Lactation

• VSC262 202530 covers Lactation
• Learning objectives include the ability to:
• Discuss and describe the development and anatomy of the mammary gland
• Describe milk flow within the mammary gland
• Describe and discuss the endocrinology and terminology associated with milk production
• Describe the basic milk components
• Briefly describe the pathology associated with milk production in dam (mastitis) the neonate (FTPI/NI)

Lactation Importance

• Lactation is the udder side of pregnancy
• Food for the neonate
• Dams consume raw materials and convert them into milk
• Domesticated species may also be selected to produce excess milk for human consumption
• Examples of domesticated species include: domestic cattle, goats, sheep, water buffalo, camels, and mares

Structure and Function

• Identify the structures involved
• Outline the functions

Major Milk Components

• Describe the components of milk and colostrum

Lactation Curve

• Describe the lactation curve

Clinical Aspects

• Failure of transfer of passive immunity
• Neonatal isoerythrolysis
• Hypocalcaemia
• Ketosis
• Importance of Transition diets

Mammogenesis

• Mammary glands develop along two lateral lines called the mammary ridge
• The primary mammary bud develops inwards into the dermis
• The secondary mammary bud develops branches that penetrate into the dermis
• Tiny ducts form canals in the centre of each bud during canalisation
• Arises on mammary ridges
• Embryo develops ventrally
• Compound alveolar glands develop from ventrolateral cords of embryonic ectoderm from the axila to the inguinal region
• Isometric growth occurs between birth and puberty and does not exhibit noticeable enlargement or development
• Allometric growth and development at puberty is disproportionate to normal body growth
• Continues to develop with repeated oestrous cycles
• Ducts begin to branch and diameter increases
• Alveoli start to develop during the luteal phase
• Final development occurs during pregnancy at which point:
• Terminal alveoli grow into bunches called lobules
• 90% of the cellular mass of gland at parturition

Mammary Gland Diversity

• Diversity in position
• Diversity in number
• Diversity in teat morphology
• Cows and Camels have inguinal glands
• Ewes, goats and mares have inguinal glands
• Sows have glands along their sternum
• Rats, mice, rabbits, bitches, and queens have sternal glands
• Primates and Elephants have thoracic glands
• Cows and camels have 2 canals per teat
• Cows, ewes and goats have 1 canal or cistern per teat
• Mares and sows have 2-3 ducts per teat
• Bitches and queens have 5-6 ducts per teat
• Primates and Elephants have 8-10 ducts per nipple/teat

Gross Anatomy - Bovine

• Each quarter is discrete
• Key anatomical features:
• Body of gland (parenchyma)
• Lactiferous sinus (gland cistern)
• Papillary sinus (teat cistern)
• Lactiferous duct (streak canal, Papillary duct)
• Median suspensory ligament
• Supramammary fat
• Udder morphology is heritable
• Supernumerary teats in 25 – 50% of cows, a heritable trait

Mammary Glands - Cow: Medial Lamina

• Originates from linea alba and the symphysis of the pelvis
• Gives off sheets of connective tissue that penetrate into the mammary gland.
• Thickest dorsally.

Mammary Glands - Cow: Blood Supply

• Venous drainage occurs through the external pudendal v, perineal v, subcutaneous abdominal (milk) v
• Arterial supply occurs through the external iliac a, .external pudendal a, caudal and cranial mammary a

Mammary Glands - Cow: Lymphatic Drainage

• Lymphatics in udder drain to: Mammary L.N. (2 pairs)
• Mammary LAN drain to the Deep inguinal L.N. which drain to the Medial iliac L.N.

The pathway taken by milk through the mammary gland

• Glandular cells lining alveoli secrete milk
• Milk drains into Intralobular ducts, located ("Intra" = within) inside the lobes
• Milk then drains to the Interlobular ducts ("Inter” = between), which are ducts draining the lobules
• Finally this drains into the Lactiferous ducts
• The Lactiferous Sinus is divided into 2 parts, the 1. Gland sinus and 2. Teat sinus (teat cavity),
• This then drains to the Teat canal: Also called "Streak canal"
• The milk then exits through the Teat Orifice

Microscopic Anatomy

• Includes the Alveolus, Myoepithelial cells, Epithelial secreting cells, and Blood vessles
• Oxytocin release
• Myoepithelial cell contraction
• Increased lumen diameter
• Increased milk flow
• Lactating alveolus has a secretory epithelial cell, capillary, and a myoepithelial cell

Lactating vs. non-lactating mammary glands

• Lactating mammary grants are fully developed and functional glands
• Lactating mammary glands consist mainly of glandular tissue
• Non-lactating mammary glands are involute, which is where the glandular portion regresses
• Non-lactating mammary glands consist mainly of fibrous connective tissue

Mammary Glands - Microscopic Structure: Teat Canal

• Lined by stratified squamous epithelium
• Internal opening has longitudinal folds to narrow the lumen and is called the "Rosette of Furstenburg".

Innervation

• Inguinal nerve
• Caudal mesenteric nerve (sympathetic)
• Innervation is not critical to function

Milking and enteroceptive stimuli

• Pregnancy triggers the placenta to release Progestogens Oestrogens and Placental lactogens
• The CNS triggers the Hypothalamus to release and inhibit hormones called PIF's
• The Anterior Pituitary triggers FSH, LH, ACTH, and TSH
• This stimuates the ovaries which release Oestrogens and Progesterone, the Adrenal which releases Corticoids and the Thyroid, which releases T4, T3
• This leads to Mammary cell proliferation
• Posterior Pituitary releases Oxytocin and mammary cell maintenance
• The thyroid also releases Prolactin and releases GH Prolactin

Lactogenesis and Galactopoeisis

• Lactogenesis is the Initiation of lactation involving section from mammary epithelial cells
• This is hormonal control
• Includes endocrinology of pregnancy and parturition
• It involves Progesterone/s, Oestrogen/s, PITUITARY- 'Somatotrophins', GH, CS, PROLACTIN
• Galactopoeisis is Lactation maintenance, involving the Activity and number of secretory cells
• This includes Local Factors (FIL)
• such as parity, pregnancy, endocrinology, feeding

How Prolactin affects the body

• Stimulates lactogenesis and responsible for maternal behaviour
• Inhibited by Prolactin inhibitory factors - PIF like Dopamine, Nor-adrenaline,Gamma-aminobutyric acid), and Ergot alkaloids that block serotonin and domamine agonist
• Stimulated by: Oestrogen, Serotonin, Thyrotrophin releasing hormone, and Sucking (Sensory)
• PIF activity can be reduced with Phenothiazine derivitives like Acepromazine or Metoclopramide and Reserpine (dopamine antagonists)

Requirements for milk production

• Mammary gland Development requires Puberty and Sex steroids like Progesterone and Oestrogen
• Milk production by epithelial cells requires large amounts of energy substrate, mainly glucose
• Colostrogenesis is Lactogenesis
• This requires Pregnancy plus Sex steroids and Pituitary (GH, PROLACTIN, and other mammotrophins.)
• Galactopoeisis is the Removal of milk
• Involution is the Resolution of gland for next lactation

Colostrum

• Formed in the last 2 weeks of gestation and 2 days post partum (pp)
• Transfers passive maternal antibodies to neonates
• Pinocytosed by the neonate gut in the first 24-36 hrs due to Specialised cells and Pinocytosis, Gut is then "closed" after this time
• First 12 hours is most crucial for TRANSFER of PASSIVE IMMUNITY
• Yellow due to ẞ carotene in the fat globules (Vit A, D & E)
• Contains IgG (80%), IgM and IgA
• Includes other 'FACTORS' including epigenetic effects and Lactocrine hypothesis

Comparison of colostrum composition to milk

• Water in colostrum is 76% vs. 87% in milk
• Protein in colostrum is 14% vs. 3.1% in milk
• Butterfat in colostrum is 6.7% vs. 4.0% in milk
• Lactose in colostrum is 2.7% vs. 4.7% in milk
• Vitamin A (µg/100ml) in colostrum is 295 vs. 34 in milk
• Immunoglobulins in colostrum is 6.0% vs. 0.09% in milk

How transfer of passive immunity happens

• .Colostrum produces no more milk
• . Colostrum is only absorbed for a short time and then it decreases and stops
• Need to get good quality colostrum into all calves as soon as possible after birth.

How Colostrum is taken up

• Colostrum goes through Terminal small intestine with Globulins and other macromolecules
• This takes up larger MW molecules (≥ 70,000) and is Assisted by colostral enhancement factors
• This is Taken up by pinocytosis by Specialized epithelial cells with Vacuolar contents discharged into the Intercellular space and moves through the Lacteals to the Thoracic duct to a Systemic blood with proteinuria
• Lower MW molecules(<70,000) are Absorbed by duodenal cells or passed into intestinal capillaries - This then goes to Portal blood
• Urine will excrete Proteins and macromolecules of MW < 70,000 through the kidney

Milk Composition

• Bitch Milk: 2,300 mg Ca, 35 g/l Lactose, 85 g/l Lipids, 1,600 mg/ml P, 75 g/l Proteins, 80 % Water
• Cow Milk: 1,250 mg Ca, 50 g/l Lactose, 35 g/l Lipids, 975 mg/ml P, 35 g/l Proteins, 87.5 % Water
• Mare Milk: 1,025 Ca, 45 g/l Lactose, 15 g/l Lipids, 650 mg/ml P, 25 g/l Proteins,90 % Water

Lipids

• Mainly triglycerides
• High proportion of saturated fatty acids
• Bovine milk TG's derived from short chain FA's
• FA's synthesised in the mammary gland

Carbohydrates

• Primarily lactose

Protein

• Casein

Somatic cells in Milk

• Somatic cell count (SCC) Includes Epithelial and Inflammatory
• Inflammatory cells are are neutrophils, lymphocytes and macrophages
• Concentration of cells increased at the start and completion of the lactation
• Mastitis (inflammation/infection of the mammary gland) increases the SCC
• High SCC Indicates a reduced milk production, loss of protiens (casein), and an increase in immunoglobulins
• Measured as BMCC or individual SCCs using Rapid mastitis test – RMT or a Cow side test for SCC

Milk Energetics

• Daily lactation production increases during the first 2-4 weeks and then steadily declines by about 1.5 - 2%/ week

Bodyweight

• Nadir usually within first 10 weeks
• After nadir the cow needs to gain 150-250 g/day
• High energy requirement – prone to ketosis

Energy for lactation

• To produce 1L milk requires 5 MJ DE
• 40L of milk requires 200MJ/day, lactation
• For Maintenance 600kg cow:
• 8.3MJ + 10% bodyweight = 68MJ DE/day
• Maintenance + Lactation = 268MJ DE/day
• ~ 27kgDM lucerne hay (2 bails/day)
• Good body condition important prior to calving, with need of proper formulation

Lactation issues

• Ketosis – Cattle/sheep/goats
• A disease of negative energy status
• Rapid mobilisation of lipids and non esterified fatty acids (NEFAs) to satisfy energy requirements
• Ketogenesis resulting in accumulation of ketone bodies
• Common in high producing dairy cattle
• Loss of appetite – loss of BW and condition
• Decrease in milk production
• Sweet smell of acetone on breath
• Neurological signs when severely affected
• Prevention -Reduce impact of negative energy status with TRANSITION DIET and Prepartum and postpartum dietary composition
• Hypocalcaemia - Cattle and dogs
• An acute deficiency in Ca2+ post partum involves Loss of skeletal muscle, cardiac and smooth muscle function
• "Milk fever” in high producing dairy cows within ~ 48hrs post calving and “Eclampsia” in post partum bitches usually during peak lactation
• Prevention for this is by is Anionic salt administration – enhances Ca resorption from bone and Ca absorption from GIT
• Dogs need High quality nutritionally balanced diet for pregnant and lactating bitches

The Dry Period

• A Minimum of 60 days is required prepartum for gland involution and recovery, involving Rapid engorgement and associated inflammation for a few days and Reduction in the metabolic activity of the cells in addition to Degeneration and loss of alveolar cells
• Pregnant cows will only completely involute if they are <7months at the time of drying off, leaving Only the duct system remains after complete involution

The Neanate Immune System

• Consists of a 1st line of defence and second line of defence along with Acquired immunity
• 1st line of defence= Physical barrier, Acidic environments, Oils, and Enzymes
• 2nd line of deFence=Includes Cell mediated immunity, T-cell immunity and WBCs that are present at birth
• acquired immunity = non cellular/humoral immunity
• Maternal antibodies and immunoglobulins

How Neonates Acquire Immunity

• Immunitity is acquired within the first 24 hours when they receive colostrum, comprised of Immunoglobulins like IgG that is absorbed in the intestinal tract
• Failures occur if there is not enough colostrum consumed from a substandard source
• Or failure occurs with less that the required 800mg/dL IgG in colostrum

Failure of transfer of passive immunity

• There is a strong correlation between FPT and an increased risk of infection - including Septicaemia/Sepsis, Pneumonia, Joint ill, Navel ill, and Diarrhoea
• Prevention entails Ensure colostrum intake, Measure colostrum quality using a Brix refractometer and Identify at risk individuals

Neonatal Isoerythrolysis

• Born with normal innate immunity and Successful TRANSFER PASSIVE acquired immunity through normal colostrum intake
• Normal foal for first 6hrs up to 5 days
• After 6 hours: animals exhibit with lethargy, Yelllow or pale mucus membrane, Dark coloured urine, Elevated heart rate +/- heart murmur

Mare – Foal Blood Incompatibility

• Colostrum is transferred with ANTI – RBC antibodies
• These attack the red blood cells in the foals circulation causing HAEMOLYTIC ANAEΜΙΑ
• Reduces number of functional circulating RBCs
• Requires blood transfusion
• Mare without Aa or Qa RBC antigens are at risk, where this Usually happens in Aa or Qa negative pluriparous mares
• Can occur in mares who had previously had a blood transfusion
• Tested using Can test at risk foals with jaundiced foal test (JFT) where they can be fed an alternative source of colostrum until tested
• Treatment involved Removal of the dam/muzzling of foal if <24 hours to provide Supportive care with Fluids, Oxygen. Enteric nutrition along with Blood transfusion and Washed mare cells as a Universal blood donor in the form of a Standardbred gelding
• Prevent by blood testing broodmares for Aa and Qa RCB factors when selected to Breed mare to known tested stallions and with Aa and Qa negative animals Muzzle foal and check incompatibility with JFT If positive JFT milk mare out for 24 hours, supplement foal with alternative colostrum