biochemistry of pregnancy
TRANSCRIPT
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The Biochemistry of The Biochemistry of PregnancyPregnancyDr. Gill BurrowsDr. Gill Burrows
Consultant Chemical PathologistConsultant Chemical Pathologist
Stepping Hill HospitalStepping Hill Hospital
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Normal pregnancyNormal pregnancy
• Fluid and electrolyte homeostasis
• Acid base changes
• Carbohydrate metabolism
• Calcium homeostasis
• Lipoprotein metabolism
• Endocrine changes
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Disorders of pregnancyDisorders of pregnancy
• Hypertensive disorders– Pre-eclampsia– HELLP
• Diabetes mellitus
• Hyperlipidaemia
• Jaundice
• Acute endocrinopathies
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Fluid and electrolyte Fluid and electrolyte homeostasishomeostasis
• Markers of physiologic changes– weight gain– haemodilution– reduced plasma
osmolality– reduced sodium
concentration
• Causes
– increased fluid volume– redistribution of fluid
between ICF and ECF– sodium retention by
kidney (~900 mmol)– increased TBW by 8.5 L – increased plasma vol by
1.2 L
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Fluid and electrolyte Fluid and electrolyte homeostasishomeostasis
• Activated renin-angiotensin system (despite increased plasma volume)– ? Due to fall in vascular resistance– ? New set point of fluid volume homeostasis
• Known resistance to pressor and renal effects of angiotensin - with increased adrenal response
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Fluid and electrolyte Fluid and electrolyte homeostasishomeostasis
• Osmoregulation– resetting of osmotic control at a lower
osmolality– osmotic threshold for
• thirst decreased by 9 mmosmol/kg• AVP secretion by 6 mosmol/kg
– decreased osmolality seen by 5/40, maximal at 10/40
– ? mechanisms
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Disorders associated with fluid Disorders associated with fluid and electrolyte homeostasisand electrolyte homeostasis
• Hyperemesis gravidarum
• Pre-eclampsia
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Acid-base changesAcid-base changes
• Hyperventilation results in reduced PaCO2
(from ~39 mm Hg to 31 mm Hg)
• pH increases slightly to 7.42-7.44
• HCO3- decreases by ~ 4 mmol/L
• Respiratory alkalosis with metabolic compensation
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Disorders of acid-base Disorders of acid-base metabolism metabolism
• As for non-pregnant patients
• Metabolic acidosis– DKA– lactic acidosis
• Metabolic alkalosis– hyperemesis gravidarum
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Carbohydrate metabolismCarbohydrate metabolism
• Important for:– increasing adipose tissue in mother in early
pregnancy - to be used for energy in late pregnancy and lactation
– foetoplacental unit - foetus requires maternal glucose
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Carbohydrate metabolismCarbohydrate metabolism- early pregnancy- early pregnancy
• Basal hepatic glucose metabolism
• No change
• Postprandial hepatic glucose metabolism
• increased glucose• increased insulin• ? Degree of insulin
insensitivity
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Carbohydrate metabolismCarbohydrate metabolism- late pregnancy- late pregnancy
• Basal hepatic glucose metabolism
• increased hepatic glucose production (despite increased insulin)
• decreased serum glucose
• Postprandial hepatic glucose metabolism
• increased insulin response to glucose load
• insulin insensitivity
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Gestational diabetesGestational diabetes
• 3-5 % of pregnant women
• defined as ‘ abnormal GTT which is diagnosed or first recognised during gestation’
• confers an increased risk of developing diabetes in later life
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Gestational diabetesGestational diabetes
• Reduced suppression of hepatic glucose production - decreased hepatic insulin sensitivity
• insulin insensitivity at conception
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Gestational diabetesGestational diabetes
• Diagnosis - European Diabetes Policy Group 1999– Venous plasma glucose > 6.0 mmol/L
• perform 75 g oral GTT• manage as diabetes if
– fasting plasma glucose >= 7.0 mmol/L OR– 2 hr plasma glucose >= 7.8 mmol/L
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Calcium metabolismCalcium metabolism
• Maintenance of ionised calcium within narrow limits is important for maternal and foetal health
• State of “physiologic absorptive hypercalciuria”
• Requirement increased by 30%
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Lipoprotein metabolismLipoprotein metabolism
• Increased triglycerides (~1.7 mmol/L)
• Increased LDL cholesterol (~ 1 mmol/L)
• HDL - increased 1st trimester, peak at mid-gestation, fall in 3rd trimester
• Maternal fuel
• placental steroidogenesis
• ? Apo A-1 important in foetal development
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Disorders of lipoprotein Disorders of lipoprotein metabolismmetabolism
• Hyperchylomicronaemia– Type I
• lipoprotein lipase deficiency• apo CII deficiency
– Type V– May cause
• eruptive xanthomas• pancreatitis
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Endocrinology of foeto-placental Endocrinology of foeto-placental unitunit
• Placental peptide hormones
• hCG• hPL• others
– trophic hormones– releasing hormones– pregnancy specific
hormones
• Steroid hormones
• Oestrogens• Progesterone
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Human chorionic gonadotrophinHuman chorionic gonadotrophin
• Produced by blastocyst, then syncitiotrophoblast
• 2 chain glycoprotein• detectable by day 9• x2 every 2 days to a
peak 8-10/40 after LMP
• Plateaus at 18-20/40
• Functions– prevents regression of
corpus luteum– stimulates secretion of
oestrogen and progesterone
– stimulates foetal adrenal
– stimulates Leydig cells of foetal testes
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Human placental lactogenHuman placental lactogen
• Produced by syncitiotrophoblast
• detectable by 4 weeks after ovulation
• plasma concentration proportional to functional placental mass
• Functions:– affects fat and CHO
metabolism– mobilises FFA– inhibits gluconeogenesis– inhibits peripheral uptake
of glucose– increases uptake of amino
acids and ketones by placenta
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Weeks gestation hCG hPL5 22
10 105 0.515 30 220 18 325 19 430 20 535 19 6.840 18 7
hCG and hPL in pregnancy
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8
Weeks gestation (/5)
hC
G (
IU/m
L)
0
1
2
3
4
5
6
7
8
hP
L (
ug
/mL
)
hCG
hPL
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Steroid hormonesSteroid hormones- oestrogen- oestrogen
• In early pregnancy– FSH stimulates testosterone and
androstenedione secretion from theca cells– testosterone and androstenedione aromatised
by granulosa cells of corpus luteum– oestrogen induces FSHand LH receptors of
granulosa cells
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Steroid hormonesSteroid hormones- oestrogen- oestrogen
• In later pregnancy– androgens produced by foetal adrenal cortex
are converted into oestriol by the placenta– production of steroids by foetal adrenal cortex
at term is 5-6 x that of an adult– increase in maternal serum oestradiol
throughout pregnancy
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Steroid hormonesSteroid hormones- oestrogen- oestrogen
• Functions– myometrial and endometrial growth– growth of alveoli and breast ducts– angiogenesis– protein synthesis and cholesterol metabolism– sodium and water retention
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Steroid hormones - Steroid hormones - progesteroneprogesterone
• Produced by corpus luteum for first 10 weeks, then syncitiotrophoblast
• Increases throughout pregnancy• functions include
– decidualisation of endometrium– relaxation of smooth muscle– vasodilatation– hyperventilation– increased thirst, appetite, fat deposition
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Thyroid functionThyroid function
• Increase in TBG - 2-3x– increased hepatic synthesis– increased sialylation
• raised total T4 and T3– increased TBG
• decreased FT4• thyroid stimulation by hCG• increased iodide loss in urine
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Thyroid dysfunction in Thyroid dysfunction in pregnancypregnancy
• Hyperthyroidism
• 0.2 %• Graves disease• Pregnancy specific
– hyperemesis gravidarum– trophoblastic disease
• Hypothyroidism
• 0.3-0.7 %• Autoimmmune
thyroiditis• Iodine deficient goitre
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Hypertensive disorders of Hypertensive disorders of pregnancypregnancy
• Pre-existing hypertension
• Pre-eclampsia
• HELLP
• commonest severe complication of pregnancy
• 5-15 % associated with proteinuria
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Pre-eclampsiaPre-eclampsia
• Increased incidence– increased age– primigravida– genetic predisposition– obesity– twins
• Reduced incidence in smokers
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Pre-eclampsiaPre-eclampsia
• Loss of the insensitivity of the arterial system to angiotensin II– endothelial damage– placental ischaemia– impaired vasodilatation– reduced GFR– reduced renal blood flow– reduced plasma volume
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HELLPHELLP
• Haemolysis
• Elevated Liver enzymes
• Low Platelets
• Incidence - ? 20% of severe pre-eclampsia
• Presentation– nausea, vomiting, flu-like illness– RUQ pain– hypertension or proteinuria may be slight
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HELLPHELLP
• Haemolysis
• Raised liver enzymes
• Low platelets
• Blood film• LDH > 600 IU/L
• AST > 70 IU/L
• Platelets < 100 000/uL
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Jaundice in pregnancyJaundice in pregnancy
• 1 in 2000 pregnancies– viral hepatitis– intrahepatic cholestasis of pregnancy– drug treatment– HELLP– acute hepatic failure
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Reference rangesReference ranges