Bovine mammary gland

14-Arid-2022 PMAS

FAISAL SHAHZAD SOMROO

Front : Rear quarter = 40 : 60 Support system: ligaments and connective

tissue Secretory and duct system: exocrine gland Blood supplies and capillary structures: 400-

500 kg of blood pass through the udder 1 kg of milk

Lymph system Innervation of the udder: milk let down reflex

Mammary gland structure

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 bacte

ria.

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 ca

rry milk to the gland cistern. Between milkings approximately 40% of th

e 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 som

atic 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 oxytoci

n 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 gr

adual 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 60-day 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.

1) The period of active involution: 0-30 days after drying-off

2) The period of steady state involution: The period of time the gland is maintained in the fully involu

ted 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

Physiological Function during the Dry period

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 4

8 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 te

ats 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 n

ormal milk levels during this potentially vulnerable period (first 3 d). 5) The phagocytic cells are occupied in the phagocytosis of degener

ated 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 ba

cteria.

In the other side The gland should be more resistant to new IMI because of t

he 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.

The Relationship of Active Involution to New IMI

Steady State of Involution: Relationship to New IMI The conditions within the mammary gland during ste

ady 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 lymphoc

yte 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

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

Lactogenesis-Colostrogenesis: Relationship to New IMI

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

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

Dry Cow Treatment Procedure (2)

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).

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

Cellular Immunity

Humoral Immunity IgG1, IgG2, IgA and IgM Low during lactation High during non-

lactating 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

Produced by epithelial cells and leukocytes Prevent growth of bacteria High during inflammation and involution

Complement: a collection of proteins in serum and milk 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

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

Nonspecific Bacteriostatic Components