Week 11 Flashcards
What is colostrum?
First milk produced by mammary glands in breast (for about a week)
Why is “breast is best” for the baby?
- Reduced incidence of GI, respiratory & middle ear infection
- Decreased risk of childhood diabetes, asthma & eczema
- Reduced risk of lactose intolerance
- Improved intellectual & motor development
- Decreased risk of obesity in later life
- Possible reduced autoimmune diseases
- 27% reduced risk of sudden infant death syndrome
What does WHO/UN advise women to do regarding breast feeding?
Breast feed exclusively for 6 months for optimal lifetime benefits
Why is “breast is best” for the mother?
- Promotes recovery from childbirth
- Promotes return to “normal” body weight
- Promotes a period of infertility
- Reduces risk of premenopausal breast cancer
- Possibly reduces risk of ovarian cancer
- Possibly improves bone mineralisation
What is the physiology behind lactational amenorrhoea?
- Prolactin suppresses hypothalamic release of GnRH & therefore pituitary FSH & LH
- Prevents follicular growth, ovulation & menstruation
Describe breast development at birth?
Breast consists of lactiferous ducts without any alveoli (also male breast)
Describe breast development at puberty?
Under influence of oestrogen the ducts proliferate & masses of alveoli form at the ends of the branches
Describe breast development at each menstrual cycle?
Involves proliferative changes in alveoli & there may be some secretory activity
Describe breast development during pregnancy?
Under influence of oestrogen, progesterone & prolactin the glandular portion of breast undergoes hypertrophy replacing adipose tissue
Describe breast development from week 16 of pregnancy?
Breast tissue is fully developed for lactation but is quiescent awaiting activation
Describe breast development after parturition?
Breast produces colostrum before mature milk production begins
What are the 5 stages to breast alveoli development during pregnancy?
- Prior to pregnancy , ducts with few alveoli
- Early pregnancy, alveoli grow
- Midpregnancy, alveoli enlarge & acquire lumen
- During Lactation, alveoli dilate
- After weaning, gland regresses
Describe the anatomy of the breast?
- Nipple surrounded by pigmented skin (areola)
- Modified sebaceous glands (alveoli) empty via lactiferous ducts that are dilated to form lactiferous sinuses which open on surface of nipple
- Each alveolus surrounded by contractile myo-epithelial cells
What tissue is dominant in the non-lactating breast?
Adipose tissue
When does glandular tissue develop fully in the female breast?
During pregnancy (replaces adipose tissue)
What are the milk producing cells & what are they stimulated by?
- Secretory alveoli/acini
- Stimulated by prolactin
What stimulates contractile myo-epithelial cells?
Oxytocin
What 2 things does lactation consist of?
- Milk production
2. Let down (milk ejection reflex) as infant cannot suck milk out of alveoli where it is produced
What is lactation controlled by?
Neurohumoral reflexes, prolactin is the hormone
How is lactation initiated & controlled?
- Initiated by precipitous drop in oestrogen & progesterone after delivery
- Prolactin surges when mother nurses baby due to nerve impulses from nipples to hypothalamus
- When not nursing, hypothalamus produces prolactin inhibitory hormone
How is lactation inhibited during pregnancy?
- Prolactin is inhibited by high levels of progesterone, oestrogen & hPL (human placental lactogen)
- These steroids fall after parturition & milk production begins
Describe the suckling reflex (role of prolactin)?
Suckling stimulus inhibits hypothalamic release of dopamine (PIF) & prolactin is released in proportion to the strength & duration of suckling
Describe the milk ejection reflex (role of oxytocin)?
- Suckling stimulates neurones in hypothalamus to synthesis oxytocin which is carried to posterior pituitary
- Release of oxytocin into blood stream acts on myo-epithelial cells in alveoli causing “let down” of milk
What is oxytocin release inhibited by?
Catecholamines, stress can inhibit the reflex
Why is correct attachment important to suckle effectively for baby & mother?
- Avoid engorgement/blocked ducts for mum
- Ensure sufficient intake for baby
What 4 things make up a mammary gland?
- Breast
- Secretory lobules
- Alveoli
- Lactiferous ducts (milk ducts)
How is milk made & excreted?
- Synthesised milk fat moves through cell to surface membrane
- Enclosed lipid droplet is pinched off into the duct lumen
- Milk protein passes though Golgi apparatus & released by exocytosis
Describe the composition of Colostrum (100ml)?
- 58 calories
- 5.3g carbohydratess
- 2.9g fat
- 3.7g protein
- Fewer water-soluble vitamins
- More fat-soluble vitamins (A)
- More zinc & sodium
- Greater amounts of immunoglobulins (IgG…) & growth factors
Describe the composition of mature milk (100ml)?
- 70 calories
- 7.4g carbohydrates
- 4.2g fat
- 1.3g protein
- Relatively low protein & fat compared to other mammals means human babies do not grow as fast
What happen over 2 or 3 weeks to the composition of milk?
- Transitional –> Mature milk
- Total calorific value increasing
- IgG & total proteins declining
How much milk does a woman produce per day?
- 800ml
- Energy content of 27kJ/L (vary through lactation)
What are the specific composites of Mature milk?
- Energy source fat (easily digested emulsified globes)
- Lactose main carb
- Proteins casein & lactalbumin
- Fat soluble vitamins A,D,E,K
- Water soluble vitamins B6, B12, C, Folate, Niacin, Riboflavin, Thiamine
What does Lactose in mature milk (main carbohydrate) promote in a baby?
- Growth of Lactobacillus bifidus
- Galactose for myelin formation
Describe the gut of a newly born child?
Initially sterile & 1st feeds will contain acute dose of antigens & bacteria (600sp of bacteria identified in breast milk including beneficial Bifidobacterium sps)
Describe Benign Breast diseases?
Heterogeneous group including developmental abnormalities, inflammatory lesions, epithelial & stromal proliferations & neoplasms
Describe the frequency pattern of benign breast disease?
Increases towards menopause then decreases
How can diagnosis of benign breast disease be accomplished without surgery in majority of patients?
- Mammography
- Ultrasound
- Magnetic resonance imagine of breast
- Extensive use of needle biopsies
Describe the characteristics of a normal cell on cytology?
- Large cytoplasm
- Single nucleus
- Single nucleolus
- Fine chromatin
Describe the characteristics of a cancerous cell on cytology?
- Small cytoplasm
- Multiple nuclei
- Multiple & large nucleoli
- Coarse chromatin
What type of needle is used to get a specimen of breast tissue for histology?
Core biopsy (Tru-cut) needle
What is the Fibrocystic change (FCC) which occurs in benign breast disease?
- Exaggerated physiologic response
- Nonproliferative, includes gross & microscopic cysts, apocrine metaplasia, mild epithelial hyperplasia, adenosis & increase in fibrous stroma
- Multifocal & bilateral
How common is Fibrocystic change (FCC)?
- Over 1/3 of women 20-50 yrs old
- Declines after menopause
What are the symptoms of Fibrocystic change (FCC)?
- Most asymptomatic
- Some present with nodularity & pain
What is the risk of cancer with Proliferative Breast disease?
- Without atypia entails 2 fold increase risk of carcinoma over 5-15yrs
- Lesions with atypia involve even greater relative risk (5 fold)
What is the chain of events of breast carcinogenesis?
Normal epithelium –> Proliferative disease without atypia –> Atypical hyperplasia –> DCIS –> Invasive breast cancer
How can you distinguish a breast cyst from solid masses?
Ultrasonography & fine needle aspiration (FNA) cytology (highly accurate)
What is Gynaecomastia?
- Hyperplasia of male breast stromal & ductal tissue
- Caused by relative increase in oestrogen to androgen ratio
What can be the cause of Gynaecomastia in the young & elderly population?
- Young: cannabis, anabolic steroids, anti-ulcer drugs, antidepressants
- Old: cardiovascular & prostate drugs
What are physiological & pathological causes for gynaecomastia?
- Physiological: spontaneously in neonates, pubertal & senesence
- Pathological: undiagnosed hyperpolactinaemia, liver failure, alcohol excess, obesity & malignancy (tests & lung)
What are the 4 different types of benign breast tumours?
- Fibroadenoma
- Duct papilloma
- Adenoma
- Connective tissue tumours
Describe Breast Fibroadenomas?
- Breast lobules & composed of fibrous & epithelial tissue
- Well circumscribed & highly mobile
- Difficult to differentiate from Phyllodes tumours
Describe Phyllodes tumours?
- Sarcomas which rapidly enlarge & have variable degrees of malignant potential
- Larger than fibroadenomas & tend to occur in older age group
Describe how fat necrosis presents?
- Soft, indistinct lump than develops a few weeks after traumatic incident (older women with fatty breasts)
- Core biopsy taken
What factors can increase & decrease the risk of breast cancer?
- INCREASES risk: alcohol, contraceptive pill, X radiation, body fat, adult heigh, HRT, smoking, digoxin
- DECREASES risk: breastfeeding, body fatness, physical activity
What are the 2 forms of non-invasive precursors of breast cancer?
- Ductal carcinoma in situ: often unilateral, localised within epithelial layer
- Lobular carcinoma in situ: often bilateral, can be multifocal, malignant proliferation in lobules with no invasion of BM
Describe the 3 types of Invasive carcinoma’s?
- Most are of “no special type” 70-90%
- Infiltrating lobular carcinoma (10%) may be multifocal
- Some special types, less common
What is Paget’s disease of the nipple?
- Leads to erosion of nipple than resembles eczema
- Associated with underlying in situ or invasive carcinoma
What are the 4 different ways breast cancer can spread?
- Direct
- Lymphatics
- Blood stream
- Transcoelomic
What are the different prognostic factors for breast cancer?
- Tumour type
- Tumour grade (A)
- Tumour stage (size, node metastasis (B), other metastases)
- Oestrogen receptor (C)
- HER-2 amplification
What are the different screening strategies for breast cancer?
- Breast self examination
- Clinical breast examination
- Mammography
- Ultrasonography
- Magnetic resonance imaging (MRI)
What is the NHS Breast screening programme?
- Invited all women 50-70yrs for screening every 3 yrs
- Around 4/100 called back for further tests
- Finds cancer in ~8/1000 women
What chance of survival for 5yrs does women diagnosed with breast cancer at earliest stage have?
9 in 10 chance (90%)
What do NICE recommend for women that have a gene mutation known to increase risk of breast cancer (family history)?
Yearly MRI scans from age 20 for women with TP53 mutation, age 30 for women with BRCA1 or BRCA2 mutation
What scenarios would you refer urgently for suspected breast cancer?
- > 30yr & have unexplained breast lump with/without pain
- > 30yr with unexplained lump in axilla with skin changes that suggest breast cancer
- > 50yr with any of the following in 1 nipple only: discharge/retraction/other
When would you consider non-urgent referral for suspected breast cancer?
Under 30yrs with unexplained breast lump with/without pain
What is the commonest cervical cancer?
Invasive tumour of epithelial origin with squamous differentiation
What is the main aetiological factor of cervical squamous neoplasia?
Human papillomavirus
What are the 2 immune modulations of cervical squamous neoplasia?
- Smoking
2. HIV infection
How is the pre-invasive phase of cervical squamous neoplasia detectable?
Cervical cytology
What is the grading system (Bethesda Classification) for pre-invasive cervical squamous neoplasia?
- “Low grade squamous intraepithelial neoplasia” LSIL versus “high grade” HSIL
- Cervical intraepithelial neoplasia (CIN) grades 1 to 3 (2 & 3 correspond to HSIL)
Describe how common Human papillomavirus is & what it causes?
- Most common STI, 70-80% sexually active women affected in lifetime
- 80% cases HPV produces transient infection & cleared from body within 2yrs without clinical consequence
Describe what happens when Human Papillomavirus (HPV) is left untreated?
- Virus may incorporate DNA into host cell’s genome
- Production of viral oncoprotein can go unchecked & host’s genes that suppress tumours inactivated
- Damaged DNA replicated without being checked & repaired
- Malignantly transformed cells proliferate uncontrollably
When is HPV cleared?
93% by 3yrs
What is the female transformation zone?
- Most common site for cervical cancer=
Squamo-columnar junction - It goes through a lot of change through life (menstruation)
- Get neoplastic changes, high proportion will resolve without any intervention
What are precursors of invasive cancer?
Squamous intraepithelial lesions
What are the different ways of cervical screening & intervention?
- Cytology/Pap test: spatula, cytobrush, glass slide, liquid based
- HPV detection
- Visual inspection with acetic acid/iodine
- Vaccination
- Colposcopy & biopsy
- Local excision
- Cryotherapy
What does LEEP & LLETZ stand for?
- LEEP= Loop Electrosurgical Excision procedure
- LLETZ= Large Loop Excision of the Transformation Zone
What are the 2 types o invasive cervical cancers?
- 70-75% squamous cell carcinomas
2. Minority are adenocarcinomas: precursor lesion cervical glandular intraepithelial neoplasia (CGIN)
What are the classical symptoms of invasive cervical cancer?
- Post coital bleeding
- Many asymptomatic in early stages
What is the mean age at which women develop Squamous intraepithelial lesions (SIL/CIN)?
25-30yrs
How often does LSIL (CIN1) progress to HSIL (CIN2&3)?
6% & less than 1% become invasive cancer
What % of HSIL (CIN2&3) progress to invasive carcinoma if untreated?
10-20%
What are the average ages of patents with stage 0 (HSIL), stage 1A, stage IV squamous cell carcinoma of cervix?
- Stage 0 (HSIL): 35-40yrs
- Stage IA: 43yrs
- Stage IV: 57yrs
What is the % of 5yr survival for the different stages of squamous cell carcinoma of the cervix?
- Stage I: 90%
- Stage II: 75%
- Stage III: 35%
- Stage IV: 10%
How common are congenital uterine abnormalities?
- ~5% of women
- Lower rate in general population
- Higher in infertile
- Highest in women with recurrent pregnancy losses (10%)
What are most Müllerian malformations associated with?
- Abnormalities of the renal & axial skeletal systems
- Function of ovaries
- Age-appropriate external genitalia
What 2 procedures can detect uterine malformations?
- Hysterosalpingogram
- MRI image
What are ~90% of vulvar cancers?
Squamous cell carcinomas, typically develop at edges of labia majora/minora or in vagina
Since vulvar squamous cell cancers are slow growing, what do they usually develop from?
“Precancerous”, pre-invasive areas called vulvar intraepithelial neoplasia (VIN)
Describe the 2 subtypes of squamous cell vulvar cancer?
- Common in young women: HPV
2. Common in older women: vulvar dystrophy, including lichen sclerosus