Physiology and Pathophysiology of Pregnancy 7.3 Flashcards
Pathophysiology: Explain the basis for treatment/management
PTL: Prevention/delay, management
Prevention/delay:
- Progesterone
- Cervical cerclage
Management:
- Tocolytics (suppress childbirth)
- Ca2+ blockers
- NO donors
- COX-2 inhibitors
Pathophysiology: Explain the basis for treatment/management
Pre-eclampsia: Definition, aetiology, risk factors, management, maternal complications
Definition: A multisystem disorder. Decidua vessels are narrowed causing increased vascular resistance.
Characterised by hypertension, proteinuria, oedema and epigastric pain. Late onset is less severe.
Aetiology:
- Poor cytotrophoblast invasion
- Poor response to vasodilators
- Endothelial dysfunction (poor dilation leading to endothelial damage)
- ROS-lipid peroxidation
Risk factors:
New partner, family Hx, maternal age, pre-existing renal or CV disease
Management:
- Low dose aspirin
- Vitamins
- Mg sulphate
- Resolution seen upon delivery of the placenta
Maternal complications:
- Increased risk of TIA/stroke
Pathophysiology: Explain the factors/mechanisms underlying key pregnancy pathophysiology
Pre-term:
- Spontaneous onset, infection, previous hx of pre-term birth, socioeconomic status, premature myometrial contractions, short cervix
Haemorrhage:
- Antepartum
- Postpartum
Placental:
- Pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption, miscarriage
Dystocia
Definition: Failed feotal descent despite normal uterine contraction, due to obstruction. Shoulder dystocia may also be seen.
Physiological adaptations to pregnancy: Outline the first stages of labour
‘Show’ - Dislodging of the cervical mucus plug. Followed by bleeding
‘Waters breaking’ - Amnioic fluid ‘leaks’ from a weak spot in the amniotic membrane
Regular and strong myometrial contractions
Cervical effacement (thinning), dilation and shortening
Physiological adaptations to pregnancy: Triggers for labour
Pregnancy: Relaxation associated proteins
- Progesterone, NO and open K+ channels
- Myocyte RMP is hyperpolarised
Parturition: Contraction associated proteins (CAPs)
- Membrane depolarises as pregnancy progresses.
- Volatage gated calcium channels open and intracellular calcium stores are released.
- An action potential is generated
- CRH, oxytocin, PGE, IL-1
- Gap junctions formed. Uterus contracts as a syncytium: beginning at the fundus.
- NOT dependent on progesterone withdrawal
Physiological adaptations to pregnancy: Immunological
- Cervical mucus plug: Rich in anti-microbials
- Amniotic fluid: Rich in AMPs (histones, defensins)
- TH2 skewing - less inflammatory subset
- Treg upregulation via FOXP3
- High levels of HLA-G: Allows for recognition of self as not as polymorphic
- Decidua abundant in uNK - HLA-G binds KIR receptors on the NKs to prevent cytotoxic action
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Pathophysiology: Explain the basis for treatment/management
Abruptio placenta: Definition, presentation
Definition: Premature separation of the placenta
Presentation:
- +/- vaginal bleeding
- Increased uterine activity
Pathophysiology: Explain the basis for treatment/management
Gestational diabetes: Definition, aetiology
Definition: Glucose intolerance correlated with the onset of pregnancy
Aetiology: Plasma [glucose] is increased during pregnancy to maximise foetal transfer, leading to insulin resistance. In most pregnancies pancreatic beta cells are able to compensate for the increased demand for insulin (secreting more insulin). Gestational diabetes arises when the pancreatic beta cells are unable to compensate for the increased insulin demand, leading to the development of diabetes.
Pathophysiology: Explain the basis for treatment/management
Antepartum haemorrhage: Definition, aetiology
Definition: Bleeding after 24 weeks of gestation
Aetiology:
- Abnormalities in placental site or uterine cavity
- Vaginal or cervical lesions
- Placenta praevia (low lying placenta, may obstruct the internal Os)
Pathophysiology: Explain the basis for treatment/management
Dystocia: Definition, aetiology, management
Definition: Failure of foetal descent despite the presence of normal uterine contractions, resultant of obstruction
Aetiology:
- CPD (cephalopelvic disproportion)
- Abnormal foetal presentation
Management:
- Oxytocin may be used to stimulate uterine activity
- C-section
- Instrumental delivery
Physiological adaptations to pregnancy: Cardiovascular
- Increased plasma volume: Allows for increased nutrient delivery
- Increased erythrocyte mass BUT does not match plasma volume increase ⇒ haemodilution
- Increased CO and SV
- Vasodilation - oestrogen mediated
- Hypercoaguable state (more clotting factors)
- BP decreases until 2nd trimester (12-26 weeks)
Physiological adaptations to pregnancy: Renal
- Length and weight of kidneys increased
- Ureter dilation ⇒ urinary stasis - increased risk of pyelonephritis
- ↑ renal blood flow
- ↑ GFR
- ↑ resorption of Na+ (induced by initial vasodilation)
- Glycosuria: due to increased filtered load
- Increased erythropoietin
Pathophysiology: Be able to name common microorganisms implicated in onset of pre-term labour
Mostly gram positive bacteria: Ureaplasma parvum, ureaplasma urealyticum and streptococci
Shigella flexneri
Salmonella typhirium
Gardnerella vaginalis
Toxoplasma gondii
Plasmodium falciparum
Candida albicans
Adenovirus
Infection → inflammation → pro-inflammatory cytokines are raised with the amniotic fluid/cord
State the stages of labour
First stage:
Onset of labour to full cervica dilation. Longest stage.
Second stage:
From full dilation to delivery of the baby
Third stage:
From delivery of the baby to expulsion of the placenta
- As the baby descends it compresses fibres in the cervix. This creates a positive feedback loop for oxytocin. Increases contractions.
Physiological adaptations to pregnancy: Endocrine
Functions of: oestrogen, progesterone, relaxin, hPL, hCG, oxytocin and prolactin
- Placenta secretes high levels of progesterone and oestrogen
- Oestrogen: Stimulates uterine growth; initiates CV changes; ductal development in breast; effects on CT e.g. cervical softening
- Progesterone: Decidualisation; keeps uterine resting membrane potential low (relaxes smooth muscle): MSK relaxant; acts on respiratory centre in medulla; promotes breast alveolar development
- Relaxin: Relaxes ligaments and bones during pregnancy
- hPL (human placental lactogen): Released from syncytiotrophoblast. Promotes breast development and inhibits maternal glucose uptake (more available for foetus)
- hCG: Secreted from syncytiotrophoblast. Maintains the corpus luteum.
- Oxytocin: From the posterior pituitary gland. Causes uterine contraction (via PLC, generates IP3, increases Ca2+ levels) and milk ejection reflex (myoepithelial cell contraction), promotes placental expulsion, controls postpartum haemorrhage and aids uterine involution, bonding
- Prolaxin: From the anterior pituitary gland. Responsible for amniotic fluid generation and maintainence, stimulates milk production
Outline the triggers for the onset of labour
Physiological adaptations to pregnancy: Lactation
Progesterone → Alveolar development
Oestrogen → Duct development
- Oestrogen and progesterone (placental origin) inhibit the action of prolactin, preventing lactation
- Removal of placenta ceases this inhibition, allowing prolactin to establish milk production
Lactogenesis
- Suckling stimulates prolactin release
- Suckling activates oxytocin releasing neurons. Oxytocin (OT) then induces the contraction of myoepithelial cells, causing milk to pass to milk ducts.
- Intramammary pressure increases, leading to the milk ejection reflex.
Physiological adaptations to pregnancy: Structural/anatomical changes
- Syncytiotrophoblast invasion of the endometrium; Spiral artery enlargement
- Placental formation
- Growing foetus displaces the diaphragm, heart and bladder
- Myometrial hyperplasia and hypertrophy
- Cervix is firm and non-compliant
- Mucous plug formed: Creates a closed uterine environment - prevents pathogenic entry
- Melasma (oestrogen → MSH production), linea nigra and striae gravidum
Pathophysiology: Explain the basis for treatment/management
IUGR: Definition, aetiology
Definition: Foetal intrauterine growth restriction.
- Failure of the foetus to achieve growth potential
- May co-exist with pre-eclampsia
Aetiology: Shared with pre-eclampsia
- May also be linked to ethinicity and smoking
Physiological adaptations to pregnancy: GI tract
- Progesterone induces smooth muscle relaxation
- Reduced GI motility: allowing for increased nutrient absorption ⇒ constipation
- Relaxation of the lower oesophageal sphincter ⇒ acid reflux
Puerperium: Outline the changes observed
- Gradual return to non-pregnant state: 6 weeks
- Sex steroid hormone levels decrease
- Uterus diminishes: Mediated by oxytocin and enzyme (collagenases and MMP)
- Endometrial regeneration
- Breastfeeding ⇒ Oxytocin levels remain high - menstruation will resume once no longer breast feeding
Pathophysiology: Explain the basis for treatment/management
PPROM: Definition, risk factors, detection, management
Premature placental rupture of membranes (PPROM)
Definition: Spontaneous placental membrane rupture prior to the onset of labour
Risk factors:
- Choriodecidual inflammation
- Uterine distension
- Smoking
- Cervical cerclage (cervical stitch used for premature cervical shortening)
Detection:
- +ive fetal fibronectin test (helps adhere the amniotic sac to the uterus)
- Shortened cervix
Management:
- Antibiotics
- Antenatal corticosteroids (to induce surfactant production)
Physiological adaptations to pregnancy: Respiratory
- 15 % increase in oxygen consumption
- ↑ tidal volume: Diaphragm moves superiorly but as ligaments are softens it ‘flares’, allowing for increased tidal volume
- PCO2 decreased ⇒ respiratory alkalosis
- Greater concentration gradient for the removal of foetal CO2
- Progesterone acts at the respiratory centre in the medulla: enhances respiratory drive
- Dyspnea
- Foetal haemoglobin has > O2 affinity, gamma chains
Pathophysiology: Outline the possible complications of pre-term birth
- Respiratory disorders
- Visual problems
- Hearing difficulties
- Impaired neurocognition
- Periventricular leukomalacia
- Neonatal sepsis
Long-term follow up required
Outline the cervical changes observed during labour
- Effacement
- Shortening of the cervical canal
- Dilation
- Softening of the cervix: Mediated by relaxin and oestrogen
