Uterine diseases. Essential guides on cattle farming

Presentation brochure

ESSENTIAL G IDES ON CATTLE FARMING

Uterine diseases Servet (División de Grupo Asís Biomedia S.L.) Centro Empresarial El Trovador, planta 8, oficina I Plaza Antonio Beltrán Martínez, 1 • 50002 Zaragoza (España) Tel.: +34 976 461 480 • Fax: +34 976 423 000 • www.grupoasis.com

Luis Ángel Quintela Arias Juan José Becerra González Pedro García Herradón

The publishing strength of Grupo AsĂ­s Editorial Servet, a division of Grupo AsĂ­s, has become one of the reference publishing companies in the veterinary sector worldwide. More than 15 years of experience in the publishing of contents about veterinary medicine guarantees the quality of its work. With a wide national and international distribution, the books in its catalogue are present in many different countries and have been translated into nine languages to date: English, French, Portuguese, German, Italian, Turkish, Japanese, Russian and Chinese.

Its identifying characteristic is a large multidisciplinary team formed by doctors and graduates in Veterinary Medicine and Fine Arts, and specialised designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design and excellent contents.

Servet works with the most renowned national and international authors to include the topics most demanded by veterinary surgeons in its catalogue. In addition to its own works, Servet also prepares books for companies and the main multinational companies in the sector are among its clients.

Essential guides on cattle farming

Uterine diseases

ESSENTIAL G IDES ON CATTLE FARMING

Uterine diseases Luis Ángel Quintela Arias Juan José Becerra González Pedro García Herradón

Authors: Luis Ángel Quintela Arias,

Juan José Becerra González, Pedro García Herradón.

Format: 17 x 11 cm.

Number of pages: 74.

Number of images: 65.

Binding: paperback, wire-o.

RETAIL PRICE

35 €

Atlas focused on the main uterine diseases affecting bovine species, with a practical and visual approach, and written by renowned authors with a wide experience in the study of these conditions and their management and control in the field. All the diseases included in this work (clinical metritis, clinical/subclinical endometritis, pyometra...) have been thoroughly reviewed to help readers better understand them and include the most updated information, emphasizing diagnosis and treatment. Numerous graphic resources (images, graphs, tables, flow charts) have been included to complement the information provided and make the contents more understandable and accessible to readers.

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Uterine diseases

Presentation of the book Uterine diseases in dairy cows include several conditions as puerperal metritis, clinical metritis, clinical endometritis and subclinical endometritis. These diseases are highly prevalent in high-producing dairy cows, being related to extended interval to pregnancy, decreased pregnancy per artificial insemination, increased culling and economic losses.

Metritis entails a fetid red-brownish uterine discharge within the first 21 days in milk, affecting about 20 % of lactating dairy cows, while clinical endometritis implies a purulent uterine discharge after 21 days in milk, mucopurulent after 26 days in milk, affecting about 20 % of lactating dairy cows. On the other hand, subclinical endometritis is the most prevalent of all uterine diseases.

According to this situation, an updated review has been carried out including numerous graphic resources (images, tables, illustrations, etc.) and precise information in order to depict the topic. The authors, renowned and prestigious experts with a wide experience in this field, have mentioned and developed the most highlighted features of these diseases, as well as indicating the main control measures to prevent them as much as possible.

The authors Luis à ngel Quintela Arias Professor at the Department of Animal Pathology of the Faculty of Veterinary Medicine of Lugo, University of Santiago de Compostela (USC). Degree in Veterinary Medicine in 1989 and PhD in 1996 from the USC. He teaches Reproduction and Obstaetrics, Veterinary Clinical Ultrasonography and Dairy Cattle Medicine to undergraduate veterinary students, and Ultrasonography Applied to Cattle Reproduction to master’s degree students. Member of the Spanish Association for Animal Reproduction (AERA) and Spanish Association of Specialists in Bovine Medicine (ANEMBE). Consultant in reproduction for a pharmaceutical company since 2007. He has participated in or directed different research projects and collaborated with the R&D departments of several pharmaceutical companies. He is the author/co-author of more than 90 articles published in scientific journals and magazines, more than 120 papers for Spanish and international congresses, four books or chapters of books and a licensed patent. Most of these works were published in the field of cattle reproduction.

Uterine diseases

Juan José Becerra González Professor at the Department of Animal Pathology of the Faculty of Veterinary Medicine of Lugo, University of Santiago de Compostela (USC). Degree in Veterinary Medicine in 1990 and PhD in 2003 from the USC. 14 years of experience as a veterinary practitioner in the field of cattle reproduction. Professor of Reproduction and Obstaetrics since 1995.

Member of the Spanish Association for Animal Reproduction (AERA). He has participated in numerous research projects. He is the author/co-author of more than 90 articles published in scientific journals and magazines and more than 120 papers for Spanish and international congresses. He has participated in the writing of five books or chapters of books and is also the co-author of a licensed patent. Most of his work has focused on cattle reproduction.

Professor at the Department of Animal Pathology of the Faculty of Veterinary Medicine of Lugo, University of Santiago de Compostela (USC). Degree in Veterinary Medicine in 1982 and PhD in 1988 from the University of León. He teaches Reproduction and Obstaetrics, Biotechnology of Animal Reproduction and Dairy Cattle Medicine to undergraduate veterinary students, and Biotechnology of Reproduction Applied to Domestic Animal Species to master’s degree students. He was a member of the Spanish Association for Animal Reproduction (AERA) Board of Directors and has directed numerous research projects.

He is the author/co-author of more than 90 articles published in scientific journals and magazines, over 120 papers for Spanish and international congresses, six books or chapters of books and a licensed patent. Most of these works were published in the field of cattle reproduction.

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Pedro García Herradón

Communication services Website Online visualisation of the sample chapter.

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ESSENTIAL G IDES ON CATTLE FARMING

Uterine diseases Luis Ángel Quintela Arias Juan José Becerra González Pedro García Herradón

Table of contents Introduction 1. Structure of the uterus

5. Diagnosis Aspects to be considered in the diagnosis of metritis

Macroscopic anatomy of the uterus

Early diagnosis of metritis

Microscopic anatomy of the uterus

Methods Traditional methods

2. Defence mechanisms of the uterus Anatomical barriers Chemical barriers Immune barrier Endocrine regulation Pathogenic agents

3. Classification Clinical metritis Endometritis Clinical endometritis Subclinical endometritis Purulent vaginal discharge (PVD) Cytological endometritis (CE)

Pyometra

4. Incidence

Ultrasonography Cytology Other methods

6. Predisposing factors Factors that determine the magnitude of bacterial contamination Factors that determine the capacity to eliminate bacterial contamination

7. Negative effects 8. Treatment Metritis Endometritis Pyometra

9. Prevention 10. Conclusions References

1

Structure of the uterus

Uterine diseases

Microscopic anatomy of the uterus Âť Endometrium: covered by cylindrical epithelial cells, which have microvilli on their apical border and are supported by a lamina propria formed by connective tissue. The submucosa is located under the lamina propria and is characterised by having many simple tubular or branched endometrial glands, disseminated throughout the whole endometrium, except at the caruncles. It also contains nerves as well as blood and lymphatic vessels. In addition to this base formed by stable cells, a population of migrating immune cells (polymorphonuclear neutrophils, monocytes, macrophages, T cells, B cells and plasma cells) also travel to the uterus from a common network.

8

Âť Myometrium: formed by two layers of smooth muscle fibres arranged in a circular fashion (internal) or longitudinal fashion (external).

Âť Perimetrium: layer of squamous epithelial cells that cover the external surface of the genital tract to form the peritoneal epithelium.

Structure of the uteruS Endometrium

Myometrium

Perimetrium

9

Epithelium

Submucosa Endometrial glands

Figure 3. Microscopic structure of the uterine wall.

Vessels

Round muscle fibres

Longitudinal muscle fibres

2

Defence mechanisms of the uterus

Uterine diseases

Endocrine regulation » Oestrogens increase the uterine blood flow and favour leukocyte migration towards the lumen of the organ, thus facilitating the phagocytosis of bacteria. Moreover, they increase the secretion of cervical and vaginal mucus and myometrial contractility.

» Progesterone causes a reduction in the uterine pH, which favours bacterial growth, reduces endometrial permeability and delays the migration of neutrophils towards the uterine lumen. In addition, it reduces the production of cervical mucus and myometrial contractility. It also has an anti-inflammatory action and reduces the synthesis of uterine proteins and the activity of neutrophils and lymphocytes. Moreover, it increases PGE2 levels, a substance known for its immunosuppressive activity.

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» Eicosanoids, represented by PGF2α and leukotriene B4, have a chemotactic effect: they favour

phagocytosis, stimulate the release of proinflammatory cytokines and promote the activity of lymphocytes and neutrophils.

» The elevated concentrations of corticoids at the time of calving increase the number of leukocytes (polymorphonuclear neutrophils, monocytes and macrophages) present in the endometrium, which then decreases in the following week due to the migration of the leukocytes towards the uterine lumen.

Defence mechanisms of the uterus

Ovary

Epithelium

Progesterone ↑ pH ↓ Permeability

Oestrogens Corticoids

13

↑ Permeability

↓ Activity

↑ Activity

Figure 5. Endocrine regulation of uterine defence mechanisms.

PGF2α Leukotriene B4

↑ PGE2 Stroma

3

Classification

Uterine diseases

Endometritis Clinical endometritis

a

b

Inflammation of the endometrium with purulent or mucopurulent discharge through the vagina, which is not accompanied by systemic clinical signs.

18

Figure 9. Observable signs in a cow with clinical endometritis: (a) abnormal secretion through the vulva and (b) presence of abnormal content in the uterine lumen.

ClassifiCation

Subclinical endometritis Inflammation of the endometrium with absence of clinical signs. It is characterised by an infiltrate of neutrophils, with or without some accumulation of exudate in the uterus, resulting in the complete lack of cervical discharge.

Figure 10. Observable signs in a cow with subclinical endometritis: (a) elevated percentage of polymorphonuclear neutrophils; (b) absence of abnormal content in the vagina; (c) absence of abnormal content in the lumen of the uterus and slightly thicker endometrium.

a

b

19

c

3

Classification

Uterine diseases

Purulent vaginal discharge (PVD) Purulent or mucopurulent discharge in the vagina.

Clinical endometritis

Cervicitis

20

PVD Nephritis Pyelonephritis Cystitis

Vaginitis

Figure 11. Different diseases that may cause PVD.

Figure 12. Only sign used to diagnose a PVD.

ClassifiCation

Cytological endometritis (CE)

a

Presence, in the uterine lumen, of neutrophils in an abnormal proportion.

Clinical endometritis 21

CE

b

Subclinical endometritis

Figure 13. Different diseases that may cause CE.

Figure 14. Only sign used to diagnose CE: (a) negative cytology result; (b) positive cytology result.

5

Diagnosis

Uterine diseases

Methods Table 3. Diagnostic methods according to the disease.

Disease

Clinical endometritis

Clinical signs

Images

Diagnostic methods

Gloved hand.

Local: abnormal uterine discharge that may flow towards the exterior when the cervix is open.

Metricheck®.

Speculum.

Ultrasound scan.

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Local: the cow does not apparently show

Subclinical endometritis

any clinical signs.

Cytology.

Increased number of polymorphonuclear

Ultrasound scan.

leukocytes (PMN) in the uterine lumen with no or little abnormal fluid.

Diagnosis Disease

Cytological endometritis

Clinical signs

Local: increased number of PMN with or without fluid in the uterus.

Images

Diagnostic methods

Cytology.

29

Gloved hand.

Purulent vaginal discharge

Local: abnormal secretion through the vagina, not necessarily accompanied by uterine disease.

Metricheck®.

Speculum.

Ultrasound scan.

5

Diagnosis

Uterine diseases

Traditional methods Table 4. Traditional diagnostic methods used in the field.

Methods

Signs to look for

Images

It is only useful when the

Diameter of the cervix.

Rectal examination

Vaginal examination/ Gloved hand

Comments

discharge is abundant.

Size and consistency of the

uterus.

Presence of discharge.

Ovarian structures.

The consistency varies depending

Presence of vaginal discharge.

It only informs about the presence

on the time of the cycle and the examination itself, which makes it difficult to reach a diagnosis.

Characteristics of the discharge:

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of abnormal discharge in the vagina, but not about its origin.

The type of discharge may give an idea of the predominant organisms.

Mucous.

Mucopurulent.

Purulent.

Foul-smelling.

Diagnosis Methods

Signs to look for

Images

Comments

Similar to using a gloved hand,

Metricheck®

although quicker to perform.

Information similar to that obtained with a gloved hand.

It must be disinfected between

one cow and another.

a

It allows the presence of

Information similar to that

Vaginoscope

obtained with a gloved hand.

(a) Absence of abnormal fluid in the vagina.

(b) Purulent exudate in the vagina.

b

abnormal exudate in the vagina to be confirmed and its characteristics to be determined.

On some occasions, its origin can be established if it is seen coming out of the cervix.

It must be disinfected between one cow and another.

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5

Diagnosis

Uterine diseases

Other methods Table 8. Diagnostic methods used on a less frequent basis in cattle, but useful in some situations.

Methods

Observable signs

Images

Comments

a

Degree of involvement of the

Relatively simple and

endometrium:

non-traumatic for the animal.

However, processing the samples and analysing them is laborious and requires qualified personnel.

Knowing the degree of involvement of the endometrium may give an idea of the cow’s fertility. The more involvement, the less fertile the cow.

Aspect of the epithelium.

Inflammatory cell infiltrate.

Biopsy

Degree of fibrosis.

Aspects of the endometrial

glands.

b

(a) Normal endometrium;

(b) affected endometrium, cystic ( ), dilated (+) glands and abundant fibrosis (blue).

38

Diagnosis Methods

Observable signs

Images

Comments

a

With a culture, it is possible

Presence and type of

microorganisms in the uterus.

Culture

(a) Culture result positive for

Trueperella pyogenes; (b) culture result positive for Escherichia coli.

b

to know whether the uterus is contaminated and the type of microorganisms responsible for the infection. An antibiogram can also be carried out, which allows the treatment to be adapted.

There are cases (many cases of subclinical endometritis and some of clinical endometritis) in which there are no microorganisms in the uterus.

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7

Negative effects

Uterine diseases

EndomEtritis

infEction

Bacteria

inflammation

Endo/exotoxins

Cytokines

46

Eicosanoids

Figure 19. Mechanisms through which endometritis affects reproduction.

Negative effects

Figure 20. Mechanism of action of uterine infectious/ inflammatory conditions on reproduction. Bacteria reach the uterus mainly through the cervix.

Once in the uterus, bacteria and some associated molecules (endo/exotoxins) are detected by means of TLRs. The innate immune system, which is the first barrier against infection, is then activated. Cytokines are released and attract PMN and PGE. Cytokines, PGE and endo/exotoxins act on different reproductive organs (hypothalamus, pituitary gland and ovaries), while bacteria cause the destruction of the epithelium by apoptosis.

Hypothalamus Pituitary gland

Ovary

Bacterial endo/exotoxins

Bacteria Bacterial endo/ exotoxins

47

Bacteria

TLR TLR

PGE

Bacteria

Cytokines

Blood vessel

PMN

7

Negative effects

Uterine diseases

cytokinEs and Eicosanoids

Effect on the hypothalamicpituitary gland axis

Effect on the ovary

Effect on the embryo

Reduced LH and FSH secretion

Intervention in follicle genesis, ovulation, luteinisation and luteolysis

Reduced viability of the embryo and conception rate

50

Figure 22. Effects of cytokines, released during inflammation, on reproduction.

Negative effects

Follicle development

Atresia and selection of a dominant follicle

Ovulation 51

TNFÎą

Figure 23. TNFÎą is a proinflammatory cytokine present in endometritis, which intervenes at different moments of the ovarian cycle.

Corpus luteum development

Luteal phase Gestation

Luteolysis

8

Treatment

Uterine diseases

Endometritis There is no consensus on what is the most effective treatment for endometritis.

Several authors indicate that > 75 % of cases of clinical endometritis in the postpartum period resolve spontaneously.

The ideal treatment should: Reduce pathogenic bacterial loads.

Improve the defence and recovery mechanisms of the uterus.

Slow down and reverse the effects caused by inflammation on fertility.

54

Table 11. Types of treatment of endometritis.

Antimicrobial substances

Hormonal substances

Intrauterine treatments.

PGF2α.

Systemic treatments.

Oestrogens.

Other treatments

Antiseptic agents, proteolytic enzymes, dextrose,

ozone, NSAIDs and vaccines.

TreaTmenT

Table 12. Intrauterine treatment of endometritis.

Intrauterine treatment

Achieve high concentrations of antimicrobials at the

site of the infection (endometrium).

A small penetration of these substance is achieved towards deeper areas of the uterus and other genital structures (vagina, cervix, ovaries and oviducts).

The use of numerous antimicrobial substances has been proposed: tetracyclines, penicillins, chloramphenicol, Lugol’s solution, gentamicin, spectinomycin, sulphonamides, nitrofurans, chlorhexidine, cephalosporins, etc.

Precautions

Some substances have a low activity under anaerobic

conditions and others are inactivated by the purulent material.

Be careful when combining several antibiotics as they may produce residues in milk.

Using antimicrobials that have not been designed for uterine administration may produce residues in milk.

Some substances may be irritating and cause necrosis of the endometrium due to coagulation.

Some antibiotics may be degraded by enzymes produced by germs.

Although many studies describe improvements in the treatment of infections with antimicrobials, few have demonstrated clear benefits on the improvement of reproductive efficiency.

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8

Treatment

Uterine diseases

Table 13. Antibiotics for the intrauterine treatment of endometritis.

Antibiotic Penicillins

Considerations Susceptible to penicillins.

They are not inactivated in the uterine environment.

Tetracyclines

Some degree of resistance of Bacteroides spp. and Trueperella pyogenes.

May cause necrosis of the endometrium due to coagulation.

Aminoglycosides

Reduced activity in anaerobic environments.

Sulphonamides

Low activity in the presence of purulent material.

Macrolides

More effective against Gram-positive germs.

Cephalosporins Quinolones

56

Resistance of Trueperella pyogenes.

Maintains its activity in the presence of pus and under anaerobic conditions.

Effective against Trueperella pyogenes.

Good spectrum of action and distribution.

TreaTmenT

Table 14. Systemic treatment of endometritis.

Considerations

Image

Use antibiotics that reach the

deeper parts of the uterine wall.

Bear the withdrawal period in

mind.

Be effective against the main

uterine pathogens (Trueperella pyogenes, Escherichia coli, Fusobacterium necrophorum, etc.).

Some antibiotics have a low activity under conditions of low oxygen tension and elevated amount of purulent material.

57

The publishing strength of Grupo AsĂ­s Editorial Servet, a division of Grupo AsĂ­s, has become one of the reference publishing companies in the veterinary sector worldwide. More than 15 years of experience in the publishing of contents about veterinary medicine guarantees the quality of its work. With a wide national and international distribution, the books in its catalogue are present in many different countries and have been translated into nine languages to date: English, French, Portuguese, German, Italian, Turkish, Japanese, Russian and Chinese.

Its identifying characteristic is a large multidisciplinary team formed by doctors and graduates in Veterinary Medicine and Fine Arts, and specialised designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design and excellent contents.

Servet works with the most renowned national and international authors to include the topics most demanded by veterinary surgeons in its catalogue. In addition to its own works, Servet also prepares books for companies and the main multinational companies in the sector are among its clients.

Presentation brochure

ESSENTIAL G IDES ON CATTLE FARMING

Uterine diseases Servet (División de Grupo Asís Biomedia S.L.) Centro Empresarial El Trovador, planta 8, oficina I Plaza Antonio Beltrán Martínez, 1 • 50002 Zaragoza (España) Tel.: +34 976 461 480 • Fax: +34 976 423 000 • www.grupoasis.com

Luis Ángel Quintela Arias Juan José Becerra González Pedro García Herradón