for oxygen (ie 70% SO2 at PO2=30mmHg)
What is the intentional control or violent behavior by a perpetrator with an intimate relationship with the victim?
Domestic violence
The following are examples of what:
Verbal abuse (about power and control), intimidation, physical assault, social isolation, sexual assault, economic control
Intimate partner violence
What is the cycle of violence w/ intimate partner violence?
Triangle b/w tension building phase, explosive phase and calm phase
How many women presenting to Er have been threatened or injured at some point in their life by an intimate partner?
50%
What percentage of women presenting to ER are due to domestic violence/sexual assault?
9%
Percentage of sexual assaults by known perps? Elder abuse percent from a family member?
70% for both
How does the risk of abuse change during a pregnancy?
Risk of abuse increases w/ each trimester and postpartum
How much greater is the risk of abuse in a person w/ an unintended pregnancy?
3x greater
When is the most dangerous time for a women in a domestic violence situation? (talking about pregnant women)
When she decides to leave
What is replacing postpartum hemorrhage, pre-eclampsia and pulmonary embolism as a cause of pregnancy related death?
Murder
What are the SAFE questions?
Safety: do you feel safe in relationship?
Afraid/Abused-Have you ever been in a relationship where you were threatened, hurt or afraid?
Friends/Family: are your friends or family aware that you have been hurt? Could you tell them and would they be able to give you support?
Emergency plan: do you have a safe place to go and the resources you need in an emergency?
What are the following signs indicative of?:
Inadequate explanation of injury, central bruising, defensive wounds, head wounds, frequent ER visits to different ERs, difficulty with GYN exam, oversolicitous partner, suicidal ideation, unintended pregnancy, eating disorder, noncompliance, late prenatal care, repeated abortions HIV+
Abuse
If the patient tells you not to, can you call police?
No. But if there is a gun or knife that has been used, you have to call police.
Are many women turned away when seeking refuge?
Yes, 30% (due to lack of space)
What are the major reasons the abused deny abuse?
SELF BLAME, not emotionally ready to admit the reality of the situation, fear of failure, shame, fear of rejection, fear reprisal, believe no alternative exists, believe abuse will not occur again, lack of resources
Any sexual act performed on a person without his or her consent:
Sexual assault
Any unwanted part genital anal or oral penetration by any body or object as a means of control over another person:
Rape
How long after is the window to gather forensic evidence?
Up to 72 hours; can take 2 hours to collect
Where do you dismiss rape victims to?
Safe refuge--not home
Where is DNA obtained from in a rape evaluation?
Saliva, blood, fingernail scrapings, bed sheets, underclothes, hard surfaces, condoms, dry swabs
What are the major treatments that rape patients require?
TETANUS*, Gonorrhea, chlamydia, wet smear for trich or sperm, bacterial vaginosis, HIV, syphyllis, Hep B, Pregnancy (while waiting for police)
What treatments do you give patients who have been raped?
Azithromycin 1gm po (chlamydia) AND Cefiximine 400mg po (gonorrhea).
-If allergy to Azithromycin, then use Doxycycline 100mg BID for 7 days. Allergy to cephalosporins, then Cipro 500mg po
Treatment for Trichamoniasis after rape?
Metronidazole; 2 gm po today
Treatment for Syphyllis?
Pen G, Benzathine 2/4 million units IM
Treatment for Hep B?
3 dose vaccine
What is the pregnancy prophylaxis indicated by rape?
Within 72 hours of assault, Levonorgestrel (Plan B) 0.75 mg )(1now and 1 in 12 hours). OCP 0.05/0.03mg 4 tabs now and 4 in 12 hours.
-Also antiemetics (Zofran or Phenergan 1 hr prior to dose).
-Pt needs to sign if they do not want to take it
What is the most common drug facilitated sexual assault cause?
ALCOHOL*, Benzodiazepines, Gamma-hydroxybutyrate (GHB), Flunitrazepam (Rohypnol), Last 2 drugs cleared in 12 hours
What are the long term effects of sexual abuse?
PTSD*, Pregnancy, STDs, HIV, HPV, infertility
The complex of somatic, cognitive, affective and behavioral effects of psychological trauma:
Post Traumatic Stress Disorder
The following medical disorders are all linked to what?:
Chronic pelvic pain, sexual dysfunction, IBS, recurrent vaginitis and/or STDs, sleep disorder, eating disorder, somatic disorder, chronic headache
Abuse
What are the 2 phases of PTSD?
1) Acute and disorganization phase (lasts days to weeks; irritable, nightmares, etc)
2) Integration and resolution phase
What is the lifetime prevalence of PTSD?
12% (50% of the time it is sexual assault)
What is the ACOG and AMA Guideline for domestic abuse?
Physicians should routinely assess all pregnant women for domestic violence. Clinician should be aware of characteristics of abuse such as bruising, improbable injury, depression, late prenatal care and missed prenatal appts.
What ay be the most effective method of preventing child abuse?
Routinely asking about domestic violence
Occurs when women wanted to postpone conception for at least 2 years or did not desire pregnancy at all:
Unintended pregnancy
The following are all examples of what: Induced abortion for maternal physical or mental health, fetal congenital anomaly, selective reduction of # of fetuses to decrease risks assoc w/ multiple gestation, result of rape or incest, nonviable pregnancy:
Therapeutic abortion
Induced abortion for any other reason:
Elective abortion
What happens in 1910 regarding abortion?
45 states banned abortion. Prohibited under Comstock (anti-obscenity) laws (contraception was also banned)
What happened between 1967 and 1973 regarding abortion laws?
1/3 of states liberalized abortion laws
What was the first state to liberalize its abortion laws?
Colorado in 1967
When did the Supreme Court uphold Roe vs. Wade?
1973 (Said right to privacy extends to reproductive health. States cannot limit access to abortion before viability, which is a gray area)
How many pregnancies are there in the US annually and how many end in abortion?
~6.4 annually with 1/4 ending in abortion.
What percentage of pregnancies are intended vs unintended?
51% intended; 49% unintended
How many abortions were there in 2008?
Approximately 1.21 million
By the age of 45, how many women will have had an abortion?
1/3
How is the abortion rate changing?
Slow, steady decline
How have overall unintended pregnancy rates changed? How have unintended pregnancies changed among poor women? Among Higher income women?
Overall unintended pregnancy rates have stagnated. Unintended prego has inc by 29% among poor women while dec 20% among higher income women.
Which age group most commonly has abortions?
20's (esp 20-24)
When do most abortions occur?
in first 12 weeks (90%)
T or F: Abstinence education has not been shown to dec unintended pregnancy
True
What are the following all reasons for?: Not ready, financial, education/career, completed childbearing, abuse, fetal anomaly
Reasons women have abortions
What is the mortality of abortions?
0.6/100,000 procedures (10x safer than carrying to term)
Is there an association b/w abortion and breast CA?
No
According to our lecturer, does abortion pose hazard to women's mental health?
No
Worldwide, how many pregnancies are unintended and how many end in abortion?
2/5: unintended
1/5: end in abortion
What percentage of women WW live under highly restrictive abortion laws?
40%
How many unsafe abortion deaths are there per year?
46,000 (13% of maternal deaths)
What does the newer model of estrogenic activity lead to?
Newer model leads to purely estrogenic activity in some tissues while partially estrogenic/anti-estrogenic activity in others
What is the goal of SERMs?
Beneficial estrogenic actions in select tissues w/ anti-estrogenic action in other tissues (bone, brain, liver breast, endometrium)
Drugs w/ indication of prevention and treatment of ER+ Breast CA:
Tamoxifen, Toremifene
What do Tamoxifen and Toremifene do in regards to prevention?
Prevents CA in high risk women (c/l breast)
What do Tamoxifen and Toremifene do to bone and breast?
Receptor antagonists in breast.
Agonist in bone
What do tamoxifen and toremifene do to estrogen in ER positive cells?
Block the binding of estrogen to ER positive cells
What is the difference between cis and trans conformations of tamoxifen class?
Cis has estrogenic activity.
Trans has anti-estrogenic activity (target tissue/gene/species variability)
Which configuration is the tamoxifen class customarily used for?
Its trans-conformation (inhibits proliferation of BC cells and reduces tumor size); (Trans- has anti-estrogenic activity).
What does Tamoxifen do to overall survival?
Increases disease free and overall survival--treatment lasts up to 5 years
What is the response rate of Tamoxifen in ER+ vs. ER-/PR+ patients?
50% response rate in ER+; 70% in ER-/PR-
What are the effects of tamoxifen on bone?
Anti-resorptive effect on bone (clinical decrease in vertebral and hip fracture)
What is the effect that tamoxifen has on TC, LDL, Lp(a)?
Decrease
What affect does tamoxifen have on HDL/TH and Apo-A1?
No change in HDL/TH, raises Apo-A1
T or F: Tamoxifen is useful to prevent osteoporosis
True
What are the side effects of Tamoxifen?
2-3x increased risk of DVT/PE/Stroke; 2x increased risk of endometrial carcinoma via partial agonist effects; "hot flashes." If post-menopausal and has breast CA, will re-introduce menopausal symptoms. Pregnancy category D
What is the MOA of Toremifene?
Analog of Tamoxifen and has similar pharmacological actiosn. Competitive inhibition of E binding to ER. Promote production of transforming growth factor-beta (TGF-Beta: inhibitory GF)
What is the lipid profile of Toremifene compared to Tamoxifen?
Toremifene has a slightly greater and more beneficial lipid profile effect (increases HDL)
What is Raloxifene indicated for?
Prevention and treatment of osteoporosis. Breast CA prophylaxis in high risk pt defined as: at least 1 breast biopsy showing lobular CIS or atypical hyperplasia. 1 or > 1st degree relatives w/ breast CA. 5 yr predicted risk of breast CA>1.66%
What effect does Raloxifene have on bone?
Has estrogenic actions on bone. Anti-resorptive effect (increased bone mineral density in lumbar spine, hip and femoral neck). Reduces vertebral fx by 30-50% and increases spinal BMD by 2%. No significant effects on non-vertebral fx.
What effect does Raloxifene have on lipids?
Has + effects on lipids. Reduces LDL and +/- reduction in TG (no increase in HDL). Shown to reduce coronary events (nonfatal MI, death, hospitalization) in at-risk pt--not in those with existing CVD
What effect does Raloxifene have on invasive breast CA tumors and cell lines?
Anti-proliferative effect. There is a decreased relative risk over yrs (RRR of up to 75% after 3 yrs vs. placebo; up to 72% after 4 yrs vs. placebo; up to 66% after 8 years vs. placebo).
Does raloxifene have any effect on non-invasive BC?
NO; only invasive
Does raloxifene induce proliferation or thickening of endometrial tissue?
No; no apparent risk of endometrial CA
What are the SE of Raloxifene?
Hot flashes, leg cramps, increased risk of DVT/PE (yet 30% < tamoxifen). Pregnancy category X.
Does Raloxifene have an increased risk in endometrial CA?
No, Because it is an endometrial antagonist.
What is Clomiphene indicated for?
Infertility in anovulatory women. PCOS
What does Clomiphene have the most significant effect on?
Induction of ovulation in women w/ amenorrhea, PCOS, and dysfunctional bleeding w/ anovulatory cycles.
What is the primary MOA of Clomiphene?
Primarily blocks inhibitory actions of estrogen on hypothalamus GnRH and pituitary gonadotropin release.
What does Clomiphene do to gonadotropin secretion?
Increases it thereby stimulating the ovaries to develop oocyte follicles--customarily dosed b/w cycle--days 5&9.
What is Clomiphene a partial agonist of?
Estrogen receptors in hypothalamus; prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation.
What is the effect of Clomiphene?
Most significant effect on induction of ovulation in W w/ amenorrhea, PCOS, dysfunctional bleeding w/ anovulatory cycles
What are the SE of Clomiphene?
Multiple births (3-5%, 99% twins)--multiple simultaneous pregnancies
-Ovarian cysts (ovarian CA w/ prolanged use)
-Ho flashes
-Blurred vision
-Luteal-phase dysfxn (inadequate progesterone production)
-Ovarian enlargement
What is Fulvestrant indicated for?
Metastatic ER+ breast CA in W w/ dz progression after tamoxifen therapy (tamoxifen failure)
What is the MOA of fulvestrant?
Anti-estrogenic on breast CA cells/tumors; Used b/c of bulky side chain, fulvestrant hinders ER dimerization and increased degradation thereby abolishing ER mediated gene transcription (not just a receptor blocker).
Why can Fulvestrant be used when Tamoxifen doesn't work?
Tamoxifen can't hinder ER dimerization and increase degradation thereby abolishing ER mediated gene transcription
How is Fulvestrant administered?
Administered as monthly IM depo-injection
What are the SE of Fulvestrant?
Hot flashes; GI distress (N/V); HA/back pain/asthenia
What is the most commonly diagnosed CA among Am W?
Breast CA
Where does Breast CA rank with cause of death?
Second leading cause of CA-related death among W--2nd to lung CA
What are the gene mutations associated w/ hereditary breast cancer?
BRCA1, BRCA2
What are the risk factors for Breast CA?
Increasing age*-Greatest risk;
-Also family history, mutations in BRCA1/2, early menarche, nulliparity, late menopause, estrogen use, dietary factors
What are the majority of breast cancers classified as?
Sporadic (70-80%: idiopathic, or genes that have not been discovered)
How often is familial clustering present in breast CA and what is the importance of it?
15-20%; No evidence of Mendelian inheritance; May be weaker predisposition. Non-genetic influences: env't/toxins, socioeconomic factors, diet, etc
What (according to Dr. Adkison) is the deadliest of all GYN cancers?
Ovarian CA (5th leading COD from CA among US W)
What is the 5 year survival rate of ovarian CA?
~46% (better survival rate in women <62 yo)
-Non-mets 5 yr survival rate ~93%, but early dx is difficult
Of the hereditary causes of ovarian CA, what are the MCC?
BRCA1 (70%), BRCA2 (20%), HNPCC (2%), Other single genes (8%)
What are BRCA1 and BRCA2 adn what do they do?
Theya re tumor suppressor genes; Different types do cell division, controlling genes, DNA repair genes, apoptotic genes
What chromosome is BRCA1 located in?
Chr17
What are the two motifs of BRCA1?
-Ring-finger domain @ N-terminus
-BRCT domatin at the C-terminus
Protein function of BRCA1 is expressed when?
In most tissues during G1 through S, may be involved in DNA repair during homologous recombination. Can activate p21 CDK inhibitor (growth suppressor at G1/S checkpoint)
Where is BRCA2?
Chr 13
What is the size of BRCA2 compared w/ BRCA1 and are there recognizable motifs?
Twice as large as BRCA1; No recognizable motifs
What 1 or more of the following, what do you suspect?:
History of early onset breast CA(<50yo), Early onset breast CA adn ovarian CA (any age), FH of breast CA or breast and ovarian CA consistent w/ AD inheritance. Personal or FH of M breast CA?
BRCA1 or 2
Personal or FH of M breast CA is very highly associated w/ what?
BRCA2
What are the associated CA risks with BRCA1?
Breast CA 50-85% (often early age onset), 2nd primary breast CA (40-60%), Ovarian CA (15-45%), Possible inc risk for other CA: prostate, colon.
What are BRCA2-associated CA risks?
Similar but different from BRCA1. Breast CA 50%-85%, Ovarian CA 10-20%, Male breast CA (6%). Inc risk of prostate, laryngeal, pancreatic CAs
What is the penetrance of BRCA1 and BRCA2?
Incomplete penetrance (Variable inheritance)
T or F: You are at more of a risk w/ 1st degree relatives having BRCA1 and BRCA1 mutations
True (more genes, more risk)
What is the cumulative risk of breast CA?
The longer you live w/ mutations, more likely to get CA (BRCA1>BRCA2)
The 187delAg, 5385insC and 617delT mutations are seen w/ what?
Ashkenazi Jewish population. Account for most of the BRCA1 and BRCA2 breast CA
Which gene has male involvement in breast cancer?
BRCA2
What are some benefits of BRCA testing?
ID high risk individuals. ID non-carriers in families w/ known mutations=dec risk. Allows early detection and prevention strategies. May relieve anxiety.
What are the risks and limitations of BRCA testing?
Does not detect all mutations, continued risk of sporadic CA, may result in psychosocial or economic harm.
Chromosome for BRCA1 and BRCA2
BRCA1: 17q21
BRCA2: 13q12.3
Difference in age of onset of breast cancer in BRCA1 vs BRCA2?
Younger age of onset in BRCA1 than BRCA2
When you see Li-Fraumeni Syndrome, think what?
p53
What is Li-Fraumeni associated w/?
Breast CA< soft tissue sarcoma, leukemia, osteosarcoma, melanoma, colon CA, pancreatic CA, adrenal cortex CA, brain CA--has a lot of different types of CA in same family at young ages
What is the lifetime cancer risk for Li-Fraumeni Syndrome?
90% for W, 70% for M; Breast CA: most frequent CA in adults; Bone and soft tissue sarcomas are MC in kids. Other CA: sarcoma, brain, adrenocortical, leukemia and other early onset CA
What is p53?
A tumor suppressor: the last stop for a gene before the cell goes into uncontrolled cell cycle replication and growth.
What happens normally when DNA damage or hypoxia occurs?
p53 activated, p53 ptn binds to DNA, upregulates transcriptional target ptns-p21 (CDK inhib) and GADD45 (DNA repair), p21 causes cell to arrest in G1 until successful repair occurs. If repair doesn't occur, GADD45 recognizes that and induces apoptosis along w/ BAX
Pt has multiple primary tumors. Bilateral tumors. Their kids have CA. What do they have?
Li-Fraumeni Syndrome
When do men present w/ Li-Fraumeni Syndrome vs. women?
May be later because lack of breast development (protective)
Multiple hamartoma (a benign tumor-like growth consisting of a disorganized mix of cells and tissues):
Cowden Syndrome
What are the characteristics of Cowden Syndrome?
Macrocephaly, trichilemmomas (mimic basal cell CA or wart), papillomatous papules by late 20s. Present w/ warts or facial papilloid. Hyperkeratosis. Nasal polyps. Thyroid abnormalities, fibrocystic breast and uterine dz, GI hamartomas, early onset uterine leiomyomata, macrocephaly, mental retardation
Where can hamartomas occur?
in any organ
What is the MOI of Cowden Syndrome?
AD
Where is the mutation in Cowden Syndrome?
PTEN on Chr10
What is PTEN?
Phospholipid phosphatase (tumor suppressor gene). Mutated in Cowden Syndrome
What does PTEN do when mutated?
Loss of fxn--no dephosphorylation, PIP 3 does NOT get turned back to PIP2--constitutive upregulation of PKB/AKT oncogenes--> accelerate/uncontrolled cell growth (tumors)
What CA's are associated w/ Cowden Syndrome
Breast, thyroid, uterine
What does PTEN normally do?
Stimulus binds receptor, activates P13 kinase, P13 kinase phosphorylates PIP2 to PIP3 (phosphatidylinositol 3,4,5 triphosphate, pathways actiates, PIP3 lipid signaling molecule--> PTEN dephosphorylates PIP3 to PIP2 to control growth pathway*
What are the two most common cancers that occur w/ Cowden Syndrome?
Breast (25-50% increase risk) and follicular thyroid CA (~10%)
What is Hereditary Non-Polyposis Colon CA AKA?
Lynch Syndrome
What is HNPCC?
Lynch I: Rt sided predominance, multiple primary tumors
Lynch II: 1+ extracolonic colorectal CA< particularly endometrial carcinoma, followed by carcinoma of the ovary, small bowel, stomach and pancreas and transitional cell carcinoma of the ureter and renal pelvis
What is there an increased risk of w/ HNPCC?
CA of stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin and prostate. Women w/ this also have high risk of endometrium and ovarian CA
What genes are affected in HNPCC?
MLH1, MSH2, MSH6, PMS2 genes (w/ any of these there is an inc risk of CA bc they are tumor suppressor gnes)
What is the mechanism in which cancer is caused in HNPCC?
DNA repair genes (mismatch repair)--microsatellite instability
What is the most common type of DNA repair mutation in HNPCC?
Dinucleotide repeats: stable repeats can be polymorphic (CA12, CA14, CA16 are used as markers for forensics)
What are BAX genes?
Genes that say "cell you're going to die" when p21 and GADD45 fail.
What is the repeat in TGFBR2 gene associated w/ HNPCC that is associated w/ breast cancer?
A10 repeat--if there is a frameshift and inc #, inc risk fo HNPCC which are associated w/ breast cancer
What are the most common trinucleotide repeats?
Fragile X syndrome, Huntington's (can occur in promoter, intron and exon regions)
What effect does breastfeeding have on the uterus?
Accelerates involution of uterus postpartum
Why does breastfeeding have immunologic benefits in newborns?
Maternal antibodies in breast milk. Immunoglobin A (IgA) provides protection to infant's gut. Passive immunity from maternal lymphocytes
Which hormones play role in preparation for breastfeeding?
E, P, hCT, cortisol, insulin, prolactin, placental lactogen
What happens first at delivery to the hormones?
Drop in placental hormones (esp. estrogen). Prior to delivery these hormones alter lactogenic effect of prolactin.
What does suckling cause?
The secretion of prolactin and oxytocin- results in contraction of myoepithelial cells in the alveoli and milk ducts
What effect does prolactin have on breastfeeding?
Principle hormone for the synthesis of milk and the maintenance of lactation. Released from the AP as well as mammary gland
What is Oxytocin's role in breastfeeding?
Responsible for the release of stored milk (let down). Secreted from the post pituitary by sensory stimulation from the nipple-areola complex
What happens on the 2nd day of delivery?
Colostrum is secreted: made of proteins, fat and minerals. Contains secretory IgA
What happens on Days 3 to 6 post delivery?
Colostrum is replaced by mature milk: content varies w/ mother's nutrition and gestational age at delivery
What are the major components of breast milk?
Proteins, lactose,w ater, fat
What components are unique to breastmilk?
Casien, lactalbumin, beta-lactoglobulin (not found in formula)
How much is considered a mature milk secretion?
~1-2 ml/g of breast tissue/day
What is the rate of lactation in the first 6 mos of lactation?
Constant for the first 6mos of lactation. Not stimulated as much bc baby storing food and sleeping through night
What is the avg frequency of breast feeding?
Avg q 2-3 hours. Depends on age of infant, varies infant to infant.
This is common (usually occurs bw 2-4 weeks post-partum). Symptoms include F, erythema, pain and induration, Can get really sick; feels like flu--can get abscess:
Mastitis
What is the typical infectious agent in mastitis?
Staph aureus. Yeast is also very common and hard to treat. Pts c/o "stinging sensation."
How do you treat yeast infections of breast?
Diflucan (also will need to inspect for thrush). Rx: penicillinase-resistant antibiotic like dicloxacilin 7-10 days. May result in breast abscess that requries surgical drainage. Do not need to discontinue breastfeeding! Discontinuing would leave milk stagnant, which puts more pressure on breast.
What are some suggestions for increasing milk production?
Inc frequency or duration of feedings, inc fluid intake, herbal meds like fenugreek, other meds like reglan (metoclopramide), seek help from lactation consultant. Intranasal oxytocin (for let down probs like stress)
Are there meds to prevent mild production?
NO. Use tight fitting bra, analgesics such as Tylenol or Motrin. Ice for discomfort--painful for 24-48 hours. Avoid stimulation of breast
What is weaning?
The process of cessation of breastfeeding. Timing varies based on experience, desire and infant. After weaning, breast involutes and returns to a pre-pregnancy state (meaning it won't lactate, not appearance of breast).
What components are unique to breastmilk?
Casien, lactalbumin, beta-lactoglobulin (not found in formula)
How much is considered a mature milk secretion?
~1-2 ml/g of breast tissue/day
What is the rate of lactation in the first 6 mos of lactation?
Constant for the first 6mos of lactation. Not stimulated as much bc baby storing food and sleeping through night
What is the avg frequency of breast feeding?
Avg q 2-3 hours. Depends on age of infant, varies infant to infant.
This is common (usually occurs bw 2-4 weeks post-partum). Symptoms include F, erythema, pain and induration, Can get really sick; feels like flu--can get abscess:
Mastitis
What is the typical infectious agent in mastitis?
Staph aureus. Yeast is also very common and hard to treat. Pts c/o "stinging sensation."
How do you treat yeast infections of breast?
Diflucan (also will need to inspect for thrush). Rx: penicillinase-resistant antibiotic like dicloxacilin 7-10 days. May result in breast abscess that requries surgical drainage. Do not need to discontinue breastfeeding! Discontinuing would leave milk stagnant, which puts more pressure on breast.
What are some suggestions for increasing milk production?
Inc frequency or duration of feedings, inc fluid intake, herbal meds like fenugreek, other meds like reglan (metoclopramide), seek help from lactation consultant. Intranasal oxytocin (for let down probs like stress)
Are there meds to prevent mild production?
NO. Use tight fitting bra, analgesics such as Tylenol or Motrin. Ice for discomfort--painful for 24-48 hours. Avoid stimulation of breast
What is weaning?
The process of cessation of breastfeeding. Timing varies based on experience, desire and infant. After weaning, breast involutes and returns to a pre-pregnancy state (meaning it won't lactate, not appearance of breast).
What factors affect secretion fo a drug into breast milk?
Maternal dose, rate of maternal clearance, physiochemical properties of drug, composition of breast milk (fat and protein content), gestational age of infant
When breast feeding, what effect do sedatives have on infant?
Sedation
When breast feeding, what effect do antipsychotics have on infant?
no effect
When breast feeding, what effect do salicylates have on infant?
Platelet dysfunction
When breast feeding, what effect do anticonvulsants have on infant?
Sedation and dec suckling
When breast feeding, what effect do antibiotics have on infant?
May alter gut flora, cause allergy or interfere w/ infection workup (avoid doxycycline and fluoroquinolone)
When breast feeding, what effect does propylthiouracil have on infant?
nodular goiter
When breast feeding, what effect does Acetaminophen have on infant?
No effect
Is there evidence that self exam improves mortality?
No, but it may lead to earlier detection.
If the patient is upright for a breast self exam, how should she examine her breasts?
Examine w/ arms up and down, palpate for nodes (supraclavicular and axillary)
When pt is laying down for her breast self exam, how should she examine her breasts?
Examine w/ arms up and down, palpate of nodes (supraclavicular and axillary)
When do you do breast self exams?
Right after period bc less tender and else likely to find cycle induced cysts. Look for contour and size changes.
How often should women have physician breast exams?
At least annually
If upright on a physician breast exam, what do you look for?
Contour, shape and symmetry, skin and nipple retraction.
Explain palpation done on physician breast exam?
Done w/ flat of hand, examine axillary and supraclavicular regions of lymphadenopathy, nipple for discharge
If patient complaining of nipple discharge and you suspect PRL issues, then do you check nipple discharge?
Might not want to check nipples b/c could inc. PRL level
What do you think about when you see skin/nipple retraction?
Can be from old biopsy of CA, ulcerations (carcinoma), lesions, nipple discharge (bloody--trauma, breast-feeding, CA)
-Bloody discharge is always abnormal until proven otherwise
-Describe findings based on quadrants
Who do you screen with mammograms?
Asymptomatic and symptomatic women
What does the ACS recommend?
Routine screening begin at 40 y/o (could screen earlier if family hx or high risks)
What do you look for in mammograms?
Calcifications (need to watch + repeat in 6 mo OR biopsy), densities/nodes
Who is ultrasound of the breast beneficial for?
Particularly beneficial in women <30y.o.
Do you do ultrasounds in asymptomatic women?
No. Do if something palpated or if mammogram is inconclusive.
How do you know solid vs. cystic masses on ultrasounds?
Solid mass shows shadowing where rays can't penetrate. Solid masses are more worrisome.
What helps to ID whether cystic structure is masking solid mass
Ultrasound
Is MRI useful in breast exam?
It is a useful adjunct but is expensive. The benefits are that it improves staging and treatment planning, enhances evaluation of augmented breasts, better for detection of recurrences. improves screening for those considered high risk, expensive, so only for special circumstances.
How is FNA used in Dx of Breast lesions?
Aspirate of palpable mass; can be done in outpt setting/now usually surgeons. Can use US guidance. Smears are made of aspirate to view cytology.
When should FNA be avoided in Dx of Breast lesions?
Should not be used if there is clinical or mammographic evidence of malignancy
When do you do open breast biopsy?
If either too deep for others OR for removal: excisional for small masses, incisional for large masses. Can be outpt w/ local or inpt w/ general anesthesia. Indicated for woman with clinically benign appearing lesion but (+) personal/FH of equivocal finding on mammo or FNA
What are absolute contraindications of Open Breast Biopsy?
-Suspicious mass that persists through a menstrual cycle
-Cystic mass that doesn't completely resolve w/ aspiration or contains blood fluid
-Spontaneous serous or seroanguineous nipple discharge
What is the most common breast tumor?
Fibroadenoma
What are fibroadenomas made of?
Fibrous and glandular tissue
Who more commonly gets fibroadenomas?
Women 15-25 yo (MC breast tumor <35yo)
How would you describe a fibroadenoma?
Solitary, well circumscribed, freely mobile, usually non-tender.
What effect does pregnancy have on fibroadenomas?
Can stimulate growth; estrogen increases cause growth (prego, period)
What does a fibroadenoma look like on ultrasound?
Dark, but shadowing bc its solid
What does a fibroadenoma look like on gross?
Rubbery orange
What is the treatment of fibroadenoma?
Excised typically when reach 2-4 cm (for cosmetic purposes--destroys breast architecture)
-If >15cm then have malignant potential and should be excised
-Could do a FNA
Papillary growth within the ducts of the breasts that are more common post-menopause?
Intraductal papillomas
Where are intraductal papillomas found?
Within the lactiferous ducts of the breasts
How are intraductal papillomas usually found?
Discovered by bloody, serous or turbid nipple discharge. Rarely found on exam bc typically not big enough to be picked up
How do you obtain a diagnosis?
Use mamogram and cytology to obtain dx.
What does an ultrasound show for an intraductal papilloma?
Floating in duct
Treatment of intraductal papilloma?
Excision of lesion and involved duct
Cystic dilation of duct filled with milk that is found during or shortly after lactation?
Galactocele
What is the usual cause of a galactocele?
usually due to some form of ductal occlusion-inflammation hyperplasia or neoplasm
A secondary infection in a galactocele may result in what?
Mastitis or abscess
What is the treatment of a galactocele?
Needle aspiration
"Lumpy bumpy" breast:
Hyperplasia (formerly known as fibrocystic disease)
Is breast hyperplasia a tumor?
No
How common is hyperplasia of the breast?
May be present in ~50% of women. Can involve any/all breast tissues
When hyperplasia is associated with cellular atypia, what do you see clinically?
Increased risk of malignancy, so may biopsy/inc mammogram protocols
What do they think causes breast hyperplasia?
Thought to be due to decreased progesterone and increase in estrogen. Estrogen promotes growth of ducts and periductal stroma. Improve during pregnancy due to predominance of progesterone.
Are hyperplasia lesions usually u//l or b/l? Single or multiple?
Usually bilateral and multiple.
What is the clinical presentation of a patient w/ breast hyperplasia?
Characterized by pain and tenderness. Tends to be cyclic (pre-menstrually). Exquisite breast pain right before onset of period.
What is the treatment of breast hyperplasia?
Depends on age, severity of sx and risk of developing breast CA. May need imaging w/ US or mammo if suspicious. Cysts may be aspirated to relieve pain
Treatment for mastalgia?
Avoid caffeine. Low fat diet. Good support bra. Evening of primrose oil (not sure why it works, but it does). OC's may improve cyclic pain (don't get the estrogen inc.), NSAIDs
Even if you can't feel a mass/nodule, do you do a work-up if the patient is worried?
Yes.
What are the maternal short term benefits of breast feeding?
Acceleration of recovery. Oxytocin's action on uterine involution (helps w/ bleeding).
Reduction in maternal response to stress (neuroendocrine pepties, oxytocin and prolactin, produce positive impact on social behaviors and maternal-infant bonding. Weight loss (a significant effect if BF continued). Prolongation of postpartum anovulation. Not a reliable method of BC.
What are the maternal long term benefits of breastfeeding?
Cancer: breast and ovarian cancer. Osteoporosis: maybe-more studies needed. Cardiovascular disease: studies show that must be significant time (at least 3 mo/child...up to 2 years in total time breastfeeding).
What are the economic benefits of breastfeeding?
Family: approx $1000more/yr
Societal: - decrease medical costs of $331/child in acute costs; up to 20% reduction in medical costs over childhood; decrease parental work absences--unable to calculate. If all mothers who could breastfeed did, $13 billion/yr could be saved. 911 deaths per year avoided
What GI disease are growth factors from breast milk protective of?
Development of NEC (Necrotizing enterocolitis) in animal studies
What factors play roles of protection in GI from breast milk?
IgA and IgG
Compared to formula, breast milk does what to gastric emptying, lactase activity, permeability?
Increases rate of gastric emptying (inc function), incrase intestinal lactase activity in the preemie. Decrease intestinal permeability, especially in the preemie
What happens in the respiratory tract due to breast milk?
Decreased incidence of otitis media. Other respiratory infections.
What does breast milk do to the prevalence of UTI?
Decreases their incidence
What does breast milk do to acute illness over the 1st year of life?
Decreases the incidence
What does breast milk do to the incidence of childhood/adulthood obesity?
Decreases incidence
How long are the beneficial effects on cognitive development in infants due to breastfeeding?
Through middle school
What should all breastfed babies receive in addition to the milk?
Supplemental Vitamin D and probabl ysupplemental Fe (Vit D-400 units/day) b/c stress on mom has depleted stores and don't expose ourselves to enough sun
Does mouth on breast equal feeding?
NO
What are the criteria for assessment of breast feeding?
Alignment, Areolar Grasp, Areolar Compression, Audible Swallowing, Total Seal Around Breast
How should the infant be aligned when breast feeding?
Infant flexed at neck and hips, head level w/ breast; ear, shoulder, hip aligned. Mom comfy.
If the cheeks are dimpled when breast feeding, what does this indicate?
A suction issue
The following characteristics indicate what?:
Sustained, rhythmic suckling, good jaw movement, moderate vigor, audible swallow
Nutritive
Is the following a correct or incorrect sucking pattern?
Protruding or thrusting tongue, tongue against hard palate, back of tongue elevated, flat tongue, infant bites w/ gums, weak suck
Incorrect
Is the following a correct or incorrect suck?:
Tongue curves around fingers, tongue beneath the finger, tongue over the gum line, complete seal formed around the finger, negative pressure, rhythmic pattern of suck
Correct
When do you use nipple shields?
Flat or inverted nipples, pre-term (sometimes)
When to use pump for breast feeding?
Poor stimulation (like if using a shield), if baby nursing great and no risk factors, don't pump. Risk factors preterm, poor nurser, breast surgery (esp reduction), hormones (ex is thyroid meds- may not have enough milk supply)
When do you supplement the breast feeding?
Not nursing at all 6-8 hrs, low blood sugar, breast reductions, weight loss >10% or approaching. If PRE-TERM, weak suck, mom sick, etc
How much do you supplement when breast feeding?
1st day=7mL (stomach marble size)
2nd day=10mL (shooter marble)
3rd day= 15 ml (maybe even 25-30mL)
4th = 20mL (hopefully milk in by this time)
If you choose to supplement w/ a bottle, must document what?
That the mom chose to do this even though she knew it might it might interfere w/ successful breast feeding
What are the advantages of frequent, unrestricted breastfeeding in early days?
Provides baby with the colostrum, prevents painful engorgement, stimulate uterine contractions and lessens chance of hemorrhage, prevents newborn jaundice, gives baby practice nursing before the mom's breasts became full, stimulates mom's milk to increase more quickly
When do you first put the baby to breast?
Birth-2 hrs: alert and eager
What are the sleeping patterns like in the first day?
2-20 hours: light and deep sleep
20-24 hours: increased wakefulness
What is the most important breast feeding?
In the delivery room. The mom and baby will thank you, as will the lactation team
What are some feeding cues for breast feeding?
Arms bent, hands fisted; hands at face and head; sucking on hand, arm, wrist; open mouth; tongue out, mouth motions; head bobbing; trying to assume nursing positions
If a baby has weight loss >7%, how soon should they be seen?
Within 2 days post-discharge (re-gain birth weight by 10 days-2 weeks)
What are some wake-up techniques for SLEEPY infants?
Talk to infant, unswaddle, undress infant, change diaper, stroke or massage extremities and back, sit-ups, apply cool cloth to face, rub feet, roll kid back and forth and lift up-takes 4-5x; takes 3-45 sec to wake up infants
What are the positions for feeding?
Cradle, Cross Cradle, Football, Side-sitting, side lying
What is considered acceptable weight loss for an infant in the first few days of life?
5-10%.
What is a sensitive indicator of adequancy of milk intake?
Void/stool records
What is considered normal in the first 48 hours?
Urine w/ uric acid crystals (brick dust).
What is brick dust considered after the first 48 hours?
Dehydration
What is considered normal for voiding on days 1-5?
Day 1: 1-2 wet diapers
Day 2: 2-3 wet diapers
Day 3: 3-4 wet diapers
Day 4: 3-4 wet diapers
Day 5: 6 or more, MOST CRITICAL
What is an indication of insufficient intake in an infant that is more than 5 days old?
Dark meconium (want out as quick as possible) or scant vol of stools. Should have transitional stools by the third day. By 4-5th day of life, the BM should be yellow with small curds--"mustard poops"; sweet smelling
What are indicators of sufficient intake?
6+ voids/24 hours
4+ stools/24 hours
Content after feeds
Wakes to be fed (every 3 hours or so)
How many times should a baby nurse in 24 hours to indicate that it is getting enough milk?
8x in 24 hours
Is this baby getting enough milk?
1 wet diaper on 1st day of life, 3 on days 4 and 5, and at least 6 a day after 6th day of life?
Yes
What are some symptoms of dehydration?
Fever, listlessness, skin losing its resiliency, weak cry
Do the outer layers of the placenta (trophoblasts) exposed to the uterus or maternal blood have activation of CD4+ cells?
No, because they never express MHC class II Ag's
Is there MHC Class I expression on the inner trophoblasts in contact w/ maternal blood? What does this mean?
No, so no activation of CD8+ cells
What threat does the lack of MHC class I expose the cells to?
Maternal NK cells
If trophoblasts in human chorionic villi are MHC class I (-), are they activated? Why?
No, they are not. This is because the villous torphoblasts express a soluble form of HLA-G (sHLA-G). sHLA-G induces activated T cells to undergo apoptosis and downregulate NK lytic activity
Where is HLA-G protein expression restricted to?
Immune privileged sites such as thymus and palcenta
What are the main actors in the immune response of the HLA region?
Genes HLA-A, B, and C are called classic (HLA-Ia) because they are the main actors in the immunologic response
Which genes are called HLA-Ib?
Genes HLA-E, F and G
What is the function of HLA-G?
Placental immunosupression
What controls the metabolism of tryptophan?
IDO (indoleamine 2,3-dioxygenase)
How does IDO control metabolism of tryptophan?
Degrades and depletes it, which inhibits the growth of viruses, bacteria and parasites, because tryptophan is the least available and most important essential aa for growth
What does the byproduct of IDO do?
Many things including decreased proliferation of T cells and prevention of fetal rejection
What do placental fibroblasts express and what does this do?
Express CTLA-4-> interact w/ T-cells -> activate IDO -> metabolize tryptophan, T-cells are suppressed, and immunoregulation is achieved via apoptosis
What are some immunosuppresors that the placenta secretes?
Th2 cytokines (IL-10 and TGF-beta) and PGE-2.
What do T cells (CD8+ and NK) do when they "see" paternal alloantigens?
Express the progesterone receptor (rPg), which resting cells do not.
What are the two potent immuno-regulators that progesterone at high doses secretes?
RTF (Regeneration and Tolerance Factor)
PIBF (Progesterone Induced Blocking Factor)
What is RTF?
aka TJ6; a cell-surface protein ID'ed in trophoblasts of early pacentas (7-9 weeks). It is cleaved to ield a soluble fragment which up-regulates teh production of IL-10 and interferes w/ IL-2 signaling (which is normally required for Th1 response and proliferation of T-cells), shifting the balance towards a Th2 T-cell response
What is PIBF?
It exerts a substantial anti-abortive activity: inhibits cytotoxicity of NK cells by blocking their degranulation and perforin release; also favors Th2 response :stimulates IL-3, IL-4 and IL-10; inhibits interferon, TNF-alpha, and IL-2. In B cells, it induces production of non-cytotoxic Abs which do not fix complement
What is an example of an immune modulator that blocks Pg receptors and prevents PIBF production?
RU 486/Mifepristone (RU 486 induced abortion can be thought of as an immuno-endocrine event)
What do the classical recognition mechanisms for Allo-recognition generate?
Complement fixing IgG-2 cytotoxic Abs
What can allo-Abs, if generated, do to the embryo?
Kill it by mechanism of complement dependent cytotoxicity
What does the placenta use in order to prevent complement activation?
Complement regulatory proteins
What is membrane cofactor protein?
MCP: cofactor for the inactivation of C3b and C4b
What is DAF?
Decay accelerating factor. It prevents the assembly of the C3bBb complex (the C3-convertase of the alternative pathway), or accelerates the disassembly of preformed convertase
What kind of resistance do trophoblasts display to NK/T-cell mediated lysis?
Intrinsic resistance; also express Fas ligand (FasL), which normally induces T-cell apoptosis upon immune withdrawal.
In animal models, what do excess Th1 cytokines correlate w/?
Abortion (TNF-alpha, TNF-gamma)
What do aboriton prone mice have low levels of?
Uterine Th2 cytokines (Il-3, Il-4, IL-10)
Allopregnancy is proposed to be what kind of phenomenon?
Th2
When should Th2 be established?
Before maternal allorecognition occurs
What are the different immune factors for pregnancy and abortion?
Abortion: Th1=IL-2, IL-12, IFN-gamma, TNF
Pregnancy: Th2= IL-3, 4, 5, 6, 10, 13
What does the pregnancy "tolerance" require?
Immune suppression and promotes a Th2-like state at the time of implantation in the uterus.
What immuno components help to "prepare the uterus?"
Cytokines in the seminal fluid such as GM-CSF
What does the "cleaning up" require?
Intense influx of activated macrophages in teh post-coital uterus, by inflammatory cytokines such as IL-1, IFN-gamma, and TNF-alpha. This low intensity inflammatory response is then down-regulated by day 3.5 post-coitum
What do cytokines stimulate?
The expression of adhesion molecules on both the pre-implantation blastocyst and in the uterus, which facilitates embryo adhesion, attachment, and invasion. They also induce embryonic production of enzymes such as matrix metalloproteases, which are required for penetration of the stroma.
What can fertilization be stopped by?
Anti-sperm Abs (ASAs), which block binding of sperm to the zona pellucida and can be produced by both genders
What is the incidence of sperm autoimmunity in infertile couples?
9-36% (male/autoantigenic=8-21%, female/isoantigenic=6-23%)
What do female repro tracts protect against?
Invading pathogens, but should not attack sperm cells or the developing embryo. Protects against infectious agents. Protects establishment and maintenance of pregnancy. Acts adversely on fertility by generating ASAs.
If the female repro tract an immuno privileged site?
No, all immune mechanisms are there, but work in unique ways; has all components of mucosal immunity=secretory component, IgA, IgG
Do ASAs fix complement? Which isotypes are they primarily?
No, both are primarily of the IgA and IgG-4 isotypes
What might happen if IgG-3 is present in the female reproductive tract?
Complement activation and sperm damage may result
What do ASAs in the cervical mucus do in regards to fertility?
Can interfere via various mechanisms: inhibition of sperm migration into/through the cervical canal, complement-dependent damage (IgG-3) of sperm membrane damage, phagocytosis of Ab-bound sperm by phagocytic cell (IgA, IgG), pregnant women w/ ASAs may have higher rate of spontaneous abortion
What are the major APCs in the female genital tract?
Macrophages and DC's
If a concurrent infection in the female genital tract, what might happen to the sperm?
They might become "innocent bystanders." Women w/ PID have high incidence of ASAs
Why might ASAs arise in women?
Because of a deficiency of one or more of the immunosuppressive factors in the partner's semen.
What generates the immune response to sperm?
After exposure to sperm in both fertile and infertile women.
How is an immune response elicited in fertile women?
ASAs elicit the production of anti-idiotypic Abs which neutralize the ASA response
How is an immune response elicited in infertile women?
Anti-idiotypic AB production is weak/absent
What is anti-idiotype?
An Ab that binds to the Ag-combining site of another Ab to either suppress or enhance the immune response, in this case essentially neutralizing Abs
How does the insufficiency to neutralize the ASA response result in infertility?
1) An inherent lack of anti-idiotypic AB response to the ASA production
2) A hyperimmunization w/ sperm Ags as a concurrent event w/ pre-existing infection
When does tolerance to auto-Ags develop in males?
In the early stages of development and sperm cells are not formed until puberty. Thus, sperm-specific Ags are NOT recognized as "self" by the adult immune system-> an immune response can be generated against them.
What forms the blood-testis barrier?
Sertoli cell tight junctions (immune-privileged site)
When the blood-testis barrier is damaged, what is produced?
ASA
When does ASA binding to sperm occur?
Only after ejaculation
What are the 3 treatment approaches of Immuno-Infertility?
1) Immunosuppressive therapies
2) Assisted reproductive technologies
3) Lab techniques
How does immunosuppressive therapy work?
MC= corticosteroids; Increase in pregnancy rates and decrease in Ab titers with steroid therapy, weigh benefit/SE's
What are the assisted reproductive technologies discusses in Shnyra's lecture?
IUI: modest increase; Ovarian stimulation: better results; IVF: substantial improvement in helping transport problems, but does NOT overcome Ab0induced fertilization defects; IVF w/ intracytoplasmic sperm injection (ICSI): reserved for severe male factor infertility or couples who have failed IVF
What are some lab techniques for treating immuno-infertility?
Methods to prevent binding or to separate Ab sperm: recombinant soluble FA-1 Ag (increases acrosome rxn rate), immuno-adsorption w/ FA-1 increases Ab-free swimming sperm, 78% improvement after FA-1 adsorption, may have clinical applications in treatment of immuno-infertile men
What are some suppressing factors in repro immuno?
Seminal plasma (PGs, TGF-beta, large molecules, cytokines), sperm surface molecules (anti-complement, IgA), idiotypic Ab network, immune suppressor cells in tract
What are some stimulating factors in repro immuno?
Infectious agents, inflammatory cells, cytokines in semen, infection, inflammation, trauma in tract, decreased immunosuppressive factors in semen, ASA sperm activation of macrophages and immune cells, immune system deficiencies (lack of idiotypic Abs, lack of suppressor T-cell response)
How many lobes and ducts are in the breast?
15-20 lobes, varying # of ducts/lobules surrounded by CT
How many ductules are in each lobule?
~30 ductules; also there are acini
What does the terminal duct contain that goes to the nipple?
A lactiferous duct that goes to the nipple.
What is a phyllodes tumor made of?
Fat and CT stroma
If you don't see the muscle on CT breast imaging, why may this be concerning?
Because may be missing imaging of tissue
Are cysts commonly seen on breast imaging?
Yes, esp in younger patients. They can be followed and/or removed w/o going into surgery
How often is mammography recommended?
Annually after the age of 40
How do you line up the projections in a mammogram?
MLO and CC (Med to lat oblique and cranial-caudal). Make sure to see m and margins of breast, contour. Also ensure that the edges are not burned out
Why does it make sense to screen w/ a mammogram?
Low dose radiation/ low cost/ readily available
How do you line up the breast images when reading mammograms?
Look at the breasts side by side for parenchymal layout--thickest at upper and lateral portions
When do you image with an ultrasound?
If requested by mammogram findings (lesion seen). Not a screening tool.
What is the first line imaging for patients <25 yo?
Ultrasound
Does ultrasound have radiation?
No
When do you image the breast with MRI?
Implant rupture. Good for implants (do not have to inject dye). Help dx cancer, esp high risk pts
How do you differentiate C from a fibroma w/ dye and MRI?
How the dye is taken up in a lesion. CA has high vasc and break down of membrane. Dye rushes in quickly and out quickly vs fibroma where the dye does not leak out.
On MRI in post-surgical patients, what do you need to know about scarring?
Scar appears like a mass and should not enhance after 1 year. If it does, biopsy it.
Where does accessory breast tissue show up?
In axillary region and along the normal developmental nipple line extending in animals from the axilla along the chest to the abd, rarely attach to an extra nipple
Common lumpy bumpy breast. Non-proliferative changes in the breast. Not a/w increased risk of breast cancer. A/w hormonal changes
Fibrocystic breast disease
What are the 3 predominant morphologic features of fibrocystic breast disease?*
Cyst formation, fibrosis, adenosis
What are some changes that occur with fibrocystic breast disease?
Adenosis, sclerosis adenosis, apocrine metaplasia, cyst formation with or without rupture, ductal ectasia
What does a radiologist do when a cyst is found in the breast?
Tx w/ simple aspiration, but DO NOT aspirate w/o imaging first (if try to aspirate and nothing comes out--> solid).
What do cysts of the breast look like on imaging?
Lobulated, well circumcised, smooth margins (>75%); Simple: anochoic (no shadows), thin walled, no lobulations. Non-simple: internal grey=debris or hemorrhage
What do normal ducts look like on imaging of the breast?
Thin and smooth walled, have no filling defects/irregularities. Ductal ectasia is common.
Presence of inspissated calcified secretion within subareolar ectatic ducts
Plasma cell mastitis=benign
What does periductal inflammation cause?
Dense calcification oriented along the breast ducts and pointing at the nipple.
What do calcifications look like on breast imaging?
Coarse
What causes oil cysts as a sequelae of blunt trauma or prior surgery (esp reduction). Have lucent centers and a thin dense rim. May calcify and result in eggshell calcifications.
Fat necrosis
What is the MC solid benign tumor in young women?
Fibroadenoma
Where are fibroadenomas thought to arise from?
Terminal ductal lobular unit due to localized hypertrophy
What are the different variations of fibroadenomas?
Single or multiple and can be of any size, may resemble LN
What do fibroadenomas contain?
Breast ductules adn stromal tissue, may undergo adnenosis or hyperplasia
What is a juvenile fibroadenoma?
Fibroadenoma occuring in adolescents, can grow rapidly (cause a lot of problems)
What is a Giant fibroadenoma?
>8cm- can remove surgically or may tx with the vacuum and mammotome, may come back esp in younger pts--can have a phyllodes tumor hiding w/in it so best to remove
What is a fibroadenoma is <4cm?
May not need to remove, but may remove through a needle; most are between 1-2.5cm
Is fibroadenoma associated w/ increased risk for cancer?
No
What are the different variations of fibroadenomas?
Different shape and sizes, may resemble LN's, Hypoechoic, smooth margins, through transmission, solid, may have a lot of debris w/ a lot of echos w/in them; solid, firm and mobile on palpation
What does a fibroadenoma look like on mammogram?
Oval/lobular mass w/ well-defined margins. With age, may become sclerotic and contain peripheral popcorn-like calcifications, eventually may become replaced by calcification
What does a fibroadenoma look like on sonograph?
Oval, well-marginated homogenous masses. Wider than tall=indicates benign; like elongated since its not growing to skin or wall. May have gentle lobulations. HYPOechoic.
Name the tumor: uncommon, most are benign (10% malignant), occurs in 5th decade, may be up to 5cm in size when detected. Rapidly growing, has stromal and epithelial compnents, w/ fluid-like spaces in a leaf-like pattern. Incomplete excision may result in local recurrence
Phyllodes Tumor
Is there an imagine feature that can distinguish a phyllodes tumor from being benign or malignant?
No.
Mammo: dense round/oval, lobulated, well-circumscribed mass
US: well-marginated heterogenous mass which may contain cystic spaces; can hide masses
The incidence of breast cancer in males is what?
<1% of all breast cancers
What do males seek medical attention for when it is u/l or b/l breast enlargment, palpable lump or breast pain:
Gynecomastia
How does gynecomastia show up?
As subareolar glandular tissue: may be u/l or b/l, symmetric or asymmetric
What are most causes of gynecomastia due to?
Benign gynecomastia= abnormal proliferation of benign ducts and supporting tissue which can cause subareolar mass, enlargement, pain
Is gynecomastia reversible?
Yes in early stage if the cause is corrected, however it may progress to stromal fibrosis
What do you begin imaging w/ if gynecomastia?
Mammo
Who is gynecomastia commonly seen in?
Neonates (maternal estrogens crossing the placenta), Adolescent boys (1 yr after the onset of puberty due to high estradiol), older men (decreasing testosterone levels)
These are less dense than cysts and more lucent. Show as a dark spot on mammogram. Sharp, well demarcated border:
Lipoma
These are very common; can be anywhere in the breast, but esp near the upper outer portions, not always axillary, or can be scattered throughout. Round, ovoid, kidney bean shaped. Fatty hilum- fat centrally w/ low density in the middle:
Intramammary LN
Over time, what does the body do around an implant?
Forms a fibrous capsule around it; contains all the fluid so can rupture the implant and the fibrous capsule will contains the fluid.
What is the MC type of rupture of a breast implant?
Intracapsular rupture. Surgically remove.
How do you know it is an intracapsular rupture of an implant on imaging?*
Linear lines w/in implant; Snaky lines seen w/ rupture of implant= "Linguine Sign"
Saline saturate exam-saline fluid is dark, helps to see where fluid has leaked. Fib capsule is missing in parts (decreased signal), Internal integrity of implant has ruptured, so has the fibrous capsule from the body-> so fluid leaks through the breast tissue
Extracapsular rupture
Normal- on teh margin of implant, there are folds and lines, should see it extend from one side to the other, connect the line side to side
Implant fold: do not call these ruptures
These may cause a nipple discharge. Remove via a needle biopsy.Show up as linear, hypoechoic, dilated ducts:
Superficial ducts
Is it common to find an intraductal papilloma? What does it show up as?
yes, it is common. Can see a shadow on mamow, confirmed w/ ultrasound. Can see a duct leading all the way to a small mass that's inside the duct; can be benign (most) or malignant, may will cause a nipple discharge, tx is removal via needle biopsy
What are characteristics of suspicious calcifications?
Mostly benign, do not biopsy every single one. Benign-round, ovoid, coarse appearance, dense, primarily benign features
Cannot make out margins in some areas while other areas the borders can be defined and are smooth, suspicious characteristic so biopsy to determine if malignant:
Lobulation
Lines, and areas of density scattered, ooks like scar that lines are leading towards, may have calcifications assoc w/ lesion (malignant)
Stellate finding in breast
Speckled, linear, rod like, different densities, punctuate, rtiny margins. Biopsy can be difficult, cannot see under US unless they are large; need to be removed:
Calcifications of breast on imaging
Metal tag (marker) placed where lump ifs felt; margins are not smooth/sharp, zone of transition not sharp; taller than wide, no through transmission:
Invasive ductal carcinoma
A marker is placed, dense breast tissue, scattered calcifications, more of isoechoic (similar to the surrounding tissues); biopsy w/ US
Infiltrating ductal carcinoma
Free, round mass, ill-defined margins, may have a stellate and linear appearance coming from the margin, hypoechoic on US with ill-defined margins
Mucinous (colloid) adenocarcinoma
Pre and post-contrast imaging (shows enhancement) in a dynamic series--use MRI for a more clear dx (after no clear dx after mammo/US), post-op if there is a change in a scar and extensive fibrocystic dz (nodules everywhere):
Ductal carcinomas in situ
Malignancy that redeveloped in a scar, can use contrast to enhance, hypoechoic enhancement w/in a scar:
Post biopsy scar
Biopsy done by guiding a wire into suspicious mass (or clip left from a previous suspicious mass), then surgeon follows wire in for a small lumpectomy, often target micro-clips that are placed:
Needle localization for open biopsy
Aside from melanoma, what is the MC CA detect in US women?
Breast CA
True or false: 70% have no risk factors for Breast CA except for gender and older age
True
What is the most important risk factor for breast cancer?
Being female (1:8 women in 90 year life span)
What does the ACS recommend for breast cancer screening?
Clinical breast exam x3 years from 20-30, yearly at 40yo
Clusters of calcifications are suspicious findings; if they come to each other and are different looking= bad sign...what do you do?
Biopsy
The finding in the breast is ill defined, irregular, lobulated, taller than wide. What do you suspect?
Infiltrating ductal carcinoma
What do you do with a palpable mass?
Gets a mammogram and then US immediately
What do you look for in the margins of breast imaging?
Irregular, ill-defined borders, projections
Is shadowing in breast tissue a good or bad sign?
Bad
What are the 3 important initial steps in evaluation of the newborn?
Drying, Warmth, Clearing airways
What are the three important initial questions in evaluation of the newborn?
Is the infant full term? Is the infant crying or breathing comfortably? Does the infant have good muscle tone?
What are the next steps if the infant is not full term, crying/breathing comfortably or has poor muscle tone?
Oxygen, positive pressure ventilation, chest compressions, meds (ie epinephrine)
What are the components of the APGAR scores?
Heart rate, respiratory effort, muscle tone, reflex irritability, color
Where are 90% of babies on the APGAR score chart?
between 7-10
What should a baby present like during the transition period?
Generally 4-6 hrs, temp 97.7-99.5, RR 40-60bpm, HR 120-160, pink color and good tone
What is the standard of care within the first 24 hrs of a babies life?
PE, feedings, Hep B vaccine, Cardiac screening, Vit K IM, Eye care (prevent GC), Erythromycine 0.5% ointment
What screenings does a newborn get?
Hearing loss, screen for metabolic and genetic disorders (PKU, congenital hypothyroidism, galactosemia, toxoplasmosis and hemoglobinopathies, critical congenital heart disease
What should we know about feeds and early weight loss in newborns?
Early and often; esp. important in IDM, small, LGA, 7% or greater weight loss demands close follow-up (up to 10% is acceptable in most situations). Birth weight regained by 10-14 days.
What are sx of hypoglycemia in a newborn?
Hypothermia, jitteriness, tremors, hypotonia, irritability, lethargy, stupor, apnea, poor feedings, seizures
What do you worry about with jaundice/hyperbilirubinemia in the newborn?
Values above 25mg%; Can result in BIND (Bilirubin-induced neurologic dysfunction and/or kernicterus)
What is the mean time to readmission? What is the most frequent diagnosis causing readmission and some other common ones?
62 hours after initial discharge. Jaundice is by far the most frequent diagnosis (92%) other reasons include feeding problems, dehydration, and/or associated electrolyte abnormalities. Most readmissions are first time moms, older moms (>30), Asian or Pacific Islander ancestry, maternal diabetes, PIH
What are "see-saw" respirations in a newborn?
Respirations due to chest wall being so compliant, but without other signs of distress is acceptable and subsides in 4-5 hours
What do you look for in newborns at the suprasternal/supraclavicular areas?
Retractions; these are not a normal finding
If retractions of the suprasternal/supraclavicular areas are found...what else might be present that is alarming
Grunting; this is very significant.
Also might find "singing." These are to keep the airways open.
What is worrisome about a barrel shaped chest in a newborn?
Meconium aspiration, air trapping or TTN/"wet lung", cardiomegaly, pneumothorax
What could asymmetry of the chest wall indicate in a newborn?
Diaphragmatic lesions: Paralysis (dificult delivery-brachial plexus injury, congenital rare), hernia-true life threatening emergency
On a normal CXR, how many ribs do you see w/ inhalation in a neonate?
7 or >
What does the head look like in a neonate w/ chronic lung dz?
Flat
What does a purple baby mean?
Large or small kids, push cord blood into baby=increase Hct=slugging;
Also IDM, SGA, LGA
Green baby?
Early passage of meconium
Mottled or pale baby?
Cold stress, acidosis, infection
Blue discoloration of the perioral area, feet and hands in a newborn?
Acrocyanosis. Normal for first 24 hours- due to vasoconstriction as they are trying to learn how to maintain body temp. Closely assoc w/ cool surroundings. Perioral changes seen w/ sucking/feedings
Bluish discoloration of tongue/mucus membranes in a newborn?
Central cyanosis; persisting after 1st few mins of life is always abnormal-think cardiac dz/pulmonary dz
What are some vascular "birthmarks" that initially appear pale and take on purple/bluish discoloration w/ time?
Port Wine Stains (Sturge-Weber, Klippel-Trenaunay), Salmon patches (Angel Kisses (Nevus flammeus, stork bite), Cafe au late
Elevated direct bilirubin can be a rare cause of what color babies?
Greenish
What is mottling?
May be the result of the infant being cold stress or an indicator of significant systemic illness. If warm and stays, worrisome, think cardiac or acidosis due to infection.
Is pallor ever normal?
No... Think of stuff below and that twins could have had ignificant differences in cord blood. Poor cardiac output, asphyxia, severe anemia/anemia-very pale, acidosis, subcutaneous edema
What does a grayish hue in a newborn indicate?
Most often indicates severe acidosis in the newborn and often a poor outcome; seen in severe infections and cardiac disease w/ poor perfusion of tissue
What scale describes muscle tone in newborns?
Ballard scale: development progresses in a caudocephalic manner (foot to head)
What is tone like in infants of 28 wks, 32 wks, 36 wks?
28: little tone
32: LE tone develops resulting in flexion of hips and knees
36: UE and LE tone is apparent, but strong flexor tone of legs exceeds early flexor tone of arms
What do term infants do w/ their limbs?
Hold all four extremities off bed while in supine position/at rest. Hands of term newborn are open periodically, but generally are closed (fisted) w/ the thumb adducted and folded.
Is joint mobility of a preemie more or less than a term baby?
Less
If there is an asymmetric droop i a newborn, which side is the side of the problem?
Side that does not droop
If you see an area of the forehead not wrinkle with cry, which CN do you think?
CN VII
Bilateral droop in a newborn...think what?
Mobius Sequence (congenital absence of CN VI and VII nuclei)
What is a weak/whiney cry in a newborn indicative of?
Illness, respiratory depression (maternal pain meds), or CNS disturbance; infants w/ CNS/head trauma often exhibit a "high pitched" cry (scary)
What can hoarseness in a newborn indicate?
Over zealous suctioning at delivery, hypocalcemia (rare), airway anomalies
If stridor when crying hard, what do you think?
Vascular ring or web (from pressure on airway--rare), Vocal cord paralysis or laryngomalasia or tracheomalasia--most common)
What is the normal cornea diameter in a newborn infant?
10mm diameter;
Total eye diameter is 17mm in the newborn
Microphthalmia (small eyes) is seen in a variety of syndromes including what?
Trisomy-13
What is enlarged corneal diameter seen with (often increase AP dimension)?
Congenital glaucoma (milky eyes)
What is the palpebral fissure angle in newborn eyes? What are some variations w/ this?
Medial to lateral. Downs is upward; Treacher Collins/FAS/Apert/DiGeorge all have slant downward (medial canthus to lateral_. Many syndromes including Trisomy 13 and Apert have hypertolerorism.
What kind of gaze do newborn exhibit and when should this be gone by?*
RANDOM and at times disconjugate gaze. Should be gone by 4mos
How long does subconjunctival hemorrhage take to go away?
3 weeks
When does pupillary reaction ot light begin?
At about 30 wks gestation, but may not be consistently seen until 35 weeks gestation.
What is the Red Reflex for and what do we look for?
Evaluated ot insure lack of opacity of the lens and cornea and to look for intraocular mass (retinoblastoma). In whites the reflex is red. Darker skinned infants, teh redreflex may be more of a pearly gray color. Finding a "white" red reflex indicates pathology (tumor, trauma, retinopathy of prematurity) and needs and urgent referral
What does the iris look like in infants?
Most have "blue" iris coloration, but in some darker skinned infants, the iris color may just be "dark," generally brown-dark brown.
When babies are born, at what % of capacity does the heart beat?
95%
What is the normal HR for a newborn?
100-160
What is the difference bt BP in legs vs arms?
Legs is slightly higher than arms. Pulse pressure 25-30mmHg in term & 15-25 mmHg in preterm
Should examiners focus in newborn assessment be listening for murmurs?
No, because most babies have murmurs in the newborn period, most are transient and innocent.
What is S1 in a newborn?
Typically single and accentuated shortly after delivery (increased flow across AV valve) and w/ lesions that increase this flow (ie ASD)
Where is S2 best heard?
At the upper left sternal border and is normally split--listen for the split (absence can mean pathology): aortic atresia, pulmonary atresia, truncus arteriosus, transposition of the great vessels (due to position).
Widely split S2 (ASD, total anomalous venous return)
What does persistent pulmonary hypertension produce?
A narrow split, but accentuated S2
What do Loud murmurs (grade 2 or more) with harsh qualities, to and fro murmurs and pansytolic murmurs persisting past first few hours of life deserve?
Deserve a further evaluation
What does the disappearance of a murmur in a clinically deteriorating infant indicate?
A ductal dependent lesion (coarctation of the aorta is most common), tricuspid atresia or pulmonary atresia
What do stridor, crepitance and rales indicate in a newborn?
Stridor (narrowing), crepitance (secretions), rales (atelectasis/pneumonia-generally end of inspiration)
What might a scaphoid abdomen in an infant indicate?
Diaphragmatic hernia and in SGA infants
What is a full upper abdomen w/ a flattened lower abdomen indicative of?
Proximal obstruction or atretic lesion
What can cause extreme distension of hte abdomen at birth?
Ascites (hydrops), Meconium ileus, Intrauterine midgut volvulus
How is palpation of the abdomen of a newborn best done?
W/ legs flexas as teh infant is sucking (pacified or gloved finger). Begin in lower abdomen, press long enough to allow infant to realx.
In a newborn, renal enlargement can mean what?
Result of hydronephrosis or cystic kidney disease--MC abdominal mass found in newborns
Where should the liver be palpable in a newborn? What about the spleen?
Liver: 1-3 cm below the RCM, with the left lobe extending across the midline. Smooth edge (normally), Soft;
Spleen should not be palpable (should be considered enlarged if palpable--infection/hematopoeisis)
What is normally seen in the umbilical cord?
Normally 3 vessels (2 arteries, 1 vein). A single artery is most often a normal variant. A single artery accompanied by any other abnormal (minor or major) is of concern; some feel teh history of a "short" cord may be related to syndromes (Downs)
In newborn, may be bilateral, increases in size after delivery, can be tense or fluctuant, late can mimic a fracture on x-ray, weeks to months for resolution?
Cephalohematoma (sub-periosteal blood extending to bone/doesn't pass midline) occurs in 1-2% of deliveries
Boggy area of edema and or bruising, crosses suture lines, gone in days, present at birth (generally doesn't enlarge)
Caput Succadaneum
Least common fo the extracranial injuries, but the most dangerous:
Subgaleal hemorrhage
(very significant amt of blood loss is possible, enlarges after birth, crosses suture lines, can cover entire scalp and extend into the neck)
On newborn, what can double whorls and/or cowlicks be associated w/?
Scalp, skull, CNS abnormalities
These lesions of atretic skin/scalp/bone (skull) can be associated w/ CNS problems or syndromes (trisomy-13). Generally 2-5 cm in size:
Ectodermal defects
Where is the largest circumference found on head size?
Frontal--> occipital
What is craniosynostosis?
Tends to be familial; most comonly seen in teh saggital suture (dolichocephaly-keel head*)-lethal in femals?
What is a palpable ridge along suture lines indicative of?
Closure
What is Plegiocephaly?
Flats head common bc back is the best for baby to lay
Craniotabes-Flexible skull table:
Saggital suture most common, now thought to be due to relative intrauterine Vitamin D deficiency
Which fontanelle has the greatest variation in size?
Anterior (large variations can be concerning--associated w/ thyroid fxn/Calcium levels)
If there are signs fo CHF (tachy, tachypnic, poor feeding, edema late) in a newborn, what do you do?
Listen to the head--over hte temporal regions and the anterior fontanelle (bruit-*AV-malformation)
Real low set ears are positioned how?
Posterior rotation. If normal, the top will be in line w/ the eye
What is the MC abnormal finding of the nose?
Being misshapen secondary to birthing or intrauterine positioning; If you suspect or find evidence of septal deviation, call ENT for eval/tx. Most often, just soft tissue swelling, which resolves in a few days
Small nose seen w/ what syndrome?
Fetal alcohol syndrome
Large nose seem w/ what syndrome
Trisomy 13
Low nasal bridge seen w/ what syndrome?
Achondroplasia
Prominent nasal bridge seen w/ what syndrome?
Seckel syndrome (extreme short stature, large nasal bridge, microcephaly)
Nasal obstruction can be caused by what?
Mucus, edema (from well intentioned suctioning), real anatomical (tumor, encephalocele, Choanal atresia)
What is Choanal atresia?
CHARGE syndrome: Coloboma, Heart defect, Atresia choanne, Retarded growth/development, Genital abnormalities, Ear abnormalities)
What is a coloboma?
Defect of iris, keyhole looking; defect of eyelid
What is the most well known cause of Micrognathia?
Pierre-Robins sequence
What are the little white balls on the palate? Are they normal?
Epstein Pearls (epithelial cysts); Yes, they are normal
If a baby is found to have a bifid uvula, what else do you check?
Hard palate bc tend to have floppy palates
Excess or redundant skin along the posterolateral line (webbing) is seen in 1/2 of F infants w/ what?
Turner's syndrome (XO) and Noonan Syndrome
Excess skin at the base of the neck is common w/ what?
Trisomy-21 (Down's)
What is the MC neck mass in the newborn?
Cystic hygroma (lymphangioma), which is composed of dilated lymphatics. Most commonly lateral/posterior to SCM muscle
What do we examine on the anterior neck exam?
Is the trachea in midline? Is the thyroid enlarged or is there a medial neck mass? Is there a lateral neck mass?
What do we need to know about LN in a newborn?
LN up to 12mm are found in about 25% of healthy newborns. MC site is in teh inguinal area. Cervical nodes are not unusual. Can be related to congenital infections. Supraclavicular nodes are never considered normal.
What might indicate a fractured clavicle?
Asymmetrical startle or Moro reflex- one hand will not elevate as high as other when startled.
Pigeon breast vs. Funnel chest?
Pectus excavatum (funnel); Pectus carinatum (pigeon breast)
What is Witches Milk?
When kids produce milk (white dot on nipple), may occur especially w/ repeated palpation so don't try ot milk them down.
Nerves of concern in Erb's Palsy? What do you see w/ Erb's Palsy?
C4, C5, C6, C7 (Arm extended and internal rotation=waiter's tip position). Palmar grasp is present. Can be just from stretching of nerve roots and can disappear (if doesn't in 3 weeks, then it won't)
What are the following developmental dysplasia of the hip: Barlow/Ortalanti?
Ortalanti: feeling click where head of femur is sliding back into place; Barlow: actually dislocating hip;

More common in female, if there are CNS abnormalities, w/ breech presentation. Re-examination hips before discharge--shown to be only consistent portion of the PE to pick up an abnormality not seen prior
How big is the penis at birth?
~2.5 cm
If infant has cryotporchidism (testes not down), when should this resolve by? If not, then what?
Should resolve by 3 mos. If not down by 9-12 mos, evaluation by surgeon: see if warm bath will drop the testes to scrotum or do US
Absence of anus is often associated w/ what other abnormalities
VATER (Vertebral defects, VSDs, Anal atresia, TE fistula/esophageal atresia, radial dysplasia
What is the white yucky stuff that babies have all over when they are born? Especially inguinal/axillary, appears about 35 wks and may be gone at 41 weeks?
Vernix (marker for maturity when gone)
What is lacking in the skin in the extremely immature infant (<28 weeks gestation)
Stratum corneum; this allows for very significant water loss and is extremely susceptible to mechanical injury; but by 7-14 days of age, the stratum corneum matures reducing the loss of water
Long nails, lack of vernix, peeling/dry skin are signs of what?
Post-maturity
Benign rash of newborn (40-50%), usually appears 2nd to 3rd day of life (gone in 7-14 days approx). Erythematous base w/ 1-2 mm pustules or papules. Spares palms, soles. Pustule/vesicles contain debris and Eos:
Erythema toxicum neonatorum
1-2 mm whitish papules most often face and neck/shoulders, sweat duct obstruction, gone in days to weeks, benign, maybe associated w/ areas over heat:
Miliaria (miliaria rubra/heat rash)
Appear on face and scalp; 1-2mm white, firm papules on the face and bridge of nose--sign of maturity?
Milia (white head looking)
When does Milia appear?
at ~36 weeks gestation. Resolve spontaneously by a few mos
Genearlized benign eruption of superficial pustules overlying hyper pigmented macular base--often associated w/ stress. Appears without evidence of inflammation and are present at birth. More common in darker skinned races. Can mimic Herpes if severe. Break open in a few days and then resolve. Usually come off in 1st bath:
Transient Neonatal Pustular Melanosis
Slate blue/gray or black, macular to patch size, more common in darker skinned races, but affects all. Benign. Those on the lower back/buttocks tend to resolve over several years.
Mongolian spots (dermal melanosis)
Where do high rates of abortion occur?
In countries that severely restrict abortion-> laws that legalize abortions= increased mortality of death associated w/ abortion
What did Romania prove about abortion?
With the stats that when under dictatorship, abortion was illegal. When it was illegal, death was higher. When legal, lower death rates.
What happened in South Africa when they changed their abortion laws?
Bt 1994 and 2000, severity of abortion related complications dropped. Fewer postabortion infections, largest gains by young women. Deaths due to unsafe abortion declined by at least 50%!
What happened in the Russian Federation when modern contraceptives increased use?
Abortion rates declined (Important: any type of contraceptive--not including traditional types)
Who has the lowest abortion rates in the world?
Europe (also has high contraceptive use)
Procedure for terminating an unintended pregnancy carried out either by persons lacking the necessary skills and termination in an environment that does not conform to minimal medical standards:
Unsafe abortion
Complications from unsafe abortion procedures account for what percent of maternal deaths?
13% (67,000/year)
What are the recommendations for reproduction according to planned parenthood guy?
Prevent unintended pregnancy, make abortion care safer, improve postabortion care, improve postabortion services
When can you do a dilation and evacuation for an abortion?
13+ weeks up to 24+ viability
When can you do a medication abortion?
Up to 9 weeks EGA
What drug class is mifepristone?
Antiprogestin
What drug class is methotrexate?
Antimetabolite
How many visits are required for a medical abortion?
Three: Consent, 24 hours later take med, third for follow up
How early can surgical abortion be provided?
4-5 weeks from LMP
What are the instruments/supplies for a surgical abortion?
Speculum, tenaculum, dilators, suction cannulae, MVA syringe or cannulae, MVA syringe or electric suction devide
What do you do to prevent infection in abortion?
Give prophylactic antibiotics (doxy) (get infection in <2% of procedures)
How often do you get an incomplete abortion?
0.5-3% of procedures
What is the leading cause of maternal and surgical methods of prego termination?
Unsafe abortion