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Life Cycles > Week 4 > Flashcards

Week 4 Flashcards

1
Q

Organization of adult breast tissue

A

Lobes: glandular units of the breast
-Composed of multiple lobules containing alveoli (milk producing units) that are connected by a ductal network that empties into single milk duct

Milk ducts from multiple lobes feed into the nipple

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2
Q

Terminal ductal lobular unit

A

TDLU = functional unit of breast

Each terminal duct has grapelike cluster of small acini (tubules) that form a lobule

Composed of:

  • epithelial (myoepithelial, luminal)
  • stromal components (intra, and interlobular stroma)
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3
Q

Non-lactating vs. lactating gland composition:

A

Non-lactating gland composition:
20% glandular, 40% intra gland fat, 24% subcutaneous fat, 7% retro fat

Lactating gland composition:
62% glandular, 7% intra gland fat, 24% subcutaneous fat, 7% retro fat

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4
Q

Embryogenesis of breast development:

_________ is secreted by epithelial cells → induce differentiation of _______ _________ → _________ ___________

A

PTHrP secreted by epithelial cells → induce differentiation of DERMAL mesenchyme → MAMMARY mesenchyme

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5
Q

Role of PTHrP in breast development

A

PTHrP secreted by epithelial cells → induce differentiation of DERMAL mesenchyme → MAMMARY mesenchyme

Mammary mesenchyme triggers morphogenesis of mammary gland and stimulates nipple formation

NO PTHrP → dermal mesenchyme fails to differentiate → Blomstrande Chondroplasia (no mammary gland)

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6
Q

“Witch’s Milk”

A

temporary milk secretion in both male and female neonates caused by elevated prolactin and decreased progesterone at parturition

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7
Q

Breast development during puberty is driven by what?

A

Estrogen and Progesterone increased → elaboration/growth of ducts and alveoli - driven by menstrual cycle

Formation of ductal network and lobules are regulated independently

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8
Q

Breast development during puberty:

Estrogen + GH –> ?

A

Estrogen + GH → elongation and branching of ductal network by increasing IGF-1 production in stromal cells

Once final stages of puberty are reached, growth hormone levels will be decreased → stop proliferation of branches even though estrogen continues

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9
Q

Breast development during puberty:

Progesterone –> ?

A

Progesterone (luteal phase of menstrual cycle) → stimulates side-branching and lobuloalveolar (TDLU) formation during menses

TDLUs capable of making milk proteins

Even after puberty ends, TDLU development continues

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10
Q

Breast development during puberty:

Macroscopic breast development

A

due to increase in fat accumulation in mammary adipose tissue

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11
Q

Mature nulliparous breast contains what?

A

Extensive branched-ductal network with attached lobules are present

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12
Q

What changes to breast tissue occur during pregnancy? (3)

A

Get extensive lobule formation

Differentiation of alveolar cells

Minimal or no milk secretion

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13
Q

Breast tissue during pregnancy:

Progesterone (3 functions)

A

Progesterone → alveoli elaboration, side branching, inhibits milk secretion

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14
Q

Breast tissue during pregnancy

Prolactin (2 functions)

A

Prolactin → side branching, lactogenesis

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15
Q

Breast tissue during pregnancy

Placental lactogen (1 function)

A

Placental lactogen → lactogenesis

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16
Q

Lactogenesis

A

differentiation of mammary gland to produce milk

Milk product synthesis initiated during pregnancy by actions of prolactin and placental lactogen, but milk secretion is held in check by high progesterone

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17
Q

Lactation

A

Copious milk secretion
Coordinated production and secretion of diverse milk components

Regulated by pituitary hormones - prolactin and oxytocin

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18
Q

What happens after lactation is finished?

A

Involution: apoptosis, glandular regression, and return to quiescence

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19
Q

Lactation initiation:

Milk secretion initiated by ____________ at parturition due to __________

Elevated _______ levels required to maintain milk synthesis and secretion

A

Milk secretion initiated by FALL in PROGESTERONE at parturition due to removal of placenta

Elevated prolactin levels required to maintain milk synthesis and secretion

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20
Q

Lactation requires ________ and ___________ of milk with feedback regulation

A

SECRETION and EJECTION

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21
Q

Milk Secretion requires __________ and __________

A

prolactin (for milk synthesis and secretion)

Milk removal

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22
Q

Milk removal is required for what?

A

Milk removal required to maintain glandular integrity and milk production

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23
Q

Milk Ejection requires ________ and _________

A

oxytocin and suckling

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24
Q

Suckling stimulated afferent activation of hypothalamus causes what?

A

→ Inhibit dopamine → release of prolactin from anterior pituitary in pulses

→ Oxytocin release from posterior pituitary

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25
Q

Oxytocin stimulates what?

A

contraction of myoepithelial cells that surround alveoli stimulating milk ejection

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26
Q

Prolactin pulse size and frequency regulated by _________

A

Pulse size and frequency regulated by SUCKLING stimulus - suckling required to maintain prolactin levels

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27
Q

Factors affecting lactation:

A

Anxiety, stress

Delayed lactation initiation

Pituitary disorders or damage

Excessive weight
-Obesity can also impair mom’s ability to mobilize energy for milk production

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28
Q

Cellular pathways of milk secretion: (5)

A

1) Classical secretion proteins
2) Apocrine secretion - lipids
3) Ion transport
4) Transcytosis
5) Paracellular serum substances

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29
Q

Main difference between human and cow milk

A

High oligosaccharides in human milk

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30
Q

What happens to the tight junctions during lactation?

A

During lactation tight junctions closed, but prior to lactation up to day 3 - tight junctions are open and allow movement of IgA, lactoferrin, etc. into breast milk

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31
Q

3 main phases of breast milk

A

1) Colostrum
2) Transitional
3) Mature milk

Milk also varies DURING feeding (foremilk vs. hindmilk), varies throughout the day, and varies in volume

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32
Q

Colostrum - 4 main features

A

1) Yellow in color
2) High in IgA and lactoferrin (anti-infection properties)
3) Higher protein, lower fat and lactose
4) Facilitates establishment of lactobacillus and passage of meconium

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33
Q

Transitional milk - 4 main features

A

day 2-14

Immunoglobulins and protein decrease

Lactose and fat increase

Increase in calories

Vitamin changes

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34
Q

Mature milk:

water and lipid content?

A

Water: largest quantity of any constituent, maintains infant hydration

Lipids: provides 50% of calories, variety of lipids, varies during feeding

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35
Q

Mature milk

Proteins

A

Casein and whey (PRIMARILY WHEY)

Lactoferrin - inhibits growth of Fe dependent bacteria in GI tract

Immunoglobulins (sIgA) + other antimicrobial factors

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36
Q

Mature milk

carbohydrates, trace elements, and vitamins

A

Carbohydrates - Lactose (galactose and glucose)

Trace elements: iron (no risk of deficiency in 1st 6 months), zinc

Vitamins: Vitamin D

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37
Q

How does milk volume vary as infants grow?

A

Volume increases as infant grows - 1st month (22oz), 6 months (30oz), 12 months (25 oz)

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38
Q

How does maternal malnutrition effect milk content/production?

A

Maternal malnutrition → reduced milk supply, but minimally alters macronutrient content

Consumption > maintenance needs does NOT enhance milk production

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39
Q

How does maternal diet effect mineral content of milk

A

Diet affects content of vitamins in human milk, however, most mineral content is independent of maternal intake

EXCEPTIONS: selenium, iodine

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40
Q

How does maternal fluid consumption effect milk?

A

Fluid consumption important for milk synthesis

Fluid consumption > maintenance needs does NOT enhance milk production

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41
Q

Advantages of breast milk over formula:

For infant: (3)

A

Immunologic protection

Neurodevelopmental benefits (bonding)

Reduced likelihood of atopy, diabetes, obesity later in life

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42
Q

Advantages of breast milk over formula:

For Mother: (6)

A 
Prevent postpartum hemorrhage
Weight loss
Lactational amenorrhea/birth spacing
Reduced risk of chronic conditions
Bonding/stress reduction
Economic benefits
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43
Q

Hospital practices that support vs. undermine breastfeeding:

Positive: (6)

A 
BF in 1st hour
Skin to skin contact
Rooming in
Lactation consultants
Peer role modeling
Ad lib nursing/feeding
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44
Q

Hospital practices that support vs. undermine breastfeeding:

Negative: (6)

A 
Separation for infant and mom
Mother discouraged BF/limited time suckling
Convert formula feeding
D/C packs with formula
Lack of support
Pacifier use
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45
Q

Baby friendly hospital initiative (BFHI)

A

promotes, protects, and supports breastfeeding through “10 Steps to Successful Breastfeeding for Hospitals” as outlined by UNICEF and WHO

46
Q

“The Golden Hour”

A

infant nursed (skin to skin) within first hour after birth

47
Q

Medical contraindications for breastfeeding

A

medications, active untreated alcohol or drug abuse, infections (untreated TB, HIV)

Breastfeeding recommended in developing countries unless women have access to formula AND clean water

Galactosemia - infant can’t metabolize breast milk

48
Q

Recommendations for infant feeding practices:

A

Recommend that women exclusively breastfeed for about 6 months, continue to breastfeed through first or second year of life with appropriate complementary feeding initiated at 6 months

49
Q

Newborn’s Adaptation to Extrauterine Life:

First 1-3 days:

A
  • Colostrum (high fat, protein, Igs, low volume)
  • Practice breastfeeding

Energy source:

1) Glycogen stores last about 12 hours (stimulated by intrauterine GCC)
2) Low glucose → low insulin, increased glucagon → increased gluconeogenesis
3) “Stress” → lipase → release of TG → glycerol and fatty acids

50
Q

Frequency of breastfeeding:

A

Variable time between feeds, on demand (30 min to hours)

8-12 times per day

Thorough emptying of breast is important

Duration of 10-30 min

51
Q

Patterns of weight loss and regain by the infant:

A

Infants expected to lose 5-7% of their birth weight

Typically stop losing weight by 5 days (because mom’s breast milk has come in)

Start gaining 15-30 g/d

Regain of BW by 7-14 days

52
Q

Common issues with breastfeeding:

A

Poor attachment

Primary lactation failure - RARE

“Insufficient milk syndrome” - COMMON

Mastitis

Maternal return to work

Poor infant growth

53
Q

“Insufficient milk syndrome”

A

COMMON

Inadequate milk removal → inadequate milk production

Factors:

Maternal - stress, medical problems, separation from infant, older maternal age

Infant - LBW/prematurity, poor suck/latch neurologic issues, lethargy, illness, formula supplementation

54
Q

Formula vs. Breastfeeding:

1) Atopy:

A

Expose infants to allergens present in formula, increase risk of atopy

Breast feeding has less risk of atopy compared to formula fed infants

55
Q

Formula vs. Breastfeeding:

2) Diabetes

A

Infants fed with BM vs. cow’s milk formula → lower risk of autoantibody in breastfed group 10 years later

56
Q

Formula vs. Breastfeeding:

3) Obesity

A

evidence is mixed if BF protects infant from obesity later on

57
Q

Formula vs. Breastfeeding:

4) Infant growth

A

Formula fed infants 0.65 kg more than a BF infant

BF infants at risk of being labeled as “growth faltering” due to slower growth → WHO growth standards for infants through age 2 are new standard

58
Q

Breast histology

transition from outer skin to inner ductule?

A

Squamous epithelium overlying skin → enters nipple and becomes a double-layered cuboidal epithelium lining the ducts

Anything more than 2 cell layers is ABNORMAL

Successive branching of large ducts → terminal duct lobular unit (TDLU)

59
Q

Male breast histology

A

NO tubules (acini), ductal structures surrounded by small amount of adipose and fibrous tissue

60
Q

TDLU:

Epithelial Component: (2)

A

1) Contractile Myoepithelial cells (MEC)

2) Luminal epithelial cells

61
Q

Contractile Myoepithelial cells (MEC)

A

contain myofilaments, form mesh like pattern on basement membrane

Assist in milk ejection during lactation

Structural support for lobules

MEC layer LOST in invasive breast cancer

62
Q

Luminal epithelial cells

A

overlay myoepithelial cells

ONLY lobular luminal cell capable of producing milk

63
Q

TDLU:

Stromal Component (2)

A

1) Interlobular stroma

2) Intralobular stroma

64
Q

Interlobular stroma

A

dense fibrous CT + adipose

65
Q

Intralobular stroma

A

envelopes acini of lobules, contains breast-specific HORMONALLY RESPONSIVE fibroblast-like cells + scattered lymphocytes

66
Q

Breast histology:

Childhood:

A

breast composed of branching ductal system without lobular units

67
Q

Breast histology:

Puberty

A

estrogen + progesterone stimulation → proliferation of glandular tissue

→ formation of lactiferous ducts and interlobular duct system that are stable and unaffected by fluctuating hormone levels during menstrual cycle, pregnancy, and lactation

TLDUs are dynamic and change with hormone levels

68
Q

Breast histology:

Menstrual cycle

A

increased size/nodularity
1st half → lobules quiescent

After ovulation → estrogen and progesterone rise → cell proliferation, proliferation of acini per lobule, intralobular stroma become edematous

Menstruation → fall in estrogen and progesterone induces regression of lobules and stromal edema disappears

69
Q

Breast histology:

Pregnancy - onset

A

breast completely mature and functional

Lobules increase progressively in number and size

By end of pregnancy breast composed almost entirely of lobules with scant stroma separating them

70
Q

Breast histology:

Pregnancy - After delivery

A

luminal cells of lobules produce colostrum (high protein), which changes to milk (higher fat and calories) over next 10 days as progesterone levels drop

71
Q

Breast histology:

Cessation of lactation:

A

breast epithelium/stroma remodeled extensively

Epithelial cells undergo apoptosis, lobules regress/atrophy and total breast size is diminished

Full regression does NOT occur

Permanent increase in size and number of lobules

72
Q

Breast histology:

Postmenopausal involution

A

lobules and specialized stroma start to involute
Involution of TDLUs

Duct system remains

Decrease in intralobular stroma, increase in fatty tissue

Lobular atrophy complete in elderly

73
Q

Accessory Breasts of nipples:

A

can occur anywhere along embryonic mammary ridges

Accessory nipple usually just below normal breast

Accessory/ectopic breast tissue may be in lower axilla

74
Q

Congenital Inversion of Nipples

A

benign, but similar to a change that may indicate underlying cancer

75
Q

Juvenile hypertrophy

A

rare condition in adolescent girls
Breasts (usually both) markedly enlarge due to hormonal stimulation
No endocrine abnormality detected

76
Q

Gynecomastia

A

enlargement of one or both breasts in a male

Typically idiopathic, caused by excessive estrogen stimulation

Other causes: liver disease, drugs, testicular tumors, metabolic or endocrine disorders

77
Q

Gynecomastia

Microscopic features

A

normal breast tissue, ductal epithelial hyperplasia, stromal edema, loose fibrosis around ducts

78
Q

Apocrine metaplasia:

A

Histologic alteration of epithelium of TDLUs → cells resemble apocrine sweat gland epithelium

-fibrocystic change

79
Q

Blue-dome cysts:

A

Larger cyst that arise in TDLU

Unilocular

Contain brown fluid which give a blue color to intact cyst

-fibrocystic change

80
Q

Sclerosing adenosis

A

can be mistaken clinically for INVASIVE CARCINOMA

NO cysts - proliferation of acini with marked fibrosis that can compress/distort lumens of acini and ducts
→ solid cords of cells

Myoepithelial cells are not lost

Diffuse microcalcifications which may mimic carcinoma on mammography

-fibrocystic change

81
Q

Acute mastitis and abscess:

A

Occurs usually at onset of lactation → cracks in nipple and stasis of milk predispose to infection

Staph. Aureus is most common infecting agent

Mastitis → redness, swelling, pain and tenderness
If abscess forms → requires drainage of pus

MUST rule out INFLAMMATORY BREAST CARCINOMA

82
Q

Chronic mastitis

A

uncommon

NOT due to lactation

NO infectious agent

Occurs in perimenopausal women due to obstruction of lactiferous ducts by inspissated luminal secretions

83
Q

3 types of chronic mastitis

A

Mammary duct ectasia
Plasma Cell Mastitis
Granulomatous mastitis

84
Q

Granulomatous mastitis

A

Rarely get foamy histiocytes and fibrosis

85
Q

Plasma Cell Mastitis

A

Primary infiltrate is PLASMA CELLS

86
Q

Mammary duct ectasia

A

Obstruction → dilation of ducts (mammary duct ectasia) and periductal chronic inflammation

87
Q

Periductal Mastitis

A

painful erythematous subareolar mass, recurrent

Usually in smokers

Squamous epithelium extends down into nipple and duct → formation of abscess

Occurs in both men and women

NOT associated with lactation, age or reproductive history

NOT infectious

88
Q

Fat necrosis of breast

-early vs. late phase

A

uncommon disease

Stretching and narrowing of arteries in pendulous breasts → ischemia

Early phase: neutrophil + necrotic fat cells

Later phase: macrophages, giant cells, fibrosis, and calcification

May present as a HARD MASS - suspicious for carcinoma on physical exam

89
Q

Fibroadenoma

A

solitary, discrete, regular, mobile mass

Composed of proliferating ducts in proliferating fibroblastic stroma

Most common benign neoplasm in breast, typically in young women

Origin is TDLU

Can have complex features (epithelial hyperplasia) → predispose to breast CA

TX = surgical excision

90
Q

Lactating adenoma

A

palpable mass in pregnant or lactating women

Normal appearing breast tissue with physiologic adenosis and lactational changes - exaggerated focal response to hormonal influence

Discrete, soft, well circumscribed, rounded mass

91
Q

Intraductal papilloma

A

benign neoplasm originating in major lactiferous duct near nipple

Presents with bloody nipple discharge and small subareolar mass

92
Q

Intraductal papilloma

Appearance

A

Papillary mass projecting into lumen of large duct

Numerous delicate papillae composed of fibrovascular core covered by layer of epithelial and myoepithelial cells

Must distinguish from PAPILLARY CARCINOMA

93
Q

Phyllodes tumor

A

rare, composed of intralobular stroma and ductal epithelium

Range from benign to malignant

94
Q

Benign Phyllodes tumor

A

Benign Appearance: massive size, leaf-like clefts and slits

Benign epithelium overlying a stromal overgrowth

Benign ones have NO cytologic atypia or mitoses

95
Q

Non-Proliferative Fibrocystic Changes:

A

Cysts / fibrosis

Epithelial hyperplasia ABSENT

96
Q

Fibrocystic change

A

asymptomatic or pain + nodularity

Due to hormonal changes

97
Q

Proliferative Fibrocystic Changes:

A

Cysts / fibrosis

Epithelial hyperplasia PRESENT

98
Q

Lobular hyperplasia includes _______ and ________

A

hyperplasia of acinar epithelium

Atypical lobular hyperplasia

LCIS (Lobular Carcinoma in situ)

99
Q

Atypical lobular hyperplasia

A

< 50% of lobules filled with epithelial cell proliferation

Acini have increased number of cell layers

100
Q

LCIS (Lobular Carcinoma in situ)

A

> 50% of lobules filled and distended by epithelial proliferation

Higher risk of malignancy (BILATERAL - not just in the one side)

101
Q

Ductal hyperplasia includes _______, __________, and ___________

A

terminal duct hyperplasia

Usual hyperplasia, atypical ductal hyperplasia, DCIS

102
Q

Usual hyperplasia

A

mild, moderate, florid hyperplasia

Increase in epithelial layer (>2 cell layers) which distends terminal ducts

103
Q

Usual hyperplasia: MILD

A

papillary tufts projecting into lumen

104
Q

Usual hyperplasia: MODERATE

A

epithelial cells proliferate to bridge and create arcades

105
Q

Usual hyperplasia: FLORID

A

solid mass which fills duct and distends lumen, may have irregular fenestrations - cell crowding, overlapping, mixed proliferation of epithelial cells and myoepithelial cells

106
Q

Atypical ductal hyperplasia:

A

Architectural cytologic features of carcinoma in situ, but lack complete criteria for diagnosis

Associated with higher risk of cancer than usual hyperplasia

107
Q

DCIS (Ductal carcinoma in situ):

A

Malignant cells confined within basement membranes of ducts without invasion of surrounding stroma

108
Q

Cancer Risk and Hyperplasia:

Minimal / no risk: (6)

A

1) Duct ectasia
2) Cysts
3) Apocrine metaplasia
4) Fibrosis
5) Mild hyperplasia (>2 but < 4 cells thick)
6) Fibroadenoma without complex features

109
Q

Cancer Risk and Hyperplasia:

Slightly increased risk: (4)

A

Hyperplasia (moderate to florid)

Papilloma

Sclerosing adenosis

Fibroadenoma with complex features

110
Q

Cancer Risk and Hyperplasia:

Moderate increased risk: (2)

A

Atypical ductal hyperplasia (ADH)

Atypical lobular hyperplasia (ALH)

111
Q

Cancer Risk and Hyperplasia:

Markedly increased risk: (2)

A

Ductal carcinoma in situ (DCIS) → risk of invasive ductal CA

Lobular carcinoma in situ (LCIS) → risk of BOTH ductal and lobular CA and can be ipsilateral or other side

Life Cycles (8 decks)

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