Lactation exam 1

in reproductively competent animals the mature mammary gland consists of a teat or nipple, associated ducts that provide for passage of milk and the alveoli composed of epithelial secretory cells and supporting tissues.

The epithelial cells. They are in the internal lining of the spherical alveoli.

secretions are stored within the internal space of the hollow alveoli and larger ducts between suckling episodes.

It provides the calf with a spectrum of all the nutrients necessary for good health and early development. It provides carbs, fats, and proteins

sweat or sebaceous gland

Each gland is arranged with clusters of lobules, each with a separate duct that opens on the surface of the skin in a small depression. However there are no teats or nipples. For echidna there are two mammary glands on either side of the abdomen.

The holocrine cells are sloughed to become a part of the secretion. Ex: Sebaceous glands

Sweat glands follow an apocrine mode of secretion in which only portions of the cells are lost so that individual cells are capable of periodic secretion.

Other glands follow a meocrine mode of secretion in which products are secreted but the secretory cells remain intact.

Cow- 4 glands and one opening per teat, 4 inguinal
elephant-2 glands and 10-11 openings per teat, 3 thoracic
sow- 12 glands and 2 openings per teat, 4 thoracic, 6 in the abdominal and 2 iguinal
woman- 2 glands and 15-25 openings. 2 thoracic

some species have large litters like cat, dogs, pigs so they need more teats. we don't know why the cow has 4.

The mammary bud appears at about day 40 of gestation. By day 80 the teat and primary sprout have formed. The primary sprout gives rise to the teat cistern. Secondary sprouts occur by day 90 and by day 100 the primary and secondary sprouts are canalized by apoptosis. At birth the teat cistern and gland cistern are formed.

epithelial glands follow several distinct patterns of development based on the arrangement of cells within the secreting unit of the glands. simple glands have a duct that opens on to the surface. usually cells that create the duct opening or neck are nonsecretory and serve as a passageway for products made deeper within the gland. The gland mimics the shape of tubes or rounded flasks called alveolior acoli.

Within the alveolus, lining epithelial cells are a single layer thick (simple epithelium) but the nonsecretory ducts are satisfied with two or more layers of cells.

secretions begin to accumulate soon after the formation of alveoli during pregnancy

alveolar cells->ducts->gland cistern->teat cistern

The stromal tissue, alveoli, parenchyma as well as spaces for passage of blood and lymphatic vessels. Secretory epithelial cells, adipose tissue, myoepithelial cells (they contract when they receive oxytocin). The vascular bed circulates the blood (surrounding the alveoli)

Prepartum milking of dairy heifers is sometimes initiated during the month before parturition as a management technique to relieve intra mammary pressure. Secretions obtained prior to calving are generally high in protein and low in lactose compared with normal milk but with relatively small concentrations of specific milk proteins. (casein and whey) so high in immunoglobulins.

Colostrum is important for the calves because it provides the necessary immunogloblins as well as enzymes, proteins, carbs, and fats (energy) to the calve as well as water.

high in immunoglobulins b/c of synepithelial coral

The variation likely reflects evolution. Induced responses, which provide the best stratagem for offspring survival. Because seal pups are born on potentially unstable pack ice, they must rapidly gain sufficient strength and insulation to survive.

seal milk is 50% fat
cow milk is 3.4 fat
whales have to be sedated to milk them

The stromal tissue, surrounds the milk synthesizing alveoli, providing a framework for structural support and anchorage of parenchyma as well as spares for passage of blood and lymphatic vessels.
parenchyma-where the milk is
nonparenchyma- stromal tissue ex

As the gland continues to develop, the relative area occupied by the epithelium increases at the expense of the surrounding stromal tissue

Because the mammary glands of rodents are relatively flat, whole mounts of entire mammary glands can be easily prepared for examination. Its possible to measure and observe whole glands

parenchymal (secretory, epithelium,and ducts) and nonparenchymal tissue

palpatating the parenchymal tissue just above the teat in heifer calves or ewes lambs

Palpation of the udder is useful in assessing mammary health related to milk removal and mastitis.

The DNA content of cells is constituent in estimating mammary cell numbers.
Correlation means relation.
DNA is not the only thing from epithileal cells.

Collagen; the major extracellular protein component of the mammary stromal tissue. Assay of tissue content of hydroxyproline provides a quantitative measure of stromal tissue

Mammary growth is greatest during gestation (late gestation into lactation)

RNA is most useful in evaluating synthetic capacity in the mammary gland because as secretory cells differentiate in concert with parturition, there is a marked increase in the presence of rough endoplasmic reticulum and corresponding product of mRNA for specific milk proteins. The onset of milk synthesis and secretion corresponds with a marked increase in the mammary tissue RNA.

milk proteins-> casein and whey

Late in gestation after alveoli have formed but before the onset of copious milk synthesis and secretion, this ratio is generally about one. During established lactation the RNA content of the secretory cells increases dramatically and this ratio maybe three or more.
Protein synthesis is going on
Methionine and Lysine->limiting amino acids for milk production

MRI is magnetic resonance imaging.

Specific changes in the MRI signal characteristics, T2, are related to expected changes in cellular composition of the parenchymal tissue during development
T1 values reflect changes in tissue development
parenchymal-milk synthesizing

late in gestation, the alveolar cells are very poorly differentiated. The fully differentiated cells display abundant supranuclear vacuoles, apical lipid droplets,basally located (toward lumen), spherical nuclei, and a large cytoplasmic to nuclear ratio.
lipid droplet- apocrin secretion

There are no easy solutions. The best choice depends on the circumstances. The best advice is to include a variety of measures that allow a full characterization of the parenchymal tissue mass combinations of anatomical and biochemical measures are more likely to yield satisfactory results than either alone.
THe organization of and arrangement of cells.

the term refers to the development of mammary gland parenchymal structures.

The mammary band first appears at about 30 days in the bovine embryo.
30 days- mammary band first appears
At week five the mammary streak becomes mammary line

Up to the mammary bud stage, it is not possible to distinguish any differences in mammary development between males and females. After, female buds are more oval and have a smaller volume compared with males. The buds in the female appear closer to the surface. Early teat formation at about day 65 of gestation produces a more pointed teat in females compared with a somewhat flattened teat end in males. Thereafter development in males slows.

Bovine teat development begins with rapid growth of the mesenchyme surrounding the mammary bud so that the bud is pushed up toward the ventral surface. These events lead to an invasion of the mammary bud cells into the mesenchyme so that the mesenchymal cells are pushed aside. During this early development the mammary epithelium proliferates into relatively undifferentiated embryonic mesenchyme theereafter blood vessels also begin to form in the mesenchymal area surrounding the epithelial bud.
Mesenchymal precursors develop into a fat pad

the law of simple allometry is y=bxalpha
if alpha>1 growth is positively allometric (simple allometry)
adlibidum intake-as much food as they want
endogenous somatotropin have higher in limit fed study: 800 g/d

everything grows at same rate in the body. growth is proportional to the rest of the body. alpha=1

one part of the body grows faster than the others ex: mammary gland
Homeorrhesis: repartitioning of nutrients. after day 80 mammary gland. repartitioned for colestrogenesis. BST can do this

alpha<1 one part grows slower than the rest

from birth until 2 months, the mammary gland grows isometrically with the body positive allometric growth begins at about 3 months of age and continues until about 9 months
Prepartum becomes allometric

Yes. Rapid prepubertal weight gain inhibits the growth of mammary parenchymal tissue and reduces milk production.

Yes, mammary growth and development are stimulated by the onset of ovarian activity at puberty. Growth is 3 to 10 fold great in intact compared with ovariectomized animals. It prevents the onset of allometric mammary growth. Inhibits mammary growth except in ewe.

Yes. It can be hormonally induced with lactogenic milk.

pregnancy and its associated hormonal and physiological changes.
involuted- when mammary production ceases.

It is useful to quantify rates of mammary growth but the measurement doesn't distinguish differences among cell types.
Problem trying to distinguish between stromal and parenchymal tissue
Measure DNA and parenchymal mRNA would be best
ewes- 5 month pregnancy

Changes in weight, total DNA or percentage epithelium illustrate a marked increase in parenchymal tissue between day 80 and 115 of gestation. Between day 115 and 140 quantitative histology alone suggests there is no continued parenchymal development. This is clearly not the case since both tissue weight and total DNA doubles. Lack change in epithelial area between day 115 and 140 reflects that alveoli are present at these stages of gestation, but an increase in lumen and decrease in stromal tissue are reflect accumulation of some secretions and compression of stromal tissue between alveoli

Certain measurements can be misleading increased weight of parenchymal mass between day 260 prepartum and day 49 of lactation for holsteins is not observed when growth is measured based on DNA content
one measure is not good enough with it growing so fast. Adipose, DNA, RNA, alveolar
look at hydroxyprolene for stroma

Its important because greater alveolar volume means greater storage or secretory capacity therefore increased milk production. Milk yield is a function of the # of secretory cells and their activity. When it gets bigger has more capacity. An increase of only 10um (-width of an epithelial cell) nearly doubles the average alveolar base.

There is a difference in milk production between hereford and holstein cows because holsteins have a greater average number of cells per alveolus during lactation. (49 vs 76)-> 2.6 fold greater average alveolar volume for hostein heifers

alpha lactobumin found in mammary gland only
+galactosyl transferase=lactose synthase

Day 140 of gestation: cells have accumulated large lipid droplets and the spaces of the alveolar lumina are darkly stained, indicating the accumulation or protein (primarily Ig's) associated with colostrum formation. The alveolar cells have incorporated tritiated thymidine into their nuclei;their density indicates that it is associated with DNA synthesis rather than DNA repair. Atleast initial stages og lactogenesis are compatible w/ continued cell proliferation of the cells.
2 wks before calving: alveolar lumina stain darkly, lipid droplets are present in cells and luminal spaces. Secretions have accumulated so that the alveolar cells are composed.
2 weeks after calving: highly differentiated alveolar cells (common with onset of lactation) actively secreting cells. cells have acquired the structural features of actively secreting cells.

lactation depends on regular suckling or milking of the mammary gland. Involution for dairy cows is 40-60 days if this doesn't happen production lowers in subsequent lactation
FIC-feedback inhibitor location

although the time required for regression varies markedly between species(days for rodents vs weeks for ruminants). without milk removal the alveolar structure is eventually degraded, alveolar cells differentiate and many cells undergo apoptosis. Without the stimulus of another gestation, the gland progressively reverts to a structure similar to that of the mature virgin.

It subsequently increases in Dairy cows after first lactation. Suggesting cumulative mammary growth. Typically only in dairy animals.

hormonal and metabolic changes associated with late gestation and preparation for parturition are conducive for mammary development lactation.

For other species direct measurements of milk yield require that the animals are often sedated and/or injected with exogenous oxytocin to obtain milk. Its hard to know whether these numbers are accurate. Gives 10% more.

scaling milk production relative to body weight or mammary gland weight suggest common relationships and illustrates the effect of genetic selection for milk production. Although only a small amount have been studied.

The energy and substrate demands to support increased milk production are met by a combination of increased feed intake and mobilization of body reserves.

if energy expended is greater than energy obtained.

lactation in small animals generally involves a relatively short period of intense metabolic demand but in larger animals a longer period of lesser demand

Data points for these animals are above the calculated regression line for the nonselected species, reflecting greater than expected milk production
bred towards high MY

mammary involution can be stimulated at any stage of lactation by removal of suckling young or in dairy animals by suspending milk

Apoptosis of alveolar epithelial cells.(they die)

Marked changes in gene expression are evident within 24 hours and evidence of widespread apoptosis observed by 48 hours. In rats expression or mRNA for the caseins is reduced as percent and that of acetyl-CoA carboxylase a key lipogenic enzyme 98 percent within 24 hours

When both glands were nonsuckled for the first 15 days postpartum, mammary prolactin receptor was reduced 84% but in the nonsuckled gland of ewes with the opposite gland having continuing suckling stimulation the prolactin receptor was reduced only 36%.

After three days of nonmilking casein and alpha lactalbumin(lactose synthesis) mRNA were reduced but B-lactoglobulin mRNA was unchanged. After a week lowered 95%

The production of milk by the mammary glands

A dry period that is too short(less than 40 days) impairs subsequent milk production.

if energy expended is greater than energy obtained.

lactation in small animals generally involves a relatively short period of intense metabolic demand but in larger animals a longer period of lesser demand

Data points for these animals are above the calculated regression line for the nonselected species, reflecting greater than expected milk production
bred towards high MY

mammary involution can be stimulated at any stage of lactation by removal of suckling young or in dairy animals by suspending milk

Apoptosis of alveolar epithelial cells.(they die)

Marked changes in gene expression are evident within 24 hours and evidence of widespread apoptosis observed by 48 hours. In rats expression or mRNA for the caseins is reduced as percent and that of acetyl-CoA carboxylase a key lipogenic enzyme 98 percent within 24 hours

When both glands were nonsuckled for the first 15 days postpartum, mammary prolactin receptor was reduced 84% but in the nonsuckled gland of ewes with the opposite gland having continuing suckling stimulation the prolactin receptor was reduced only 36%.

After three days of nonmilking casein and alpha lactalbumin(lactose synthesis) mRNA were reduced but B-lactoglobulin mRNA was unchanged. After a week lowered 95%

The production of milk by the mammary glands

A dry period that is too short(less than 40 days) impairs subsequent milk production.

the proportion of epithelial cells in nonlactating cows was greater than in lactating. Rate of H-thymidine incorporation was consistently greater mammary tissue from nonlactating. Total cell numbers are not different. Increase DNA in dry cow.

dairy species: loss of secretory capacity(days) maintain alveoli(weeks/months) renew progenitor cells and MEC, gradual loss of MEC
Rodents: loss of alveolar structure (days) eventually only ducts appearing in fat pad. renew progenitor cells and MEC

these stem cells are capable of reproducing all of the differentiated cells in the mammary gland as well as sets of progenitor cells with a more limited capacity to generate either ductular or alveolar cells. This subset of progenitor cells has limited replication potential and is renewed from the primordial stem cell population.

Homeorrhesis is a term used to describe physiological processes and tissue metabolism to support a particular physiological activity.

Homeorrhesis in dairy cows refers to BST(or other factors) that mediate physiological changes to increase mobilization of tissue nutrients, absorption of dietary nutrients, changed blood flow, and increased feed consumption to meet the requirements for increased milk production.
Two types of BST: endongenous and exongenous

angiogenesis refers to the formation of capillaries from pre-existing vessels in the embryo or adult organism.

vasculogenesis concerns the development of new blood vessels from the differentiation of endothelial cells precursors called angioblast in situ.

vascular endothelial growth factor and its family related proteins are believed to be major regulators of vasculogenesis and angiogenesis in normal tissue development as well as pathological conditions. Mammogenic growth factors insulin like growth factor 1(IGF-1) and epidermal growth factor (EGF) are known to stimulate the tissue expression of VEGF.

likely important in mammary tissue remodeling. It can degrade a host of extracellular proteins.
mammary tissue remodeling

estrogen can mediate the synthesis or secretion of a number of local tissue growth factors. It is unclear if its effect on endothelial cell proliferation is direct. Since the mammary gland is ultimately a reproductive organ, a relationship between estrogen and angiogenesis during periods of stimulated mammary growth is logical but unproven.

The valves of the subcutaneous abdominal veins and perineal vein drains blood from the vulva region where it is mixed with external pudic vein blood to travel back to the heart. Therefore blood sampled from the subcutaneous abdominal vein may be unrepresentative in metabolic structures because of mixing and back flow. You make the assumption that its all the arteries provide O2 + nutrients, same measure aa for casein production.

Tidal volume is delivered from bellows
Consists of :
Rubber or latex free material
Enclose in clear rigid plastic container

Three types are: Double circuit syst, Piston, Spill valve

An accumulation of interstitial fluid leads to swelling of connective tissue spaces and thus udder edema. Back up of lymph.

Once lymph gets to the supramammary lymph nodes, larger lymph vessels transport the fluid through the inguinal ring and via branches toward the deep inguinal, external iliac, or prefemoral lymph nodes. These paired nodes connect with a single lumbar lymphatic trunk. This vessel progresses cranially to form cisterna chyli. The vessel continues to become the thoracic lymph duct, which empties into the anterior vena cava.

About 10% of cardiac output even after considering cardiac output increases about 45% in late pregnancy and into early lactation.

500:1

The flow of blood from an arteriole to a venule is called microcirculation. Blood is supplied by the terminal arteriole which delivers blood into a metarteriole. The metarteriole is continuous with a thoroughfare channel, which connects with a postcapillary venule and to larger veins.

While development of the mammary gland and milk synthesis there is only a minimal requirement for nervous system input.
Innervation of the mammary gland acts to maintain the mammary vascular sphincters in a tunic state of constriction.

mammary blood flow increases.
PTH increases MBF but not necessarily MP. IGF increases both. BST increases IGF

Lamivudine or 3TC is an NRTI

If they occur sufficiently, rapidly or from simultaneous multiple events, allow the affected neuron to depolarize sufficiently for induction of an action potential.

Central nervous system- brain and spinal cord
peripheral nervous system- consisting of the somatic nervous system under voluntary control and the autonomic nervous system under involuntary control.

sympathetic nerves (thoracolumbar division) exit the spinal cord primarily from the thoracic and lumbar vertebrae parasympathetic nerves-head and neck or sacral region of the spinal cord (craniosacral division)

Nerve terminals that secrete acetylcholine are called cholinergic fibers, and those that secrete norepinephrine are called adrenergic fibers.

Nerve impulses travel via afferent nerves (branches of the iguinal nerve) to the dorsal root ganglia of the spinal cord and ultimately ascend the spinal cord along the dorsal funiculus to the midbrain. Branches project to impact clusters of nerve cells in the hypothalamus called paraventricular and supraoptic nuclei. These cells synthesize oxytocin and a carrier protein neurosecretory cells.

Oxytocin and neurophysin are stored in the terminals of neurosecretory cells, which pass from the hypothalamus to the posterior lobe or the pituitary gland. Carrier protein of oxytocin.

failure of oxytocin to be secreted as an explanation for impaired milk let down.

failure of delivery to the myoepithelial cells. Oxytocin to reach.

roughly 5 minutes

epinenphrine and norepinephrine is released by binding to the receptors it shuts down oxytocin inhibiting milk to be released. Failure of oxytocin to be secreted as an explanation for impaired milk.

alpha-adrerngenic

also known as growth factors have an effect on the growth and development of the mammary gland.

lactogenic molecules act to promote the structural and/or biochemical differentiation of the alveolar epithelial cells to synthesize and secrete milk.

At the simplest level they either interact with target cell receptors located in the plasma membrane or with intracellular receptors. Others may act by opening or closing an ion channel in the plasma membrane.

Hormone binds to a receptors located on the plasma membrane. The binding reaction often initiates a series of biochemical events that ultimately change the intracellular concentration of potent regulators. The change in internal ion concentration is thus responsible for the effect attributed to the hormone some might act by opening and closing.