Physiological Changes in Pregnancy

Presented by: Mohd Amir & R.Nandinii

Uterus

Non Pregnant Non Pregnant UterusUterus

Pregnant UterusPregnant Uterus

MusculaMuscularr

StructurStructuree

Almost Solid Almost Solid Relatively thin – Relatively thin – walled (≤ 1.5 cm)walled (≤ 1.5 cm)

weightweight ≈ ≈ 70 gm70 gm Approx. 1100 gm Approx. 1100 gm by the end of by the end of pregnancypregnancy

VolumeVolume ≤ ≤ 10 mL10 mL ≈ ≈ 5 L by the end 5 L by the end of pregnancyof pregnancy

Mechanism Of Uterine Enlargement

Uterine size, shape & position

• First few weeks, original peer shaped organ

• As pregnancy advances, corpus & fundus assumes a more globular form.

• By 12 weeks, the uterus becomes almost spherical .

• Subsequently, uterus increases rapidly in length than in width & assumes an ovoid shape.

• With ascent of uterus from pelvis, it usually undergoes Dextrorotation (caused by the rectosigmoid colon on the left side)

CERVIX

• Estradiol + progesterone swollen and softer during pregnancy

• Estradiol stimulates growth of columnar ep. of cervical canal ectropion (visible on ectocervix) prone to contact bleeding

• ↑ vascularity look bluer

• Mucous glands distended + ↑ complexity ↑ secretion mucus thickened operculum @ os (protective plug)

• PG (remodelling of cervical collagen) + collagenase (from leukocytes) softening

• Estrogen vaginal epithelium thicker ↑ desquamation rate ↑ vaginal discharge > acidic protect against ascending infection

• Vagina become more vascular

BREAST

• Deposition of fat around the glandular tissue

• Estrogen ↑ number of glandular ducts

• Progesterone + hPL ↑ number of gland alveoli

• hPL stimulate synthesis of alveolar casein + lactoglobulin + lactalbumin

• ↑ [serum prolactin] in pregnancy antagonized by estrogen no lactation

• 48 hours after birth rapid ↓ of [estrogen] lactation

• End of pregnancy and early puerperium colostrum produced (thick yellow secretion + ↑ immunoglobulin)

• Early + frequent suckling stimulates ant. and post. Pituitary gland prolactin + oxytocin promotion of lactation

• Stress + fear ↑ dopamine ↓ synthesis and release of prolactin

• 2-3 days of puerperium prolactin alveoli distended by milk breast engorgement

• oxytocin myoepithelial cells surrounding alveoli and small ducts contract squeezes milk into larger ducts and subareolar reservoirs

• Oxytocin inhibit dopamine ↑ prolactin successful lactation

Endocrinological Changes in Pregnancy

• Peptide and steroid hormones produced by• Non-pregnant: endocrine glands• Pregnant: intrauterine tissues

Hormones

Pregnancy specific

• Human chorionic gonadotrophin (hCG)

• α and β (pregnancy specific; produced by trophoblast detectable w/in days of implantation)• production influenced by leukemia inhibitory factor (LIF) and isoform of GnRH• Maintain corpus luteum’s fx• peak values @10w progesterone by placenta ↓ to plateau @>12w• α hCG ≈ α of LH, FSH, TSH supress FSH and LH secretion by ant. pituitary

• Human placental lactogen (hPL)

• Produced by placenta• partial homology with prolactin and hGH

Hormones

Steroids • produced by placenta and fetus• Concentration ↑ earliest weeks of pregnancy plateau•Effects upon myometrium and (+prolactin) breast tissue • effects on smooth muscle of vascular tree, GIT, GUT

• estrogen • max ↑ 30-40mg/day (80% estriol)• encourages cellular hypertrophy (uterus, breast)•Alter chemical constitution of con. tissue more pliable• Water retention• Reduce sodium excretion

• progesterone • reduce smooth muscle tone• ↓ stomach motility nausea• ↓ colon activity delayed emptying ↑ water reabsorb constipation• ↓ uterine tone prevent contraction

• ↓ vascular tone diastolic P ↓ venous dilatation• ↑ temperature• ↑ fat storage• Induce over-breathing• Induce development of breast

Hormones

Pituitary related

• Prolactin • produced by lactotrophs of ant pituitary and cells of decidua• Rc in trophoblast cells and w/in amniotic fluid• Stimulated by estrogen and sleep•Inhibited by hPL and dopamine agonist• essential of lactation

•Human growth hormone (hGH) • production by ant pituitary supressed in pregnancy• [hGH] ↓• hPL supress hGH

•Adrenocorticotrophic hormone (ACTH)

• placental clock theory

Pituitary gland increase 30% in weight in first pregnancy (50% in next pregnancy) can produce headache

Hormones

Hypothalamus related

• Gonadotrophin-releasing hormone (GnRH)• Corticotrophin-releasing factor (CRF)

CRF placental clock theory

Other peptides

• Insulin-like growth factor I and II (IGF)•1,25-Dihydroxycholecalciferol•Parathyroid hormone-related peptide•Renin•Angiotensin II

• IGF regulates fetal growth• IGF I and II: produced by fetal cells (in liver) and maternal cells (in uterus)• IGF II predominated in fetal circulation• 1,25-(OH)2D3: ↑ calcium absorption

Carbohydrate metabolism

• First half of pregnancy• Fasting plasma glucose concentration ↓• Little change in plasma insulin level• OGGT enhance respond compared to non-pregnant, normal insulin

release but ↓ blood glucose value

• Second half of pregnancy• Delay in reaching peak glucose value• ↑ glucose value + ↑ [plasma insulin] = relative insulin resistance

(↓ sensitivity by 80%)• May involve hPL or other growth-related hormones• Reduced peripheral insulin sensitivity• Characteristic of insulin binding to Rc also altered (= obese and NIDDM)

• In pancreas:• ↑ size of Langerhans cell• ↑ number of β cell• ↑ Rc for insulin

Fat metabolism

• 4kg fat is stored by 30 weeks of gestation

• Mostly in form of depot in abdominal wall, back and thighs.

• Modest amount stored in breast

• Three points to be noted• Total metabolism and energy demand ↑• Glycogen stores are diminished energy from KH ↓ • Although blood fat in greatly increase only a moderate amount stored

Thyroid function

• hCG ≈ TSH hCG maximal suppress maternal TSH production @ trimester I• hCG or TSH nausea and vomiting improve after

trimester I• Biochemical hyperthyroidism + ↑ free T4 + suppressed

TSH hyperemesis gravidarum• Iodine active transport to feto-placental unit + ↑ urine

excretion plasma level ↓ ↑ uptake of iodine from blood by thyroid gland• Diet insufficiency of iodine hypertrophy of thyroid

gland trap iodine• ↑ thyroid-binding globulin, bound T4 and T3• Free T4 and T3 fall a little in trimester II and III

Calcium metabolism

• 40% bound to albumin

• Pregnancy: ↓ [plasma albumin] ↓ [plasma calcium]

• Little changes to unbound calcium

• ↑ demand from fetus transplacental flux 6.5 mmol/day (~ 80% absorbed in GIT by non-pregnant)

• Mother: ↑ absorption and ↓ excretion little changes in bone (failed = osteopenia)

• ↑ calcium absorption by 1,25-dihydroxycholecalciferol (metabolite of vit D3) which is influenced by PTH

• PTH ↑ 1/3 in pregnancy

• No changes in calcitonin or other D3 metabolites

• [plasma calcium] fetus > maternal and independent regulation of PTH and calcitonin

Placental corticotrophin-releasing factor

• Mid-pregnancy: trophoblast produces CRF stimulates fetal pituitary ↑ ACTH fetal adrenal ↑ fetal dihydroepiandrosterone (DHEA) precursor of placental estrogen secretion ↑ estrogen @ end of pregnancy ↑gap junc synthesis @myometrial aid conduction regular uterine contractions labour = placental clock theory

• CRF synthesis regulated by +ve feedback by estrogen

Corticosteroid and renin-angiotensin system

• Trophoblast cell CRF and ACTH regulate activity of fetal adrenal glands, myometrium and possibly maternal adrenal glands.

• Cortisol ↑ progressively, mostly bound to cortisol-binding globulin (CBG)

• ACTH may regulate maternal cortisol level because there’s lack of diurnal fluctuation of cortisol and attenuated response to dexamethasone supression

Weight Increase in Pregnant Women

• Metabolic changes + fetal growth ↑ increase weight ~25% of non-pregnant (~12.5 kg)

• First half: weight increase is varied

• Second half: ↑ 0.5kg/week (2kg/month)

• At term the gain stopped

• After 40 weeks, may fall

• Weight increase due to:• Growth of conceptus• Enlargement of maternal organs• Maternal storage of fat and protein• ↑ maternal blood volume and interstitial fluid

Breast 1-1.5 kg

Uterus0.5-1 kg

Fetus and placenta 5 kg

Hematologic Changes in Pregnancy

concentrations of estrogen & progesterone

Directly act on kidney

Causing release of renin

Activates aldosterone-renin-angiotensin mechanism

Renal sodium retention & in total body water

in plasma volume (45%)

Blood volume

PREGNANCY

hb

htPhysiological

anemiaPhysiological

anemia

•To allow adequate perfusion of vital organs including placenta and fetus•To anticipate blood loss a/w delivery

Hypercoagulable State

Increase in: Decrease in:

PROCOAGULANT FACTORS•Factor VII•Factor VIII•Factor IX•Factor X•Factor XII•Fibrinogen

ANTICOAGULANT•Protein S activity•Antithrombin IIIa

•Activated Protein C resistance

ESR

Increased production of:

RBC mass (20%) WBCPlatelet

Due to increase in renal erythropoietin production

Supports higher metabolic requirement for O2 during

pregnancy

BUT platelet consumption

increase more

Fall to low normal value

Mild thrombocytopenia

Mainly due to increase in no of

PMN cells as early as 3 wks AOG

Difficult to differentiate with

infection

Neutrophilia

Immunosuppresive State

Approximately 30% of women develop IgG abs against the

inherited paternal human leukocyte ag of fetus

BUT, the role of these abs is UNCLEAR & there is no evidence of

attack on fetus

Lack of maternal immunity towards the fetus

Due to reduced no of cytotoxic T cells (CD8+) during pregnancy

Potentially harmful T cell-mediated immune responses downregulated &

components of innate immune system activated instead

Allowed fetal allograft to implant & develop

Physiological Changes in Cardiovascular

System

Anatomic Changes

Blood volume changes

Cardiac Output

Blood Pressure

Clinical findings in cardiovascular system examination

Changes of the respiratory function in

pregnancy

Airway

Ventilation

Oxygenation

Arterial Gases

Gastrointestinal and Hepatobilliary

Difference in Gastrointestinal tract in Pregnancy and Non pregnant state

Gastrointestinal

• As the gestational age in pregnancy increase so does the size of uterus.

• This increase in size of the uterus causes the stomach and the intestine to be displace upwards

• The position of the appendix is usually displace upwards towards the right upper flank region.

• Because of the alteration of the intra-abdominal structure this makes it very difficult to diagnose any disease associated with the intra abdominal

• Increase in progesterone level causes• Lower esophageal sphincter tone to be reduced (esophageal reflux)• Increase placenta production of gastrin, which increases gastric

acidity. (heart burn)• Reduced motility of the gut which result in delay of the gastric

emptying time. (constipation)

• During labour the motility of the gut decreases further and even during the pueriperium period, emptying of the gut is still delayed.

• This increases the risk of pregnant women to develop aspiration of gastric content-especially if they are sedated after 16 weeks of gestation.

Liver

• Liver may become more difficult to examine during pregnancy due to the expanding uterus.

• Due to hyperoestrogeninc state in pregnancy, clinical findings such as telangiectasia and palmar erythema that are associated with liver disease in non pregnant state are found in 60% of the pregnant woman

• Despite of the increase of the portal vein pressure in pregnancy, the size of the liver and the hepatic blood flow remains unaltered.

• Liver function also remains mostly the same.

• Total alkaline phosphate serum increases up to double the normal amount due to fetal and placenta production.

• Hepatic production of protein increases but because of the expanding maternal placenta volume serum albumin level still remain low.

• Most important changes in pregnancy to the liver is the increased in production and plasma fibrinogen and the clotting factors

Gall bladder

• During pregnancy, contractility of the gallbladder is reduced.

• Progesterone may impairs gallbladder contraction by inhibiting cholecystokinin-mediated smooth muscle stimulation (primary regulator of gallbladder contraction).

• This impairment leads to stasis, and is associated with the increased cholesterol saturation of pregnancy

• Intrahepatic cholestasis has been linked to high circulating levels of estrogen, which inhibit intraductal transport of bile acids

Gastrointestinal symptoms associated with Pregnancy

• Constipation

• Morning sickness

• Gastroesophageal reflux

• Haemorrhoids

Kidneys & Urinary Tract Changes

Kidney

Anatomic Changes

• Increase in length for about 1 - 2 cm.

• Calyces, renal pelvis & ureters dilate → impression of obstruction.

• Anatomical changes predispose pregnant women to ascending UTI.

• By 6 weeks postpartum, renal dimensions return to pre-pregnancy values.

Functional Changes

• Renal vascular resistance decreases → renal plasma flow increases 50 – 85% above nonpregnant values during first half of pregnancy.

• Renal perfusion increases → rise in GFR by approximately 50%.

• GFR returns to normal within 12 weeks of delivery.

Functional Changes

• Renal clearance of creatinine increases as the GFR rises.

• Urinary protein loss normally does not exceed 300 mg over 24 hours, which is similar to nonpregnant state.

Functional Changes

• Increase in GFR plus saturated ‘renal threshold’ in the proximal convoluted tubule explain the increase amount of glucose in urine → glycosuria.

• More than 50% of women have glycosuria sometime during pregnancy.

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