Transcript Bovine mammary gland

Bovine mammary
gland
Sukolrat Boonyayatra
DVM, MS
Clinic for Ruminant, FVM. CMU.
Mammary gland structure






Front : Rear quarter = 40 : 60
Support system: ligaments and connective
tissue
Secretory and duct system: exocrine gland
Blood supplies and capillary structures: 400500 kg of blood pass through the udder  1
kg of milk
Lymph system
Innervation of the udder: milk let down reflex
The udder of a cow producing 40 lbs. of milk
in a 12-hour period can weigh up to 100 lbs.

Skin and Subcutaneous Tissue :

a minor capacity to suspend and stabilize the udder

protects the interior of the udder from injury and
bacteria.
Median Suspensory Ligament
-The most important support for the udder (MSL)
-Clearly divides the udder into the right and left halves
-The MSL is composed of elastic tissue that stretches
to allow the udder to expand as it fills with milk.
Lateral Suspensory Ligament
-Chiefly fibrous and non-elastic (don't stretch).
-The LSLs extend along both sides of the udder
and at intervals send sheets of tissue into the gland
to provide support to the inside contents of the udder

Pendulous Udder
If the Medial and Lateral
suspensory ligaments
weaken and the cordlike
structure that attaches the
fore udder to the body wall
stretches, the result can be
a pendulous udder.

Disadvantages of a
pendulous udder include:




Cleaning difficulty
Milking difficulty
Risk of injury
Risk of mastitis
Streak Canal
- approximately ¼ to ½ inch in length,
-closed by sphincter muscles.
The streak canal serves two very important purposes.
1. it prevents the escape of milk between milkings
2. it acts as a barrier to the entry of bacteria and
other foreign material.
-Milking speed is related to the size of the canal
and also the tightness of the sphincter muscles.
Keratin
- The cells that line the streak canal contain keratin.
- Keratin is a waxy substance similar to ear wax.
- This substance helps to seal the teat end between milkings.
- Keratin also has properties that inhibit the growth of bacteria
(disease organisms).
- The physiological process of the teat canal forming a keratin
plug after drying off appears to be a major front-line defensive
mechanism.
Fürstenburg's Rosette
- Fürstenburg's rosette is located
directly above the streak canal.
-It is made up of loose folds of
membrane that smooth out as milk
accumulates in the udder.
-This aids in blocking the escape of
milk between milkings.
-This can be damaged by improper
milking or by improper use of
mastitis infusion nozzles.
Teat Cistern
-The teat cistern is the cavity inside
the teat that holds from 1/2 to 1 1/2
ounces of milk, depending on the
size of the teat. -The teat cistern is
the holding chamber where milk
accumulates before it is removed
through the teat end during milking.
-It refills continuously during
milking.
-This is where the first milk to be
removed accumulates between
milkings.
Gland Cistern
The gland cistern joins to the
teat cistern at the base of the
udder. The gland cistern,
which can vary greatly in
capacity, functions as a
collecting vessel for milk from
the major milk ducts that flow
into it. The gland cistern fills
rapidly during milk letdown.
Secretory System

Milk is released by alveoli into ducts which
carry milk to the gland cistern.

Between milkings approximately 40% of
the milk is stored in the teat and gland
cisterns and the major ducts while the
remaining 60% is stored in the alveoli.
Alveoli
-grape-like clusters
-Each alveolus is composed
of a single layer of epithelial
cells surrounding a central
cavity.
-These cells absorb nutrients
from the blood, transform
them into milk and discharge
the milk into the cavity of the
alveolus.
-Each alveolus is also
surrounded by specialized
muscle cells known as
myoepithelial cells that are
responsible for milk ejection
during letdown.

Around the time of calving, the secretory cells of the
alveoli start to produce milk.

During parturition, there is a large surge of prolactin
and this is the signal to start lactation.

The important hormones for milk production and the
maintenance of lactation are prolactin, insulin-like
growth factor (IGF)-1 and growth hormone.
Milk Let-Down




Neuro-hormonal reflex
The suckling stimulus or massaging of the udder stimulates
somatic nerves in the teat, which send a signal to the posterior
pituitary gland and causes the release of the hormone oxytocin.
Oxytocin causes the myoepithelial (muscle) cells around the
alveoli to contract.
For efficient milking, there are several important factors to
remember.
 Stimulate 1 min before milk let-down
 The maximal effect of oxytocin occurs during tfirst 2 to 3 minutes
of milk let-down.
 Stress during cow preparation or during milking will inhibit
oxytocin release.
 Inhibition of oxytocin release
Dry period
Lactation Cycle

4 phases of mammary gland




1. Dry period:Development
2. Around calving (-4 to +4 days): Differentiation
3. Lactation: All cell activity directed towards milk
synthesis and no further mammary growth.
4. Involution of the mammary gland: This is the
gradual but irreversible regression of the gland
(i.e. a reduction in the numbers of active alveoli).
This starts after the peak of lactation, but is more
pronounced during late lactation.
Dry period



The mammary gland of the dairy cow requires a
non-lactating period prior to an impending parturition
in order to optimize milk production in the
subsequent lactation.
There is general agreement that an approximate 60day non-lactating period is required and that dry
periods of less than 40-50 days result in less than
optimal milk yields.
The dry period is critically related to the dynamics of
intramammary infection (IMI) within a dairy herd.
Physiological Function during the
Dry period

1) The period of active involution:


2) The period of steady state involution:


0-30 days after drying-off
The period of time the gland is maintained in the fully
involuted state.
3) The period of lactogenesis and colostrogenesis:




15-20 days prepartum
Regeneration and differentiation of secretory epithelial cells
Selective transport and accumulation of immunoglobulin
The onset of copious secretion
Active Involution: Early Dry Period

Milk composition



Lactose ↓
Total protein ↑
 Lactoferrin ↑ : major protein
 Serum albumin ↑
 Immunoglobulin ↑
 Casein ↓
Mammary cells



Involution-associated ultrastructural changes begin within
48 hours after cessation of milk removal.
Large stasis vacuoles in the epithelial cells
Cell apoptosis and Phagocytosis
The Relationship of Active
Involution to New IMI
Factors may favor new infection during the early dry period







1) A large volume of milk is accumulated and leakage of milk from
teats is often observed.
2) The contents of the gland are no longer being removed at regular
intervals.
3) Teat end disinfection is stopped.
4) The factors of natural defense are only marginally elevated over
normal milk levels during this potentially vulnerable period (first 3 d).
5) The phagocytic cells are occupied in the phagocytosis of
degenerated epithelial cells, fat and casein.
6) The phagocytic capabilities of the macrophage and PMN and the
responsiveness of lymphocytes to antigen stimulation are reduced.
7) Secretion components can act as growth stimulants for certain
bacteria.
The Relationship of Active
Involution to New IMI

In the other side



The gland should be more resistant to new IMI because of
the elevation in phagocytic cells, lymphocytes,
immunoglobulins and Lf
These changes occur too slowly and their antibacterial
action is compromised by other normal events of
involution.
Treatment of glands at or near drying off with colchicine,
endotoxin or the combination of the two compounds
resulted in a more rapid involution, earlier elevation of
resistance factors and reduced IMI during the first week of
the dry period.
Steady State of Involution:
Relationship to New IMI

The conditions within the mammary gland during
steady state involution can resist the establishment
of new IMI.





A few volume of fluid
Greatly reduced of the major constituents of milk
The concentration of immunoglobulins and Lf are elevated
The predominant cell type would appear to be the
lymphocyte in uninfected quarters but substantial numbers
of macrophages are present.
The PMN are generally found in low numbers by
comparison to lymphocytes and macrophages.
Lactogenesis-Colostrogenesis:
Relationship to New IMI








Destructive processes
Hormonal control
Formation and accumulation of colostrum: IgG1
The major components of milk increase 2 wks before
parturition.
Fat, casein and lactose increase in the 5 days preceding
parturition.
Volume increase 1-3 days prepartum
Citrate↑ (harbinger)The molar ratio (citrate:Lf)
increases by approximately 100 fold over the last few
days prepartum.
 A loss of the antimicrobial properties of Lf
Lactogenesis-Colostrogenesis:
Relationship to New IMI





Number of cells in secretion of uninfected quarters
gradually decline over the 2 week prepartum period.
The macrophage appear to be the predominant cell
type.
The phagocytic ability of macrophages and PMN
appear to be inhibited.
The susceptibility to new IMI increase caused by the
environmental pathogens
Little or no protection from dry cow therapy products
Summary

The susceptibility of the bovine mammary gland to new IMI ↑at both
the beginning and the end of the dry period.

The early dry period is associated with decreased synthesis of milk
constituents, regression of synthetic tissue (active involution) and
increased levels of antibacterial factors and/or systems.

The late dry period is associated with development and
differentiation of synthetic tissue, increased selective transport of
IgG1 immunoglobulin (colostrogenesis), increased synthesis of milk
constituents (lactogenesis) and decreased levels of antibacterial
factors and/or systems.

During both periods fluid is accumulated in the gland.

A lack of flushing action, teat leakage  bacterial colonization
Summary of Changes in Composition of
Mammary Secretion During the Dry Period
Dry Cow Therapy
Dry Cow Therapy

The Advantages






A reduced incidence of new infections during the first 3 to 4
wks of the dry period
A much higher cure rate than lactational treatment of some
organisms
An aid in the regeneration of damaged milk secretory
tissues
A reduced incidence of mastitis in the next lactation
An avoidance of milk loss due to treatment of mastitis in
lactation
A reduced level of mastitis, translating into increased milk
production, better quality milk and greater money returns
Types of Antibiotic Treatment

Intramammary infusion products


1. the quick-release, short-acting types designed
specifically to treat mastitis in lactating cows
2. the slow-release, long-acting types formulated
specifically to treat subclinical mastitis in dry cows
and to prevent new infections in dry cows: remain
in the udder for  21 days
Drying-off




Regeneration of new milk secreting cells
Restore body energy and nutrient reserves
50-70 days, never less than 40 days before
the expected calving date
Reducing the concentrate reduce milk yield


Intermittent milking
Sudden cessation of milking
Dry Cow Treatment Procedure (1)





Milk the udder out completely.
Clean and dry teats with a single paper towel or cloth.
Dip all teats in an effective teat dip. Allow 30 sec before
wiping teats with single service paper towel or cloth.
Starting with the teats on the far side of the udder,
disinfect the teat ends by scrubbing each for a few
seconds with a separate alcohol-soaked cotton swab
Treat quarters in reverse order; near side first, far side
last
Dry Cow Treatment Procedure (2)

Insert only the tip of the cannula (6 mm or ¼ in) into
the teat end prior to infusing. Massage the treatment
up into each quarter.

Dip teats in an effective germicidal product after
treatment.
Practical teat dip all treated cows at least once a
day for two weeks after drying-off and for two weeks
before calving.
Remove the cows from the milking herd to prevent
antibiotics from entering the milk supply


General Considerations








Laboratory culture and sensitivity test
Early dry off
Number of infusions
Teat dips
Vaccination or Immunization
Sanitation
No dry period
Dry cow therapy to Bred Heifers
Blanket vs. selective dry cow
therapy

Blanket dry cow therapy when either;
 BTSCC > 500,000
 4 or more clinical cases /100 cows /3 days
 The quarter infection rate > 15%
 The individual cow SCC average for all cows > 250,000

Use selective dry cow therapy when the monthly BTSCC stays
consistently <200,000 and the quarter infection rate <15%. Treat
only the following cows;
 Individual cows with peak SCC>250,000
 Cows that had clinical mastitis during lactation
 Cows from which a major organism has been cultured from the
milk.
Defense Mechanism
and Immunity of
Mammary Gland
Natural Disease Resistance
Factors in the Mammary Gland




Physical Barrier
Cellular Immunity
Humoral Immunity
Phagocytosis
Physical Barrier








Teat shape
Streak canal
Teat sphincter
Keratin
Streak canal diameter
Furstenberg’s rosette
Intramammary infection
Bacteria
Cellular Immunity







Leukocyte ~ Milk Somatic Cell
~60% are macrophages
~30% are lymphocytes
~10% are polymorphonuclear cells
Innate immunity = first line defense
mechanism
Chemotactic activity by cytokines released
from lymphocytes
Phagocytosis
The process of PMN chemo-attraction into the mammary
gland (From Suriyasathaporn et al. 2000b).
Cellular Immunity

Processes are limited by



Limit of sources of energy in milk
Diluted the concentration of cytokines
Milk fat and protein can interfere the function
Cellular Immunity

Neutrophils





Predominant cell type in early inflammation
Phagocytosis
Oxygen-dependent killing mechanism
Small antibacterial peptides: the defensins
Macrophages



Predominant cell type
Phagocytosis
Antigen presenting cell: MHC class II
Cellular Immunity

T-lymphocytes : CD4+ : CD8+ ratio<1 in milk

T-helper lymphocytes (CD4+):



Recognition of MHC antigen
Activating B-lymphocytes
T-cytotoxic or T- suppressor lymphocytes (CD8+):


Cytotoxic T lymphocytes: removing old or damaged
secretory cells
Suppressor T-lymphocytes: control or modulate the
immune response
Cellular Immunity

B-lymphocytes



Produce antibodies
Specific pathogen recognition
Present MHC class II
Humoral Immunity




IgG1, IgG2, IgA and IgM
Low during lactation  High during nonlactating period Peak during
colostrogenesis
IgG1, IgG2 and IgM: Bacterial opsonin
IgA: agglutination, preventing bacterial
colonization, toxin neutralization
Nonspecific Bacteriostatic
Components

Lactoferrin: an iron-binding protein




Complement: a collection of proteins in serum and milk




Produced by epithelial cells and leukocytes
Prevent growth of bacteria
High during inflammation and involution
Lysis of invading bacteria
Highest in colostrum, inflamed mammary glands, during
involution
Lowest during lactation
Lysozyme: a bactericidal protein in milk


Cleaving the peptidoglycans from the cell wall or cell
membrane of bacteria
Little protection to the bovine mammary gland
Nonspecific Bacteriostatic
Components

Lactoperoxidase-thiocyanate-hydrogen
peroxide system




Bacteriostatic for Gram+ bacteria
Bactericidal for Gram- bacteria
Low oxygen tension of the mammary gland can
limit the effective of this system.
Cytokines: G-CSF, GM-CSF, IFN-, IL-1, IL-2