biochemistry of pregnancy

The Biochemistry of The Biochemistry of PregnancyPregnancyDr. Gill BurrowsDr. Gill Burrows

Consultant Chemical PathologistConsultant Chemical Pathologist

Stepping Hill HospitalStepping Hill Hospital

Normal pregnancyNormal pregnancy

• Fluid and electrolyte homeostasis

• Acid base changes

• Carbohydrate metabolism

• Calcium homeostasis

• Lipoprotein metabolism

• Endocrine changes

Disorders of pregnancyDisorders of pregnancy

• Hypertensive disorders– Pre-eclampsia– HELLP

• Diabetes mellitus

• Hyperlipidaemia

• Jaundice

• Acute endocrinopathies

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


• 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


• 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

Disorders associated with fluid Disorders associated with fluid and electrolyte homeostasisand electrolyte homeostasis

• Hyperemesis gravidarum

• Pre-eclampsia

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

Disorders of acid-base Disorders of acid-base metabolism metabolism

• As for non-pregnant patients

• Metabolic acidosis– DKA– lactic acidosis

• Metabolic alkalosis– hyperemesis gravidarum

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

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

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

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


• Reduced suppression of hepatic glucose production - decreased hepatic insulin sensitivity

• insulin insensitivity at conception


• 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

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%

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

Disorders of lipoprotein Disorders of lipoprotein metabolismmetabolism

• Hyperchylomicronaemia– Type I

• lipoprotein lipase deficiency• apo CII deficiency

– Type V– May cause

• eruptive xanthomas• pancreatitis

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

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

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

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

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


• 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


• Functions– myometrial and endometrial growth– growth of alveoli and breast ducts– angiogenesis– protein synthesis and cholesterol metabolism– sodium and water retention

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

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

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

Hypertensive disorders of Hypertensive disorders of pregnancypregnancy

• Pre-existing hypertension

• Pre-eclampsia

• HELLP

• commonest severe complication of pregnancy

• 5-15 % associated with proteinuria

Pre-eclampsiaPre-eclampsia

• Increased incidence– increased age– primigravida– genetic predisposition– obesity– twins

• Reduced incidence in smokers

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

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

HELLPHELLP

• Haemolysis

• Raised liver enzymes

• Low platelets

• Blood film• LDH > 600 IU/L

• AST > 70 IU/L

• Platelets < 100 000/uL

Jaundice in pregnancyJaundice in pregnancy

• 1 in 2000 pregnancies– viral hepatitis– intrahepatic cholestasis of pregnancy– drug treatment– HELLP– acute hepatic failure

Reference rangesReference ranges

biochemistry of pregnancy

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