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PATHOPHYSIOLOGY
OF UTERINE INVOLUTION
AND ITS
THERAPEUTIC MANAGEMENT
Himanshu pandey
M.V.Sc Scholar
Div. Of Animal Reproduction
Roll No.- 16-M-GO-03
 Uterine involution is very much essential for a Normal
puerperal period
 Extension of puerperium may have detrimental effect on
reproductive performance of animal
 Disturbances during this period due to delay of uterine
involution reduce the lifetime reproductive and productive
efficiency
INTRODUCTION
 Reduction in size of genital tract is called involution
 Reduction is size of myofibrils from 400-750 µm on first day to
less than 200 µm over the next few days
(Gier et al., 1968)
 Diameter of the previously gravid horn halved by 5th days and its
length halved by 15 days
(Gier and Marion., 1968)
 Uterus is palpated per rectum by 8 and 10 days postpartum in
primiparae and pluriparae respectively
Involution
Days Postpartum Diameter of gravid uterine horn
Between 4-9 days 12-14 cm
By Day 14 7 cm
By day 25 2-4 cm
(Morrow et al., 1986)
(Gier and Marion, 1968)
Mechanism of uterine involution
Uterine contractions & physical shrinkage
Necrosis, and sloughing of the caruncles
Regeneration of the endometrium
(Sheldon et al., 2007)
Myometrial
contractions
Reduction in over
all size of uterus
Discharge of
fluid and debris
Compression
of uterine
vasculature
 Smooth muscles play an important role in the expulsion of the
uterine contents and reduction of the uterine size
(Bajcsy et al., 2005)
Uterine contraction & Physical shrinkage
Contraction
FREQ
after calving
8.9 per hour < 1 per hour Decrease to
Minimum
Time 12 h 42 h 48 hour
(Bajcsy et al., 2005)
 By 24 hours post calving decreases by over 50% of that present at 6
hours postpartum
(Burton, 1986)
 The force of uterine contraction can be augmented by the action of
some agonists such as oxytocin and PGF2α by promoting the action
potential and increasing the intracellular calcium concentration
(Shmygol et al., 2006)
 Normal healthy cows decline immediately after calving and start to
increase again from 24 to 36 h onwards
(Szenci et al ., 1994)
Reduce uterine activity Milk fever
Faccid uterus
Blood Ca2+ concentration
Severe Hypocalcaemia
Delayed involution
Experimentally
induced
(Noakes, 1989)
(Bajcsy, 2001)
OXYTOCIN IN MYOMETRIAL CONTRACTION
Directly Indirectly
Myometrial oxytocin
receptors
Release of pgf2α,
Paracrine route.(Ivell et al., 2000)
(Lye and Challis, 1989)
Myometrial contraction
 Marked decline in receptors in first day post partum
(Fuchs et al., 1992)
Oxytocin induced prostaglandin response also decreased with the
advancing of the postpartum period
` (Vecchio et al., 1990)
Uncomplicated puerperium RFM/Endometritis
 Massive release of PGF2α can be seen as PGFM for 2- 3 weeks
Involutrion- 21 days
Duratiom of pg release – 15 days
32 days
10 days
Role of Prostaglandins
Uncomplicated puerperium RFM/Endometritis
Involution 21 days 32 days
Duration of pg release 15 days 10 days
(Kindahl et al.,1999)
Decrease in total collagen accompanies the decrease in uterine
weight during involution.
(Woessner, 1980)
The average collagen content of the genital tract was found to rise
from a non-pregnant value of 84 g to 439 g at term
(Kaidi, 1989)
collagen
Pre-partum 5th day 24th
day
Molar ratios of urinary pyridinoline
and deoxypyridinoline
12.5 28 11.5
(Kaidi, 1991)
Early necrotic changes in septal mass of caruncle
Constriction of caruncular blood vessels and
Sloughing of necrotic material
Small blood vessels protrudes from surface of caruncles
(McEntee, 1990)
bw day 10 and 15
First 48 hour
Day two
Day five
• Proliferation of spindle shaped cells
 A necrotic leukocyte layer covers the endometrium
Necrosis, and sloughing of the caruncles
 Regeneration of inter caruncular area is completed by Day 8
 Complete re epitheliazation of caruncle 25 day onwards
 Acute phase protein increase rapidly after calving, reaching peak
at 1-3 days and decline to basal levels by 2-4 week.
(Sheldon et al., 2001)
 Majority of first dominant follicles (70- 82%),and ovulations, occur
in the ovary contralateral to the previously gravid horn
(Nation et al., 1999)
Larger follicles on the ipsilateral ovary are associated with better
fertility
(Bridges et al., 2000)
Appearance of large follicle in cyclic animals during early
postpartum period enhanced uterine involution
(Lohan et al., 2004)
Post partum cyclicity and involution
Age Primiparae
Season of year spring and summer
nutrition
Periparturient abnormalities-
Delayed return to cyclicity
 Dystocia
 Retained
placenta
 Hypocalcemia
 Ketosis
 Twin calves
 Metritis
(Maizon et al., 2004)
Factors influencing involution process
(Zhang et al., 2010)
(Noakes, 2009)
(Lohan et al., 2004)
 After parturition the vulva is relaxed and cervix dilated leads to
Contamination of the uterus by microbs
Chemokines
Nutrophils migration
 Cytoplasmic granules
 ROS
 NO
 Protease
 phospholipase Formation of Pus
TNFα, IL1 & IL6
Pyrexia & +ve feedback to nutrophils
Phagocyte die
Uterine infection delays involution
(Sheldon, 2007)
 Intrauterine administration
of most antiseptics and disinfectants
(Noakes et al., 2002)
 Impaired immune system
 Unhygienic conditions
Leukocyte phagocytic
activity
Uterine infection and inflammation can result in uterine atony
(Frazer, 2005)
Cont..
1
• Provide balanced nutrition
2
• Careful surveillence and assistance at the time of
calving
3
• Prevention of postpartum diseases
4
• Early diagnosis and treatment of postpartum
uterine abnormalities
Strategies for improving
uterine involution
 Diets rich in fermentable energy and diet with CP content higher
than 11%
(Curtis et al., 1985; Grummer, 1998)
 Fat supplementation (Staples et al., 1998)
 Protected source essential fatty acids (linoleic acid)
(Santos et al., 2003)
 High Calcium level 200 gm daily along with vitamin D
(Otterby et al., 1983)
 Vitamin A supplementation 30,000 to 50,000 IU daily
 Prepartum injection of Vit. E + selenium (Qureshi et al., 1997)
Good quality nutrition
Careful surveillance and assistance at the time of calving
Avoid
excessive
interventions
Regular
involution check-
ups
Interventions
related to
calving
 Using 50 IU of oxytocin i.m on the first day postpartum.
(Bajcsy et al., 2006)
 Methyl Ergometrin injection 5 mg directly after parturition (day 2)
(Alagar., 2016)
 Injection of GnRH at 13 to 14 days postpartum
(Foote and Rick, 1999)
 Single injection of PGF2α during 2nd or 3rd week or double
injection of PGF2α in 2nd week accelerate reproductive
performance
(Elsheikh and Elzubeir, 2005)
 Indigenous herbal preparations
 Uterotone @ 100-125 ml
 Exapar @100 ml initial dose followed by 50 ml bid
Prevention of postpartum diseases
Early diagnosis and treatment of postpartum
uterine abnormalities
Retained placenta- Retain for more than 24 hr
Rx
 Oxytocine 20 IU three to four times daily
(Youngquist and Threlfall, 2007)
 Manual removal after 24 hour
 Antibiotics systematically and NSAID’S in fever
 Indigenous preparations- Harera , uterotone etc
 Calcium boroguconate (if associated with milk fever)
 Collagenase therapy (Elier et al., 1993)
Precaution
 Manual removal (fever) & use of glucocorticoids
Metritis
Puerperal metritis- Enlarged uterus + fetid watery red brown
discharge + systemic sign within 21 days
Rx
 Systemic antibiotics
 NSAIDS
 Antihistaminics
Clinical metritis- Enlarged uterus purulent discharge + no systemic
sign within 21 days
• Systemic antibiotics.
• Uterine lavage
Clinical endometritis– Purulent discharge (50% pus) 21 days or
more after
 Intrauterine antibiotics
 Pgf2 alpha (if CL is present) (Sheldon, 2004)
conclusion
 The main aim of any farm is to obtain one calf a year for this
this proper reproductive management is required
 Puerperium is the period in which animal is most susceptible
for the disease, And involution of uterus is very much
required for the timely breeding of animal
 The prolongation of involution in cow depend on the degree
of infection and damage to endometrium and then clinical
uterine involution can be prolonged 50 to 60 days
 But if proper care is provided in peripartum period like
proper feeding, hygienic practice and other preventive
measures, the chances of delayed uterine involution can be
minimize.
PATHOPHYSIOLOGY AND MANAGEMENT OF UTERINE INVOLUTION

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PATHOPHYSIOLOGY AND MANAGEMENT OF UTERINE INVOLUTION

  • 1. PATHOPHYSIOLOGY OF UTERINE INVOLUTION AND ITS THERAPEUTIC MANAGEMENT Himanshu pandey M.V.Sc Scholar Div. Of Animal Reproduction Roll No.- 16-M-GO-03
  • 2.  Uterine involution is very much essential for a Normal puerperal period  Extension of puerperium may have detrimental effect on reproductive performance of animal  Disturbances during this period due to delay of uterine involution reduce the lifetime reproductive and productive efficiency INTRODUCTION
  • 3.  Reduction in size of genital tract is called involution  Reduction is size of myofibrils from 400-750 µm on first day to less than 200 µm over the next few days (Gier et al., 1968)  Diameter of the previously gravid horn halved by 5th days and its length halved by 15 days (Gier and Marion., 1968)  Uterus is palpated per rectum by 8 and 10 days postpartum in primiparae and pluriparae respectively Involution
  • 4. Days Postpartum Diameter of gravid uterine horn Between 4-9 days 12-14 cm By Day 14 7 cm By day 25 2-4 cm (Morrow et al., 1986) (Gier and Marion, 1968)
  • 5. Mechanism of uterine involution Uterine contractions & physical shrinkage Necrosis, and sloughing of the caruncles Regeneration of the endometrium (Sheldon et al., 2007)
  • 6. Myometrial contractions Reduction in over all size of uterus Discharge of fluid and debris Compression of uterine vasculature  Smooth muscles play an important role in the expulsion of the uterine contents and reduction of the uterine size (Bajcsy et al., 2005) Uterine contraction & Physical shrinkage
  • 7. Contraction FREQ after calving 8.9 per hour < 1 per hour Decrease to Minimum Time 12 h 42 h 48 hour (Bajcsy et al., 2005)  By 24 hours post calving decreases by over 50% of that present at 6 hours postpartum (Burton, 1986)  The force of uterine contraction can be augmented by the action of some agonists such as oxytocin and PGF2α by promoting the action potential and increasing the intracellular calcium concentration (Shmygol et al., 2006)
  • 8.  Normal healthy cows decline immediately after calving and start to increase again from 24 to 36 h onwards (Szenci et al ., 1994) Reduce uterine activity Milk fever Faccid uterus Blood Ca2+ concentration Severe Hypocalcaemia Delayed involution Experimentally induced (Noakes, 1989) (Bajcsy, 2001)
  • 9. OXYTOCIN IN MYOMETRIAL CONTRACTION Directly Indirectly Myometrial oxytocin receptors Release of pgf2α, Paracrine route.(Ivell et al., 2000) (Lye and Challis, 1989) Myometrial contraction  Marked decline in receptors in first day post partum (Fuchs et al., 1992) Oxytocin induced prostaglandin response also decreased with the advancing of the postpartum period ` (Vecchio et al., 1990)
  • 10. Uncomplicated puerperium RFM/Endometritis  Massive release of PGF2α can be seen as PGFM for 2- 3 weeks Involutrion- 21 days Duratiom of pg release – 15 days 32 days 10 days Role of Prostaglandins Uncomplicated puerperium RFM/Endometritis Involution 21 days 32 days Duration of pg release 15 days 10 days (Kindahl et al.,1999)
  • 11. Decrease in total collagen accompanies the decrease in uterine weight during involution. (Woessner, 1980) The average collagen content of the genital tract was found to rise from a non-pregnant value of 84 g to 439 g at term (Kaidi, 1989) collagen Pre-partum 5th day 24th day Molar ratios of urinary pyridinoline and deoxypyridinoline 12.5 28 11.5 (Kaidi, 1991)
  • 12. Early necrotic changes in septal mass of caruncle Constriction of caruncular blood vessels and Sloughing of necrotic material Small blood vessels protrudes from surface of caruncles (McEntee, 1990) bw day 10 and 15 First 48 hour Day two Day five • Proliferation of spindle shaped cells  A necrotic leukocyte layer covers the endometrium Necrosis, and sloughing of the caruncles
  • 13.  Regeneration of inter caruncular area is completed by Day 8  Complete re epitheliazation of caruncle 25 day onwards  Acute phase protein increase rapidly after calving, reaching peak at 1-3 days and decline to basal levels by 2-4 week. (Sheldon et al., 2001)
  • 14.  Majority of first dominant follicles (70- 82%),and ovulations, occur in the ovary contralateral to the previously gravid horn (Nation et al., 1999) Larger follicles on the ipsilateral ovary are associated with better fertility (Bridges et al., 2000) Appearance of large follicle in cyclic animals during early postpartum period enhanced uterine involution (Lohan et al., 2004) Post partum cyclicity and involution
  • 15. Age Primiparae Season of year spring and summer nutrition Periparturient abnormalities- Delayed return to cyclicity  Dystocia  Retained placenta  Hypocalcemia  Ketosis  Twin calves  Metritis (Maizon et al., 2004) Factors influencing involution process (Zhang et al., 2010) (Noakes, 2009) (Lohan et al., 2004)
  • 16.  After parturition the vulva is relaxed and cervix dilated leads to Contamination of the uterus by microbs Chemokines Nutrophils migration  Cytoplasmic granules  ROS  NO  Protease  phospholipase Formation of Pus TNFα, IL1 & IL6 Pyrexia & +ve feedback to nutrophils Phagocyte die Uterine infection delays involution (Sheldon, 2007)
  • 17.  Intrauterine administration of most antiseptics and disinfectants (Noakes et al., 2002)  Impaired immune system  Unhygienic conditions Leukocyte phagocytic activity Uterine infection and inflammation can result in uterine atony (Frazer, 2005) Cont..
  • 18. 1 • Provide balanced nutrition 2 • Careful surveillence and assistance at the time of calving 3 • Prevention of postpartum diseases 4 • Early diagnosis and treatment of postpartum uterine abnormalities Strategies for improving uterine involution
  • 19.  Diets rich in fermentable energy and diet with CP content higher than 11% (Curtis et al., 1985; Grummer, 1998)  Fat supplementation (Staples et al., 1998)  Protected source essential fatty acids (linoleic acid) (Santos et al., 2003)  High Calcium level 200 gm daily along with vitamin D (Otterby et al., 1983)  Vitamin A supplementation 30,000 to 50,000 IU daily  Prepartum injection of Vit. E + selenium (Qureshi et al., 1997) Good quality nutrition
  • 20. Careful surveillance and assistance at the time of calving Avoid excessive interventions Regular involution check- ups Interventions related to calving
  • 21.  Using 50 IU of oxytocin i.m on the first day postpartum. (Bajcsy et al., 2006)  Methyl Ergometrin injection 5 mg directly after parturition (day 2) (Alagar., 2016)  Injection of GnRH at 13 to 14 days postpartum (Foote and Rick, 1999)  Single injection of PGF2α during 2nd or 3rd week or double injection of PGF2α in 2nd week accelerate reproductive performance (Elsheikh and Elzubeir, 2005)  Indigenous herbal preparations  Uterotone @ 100-125 ml  Exapar @100 ml initial dose followed by 50 ml bid Prevention of postpartum diseases
  • 22. Early diagnosis and treatment of postpartum uterine abnormalities Retained placenta- Retain for more than 24 hr Rx  Oxytocine 20 IU three to four times daily (Youngquist and Threlfall, 2007)  Manual removal after 24 hour  Antibiotics systematically and NSAID’S in fever  Indigenous preparations- Harera , uterotone etc  Calcium boroguconate (if associated with milk fever)  Collagenase therapy (Elier et al., 1993) Precaution  Manual removal (fever) & use of glucocorticoids
  • 23. Metritis Puerperal metritis- Enlarged uterus + fetid watery red brown discharge + systemic sign within 21 days Rx  Systemic antibiotics  NSAIDS  Antihistaminics Clinical metritis- Enlarged uterus purulent discharge + no systemic sign within 21 days • Systemic antibiotics. • Uterine lavage Clinical endometritis– Purulent discharge (50% pus) 21 days or more after  Intrauterine antibiotics  Pgf2 alpha (if CL is present) (Sheldon, 2004)
  • 24. conclusion  The main aim of any farm is to obtain one calf a year for this this proper reproductive management is required  Puerperium is the period in which animal is most susceptible for the disease, And involution of uterus is very much required for the timely breeding of animal  The prolongation of involution in cow depend on the degree of infection and damage to endometrium and then clinical uterine involution can be prolonged 50 to 60 days  But if proper care is provided in peripartum period like proper feeding, hygienic practice and other preventive measures, the chances of delayed uterine involution can be minimize.