WEEK 11 Flashcards
What is the first milk produced?
colostrum
WHO/UN advises for women to breast feed exclusively for 6 months for optimal lifetime benefits. What are the advantages, to the BABY, of this?
- reduced incidence of GI, resp and middle ear infection
- decreased risk of childhood diabetes, asthma and eczema
- reduced risk of lactose intolerance
- improved intellectual and motor development
- decreased risk of obesity in later life
- possible reduced autoimmune diseases
- 27% reduced risk of sudden infant death syndrome
Why is breast feeding beneficial to the mother?
PROMOTES: - recovery from childbirth - return to 'normal' body weight - promotes period of infertility REDUCES risk of premenopausal breast cancer POSSIBLY: - reduces risk of ovarian cancer - improves bone mineralisation
What is the role of prolactin in lactational amenorrhoea?
- suppresses hypothalamic release of GnRH and therefore pituitary FSH and LH
- prevents follicular growth, ovulation and menstruation
Describe the development of the breast, from birth to after parturition.
- at birth breast consists of lactiferous ducts w/out any alveoli
- at puberty, under the influence of oestrogen, ducts proliferate and masses of alveoli form at ends of branches
- each cycle involves proliferative changes in alveoli and may be some secretory activity
- during pregnancy, due to oestrogen, progesterone and prolactin, glandular portion of breast undergoes hypertrophy replacing adipose tissue
- from wk 16, breast is fully developed for lactation but is awaiting activation
- atfer parturition breast produces colostrum before mature milk production begins
What happens to the alveoli during pregnancy?
- prior to pregnancy few alveoli exist
- in early pregnancy alveoli grow
- in mid-pregnancy, alveoli enlarge and acquire lumen
- during lactation, alveoli dilate
- after weaning, gland regresses
What do alveoli empty via?
Lactiferous ducts that are dilated to form lactiferous sinuses which open on the surface of the tissue
What are (i) secretory alveoli/acini (ii) contractile myo-epithelial cells surrounding stimulated by?
(i) prolactin
(ii) oxytocin
What is lactation initiated by? Explain the points when prolactin is increased, and then decreased.
Initiated by precipitous drop in oestrogen and progesterone after delivery
- prolactin surges each time mother nurses baby due to nerve impulses from nipples to hypothalamus
- when not nursing, hypothalamus produces prolactin inhibitory hormone
- lactation inhibits FSH and LH and thus lactation interferes with repro function
How is lactation inhibited during pregnancy?
- prolactin controls/promotes milk production
- prolactin is secreted during pregnancy but its action is inhibited by high progesterone and oestrogen levels in hPL
- these steroid levels fall after parturition and milk production begins
What is the role of prolactin in the sucking reflex?
- suckling stimulus inhibits hypothalamic release of dopamine (PIF) and prolactin released in proportion to the strength and duration of the suckling
What is the role of oxytocin in the milk ejection reflex?
- suckling stimulated neurones in hypothalamus to synthesise oxytocin which is carried to the posterior pituitary
- release of oxytocin into blood stream acts on myo-epithelial cells in alveoli, causing ‘let down’ of milk
- conditioned reflex: let down in response to cry of baby, oxytocin release inhibited by catecholamines and stress can inhibit this reflex
When does the coordination of suckling develop? What is the correct way for baby to suckle? Why is it important?
- between 32 to 35 eek gestation
- correct attachment important to suckle effectively to avoid engorgement/blocked ducts for mum and ensure sufficient intake for baby
What happens to (i) synthesised milk fat (ii) milk protein?
(i) moves through cell surface membrane. Enclosed droplet pinched off into duct lumen
(ii) passes through Golgi apparatus and released by endocytosis
What is the difference between colostrum and mature milk?
- colostrum has greater amounts of immunoglobulins (IgG, IgA) and a no. growth factors, conferring passive immunity
- relatively low protein and fat compared to other mammals means that human babies don’t grow as fast
What is the composition of mature milk?
- main energy source = fat
- lactose = main carb, it promotes growth of lactobacillus bifidus and provides galactose for myelin formation
- proteins casein and lactalbumin
- fat soluble vitamins A, D, E, K
- water soluble vitamins B6, B12, C, folate, niacin, riboflavin, thiamine
- gut is initially sterile and first feeds will contain acute dose of antigens and bacteria
What does benign breast disease consist of?
- a heterogeneous group of lesions including developmental abnormalities, inflammatory lesions, epithelial and stromal proliferations, and neoplasms
When in a womens life is it most common to acquire benign breast disease?
- increases in frequency towards menopause, then decreases
How is benign breast disease diagnosed?
with use of mammography, US, MRI and extensive use of needle biopsies
For BENIGN breast lumps, describe the (i) shape (ii) alignment (iii) margins (iv) lateral shadowing?
(i) oval/ellipsoid
(ii) wider than deep; alligned parallel to tissue planes
(iii) smooth/thin
(iv) present
For MALIGNANT breast lumps, describe the (i) shape (ii) alignment (iii) margins (iv) lateral shadowing?
(i) variable
(ii) deeper than wide
(iii) irregular or spiculated
(iv) absent
What is fibrocystic change (FCC)?
An exaggerates physiologic response
- nonproliferative change which induces gross and microscopic cysts, apocrine metaplasia, mild epithelial hyperplasia, adenosis and an increase in fibrous stroma
Who does FCC affect? What symptoms do women tend to have?
- over one third of women 20-50 years old, then declines after menopause
- most are asymptomatic but some present with nodularity and pain
Does FCC increase your risk of breast cancer? Explain/
- doesn’t increase risk of getting breast cancer but it can make it more difficult to identify potentially cancerous lumps during breast examination & on mammograms
What is the difference for proliferative disease (i) without atypia (ii) with atypia?
(i) entails a 2 fold increased risk of developing carcinoma over 5-15 yrs and classified simply as proliferative breast disease
(ii) even greater relative risk (5 fold). Such patients require close clinical monitoring
What are the stages of breast carcinogenesis?
- Normal epithelium
- Proliferative disease without atypia
- Atypical hyperplasia
- DCIS (ductal carcinoma in situ)
- Invasive breast cancer
How is benign breast disease diagnosed?
- cysts can’t reliably be distinguished from solid masses by clinical exam or mammography, so in these cases ultrasonography and FNA cytology are used
What are the causes of gynaecomastia? What does it involve in older and younger pts?
- usually caused by a relative increase in oestrogen to androgen ratio in circulation or breast tissue
- most common cause is secondary to drugs
- in older pts it involves CV & prostate drugs, and in younger pts, cannabis, anabolic steroids, anti-ulcer drugs and antidepressants
What are other pathological causes of gynaecomastia?
- undiagnosed hyperprolactinaemia
- liver failure
- alcohol excess
- obesity
- malignancy (testes and lung)
What are the 4 types of benign breast tumours?
- fibroadenoma
- duct papilloma
- adenoma
- connective tissue tumours
What are fibroadenomas? What do they look like? What are they composed of? What is the difficulty of them?
BENIGN
- arise from breast lobules and are composed of fibrous and epithelial tissue
- well circumscribed and highly mobile, because of the encapsulation and pliability of young breast tissue
- clinically fibroadenomas are difficult to differentiate from Phyllodes tumours, which is a distinct pathology
What is the difference between fibroadenomas (benign) and Phyllodes (malignant) tumours?
- phyllodes are sarcomas which rapidly enlarge and have variable degrees of malignant potential
- phyllodes are larger than fibroadenomas and tend to occur in an older age group (15-20 yrs later)
- fibroadenomas appear well-defined, smooth, oval-shaped lump, distinctly mobile and easily identified on US
- young pts (less than 25) with clearly benign clinical and imaging findings are usually spared a core biopsy but in older pts we must rule out occult malignancy/Phyllodes tumour
What does fat necrosis present like? What can be an issue with imaging?
- presents as a soft, indistinct lump that develops a few weeks after a traumatic incident, and often in older women with fatty breasts
- on imaging, some are difficult to distinguish from breast cancer and a core biopsy is often indicated
What is the commonest cause of death in women aged 33-35?
breast carcinoma
What are the main types of invasive carcinoma?
- most are of ‘No special type’ 75-90%
- infiltrating lobular carinoma 10% may be multifocal
What does Paget’s disease of the nipple (i) lead to (ii) associated with?
(i) erosion of the nipples that resembles eczema
(ii) with underlying in situ OR invasive carcinoma
What are the 4 ways that breast cancer can spread?
- direct
- lymphatics
- blood stream
- transcoelomic
What factors have led to steady improvements in the long-term survival rates for breast cancer? (HINT: there’s 4)
Better diagnosis, improved treatments, screening programmes and public awareness
What are the screening strategies for breast cancer?
- breast self exam
- clinical breast exam
- mammography
- ultrasonography
- MRI
- risk factor based vs universal
- age
- does it change the outcome?
Describe the NHS screening programme.
- invites all women 50-70 yrs for screening every 3 yrs
- the earlier breast cancers are diagnosed, the easier to treat.
What does NICE recommend for women who have a change in gene (mutation) known to increase the risk of breast cancer?
Yearly MRI scans from:
- age 20 for women with a TP53 mutation
- age 30 for women with a BRCA1 or BRCA2 mutation
When are urgent referrals for suspected breast cancer done?
- aged 30 and over and have an unexplained breast lump with or w/out pain
- aged 30 or over with an unexplained lump in the axilla with skin changes that suggest breast cancer
- Aged 50 or over with any one of the following symptoms in one nipple only: discharge/retraction/other changes of concern
What is the commonest cervical cancer? What is its main aetiological factor?
- An invasive tumour of epithelial origin with squamous differentiation
- HPV = main aetiological factor
How is the pre-invasive phase of cervical squamous neoplasia detected? What is the grading systems for pre-invasive disease?
- detected by cervical cytology
GRADING SYSTEM:
Bethesda classification - low grade squamous intraepithelial neoplasia LSIL vs high grade HSIL
- cervical intraepithelial neoplasia (CIN) grades 1-3 (2+3 correspond to HSIL)
80% of cases HPV produces a transient infection and cleared from body w/in 2 years w/out any clinical consequences. What can happen, if HPV infection persists?
- the virus may incorporate its DNA into the host cell’s genome
- once incorporated, the production of viral oncoproteins can go on unchecked and the host’s gene that suppress tumours (p53 and pRb) can be inactivated
- damaged DNA is replicated w/out being checked and repaired, and malignantly transformed cells proliferate uncontrollably
Screening and intervention strategies q?
- cytology (spatula, cytobrush, glass slide, liquid based)
- HPV detection
- Visual inspection with acetic acid/iodine
- vaccination!
- colposcopy and biopsy
- local excision (‘large loop excision’)
- cryotherapy
What are most types of invasive cervical cancer? What are the classical symptoms?
- most (70-75%) are squamous cell carcinomas and a minority are adenocarcinomas (precursor lesion cervical glandular intraepithelial neoplasia CGIN)
- symptoms = post coital bleeding but many asymptomatic in early stages
What is the mean age that women develop SIL (CIN)? (squamous intraepithelial lesions, cervical intraepithelial neoplasia)
25 - 30 years
What are the various outcomes of SIL?
- 70% SIL (CIN 1) regress
- 6% progress to HSIL (CIN 2 +3)
- less than 1% become invasive cancer
What are the 2 forms of non-invasive precursors for breast cancer?
- ductal carcinoma in situ (DCIS)
- often unilateral - lobular carcinoma in situ (LCIS)
- often bilateral, can be multifocal
How do you check if breast cancer has spread?
sentineal node biopsy
What are the prognostic factors for breast cancer?
- tumour type
- tumour grade (A)
- tumour stage = tumour size, node metastasis (B) or other metastases
- oestrogen receptor (C)
- HER-2 amplification
What are you looking for upon breast clinical examination in suspected breast cancer? (HINT: there’s 6)
- lump
- pulled in nipple
- dimpling
- dripping
- redness/rash
- skin changes
Where does cervical cancer occur?
Transformation zone
- where lining of womb meets lining of vagina
WHat is the average age of women with (I) stage 0 HSIL tumour (ii) stage IA (iii) stage IV?
(i) 35-40 years
(ii) 43 years
(iii) 57 years
When/where is the best predictor of survival of cervical cancer?
the anatomic stage
What is the 5 year survival of squamous cell carcinoma of the cervix in (i) stage I (ii) stage II (iii) stage III (iv) stage IV?
(i) 90%
(ii) 75%
(iii) 35%
(iv) 10%
What is gender based violence?
- violence which is directed against a woman because she is a woman, or violence that affects women disproportionately.
- includes acts that inflict physical, mental or sexual harm or suffering, threats of such acts, coercion and other deprivations of liberty.
What is domestic abuse?
- occurs w/in a current/previous intimate relationship and can be physical, sexual or emotional and includes controlling and coercive behaviours
- most victims women but men can also experience DA and it occurs in same sex relationships
What are the other terms used to describe domestic abuse?
- domestic violence
- intimate partner violence
- spouse abuse
- battering
- wife beating
What % of female and make homicide victims are murdered by current or ex-partners?
Female = 50% Male = 12%
What is the lifetime prevalence rates (%) of DA for women?
25%
What is the link between DA and pregnancy?
- 1/3 of all women who experience DA are assaulted for 1st time whilst pregnant
- women at highest risk of homicide whilst pregnant/post-partum
- 14% of maternal deaths occurred in those who disclosed DA