Biomed Pregnancy

Pre-eclampsia/ eclampsia

unpredictable onset of convulsion during pregnancy or postpartum unrelated to cerebral pathological conditions

significant cause of maternal death

incurable except for removal of fetus (balance between fetus being viable and mums health)

risk factors = genetic predisposition, maternal characteristics, comorbidities, placental disease, immune factors and multifetal pregnancy

Eclampsia Characteristics

increase in BP >15mHg diastolic or >30 mmHg systolic (pregnancy increase BP naturally)

protein uria (0.3g/24hr) when it is sustained

and/ or edema

HELLP (H-haemolysis, EL - elevated liver enzyme activitym LP - Low platelets)

Eclampsia Clinical Manifestations

suspected in absence of proteinuria when patient has headache, blurred vision, abdominal/ epigastric pain, altered biochemistry (low platelets and abdominal liver enzymes: ALT, AST and GGT)

2 types

1. middle of pregnancy (more serious)

2. later stages of pregancy (less serious)

eclampsia pathological changes if not managed

1. brain - haemorrhage

2. liver - haemorrhage and necrosis

3. heart - subendocardial necrosis

4. kidney - endothelial glomeruloendotheliosis

5. decidual vessels - decreased limunal diameter

pre-eclampsia superimposed on hypertentsion (women that have hypertension previous to pregnancy)

1. may occur in women with pre-existing hypertension <20 weeks gestation who develops

2. new proteinuria >0.3g / 24 hr

3. sudden increase in pre-existing hypertension and proteinuria

4. thrombocytopenia (platelet count < 100 × 10 ^9/L)

Placentae of pre-eclamptic women

Due to smaller cleft it is poorly perfused, abnormally implanted and excessively large in size

Need broad opening for pulsatile blood flow in pre-eclamptic women there is a small trickling of blood

ENVT = extravillous trophoblasts (placental cells) that grow into endometrial and myometrial layer

Pre-eclampsia pathophysiology

1. inadequate invasion of the spiral arteries by the trophoblastic cells

2. decreased uteroplacental perfusion occurs

3. vasoconstriction and decreased plasma volume, haemoconcentration and edema

4. vasoconstriction and DIC

what are sFlt-1 and sEND

2 hallmark antigens in ciruclation, if increased then increases chance lady develops pre-eclampsia

Pre-eclampsia: pathology - blood

1. hypertension and endothelial damage affects capillary permeability

2. plasma leaks from damaged blood vessels = decrease in colloid osmotic BP and edema in the intracellular spaces

3. produced hypovolemia nd haemoconcentration reflected in increase in haematocrit

4. severe cases the lungs become congested as consequence of pulmonary edema (impaired oxygenation & cyanosis)

Pre-eclampsia: pathology - Coagulation

1. increase platelet consumption - thrombocytopenia

2. may be responsible for disseminated intravascular coagulation (DIC)

3. characterised by —> low platelets, prolonged prothrombin time and low fibrinogen levels

4. fibrin and platelets subsequently laid down occludes (damages) blood flow to kidneys, liver, brain and placenta

Pre-eclampsia: pathology - kidneys

1. Vasospasm of afferent arterioles leads to decrease renal blood flow = hypoxia and edema

2. Glomerular-endotheliosis allows plasma proteins in the form albumin to fitler into the urine - proteinuria

3. renal damage is reflected by reduce creatinine clearance and increase serum creatinine and uris acid levels

4. oliguria ensures (increase volume of urine)

Pre-eclampsia: pathology - liver

1. vasoconstriction of the hepatic vascular bed

2. leads to hypoxia and edema of liver cells

3. extreme swelling of the liver may lead to epigastric pain and rupture

4. falling albumin

5. increase in liver enzymes - ALT, AST, GGT

Pre-eclampsia: pathology - brain

1. hypertension with cerebrovascular endothelial dysfunction leads to increase in permeability of blood brain barrier

2. lead to edema and microhaemorrhage

3. headaches, visual disturbances and CONVULSIONS (if this occurs tipping over into eclampsia)

4. hypertensive encephalopathy autoregualtion of cerebral blood flow impaired leading to cerebral vasospasm, cerebral edema and blood cot formation)

Pre-eclampsia; pathology - feta placental unit (baby and placenta)

1. hypertension induced vasoconstriction decrease uterine blood flow

2. decrease blood flow to choriodecidual spaces diminished amount of O2 that diffuses

3. ischemia of placental tissues ensures

4. capillaries in choronic villi thrombose, infarction occurs and baby born small

5. hormonal output is impeded (e.g., leptin)

Pre-eclampsia affect Brain

Symptoms - headaches and visual disturbances

Signs - brisk reflexes and clonus (involuntary, rhythmic, and jerking muscle contraction)

Investigations - N/A

Complications - Eclampsia, posterior reversible encephalopathy syndrome, and intracranial haemorrhage

Pre-eclampsia affect Renal (Kidneys)

Symptoms - N/A

Signs - N/A

Investigations - proteinuria and raised serum creatinine

Complications - Acute kidney injury

Pre-eclampsia affect hepatological (Liver)

Symptoms - epigastric pain

Signs - right upper quadrant tenderness

Investigations - elevated serum liver enzymes (ALT, AST, GGT)

Complications - hepatic haematoma or rupture

Pre-eclampsia affect Haematological (Blood)

Symptoms - N/A

Signs - dark brown urine and petechiae

investigations - low platelets, abnormal clotting tests and haemolysis

Complications - coagulopathy

Pre-eclampsia affect uteroplacental and fetal

symptoms - vaginal bleeding and reduced fetal movements

signs - hard uterus and reduced fundal height

investigations - fetal growth restriction

complications - placental abruption and intrauterine fetal death

pre-eclampsia affect cardiorespiratory

symptoms - breathless, chest pain, and confusion

signs - tachypnoea (rapid breathing)

investigations - decreased oxygen saturation and diastolic dysfunction

complications - pulmonary edema

Pre-eclampsia treatment

1. aim to prolong pregnancy till fetus is mature to survive (deciding when to deliver baby depends on materal conditions vs fetal maturity)

2. antihypertensives assist in protecting against cerebrovascular accident

theories that are looking at viagra (increases blood flow)

Affect on Mother

miRNA 21-23 nucleotides dont get reduced —> go from placenta to mothers circulation target and stops transcription —> downregulated causes order expression of gene

Development of pre-eclampsia

1. Mix of genetic, environmental, immunological and metabolic factors

2. abnormal trophoblast invasion and differentiation

3. placental ischemia/ hypoxia

4. angiogenic factor imbalance (decreased PIGF absence (sFlt) and increase VEGF and PIGF

5. endothelial dysfunction = hypertension proteinuria edema, hepatic ischemia, activated coagulation system and cerebral edema

Ectopic Pregnancy

implantation of enbryo within fallopian tube, ovary wall, cervix or peritoneal cavity

termination of pregnancy or rupture of structure = haemorrhage

typically non viable

Ectopic pregnancy symptoms

• severe abdominal pain

• spotting

• amenorrhea

Gestational Diabetes Mellitus

diabetes 1st identified during pregnancy (if mum already had diabetes not GDM)

OGTT @ 24-28 weeks

fasting blood sugar already higher

GDM Risk Factors

• previous GDM/ family history of GDM

• enthnicity —> when mother in utero has insuffiecient nutrients therefore pancreas not developed fully therefore when come to Aus pancreas cant handle food therefore increases change of GDM

• Age >40 years

• obesity, especially BMI > 35 kg/m2

• previous macrosomia ( baby birth weight >4 500g or >90th percentile

• PCOS

• medications (e.g., corticosteroids)

GDM Diagnostic Values

All women undergo OGTT (75g) 24-28 weeks gestation

other evaluations may be required if Hx indicated

• Fasting PG: (>5.1 mmol/L)

• 1 hour PG: (>10.0mmol/L)

• 2 hour PG: (>8.5mmol/L)

GDM symptoms

GDM symptoms usually uncommon, however if blood sugar levels to high

• polydipsia (excessive thirst)

• polyurea (increase in the frequency of urination)

• xerostomia (dry mouth)

• gential itching

• blurred vision

• general malaise

Effects of GDM

1. high blood glycose caused hyperglycemia

2. hyperglycemia stimualted B cells to secrete more insulin

3. insulin targets cells in maternal tissue to uptake more glucose = insulin resistance

4. placenta secreted various hormones that inhibit the functioning of insulin

5. insulin resistance occurs due to blood glucose not being taken efficiently = hyperglycermia

6. increase in blood glucose circulated in fetal blood which leads the fetal pancreas to secrete its own insulin

7. fetus tissue uptake of more glucose causes fetal macrosomia (baby born big = increase illnesses later in life, trauma @ birth, hip dislocation

what id DoHAD

Development Origin of Health & Disease

• fetal programming: 1st introduced by David Barker

• correlation between maternal condition and development of disease in adult life

Role of placenta in fetal programming

decrease utero placental blood flow impairs supply to fetus therefore impair development (increase change for fetus to develop disease later in life)

placental weight/ birthweight ratio = better representation than birthweight

Programming of Adult Diseases

• cardiovascular disease

• renal disease

• metabolic disease and obesity

• osteoporosis

• PCOS

• neuroendocrine dysfunction

• respiratory dysfunction

• sarcopenia

• behavioural —> schizophrenia

Effect of Stress on boy and girl placentas

Generally boys tend to be worse off

Female

• slow growth trajectory

• increases feto-placental adaptability

• increases placental reserve capacity

• Increased survival

slows down growth so impacted as much

Male

• increase growth trajectory

• decreases feto-placental adaptability

• decrease placental reserve capacity

• increased intrauterine morbidity and mortality risk

keeps growing at full rate

Example of DoHAD: Cannabus Research

Maternal Obesity

Effect on Mother

• inflammation

• pregnancy related complications

• altered gut microbiota

Effect on Placenta

• altered morphology

• altered nutrient transport

• inflammation (reduced IL6, Tnf in female placenta)

• lipid accumulation

• oxidative stress

Effect on Offspring

Male

• compromised mitochondrial respiration

• increase adipocyte area

• impaired glucose tolerance

Female

• increased insulin secretion

• developed hypertension

• increased anxiety

Pre-eclampsia pathophysiology (2 stages)

Stage 1

• impaired spiral artery transformation

• placental oxidative stress and ischemia

• disrupted devlopment of placental villi

Stage 2

• release of placental factors into maternal circulation

• pro-angiogenic and anti-angiogenic imbalance (decrease PIGF, increase sFlt-1 & increase sENG)

• systemic maternal endothelial activation

• vascular injury and hypertension