Week 5 Flashcards
What is the difference in mammary glands in males and females?
In males, mammary glands are rudimentary and functionless whereas in females, mammary glands are accessory to reproduction.
Describe the structure of the breast and the path taken by milk during lactation?
Breast is composed of 15-20 lobes divided by adipose tissue. These lobes contain alveoli which is the site of milk production and secretion. The milk then drain into the lactiferous ducts, which themselves drain into the lactiferous sinus, which is a small reservoir under the areola; which converges, and opens onto the nipple.
What is an alveolus in the context of the life cycle?
The site in which milk is produced in the breast.
How do the alveoli push milk out into the lactiferous duct?
They do that through the use of surrounding myoepithelial cells which contract to push the milk out into the lactiferous duct.
Describe hormone levels (pre-birth, after birth) and describe why these levels fluctuate in the way they do? Progesterone, estradiol, hPL, prolactin?
Progesterone, estradiol and human placental lactogen all rise significantly during pregnancy but fall very quickly after the delivery of the placenta. Prolactin, however, does not fall as it is necessary to complete the process of lactation for the newborn baby.
Describe the development of ducts and alveoli throughout the women’s development as well as the factors causing these changes?
At birth/pre-puberty: The ducts and alveoli have a very rudimentary structure, and are heavily underdeveloped
During puberty: The effect of progesterone and estrogen during puberty cause the development of the ducts as well as the alveoli. Oestrogen is mostly responsible for the development of the ducts while Progesterone is mostly responsible for the development of the alveoli.
During pregnancy: The effects of hyper increased hormonal levels of oestrogen and progesterone as well as prolactin and hPL cause an exponential proliferation of the ducts, and alveoli as well as maturation of these cells. Moreover, there is fat deposition making the breasts larger as well.
After birth: The ducts and alveoli are fully formed, matured, and producing milk.
What stimulus is needed to cause the initiation of the production and the maintenance of the secretion of milk? What is the hormonal control in charge of it?
The main stimulus in charge of this is regular suckling and removal of the milk that was produced. With every time the baby feeds, there is a spike in both prolactin and oxytocin, which are paramount to milk production and secretion postpartum.
Why do prolactin levels fluctuate postpartum?
The levels of prolactin generally go down progressively after birth, however, they are constantly stimulated and spike every time the baby suckles. Generally prolactin is controlled through constant inhibitory control of prolactin inhibitory hormone (PIH = dopamine), however, when there is the physical stimulation of the nipple through the baby sucking, there is a signal sent through the spinal cord to the hypothalamus, which causes an increased release in the secretion of prolactin from the anterior pituitary and a decrease in the release of PIH.
Why is milk unable to be pushed out until after pregnancy?
Because although the breasts, ducts, and alveoli are fully ready to produce and secrete milk, the high oestrogen and progesterone levels prepartum actually inhibit milk secretion through the inhibition of prolactin receptors. It is until delivery, where there is a sharp drop in oestrogen and progesterone levels, that breasts can respond to prolactin and secrete milk.
What is oxytocin responsible for in milk and how is it secreted?
Oxytocin is responsible for the milk let down (ejection) towards the nipple, as the presence of oxytocin triggers the contraction of myoepithelial cells surrounding the alveoli (full of milk) which causes the letdown of milk. The production of oxytocin is a response to the physical stimulation of the nipple which causes a signal to be passed through the spinal cord into the hypothalamus which triggers release of oxytocin from the posterior pituitary.
What drug mechanism do we need to target if we want to suppress lactation pharmacologically? Why? Give an example?
In order to suppress lactation, we need to drive down the production of prolactin, and therefore, give dopamine receptor agonists, as they act as prolactin inhibitory hormone. An example is bromocriptine.
What drug mechanism do we need to target if we want to promote lactation pharmacologically? Why? Give an example?
In order to promote lactation, we need to drive up the production of prolactin, and therefore, give dopamine receptor antagonists, as they act antagonize prolactin inhibitory hormone. An example is domperidone.
What is an important side effect of lactation? What is the physiological explanation for it?
Breastfeeding provides a 98% protection from pregnancy. This is due to the fact that lactation provides high prolactin levels. Prolactin directly inhibit GnRH (gonadotrophin releasing hormone), therefore inhibiting LH and FSH secretion. This inhibits menstrual cycles, and enter into a state of amenorrhea and anovulation for around 6 months postpartum.
What is galactorrhea? What is its cause?
Flow of milk in the absence of pregnancy or lactation. It is caused by hyperprolactinemia.
What is gynecomastia? What is its cause?
Breast development in males, either unilateral or bilateral. It is caused by increased estrogen:androgen ratio.
What is colostrum? What is its composition?
The milk excreted by the woman in the first few days postpartum. It is rich in proteins, vitamins, and minerals. It is especially rich in immunoglobulins (IGAs) in order to give the baby some kind of protection and immunity.
Describe the transition from colostrum to fully mature milk and how their compositions differ?
While colostrum is rich in proteins, vitamins, minerals, and immunoglobulins, it is low in fats and sugars. As milk matures, it loses immunoglobulins and proteins and allows for more fat and sugars, essentially making the milk more caloric. The volume is also widely different. While colostrum will be only produced at a rate of 40ml/day, fully mature milk can be produced at a rate of up to 500ml/day.
What is obesity? How is it identified?
Obesity is the condition caused by an excessive amount of adipose tissue. It is identified according to the Body Mass Index (BMI) which is a value gotten by the following equation: weight (kg)/height in m2
What are the BMI cutoffs?
Under 18.5 = underweight 18.5-24.9 = normal 25-29.9 = overweight 30-39.9 = obese >40 = Morbidly obese
What is the relationship between BMI and mortality risk?
Any BMI lower than 18.5 or higher than 25 increases the risks of mortality through cancer, CV disease or other causes. These risks of mortality increase as the difference from the normal BMI range increases.
Describe a drawback with using BMI?
- It is a measure tailored mostly to Caucasians. For instance, the cutoff points are lower in south Asians (e.g. overweight starts at 23 instead of 25 and obese starts at 25 instead of 30).
What other measures should be considered alongside BMI? How do they relate to risk of CV disease?
Waist circumference. The higher the waist circumference the higher the risk of CV disease.
What are the trends of overweight and obesity in the population?
Over the last 20 years the number of overweight individuals has doubled from 15% to 29%, and the amount of obese individuals has increased by 11% as well.
Who is more likely to be overweight or obese, men or women?
Men
What are the pathologies that can develop alongside obesity?
- CV disease (e.g. coronary heart disease)
- Type II diabetes
- Cancers
How is BMI used in children? Why?
BMI is used according to age and gender in children, unlike in adults where age and gender are irrelevant variables in the calculation of BMI. The reason for that is that the bodies of children are growing and therefore it makes the equation more complex; especially that growth patterns differ in boys and girls, as well as individuals delays …
What is the relationship between socioeconomic upbringing and BMI in children?
Children raised in more deprived socioeconomic backgrounds will be more likely to be overweight or obese.
How do the cutoffs of the WHO differ from that of Public Health England in children?
WHO, Royal College of Pediatrics and Child Health, UK Government’s Scientific Advisory Committee on Nutrition: <0.4 %tile = very thin <2%tile = underweight >91%tile = overweight >98%tile = obese
Public Health England:
<2%tile = underweight
>85%tile = overweight
>95%tile = obese
Essentially, PHE considers more children overweight and more children obese than the WHO, RCPCH, and SACN.
Why does it matter if a child is overweight/obese?
Because the patterns show that overweight and obesity in childhood will most likely track into adulthood, and that will in turn cause increased risks of comorbidities and mortalities later in life. Furthermore, the development of metabolic morbidities starts in childhood and will be carried on throughout life.
What are the metabolic morbidities that arise out of obesity?
- Atherogenic dyslipidemia: high blood triglycerides, and cholesterol
- Insulin resistance: type II diabetes
- Thrombotic state: increases chances of thrombosis (and in turn M.I)
- Inflammatory state: increases inflammation (and formation of atherosclerotic plaques)
What are the solutions to treating childhood obesity?
There are many, though the biggest is changing health behaviors through the use of interventions that promote the following and in the following settings:
- Eating well
- Active lifestyle
- Family centered and school-based
- Can use adjunctive pharmacotherapy in those with the greatest metabolic perturbation (e.g. statins, blood pressure controls …)
What are the macro and micro strategies we can use to prevent childhood obesity?
- Healthy ethos in schools, promoting good diet and active lifestyles
- Parents being good role models for a healthy lifestyle
- Local government providing opportunities for leisure activities and play areas
- National government bringing the rates of poverty down and targeting prevention strategies
- Food industry marketing foods in a more moral manner, as well as bringing the cost of healthy foods down
What main factors affect linear growth?
Genetic, nutrition and hormonal
Describe the patterns of growth from 0-18?
The human body grows the most rapidly from the ages of 0-4. There is then a deceleration that occurs in which the human body grows quite constantly from 4-12, until the point at which puberty starts and there is a huge spike in growth once again, and finally decelerates around the ages of 16 where the individual will continue to grow a little bit until the final height around the age of 18.
What factors affect linear growth in which periods of life?
In infancy, biggest factor affecting growth is nutrition, during childhood the biggest factor affecting growth is hormonal (GH-IGF1 axis) as well as nutrition, and lastly during puberty, the biggest factor affecting growth is sex hormone and GH.
What controls and is responsible for the release of GH?
Growth hormone is released from the anterior pituitary which is under the control of the hypothalamus.
What does GH do once released from the anterior pituitary?
GH is released from the anterior pituitary and binds in the blood to growth hormone binding protein and circulates around the body. It then reaches the growth hormone receptor in the hepatocytes which stimulates the synthesis of IGF-1 which is released from the liver, in a ternary complex and travels around the body and targets IGF-1 receptors in different organs (e.g. growth plate which causes lengthening of the bones).
Growth hormone will also however have a direct effect in tissues through direct binding at growth plates which will stimulate paracrine (local) production of IGF-1 which will stimulate growth without having to go through the liver.
What is the role of IGF-1 and GH in prenatal and postnatal growth?
Prenatally, IGF-1 deficiencies or conditions that cause IGF-1 resistance cause a small baby at birth. While IGf-1 is controlled by growth hormone throughout life, it seems to be that prenatally IGF-1 is completely independent from GH because fetuses with GH deficiencies are born with normal birth weights and heights. However, GH deficiencies will cause growth problems throughout life, even if it did not affect birth weight/height.
What are the main factors affect linear growth prenatally?
IGF-I, IGF-II, and insulin
List some non-pathological factors that can affect growth?
Age, sex, familial tendencies, environment …
Why is it important to look at the birth height/weight when taking the history of someone suffering from short stature?
In order to judge whether there is a prenatal problem with height which would hint at a possible IGF-1 deficiency.
Name a non-pathological cause for short stature?
Familial short stature.
What is constitutional delay of growth and puberty? What is a possible solution?
It is a non-pathological pattern of growth by which an adolescent will be below the expected centile they should belong to based on their genetic determinants due to delayed growth. They will eventually grow however, making their final height belong to the centile predicted by their genetic determinants, though delayed. A possible solution is hormone therapy, by which boys are given testosterone and girls estradiol.
What are some of the possible etiologies for intra-uterine growth retardation?
- Poor maternal nutrition
- Placental failure
- Congenital infection
- Chromosomal abnormalities
What is intra-uterine growth retardation and why are children born with IUGR looked at closely?
IUGR is a condition in which a baby is born at less than 10 percent of predicted fetal weight for gestational age. The reason this poses a risk to the baby is that depending on the etiology behind the low birth weight, it may lead to more problems in later life. For instance IUGR due to IGF-1 deficiency will lead to short stature and hindered growth.
Give two examples of genetic conditions that can lead to short stature?
- Silver-Russel Syndrome
- Turner’s Syndrome
Why is no treatment given to maximize height before the age of 4 even with indicators of short stature?
Because even with indicators of short stature such as IUGR, 80-85% of babies are simply constitutionally small at birth, and will have postnatal catch up growth. This should occur by age 4, which is why if it hasn’t happened by age 4, pharmacotherapy can be sought after.
What is postnatal catch up growth?
A period of exponential growth after birth (before the age of 4) usually to make up for poor intrauterine growth.
What pharmacotherapy is used in children with IUGR who have not had catch up growth? What is the prognosis?
GH therapy; in most cases, the therapy allows the child to fit within their expected genetic centile range.
What is menopause?
12 months of amenorrhea and the neuroendocrine symptoms that arise during the last decade of reproductive life.
What is the physiological process behind menopause?
Ovary failure or insufficiency which causes the stop in menstruation. At 7 months of gestation, the ovaries will contain the peak number of oocytes (around 7 million). They will sharply decline until birth to around 2 million, keep declining until puberty to around 1 million, at which point they will gradually decline until menopause.
What are the endocrine effects of menopause? Why?
Sharp drop in estrogen, progesterone, and testosterone levels, as ovaries are responsible for most of their production.
Describe the levels of estrogen and progesterone throughout a woman’s life?
Progesterone: Very low level at birth until puberty. Sharply rise at puberty, and stay constant (slightly fluctuating) throughout the woman’s reproductive life, until they sharply decline around perimenopausal age. A complete drop-off will occur at menopause.
Oestrogen: Very low level at birth until puberty. Sharply rise at puberty, and stay constant (slightly fluctuating) throughout the woman’s reproductive life. At perimenopausal age, the oestrogen levels will peak and fluctuate very heavily, until a complete drop-off occurs at menopausal age.
What hormones rise after menopause? Why?
LH and FSH because there is no more estrogen inhibition.
What are the most common symptoms of menopause?
- Night sweats
- Hot flushes
- Anxiety
- Insomnia
- Irritability
How long do menopause symptoms usually last?
Usually last for four years
What are the associated physical changes that occur with menopause?
- Vagina narrows and shortens
- There is decreased blood flow to vaginal tissue
- Vaginal elasticity decreases
- Less secretion of fluids
List some of the long term effects that menopause has on a woman?
- Hypertension (oestrogen is a vasodilator)
- Increased cholesterol and LDL, decreased HDL
- Increased insulin resistance
- Osteoporosis
What is a T-score? What are the ranges?
A T-score is a bone mass comparison to that of an average 30 year old. >-1 is normal, -2.5 is osteoporosis
What is the management of menopause?
- Individualized care
- Symptomatic relief
- Long-term risk management (bones, heart disease …)
- Clonidine – for hot flushes and night sweats if not taking HRT
- HRT
What is HRT?
Hormone Replacement Therapy is a form of pharmacotherapy used as the first line treatment for menopause in order to replace the hormones being lost due to menopause (oestrogen and progesterone). Recommended at the lowest dose for the shortest amount of time.
What are the hormones given during HRT and what do each one achieve?
Oestrogen: Symptomatic relief (hot flushes, night sweats …)
Progesterone: Endometrial protection (to avoid hyperplasia/cancer)
Testosterone: ** Not systematically given, but given to women with low libido despite being on HRT
What are the benefits of using HRT?
Improves symptoms related to menopause generally. These changes range from improved depression, sleep, concentration to improved skin, vaginal dryness, libido and decreased risk of osteoporosis.
What are the risks associated with HRT?
Increases endometrial, ovarian and breast cancer risk, as well as increasing the possibility of cardiovascular events happening such as venous thromboembolism, stroke and coronary heart disease.
Do we need to test for FSH in order to definitively diagnose menopause?
No because symptoms of menopause alongside the clinical profile of the patient will be enough to diagnose it if they are over the age of 45. If the presenting patient is under the age of 45, FSH will need to be tested for in order to diagnose premature menopause.
What are the administration methods of HRT?
Oral, patch, gel, ring/pessary.
