Reproductive Physiology PDF

# Reproductive Physiology ## **Physiology** ### Lactation - Breast-feeding in first 6 months of life with complementary feeding until 2y is recommended. - Normal for L&R breasts to produce different milk amounts; 70% mothers produce more milk with the right breast - From before conception to 1...

# Reproductive Physiology ## **Physiology** ### Lactation - Breast-feeding in first 6 months of life with complementary feeding until 2y is recommended. - Normal for L&R breasts to produce different milk amounts; 70% mothers produce more milk with the right breast - From before conception to 1 month of lactation, breast increases 211 ± 16 mL → total breast milk production/intake of 516-1125 ml. - 63% glandular tissue, 37% fat; 9 ducts per breast - Breast reduction = removal of secretory tissue + patent milk ducts - Breast augmentation = decrease nipple sensation, associated with lactation insufficiency - Nipple piercing = scar tissue blocks milk ducts - Increased human placental lactogen correlated with increased breast growth - Increased lactose output in urine in pregnancy reflects breast lactose synthesis. - Increased blood prolactin correlated with increased breast lactose synthesis. - Prolactin needed for milk production (but drainage controls amount of milk produced). - Areola growth and nipple growth → +ve correlation with pregnancy progression time. - Risk of breast ptosis increases with each pregnancy, but breastfeeding does not seem to worsen these effects (breast shape; ligaments, don't change with feeding). ### Breast-feeding Benefits - **Mother:** Childbirth recovery, body weight loss, maternal fertility suppression, cholesterol clearance, diabetics (glucose control), less ovarian/breast Ca risk. - **Human milk:** 4.5% fat, 1.1% protein, 6.8% lactose, 12.6% total solids - Contains: protein, fat, carbohydrate, vitamins, minerals. - Milk fat content is low when breast is full, high when breast is drained. - **Baby:** 'Gold standard' infant food, growth, protection against illness. - CNS: higher DHA in parietal cortex. - Immune system: Immunoglobulins (sIgA), lactoferrin, lysozyme, lipids, oligosaccharides, cytokines. - **Community:** Reduced healthcare costs, less pollution (packaged milk), land clearance for farmland. ### Premature Delivery - Secretory differentiation has occurred ⇒ milk production needs to be initiated + established by pumping early. ### Milk Synthesis & Secretion Pathways - Protein + lipids + iodine + VitA, VitB6, VitB12, VitC, VitD, VitE, VitK + thiamin, biotin + folate = increase milk composition. - Drugs can transfer into milk if high concentration, LMW & lipid soluble (if protein bound ⇒ can't enter). ### Lactation Initiation - Requires progesterone withdrawal + presence of prolactin, insulin & corticosteroids. - Secretory activation inhibition: by retained placental fragments. ### Optimising Milk Production - Breastfeed within 1hr of birth + skin to skin care. - Unrestricted access to breast, day & night. - Feed on cue (not schedule). - Avoid formulas. ### Low Milk Production 1. Maternal health → anemia, postpartum hemorrhage, smoking 2. Mammogenesis → Insufficient breast tissue (asymmetric, hypoplastic) 3. Breast surgery → reduction, periareolar incision, abscess. nipple piercing 4. Secretory activation → retained placenta ### Secondary Breastfeeding Issues - 15% healthy primiparous women have insufficient lactation at 2 to 3wk postpartum. 1. Delayed breastfeeding (breastfeed within 1hr of birth). 2. Inadequate prolactin → domperidone if appropriate. 3. Inadequate infant suction → check baby. 4. Nipple pain → positioning & attachment, infection (S. aureus, C. albicans), infant tongue tie. 5. Blocked duct → clear blockage. 6. Mastitis (blood duct; milk stasis) → antibiotics. ### Changes in Milk Composition | Category | Colostrum | Mature Milk | |---|---|---| | Total solids (g/L) | 180 | 120 | | Total protein (g/L) | 85 | 10 | | Lactose (mM) | 80 | 195 | | Sodium (mM) | 60 | 10 | | Citrate (mM) | 0.5 | 5 | | Calcium (mM) | 5 | 8 | ### Milk Ejection - Suckling stimulates supraoptic + paraventricular nuclei (hypothalamus) ⇒ oxytocin released (post pituitary) into bloodstream. - Assessment of milk ejection: - Subjective = mother's sensations. - Objective = oxytocin blood sample, intraductal pressure measurement, milk duct diameter & flow. - Inhibition of milk ejection: 1. Impaired oxytocin release (alcohol, opiates). 2. Impaired innervation (reduction mammoplasty). 3. Stress (adrenaline causing vasoconstriction). ### Normal Breastfeeding Behaviour (in a day) - 11 feeds (each 75ml; up to 179ml stored; 788ml produced in 24h) with 67% milk available & fat content of 41g/L. ## Reproductive Physiology (MALE) - 1923 (Painter described human X & Y chrs); 1947 (Jost castrated XX & XY rabbit fetuses in utero before sexual differentiation ⇒ develop as with ducts & external genitalia) = female as default state); 1989 (Palmer identified human testis-determining factor genetic region); 1991 (Koopman & Lovell-Badge made transgenic XX mice carrying genomic fragment containing Sry gene ⇒ develop as male). ### SRY Gene 1. SRY ⇒ SOX9 ⇒ Sertoli cell → Leydig cell, testes → hormones → male ducts, genitals 2. Wnt4, Rspo1, FoxL2 ⇒ Granulosa cells → Theca cells, ovaries → hormones ⇒ female duct, genitals ### Bipotential Gonad - Embryo: Bipotential genital ridge with both Wolffian & Müllerian ducts - Wolffian ducts differentiate into epididymis, vas deferens. - Müllerian ducts regress (apoptosis). - Müllerian ducts differentiate into oviducts, Fallopian tubes, uterus, cervix, & upper vagina. - Wolffian ducts regress (apoptosis). ### Development of Reproductive Axes - 7wk gestation: 1st identifiable step differentiating ovo-testis pathways = movement of primordial germ cells into medullary cords. - 7-8wk → primitive gonad cortex develops (SRY activation). - SRY controls early testis differentiation into Sertoli & Leydig cells. - Sertoli Cells: secrete AMH ⇒ ♀ reproductive structures to regress. - Leydig Cells: secrete Testosterone ⇒ induces differentiation of Wolffian duct system (epididymis, vas deferens, sex accessory glands). - ♀ (no SRY) - 7-8wk ⇒ primitive gonad cortex develops into ovary (medulla regresses). - Embryonic ovary doesn't secrete hormones. ### Puberty - Puberty regulated by the HPG axis (initiated via pulsatile Hypothalamus GnRH release). - Adrenal cortex also secondarily involved. - Brain stimulates hypothalamus ⇒↑GnRH → A. pit ⇒ ↑LH & FSH ⇒ gonads produce sex hormones ⇒ ovaries: oestrogens (oestradiol); testes: testosterone. - FSH + LH also stimulate the development of oocytes (♀) & spermatozoa (♂). ### Hypothalamus - Hypothalamus generates GnRH pulses (12th yr of life; at night due to gradual nocturnal melatonin secretion decrease from pineal gland + nutrition influence). - Also influenced by: - GH & IGF-1 stimulate reproductive function. - Leptin/Ghrelin ⇒ metabolic hormones determine size of fat stores. - Kisspeptin: Kiss1 or KissR null mutations = hypogonadotropic hypogonadism (HH) ⇒ pathological impuberism + infertility of CNS origin. - Testosterone in male (lifetime fluctuation). ### Testosterone - T is secreted by testes Leydig cells in response to LH (LH+FSH ⇒ Leydig-tropic). - Drives 1° + 2° ♂ sexual characteristics. - T ⇒ DHT by 5a-reductase in some target cells. - DHT + T bind androgen receptor, stability DHT-R >> T-R complexes. - Amplifies action of T in some target tissues (*DHT-R complexes required for external genitalia). ### T Feedback Control - Systemic T inhibits GnRH + LH secretion (↓ T). - Blood-testes barrier (Sertoli). - Leydig cells secrete T → bathes seminiferous epithelium, provides 100x↑ local [androgen]. - Sertoli cells also secrete ABP. - **IV T doesn't raise testes androgen Ivl as much ⇒ so, net effect of systemically administered T = ↓ sperm count.** ### Functions in Male Reproduction 1. Spermatogenesis A. Sperm formed in ~900 coiled seminiferous tubules (each >0.5m long). B. epididymis (coiled tube ~6 m long) ⇒ vas deferens ⇒ enlarges (ampulla) → enters prostate gland ⇒ contents pass into an ejaculatory duct ⇒ internal urethra + mucus supplied from urethral glands & bilateral bulbourethral glands. I. prostatic ducts also empty ⇒ ejaculatory duct ⇒ urethra C. Seminiferous tubule I. Germ cells: spermatogonia (immature) ⇒ spermatozoa. II. Sertoli cells: 1. nourish germs cells (lose contact = death); contain lipid, glycogen. 2. secretory: AMH, inhibins/activins, ABP, oestradiol. 3. create blood-testis barrier (apical sp. movement reqs constant reforming of gap junctions). 4. modify seminiferous tubule fluid (↑ local [steroid], [nutrients]). III. Leydig cells (interstitial): secrete androgens (LH-responsive). IV. Myofibroblasts: contractile, support. D. Spermatogenesis. I. primordial germ cells (embryonic) migrate ⇒ spermatogonia. II. @puberty, spermatogonia mature, proliferate & differentiate ⇒ 1° spermatocyte. III. Meiosis I ⇒ 2× 2° spermatocytes. IV. Meiosis II → 4x spermatids. V. Differentiate into mature spermatozoa. VI. 1 spermatogonium = ~512 sperm, takes ~74d. E. Spermatozoa. I. Head ⇒ haploid genome (X or Y) + Acrosome (hyaluronidase & proteolytic enzymes to facilitate ovum penetration) + minimal cytoplasm. II. Tail mitochondria-packed + motile microtubules flagellate (propulsion; 1-3mm/min). F. Epididymal sperm maturation. I. Testicular spermatozoa incapable of fertilizing eggs (unless injected). II. Maturation achieved at distal corpus or cauda (6-8d). III. Acquire progressive motility: eff. ducts (0%), caput (3%), proximal corpus (12%), distal corpus (30%), cauda (60%), IV. Biochemical changes: 1. ↑ capacity for glycolysis. 2. ↑ phospholipid & phospholipid-like FA content. 3. Activation of CatSper (Ca2+ receptor reqd for acrosome rxn). G. Accessory Glands. I. Seminal vesicles ⇒ paired glands w/ 65% alkaline fluid containing Prostaglandins, fibrinogen & fructose. Semenogelin (prevents early sperm capacitance, limits motility). II. Bulbourethral glands (paired) ⇒ <5% alkaline, pre-ejaculatory fluid seminal fluid. III. Prostate ⇒ 30% of seminal fluid w/ liquefying enzymes, fibrinolysin, PSA (serine protease; hydrolyses semenogelin ⇒ sperm motility inhibitor). 2. Sexual Performance. A. Erection. I. Vasodilation ⇒ increased arterial blood flow to corpora cavernosa ⇒ turgor compresses veins = limits loss of blood ⇒ erection. 1. corpus spongiosum remains pliable = prevents urethral occlusion. II. Controlled by integrating centres (lumbar) activated by desc. paths (arousal) & aff. from genitalia. III. Parasympatheic nerves in penis release. 1. ACh + VIP (co-transmitters) = vasodilate. 2. NANC fibres release nitric oxide ⇒ cGMP. IV. ED. VASODILATE. Sexual stimulation Nitric oxide Inactive guanylate cyclase Active guanylate cyclase GTP CGMP Vasodilation and erection Viagra Levitra Cialis Phosphodiesterase inhibitors Degraded by PDE5 Loss of erection B. Ejaculation (sympathetic control). I. Emission = semen movement through urethra. 1. Vas deferens SM contraction move sperm fwd w/ prostate, seminal vesicle SM contraction move prostatic + seminal fluid fwd internal urethra + bulbourethral secretions. II. Ejaculation = propulsion, expulsion via bulbospongiosus SkM contraction. 3. Hormonal regulation of male reproductive functions - **Capacitation & Acrosome Rxns** - *Sperm uses chemotaxis (progesterone) & thermotaxis (~2°C gradient between oviduct & ampulla) to find way.* - **Capacitation** → PSA degrades semenogelin = ↑ motility, alkaline uterine/fallopian fluid alters membrane (↓chol., ↑Ca2+ perm). - **Acrosome rxn.** - Hyaluronidase & proteolytic enzymes digest proteins in ovum ECM. - Sperm reaches zona pellucida ⇒ sperm membrane binds receptor proteins (ZP3), entire acrosome rapidly dissolves = enzyme release. - Open penetrating pathway for passage of sperm head through zona pellucida = inside ovum. - Sperm head + oocyte membranes fuse (cortical rxn) = deliver sperm genome. - Protein receptors. Jelly coat Acrosome Sperm head 1 Contact 1 Acrosomal reaction Egg plasma membrane EGG CYTOPLASM Vitelline layer Hydrolytic enzymes Cortical 2 Perivitelline space granule Fused plasma membranes Cortical granule membrane Acrosomal process GNAME Fertilization membrane Cortical reaction Sperm nucleus Growth of acrosomal process Sperm plasma membrane Entry of sperm nucleus Fusion of plasma membranes - **Oocyte activation:** Sperm entry causes Ca2+ release ⇒ triggers cortical reaction. - **Cortical Reaction:** Cortical granules exocytosed into perivitelline space. - Proteases that sever ZP3 receptors – any bound sperm falls off, new sperm can't bind. - Hyalin forms layer hardening vitelline membrane making it impenetrable. - Hygroscopic mucopolysaccharides (GAGs) expand vitelline space. ## Reproductive Physiology (FEMALE) ### Ovaries - **Gametogenic function:** Germ cells ⇒ oocytes ⇒ ova. - **Endocrine function:** - **Oestrogens** (potency: β-oestradiol > oestrone > oestriol) = Granulosa cells (also corpus luteum) which need aromatase activity; regulated by LH & FSH - **Progesterone** = corpus luteum (small amt from follicular theca cells); regulated by LH (via cAMP) - **Inhibin B (inhB)** = secreted by CL granulosa cells ⇒ inhibit ant. pit. FSH secretion. - LH - AC - ATP - Theca cell - Cholesterol - CAMP - Pregnenolone - Progesterone - LDL - LDL - Granulosa cell - Cholesterol - Pregnenolone - Progesterone - LH - Androgens - Androgens - ATP - FSH - AC - Capillaries/ - Extracellular - fluid - Aromatase CAMP - Estrogens - Hall: Guyton and Hall Textbook of Medical Physiology, 12th Edition - Copyright © 2011 by Saunders, an imprint of Elsevier, Inc. All rights reserved. ### Oestrogen - Stimulated by LH + FSH ⇒ bind nuclear oestrogen receptors (**ERa, ERB** ⇒ TF). - **Effects** - Facilitate growth of ovarian follicles + uterine tube motility. - Cyclical changes in endometrium. - Increases blood flow + uterus SkM contractility. - Oestrogen-dominated uterus more sensitive to oxytocin. - Increases breast duct growth. - Feedback: Inhibits FSH... LH (either↑ or↓) . ### Progesterone (Pro-gestational-hormone) - Stimulated by LH, bind nuclear progesterone receptors (**PRA,PRB** ⇒ TF). - Mifespristone (RU486) blocks progesterone binding. - **Effects** - Uterus: progestational changes in endometrium, cervix + vagina. - Antioestrogenic effects ⇒ prevents uterine contraction. - ↑ excitability, oxytocin response, number of ERs. - Breast: stimulates lobule + alveoli devt, supports lactation. - Brain: stimulates thermogenesis & respiration. - Feedback: inhibits LH (large doses prevents ovulation); mainly pulse freq. ### 28 Day Cycle - Hypothalamus controls gonadotropin secretion. - GnRH secreted in episodic bursts ⇒ menstrual cycle. - Oestrogen increases freq, Progesterone decreases freq. - Pituitary hormones (FSH, LH) ⇒ Ivl depend on GnRH & ovarian hormone -ve feedbk. - Ovarian hormones → Ivl depend on pituitary hormones, -ve feedbk & number/size of secretory cells. - - Plasma hormone level - (arbitrary units) - 50 - 40 - LH - 30 - 20 - 10 - (a) Fluctuation of gonadotropin levels - Plasma hormone level - (arbitrary units) - 15 - FSH - Follicular phase Luteal phase - Estrogens - 10 - 5 - 0 - Progesterone - (b) Fluctuation of ovarian hormone levels - Gonadotropins, oestrogen and progesterone - Hypothalamus - ① - GnRH - Anterior - pituitary - ④ - High estrogen level - FSH. - ⑥ - LH - Slightly elevated - estrogen level - and rising inhibin - levels - Estrogen. - Progesterone. - and inhibin - LH. - Estrogen - FSH - surge - Key: - Growing - follicle - Stimulates - = Inhibits - ⑥ - Mature follicle - Ovulation - Corpus luteum - Oogenesis - Fetal beginnings → All oocytes made by 7th mth. - Around birth ⇒ meiosis ⇒ arrest at prophase of MI (now 1° oocyte). - At puberty: begin ovulation. - 6-12 1° oocytes re-enter cycle ⇒ 1 matures (dominant oocyte) ⇒ completes MI. - 2° oocyte (↑cytoplasm) + polar body (regresses). - 2° oocyte begins MII ⇒ arrests at metaphase. - Granulosa cell AMH of pre-antral or antral follicles inhibits other primordial ⇒ 1º follicle transition. - If fertilised ⇒ Meiosis II completed (ovum) 2nd polar body cast off. - Metaphase arrest: caused by pp39mos ⇒ destroyed by calpain upon fertilisation. ### Ovarian Cycle - Tunica - albuginea - Cortex - Primary - follicles - Degenerating - corpus luteum - (corpus albicans) - Germinal - epithelium - Primordial - follicles - Ovarian - ligament - Medulla - (a) - Granulosa - Oocyte cells - Secondary - follicle - Mesovarium and - blood vessels - Vesicular (Graafian) - follicle - Theca - folliculi - Ovulated - oocyte - Corona - radiata - Corpus luteum - Developing - corpus luteum - Antrum - Oocyte - Zona - pellucida - 1. Follicular (1st 14d) A. Several follicles enlarge, cavity forms around ovum (antrum) filled with follicular fluid. B. 10-15d before ovulation: dominant follicle starts to grow rapidly, others regress (apoptosis – atretic follicles). C. Oestrogen is now produced from ovary granulosa cells (via theca cells) D. Oocyte increases zona pellucida (glycoprotein shell). - 2. Ovulation (LH surge) A. Day of ovulation ⇒ distended follicle ruptures ⇒ ovum extruded into abdominal cavity ⇒ oviducts ⇒ transported ⇒ uterus. B. 1 ovum/cycle, <450 ova per lifespan. I. When formed (7 mo foetus) - >7×106 primordial follicles. II. At birth: ~2×106 follicles. III. At puberty: 200k-300k ⇒ only 400-500 become ova. IV. Atresia: 1. Granulosa cells TNFα + Fas ⇒ apoptosis. 2. Inhibited by FSH (induces follicle oest + inhB = ↓FSH). - 3. Luteal (2nd 14d) A. After ovulation (d14), ruptured follicle fills with blood ⇒ corpus haemoragicum. B. Granulosa/theca cells proliferate ⇒ corpus luteum (lipid-filled). I. CL secretes megadoses of progesterone + oestrogen AND VEGFa + Fgf2 ⇒ vasculogenic. C. Day 24: I. Pregnant? = CL persists. II. Not pregnant? = replaced by scar tissue (corpus albicans). - 4. Pregnancy or regression - ** LH Surge** - (a) Early to mid-follicular phase - Pituitary - GnRH - Hypothalamus - (b) Late follicular phase and ovulation - + - GnRH - - - FSH - LH - FSH - LHIF - Follicle - Follicle - + - Granulosa - cells - Thecal - cells - Granulosa - cells - Thecal - cells - - Estrogens - Androgens - Inhibin - Androgens - High estrogen Small amount of - output - progesterone - FSH - Follicle - Estrogen - Inhibin - LH - Ovum - Corpus luteum - Progesterone - **LH surge triggers ovulation (no LH surge = no ovulation)** - LH secretion ↑ 6-10-fold, 2d before ovulation = peak 16h before. - LH & FSH synergistically cause rapid swelling of follicle. - LH kicks off theca cell progesterone secretion (CL). - Halts oestrogen secretion, initiates prostaglandin secretion. - Reinitiates oocyte meiosis (blocks 'oocyte maturation-inhibiting substance'). - **Results in 2 effects:** 1. Theca cells release proteolytic enzymes (collagenase) ⇒ dissolve follicular capsule wall ⇒ degeneration of preovulatory opening. 2. Prostaglandins ⇒ follicular tissue ⇒ follicle SM contraction ⇒ ovum expulsion. ### Cause of Surge? - GnRH ⇒ LH+FSH ⇒ Prog, inhB (-ve fbk), + oest - moderate, constant oestrogens = suppress GnRH + LH secretion. - elevated oestrogens = increase GnRH + LH secretion. - LH surge = GnRH release rises throughout follicular phase. - Early follicular phase = ↓inhB, ↑FSH, LH restrained by oest fbk. - 36-48h before ovulation = ovarian growth tips oest fbk to +ve ⇒ LH surge ⇒ ovulation ⇒ luteal phase ⇒ ↑inhB + prog = ↓LH/FSH = ↓oest ### Menstrual Cycle - Early menstrual phase - Proliferative phase - Secretory phase - Rich blood supply; highly glandular. - Undergoes cyclical growth, loss & repair ⇒ menstrual cycle. - Influenced by cyclic changes in oestrogen & progesterone. - Proliferative ⇒ tubular glands with pseudostratified nuclei & mitoses. - Ovulation ⇒ slow growth. - Early secretory ⇒ coiled glands, secretory vacuoles below nuclei. ### Uterine Cycle 1. Menstrual Phase (d1-5) A. CL regresses = sudden drop in oes/prog levels. B. No hormonal support for endometrium = thinning & degeneration with spiral arteries coil+ spasm (prostaglandins). C. Menstruation ⇒ haemorage (30mL, mostly arterial), superficial endom. shed. D. Fibrinolysin (to lyse clots). 2. Proliferative Phase (d5-14) A. late follicular phase of ovarian cycle ⇒ ↑Oestrogen. B. rapid endometrial thickening, proliferation of blood vessels & endometrial cells. 3. Secretory Phase (d15-28) A. CL develops corresponds to Luteal phase of ovarian cycle. B. Endometrial glands secrete fluids, becomes oedematous. C. LATE ⇒ begins to secrete PL = prepare uterus for implantation. - **Corpus luteum regression** -*drives next cycle).* - **Once luteolysis begins ⇒ FSH & LH levels re-set = new crop of follicles develop.** - **Conception** 1. Fertilisation A. chemoattraction ⇒ adherence to zona pellucida (ZP3 receptors) ⇒ penetration + acrosome rxn ⇒ adherence to cell membrane, digestion (cortical rxn), fusion. B. Cortical rxn: Ca2+ ⇒ serine proteases destroy ZP3 receptors (prevent polyspermy). 2. Blastocyst A. Cleavage (cell division). B. Blastocyst stage by day 4: now in uterus. 3. Implantation A. 6-9d post conception ⇒ burrows into endometrium. B. CL fails to regress ⇒ enlarges & secretes oest, prog, relaxin (inhibits myometrial contraction = maintains pregnancy). C. Implanting syncytiotrophoblasts form placenta. D. Mother's endometrial tissue also contributes to placenta (hormone production). ### Important* | Hormone | Function | |---|---| | Human Chorionic Gonadotropin (hCG) | Maintains the corpus luteum of pregnancy. Stimulates secretion of testosterone by the developing fetus. | | Estrogen (also secreted by the corpus luteum of pregnancy) | Stimulates growth of the myometrium, increasing ut parturition. Helps prepare the mammary glands for lactation. | | Progesterone (also secreted by the corpus luteum of pregnancy) | Suppresses uterine contractions to provide a quiet environment. Promotes formation of a cervical mucus plug to prevent ascending infection. Helps prepare the mammary glands for lactation. | | Human Chorionic Somatomammotropin (has a structure similar to that of both growth hormone and prolactin) | Reduces maternal use of glucose and promotes the supply of free fatty acids (similar to growth hormone) so that greater quantities of free fatty acids may be shunted to the fetus. Helps prepare the mammary glands for lactation (similar to prolactin). | | Relaxin (also secreted by the corpus luteum of pregnancy) | Softens the cervix in preparation for cervical dilation. Loosens the connective tissue between the pelvic bones in preparation for parturition. | | Placental PTHrp (parathyroid hormone-related peptide) | Increases maternal plasma Ca2+ level for use in calcification of the fetal skeleton, promotes localized dissolution of maternal bone stores for use by the developing fetus. | ## Maternal changes (Pregnancy) - *Weight gain in pregnancy: mostly baby + nutrients/muscle development + body fluid + blood + amniotic fluid.* - *Most change are hormone driven.* - Progesterone, oestrogen, renin-aldosterone, cortisol, insulin, human placental lactogen, prolactin. - Some mechanically driven (decreased lung capacity, vena caval compression). - UTI - Profuse vaginal - discharge - Urinary - urgency and - frequency - Candidiasis - Fatigue - Genitourinary - Insomnia - Pruritis - Respiratory - Breast soreness - Other - Polymorphic - eruption of - pregnancy - Striae - (Stretch marks) - Dyspnoea - Cholasma - Anaemia - Dermatological - Pregnancy - Complications - Oedema - Cardiovascular - Palpitations - Varicose veins - Back Pain - Musculoskeletal - Pubic symphisis - diastasis - Leg Cramps - Labour Specific - Prolonged labour - Gastrointestinal - Neurological - Headaches - Carpal Tunnel - Syndrome - - Abnormal fetal - presentation - Constipation - Nausea and - vomiting - Heartburn - Haemorrhoids - Spontaneous - abortion - PROM - fastbleep ### Changes in pregnancy - **Uterus** - ht; 7.5cm → 35cm & wt; 50g ⇒ 1kg (hyperplasia). - Uterine ligaments (stretch + hyperthropy). - Right dextro-rotation. - **Cervix** - Oedematous, congestion. - Eversion of columnar cells. - Increased cervical glands secretion. - Mucus plug ⇒ operculum. - Increased vascularity & varicosities. - **Vagina** - Increased vascularity + distension at birth. - **Ovary** - Increased vascularity + CL present. - **Pelvic ligaments** - Relaxed, more mobile pelvis (increased capacity). - **Breast** - Increased size, vascularity, pigmentation of nipple/areola. - Montgomery tuberacles on areola (dilated sebaceous glands). - Colostrums from wk16. ### Endocrine - **Pituitary** - Ant pituitary increases in size + activity. - Post pituitary releases oxytocin at onset of labour & during lactation. - **Thyroid** - Increased size & activity (physiological goitre). - TBG Ivl doubles, increased total T3 & T4. - **Parathyroid** - Increased size, activity, Ca2+ metabolism. - **Adrenal** - Increased size, activity, increased total cortisol. ### Hormones - **Placental hormones** - **Progesterone** - Produced by CL, then placenta. - Ivl rises steadily through pregnancy, until output reach 250mg/d. - Actions: relaxation, nausea, constipation, diastolic BP reduced, venous dilation, raised temp, anti-inflammatory. - Human chorionic - gonadotropin - Estrogens - Plasma hormone concentration - Progesterone - 0 1 2 3 4 5 6 7 8 9 - Months since start of - last menstrual period - 10 - Parturition - **Oestrogens** - Source: ovary early, placenta, fetal adrenals. - Oestrone & oestradiol produced by placenta (100x increased). - Oestriol produced by placenta & fetal adrenals (1000 x increased). - Reaches max of 30-40mg/d. - Actions: induces uterus growth, lowers Na+ excretion, water retention, breast devt. ### Metabolic - **Carbohydrate** - Pregnancy = hyperlipidaemic & glycosuric. - After pregnancy ⇒ insulin resistance develop (due to cortisol & hPL). - Plasma glucose conc rises (4.5mmol) ⇒ crosses placenta + primary energy for fetus. - Conc for glucagon & catecholamines unaltered. - **Protein metabolism** - +ve nitrogen balance; 500g protein retained at end of pregnancy. - - - - - glycerol - ↑ ketones - glucose - 111 - fats - amino - acids - amino - acids - fatty acid - glucose - glycerol - ketones - amino acids - **Fat metabolism** - 4kf stored in depot fat (abd wall, back, thighs, breasts) by wk30. ### Skeletal - Increased lordosis (relaxed pelvic joints due to relaxin, progesterone). - Widened costovertebral angle. - Altered centre of gravity. ### Urinary - Increased size kidneys (ureteral & renal pelvis dilation by wk8). - SM relaxation by progesterone + Urinary stasis. - Increased renal blood flow (increased GFR, lower colloid oncotic pressure due to decreased albumin). - Increased renin (stimulated by progesterone; made in placenta) ⇒ Na+ retention, K+ excretion = decreased osmolality. - Output: 1ml/kg/hr BUT ⇒ increased tubal resorption + glycosuria. - = FREQUENCY - Increased UTI risk (stasis, reflux, glycosuria) ⇒ pyelonephritis. - Increased oedema (low oncotic pressure, fluid retention). - Right physiological hydronephrosis (increased rise of calyces, renal pelvis). ### Gl changes - Increased salivation & appetite & thirst, altered taste. - Slower Gl motility (progesterone). - Nausea + vomiting. - Constipation ⇒ decreased motility, increased water + salt absorption. - Decreased gastric acidity ⇒ risk of aspiration (early intubation). - Gastro-oesophageal sphincter relaxation ⇒ reflux oseophagitis (via progesterone & relaxin). - Liver: - Increased synthesis albumin, globulin, fibrinogen, clotting factors (via oestrogen). - Increased hormone binding globulins (thyroid, steroid, vitD). - Increased gall bladder size & slower emptying (higher risk for gall stone formation). - Bile secretion unchanged. ### Haematological changes - Increased BV (50-100%)+ RBC production (25-40%) ⇒ physiologic anaemia of pregnancy. - Potential protection from haemodynamic instability + dissipate fetal heat production + increased renal filtration + decreases blood viscosity + improves intervillous perfusion. - Decreased Haematocrit + platelets; but increased WBC (gestational thrombocytopenia). - Hypercoagulable. - Increased Fibrinogen, all coagulation factors except II, V, XII. - Decreased protein S & sensitivity to APC. - Bleeding & clotting time unchanged. ### CV changes - Increased CO (30-50%); increased HR (by 15-20bpm). - Approaching term, decreased SV & increased HR maintains CO. - Uterus: 75mL/min to 7