Adaptive Changes In Pregnancy Dr.Nandakumaran Moorkath Assoc.Professor Obstet.Gynec Department Kuwait Medical Faculty
First Maturation DivisionReduction/Meiotic
Division-inside ovary
Large secondary oocyte+ small polar body of 23 chromosome each
2nd maturation Division - Mitotic Division Completed in Fallop Tube
Second
Polar Body released at time of fertilization
Fusion
with "x" sperm, female ; with "y" sperm, male
*
In females, inactive x-chromosome in somatic cells-- as drumstick in nuclei of poly- morphonuclear leucocytes and as chromtain thickening on nuclear membrane
TRANSIT OF OVUM AND FERTILIZATION Transport
to Fallop.Tube by actions
of Cilia Fertilization
in Ampulla of
Fallop.Tube After
coitus,sperms reach fallop.tube few minutes-3 hours
Sperm
movement by motility and by uterine&tubal peristalsis
Increase
peristalsis---caused by prostaglandins in semen
Fructose
in semen—provide energy
Enzymes, acrosin and hyaluronidase help in coagulation and liquefaction of semen and help to penetrate the cervical mucus and corona radiata as well as zona pellucida of ovum
Sperms attracted towards by chemotaxis— exact meachanism not clear
After sperm penetration, segmenatation nucleus aligning ovum and sperm chromosomes (46) formed
First
Mitotic division 24 Hours after sperm penetration
Further
divisions every 22 Hours
MORULA-
Clump of Cells – in Fallop.Tube
Turns
to Blastocyst with a cavity within 24 hours of entry to uterus
About
3 and half days after fertilization
Implantation
5-6 day after fertilization, completed by 9th Day
Implantation
Usually in Upper Posterior Part of Uterus
Outer
blastocyst covering----becomes placenta
Inner
core--- Fetus Proper
Till
about 8 weeks of gestation, till placenta becomes functional,
nutrition
for embryo from fallopian tube secretion and from endometrial nutrients released from invading trophoblast
Invading
Trophoblast--------Intermediate Cyto-Trophoblast
Human
Placenta--- Hemochrial Placenta --- Also Chrio-allantoic Placenta
Placenta---
Vital Organ, Essential Organ for Fetus till Birth Chroionic villi (Fetal Part) dip in maternal lake of blood (intervillous space)
2
Umbilical arteries (Deoxygenated Blood)and One Umbilical Vein (Oxygenated Blood) Maternal side—consists of 15-20 cotyledons Each lobe with separate fetal villi system Maternal Venous Drainage--Through Decidual Veins Exchange Across Chorionic Villi
Consists of syncyiotrophoblast and Cytotrophoblast in initial stage---Towards gestation, only syncitiotrophoblast layer!
Maternal Blood Flow : 500-700 ml/min
Blood Flow on Fetal Side of Placenta : 300 ml/min
Intervillous Space Volume : 140 ml
Pressure in intervillous space : 15 mm Hg
Volume
of fet.capillaries : 60 ml
Surface
Area of Chorionic Villi ----11 Square Metres
Placental
Transport--- Mainly by passive diffusion----along a concentration gradient from mother to fetus or fetus to mother depending on gradient Majority of Drugs----- By passive diffusion
In the case of Glucose and Hexoses---Facilitated Diffusion--- with the help of specific carriers Active Transport---- In the case of amino acids, certain vitamins, trace elements
Thyroxine, estrogens,androgens cross placental membrane easily Insulin and Parathormone ----do not cross---due to high molecular weight Heparin----Does not cross---due to high Mol.Wt--- drug of choice for anti-coagulant treatment in pregnancy----no fetal effect
DIAGNOSIS OF PREGNANCY By
detection of Human Chorionic Gonadotrophin (HCG) in urine/blood
Trophoblast---secretes
HCG --Basis of Pregnancy Diagnosis
Trophoblast
secretes large amount of HCG, appears in blood and urine
IMMUNOLOGIC TEST 2 STEPS
STEP 1 : ADDITION OF HCGANTIBODY (anti-hcg) to urine sample
STEP
2 : Use of Indicator to see if reaction occured
If
Pregnant, HCG in urine will react with anti-hcg and Neutralise HCG
If
no anti-hcg found, Test is positive
If
non-pregnant, NO Hcg in urine, Anti-hcg Not neutralized-
Anti-Hcg
in sample- Test Negative
Pregnant (Urine contains HCG)
Non Pregnant (Urine No HCG)
(ADD ANTI SERUM CONTAINING HCG ANTIBODIES) HCG ANTIBODIES NEUTRALISED
HCG ANTIBODIES NOT NEUTRALISED
(ADD LATEX PARTICLES COATED WITH HCG)
NO FLOCCULATION
FLOCCULATION
RADIO
IMMUNO –ASSAY OF MATERNAL SERUM FOR PRESENCE OF HCG (BETA UNIT)
PREGNANCY
CAN BE DIAGNOSED AS EARLY AS 7-8TH DAY AFTER FERTILISATION!!!
IMMEDIATELY
AFTER THE IMPLANTATION IN THE UTERUS
***HCG
VALUES……HIGH IN MULTIPLE PREGNANCY
**VERY
HIGH HCG…….CHORIOCARCINOMA
**LOW
VALUES ……IN ECTOPIC PREGNANCY
ULTRASONIC DIAGNOSIS OF PREGNANCY WITH
ULTRASOUND SCAN PREGNANCY(GESTATIONAL SAC)CAN BE DIAGNOSED AS EARLY AS 6TH WEEK AFTER LMP
FETAL
HEART BEAT CAN BE RECOGNISED AS EARLY AS 10TH WEEK
OVARIAN
CYSTS UTERINE FIBROMYOMATA DISTENDED BLADDER ETC CAN BE MISTAKENTO BE PREGNANCY….USE OF ULTRASOUND CAREFUL EXAMINATION AND PREGNANCY DIAGNOSTIC TESTS NECESSARY TO ENSURE PROPER DIAGNOSIS
PSEUDOCYESIS PATIENT
….PRETENDS AND IS CONVINCED TO BE PREGNANT………. MAY GIVE PREGNANCY SYMPTOMS…….SEEN IN WOMEN HAVING STRONG DESIRE TO HAVE CHILDREN AND HAVE INFERTILITY PROBLEMS
HEGAR'S SIGN ON
EXAMINATION, SOFT UTERUS IN PRESENCE OF UNSOFT CERVIX………INDICATION OF PREGNANCY
ESTIMATION OF EXPECTED DATE OF DELIVERY AVERAGE
DURATION OF PREGNANCY -266 DAYS
FROM
DATE OF LAST MENSTRUAL PERIOD -280 DAYS OVULATION ………..NORMALLY ON 14TH DAY
CALCULATION OF EXPECTED DELIVERY DATE
ADD 9 MONTHS FROM THE LAST MENSTRUAL PERIOD (LMP) AND ADD 7 DAYS TO IT
IN 40% CASES,DELIVERY OCCURS 7 DAYS BEFORE THE EXPECTED DATE!!!!
IF WOMEN CANNOT REMEMBER LMP,OR PREGNANCY OCCURED DURING LACATION PERIOD OR WHEN SHE MISSED TO TAKE CONTRACEPTIVE PILL,CALCULATION BASED ON CLINICAL OBSERVATIONS!!!!!
DATE OF NOTING FIRST FETAL MOVEMENT IN
PRIMIPARA ……..BETWEEN 18-20 WEEKS IN MULTIPARA …….LITTLE LATER BETWEEN 6-12 WEEKS ,EXMAMINATION OF UTERUS BY AN EXPERIENCED CLINICIAN CAN ASSESS PREGNANCY(BUT NOT FOOLPROOF)
ULTRASONIC SCAN IS THE MOST ACCURATE METHOD OF DETERMINING DURATION OF GESTATION BETWEEN 7-14 WEEKS ,MEASUREMENT OF CROWN-RUMP LENGTH ….LINEAR RELATIONSHIP BETWEEN 14-30 WEEKS ,MEASUREMENT OF BIPARIETAL DIAMETER …..USING STANDARD CURVECAN ASSESS DURATION OF PREGANCY LATER THIS ANALYSIS ,LESS ACCURATE
RADIOLOGICAL
EXAMINATION OF FETAL FEMUR AND TIBIA
CALCIFICATION BUT
,ETC CAN BE USED
NOT IN USE NOW,DUE TO RADIATION RISK!!!
CYTOLOGICAL TESTS OF
AMNIOTIC FLUID AND STAINING OF EPITHELIAL CELLS, IF MATURE ORANGE –STAINED CELLS ……GREATER THAN 10% THAN BLUE STAINED CELLS , MATURITY 36 WEEKS OR MORE IF "ORANGE CELLS" MORE THAN 50%......GESTATION PERIOD 38 WEEKS OR MORE
ANALYSIS OF CREATININE AND UREA-IN AMNIOTIC FLUID TOWARDS
36 WEEKS OR MORE CAN BE USED TO ASSESS FETAL KIDNEY AND LIVER FUNCTION ASSESSMENT OF SURFACTANT LEVEL AND LECITHIN/SPHYNGOMYELIN RATIO (Normally, Ratio Greater than 2.00) CAN DETERMINE LUNG MATURITY AT 36 WEEKS AND MORE
PHYSIOLOGICAL CHANGES IN PREGNANCY CHANGES
MAINLY IN GENITAL TRACT AND THE BREASTS.ALSO RELATED CHANGES IN OTHER SYSTEMS-INITIATED BY THE HORMONES FROM FETAL CHORIONIC TISSUE.
HORMONAL CHANGES ON
FERT ,CORPUS LUTEUM PERSISTS ENLARGES IN RESPONSE TO HCG(HUMAN CHORIONIC GONADOTROPHIN) CL SECRETES ESTROGENS,PROG AND RELAXIN.AFTER 6TH WEEK CL FUNCTION OVER BY PLACENTA HCG (GLYCOPROTEIN) CONTAINS LACTOSE AND HEXOSAMINE PRODUCED BY SYNCITIO TROPHOBLAST .
LIKE
PIT.GL.PROT.HORMONES MADE OF α AND β SUBUNITS WITH MINOR DIFFERENCE IN AMINO ACID RESIDUES. M WT. α –HCG-18000 Β- HCG-28000 HCG HAS MORE LH ACTIVITY LITTLE FSH ACTIVITY DETECTED IN BLOOD AS EARLY AS RIA 8-9TH DAY OF CONCEPTION(IMMEDIATELY AFTER IMPLANT)
MAX
LEVEL 10TH WEEK (about 110 IU/ml) BASAL LEVEL 24TH WEEK (about 20 IU/ml) IN URINE DETECTABLE AS EARLY AS 14TH DAY AFTER FERTILISATION HCG
NOT SPECIFIC FOR PREGNANCY.OTHER TISSUES PRODUCE SMALL AMOUNTS TOO.HCG STIMULATES LEYDIG CELLS IN MALE FETUS TO SECRETE TESTOSTERONE.
HCS(HUMAN CHORIONIC SOMATO MAMMOTROPIN) ALSO CALLED HPL (HUMAN PLACENTAL LACTOGEN) AND CGP(CHORIONIC GROWTH HORMONE-PROLACTIN) HCS STRUCTURE SIMILAR TO HUMAN GROWTH HORMONE AND PROLACTIN ; HCS SECRETED BY SYNCITIOTROPHOBLAST (LIKE HCS PROLACTIN IN MOTHER'S BLOOD IN PREGNANCY LITTLE IN FETUS) PROTEIN HORMONE M W:38000 1)SECRETION STARTS FROM 5TH WEEK OF PREGNANCY PROGRESSIVELY:PROGRESSIVELY THRO PREGNANCY SECRETION DIRECT PROPORTION TO WEIGHT OF PLACENTA.
HCS FUNCTION
A) DEVELOPMENT OF BREASTS AND IN SOME CASES LACTATION IN EXPERIMENTAL ANIMALS(HENCE THE EARLY NAME PLACENTAL LACTOGEN)BUT NOT IN HUMANS?
B) SIMILAR STRUCTURE AS GROWTH HORMONE –BUT 100 TIMES LESS POTENTPROMOTES DEPOSITION OF PROTEINS IN TISSUES
C)
CAUSES LOW GLUCOSE UTILISATION IN MOTHER(MAKING NORE GLUCOSE AVAILABLE FOR FETUS) D) RELEASES FFA FROM FAT STORES IN MOTHER (ALTERNATE FUEL FOR MOTHER) SO HCS IS A GENERAL METABOLIC HORMONE.
ESTROGEN SECRETION BY PLACENTA 1)PLACENTA
SECRETES BOTH ESTROGEN AND PROG( 2)MAJORITY SECRETED AS ESTRIOL(CONTRARY TO SMALL AMOUNTS IN NONGRAVID O+) 3)NOT SYNTHESISED DE NOVO BY PLACENTA
ANDROGENIC STEROID COMPOUNDS DEHYDROEPIANDROSTERONE AND 16 HYDROXYDEHYDRO EPIANDROSTERONE FORMED IN MOTHERS ADRENAL AND ALSO FETAL ADRENALS TRANSPORTED BY BLOOD TO PLACENTA AND CONVERTED TO ESTRADIOL,ESTRONE AND ESTRIOL
MONITIORING OF URINARY ESTRIOL SECRETION GOOD INDICATION OF FETO PLACENTAL WELL BEING.
4)FET
AD CORTEX SECRETES MAINLY DEHYDRO EPIANDROSTERONE
FUNCTIONS OF OEST IN PREGNANCY 1)ENLARGEMENT
OF UTERUS
2)ENLARGEMENT
OF BREATS AND DUCTAL STRUCTURE
3)ENLARGEMENT
OF FEMALE EXTERNAL GENITILIA
4)RELAX
THE VARIOUS PELVIS LIGAMENTS AND VARIOUS JOINTS FOR EASY PASSAGE OF FETUS DURING BIRTH THROUGH BIRTH CANAL. 5)FACILITATES CELL PRODUCTION OF EARLY EMBRYO.
PROG SEC BY PLACENTA PROG
ESSENTIAL HORMONE FOR PREGNANCY EQUALLY IMPORTANT AS ESTROGEN
THE
RATE OF PROG SECRETIONS RISES 10 FOLD IN COURSE OF PREGNANCY
FUNCTIONS OF PROG IN PREGNANCY 1)
ESSENTIAL FOR NORMAL PROGRESSION AND MAINTENANCE OF PREGNANCY
2)PROGESTERONE
CAUSES DECIDUAL CELLS TO DEVELOP IN THE UTERINE ENDOMETRIUM PLAY AN IMPORTANT ROLE IN NUTRITION OF EARLY EMBRYO.
3)
LOWERS THE UT.CONTRACTILITY PREVENTING SPONT ABORTION. 4) FOR DEVELOPMENT OF CONCEPTUS EVEN BEFORE IMPLANTATION INCREASES THE SECRETION OF FALLOPIAN TUBES AND UTERUS TO PROVIDE NUTRITION FOR MORULA AND BLASTOCYST. 5) PREPARES THE BREASTS FOR LACTATION.
PREGNANCY EFFECTS ON OTHER ENDCRINE GLANDS ON PITUATARY: ANTERIOR
PITUATORY INCREASES IN SIZE (50%)AND FUNCTIONS . HIGHER SECRETIONS OF CORTICOTROPIN THYROTROPIN AND PROLACTIN BUT NOT GH. LOWERS THE SECRETION OF FSH AND LH(INHIB EFFECT OF EST AND PROG)
CORTICOSTEROID SECRETION
1) HIGHER IN PREG GLUCOCORTICOIDS HELP TO MOBILISE AMINO ACIDS FOR USE BY FETUS.
2) HIGHER ALDOSTERON SECRETION (2 FOLD HIGHER) HELPS WITH ESTROGEN TO RETAIN MORE SODIUM AND FLUIDSOMETIMES CAUSE OF HYPER TENSION IN PREGNANCY
HIGH THYROID SECRETION (HIGHER
50%) AND THYROXINE SECRETION DUE TO EFFECT OF HCG AND PLACENTAL THYROTROPIN(TSH)
PARATHYROID GLANDs 1)PARATHYROID GLANDS ENLARGE IN PREGNANCY IF ON Ca++ DEFICIENCY DIET. 2)HIGHER PARATHORMONE SECRETION HIGHER Ca++ RESORPTION FROM MOTHER'S BONES TO COMPENSATE FOR FETAL REMOVAL OF Ca++ GROWTH. 3)HIGHER PTH SECRETION DURING LACTATION TO MEET HIGH Ca++ REQUIREMENTS OF BABY.
SECRETION OF RELAXIN
1) POLYPEPTIDE HORMONE M.W:9000
2) SECRETED BY OVARIES AND PLACENTA(HIGHER SECRETION BY EFFECT OF HCG RELAXES CERVIS AND PELVIC LIGAMENTS(SECRETED BY SYNCITIOTROPHOBLASTS)
HIGHER APPETITE AND HIGHER INTAKE IN PREGNANCY-DUE TO FETAL REMOVAL OF SUB FROM MOTHERS BLOOD.
METABOLISM DURING PREGNANCY 1)DUE
TO HIGH HORMONES HIGH BASAL MATERIAL METABOLIC RATE
(BMR)
WITH 15% HIGH BMR)
2)GREATER
ENERGY REQUIRED FOR MUSCULAR ACTIVITY.
NUTRITION DURING PREGNANCY
1)GREATEST FETAL GROWTH IN LAST 2 TRIMSTERS WEIGHT DOUBLES DURING LAST 2 MONTHS
2)STORAGE IN THE MOTHERS NUTRIENTS(PROT,Ca++,PO4,IRON)HELPS TO MEET FETAL NEEDS.IF STORAGE NOT ADEQUATEMATERNAL DEFICIENCIES OCCUR.EG:-375 MG IRON FOR FETUS
600 MG IRON FOR MOTHER
NORMAL MATERNAL STORE ONLY ABOUT 100 MG.HENCE THE NEED FOR MATERNAL IRON SUPPLEMENTSOTHERWISE PREGNANCY ANAEMIA.
VITAMIN D SUPPLEMENT ALSO NEEDED.ALSO VITAMIN K SUPPLEMENT IN MOTHER BEFORE BIRTH OF BABY-TO PREVENT HEMORRAGE IN BABY AT BIRTH.(VITAMIN K-FOR PROTHROMBIN FORMATION)
1)CARDIAC
OUTPUT HIGHER 30-40% FOR HIGHER BLOOD FLOW THROUGH PLACENTA AND UTERUS.
2)FALL
IN PERIPHERAL VASCULAR RESISTANCE ,MAX BETWEEN 25TH TO 28TH WEEK ,DUE TO DILATION OF ARTERIES OF UTERUS KIDNEY AND SKIN .
NON PREG 12 WEEKS CARD OUTPUT 6.0 (4.5)
36 WEEKS 5.5
STROKE VOL(ML) 75 (65)
65
PULSE RATE (70)
85
80
NO
INCREASE IN BP IN NORMAL PREGNANCY.ACTUALLY SLIGHT DECREASE IN BP(OF 5-10 DIASTOLIC) MIDTRIMESTER.
RESPONSE OF MOTHER'S BODY
PREGNANCY CAUSES MARKED CHANGES IN THE APPEARANCE OF THE WOMEN.
UTERUS SIZE RISES FROM 50G TO 1100G!
BREASTS DOUBLES IN SIZE-
VAGINA ENLARGES AND INTROITUS OPENS MORE WIDELY(7-16MM)
WEIGHT GAINAVERAGE ABOUT 12 KG(MOSTLY 2 TRIMESTERS)
FETUS 3.5 KG ; AMNIOTIC FLUID + PLACENTA + FETUS MEMBRANE-2KG
BREASTS – 1KG
RISE IN WEIGHT IN BODY fat,etc- 5 KG
2) RISE IN MATERNAL BLOOD VOLUME – HIGH 30% (MAINLY IN LATTER HALF OF PREGNANCY) DUE TO HIGH FLUID RETENTION BY KIDNEYS (BY ALDOSTERONE AND ESTROGEN ACTION)stable by 34th week
3)Increased BONE MARROW ACTIVITY AND RBC PRODUCTION
4)BUT RELATIVE HYPOALBUMINEMIA DUE TO HIGH B1 VOL.
5)RELATIVE REDUCTION IN HAEMOGLOBIN LEVEL DUE TO INCREASE IN BLOOD VOLUME
BUT TOTAL Hg AND TOTAL IRON CONTENT INCREASED.
PRINCIPAL BLOOD CHANGES IN PREGNANCY TOT.BL.VOL *(ML)
NON-PREGNANT 4000
PREGNANT 5500
PLASMA VOL (ML)
2500
3750
RED CELL VOL (ML)
1500
1750
HEMATOCRIT (WHOLE Bl)
37.5%
HEMOGLOBIN
14 G/100ML
TOTAL HG
492 G
587 G
TOTAL IRON
1668 G
2000 G
31.5% 12 G/100ML
NON-PREGNANT
TERM
PLASMA PROTEIN (G/100ML)
7
6
ALBUMIN (G/100 ML)
4
3
GLOBULIN
2.5
2.5
FIBRINOGEN (G/100 ML)
0.25
0.4
TOTAL PROTEIN (G)
175
215
NON-PREGNANT
PREG(LATE)
WBC
7000/CUB.MM
10500 /C.MM
ESR
9.6 MM/HR
56 MM/HR
RBC
………………
INCREASED 18%
PLATELETS Factor XIII Factor VII,VIII,IX and X
187000/C.MM ---------
NO CHANGE (NOCHANGE) (INCREASED PREGNANCY)
RESPIRATION DURING PREGNANCY
MORE O2 CONSUMPTION 20% MORE
MORE CO2 PRODUCTION MORE SENSITIVITY OF RESPIRATION.
CO2 DUE TO PROGESTERONE ACTION – HENCE MINUTE VENTILATION.(50%)
HIGH PO2 ,LOW PCO2 FOR FETAL NEEDS /ALSO HIGH RESPIRATORY RATE IN PREGNANCY.
CHANGES IN MATERNAL URINARY SYSTEM. 1)HIGH REABSORPTION OF NACL AND WATER HIGH 50% DUE TO HIGH HORMONES. 2)GLOM FILTRATION RATE 50% MORE. COMPENSATION FOR MMORE WATER RETENTION IN PRE ECLAMPSIAOR TOXEMIA OF PREGNANCY HIGH ARTERIAL BLOOD PRESSURE ,EDEMA,HIGH PROTEIN LOSS IN URINE DURING LATER MONTHS OF PREGNANCY
GLYCOSURIA
IN PREGNANCY ATTRIBUTABLE TO INCREASED FILTERED LOAD AS WELL AS DUE TO REDUCED RENAL THRESHOLD FOR GLUCOSE (reduced form 180 mg/100 ml to 160 mg/100 ml)
NAUSEA
OR MORNING SICKNESS IN 1/3 PREGNANCIES
SEVERE
IN 1ST TRIMESTER .
BEGINS
6TH WEEK –STOPS SPONTANEOUSLY BEFORE 14TH WEEK.
CAUSE
IS UNCERTAIN MAY BE RELATED TO HIGH HCG LEVELS ALSO PSYCHOLOGICAL COMPONENT)
IN
PREGNANCY HIGH GAST ACIDITY DELAYED GASTRIC EMPTYING CONSTIPATION NOT UNCOMMON ALSO CHANGES IN THE SKIN,DISTENTION OF ABDOMINAL WALL MUSCLES,PIGMENTATION OF SKIN AREAS.
CHANGES IN IMMUNE REACTIVITY THEORETICALLY
FETUS AN ALLOGRAFT-FOREIGN TO MOTHER SHOULD HAVE BEEN REJECTED (IN MAJORITY , BUT NOT REJECTED) DUE TO IMMUNO TOLERANCE MECHANISMS (NOT FULLY UNDERSTOOD)
SEVERAL FACTORS
1) HORMONAL
2) DEPRESSION OF MAT T LYMPHOCYTE FORMATION
3) DISEASES WITH AUTO IMMUNE BASE REMISSION IN PREGNANCY SUGGESTING ALTERED IMMUNE MACH OPERATION
4) CLASS 2 HLA Ags (MHC) NOT EXPRESSedIN PREGNANCy