Female Repro Patho 3 Flashcards
What are the disorders of early pregnancy (2) ?
Spontaneous Abortion
Ectopic Pregnancy
What is Spontaneous Abortion?
Loss of pregnancy within __ weeks of gestation without ___?
Most occur within __ Weeks?
Loss of pregnancy within 20 weeks of gestation without outside intervention
Most occur within 12 Weeks
How common is spontaneous abortion?
15% of pregnancies and additional 20% abort without notice (don’t even know baby was there)
What are the causes of spontaneous abortion?
Uterine defects: fibroids and polyps
Endocrine factors
Systemic: HTN and Diabetes
Fetal Chromosomal Abnormalities
Infections: TORCH
When to do chromosomal analysis?
Habitual or recurrent abortions → spontaneous loss of three or more pre-viable pregnancies
Malformed foetus
What is ectopic pregnancy?
Implanation of fetus at any site other than normal intrauterine location (1:150 pregnancies)
What are some prediposing factors of ectopic pregnancy? (many, know a few)
- Chronic salpingitis (gonoccocal) → obstruction → tubo-ovarian masses/hydrosalpinx/ hydrosalpinx follicularis
- Peritubal adhesions (appendicitis)
- Leiomyomas → most common benign neoplasms → worsen from progesterone and pregnancy → grow due to nuclear oestrogen receptor but regress when postmenopause
- Previous surgery
- Benign cysts and tumours of tube
- IUCD
What are some clinical features of ectopic pregnancy?
- Amenorrhoea 6-8 weeks
- Abdominal pain
- Vaginal bleeding
- Rupture leading to Hemorrhagic shock (Hematosalpinx, Hemoperitoneum)
- Tubal abortion → contents of pregnancy expelled into abdominal cavity where it can be reabsorbed → spontaneous regression of pregnancy
How to diagnose ectopic pregnancy?
hCG titres -> elevated in normal and ectopic pregnancy
Pelvic ultrasound → swelling of tubes appreciated
Endometrial biopsy -> no evidence of pregnancy in endometrial cavity except secretory changes
Sites of ectopic pregnancy
> 50% may appear normal looking but are actually pathogenic
90% within tubes, some can be ovarian, some can be abdominal
What are the disorders of late pregnancy? (3)
Placental inflammations/infections
Toxemias
Placental abnormalities
What are the 3 types of placental inflammation? (Think Placenta, Membranes, Umbilical cord)
Villitis (placenta)
Chorioamnionitis (chorion and amnion membranes)
Funisitis (umbilical cord)
What are the two types of infections you can get in placental infection/inflammation?
Ascending infections
Haematogeneous infections
Which type of infection is more common for placental infections (ascending or haematogeneous)
Ascending
What are the 4 different types of Ascending infections and examples?
STD (Chlamydia, Syphilis)
Viral (Rubella, CMV)
Bacterial (Strep, Listeria)
Protozoa (Toxoplasmosis)
What are the haematogeneous infections?
TORCH
Toxoplasmosis
Other (HEP B)
Rubella
CMV
Herpes
What are the consequences of placental infections (to baby)
IUGR (intrauterine growth retardation)
Low birth weight
Premature delivery
Congenital abnormalities
What is toxemia of pregnancy?
Systemic syndrome characterised by widespread maternal endothelial dysfunction
Who is more susceptible to toxemia?
3-5% of pregnant women
In primiparous (first time giving birth)
When does toxemia usually occur?
Final trimester
Symptoms of pre-eclampsia (3)
HTN (HTN can develop without proteinuria) - Diffuse endothelial dysfunction and vasoconstriction caused
Proteinuria - Increased vascular permeability
Oedema (Facial puffiness) - Increased vascular permeability
Symptoms of Eclampsia (2)
Convulsions
DIC (disseminated intravascular coagulation) in Liver kidney heart placenta brain (LKHPB)
Pathogenesis of Eclampsia
- Primary causes of eclampsia (Immune, genetic??)
- Altered placentation and functional obstruction of spiral arterioles (that bring blood back from myometrium to decidua to maternal blood)
- Decreased uteroplacental perfusion
- Giving rise to 4 changes
4a. Fall in prostaglandins (prostaglandins vasodilate) → leads to vasoconstriction
4b. Rise in renin and angiotensin II → vasoconstriction to raise BP
4c. Thromboxane rise → rise in platelet aggregation
4d. Endothelin rise and NO fall → vasoconstriction
5.These 4 changes lead to
5a. Arterial vasoconstriction → hypertension
5b. Further fall in uteroplacental perfusion
5c. Endothelial injury and DIC
What are the consequences of DIC in eclampsia?
Liver → Abnormal liver function tests
Kidneys → proteinuria and low GFR
Other organs → ischemia and fibrin + thrombi (heart AMI, brain stroke)
CNS (brain) → seizures and coma
Generalised oedema
Histological features of Liver during toxemia (DIC)
Irregular, focal, subcapsular, intraparenchymal haemorrhage + necrosis
Histological features of Kidney during toxemia (DIC)
Glomeruli show marked swelling of endothelial cell (endothelial damage) and fibrin thrombi
Histological features of Brain during toxemia (DIC)
Haemorrhage along with small vessel thromboses
Histological features of placenta during toxemia (DIC)
Generalised uteroplacental malperfusion due to spiral artery kinking - infarcts
Ischemia and vascular injury can be observed - hematomas
Fibrnoid necrosis of vessels (endothelial damage)
What are the 3 placental abnormalities
Placenta previa
Abruptio Placentae
Placenta accreta
What is placenta previa and its consequences?
Implantation of planceta over or near internal os, necessitating delivery of placenta before foetus
Antepartum hemorrahge (before childbirth)
Two types of placenta previa?
Marginal placenta previa (not completing occluding the internal os) → chance that placenta will separate from the os (good)
Complete placenta previa (completely blocking internal os) → C SECTION!!!
What is abruptio placentae and its consequences?
Premature incomplete or complete separation of normally positioned placenta from uterine wall during pregnancy/antepartum (leads to antepartum haemorrhage)
Concealed or revealed bleeding
- Severe bleeding can lead to shock or DIC
- Several fetal distress can cause death
What is placenta accreta and its consequences?
Adhesion of normal placental villi to uterine wall due to absence of decidual plate between villi and myometrium –> Leads to failure of placenta to separate during the 3rd stage of labour
Severe post partum haemorrage - shock or DIC
Hysterectomy needed: stop bleeding
How is the decidual plate formed usually?
Normally the endoemtrial stroma will undergo decidualization → to form the decidua basalis → the chorionic villi will then be attached to the decidua basalis to facilitate gaseous and nutrient exchange
But because of the failure of the formation of decidual plate, the villi will directly adhere to the myometrium..
The 3 types of placenta accreta ranked in severity is…
Placenta accreta < Placenta Increta < Placenta Percreta
What are trophoblasts?
outermost layer of cells of blastocyst that attaches fertilised ovum to uterine wall → serves as nutritional pathway of embryo (it wraps around the chorionic villi)
What is gestational trophoblastic disease?
Spectrum of tumours and tumour-like conditions characterised by proliferation of placental tissue (villous/trophoblastic)
What are the 3 types of gestational trophoblastic diseases?
Hydatidiform moles
Invasive moles
Choriocarcinoma
Who is more likely to get gestational trophoblastic disease?
AGE
- More common in extremes of reproductive age (old and young)
- Malignant sequelae frequent in older patient
OBSTETRIC HISTORY
- Term pregnancies and live births have protective effect against trophoblastic diseases
- History of previous mole increases risk
- Half the choriocarcinomas follow a molar pregnancy
What is a complete mole?
Abnormal conceptus without embryo-fetus with gross hydropic swelling of villi
Pathogenesis of complete mole?
Complete mole results from fertilisation of egg in which nucleus is lost or inactivated
Most are 46XX some are 46 XY
- XX is either due to two sperm XX or one X sperm after duplication becomes XX
- XY is due to 23X + 23Y both from the male (two sperm)
What is a partial mole?
Intimate admixture of both normal and abnormal villi. Fetal development may be present
Pathogenesis of partial mole?
Triploid: 69XXY or 69XXX
23X + 23Y from male + 23X from female = 69XXY
46XY from male + 23X from female = 69XXY
23X + 23X from male + 23X from female 69XXX
How to distinguish between the two moles (complete and incomplete)?
P57 is a surrogate marker for maternal genome ( can do immunhistochemistry) → if no maternal genome detected = complete mole
Comparison between complete vs partial mole
Complete vs partial mole
Uterine size large vs Uterine size small
Very elevated serum hcg vs Elevated serum hcg
10-30% persistant GTD vs 4-11% persistent GTD
Embryo/fetus absent vs Embryo/fetus present
Trophoblastic hyperplasia diffuse vs focal
Clinical presentations of moles?
Uterin hemorhage leading to Vagina bleeding
Pre-eclampsia toxemia in 1/4 of cases
Passage of molar vesicles
Hyperemesis
Hypercoagulation –>Pulmonary embolism
Hyperthyroidism
Serology of moles?
Raised hcg levels
Moles that have continued GTD will –>
Continued trophoblastic activity → 16% progress to invasive mole and 2.5% progress to choriocarcinoma
Histological features of moles
Hydatidiform mole shows trophoblastic proliferation and villi are hydropic and oedematous + marked dilatation
What is an invasive mole?
Hydatidiform mole in which hydropic villi
a)invade the myometrium or blood vessels
b) are transported to extrauterine sites
Do invasive moles metastasise/invade?
Low mets risk - (24-40% distant mets to lungs, vulva, broad ligament)
Locally aggressive - Penetrates into myometrium and later blood vessels
Prognosis of invasive moles
Highly chemosensitive
Usually self-limiting even without chemo
Deaths usually due to uterine perforation or intraperitoneal bleeding
What is gestational choriocarcinoma?
Aggressive malignant tumour arising from trophoblastic tissue lining chorionic villi
50% of cases are preceded by a complete mole
25% of cases are preceded by abortion
22.5% of cases preceded by normal pregnancy
2.5% due to ectopic pregnancy
Gross features of GCC
Hemorrhagic friable mass in uterine cavity
Histological features of GCC
Hemorrhage and necrosis, anaplastic trophoblast, vascular invasion, trophoblastic proliferation
Spread of GCC
Widespread metastases via blood (similar to choriocarcinoma of testes)
Usually to lung 50%
Vagina 30-40%
Brain liver marrow etc.
Lymphatic mets uncommon
Clinical features of GCC
Abnormal uterine bleeding
Distant mets leads to haermorhagic events
Serology test of GCC
hCG levels are elevated
Prognosis of GCC
Previously fatal → but now with chemo it’s survival is 80-90%
BUT
Distant mets, failure of chemo - POOR PROGNOSIS
choriocarcinoma following term pregnancy - better prognosis
figo staging of gcc
I- Tumor confined to uterus
II- Extends by mets or direction extension to other genital structures
III- mets to lung
IV - other distant metastases (w or w/o lung)
