FISIOLOGI KEHAMILAN

Physiology changes associated with pregnancy

Reproductive Tracts Breast Skin Water and Electrolit Hematology Cardiovascular

System

Respiratory System Gastrointestinal

System Urinary System Endocrine System Metabolism Skeleton

Reproductive Tracts

Uterus: from 50g-1100g

Isthmus uteri (lower segment of the uterus) Hegar sign

Braxton Hicks contraction: sporadic, irregular, asymmetrical, and painless, low pressure, lasting < 30 sec

Reproductive Tracts

Cervix and vulva —— Chadwick’s sign congestion of the pelvic vasculature, cause bluish or purplish discoloration of the cervix and vulva

Leukorrhea: increase in vaginal discharge, rich in glucose, lactic acid, low vaginal pH

Ovary: slightly enlarged, corpus luteum regresses after 10 weeks’ gestation

Breasts Early change

tenderness, tingling and heaviness vascular engorgement leads to enlargement

Ductal growth due to estrogen Alveolar hypertrophy due to progesteron

Enlargement and pigmentation of areolae Montgomery’s tubercles: enlargement of circumlacteal

sebaceous glands of the areola Colostrum may be expressed later in pregnancy Milk production

Estrogen, progesteron, prolactin, hPL, cortisol and insulin

Lactation likely due to drop in estrogen and progesterone after delivery

Skin

Spider angiomata (face, upper chest, and arm) and palmar erythemaelevated estrogen levels both regress after delivery

Striae gravidarum Increased eccrine sweating and sebum

excretion Hyperpigmentation Melasma: “mask of pregnancy”

elevated estrogen and progesteron Nevi may darken, enlarge or show increased

activity rapidly changing nevi should be excised

Body Water

TBW increases from 6.5L to 8.5L At term water content of fetus, placenta and

AF is 3.5L BV, PV, RBC, extravascular, intracellular

Pregnancy is a condition of chronic volume overload

Water retention exceeds Na retention-decreased plasma osmolality

Hematology – Blood volume

Increases progressively from 6 to 8 weeks gestation

maximum volume at 32 weeks - 45% increase

possibly due to estrogen stimulation of renin-angiotensin-aldosterone system

(Inc Prog, NO->Dec SVR->Dec MAP->Inc Na retention)

Hematology – RBC mass

Red blood cell mass increases by 250-450 cc by term

Increased production Possibly hormonally

mediated

Hematology - Iron Maternal requirement is

1000mg Increase maternal red cell mass : 500 mg Fetal development : 300 mg Compensate for normal iron loss : 200 mg

Normal pregnant woman needs to absorb about 3.5 mg/day of iron

the goal of iron supplementation is to prevent maternal iron deficiency

Iron is actively transported to the fetus

Hematologic changes

IMPLICATIONSThe increase in plasma volume and

rbc mass translates into a 45% increase in circulating blood volume

may protect from hemodynamic instability

may serve to dissipate fetal heat production and provide increase renal filtration

physiologic anemia of pregnancy may function to decrease blood viscosity may improve intervillous perfusion?

Hematology

LEUKOCYTES Peripheral wbc rises progressively during

pregnancy 1st ∆ – mean 9500/mm3 (3000-15,000) 2nd and 3rd ∆ – mean 10,500 (6000-16,000) Labor – may rise to 20-30,000

Rise is due to increase in pmns (demargination)

PLATELETS Platelets experience a progressive decline but

should remain within normal range Likely due to increased destruction

Hematology

COAGULATION FACTORSIncreased levels

Fibrinogen (Factor I) Factors VII through X

No change in prothrombin (Factor II), Factors V and XII

Decline in platelet count, Factors XI and XIII Bleeding time and clotting time are

unchanged in normal pregnancy

Cardiovascular – Cardiac output

Maternal cardiac output increases about 30-50% during pregnancy (mean 33%) pregnancy maximum of 6 L/min CO remains maximal until delivery Earliest rise in CO is due to increase in SV As pregnancy progresses

Gradual increase in mat HR (15-20 bpm rise) SV declines to near non-pregnant levels increase HR is what maintains the elevated CO

Cardiovascular – Cardiac output

CO is position dependent Lower when supine

IVC compression by the uterus reduces venous return to the heart

At 38-40 weeks, there is a 25-30% fall in CO when turning from the side to the back

Fall in CO is compensated by a rise in peripheral vascular resistance supine hypotensive syndrome (1-10% patients)

Cardiovascular – Cardiac output

Distribution of CO First trimester and non-pregnant state

Uterus receives 2-3% By term

Uterus receives 17% Breasts 2%

Reduction of the fraction of CO going to the splanchnic bed and skeletal muscle

CO to the kidneys, skin, brain and coronary arteries does not change

Cardiovascular – Arterial BP

BP varies with position

Peripheral vascular resistance falls during pregnancy

Progesterone’s smooth muscle relaxing effect ?heat production by the fetus vasodilatation

The reduction in PVR may lead to a progressive fall in systemic arterial bp during the first 24 weeks of pregnancy

Gradual rise after 24 weeks non-pregnant levels by term

Cardiovascular – Venous system

Venous compliance increases during pregnancy decrease in flow velocity and stasis progesterone effects on smooth muscle Forearm venous pressure increases by 40-50% Calf venous pressures are always higher

due to the enlarging uterus

Cardiovascular - LV function

Left ventricular dimensions and volume increase during pregnancy most parameters of LVF are the same as in the

non-pregnant state Ejection fraction, rate of internal diameter

shortening, percentage of fractional shortening, and ventricular wall thickness

Bottom line: preservation of myocardial function

Cardiovascular changes

Stroke volume +30% Heart rate +15% Cardiac output +40% Oxygen consumption +20% SVR (systemic vascular resistance) -5% Systolic BP -10mmHg Diastolic BP -15mmHg Mean BP -15mmHg

Respiratory system

UPPER RESPIRATORY TRACT Hyperemic mucosa of nasopharynx

Estrogen-mediated nasal stuffiness and epistaxis

Polyposis of nose and sinuses may occur and regress after delivery

“chronic cold”

MECHANICAL CHANGES Configuration of thoracic cage changes early in

pregnancy Increase in subcostal angle, transverse diameter and

circumference of chest With advancing gestation, the level of diaphragm is

pushed up

Changes in pulmonary function tests during pregnancy

Serial measurements of lung volume compartments during pregnancy. Functional residual capacity decreases approximately 20 percent during the latter half of pregnancy, due to a decrease in both expiratory reserve volume and residual volume. Redrawn from Prowse, CM, Gaensler, EA, Anesthesiology 1965; 26:381.

Serial measurements of lung volume compartments during pregnancy. Functional residual capacity decreases approximately 20 percent during the latter half of pregnancy, due to a decrease in both expiratory reserve volume and residual volume. Redrawn from Prowse, CM, Gaensler, EA, Anesthesiology 1965; 26:381.

Respiratory system

LUNG VOLUME AND PULMONARY FUNCTION 30-40% increase in tidal volume (Amount of

air I and E with each breath) 30-40% increase in minute ventilation (likely P4

mediated) ERV falls by 20% Vital capacity and inspiratory reserve volume

remain unchanged

Respiratory system

LUNG VOLUME AND PULMONARY FUNCTION Respiratory rate is unchanged Due to elevation of the diaphragm

Total lung volume decreases (diaphragm) by 5% Residual volume decreases (RV) by 20% FRC is reduced 20%

No change in FEV1 or the ratio of FEV1 to forced vital capacity

Respiratory system

GAS EXCHANGE Minute ventilation rises 30-40% by late

pregnancy O2 consumption increases only 15-29%

Results in higher PAO2 (alveolar) and PaO2 (arterial) Normal PaO2: 104-108 mmHg

Fall in PACO2 and PaCO2 levels Normal PaCO2 level: 27-32 mmHg

Increases gradient of CO2 facilitating transfer from fetus to mother

Arterial pH remains unchanged Increased bicarbonate excretion via kidneys

Respiratory system

DYSPNEA OF PREGNANCY Common complaint

60-70% of patients late first or early second trimester

Likely due to various factors reduced PaCO2 levels awareness of increased tidal volume of

pregnancy

Renal system

ANATOMY Kidney enlargement

increased renal vascular and interstitial volume, R>L Ureteral and renal pelvis dilatation by 8 weeks

Right > left mechanical compression by uterus and ovarian venous

plexus smooth muscle relaxation by progesterone

Implications Increased incidence of pyelonephritis difficulty in interpreting radiographs interference with studies

Renal system

RENAL HEMODYNAMICS Effective renal plasma flow (ERPF) and GFR

increase Filtration fraction falls

Returns to normal by late third Δ Endogenous creatinine clearance increases

Begins by 5 weeks

Renal system

METABOLITES increased GFR decline in serum urea and

creatinine BUN – 8-9 mg/dl by end 1st Δ Decline in serum creatinine

0.7 mg/dl by end 1st Δ 0.5-0.6 mg/dl by term

Early decline in serum uric acid levels nadir at 24 weeks same as nonpregnant level at end of pregnancy due

to increased reabsorption of urate

Renal system

SALT AND WATER METABOLISM Plasma osmolality begins to decline by 2

weeks after conception reduction in serum sodium and other anions

Sodium loss during pregnancy 50% rise in GFR Progesterone: natriuresis

Renal tubular reabsorption of Na+ increases (aldosterone, estrogen and deoxycorticosterone)

Sodium homeostasis

Renal system

NUTRIENT EXCRETION Increase in glucose excretion

1-10 g glucose excretion per day Due to 50% increase in GFR

implications inability to use urine glucose susceptibility of pregnant women to UTI

Increase in amino acid excretion during gestation no increased protein loss (100-300 mg/24 hr)

Increased urinary loss of folate and vitamin B12

Gastrointestinal - Appetite

Increase early 1st Δ

Increase intake 200 kcal by end 1st Δ RDA: 300 kcal/day during pregnancy

Sense of taste may be blunted

Pica check for poor weight gain and refractory

anemia South - clay or starch (laundry or cornstarch) UK – coal Also soap, toothpaste and ice pica

Gastrointestinal - Mouth Unchanged pH or production of saliva

Saliva production is unaltered Ptyalism – usually in women with HEG

due to inability to swallow Can lose up to 1-2 L of saliva per day Decreasing starchy foods might help

Gums – edematous and soft May bleed after brushing

Epulis gravidarum regress 1-2 mos after delivery excise if persistent or excessive bleeding

Gastrointestinal - Stomach

Decreased tone and motility progesterone possibly due to decreased levels of motility

Conflicting info about delayed gastric emptying

Reduced tone of the gastroesophageal junction sphincter Increased intraabdominal pressure leads to acid

reflux Lower incidence of PUD

may be due to decreased gastric acid secretion delayed emptying, increase in gastric mucus, and protection of mucosa by prostaglandins

Gastrointestinal - Small bowel

Reduced motility of small bowelincreased transit time in the third trimester and postpartum

Enhanced iron absorption as a response to increased iron needs

Gastrointestinal - Colon

Constipation Mechanical obstruction by the uterus Reduced motility (p4) Increased water absorption

Portal venous pressure is increased Dilation of gastroesophageal vessels

issue in those with preexisting esophageal varices Dilation of hemorrhoidal veins

hemorrhoids

Gastrointestinal - Gallbladder

Fasting and residual volumes double in 2nd and 3rd Δ Slower rate of emptying

Biliary cholesterol saturation increases and chenodeoxycholic acid decreases increased risk gallstone formation

Gastrointestinal - Liver Liver does not enlarge Hepatic blood flow remains unchanged

CO to the liver decreases by ~35% Spider angiomata and palmar erythema

elevated estrogen levels Lab data

Drop in serum albumin Rise in serum alkaline phosphatase

placental production and some hepatic production Rise in serum cholesterol, fibrinogen, ceruloplasmin,

binding proteins for corticosteroids, sex steroids, thyroid hormones, and vitamin D

No change in serum bilirubin, AST, ALT, protime and 5’ nucleotidase

Rise in GGT is controversial

Gastrointestinal system

NAUSEA AND VOMITING Morning sickness complicates 70% of

pregnancies Onset 4-8 weeks up to 14-16 weeks Cause?

Relaxation of smooth muscle of stomach, elevated levels of steroids and hCG

Rx – supportive: reassurance, support, and avoiding triggers…

HEG weight loss, ketonemia, electrolyte imbalance and

dehydration possible renal or hepatic damage IVF, antiemetics

NPO continue IV

Gastrointestinal change

Morning sickness

hyperremesis gravidarum (weight loss, ketonemia and electrolyte imbalance)

Dietary craving: pica

Decreased gastrointestinal motility: reflux and heartburn

Gallbladder function, cholestasis

Hyperemia and softening of the gums (epulis)

Hemorrhoid

Appendix displaced

Endocrine System

Estrogen Progesteron hCG

Function of hCG

Prevent involution of the corpus luteum at the end of the monthly female sexual

Instead, it causes the corpus luteum to secrete even larger quantities of its sex hormones—progesterone and estrogens—for the next few months.

These sex hormones prevent menstruation and cause the endometrium to continue to grow and store large amounts of nutrients.

Human chorionic gonadotropin also exerts an interstitial cell–stimulating effect on the testes of the male fetus, resulting in the production of testosterone

Function of Estrogen

Enlargement of the mother’s uterus Enlargement of the mother’s breasts and growth of

the breast ductal structure Enlargement of the mother’s female external

genitalia. Relax the pelvic ligaments of the mother, so that

the sacroiliac joints become relatively limber and the symphysis pubis becomes Elastic allow easier passage of the fetus through the birth canal.

Affect many general aspects of fetal development during pregnancy, for example, by affecting the rate of cell reproduction in the early embryo.

Functions of Progesteron

Causes decidual cells to develop in the uterine endometrium.

Decreases the contractility of the pregnant uterus preventing uterine Contractions.

Increases the secretions of the mother’s fallopian tubes and uterus to provide appropriate nutritive matter for the developing morula and blastocyst.

Helps the estrogen prepare the mother’s breasts for lactation.

Rates of secretion of estrogens and progesterone, and concentration of human chorionic gonadotropin at

different stages of pregnancy.

Endocrine - Thyroid The normal pregnant woman is euthyroid Changes in thyroid morphology and lab indices

Estrogen-induced increase in TBG Decreased circulating extrathyroidal iodide Thyroid enlargement usually not detected by exam Normal thyroidal uptake of iodide

Serum TSH decreases early in gestation rises to pre-pregnancy levels by end of first Δ

T4 increases early in gestation role of hCG stimulating the thyroid

Rise in TBG leads to rise in total T4 and total T3 active hormones free T4 and free T3 are unchanged

Free T4 is the most reliable method of evaluating thyroid function in pregnancy

Endocrine - Adrenal glands

Expansion of the zona fasciculata site of glucocorticoid production

Plasma corticosteroid-binding globulin (CBG) rises due to enhanced liver synthesis

Free plasma cortisol rises increased production and delayed clearance

Plasma DOC (deoxycorticosterone) rises fetoplacental unit

DHEAS (dehydroepiandrosterone) decreases

Testosterone is slightly elevated Increased SHBG and androstenedione

Endocrine - Pancreas Hypertrophy and hyperplasia of the B cells Fasting associated with accelerated starvation

maternal hypoglycemia, hypoinsulinemia and hyperketonemia

due to diffusion of glucose by the fetoplacental unit Feeding response

hyperglycemia, hyperinsulinemia, hypertriglyceridemia and reduced tissue sensitivity to insulin

glucose response greater during pregnancy peripheral resistance to insulin: diabetogenic effect

of pregnancy. hPL and cortisol mediated greater insulin resistance as the pregnancy advances

Endocrine - Pancreas

Fetus primarily depends on glucoseFacilitated diffusion

carrier-mediated but not energy dependent process

Active transport of amino acids to the fetus

Ketones diffuse freely across the placenta

Endocrine - Pituitary

The pituitary gland enlarges in pregnancy

proliferation of chromophobe cells on the anterior pituitary

stalk remains midline

Skeleton

Lordosis keep center of gravity over the legs back pain…

Relaxin relaxation of the pubic symphysis and

sacroiliac joints facilitates vaginal delivery but may lead to

discomfort Implications

unsteadiness of gait and trauma from falls

Skeleton

Total serum calcium declines throughout pregnancy until 34-36 weeks due to the fall in serum albumin

Serum ionized calcium is constant and unchanged “Physiologic hyperparathyroidism”

increased gut absorption decreased renal losses no bone loss seen in bone density studies

preservation due to calcitonin? Rate of bone turnover and remodeling

increases throughout pregnancy twice as great at term

Metabolism

Basal metabolism rate, BMR : +15-20% Weight gain : 12.5 kg (± 24 pons)

o Fetus : 3400 go Placenta : 650 go Amniotic : 800 go Uterus : 960 go Plasma, red cells : 1450 go Mammary glands : 405 go Extracellular, extravascular water : 1480 go Deposition of fat and protein : 3345 g

Insulin resistance

Conclusion

Understanding maternal physiology is crucial in understanding the changes and clinical scenarios associated in pregnancy

This knowledge will help us distinguish the physiologic and pathologic processes during pregnancy

This knowledge will also improve patient’s education about their pregnancy

Selamat Belajar