Week 5 - "Unlucky Lump" Flashcards
What is lactation?
Physiology
A combined process of milk secretion and milk ejection from the mammary glands
What is milk secretion?
Physiology
Milk synthesis by epithelial cells and passage from cell cytoplasm to the lumen of alveoli
What is milk ejection?
Physiology
Ejection of milk from alveoli and ducts
What is mammogenesis?
Physiology
Development of mammary glands
What is lactogenesis?
Physiology
Inititation of milk secretion
What is galactokinesis?
Physiology
Ejection of milk
What is galactopoiesis?
Physiology
Maintainance of lactation
What is each breast composed of?
Physiology
Glandualr epithelium and a ductal system
Where is milk produced withinn the breast?
Physiology
Withi the mammary glands (which are modified sweat glands)
What do mammary glands consist of?
Physiology
15 to 20 lobes divided into lobules, each lobule contains many alveoli
What is the transportation of milk like?
Physiology
Milk is secreted by alveolar epithelial cells into the lumen
Contraction of myoepitheium cells eject milk out through the ducts
Alveolar epithelial cells pass milk to the nipple through lactiferoys ducts
Each of these ducts enlarges to form lactifeous sinuses in which milk accumulates during ejection
What are the phases of lactation?
Physiology
- Mammogenesis: preparation of the breasts
- Lactogenesis: synthesis and secretion of milk from the breast alveoli
- Glacatokinesis: ejection of milk
- Galactopoiesis: maintainance of lactation
What are the two sub-stages of lactogenesis?
Physiology
Stage 1: initiation of lactation
Stage 2: secretory activation
What is mammogenesis like during puberty?
Physiology
Breasts begin to develop (because of estradiol) and conistists (in non-pregnant) mainly of adipose tissue and a rudimentary duct system
What is mammogenesis like during pregnancy?
Physiology
Greater growth under effecy of estriol
- Myoepithelial cells become prominent
- Progesterone synergizes estrogen, prolactin growth hormone, adrenal glucocorticoids and insulin to cause full growth of lobule-alveolar system
When does lactation begin?
Physiology
Initiated by the decline in estrogen and progesterone after delivery
What is breast size determined by?
Physiology
By the fat (it has no correlation to the ability of the breast to be able to produce milk)
Whcih is the main estrogen during pregnancy?
Physiology
Estriol
What is the role of estriol during pregnancy?
Physiology
Stimulates growth of the ductal system of breasts and fat deposition
What is the role of progesterone in mammogenesis?
Physiology
Stimulates development of lobules and conerts duct epitehlium into secretor structures (lobule-alveolar system)
When do the mammry glands have the ability to produce during the pregnancy, why don’t they?
Physiology
They are fully capable of producing milk by the middle of pregnancy, bu estriol and progesterone inhibit the production of milk until parturition
What is lactogenesis like prior to delivery?
Physiology
Estrogen and progesterone are high; breasts enter into lactogenesis stage I and produce small amounts of colostrum
What is colostrum?
Physiology
Thick and yelloweish fluid, that is high in nutrients and antibodies hat prevent pathogens from invading baby’s system (first breast-milk)
What is lactogenesis like at birth?
Physiology
Estrogen and progesterone withdrawal.. in the presence of high levels of prolactin –> stimulate copious milk production (lactogenesis II)
How long after birth does colostrum give way to mature breast milk?
Physiology
5 days
When is prolactin secreted, and from where?
Physiology
Secreted by the anterior pituitary gland from 5th week of pregnancy
What is the role of prolactin?
Physiology
It promotes milk secretion after delivery
What is the effect of prolactin during pregnancy?
Physiology
Effects of prolactin are blocked by estriol and progesterone thus no milk secretion
Which hormones are high secreted during pregnancy?
Physiology
hCS by the placenta
What is the role of hCS? (guman chorionic somatommatotropin)
Physiology
Contributes to breast growth and has lactogenic properties
What are the levels of prolactin like at delivery?
Physiology
They rise 10 to 20 times du eto sudden loss of estriol and progesterone –> which is due to the loss of the placenta
When do the prolactin levels normalize?
Physiology
Within a few weeks post partum
What happens to prolactin levels during breast-feeding?
Physiology
A 10 to 20 fold surge in PRL (for approximately 1 hour) occurs with every breastfeeding
What other hormones does milk secretion require?
Physiology
GH
Cortisol
Insulin
PTH
–> To provide the amino acids, fatty acids, glucose and Ca2+
What is the positive feedback mechanism of breastfeeding?
Physiology
- Suckling stimulates nerves in the nipple and areola that travel to the hypothalamus
- In response, the hypothalamus stimulates the posterior pituitary to relas oxytocin and he anterior pituitary to release prolactin
- Oxytocin stimulates lobules in the breast to let down (release) milk from the storage by inducing the contraction of the myoepithelial cells –> prolactin stimulates additional milk production
What is the main protein of milk?
Physiology
Casein
What does oxytocin bind to?
Physiology
Oxytocin binding receptors, which are G-protein coupled receptors (GPCRs) located on myoepithelial cells surrounding mammary alveoli.
What is the intracellular signaling pathway of oxytocin?
Physiology
OTR activation triggers a Gαq-protein signaling cascade, leading to an increase in intracellular calcium (Ca²⁺).
- Oxytocin binds to OTR, activating Gαq-coupled signaling.
- Phospholipase C (PLC) activation → Cleaves PIP₂ into DAG and IP₃.
- IP₃ stimulates Ca²⁺ release from intracellular stores (endoplasmic reticulum).
- Increase in Ca²⁺ activates myosin light chain kinase (MLCK).
- MLCK phosphorylates myosin, leading to contraction of myoepithelial cells.
What is the role of phospholipase A2 and prostaglandins in the oxytocin signaling pathway?
Physiology
Oxytocin activates PLA2 which produces prostaglandins by COX –> further enhancement of smooth muscle contraction
How is prolactin secretion normally suppressed?
Phsyiology
By tonic dopamine secretion by the hypothalamus (prolactin inhibitory homrone)
Which factors increase prolactin secretion?
Physiology
Tyrotrpopin releasing hormone (TRH)
Nursing
Breast manipulation
Oxytocin
Sleep
Pregnancy
Estrogen
Stress
Serotonin
Dopaminergic antagonists
Andregenic antagonists
How is prolactin the “nature’s contraceptive”?
Physiology
Inhibits GnRH & prevents ovulation
How does suckling stimulate prolactin production?
Physiology
- Acts on activating TRH
- Inhibits dopamine –> inhibiting the inhibitor -_> stimulating effect on prolactin
What are the factors that inhibit prolactin?
Physiology
Dopamine
Dopaminergic agonists
Somatostatin
Prolactin
GABA
How do the alveolar epithelial cells secrete milk components?
Physiology
- Secretory pathways
- Transcellular endocytosis and exocytosis
- Lipid pathway
- Transcellular salt and water transport
- Paracellular pathways
What is the secertory pathway of alveolar epitehlial cells?
Physiology
Proteins (lactabumin and casein) are synthesized in ER and stored in GA
What is the transcellular endocytosis and exocytosis of alevolar epithelial cells?
Physiology
Maternal immunoglobulins are taken up by receptor-mediated endocytosis
What is the lipid pathway of alveolar-epithelial cells?
Physiology
Short chain fatty acids are synthesized by alveolar epitehalial cells –> formed into lipid droplets secreted into the lumen in a membrane bound sac (Apocrine)
What is the paracellular pathway of alveolar epithelial cells?
Physiology
Salt and water can also move into the lumne of the alveolus via tight junctions
What is galactopoieisis?
Physiology
Maintainance of lactation which is caused by suckling
Which hormone is important for galactopoiesis?
Physiology
Prolactin it allows for continuing of milk production
What happens if there is 1 week cesation of breast feeding?
Physiology
Breast lose their ability to produce milk
What are examples that could lead to the breast to lose their ability to produce milk?
Physiology
Prolactin surge being blocked –> pituitary damage
Nursing is stoopped
When does the rate of milk production normally decreases?
Physiology
Usually after 7 to 9 months, but it can continue for years if suckling continues
Which otehr hormones are galactopoietic?
Physiology
GH
Glucocorticoids
Thyroid hormone
Estrogen (in low dosages)
What happens to the breast after weaning?
Physiology
- Cell shedding and cell death (which begins as fast as 12 hoursafter milk stasis)
- Epithelial tight junctions are disrupted
- Extracellular matrix remodeling –> MMP activation (degrade basement membrane components, leading to:
loss of alveolar structures and adipocyte repopulation) - Adipocyte differentiation (glandular tissue is replaced with adipocytic tissue)
What are the advantages of breast feeding towards the infant? (5)
Physiology
Milk contains nutrients and immune cells, antibodies and other chemicals that help protect the infent against infections:
1. Immune cells
2. IgA
3. Mucus
4. Lactoferrin
5. Bifidus factor
What is the benefit of IgA antibodies passed to the infant?
Physiology
They are resistant to destruction by the infant’s digestive system
What is the benefit of mucus being transported via the breast milk to the infant?
Physiology
Adheres to and prevents harmful bacteria from crossing intestinal mucosa
What is the benefit of lactoferrin to the infant?
Physiology
Prevents growth of harmful bacteria by decreasing iron availability
What is teh importance of bifidus factor for the infant?
Physiology
promotes multiplication of nonpathogenic microorganisms
What are the advantages of breast feeding towards the mother? (4)
Physiology
- Released oxytocin –> uterine involution
- Oxytocin also helps facilitate emotional bond between mother and infant
- Prolactin suppresses menstrual cycle
- Lactation decreases the likelyhood of another pregnancy
Breast feeding decreases the risk of developing which diseases later in life?
Physiology
Asthma
Type 1 DM
Lymophoma
Is the breast present in both sexes?
Anatomy
Ye, but functionless in males
Where is the main projection of the breast?
Anatomy
In the thorax
What does the volume and contour of the breat depends on?
Anatomy
Subcutaneous fat (the non-functioning part of the breast)
Why are breasts functionless in males?
Anatomy
They do not have much glandular tissue and the small amount that is present is ludimentray
What does the breast consist of?
Anatomy
- Fatty tissue (which is the majority of th breast)
- Functional tissue
How does the non-functioning portion of the breast make reconstructive surgeries plausible?
Anatomy
The fact that the majority of the breast is non-functional makes these kind of surgeries plausible because technically you are substituting one type of non-functioning tissue with another (silicone bags with normal saline)
Where does the base of the breast extend from?
Anatomy
Extends from thhe lateral aspect of the sternumto mid axillary line
What are the vertical extensions of the breast?
Anatomy
From the 2nd rib to the 6th
What is the nipple?
Anatomy
A small area of coloured skin (areola) where the nipple is based which contains multiple ducts made by lactoferous ducts which carry the milk from multiple lobules
Which muscles are the breats sitting on, on the thorax?
Anatomy
Pectoralis minor (deep)
Pectoralis major (superficial)
Fixed to the fascia of these two muscles
What is the space between the base of the breast and the fascia and what is the purpose?
Anatomy
Retromammary space or bursa –> it allows for some movement of the breast over the chest wall and provides a potential space that can be involved in infections, abscesses and tumor spread
What is the location of the breasts?
Anatomy
2/3 of the base lie on the pectoralise major muscle fascia
Inferiolateral 1/3 lies in serratus anterior muscle
The superolateral part sends a process into the axilla called the axillary tail or the axillary process
What is the clinical significance of the axillary tail?
Anatomy
It is responsible for many cases of breast tumor going undiagnosed because of insufficient examination that fails to address the fact that we have part of the mammary gland extending into the axilla
What is the fucntion of the fibrous septa of the breast?
Anatomy
They support the glandular tissue to the overlying skin and these septa are specially developed in the superior aspect of the breats so that they can hold the lobules and give them support
What is the function of the suspensory ligamnets of Cooper?
Anatomy
Attach the mammry gland to the skin
Support mammary lobules
What are different signs of carcinoma of the breast?
Anatomy
Skin dimpling
Edema of the skin (orange skin)
Nipple retraction
Abnormal contours
What is the parenchyma of the breast?
Anatomy
Functional tissue (glandular tissue that produces milk for lactation)
What is mammography?
Anatomy
X-ray of the mammary glands of the breast
What are the lobes of the breast?
Anatomy
The entire breast is considered one mamary gland, this mammary gland is then divvided into 15 to 25 lobes of glandular tisse
What is each lobe of the breast then divided into?
Anatomy
Each lobe is separated by fibrous septa called suspensory ligamnets & within these septa each lobe is composed of smaller lobules
What are the lobules of the breast further divided into?
Anatomy
Alveoli which produce milk when a woman is lactating
Where does each lobe drain?
Anatomy
Lactiferous duct
What does each lactiferous duct have at its terminal ?
Anatomy
Lactoferous sinus
Where do the glandular lobes radiate and open?
Anatomy
At the nipple
What is the glandular structure of the breast in non-pregnant women?
Anatomy
Glandualr structure is undeveloped –> hence the breast size is largely due to the amount of fat deposits
How do the mammary glands develop embryologically?
Anatomy
As invaginations of surface ectoderm
What do the mammary glands resemble?
Anatomy
Highly modified sweat glands
WHat is the mammary gland divided into?
Anatomy
15 to 25 lobes of compoiund tubuloalveolar type glands
Does ecah lobe of the mammary gland drain into a sepearte lactiferous duct?
Anatomy
Yes, and each lactiderous duct has a lactiferous sinus at its terminal
What are the lactiferous ducts like?
Anatomy
They are 2 to 4.5cm long, emerge independently in the nipple which has 15 to 25 pore-like openings, each about 0.5mm in diameter
What is the epithelium of the alveoli like?
Anatomy
Simplementation cuboidal epithelium but it is surrounded by myoepithelium cells (which can contract and eject milk during lactation)
What is the purpose of the milk droplets containing lipids and proteins in the mammary glands?
Anatomy
Will start the process of exocytosis from the cells, it will varry part of the apical cell membrane with it
What are the small ducts that are collections of alveoli and lead to lactiferous ducts lined by?
Anatomy
Simple columnar epithelium
What is the epithelium of the lactiferous sinus and the lactiferous ducts?
Anatomy
Stratified cuboidal epithelium
What is the epithelium of the very last segment of the lactiferous ducts that are near the nipple opening?
Anatomy
Keratsized stratified squamous epithelium
During lactation where is milk produced from?
Anatomy
By the epithelial cells of the laveoli and accumulates in their lumen and inside the lacttiferous ducts
These lipid droplets pass out of the cels into the lumen and in the process are enveloped with aportion of the paical cell membrane (exocytosis)
What % of human milk is lipids?
Anatomy
4%
What is the mmary gland like priro to pregnancy?
Anatomy
The gland is inactive
The ducts are small
Presence of only a few secretory alveoli
What is the mammary gland like is early pregnancy?
Anatomy
Alveoli develop and begin to grow, branching is getting more complex
What is the mammary gland like mid-pregnancy?
Anatomy
The alveoli and ducts have become large and have dilated lumens
What is the mammary gland like at parturition and during the time of lactation?
Anatomy
The alveoli are greatly dilated and mazimally active in production of milks components (large alveoli, complex branching, lumens are filled with milk)
What is the mammary gland like after weaning?
Anatomy
The alveoli and lactiferous ducts will regress with apoptotic cell death
Return to inactive form
What is the blood supply of the medial mammary branches?
Anatomy
Internal thoracic artery which is also knwosn as the internal mammary artery
a. Perforating branches of the internal thoracic artery (superior part of the mammary gland)
b. medial mammary branches of internal throracic artery (medial apsects of mammary gland)
What is the blood supply of the lateral mammary branches?
Anatomy
Axillary artery
a. Lateral thoracic artery (lateral upper part of mmary gland)
b. thoracoacromial artery
Thoracic aorta
a. Posterior intercostal arteries (lateral branches) –> lateral low part of mammary gland
What is the venous drainage of the mammary gland?
Anatomy
Mainly axillary vein
Some to internal thoracic vein
What is the clinical importance of the lympatic drainage of the breast?
Anatomy
In the presence of breast cancer, lerhal when breast cancer metastasizes –> lymophatic drainage is the main means of metastasis
–> Lymphatic drainage is coming and oing all over the body (can go superior, lateral, medial, inferiorly) thus metastasis is a very serious complication
What is the initial lymphatic drainage of the breast?
Anatomy
All the areas of the breast drain to a plexus known as the subareolar plexus (located in teh subcutaneous part near the areola)
Following the subareolar plexus, most lymph will drain where?
Anatomy
Most lymph especially from the lateral breast quadrants will drain into axillary lymph nodes
Where does the lymph from the lateral quadrants of the breast go if it bypasses the axillary lymph nodes?
Anatomy
Deep cervical nodes
What is the path the lymph will follow in the axillary lymph nodes?
Anatomy
Initially anterior (pectoral lymph nodes), then humeral, subcapsular, central and apical
Where does lymph from the medial quadrants of the breast drain into?
Anatomy
Parasternal lymph nodes, this can lead to superior groups like right bronchomediastinal lymohatic trunk
–> in some cases it may drain immediately to contralateral breast
Where does the lymph from the inferior quadrants of the braest may drain?
Anatomy
Abdominal lymph nodes (subdiphgramatic inferior phrenic lymph nodes)
What is the innervation of the breast like?
Anatomy
Sensory and sympathetic innorvation is form intercostal nerves
–> they provide sensory branches to the skin and provide sympathetic fiber to the smooth muscle within the glandular tissue and nipple
What is a differential diagnosis of mastitis is patients who are not lactating?
Pathology
Inflammatory carcinoma!!
What is mastitis?
Pathology
Inflammation of the breast tissue
What are the subtypes of mastitis?
Pathology
Acute mastitis
Plasma cell mastitis
What is the causative agent of acute mastitis?
Pathology
Staph aerus
When does acute mastitis usually present?
Pathology
Early nursing
What is plasma cell mastitis?
Pathology
Duct ectasia, chronic, non-bacterial inflammation
What usually causes plasma cell mastitis?
Pathology
Inspissatiom of breast secretion in the large ducts
What are the common changes with mastitis?
Pathology
Multiple nodules (infected ductal and alveolar contents)
Diffuse swelling
Large abscesses
What are examples of of fibrocystic changes?
Pathology
- Fibrosis
- Cystic changes within the ducts
- Sclerosing adenosis
- Apocrine metaplasia
- Ductal epithelial hyperplasia (proliferative)
What are fibrocystic changes?
Pathology
They are benign changes of the breast tissue, some features may confer an increased risk for development of cancer
Which fibrocystic changes have minimal or no increased risk of breast carcinoma?
Pathology
Fibrosis, cystic changes, apocrine metaplasia
Which fibrocystic changed have a slightly increased risk of breast carcinoma?
Pathology
Hyperplasia without atypia, ductal papillomatosis, sclerosing adenosis
Which fibrocystic changes significantly increase the risk of breast carcinoma?
Pathology
Atypical hyperplasia: ductal or lobular
What are proliferative fibrocystic changes like?
Pathology
Usually bilateral and multifocal and are associated with increased risk of subsequent carcinoma in both breasts
What is a blue-dome cyst?
Pathology
A benign cyst filled with straw-colored fluid that showed a blue color when cut down on.
What is fibroadenoma?
Pathology
Benign and common breast tumor
What are the characteristics of fibroadenoma?
Pathology
- Well-encapsulated mass, 2 to cm in diameter
- Composed of fibrous stroma and glandular epithelium (biphasic tumor)
What is the traget population of fibroadenomas?
Pathology
Young women, 15 to 35 years of age
What is the treatment for fibroadenomas?
Pathology
Easily removed surgically, does not recur and does not become malignant
What is the gross apperance of fibroadenoma? (6)
Pathology
- Well-circumscribed, round or oval, firm mass.
- Freely mobile within the breast tissue (“breast mouse”).
- Gray-white/tan color on cut section.
- Slit-like spaces due to stromal compression.
- No necrosis or hemorrhage
- Typically 2–3 cm
What are the microscopic features of fibroadenoma? (4)
Pathology
- Well-demarcated tumor with biphasic composition (stromal and epithelial components).
- Dense fibrous stroma compressing and distorting the ducts.
- Slit-like or elongated ducts due to compression.
- Lined by bilayered epithelium (luminal and myoepithelial layers intact).
- Two histologic patterns:
a. Intracanalicular – Stromal overgrowth compresses ducts into narrow slits.
b. Pericanalicular – Stromal proliferation surrounds ducts without compression.
What is phyllodes tumor?
Pathology
Another biphasic tumor of the breast, less common that fibroadenomas
What is the characteristic of phyllodes tumor?
Pathology
Stromal component is more prominent, leading to epithealial leaf-like projections
What is the size of phyllodes tumor like compared to fibroadenomas?
Pathology
Larger than fibroadenoma, > 5cm
What is the target population of phyllodes tumor compared to fibroadenomas?
Pathology
Affects older patients
Are phyllodes tumors benign or malignant?
Pathology
Typically benign but 10 to 15% may be malignant with a metastatic potential
–> May recur
What is the microscopy of malignant phyllodes tumors?
Pathology
proliferating stromal cells distrort glandular tissue, forming cleft like spaces and buldge into surrounding stroma
