INTRODUCTION
Placental Inflammation and Intrauterine Infection - the character of a given inflammatory infiltrate and pattern of involvement determine the etiology and its clinical significance.
ETIOLOGY OF PLACENTAL INFECTIONS
CAUSATIVE ORGANISMS
Bacteria
Fusobacterium,
Ureaplasma urealyticum,
Mycoplasma hominis,
Gardnerella vaginalis,
Bacterioides and
Peptostreptococcus species.
Viruses
Candida
THE CONSEQUENCES OF INTRAUTERINE INFECTION AND INFLAMMATION
abortion,
stillbirth,
preterm birth(PTB),
fetal malformation,
active postnatal infection, and
LONG TERM SEQUELAE
Acute Chorioamnionitis (ACA)
The term ‘‘chorioamnionitis’’ describe a symptom complex suggestive of intrauterine infection charecterized by maternal fever , uterine tenderness, or elevated white blood cell count correlates poorly with histologic chorioamnionitis.
ROUTE OF INFECTION
most common mode of infection is ascending infection from vagina/ cervix.
endometritis
Contiguous mode of spread of organisms occurs from the fallopian tubes or intestines or appendix or urinary bladder.
ASCENDING INFECTIONS
Rarely organisms seen in HPE sections Exceptions
Candida
FUSOBACTERIUM GRAM STAIN
Beta hemolytic streptococci
HEMATOGENOUS SPREAD
BACTERIA –Listeria monocytogenes, Treponema pallidum.
PARASITE – Toxoplasma gondi.
MECHANISM INVOLVED IN ACUTE CHORIOAMNIONITIS
GROSS PATHOLOGY OF ACUTE CHORIOAMNIONITIS VS NORMAL PLACENTA
ACUTE CHORIOAMNIONITIS GROSS PATHOLOGY - opaque , obscured by the inflammatory exudate , with loss of normal bluish tinge.
CHRONIC CHORIOAMNIONITIS - yellowish hue , membranes are more friable , decidua capsularis- detached and hemorrhagic.
SEVERE CHORIOAMNIOTIS
MATERNAL RESPONSE
The initial response is maternal, manifested by the migration of maternal polymorphonuclear cells from blood vessels and from the inter villous space in the membranous decidua.
ACUTE CHORIOAMNIONITIS
NECROTIZING CHORIOAMNIONITIS
GRADING THE SEVERITY
MATERNAL/INITIAL RESPONSE SUMMARY OF EVENTS
FETAL INFLAMMATORY RESPONSE:
Fetus response to amniotic infection depends on-gestational age and status of the fetal immune system
A fetal leukocytic response is frequently absent in gestational age less than 20 weeks and in fetuses weighing less than 500 g.
PHOTOMICROGRAPH SHOWS INITIAL FETAL RESPONSE - UMBILICAL PHLEBITIS (STAGE1).
FETAL INFLAMMATORY RESPONSE (STAGE 2) - ARTERITIS.
CHORIONIC VASCULITIS
Photomicrograph shows cresentic band of polymorphonuclear cells around umbilical vessel.
FETAL RESPONSE -GRADING
SEVERE GRADE OF FETAL RESPONSE showing chorionic vasculitis with thrombi.
HIGH POWER VIEW OF THE SAME (CHORIONIC VASCULITIS WITH THROMBI )
FETAL INFLAMMATORY RESPONSE SYNDROME (FIRS).
Fetus response to amniotic
infection depends on-gestational age and status of the fetal immune system
A fetal leukocytic response
is frequently absent in gestational age less than 20 weeks and in fetuses weighing
less than 500 g.
CONSEQUENCES
1. CEREBRAL PALSY - damage directly via a toxic effect on white matter indirectly by activating endothelium and microglia resulting in thrombosis or increased vascular permeability.
2. Periventricular leucomalacia
3. Intraventricular hemorrhage
4. Neonatal infection/ sepsis
5. Preterm birth (PTB)
SUBACUTE CHORIOAMNIONITIS
Photomicrograph shows massive infiltrate with acute and chronic inflammatory cells and single cell necrosis.
Subacute chorioamnionitis is characterized by a - mixed inflammatory infiltrate of degenerating neutrophils, mono nuclear cells are concentrated in the upper chorion.
This is because of ongoing repetitive and low grade infection.
The mother may give history of repetitive episodes of vaginal bleeding.
CHRONIC CHORIOAMNIONITIS
rare enitity , an inflammatory infiltrate occurring in the same distribution as ACA - composed of chronic inflammatory cells out of which small mature lymphocytes predominate, but histiocytes , plasma cells, and rarely large lymphoid cells and immunoblasts are seen admixed with them.
The inflammatory infiltrate is focal and typically mild and confined to the membranes , but rarely, the large fetal blood vessels of the chorionic plate and umbilical cord shows signs of chronic inflammation.
And frequently shows the features of villitis and occasionally by chronic or sub acute necrotizing funisitis.
Photomicrograph from a case Chronic Chorioamnionitis showing predominatly small lymphocytes.
VILLITIS
inflammation/ infection of villous parenchayma.
Table showing types of villitis , composition , distribution and severity of villits.
Photomicrograph from a case of VILLITIS show extensive abnormally agglutinated villi.
Photomicrograph shows Necrotizing villitis.
Photomicrograph showing non necrotizing villitis.
Photomicrograph of Granulomatous villitis.
VILLITIS OF UNKNOWN ETIOLOGY
Villitis, inflammation of the villous parenchyma is almost never due to documented infection. No causative organism has been identified.negative maternal history.
There is no seasonal or geographic pattern of occurrence and no neonatal inflammatory response.
No history of congenital infections.
pathology
non- infectious - maternal immune response in fetal tissue (host versus graft reaction) ,the villous inflammatory cells as CD8 positive maternal T lymphocytes is supporting.
hematogenous route of infection results in “infectious villitis”
features pointing to infectious etiology
clinical history
active, and resolving , healed area- active chronic inflammation
prominent fibrosis
association with acute chorioamnionits.
Photomicrograph shows Active Chronic Villitis with intervillositis and villous necrosis.
VILLOUS INFLAMMATION GRADED BY EXTENT
confirmation with special stains ,molecular techniques ,maternal/ infant serology and clinical history .
CLINICAL SIGNIFICANCE
MILD VUE (VILLITIS OF UNKNOWN ETIOLOGY )- third trimester placenta - no effect.
VUE with fetal obliterative vasculopathy Inflammatory obliteration of stem villous vessels with downstream fibrotic avascular villi has been associated with neurologic impairment.
SEVERE VUE (VILLITIS OF UNKNOWN ETIOLOGY ) --impaired placenta function
- results in IUGR, IUD, Cerebral Palsy and pre- term labour.
VUE (VILLITIS OF UNKNOWN ETIOLOGY )WITH FETAL OBLITERATIVE VASCULOPATHY
SPECIFIC INFECTIOUS VILLITIDES
TOXOPLASMA
OTHERS
RUBELLA
CYTOMEGALOVIRUS
HERPES SIMPLEX
TOXOPLASMA GONDII
Congenital infection acquired from mother ingesting food contaminated with infected cat feces.
CONGENITAL TOXOPLASMOSIS -HYDROCEPHALUS
A TOXOPLASMA CYST IS PRESENT IN THIS CHRONICALLY INFLAMED VILLUS.
Tachyzoite of T.gondii- PAS
UNDER FLORESCENT MICROSCOPY
CMV placentitis -placenta - normal, small (in cases of IUGR) or large and edematous pattern- Lymphoplasmacytic villitis , Necrotizing villitis , Vessel occlusion ,Stromal hemosiderin ,Viral inclusions – 20%.
Lymphoplasmacytic villitis
CYTOMEGALOVIRUS INFECTION - BELOW PHOTOMICROGRAPH SHOWS PLASMA CELLS ARE THE CHARACTERISITIC FINDING AND CLUE TO THE DIAGNOSIS
CYTOMEGALOVIRUS INFECTION - VIRAL INCLUSIONS ( SEEN APPROXIMATELY IN 20% OF CASES ).
CYTOMEGALOVIRUS - ANTIBODY
HERPES SIMPLEX VIRUS INFECTION
spontaneous abortion and congenital malformation- primary infection in the first 20 weeks of pregnancy.
MODE OF TRANSMISSION -hematogenous spread
Villous necrosis and agglutination, lymphocytic villitis, and fibrinoid necrosis of villous vessels.
Acute necrotizing and chronic lymphoplasmacytic chorioamnionitis,amnionic viral inclusions, and funisitis.
VARICELLA ZOSTER INFECTION
In congenital infection, the placenta may show small, grossly visible necrotic foci in the villi and
LIGHT MICROSCOPY
lymphoplasmacytic infiltrates, and granulomas with giant cells , viral inclusions ,villous necrosis, vascular occlusion.
TREPONEMA PALLIDUM
Infected placentas tend to be large and bulky- syphilis
GROSS PICTURE OF LARGE BULKY PLACENTA IN SYPHILIS
LIGHT MICROSCOPY
villous stroma is cellular , comprises of lymphoplasmacytic infiltrate ,Subendothelial and perivascular fibrosis is also seen.
characteristic changes in villous vessels- occlusion,luminal narrowing and recanalization.
Necrotizing funisitis is also seen.
LISTERIA MONOCYTOGENES
intrauterine infection, spontaneous abortion, prematurity,and neonatal sepsis
neonatal sepsis
early type of infection shows granulomatosis infantisepticum in neonatal period.
late type of infection shows meningitis in perinatl period.
GROSS PATHOLOGY
The placenta is usually normal on gross examination but occasionally it may contain small yellow-white necrotic foci or rarely it may contain larger abscesses or infarcts , so careful examination is the need for correct diagnosis and management.
The amnionic fluid is frequently meconium-stained.
LIGHT MICROSCOPY
Neutrophils aggregate in the intervillous space.
Entrapped villi undergo necrosis forming abscesses.
PARVOVIRUS B19
‘‘fifth disease,’’ or erythema infectiosum- neonates/ children
non immune hydrops- fetus.
GROSS PATHOLOGY
The placentas are large, pale, and friable.
LIGHT MICROSCOPY
polymorphonuclear cells seen accumulating eccentrically in the villous stroma beneath the trophoblast.
Erythrocytes in the villous capillaries show central nuclear eosinophilic inclusions with peripheral chromatin condensation.
HUMAN DEFICIENCY VIRUS
Transmitted to the fetus transplacentally, at the time of Labour, or post partum (through breastfeeding).
In utero transmission can be confirmed by the detection of virus in infants by PCR or co- culture within 48 h of birth.
No histopathologic lesions directly attributable to HIV have been described in the placenta.
Specifically, no villitis.
Placentas from seropositive mothers show increased incidence of ACUTE CHORIOAMNIONITIS.
PLASMODIUM VIVAX
Placental malaria - complication of malaria in pregnancy in areas of stable transmission.
Frequent and severe in primigravidae.
Malaria in pregnancy is thought to be due to failure in systemic or regional immunological response .
LIGHT MICROSCOPY
Presence of parasites and leucocytes within the intervillous spaces.
Pigment within macrophages, fibrin deposits and trophoblasts, proliferation of cytotrophoblastic cells , thickening of the trophoblastic basement membrane.
CHRONIC HISTIOCYTIC INTERVILLOSITIS
Idiopathic diffuse uniform infiltration of the intervillous space by monocyte– macrophages accompanied by variable perivillous fibrin deposition.
Placentas are often small for gestational age.
The light microscopic features are very similar to those in placental malaria, can be distinguished by the absence of malarial pigment.
Assosciated with -first-trimester recurrent spontaneous abortions , IUGR (INTRA UTERINE GROWTH RETARDATION), IUFD( INTRA UTERINE FETAL DEMISE).
CHRONIC DECIDUITIS
Defined as -
the presence of plasma cells or diffuse chronic inflammation with presence or absence of plasma cells (with or without plasma cells) in the decidua basalis defines chronic deciduitis.
The chronic inflammatory response may be directed against maternal or fetal antigens or microorganisms.
Chronic deciduitis is often associated with ACA in preterm placentas and with VUE at term.
EOSINOPHILIC/T CELL VASCULITIS
Eosinophilic/T cell vasculitis is a chronic inflammatory condition comprises of fetal eosinophils and lymphocytes involving chorionic plate and large stem villous vessels.
PREGNANCY INDUCED HYPERTENSION
• Definition
• Hypertension in pregnancy
• Pathophysiology of PIH
• Gross features of placenta in PIH
• Histopathological changes in placenta in PIH
PIH is defined as –
if systolic blood pressure (SBP) >140 mmHg and diastolic blood pressure (DBP) >90 mmHg in a previously normotensive women after 20 weeks of gestational age with or absence of proteinuria is PREGNANCY INDUCED HYPERTENSION.
PIH is also defined as new onset proteinuria ( ≥ 300 mg/24 hours) in hypertensive women who exhibit no proteinuria before 20 weeks gestation.
but both symptoms normalize by 12 weeks postpartum.
HYPERTENSION DISORDERS IN PREGNANCY
TERMINOLOGY
Gestational Hypertension (GH)
Gestational Hypertension is blood pressure ≥ 140/90 mmHg for the first time during pregnancy (after 20 weeks gestation), but without proteinuria
Eclampsia (E)
Eclampsia is defined as the onset of convulsions in a woman with PIH that cannot be defined by other causes. The Generalized seizures may appear before labour, during labour , or postpartum .
HELLP syndrome is a type of severe preeclampsia with a triad of findings including hemolysis, elevated liver enzymes, and thrombocytopenia.
CLASSIFICATION
BY SEVERITY
CLASSIFICATION BY ONSET
EARLY ONSET
PIH –
EARLY ONSET
PIH is defined as PIH that appears before 32 weeks gestational age.
LATE ONSET
PIH-
LATE ONSET
PIH is defined as PIH that appears after 32 weeks gestational age.
PATHOPHYSIOLOGY
IN PIH
PLACENTAL
IMPLANTATION WITH ABNORMAL TROPHOBLASTIC INVASION OF UTERINE VESSELS
The
maternal spiral arteries that supply
maternal blood to the placenta should expand in order to accommodate the growing placentofetal unit.
It usually occurs
simultaneously with trophoblastic
remodeling of spiral arteries.
A failure
of this process results in –
decidual
vasculopathy,
reduced
maternal flow,
placental
ischemia, and
the
maternal syndrome of preeclampsia.
NORMAL PLACENTA
PLACENTA IN PREGNANCY INDUCED HYPERTENSION
PATHOPHYSIOLOGY OF PREECLAMPSIA
GENERALIZED MATERNAL ENDOTHELIAL DYSFUNCTION
ABNORMAL PLACENTAS ARE ASSOCIATED WITH PREECLAMPSIA
abnormal
placentas associated with pre eclampsia include small placenta and large
placenta.
a)SMALL
PLACENTA WITH DECIDUAL VASCULOPATHY – most common
- maternal
vascular underperfusion
- thin
umbilical cord.
b)LARGE
PLACENTA - diabetes mellitus , placental
hydrops( immune or non immune ) , multiple gestations and vesicular mole.
A
DIFFERENCE IN THE SIZE OF NORMAL (LEFT) AND PRE-ECLAMPTIC PLACENTAE (RIGHT)
CROSS
SECTIONS OF AN ECLAMPTIC PLACENTA SHOWING MULTIPLE PALE AND RED INFARCTS
LIGHT
MICROSCOPY
Smooth
muscle - hypertrophy of smooth muscle is seen
Spiral arteriole
– atheromatous changes are seen.
Increased
number of syncytial knots
There will
be hypoplasia of distal villi.
Placental
infarction
Microscopic
necrosis of villi, which looks like ghost villi and fibrin found surrounding them.
Decidual NK
cells, can be highlighted by CD56 .
PHOTOMICROGRAPH SHOWING ATHEROSIS OF SPIRAL ARTERIES
PHOTOMICROGRAPH SHOWING INCREASE SYNCYTIAL KNOTS
 |
| seizures,cerebral edema, cerebral hemorrhage and stroke |
 |
| hepatic failure , hepatic rupture and subcapsular hemorrhage |
 |
| renal failure , oliguria and proteinuria |
 |
| DIC ,HELLP SYNDROME. |
 |
| PULMONARY EDEMA |
No comments:
Post a Comment