Question 3: Physiological Changes During Pregnancy — Heart Disease in Pregnancy & Hematological Disorders in Pregnancy

PART A: HEART DISEASE IN PREGNANCY

Physiological Cardiovascular Changes in Normal Pregnancy

• Blood volume increases by 40–50% (plasma increases more than RBC mass → physiological haemodilution)
• Cardiac output increases by 30–50%, peaking at 28–32 weeks
• Heart rate increases by 10–15 bpm
• Blood pressure falls slightly in mid-pregnancy due to reduced peripheral vascular resistance
• Venous pressure in lower limbs increases

Incidence

Etiology

• Rheumatic heart disease — most common in developing countries (mitral stenosis is the most common lesion)
• Congenital heart disease — increasingly prevalent (ASD, VSD, PDA, coarctation of aorta, Fallot's tetralogy)
• Other causes — hypertensive heart disease, cardiomyopathy, ischaemic heart disease (rare in developing countries)

Dangerous Periods in Pregnancy for Cardiac Patients

NYHA Functional Classification

• Class I: No limitation of physical activity; no symptoms with ordinary activity
• Class II: Slight limitation; comfortable at rest; symptoms with ordinary activity
• Class III: Marked limitation; comfortable at rest; symptoms with less than ordinary activity
• Class IV: Symptoms at rest; any activity causes discomfort

Diagnosis of Heart Disease in Pregnancy

• Dyspnoea at rest or on minimal exertion
• Paroxysmal nocturnal dyspnoea
• Haemoptysis
• Syncope

• Diastolic murmur
• Systolic murmur Grade III or above
• Severe arrhythmia
• Cyanosis and clubbing

Effect of Heart Disease on Pregnancy

• Increased risk of preterm labour
• IUGR and low birth weight
• Increased perinatal mortality
• Risk of congenital heart disease in baby (if mother has congenital lesion)

Effect of Pregnancy on Heart Disease

• Pregnancy may precipitate cardiac failure
• Subacute bacterial endocarditis risk
• Pulmonary oedema
• Increased maternal mortality (especially in mitral stenosis, Eisenmenger syndrome, Fallot's tetralogy)

Antenatal Management

1. Team approach — obstetrician, cardiologist, anaesthetist
2. Frequent visits — fortnightly up to 28 weeks, weekly thereafter
3. Rest — adequate physical and mental rest; avoid excessive activity
4. Diet — high protein, low salt; avoid excessive weight gain
5. Iron and folic acid supplementation
6. Treatment of infections promptly
7. Anticoagulation — heparin preferred during pregnancy (warfarin is teratogenic in first trimester); for prosthetic valves, low molecular weight heparin is used
8. Cardiac drugs as needed — digoxin, diuretics, beta-blockers

Indications for Termination of Pregnancy

• NYHA Class III/IV
• Eisenmenger syndrome
• Primary pulmonary hypertension
• Marfan syndrome with aortic involvement

Management During Labor

• Induction at term is preferred over awaiting spontaneous onset
• Position: left lateral to avoid aortocaval compression
• Adequate analgesia — epidural preferred (reduces cardiac work)
• Vaginal delivery preferred; forceps or ventouse to cut short second stage
• Caesarean section only for obstetric indications (not cardiac disease per se)
• Avoid ergometrine postpartum (causes vasoconstriction → sudden rise in BP); oxytocin in small doses is safer
• Prophylactic antibiotics (amoxicillin) during labour and delivery

Postnatal Management

• Most dangerous period: 24–48 hours postpartum (autotransfusion effect)
• Close monitoring for cardiac failure
• Continue anticoagulation if on it
• Contraception advice — OCP contraindicated; barrier methods or IUCD preferable

PART B: HEMATOLOGICAL DISORDERS IN PREGNANCY

Physiological Haematological Changes in Pregnancy

• Plasma volume increases ~50% by 34 weeks
• RBC mass increases ~20–30%
• Net effect: physiological haemodilution (haemoglobin falls to ~11 g/dL at term — normal)
• WBC increases (10,000–12,000/mm³ in pregnancy, up to 25,000 in labour)
• Platelets slightly decreased or unchanged
• Coagulation factors (I, VII, VIII, IX, X, XII) increase → hypercoagulable state
• Fibrinogen increases to 400–600 mg/dL

ANAEMIA IN PREGNANCY

Classification (Dutta)

1. Deficiency anaemia — iron deficiency (most common), folate deficiency, B12 deficiency
2. Haemolytic anaemia — hereditary (sickle cell, thalassaemia) or acquired
3. Aplastic anaemia
4. Anaemia of chronic disease/infection — malaria, hookworm, TB

Iron Deficiency Anaemia

• Fetal requirements (~300 mg)
• Expanded RBC mass (~500 mg)
• Blood loss at delivery (~200 mg)
• Total requirement: ~1000 mg
• Average Indian diet provides only ~10–15 mg/day; absorption further limited

• Fatigue, dyspnoea, pallor, palpitations
• Koilonychia, glossitis, angular stomatitis (severe cases)
• Increased susceptibility to infection

• Hb, peripheral blood smear (hypochromic microcytic RBCs)
• Serum ferritin (most sensitive early indicator; < 12 µg/L)
• Serum iron ↓, TIBC ↑

• Cardiac failure (if very severe)
• Increased risk of preterm labour
• Postpartum haemorrhage (uterus fails to contract well in anaemic patients)
• Poor wound healing, puerperal sepsis

• IUGR, low birth weight
• Increased perinatal mortality
• Neonatal anaemia in severe maternal anaemia

• Oral iron: Ferrous sulphate 200 mg (60 mg elemental iron) three times daily is standard; ferrous gluconate, ferrous fumarate are alternatives
• Take on empty stomach with vitamin C (ascorbic acid enhances absorption)
• Parenteral iron (IV iron sucrose or iron dextran): When oral iron not tolerated, non-compliant, or Hb needs rapid rise before delivery
• Blood transfusion: Only in severe anaemia (Hb < 7 g/dL near term) or symptomatic; packed red cells preferred

• All pregnant women: elemental iron 60 mg + folic acid 400 µg daily from 12 weeks till 3 months postpartum (National programme in India)

Megaloblastic Anaemia (Folic Acid Deficiency)

• Second most common nutritional anaemia in pregnancy
• Folic acid requirements double in pregnancy
• Peripheral smear: macrocytic (megaloblastic) red cells, hypersegmented neutrophils
• Treatment: Folic acid 5 mg/day orally
• Prevention: Folic acid 0.4–0.5 mg/day preconceptionally and throughout first trimester (prevents neural tube defects)

Sickle Cell Disease in Pregnancy

• Autosomal recessive disorder; HbS substitution
• Complications: Painful sickle cell crises, pulmonary infarction, acute chest syndrome, renal failure, stroke
• Obstetric complications: Spontaneous abortion, IUGR, preterm labour, increased perinatal mortality
• Management: Multidisciplinary care, hydration, oxygen during crises, exchange transfusion if needed; avoid hydroxyurea in pregnancy

Thalassaemia in Pregnancy

• Beta-thalassaemia trait (minor): Mild anaemia, microcytosis; patient generally tolerates pregnancy well; oral iron may not help (iron stores adequate); folate supplementation important
• Beta-thalassaemia major: Rarely survives to reproductive age; pregnancy very high risk
• Screening: MCV < 80 fL + Hb electrophoresis; partner testing for genetic counselling

THROMBOCYTOPENIA IN PREGNANCY

• Gestational thrombocytopenia: Most common (70–80%); benign, no treatment needed, platelet > 70,000
• ITP (Immune thrombocytopenic purpura): Autoimmune; treat with prednisolone, IV Ig; risk of neonatal thrombocytopenia
• TTP/HUS, HELLP syndrome: Severe, life-threatening; require urgent management

Question 4: Physiological Changes During Pregnancy — Pyelonephritis in Pregnancy & Asymptomatic Bacteriuria

Physiological Changes in the Urinary System During Pregnancy

• Kidneys enlarge slightly due to increased blood flow and interstitial oedema
• Renal blood flow and GFR increase by 40–50% → serum creatinine and urea fall (creatinine > 0.8 mg/dL is abnormal in pregnancy)
• Ureteral dilatation (hydroureter) occurs from as early as 10 weeks — due to progesterone-induced smooth muscle relaxation AND mechanical compression by the gravid uterus at the pelvic brim
• Dilatation is more marked on the right side (due to dextrorotation of uterus and right ovarian vein)
• Urinary stasis in the dilated urinary tract predisposes to UTI
• Glycosuria and aminoaciduria are physiological in pregnancy — they provide a good culture medium for bacteria
• Bladder capacity increases; reduced bladder tone → incomplete emptying

PART A: ASYMPTOMATIC BACTERIURIA (ASB)

Definition

Incidence

• Occurs in 2–10% of pregnant women
• Same incidence as in non-pregnant women, but the consequences are far more serious in pregnancy

Causative Organisms

• Escherichia coli — most common (80–90%)
• Klebsiella, Proteus mirabilis, Staphylococcus saprophyticus, Enterococcus faecalis

Importance / Why It Must Be Treated

• 40% of ASB cases progress to symptomatic UTI or pyelonephritis
• Risk of preterm labour and low birth weight
• Risk of maternal hypertension
• Treatment reduces progression to pyelonephritis by ~70–80%

Diagnosis

• Urine culture (midstream clean-catch) — gold standard
• ≥ 10⁵ colony-forming units/mL of a single organism = significant bacteriuria
• Routine screening: once at the first antenatal visit (ideally at booking, around 16 weeks)
• Urine microscopy: pyuria (> 10 WBC/high-power field) may or may not be present in ASB

Treatment

• Sulfonamides: avoid in third trimester (risk of neonatal jaundice)
• Tetracyclines: contraindicated in pregnancy
• Quinolones (e.g. ciprofloxacin): generally avoided in pregnancy
• After treatment: repeat urine culture (test of cure) 1–2 weeks later
• If recurrent ASB: suppressive therapy (nitrofurantoin 50–100 mg at night) for remainder of pregnancy

PART B: PYELONEPHRITIS IN PREGNANCY

Definition

Incidence

• Complicates 1–2% of all pregnancies
• Most commonly occurs in second trimester (when ureteral dilatation is maximal)
• 20–40% of untreated ASB cases progress to pyelonephritis

Pathogenesis

• Ascending infection from bladder → ureter → renal pelvis → renal parenchyma
• Facilitated by ureteral dilatation, urinary stasis, vesicoureteral reflux (which increases in pregnancy)
• Right kidney more commonly affected

Clinical Features

• Fever with rigors (high-grade, 39–40°C)
• Loin pain / flank pain (unilateral, usually right-sided)
• Nausea and vomiting
• Dysuria, frequency, urgency (lower urinary tract symptoms may precede)
• Headache, malaise

• Pyrexia, tachycardia
• Costovertebral angle (CVA) tenderness — pathognomonic finding
• Uterine irritability / preterm contractions may be present
• In severe cases: hypotension, septic shock

Investigations

1. Urine microscopy — pyuria (many pus cells), bacteriuria, red cell casts
2. Urine culture and sensitivity — essential before starting antibiotics
3. Blood culture — if septicaemia suspected (positive in ~15% cases)
4. CBC: leukocytosis
5. Renal function tests: serum creatinine, urea
6. Ultrasound kidneys: to rule out calculi, abscess, hydronephrosis
7. Blood glucose (to rule out diabetes)

Effects of Pyelonephritis on Pregnancy

• Septicaemia and septic shock
• Anaemia (endotoxin-induced haemolysis)
• Acute renal failure
• Adult Respiratory Distress Syndrome (ARDS) — rare but serious
• Transient impairment of renal function

• Preterm labour (endotoxins stimulate uterine contractions)
• IUGR
• Increased perinatal mortality

Management

Hospitalisation (Always Required)

General Measures

• Bed rest in left lateral position
• Adequate IV fluids (hydration) — 3–4 litres/day
• Monitor urine output (> 30 mL/hour)
• Temperature, pulse, BP monitoring every 4 hours
• Antipyretics (paracetamol for fever)
• Tocolysis if preterm contractions present (nifedipine or salbutamol)

Antibiotic Therapy

• IV antibiotics continued until afebrile for 48 hours
• Then switched to oral antibiotics for a total of 14 days
• Test of cure: urine culture 1–2 weeks after completing treatment
• Suppressive therapy: nitrofurantoin nightly for rest of pregnancy if recurrence occurs

If No Response to Treatment

• Resistant organism — review culture sensitivity
• Renal calculus — ultrasound/limited IVP
• Perinephric abscess — drainage required
• Surgical drainage of obstruction if needed

Recurrence

• Common — up to 30% without suppressive therapy
• Low-dose nitrofurantoin (50–100 mg at night) as prophylaxis for rest of pregnancy

Summary Table: ASB vs Acute Pyelonephritis