Function of Mammary Secretions Dr. Howard Tyler AnS 337 Lactation Biology

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Function of Mammary Secretions
Dr. Howard Tyler
AnS 337
Lactation Biology
Teleological Approach

Energetically driven processes are
developed to provide a benefit





Synthesis of some components
Active transport of some components
Milk itself
Colostrum
Needs of both dam and offspring
Importance to Newborn

Shift from placentation to lactation




Provide for nutritional needs
Regulate developmental processes
Enhance immunological status
In ruminants, reticular groove development

Milk as “by-pass feed”
Function of Milk and Colostrum
Nutrition of neonate
 Exogenous immune factors
 Influence homeorrhetic adjustments
 Developmental “jump start”

Different Species Have Different
Milk Compositions

Why?

Composition of milk matches the growth needs of
the young of a species


a rabbit doubles its birth weight in 6 days
a calf doubles its birth weight in 45 days



Rabbit milk has 5x the protein of cow’s milk
Cow’s milk has 2x the protein of human milk
Cows milk needs to have water, iron and vitamin
D added to make it suitable for human infants
Species Variation
Table 3. Composition of Milk from Different Mammalian Species
(per 100 g fresh milk).
Cow
Human
Water Buffalo
Goat
Donkey
Elephant
Monkey, rhesus
Mouse
Whale
Seal
Protein (g)
3.2
1.1
4.1
2.9
1.9
4.0
1.6
9.0
10.9
10.2
Fat (g) Carbohydrate (g) Energy (kcal)
3.7
4.6
66
4.2
7.0
72
9.0
4.8
118
3.8
4.7
67
0.6
6.1
38
5.0
5.3
85
4.0
7.0
73
13.1
3.0
171
42.3
1.3
443
49.4
0.1
502
Milk Composition
Constituent (g/100g)
Cow
Goat
Sheep
Human
Water (g)
87.9
88.9
83
88.2
Energy (kcal)
(kJ)
66
276
60
253
95
396
69
289
Protein (g)
3.2
3.1
5.4
1.3
Fat (g)
3.9
3.5
6
4.1
Lactose (g)
4.6
4.4
5.1
7.2
Calcium (mg)
115
100
170
34
Species Factors Affecting Milk
Composition



Maturity of neonate at birth
Maturity of different organs
Placental type and immunological status



Infant doubles weight in 20 weeks
Calf doubles weight in 10 weeks
Piglet doubles weight in 10 days
Importance of Milk Carbohydrates



In newborn, lactose must be hydrolyzed prior
to absorption
Lactose enhances iron absorption
Sweetness index affects intake
Importance of Milk Fats

At birth, only absorb a portion of fats



Pre-gastric esterase important in calves
Gastric lipase important in infants



Limited by amounts of lipase and bile salts
Infants have problems with cow’s milkfat
Microbicidal action of some fats
High cholesterol enhances neural
development
Major Factors Affecting Milk Composition
Completeness of milking
Milk removal ≈ 4 min. for a cow
% removed
Time (sec)
Milk
Fat
% Fat
30
16
7
1.4
60
41
18
1.6
120
83
61
4.8
240
100
100
11.1
Fat globules tend to clump, passage through ducts is slower
Fat
Proteins
Sugar
Composition of milk
Foremilk and Hind Milk ..

Fats provide satiety


High fat in the hind milk ensures that the
neonate feels full after suckling
Low fat in foremilk encourages consumption
Importance of Milk Proteins

Rennin (also pepsin and chymotrypsin)
induce casein coagulation with calcium
phosphate


Enmeshes fat and whey proteins
Low casein content of human milk lowers
buffering capacity



Less acid required for clot formation
High casein milks (cows) form firmer curds
High in cysteine and taurine
Coagulation of Secretions

Casein coagulates as pH decreases or
temperature increases


When pH falls below 5.1, casein destabilizes
Below 4.5 – casein salts form and milk curdles
Calcium phosphocaseinate

Milk forms hard curds



neutral casein + Ca++
(curd)
(whey)
Slow release nutrient delivery
Cheese making properties dependent on this
Colostrum forms soft coagulum


Very slow release nutrient delivery
Destroys cheese making properties
Peptides


Peptides formed from digestion of both
caseins and whey proteins are bioactive
Multiple functionality




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Anti-microbial – including control of gut microflora
Anti-viral
Binding of E coli and cholera enterotoxins
Immunomodulation
Anti-oxidative
Importance of Milk Minerals

Immaturity of human renal system
compensated for by low sodium content of
human milk



Cow’s milk high in sodium
Infants regulate calcium levels in first weeks
through absorption rather than excretion
Iron bioavailability higher in human milk


High vitamin C and lactoferrin
Present as iron citrate
Importance of Immunological
Factors

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Lactoferrin antimicrobial effects
Lactoperoxidase and myeloperoxidase
Lysozyme
Bile salt-stimulated lipase
Long chain unsaturated fatty acids
Phagocytic cells
T-cells
Other Immunological Components
of Human Colostrum & Milk




Cytokines
Complex oligosaccharides – inhibit adherence
of bacteria to cells
Lactoferrin – binds Fe
Lysozyme – degrades bacterial cell wall
Importance of Growth Factors,
Hormones, and Bioactive Peptides



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Epidermal growth factor
Nerve growth factor
Nucleotides
Prostaglandins
Other growth factors and bioactive peptides
In Conclusion


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Almost all components of milk have a
physiological function beyond nutrition
Milk components are multifunctional
Mammary secretions possess a natural
“cluster” of nutrients that protect health
and enhance the immune system
Passive Immunity (Colostrum)
Neonatal Immunity

Human placenta transports IgG from maternal to
fetal circulation


Babies born with IgG concentration approximately 89%
of adult values
No transport of immunoglobulins across placenta in
farm animals


Offspring born with essentially no circulating IgG
Colostrum provides IgG after birth
Ig Concentrations in Human
Colostrum & Milk
IgA
Colostrum
(g/L)
5 – 10
Milk
(g/L)
0.3 – 1
IgM
0.06
0.06
IgG
0.1
0.01
Ig
Immunoglobulin (and Bioactive
Peptide) Absorption


24 hr period of time for attainment of
passive immunity in livestock
Proteolytic activity of the digestive tract is
low in newborn animals


Further inhibited by trypsin inhibitors in
colostrum
Nutrients are able to pass the stomach
without degradation to the small intestine
where absorption occurs
Selective Transfer of IgG


Occurs in rats through binding of IgG to FC
receptors in the small intestine
Time dependent



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Non-specific absorption after birth
By 3 d of age, IgG absorption favored
By 7 d of age, IgG absorption selection 20X greater
At 21 d of age, no intact proteins absorbed into
circulation
Non-selective Transfer of IgG

Occurs in calves and sheep


Pigs and foals selectively absorb IgG compared to
other macromolecules


IgG, IgM, and IgA absorbed in proportion to amounts in
colostrum
IgA and IgM found on enterocyte surface but not inside
the cell
Absorption rate decreases with increasing age

Mean time to closure approximately 21 to 26 h of age
Absorptive Mechanism

Pinocytosis

Absorbed via intermicrovillous spaces


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Absorption permitted by lack of terminal web in
microvilli
Vacuole forms around absorbed material
Vacuole expands as more material absorbed
Vacuole fills cell

Nucleus pushed down to basolateral membrane
Absorptive Mechanism



Filled vacuole pinches off at luminal end
Nucleus and vacuole change places
Vacuole merges with basolateral membrane


Enhanced by large intercellular spaces in
neonatal intestine
Material in vacuole is “purged” into
intercellular spaces
After Absorption

Immunoglobulins are absorbed unchanged and
enter the lymphatics



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Lymphatics highly fenestrated immediately after birth
Enter circulation via thoracic duct
In circulation, IgG is distributed equally between extraand intravascular space
Equilibrium reached in 51 h
IgG can be secreted back into the intestinal lumen
through the duodenal crypt cells
Efficiency of Ig absorption
40
35
30
25
20
15
10
5
0
0
4
8
12
16
20
24
Time (hours) relative to birth
Closure



Even after closure occurs, cells continue to
take up colostral material into vacuoles
Completed vacuoles do not exchange places
with nucleus or other cellular organelles
Cell migrates to tips of villi and are sloughed
off and excreted
Failure of Passive Transfer (FPT)

Low IgG levels greatly increase risk for
death and disease in ALL species




40% of calves classified as FPT (<10 g
IgG/L)
Colostrum-deprived calves 50-74 times
more likely to die before 3 weeks of age
FPT calves are twice as likely to get sick as
non-FPT calves
NAHMS estimates suggest 22% of all
calf deaths could be prevented by
better colostrum management
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