Placenta & Hcg & Amniotic Fluid😍

Placenta

  • Dimensions:
    • Weight: 500 gm & 500 mL
    • Diameter: 15-20 cm
    • Placental weight = Fetal weight at 17 weeks
    • Central thickness: 2.5-4 cm
      • Placentomegaly:
          • Placental thickness ≥4 cm
          • Causes:
            • Diabetes, GDM
            • GTD
            • Twin pregnancy, TTTS
            • Rh negative pregnancy
      • Small Placenta
        • Pre eclampsia
        • IUGR
      GA
      Placental Wt
      At 17 weeks
      Placental Weight = Fetal weight
      At term
      Ratio of placental weight to fetus = 1:6
  • Formation:
    • Fetal side
      Maternal side
      Placenta formation
      Chorion frondosum
      Decidua basalis
      Appearance
      Smooth, shiny
      Dull
      During Placental separation
      Central separation
      Peripheral separation
      Method
      Schultze method
      Duncan method
      Better, M/c
      Retroplacental clot formed
      Decreased bleeding
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  • Features:
    • Discoidal
    • Deciduate: Shed off after delivery
    • Hemochorial: Lies in contact with maternal blood

Umbilical cord:

  • 3 vessels
    • a. Right umbilical artery
    • b. Left umbilical artery
    • c. Left umbilical vein
  • Mnemonic: Are you Very Lost (RUV lost)
  • Presence of a single umbilical artery
    • A/w congenital anomalies
    • Like Renal agenesis
  • Normal average length is 50-60 cms
  • contains a gelatinous substance called Wharton's jelly
  • Shed off by 7 - 10 days

Placental Hormones

  • M/c site of production : Syncytiotrophoblast.
      1. hCG
      1. HPL
          • Cause: Insulin Resistance
          • Fasting Hypoglycemia
          • Postprandial Hyperglycemia
      1. Progesterone
  • From DHEA-S produced by fetal adrenal gland.
    • Estriol (E3)

Maintaining Pregnancy by Progesterone

  • β hCG from Syncytiotrophoblast
    • Maintains Corpus luteum till 8 weeks
    • Corpus luteum → secrete progesterone till 8 weeks
  • After 8 weeks → Syncytiotrophoblast secrete Progestogen

Human Chorionic Gonadotropin (hCG)

  • Type: Glycoprotein hormone
    • Also AMH/MISGlycoprotein hormone
  • Secreted by Syncytiotrophoblast from implantation onwards
  • Subunits:
    • α-subunit: Similar to LH, FSH, TSH
    • β-subunit:
      • Similar to LH
      • Specific
      • Tested in UPT
    • So structurally similar to LH
  • Function:
    • Maintains corpus luteum up to 6 weeks of pregnancy
    • First stimulus for release of testosterone from fetal testis
  • Doubling time: 48 hours
  • Levels:
    • Appears in blood: Day 8-9 after fertilization (D22 of cycle)
    • Peak levels: 9-10 weeks
    • Plateau: 16-20 weeks
  • T1/2: 36 hours
    • Feature
      hCG
      LH
      37 hours
      30 minutes
      Potency
      80X
      X
  • Functions:
    • Stimulate the maternal thyroid gland during pregnancy.
    • Stimulates Leydig cells → Testosterone production
    • Stimulates corpus luteumRelaxin production
    • Exhibits immunosuppressive activityPrevents fetal rejection
    • Maintains corpus luteum up to 6 weeks of pregnancy
Subtype
Source
Clinical Use / Significance
Intact hCG
Syncytiotrophoblast
Normal pregnancy. Basis of routine pregnancy tests.
Free β-hCG
Trophoblastic tissue
↑ in Down syndrome screening. Marker of GTN, testicular tumors.
Hyperglycosylated hCG
(hCG-H)
Invasive cytotrophoblast
Early pregnancy. Marker of trophoblastic invasion. ↑ in invasive mole, choriocarcinoma.
Nicked hCG (hCGn)
Trophoblastic tumors, late pregnancy
Partially degraded form. Seen in trophoblastic neoplasia.
β-core fragment
Urinary metabolite of β-hCG
Present in urine. Used in urine tumor marker assays.
Free α-subunit
Pituitary, tumors
Nonspecific. Seen in pituitary hCG, ovarian and testicular tumors, some thyroid cancers.B

The adrenal cortex of the fetus releases

  • In early pregnancy:
    • Cortisol
  • In 2nd trimester:
    • DHEA

The fetal adrenal gland primarily produces 

  • Dehydroepiandrosterone sulfate (DHEA-S)
  • crucial for growth and development.

Fetal growth

  • D/t Fetal Insulin / IGF
  • Not d/t Maternal Insulin / GH
    • Insulin do not cross Placenta
  • Normal Newborn
    • Fetal Hyperglycemia
      • Stimulates Insulin → Fetal growth
  • In Newborn of Diabetic mother
    • Maternal hyperglycemia → ↑↑↑ Fetal insulin → Macrosomia
    • Fetal Hypoglycemia

Estrogen

  • Synthetic
    • EE
    • CEE
  • Physiological
    • E1, E2, E3

Potency

  • Ethinyl Estradiol (EE) >
  • Conjugated Equine Estrogen (CEE) >
  • Estradiol (E2) >
  • Estrone (E1) >
  • Estriol (E3)

Common Estrogen Types

Condition
Estrogen Most Common/Specific
Most common synthetic Estrogen in OCP
EE
Most common synthetic Estrogen in HRT
17-beta estradiol
Most common in reproductive age female
E2 (Estradiol)
Most common in pregnancy
E2
Most specific in pregnancy,
Synthesised
by Placenta
[From DHEA from fetal adrenal gland]
E3
Most common in menopausal female, PCOS
E1 (Estrone)

Low Estrogen

  • POI
  • Menopause
  • Gonadal dysgenesis
  • Sheehan’s Syndrome
  • Kallman’s syndrome

Progesterone challenge test is Negative

  • If Low Estrogen
    • Progesterone can only act on Estrogen primed endometrium
  • Normal Estrogen
    • Ascherman syndrome
      • d/t no endometrium
  • [Positive in PCOS]

Source of Estrogen + Progesterone :

  • Before 8 weeks:
    • Corpus luteum of pregnancy 
    • Made and maintained by LH
  • After 8 weeks:
    • Placenta

Estrogen
Target Organ
Actions
Uterus 
(Estrogen dominant)
Increases blood flow.
Increases contractility, increases excitability.
Menstruation
Vagina
Vaginal Cornification
Cervix
• Cervical mucus production
Secondary sexual characteristics
• Creates female body contour.
• Promotes fat distribution in
breast & buttocks.
DO NOT CAUSE PUBIC OR AXILLARY HAIR GROWTH
Breast
• Promotes growth.
• Aids
ductal proliferation.
Bone
• Produces Osteoprotegerin (inhibitor of RANK ligand).
↓↓ osteoclast differentiation → ⛔ bone resorptionProtects bone
Liver
↓↓ plasma LDL cholesterol
CVS
⛔ platelet activation → ↓ Clot formation
Promotes vasodilation by increasing NO
CNS
Neuroprotective:
⛔ neuronal cell death
Kidneys
• Causes salt & water retention
Progesterone
Target Organ
Actions
Uterus
Anti-estrogenic action:
Makes uterus less active, less excitable, less contractile
Breast
• Promotes lobulo-alveolar (gland) growth
CNS
Thermogenic action:
↑↑ Basal Body Temperature (BBT) by 0.5-1°C during ovulation.
Respiration
• Stimulates respiration → Leads to CO2 washout↓↓ alveolar PCO2 levels
Kidneys
Causes Natriuresis:
• Promotes
salt & water excretion
(Only steroid hormone → cause Natriuresis)

NOTE

  • Androgens are formed in Ovary
    • In Theca Interna cells
    • Not DHT, DHEA
  • Testosterone → 5α reductase enzyme→ Di-hydro testosterone (DHT) (more potent).
  • Aromatase from granulosa cells
    • convert to Estradiol (E2) → most potent
  • Aromatase from peripheral fat
    • convert to Estrone (E1)

Hormonal Changes in Pregnancy

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Hormone
Pattern in Pregnancy
Near Term / Parturition
Estrogen
Rises steadily throughout pregnancy
Progesterone
Increases initially,
then constant after 7th month
Estrogen : Progeserone ratio
↑ near term
Prolactin
Gradual rise
Peaks just before delivery

Cervical Mucous Study

Estrogen
Progesterone
Consistency
Profuse, watery, elastic
Thick, scanty, viscous
Known as
Spinnbarkeit (Stretching ⊕)
Spin → Loose
Tack (Stretching ⊝)
Tack → katti

Ferning

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  • Seen under microscope on D8
    • Proliferative phase
  • Disappears by D18 of cycle
  • If ferning persist by D18, indicates Anovulation

Endometrial Glands

  • Endometrial BiopsyNot commonly done for ovulation.
  • Timing: D26 (Pre-menstrual phase).
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• Proliferative phase
• Proliferative phase
• Secretory phase
• Glands shrink
• Prominent vessels and Hemorrhagic spots
• Secretory phase
• Glands shrink
• Prominent vessels and Hemorrhagic spots
 
Stages
Features
Early proliferative
Estrogen
Simple tubular glands
Telescoping of gland
Pseudostratification (Nuclei at different levels)
Early secretory
Progesterone
Subnuclear vacuolation: First sign of ovulation on biopsy (D17 - D18)
Late secretory
Progesterone
Corkscrew glands
Sawtooth appearance
Secretions in gland

Placental Anomalies

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  • Maternal side larger than fetal side
    • Placenta bilobata

    • Equal size lobes
    • Placenta succenturiata

    • Unequal lobes
      • Connected by blood vessels.
    • After delivery
      • Placenta shows an oval defect in chorion
      • with torn blood vessels ending abruptly at margins
    • Complications
      • Retained placenta  
        • PPH
        • notion image
      • Increased size of placenta 
      • Increased risk of placenta previa → Antepartum hemorrhage (APH).
  • Single umbilical cord
  • Battledore placenta:
    • Marginal insertion of cord
  • Circumvallate placenta:
    • Valve-like thickening
    • A/w
      • IUGR
      • Placenta Previa
      • Preterm labor
  • Circummarginate placenta:
    • No valve-like thickening

Velamentous Cord Insertion

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Velamentous + Succinturate lobe
Velamentous + Succinturate lobe
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Pathophysiology

  • Cord attaches to membranes, not directly to placenta
  • Wharton's jelly absent in membrane part
  • Vessels run freely in membranes before reaching placenta

Complications

Vasa previa

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  • Unprotected vessels may rupture
  • After ARM: Fetal distress + bleed.
    • Less blood loss + marked fetal distress
  • Leads to fetal blood losslife-threatening
 
Types
A/w
Notes
1
Velamentous cord
2
Placenta Succinturiata
• Umbilical cord attached only to bigger lobe
• Smaller lobe if left behind → cause
PPH

IOC

Condition
Screening
IOC
Vasa Previa
USG Doppler
Placenta Previa
TAS
(PP vs. AP)
TVS
Best Time for USG
T3 (32 - 36 weeks)
Placenta accreta
TVS
MRI

Placental Transfer:

Can Cross the Placenta

Nutrients

  • Glucose – facilitated diffusion
  • Amino acids – active transport
  • Fatty acids – esp. long-chain
  • Water-soluble Vitamins (e.g., B, C)
  • Minerals – calcium, iron

Gases

  • O₂ – maternal to fetal
  • CO₂ – fetal to maternal

Water & Electrolytes

  • Water, Na⁺, K⁺, Cl⁻ – passive/facilitated

Antibodies

  • IgG – receptor-mediated (passive immunity)
  • IgG2:
    • Does not cross placenta
    • protects against capsulated organisms

Hormones

  • Cortisol, Thyroid hormones – limited crossing, regulated

Drugs

  • Lipid-soluble, low MW (<500 Da)
  • Examples: alcohol, nicotine, caffeine, some anesthetics, anticonvulsants, antidepressants

Toxins

  • Alcohol, mercury, lead, pesticides

Pathogens

  • Viruses: rubella, CMV, Zika
  • Bacteria: Treponema pallidum
  • Parasites: Toxoplasma gondii

Cannot / Limited Passage

Large Molecules

  • Proteins – albumin, Hb
  • IgM – too large

Hormones

  • Insulin, LH, FSH, GH, TSH, HCG
  • Peptide hormones – limited
  • Catecholamines – degraded/metabolized

Some Drugs

  • High MW (>1000 Da), polar
  • Example: heparin
  • Efflux by P-glycoprotein

Blood Cells

  • RBCs, WBCs – normally blocked
  • Rare: microtransfusion in placental injury

Most Bacteria

  • Generally blocked
  • Exception: Listeria

Placenta Accreta Spectrum (PAS)IOC →

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IOC

Condition
Screening
IOC
Vasa Previa
USG Doppler
Placenta Previa
TAS
(PP vs. AP)
TVS
Best Time for USG
T3 (32 - 36 weeks)
Placenta accreta
TVS
MRI
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Signs on USG Placenta Accreta Spectrum:

  • Placental lakes/moth-eaten appearance.
  • Heterogenous Placenta
  • Thinning of myometrium behind Placenta
  • Loss of clear space behind Placenta
  • Loss of Bladder line
  • Absence Of hypoechoic area
    • behind placenta representing decidua basalis
  • Absence Of Continuous white line reflecting
    • bladder - uterine serosa interface.
      • notion image

Types:

Types
Featuures
Placenta accreta (M/c)
Chorionic villi superficially attached to myometrium
Placenta increta
Villi invade myometrium
Placenta percreta
Villi penetrate attached to serosa
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Pathology:

  • Absent decidua basalis.
  • Absent Nitabuch layer.

Risk factors:

  • Placenta previa +
  • Previous history of C-section.

C/F

  • Cord snapping on traction
  • PPH

Management (Mx):

  • Classical CS + Hysterectomy
 

Amniotic Fluid

  • pH : 7 - 7.5
  • Maximum at
    • 32-34 weeks
      • 1000 mL
  • At term/40 weeks:
    • 800 mL
  • ≥42 weeks:
    • 200 mL

Normal values

  • AFI (Amniotic Fluid Index): 5 - 25 cm
  • SVP (Single Largest Vertical Pocket): 2 - 8 cm

Source

  • Gestational age: Source
    • First trimester: Maternal plasma
    • 12-20 weeks: Fetal skin
    • 20 weeks: Fetal urine
    • Mnemonic: Amniotic fluid → AFP → ammede blood, fetal skin, Peee

Appearance

  • Straw coloured: Term
  • Clear to pale yellow
  • Without white specks
    • White specks → indicate meconium staining
    • Cloudy Infection
Gestational age
Amniotic fluid appearance
32nd week
Clear
No flakes
36th week
• Some flakes present
• Traces of cloudiness
42nd week (term / post-term)
Very cloudy + ↑↑ flakes

Colour

  • Colour: Seen in
    • Saffron colour, yellowish green:
      • Post term pregnancy
    • Green colour (Due to biliverdin in meconium):
        1. Fetal distress
        1. Transverse lie/Breech
        1. Listeria infection
      • Mnemonic: Green → GB → Liver → LFT
    • Golden colour (Due to bilirubin):
      • Rh incompatibility
      • Mnemonic: Gold (golden), Ruby (rubin) → Rich (Rh)
    • Tobacco juice/Brown:
      • Intrauterine fetal death
      • Mnemonic: Tobacco brings death
    • Dark red:
      • Concealed hemorrhage

Listeria infection

  • Cross placenta
  • Make Amniotic fluid Green
  • Shows differential motility

Amniotic fluid tests:

  • Ferning
  • Nitrazene blue test-alkaline,
  • Nile blue sulfatase
  • Fibronectin

Amniotic Fluid Disorders

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Oligohydramnios vs. Polyhydramnios

  • Conditions leading to both oligo & polyhydramnios:
    • TTTS
    • TORCH infections

Oligohydramnios

  • AFI: <5 cm
  • Single largest vertical pocket (SVP): <2 cm
  • M/c cause of mild oligohydramnios: Idiopathic
  • M/c cause of severe oligohydramnios: 
    • Fetal renal anomalies
      Notes
      Renal agenesis / anomalies
      m/c
      Posterior Urethral valve
      UPI / PIH
      Decreased transudation across placenta (Small placenta)
      Oligo in T3
      Ruptured membranes
      Best: P/s examination
      TORCH
      Early onset Oligohydramnios
      IUD/ Post term baby
  • Other causes:
      1. Decreased urine output:
          • Renal disorders
          • Drugs: ACE inhibitors/Indomethacin
      1. Decreased volume of Amniotic fluid:
          • Post term pregnancy
          • PROM
          • Leaking after amniocentesis
      1. Chromosomal Anomaly:
          • (69 chr) Triploidy
  • May lead to compression defects
    • CTEV
    • Potter’s syndrome / sequence

Polyhydramnios

  • AFI: >25 cm
  • SVP: >8 cm
  • Mild Polyhydramnios: Idiopathic
  • M/c cause of severe Polyhydramnios: 
    • Fetal GIT anomalies
      • Esophageal atresia
      • Duodenal atresia
      • Cleft lip/Cleft palate
      • Anencephaly
      • CDH
  • Other causes:
      1. Increased transudation across placenta:
          • Placentomegaly
              • Placental thickness ≥4 cm
              • Causes:
                • Diabetes, GDM
                • GTD
                • Twin pregnancy, TTTS
                • Rh negative pregnancy
      1. Increased urine output:
          • Hydrops Fetalis
          • Twin pregnancy, Diabetes, Bartter syndrome
          • Fetal anemia (Thalassemia, Rh negative pregnancy, Parvo virus infection)
      1. Increased transudation from fetal skin:
          • NTD, Abdominal wall defect
      1. Chromosomal anomaly:
          • Trisomy

Approach to a Case of Polyhydramnios/Oligohydramnios

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Note:

  • PSV of MCA
    • ≥ 1.5 MOM: Fetal anemia.
    • < 0.8 MOM: Fetal polycythemia.
  • Indomethacin:
    • Can be used to treat polyhydramnios
    • S/E: Premature closure of ductus arteriosus
    • C/I: >32 weeks of pregnancy

Note:

  1. M/c CTG Finding in oligohydramnios:
      • Variable decelerationDue to cord compression
  1. Persistent variable deceleration:
      • Only indication for amnioinfusion

Syndromes related to Oligohydramnios

Potters syndrome:

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  • Severe oligohydramnios due to kidney defects
    • Renal agenesis
      • B/L renal agenesis (incompatible with life).
    • PCKD
  • C/f:
    • Lung hypoplasia
      • most common cause of mortality in Potter syndrome
    • Typical flat facies
    • Potters sequence
      • Severe oligohydramnios due to non renal causes

      Clinical features:

    • Extremities anomaly.
    • Wrinkled skin.
    • Facial dysmorphism.
    • Renal agenesis B/L (primary anomaly).
    • Oligohydramnios.
    • Eyes widely separated.
    • Epicanthic folds.
    • Flat facies.
    • High forehead.
    • Receding chin.
    • Washer man's hand.
    • Potter facies.
      • notion image
       
 

Amniotic band syndrome

  • Severe oligohydramnios due to PPROM
    • C/f:
      • Distal digit amputation
      • Craniofacial abnormalities

Note:

  • Proximal limb amputation:
    • Phocomelia due to Thalidomide
    • Mnemonic: Melathe (melia) kayyi poi (Proximallimb) → thali kettan (thalidomide) pattanilla
  • Distal digit amputee
    • Amniotic band syndrome
    • Oligohydramnios
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Presentation Of Oligohydramnios

  • Early pregnancy:
    • Lung hypoplasia,
    • Limb amputation
      • notion image
  • Late pregnancy:
    • Cord compression
    • Fetal distress
    • Meconium aspiration syndrome
    • Club foot/CTEV

Amniotic Fluid Embolism

  • Diagnosis: Clinical diagnosis, no confirmatory test.
  • Prognosis: Can lead to maternal mortality within 30-40 mins.
  • Time of Occurrence: At the time of labour/within 30 mins of labour.

Phases:

  • 1st Phase:
    • Cardiorespiratory arrest (Difficulty breathing, ↑PR, ↓BP).
    • pulmonary vasoconstriction and right ventricular failure.
  • 2nd Phase:
    • DIC + excessive bleeding.

Diagnostic Criteria:

  • Unexplained shock + less bleeding.
  • Clinical onset within 30 mins of labour.
  • Abrupt cardiorespiratory arrest.
  • Overt DIC.
  • No fever.