Patho 2021/22 Exam Review (PDF)

lOMoARcPSD|40301475 Patho year 3 Integrated pathophysiology for nurses (McMaster University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Anjeza Haziri (bndxwm6j...

lOMoARcPSD|40301475 Patho year 3 Integrated pathophysiology for nurses (McMaster University) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review NORMAL FEMALE ANATOMY AND HORMONES Definitions Hypothalamic Fetal Presentations ¥ Menarche first menstrual cycle Pituitary Ovarian Axis ¥ Macrosomia when fetal head size has ¥ Os opening from uterus through cervix into vagina, can measure dilation to monitor labour (HPO) grown larger than can be passed progress ¥ Main hormonal vaginally ¥ Fundus top of uterus, during pregnancy used as measurement point for monitoring growth feedback pathway ¥ Polyhydramnios amount of amniotic of fetus (symphysis-fundal height), & after delivery palpated to monitor resolution phase responsible for fluid is >2 standard deviations above the ¥ Viability point at which if fetus delivers there is reasonable expectation of survival, usually reproductive system norm for gestational age 5gm or more than 20wks Normal Female Anatomy Pregnancy Definitions th ¥ Sexual differentiation of embryo occurs at 7 wk gestation determined by sex chromosomes (XX female, ¥ Prenatal period from conception to birth, aka XY male) & SRY protein on Y determines presence of testes antenatal period ¥ Ovaries produce secondary oocytes & hormones like estrogen, progesterone, inhibin & relaxin, at birth ¥ Postnatal period from delivery of infant until ovaries contain all primary oocytes, secondary oocytes formed after puberty once month at ovulation complete resolution of body pre-pregnancy state, ¥ Uterine/fallopian tubes transport secondary oocyte to uterus & normally the sites where fertilization usually 6-8wks occurs ¥ Parity number of deliveries woman has had over ¥ Uterus site of implantation for fertilized ovum, place where fetus develops during pregnancy & promotes 20wks gestation, number >5 considered grand progression of labour multiparity o Endometrium innermost lining layer of uterus that functions to prevent adhesions btwn myometrium’s ¥ GTPAL shorthand for describing obstetrical hx maintaining patency of uterine cavity, layer sheds in menstruation o Gravida total # of pregnancies, including o Myometrium middle layer of uterine wall consisting of uterine SM cells (monocytes) & miscarriages, abortions & stillbirths stromal/vascular tissue, functions to induce uterine contractions o Term total # of deliveries over 37wks gestation o Perimetrium outer serous layer of uterus that secretes lubricating fluid to reduce friction & part of o Preterm total # of deliveries btwn 20-37wks peritoneum that covers some organs in pelvis o Abortions spontaneous or therapeutic ¥ Uterus position born w position & remains same throughout lifetime, palpated during exam, position o Living number of living children doesn’t affect fertility Female Hormones Puberty Follicular Stimulating Hormone Estrogen Progesterone Relaxin ¥ Hypothalamic (FSH) ¥ Responsible for development ¥ Secreted mainly by ¥ Produced by corpus luteum & neurosecretory cells release ¥ Stimulates growth of follicles of & maintenance of female cells of corpus plays role in relaxation of gonadotropin releasing ovaries to produce estrogen, reproductive structures & luteum in last 2wks uterine SM hormone (GnRH) which progesterone & inhibin secondary female of menstrual cycle binds to anterior pituitary Luteinizing Hormone (LH) characteristics (adipose ¥ Works w estrogen to Inhibin gonadotropes & stimulates ¥ Responsible for stimulating tissue deposition, voice prepare & maintain ¥ Secreted by granulosa cells of them to ↑ secretion of ovulation, creates corpus luteum that pitch, broad pelvis & pattern endometrium & follicles & works w estrogen follicular stimulating are support cells making sex of hair growth) prepare mammary & progesterone to provide hormone (FSH) and hormones, & LH surge causes ¥ Works w GH to ↑ glands for lactation feedback for HPO axis, either luteinizing hormone (LH) follicle to rupture & egg be released protein/bone synthesis stimulating or inhibiting in ovulation ¥ Lowers blood cholesterol further FSH & LH release Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review The Menstrual Cycle Day 1-5: Menstruation Day 6-14: Pre-ovulatory Phase Day 15-28: Post-Ovulatory ¥ Uterus sheds all but deepest layer of ¥ Variable pre-ovulatory phase Phase endometrium (aprox 50-150mL of where FSH causes maturation of ¥ Post ovulatory phase where blood, tissue, fluid, mucus & epithelial dominant follicle progesterone & estrogen cells) ¥ Proliferative phase of uterus as secreted by corpus luteum ¥ Ovarian hormones at lowest levels estrogen promotes endometrial causes more growth & stimulating secretion of GnRH leading growth coiling of endometrial glands to FSH & LH secretion ¥ Approx. day 14 ovulation occurs & thickening of ¥ Discharge due to decreased amount of when secondary oocyte released endometrium in preparation progesterone & estrogen into pelvic cavity surrounded by for fertilized ovum ¥ Can be manipulated clinically w zona pelucida & corona radiata ¥ Without fertilized ovum, exogenous hormones like oral birth ¥ LH influences leftover cells in corpus luteum degenerates control & when woman stops taking ovary to become corpus luteum leading to ↓ progesterone → active hormones, level of progesterone which then secretes estrogen, menstruation ↓ promoting bleeding progesterone, inhibin & relaxin Implantation Development in Pregnancy ¥ Zygote fertilized ovum, must be ¥ Embryogenesis stage of rapid development of ectodermal, able to penetrate endometrial endodermal & mesodermal layers for all structures & systems layer to get pregnant in human embryo & fetus ¥ Blastocyst collection of rapidly ¥ By end of 13wk gestation, all major structures & pathways are proliferating cells (inner cell formed mass) surrounded by ¥ Chorion membrane derived from two layers of tissue trophoblast cells (become o Inner layer from ectoderm that becomes trophoblast that placenta) up to 2wks divides rapidly & creates small finger like projections to ¥ Embryo from 2-8wks uterine myometrium to begin to form chorionic villi ¥ Fetus from 8wks to birth o Outer layer mesoderm that fills in villi projections w ¥ Few hours after implantation branches of umbilical vessels so they can be vascularized trophoblasts around o Chorion contributes to development of placenta blastocytes begin to make hCG & is specifically produced during pregnancy to maintain corpus ¥ Placenta develops btwn 8-10wks to take over task of luteum which produces ↑ progesterone to support & thicken uterine lining producing progesterone & hCG enabling corpus luteum to ¥ Day 10-12 post fertilization there will be rise in human chorionic gonadotrope hormone degenerate (hCG), a beta subunit of glycoprotein used to detect pregnancy in urine & blood ¥ 10-14wks chorionic villi & intervillous spaces or maternal o If hCG levels insufficient, corpus luteum regresses, progesterone drops & sloughing of sinuses have blood flow & can facilitate nutrient & gas endometrial layer occurs exchange o Typically beta-hCG level doubles every 2 days in early pregnancy & viability of pregnancy ¥ ↑ blood flow ↑ intraplacental O2 demand & ↑ O2 tension is supported by this to rule out ectopic pregnancy contributes to oxidative stress which can lead to miscarriage ¥ Blood test more sensitive & can detect rise above 5IUs per L and for urine to be positive, level ¥ Arteries & veins ↑ in # & capacity & divide into secondary must be at 25IU/L then tertiary vessels before entering mainstem villi or ¥ Use first void of morning w urine test bc hormone levels most concentrated umbilical stalk Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review Placental Development Amniotic Fluid or Liquour Placental Anomalies Placenta Positions ¥ Formed by 10wk gestation ¥ Continues to accumulate to 1-2L at ¥ Velamentous or ¥ Risk factors for development of ¥ Filters nutrients, O2 & fetal waste term circumvallate cord insertion placental previa include grand productions by diffusion btwn mother ¥ When water breaks, opening in major umbilical vessels multiparity, recurrent abortions or & fetus through finger like projections amniotic sac permits fluid to exit & separate before reaching miscarriages or uterine surgery or interdigitations into endometrium when membranes ruptured, note placental disk, no major ¥ Placental previa placenta forms so ¥ Lochia flow occurs after delivery of quantity & colour of fluid to determine consequence in utero but it’s either completely or partially baby & is sign that location of if fetus has passed meconium prior to greater chance for cord trauma covering uterine os placental attachment is healing birth w bleeding during delivery ¥ 18-20wk ultrasounds done to see ¥ Amnion membranous sac that Fluid Abnormalities in Pregnancy ¥ Vasa previa vessels run position of placenta surrounds developing fetus for ¥ Polyhydramnios associated w unprotected through ¥ Potential for placenta position to protection as it grows gestational diabetes & involves membranes change as uterus continues to grow in o First appears as small sac that excessive amount of fluid which can ¥ Succenturiate accessory lobes pregnancy enlarges & becomes fluid filled by overextend uterine cavity & lead to develop as part of main ¥ Complete previa placenta fully over 4th or 5th wk poor descent placenta body so vessels are os, delivery by planned c-section ¥ If membranes rupture before adequate only supported btwn lobes by ¥ Low lying or marginal previa Placenta membranes descent, there is potential for prolapse vaginal delivery may be considered ¥ 2 umbilical arteries, 1 umbilical vein ¥ Placenta accreta results from of umbilical cord w c section set up to be performed at o Umbilical vein carries oxygenated lack of formation of normal ¥ Oligohydramnios associated w GHTN moment’s notice blood to fetus decidual plate so chorionic w too little fluid around baby leading to ¥ Increases risk of antepartum o Umbilical arteries remove villi extend into myometrium intolerances of stress of labour, fetal hemorrhage deoxygenated blood & placenta cannot separate HR decelerations as vessels are ¥ Diagnoses comes w recommendation ¥ Chord always inspected after delivery normally after delivery constricted & not as much blood for complete pelvic rest for presence of 3 vessels & on routine resulting in severe hemorrhage passing btwn placenta & fetus resulting ultrasound of pregnancy in lower fluid volume Hormones in Pregnancy Rise in estrogen, progesterone, appearance of hCG & placental proteins Beta hCG Maternal Thyroxin Human Chorionic Human Chorionic ¥ Chorionic gonadotrophin ¥ Crosses placenta & facilitates fetal Somatomammotropin (hCS) Corticotropin (hCC) ¥ Main role to maintain corpus development ¥ Protein hormone w immunological ¥ Role unclear, but levels luteum ¥ Dysfunction associated w ↑ risk of & biological similarities to pituitary detected in both maternal ¥ Can stimulate maternal thyroid preeclampsia, GHTN, low birth weight, growth hormone & fetal circulations gland to ↑ circulating thyroid preterm delivery, perinatal morbidity & ¥ Anti-insulin characteristics like ↓ ¥ Maternal hormones mortality glucose uptake & ↑ FFA release adrenocorticotropin ¥ Two major subunits Pregnancy Proteins ¥ Potent prolactin like or lactinogenic hormone (ACTH) doesn’t o Beta subunit measured w ¥ Ex. PAPP-A used for Downs syndrome bioactivity reach fetus & thinking is pregnancy tests of blood & screening ¥ Secreted by placenta into maternal that placental hCC isn’t urine ¥ Macroglobulin’s circulation w little reaching fetus under feedback regulations o Alpha used in fertility ¥ Placental proteins ¥ Maternal plasma [ ] linked to by maternal treatments to promote ovulation ¥ Placental membrane proteins placental mass glucocorticoids Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review Placental Corticotropin Releasing Hormone (CRH) Estrogen ¥ Synthesized in placenta ¥ Primarily formed from DHEA ¥ Has similar characteristics of hypothalamic CRH secreted by zona reticularis layer of ¥ CRH in non-pregnant woman approx 5-10picomoles/L adrenal cortex of mom & in larger but during pregnancy it ↑ to 100 early in 3rd trimester quantities by fetus & is transported & up to 500 in last 5-6wks gestation, rising another 2- to placenta where it’s converted to 3 fold w onset of labour estradiol, estrone & estriol ¥ Plays role in ¥ Causes enlargement of uterus, o Timing of parturition, w levels ↑ near end of breast ductal structure & pregnant pregnancy, SM relaxing & ↑ formation of woman’s external genitalia prostaglandins ¥ Works w relaxin to relax pelvic o Fetal lung maturation & development of fetal ligaments (mainly symphysis surfactant cortisol signals lungs to start producing pubis) to become elastic to allow surfactant so lungs can turn into functioning tissues for easier passage of fetus upon delivery Placental Progesterone ¥ W premature labour, betamethasone given to mimic ¥ Essential to maintain pregnancy natural cortisol & promote maturation of lungs especially uterine linings CHANGES IN PREGNANCY Uterine Changes Definitions Dating for EDC ¥ 12 weeks ¥ Preterm infant born before 37wks ¥ When expected date of confinement EDC it’s o Able to palpate uterus above pelvic bone during pelvic ¥ Term born btwn 37-42wks imperative to use & determine first day of last exam ¥ Post-term born after 42 wks menstrual cycle LMP o Can auscultate fetal heartbeat w ultrasound doppler ¥ Weight gain excessive weight gain ¥ Once EDC has been established & confirmed w o Uterus is shape of large avocado or softball in pregnancy put woman & fetus at ultrasound, it’s very important that date is not changed ¥ 16wks fundus of uterus halfway btwn pubic bone & umbilicus risk for gestational diabetes, ¥ It isn’t nursing responsibility to determine due date ¥ 20wks fundus is around umbilicus & can start measuring gestational HTN, fetal macrosomia & Calculate EDC symphysis fundal height SFH to measure fetal growth dystocic labour (uterus cannot get ¥ Using a pregnancy wheel ¥ Singleton pregnancy would expect SFH to be w/in 1-2cm of # into concerted, rhythmic pattern of ¥ Using an online pregnancy calculator of wks pregnant contractions to affect delivery) ¥ Using Naegele’s Rule (least common) FULL TERM PREGNANCY Fetal Position Uterus ¥ At delivery presenting position evaluated by palpating for anterior & posterior ¥ Enlarges from 50gm size to 1100gm fontanelles of infant during vaginal exam ¥ Increases volume from 10mL to 5L & up to 20L o Anterior fontanelle diamond shaped soft spot created where skull bones join ¥ Shape initially shape of pear but becomes spherical by 12wks then o Posterior fontanelle triangle shaped ovoid w ↑ length for rest of pregnancy ¥ Purpose of determining fontanelles is to determine which way occiput is pointing ¥ Position uterus starts in pelvic cavity but after 12wks rises towards o Occiput anterior presents fetus in best position to affect vaginal delivery as widest anterior abdominal wall & liver causing intestines to displace part of head goes into widest part of pelvis ¥ Becomes more elastic & fibrous in response to estrogen & progesterone, o Occiput transverse and posterior presentations put wide part of head into narrow placenta site enlarges more rapidly than rest part of pelvis & result in failure to descend ¥ Hagar’s sign uterine isthmus becomes soft & compressible Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review Breast Cardiovascular ¥ Nipple enlargement ¥ Position of heart & PMI as uterus enlarges & pushes against ¥ Increased pigmentation ↑ blood supply so veins become more visible & in second & diaphragm, heart is laterally displaced to left which directly impacts third trimester proliferation of mammary glands occur from hormones PMI landmark ¥ Montgomery’s tubercles hypertrophic sebaceous glands more pronounced elevations ¥ Increased size, intracardiac volume & myocardial mass by approx. on areola 12% to accommodate demands ¥ Mammary glands ready for lactation during pregnancy but prevented by high estrogen ¥ Cardiac output increases 30-40% peaking around 24wks, not Respiratory uncommon to hear systolic ejection murmur ¥ Tidal volume & resting minute ventilation ↑ ¥ Hypervolemia blood volume ↑40-50% to help meet metabolic demands ¥ Functional residual capacity & residual volume ↓ as uterus elevates diaphragm of placenta & enlarging uterus, potential physiological anemia can occur ¥ RR unchanged ¥ Increased aldosterone promotes water retention GI ¥ Increased erythropoietin causes ↑ bone marrow RBC production & ¥ Heartburn due to relaxed esophageal sphincter from ↑ progesterone & estrogen and reticulocytes release also bc of ↑ abdominal pressure ¥ BP changes systolic & diastolic BP decline during pregnancy but ¥ Decreased motility allows for greater absorption of nutrients, can lead to constipation typically reach pre-pregnancy levels by approx. 36wks ¥ Enlarged gallbladder contracts slower & limits ability to completely empty, can lead ¥ Venous pressure increases later in pregnancy in lower extremities to bile stasis & ↑ risk of w cholestasis leading to venous congestion in form of varicose veins, hemorrhoids & dependant edema Renal Skin ¥ Increased length, weight & volume of kidneys & can be ↑ volume in renal pelvis w ¥ Striae stretch marks common in abdomen, breast & thighs late 2nd tri dilated renal calyces ¥ Hyperpigmentation more noticeable in darker complexions due to ↑ ¥ Predisposition for UTIs ureters dilate ↑ urine volume & risk for UTI stimulation of melanocytes to produce melanin ¥ Increased renal blood flow & GFR can cause physiological glucosuria & proteinuria o Linea nigra line on abdomen o Antenatal monitoring of urine at each visit for presence of protein & glucose o Chloasma irregular patches of different sizes on face or neck COMPLICATIONS IN PREGNANCY Hypertensive Disorders of Pregnancy (HDP) Pre-Eclampsia ¥ HTN systolic ≥140 or diastolic ≥9 ¥ Definition progression of htn w clinically significant proteinuria w ¥ Pre-existing HTN diagnosed before 20wks adverse conditions like new/unusual headache, visual disturbances, ¥ Gestational HTN diagnosed after 20wks, leading cause of maternal morbidity persistent epigastric pain, chest pain, dyspnea, changing liver enzymes, ↓ ¥ Severe HTN systolic ≥160 or diastolic ≥110 & associated w ↑ stroke risk platelets ¥ Pre-eclampsia condition of htn & increasing proteinuria, 10-20% risk in pre-existing ¥ Proteinuria dipstick ≥2+ or ≥30mg/mmol urinary creatinine in random htn, up to 35% risk w GHTN urine sample or ≥0.3g/day in 24hr urine o Both pre-existing & gestational would be considered to have pre-eclampsia if ¥ Evaluation dipstick urinalysis common screening test for presence of developed proteinuria protein & BP measurement at every antenatal visit ¥ Maternal risk MI, stroke, HF & renal failure ¥ Assessment if evaluation shows progression towards GHTN w new onset ¥ Fetal risk placental complications like poor O2 transfer, placental abruption, fetal proteinuria, deep tendon reflexes & testing for presence of clonus growth restriction, preterm birth or death examined bc signs of CNS irritability or seizure activity & ↑ fetal ¥ Treatment beta-blockers (labetalol, metoprolol), CCB (nifedipine, methyldopa) or surveillance required severe cases a direct vasodilator (hydralazine) ¥ Sudden/severe onset mother hospitalized for ongoing monitoring of BP, o ACEIs and ARBs are contraindicated d/t teratogenic or fetotoxicity I&O & continuous fetal monitoring Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review COMPLICATIONS IN PREGNANCY CONT. Pre-Eclampsia Risk Factors Pre-Eclampsia Pathophysiology ¥ Advanced maternal age >40yrs ¥ Complex process first leads to ¥ First continuing pregnancy uroplacental mismatch ¥ Obesity or excessive weight gain ¥ Most of systemic endothelial ¥ Family or personal hx activation occurs in intervillous space ¥ Inter-pregnancy interval 10yrs where placental villi meet maternal ¥ Use of reproductive technologies blood ¥ Multiple gestation 1. Incomplete trophoblastic invasion & ¥ Elevated BP at initial prenatal visit placental implantations causing Pre-Eclampsia Treatment shallow vessel development 2. In addition, immunological ¥ Can begin in pre-conception period by counselling to maladaptation btwn maternal/paternal adopt healthily lifestyle & controlling pre-existing htn & fetal tissue leads to overall poor ¥ Depends on gestational age & disease severity bc only placentation cure is delivery 3. Uteroplacental mismatch where feto- ¥ Medications placental demands > maternal supply o Beta-blockers or methyldopa to control BP promotes inflam & anti-angiogenic o Antenatal corticosteroid therapy (betamethasone) mediators → endothelial activation & causes ↑ leukocytes, inflammatory cytokines, prostaglandins & given w pre-eclampsia before 34wks to facilitate fetal free radicals to contribute to oxidative stress lung maturation 4. Endothelial cells promote pro-thrombotic & pro-inflammatory state leading to maternal syndrome ¥ Bed rest commonly recommended but limited evidence causing potential organ damage (ARDS, cardiomyopathy, eclampsia, stroke, edema, ¥ Delivery after 37wks woman would be induced thrombocytopenia, liver damage, proteinuria, htn) Aspirin Prophylaxis in Potential Sequelae of Untreated Pre-Eclampsia… Post-Partum Hemorrhage (PPH) Pre-Eclampsia Eclampsia ¥ Excessive bleeding occurs in first 24hrs after delivery ¥ Daily low dose aspirin ¥ Symptoms all features of pre-eclampsia w seizures ¥ Active mngmnt of placenta delivery to prevent PPH (60-150 mg) after first ¥ When mother is seizing, uterus is too & can result in placental abruption & ¥ Treatment trimester ↓ incidence of neurological consequences for mother o Get help & start resuscitation quickly pre-eclampsia in ¥ Goal is to stop seizures & deliver baby o Assess ABCs, add O2, ensure patent IVs, VS women at risk by at ¥ Seizure prevention magnesium sulfate acts as non-specific muscle relaxant o Uterine massage promote prostaglandin/contraction least 10% ¥ Treatment delivery, consider risk/benefit ratio o Medications uterotonics promote uterine ¥ No ↑ risk of PPH, ¥ Seizures can happen post-partum, typically at 3-6 days contractions ex. oxytocin, ergotamine or maternal blood loss, HELLP Syndrome misoprostol (prostaglandin) neonatal intracranial or ¥ Further progression of htn state o Direct compression w uterine packing or balloon interventricular o Hemolysis breakdown of blood cells o Surgery last resort bleeding o Elevated Liver Enzymes signifying inflam of liver characterized by pain ¥ Risk factors four T’s ¥ Benefits reduction in under right ribcage o Tone abnormal tone w uterine atony, over IUGR and preterm o Low Platelets signals clotting disorder & if unchecked can progress to distension of uterus (polyhydramnios, fetal births, & ↑neonatal disseminated intravascular coagulopathy (DIC) macrosomia, bladder distension), prolonged labour birth weight ¥ Treatment delivery, maternal corticosteroids, blood products (platelets if o Tissue retained placental tissue ¥ Risk ↑ risk of placental 9 values 4000gm at birth), high risk ethnicity (indigenous, ¥ Imbalance btwn Hispanic, southeast Asian, African), age >35, obesity, PCOS coagulation & ability to ¥ Screening clot or ability to break o Urine dipped at each antenatal visit for presence of glucose down fibrin clots o 50g oral glucose challenge OGTT (preferred approach) pt ¥ Coagulation over btwn 24-28wks drinks 50gm syrup like drink & has blood activated promoting work drawn 1hr later & BG 11.1 confirmed GDM body consumes clotting ¥ Abnormal BG of 1SD above normal associated w fetal factors & platelets → hyperinsulinemia, ↑ birth rate, ↑ C-section rate & ↑ neonatal abnormal bleeding & hypoglycemia severe hemorrhage ¥ Treatment ¥ Main initiating factor over expression of tissue factor o Medical nutritional management 1. TF & other pro-inflam mediators (IL1, IL6, IL8 or adhesion molecules) continue to o Client education facilitate secretion of TF from endothelial cells or monocytes o Frequent blood sugar monitoring 2. TF responsible for activating coagulation cascade, especially w activation of thrombin o Use of insulin if lifestyle alone doesn’t help 3. Normally plasmin works in conjunction w thrombin limiting fibrin clot Pregnancy and Blood Sugar 4. TNF-alpha stimulates plasminogen activator inhibitor (PAI), limiting plasmin from ¥ GDM disease of insulin resistance, so mother will have elevated breaking up fibrin clots circulating glucose 5. Inflam continues to activate more monocytes by variety of cytokines expressing more TF ¥ Glucose crosses into placenta, but insulin doesn’t, leading to ↑ → more fibrin deposition & deficiency of protein C (activates to limit clots but w secretion of insulin from fetal pancreas excessive stimulation liver can’t make enough) ¥ Maternal and fetal effects 6. Microvascular clots in organs & small vessels lead to ischemia or necrosis → activate ↑ o Macrosomia insulin acts like GH, can lead to ↑ incidence of inflame cytokines & if clots persist, organ failure shoulder dystocia leading to permanent injury of brachial 7. Kinin, complement & inflam systems ↑ vascular perm, ↓BP, cause shock & further plexus platelet activation inducing ↑TF & cytokines o Perinatal mortality 8. Overwhelming consumption of platelets & clotting factors cause body to no longer clot → o ↑ risk of stillbirth hemorrhage o Potential link to pre-eclampsia ¥ Clinical indications small petechiae or large hematomas o Neonatal complications hypoglycemia, hypocalcaemia, ¥ High risk of uncontrolled placental abruption or PP hemorrhage hyperbilirubinemia & polycythemia ¥ Supportive needs frequent BP & VS, blood work, IV access, oxygenation, blood products o Long-term effects higher risk impaired glucose tolerance & (PRBC, FFP, platelets & cryoprecipitate), NS or RL, ensure mom stays warm, monitor blood obesity loss, document, provide controlled environment, help set up for delivery Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review INFERTILITY Infertility Causes of Infertility ¥ Failure of couple to conceive after 1yr of unprotected intercourse ¥ Women 40% ¥ If woman >35, its 6m period of time o Non-modifiable hormonal issues (ovulation disorders, PCOS) & genital Late Maternal Age tract issues (endometriosis & PID) ¥ Women born w all oocytes they will have in their lifetime o Modifiable age, weight, exercise, stress/psychological factors, ¥ Higher risk of spontaneous miscarriage, GD & G-HTN tobacco/alcohol/substance abuse ¥ Fertility begins to decline after age 35 ¥ Men 30-40% ¥ Multifactorial o Non-modifiable sexual dysfunction, poor semen/sperm quality, Ovulatory Disorders quantity, motility or shape ¥ Anovulation egg (ovum) doesn’t release from ovary during menstrual cycle o Modifiable smoking, exercise, factors, alcohol/abuse ¥ Amenorrhea absence of menstruation ¥ Unexplained (idiopathic) 10-20% woman have more reactive immune system than males for immediate infections protection & can lead to ¥ Irregular cycles are any cycle length less than 24d or over 36 days development of antisperm antibodies impacting fertility ¥ When evaluating amenorrhea disorders can be divided into groups based on ovarian hormone secretion & gonadotropin levels Causes of Amenorrhea In… Tubal Disorders ¥ Normal ovarian hormone secretion amenorrhea cause may be pregnancy, uterine dysfunction ¥ Blocked fallopian tubes can lead to infertility & ↑ risk caused by hysterectomy, endometrial ablation, or adhesions ectopic pregnancy ¥ Increased ovarian hormone secretion dysfunction caused by feminizing tumors, masculinizing ¥ Bilateral blockage is rare tumors or PCOS ¥ Causes ¥ Decreased ovarian hormone secretion look at HPO axis to see how hypothalamic derived o Untreated STIs ↑# & severity of infections ↓ chances gonadotropins levels are of pregnancy & can result in permanent injury of o High gonadotropin levels hypothalamus working very hard to get ovaries to respond due to fallopian tubes w loss of cilia function, fibrosis & menopause, ovarian failure, previous chemotherapy ect. complete occlusion o Normal or low gonadotropin levels other hormones may be impacting system like adrenals or o Chlamydia & gonorrhea causing PID steroid hormones (excessive DHEAS, adrenal tumors, congenital adrenal hyperplasia, excessive o Endometriosis progesterone, or testosterone) o Embryological origin o Low gonadotropin levels ↑ prolactin from prolactinoma suppressing pituitary response, ¥ Surgery can be done to alleviate blockages but doesn’t ↓ anorexia, hypothyroidism interfering w normal GnRH secretion, ↓ in LH can ↓ TH availability chance of ectopic & not commonly done as can lead to ¥ PCOS ovarian cysts resulting in chronic anovulation & endometrial hyperplasia adhesions leading to f-tube constriction or ovum motility Hysterosalpingography (HSG) Endometriosis ¥ To evaluate patency of fallopian tubes by ¥ Appearance of plaques of endometrial tissue on other structures in pelvis or peritoneal cavity like bowel, bladder, inserting speculum into vagina & injecting ovary or fallopian tubes dye through catheter in uterine cavity ¥ Tissue swells & sloughs every month w endometrial tissue, but there’s no exit point which causes significant pain ¥ Diagnostic hysteroscopy/laparoscopy w & scaring depending on where ectopic endometrial implants are dye transit pelvic structures & inside ¥ Cause unknown, some evidence supports retrograde menstruation (menstrual flow moving in wrong direction) uterus reviewed as methylene blue injected ¥ Unknown if it contributes to infertility to see if it free spills from tubes into ¥ Diagnosis initially by clinical suspicion, laparoscopy needed for more definitive diagnosis peritoneal cavity ¥ Symptoms dependent on where plaque is found & if it’s settled on nerve root or ovary can be more painful than on muscle mass Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Alterations in Reproduction Patho 2021/22 Exam Review Polycystic Ovary Syndrome (PCOS) Pathophysiology of PCOS ¥ Endocrine disorder a/w primary 1. A/w metabolic defect that presents as insulin resistance & hyperandrogenemia w or w/out hyperinsulinemia anovulation & associated infertility 2. Both muscle & adipose tissue demonstrate altered glucose uptake ¥ Key defining feature is ↑# of follicles 3. However gonadotropic effect of insulin on ovarian tissue unaffected & compared to normal ovary which over further ↑androgen production & premature cessation of follicular growth produce androgens → androgenemia 4. Insulin also reduces serum sex hormone-binding globulin (SHBG) ¥ Clinical manifestations that binds testosterone & estradiol in circulation to make them inactive oligomenorrhea (less frequent so there will be more biologically active steroids available menses), hirsutism (excess hair 5. Excessive ovarian androgen production & less SHBG, net effect is ↑free growth) & acne testosterone & estrogen ¥ Exact prevalence unknown but felt 6. FSH typically lower & elevated LH leads to androgens, particularly that ↑ obesity rates correlate w ↑ DHEA-s (dehydroepiandrosterone sulfate) levels from adrenal cortex PCOS rates secreted in up to 50% of PCOS pts ¥ Criteria to differentiate normal & 7. Blunted FSH/LH feedback leads to stimulation for new follicles but not to full maturation or ovulation ∴ accounting for polycystic ovaries anovulatory cycles o ↑ volume >9mL 8. Cycle continues o 10 or more follicles of 2-18mm ¥ Treatment re-establish normal hormonal levels using oral birth control, sometimes Metformin used to ↓ ovarian diameter steroidogenesis o ↑ in amount & density of ovarian ¥ Pregnant women w PCOS have ↑ risk of GDM, G-HTN, preterm birth & perinatal mortality stroma & thickening of tunica ¥ Potential later sequelae dyslipidemia, CV disease, DM or metabolic syndrome Uterine Anomalies Treatments for Infertility ¥ Female genital tract AKA Mullerian system ¥ Intrauterine insemination (IUI) least ¥ During embryogenesis can be small changes in usual development process invasive & involves instilling semen directly that can result in major anatomical anomalies at maturation into uterus ¥ If pregnancy carried past viable point w anomaly, higher risk of preterm ¥ Ovulatory stimulation can be done w IUI w delivery & malpresentation at time of delivery (breech or transverse lie) medications like clomiphene or follitropin to ¥ Shape fibroids can alter shape of uterine cavity & result in preterm delivery ↑ # of mature ova in given cycle to ↑ chances or malpresentation of pregnancy ¥ Fibroid tumours exist on or in muscle layers of uterus ¥ In vitro fertilization (IVF) ova collected o Pedunculated fibroid benign growths in uterus attached to uterine wall by stalk-like growth called peduncle, through transvaginal aspiration guided by can grow inside & outside uterus ultrasound & sperm combined outside body, o Submucosal fibroid develops in inner layer of uterus or in submucosal layer attached by long stalk & can permitted to develop 3-5days then zygotes block & distort fallopian tubes transferred to woman’s uterus o Intramural fibroid grow in muscles of uterus within uterine wall o Subserosal fibroid grows on outside of uterus & can be attached to uterus directly or by thin stalk Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Sepsis and Shock Patho 2021/22 Exam Review SEPSIS Factors Related to Mortality from Sepsis Sepsis-3 (2016) Septic Shock ¥ Age very young & very old are most susceptible ¥ New definition describes sepsis as “life- ¥ Septic shock subset of sepsis where o >50% children hospitalized for sepsis are neonates & 20% are threatening organ dysfunction caused by particularly profound circulatory, cellular & infants 65yrs largest hospitalized group for sepsis ¥ New sepsis guidelines described organ mortality ¥ Co-morbidities mortality rates ↑ w number of other physiological dysfunction as an ↑ by 2 or more in ¥ Pt be identified clinically by: derangements (most common HIV, cancer & diabetes) sepsis-related sequential organ failure o Elevated serum lactate levels (> than 2 ¥ Gender males linked to 31.7 sepsis associated deaths per 100,000 score (SOFA) mmol/L) associated w poorer prognosis vs. 23.8 deaths per 100,000 in females o Normal healthy individuals score 0 & o Need for vasopressor therapy to maintain ¥ Onset of sepsis nosocomial sepsis 56% higher odds of dying as organ dysfunction from infection min MAP of 65 mm Hg (i.e. fluid becomes evident, score ↑ resistant hypotension) Sepsis-3 No Longer Uses SIRS Persistent Critical Illness (PCI) ¥ Higher mortality rate so important to ¥ Criteria indicates systemic inflam response rather than localized ¥Recent capacity to support failing organs identify asap ¥ Systemic Inflammatory Response Syndrome (SIRS) previous in ICUs ↑ survival ¥ Term “severe sepsis” removed from sepsis-2 definition of sepsis described it as identified or suspected ¥Persistent critical illness (PCI) those guidelines bc it affects all pts differently infection, in presence of 2 or more of following symptoms who survive may have organ dysfunction qSOFA o Body temp >38° C or 90 beats/minute presentation of sepsis or septic shock (w bedside clinical tool used to help identify o RR > 20/min (or PaCO2 12,000 mm3 or < 4,000 mm3, or > 10% bands 1. Systolic BP ≤ 100mm Hg immune system & muscle dysfunctions ¥ Still useful for detecting infection but doesn’t denote 2. Altered mentation (GCS2 mmol/L overwhelming pro- o Obtain blood cultures then administer broad spectrum inflammatory response antibiotics ¥ Research underway to o Administration of fluids (30 mg/kg crystalloids) in case examine individual patterns of hypotension or lactate >4mmol/L of gene expression which o If hypotension persists, apply vasopressors to maintain may provide information MAP >65 mmHG about prognosis & guide ¥ Bedside rapid response team creating team consisting of treatment in future critical care nurse, physician RT to respond quickly to deteriorating pts in regular hospital beds resulted in fewer pts going to ICU w sepsis & fewer “code blue” calls Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Sepsis and Shock Patho 2021/22 Exam Review SHOCK Recognition of Shock Metabolic Consequences of Shock ¥ Prompt recognition is essential to prevent progression of organ failure & ¥ Common pathways & mechanisms that lead to organ dysfunction death 1. Switch to anaerobic metabolism → ↑ lactate ¥ Signs and symptoms 2. ↓ in efficiency of ATP production & intracellular consequences of ↓ NRG o Low BP 3. ↑ lactate can also occur from metabolic acidosis bc protons come from hydrolysis o Decreased urine output occurring during glycolysis o Poor perfusion leading to acidosis 4. Drop in pH ↓ Hbg affinity for O2, aggravating hypoxia o Body temp mainly decreased but may increase in septic shock 5. Glucose delivery may ↓ from hypoperfusion & uptake reduced from release of o Skin typically cool & clammy but warm & dry in neurogenic & septic hormones, vasoactive substances & steroids in blood o Tachycardia EXCEPT in neurogenic shock 6. Lack of glucose ↑ use of other fuels so lipolysis, glycogenolysis & ¥ Anaphylactic shock abdominal cramping, coughing, wheezing, hives gluconeogenesis enlisted for NRG Treatments for Shock 7. Liver, muscle & NRG stores quickly ↓ ¥ Prompt recognition and rapid intervention is critical 8. Lipolysis ↑FFA & triglycerides in blood (FFA cytotoxic to pancreatic B cells) ¥ Compensatory mechanisms are often ineffective at returning 9. Dysregulation of cellular metabolism can lead to cell death, gluconeogenesis can cardiac/vascular balance lead to organ failure ¥ Treatments 10. Using proteins for NRG ↑ urea & toxic ammonia & depletes plasma protein levels 1. Investigation & discovery of cause & correction or removal if possible allowing more fluid to move a. Further blood loss would be prevented in hypovolemic d/t hemorrhage out of vasculature in response b. Spine & spinal cord stabilization from trauma if neurogenic to lower oncotic pressure c. Removal or neutralization of antigen in anaphylactic shock 11. Alanine generated & converted 2. Blood volume increased through administration of colloids and to pyruvate further elevating crystalloids fluids lactate 3. If needed vasoconstrictors (vasopressors) used to ↑ BP & positive 12. Use of protein from muscles inotropes used to ↑ cardiac contractility (administered in ICU) can lead to wasting of skeletal 4. Pts in ICU undergo regular hourly monitoring to assess effectiveness of & cardiac fibers & depletion of treatment immunoglobulin proteins impairing immune function HYPOVOLEMIC SHOCK Hypovolemic Shock Patho Causes ¥ Reduction in total blood 1. RAAS retains fluid ¥ Bleeding volume due to reduced 2. ADH from pit retains fluid and increases HR ¥ Trauma preload 3. Cardiac contractility increases and vasoconstriction occurs in ¥ Hemorrhage ¥ Any event that reduces fluids extremities to keep vital organs perfused ¥ Dehydration so there is insufficient blood 4. Blood stored in liver is released into circulatory system ¥ Burns to fill vascular compartment 5. Hypothalamus stimulated thirst in effort to increase fluid volume ¥ Loss of blood >10% affect externally cardiac output & perfusion, 6. BP can be maintained by these mechanisms short term but if losses 35-45% abolish vascular volume not restored, adequate tissue perfusion can’t be cardiac output & arterial maintained and organ dysfunction occurs pressure Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Sepsis and Shock Patho 2021/22 Exam Review CARDIOGENIC SHOCK Patho Causes ¥ Cardiogenic shock occurs due to failure of heart to contract at all or in a coordinated ¥ MI matter which prevents heart from functioning effectively → reduced SV ¥ Arrhythmias 1. Decreased cardiac output ¥ Cardiomyopathy 2. RAAS attempts to compensate through fluid retention & vasoconstriction ¥ Valve problems 3. ADH released to increase blood volume ¥ Ventricular 4. Adrenal glands release catecholamines to cause vasoconstriction and increase HR flow/filling issues a. Worsens problem by making heart work harder, increasing systemic vascular resistance (SVR) and preload bc of inability to completely empty ventricle & increased blood volume 2. Pulmonary/peripheral edema may occur from fluid overload or mismatched ventricular pumping 3. Myocardial O2 demands increase bc of increased HR and perfusion impaired from decreased O2 delivery to myocardium 4. BP falls bc of reduced CO 5. Cellular metabolism can’t continue w delivery of insufficient quantities and nutrients leading to dysfunction in the heart and other organs OBSTRUCTIVE SHOCK Patho Causes ¥ Obstruction to blood flow impedes filling or emptying of heart so compromises O2 & nutrient ¥ PE delivery to organs & tissues ¥ Cardiac tamponade (obstructs filling) ¥ Due to impaired blood flow ¥ Tension pneumothorax (collapse of vena cava & R atrium) DISRUPTIVE SHOCK Patho Causes Forms ¥ Profound vasodilation & ↑ vascular perm ↑ capacity of vascular system so ¥ Systemic inflammation ¥ Neurogenic normal blood volume no longer sufficient to fill space & maintain BP ¥ Allergic reactions ¥ Anaphylactic ¥ Due to low systemic vascular resistance ¥ Loss of sympathetic input to BV from acute spinal cord injury ¥ Septic shock NEUROGENIC SHOCK Patho Causes Signs & Symptoms ¥ Form of distributive shock bc no fluid lost, just redistribution that impairs tissue perfusion ¥ Spinal cord & brain ¥ Bradycardia and ¥ Rarest form of shock, typically not permanent trauma, depressant skin warm & dry ¥ AKA vasogenic shock occurs when balance btwn parasympathetic & sympathetic NS is lost drugs, anaesthetics, from suppression of ¥ Widespread vasodilation occurs, vascular compartment has expanded so volume of blood no longer adequate insufficient glucose sympathetic NS to brain possibly from excess insulin Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Sepsis and Shock Patho 2021/22 Exam Review ANAPHYLACTIC SHOCK Patho Signs and Symptoms Treatment Common ¥ Results from overwhelming systemic allergic response ¥ Laryngeal & angio- ¥ Epinephrine via IM or IV to Antigens ¥ Vasodilatory substances released in large quantities & increase capillary edema cause vascular constriction, ¥ Nuts permeability ¥ GI cramps reverse airway constriction & ¥ Shellfish ¥ Hives curtail mast cell & basophil ¥ Bee stings ¥ Bronchoconstriction degranulation ¥ Drugs ¥ Rapid drop in BP → ¥ Antihistamines may be altered mentation required ¥ Very sudden & treatment must be immediate PANCREATITIS Pathophysiology Severe Cases Signs and Symptoms ¥ Pancreatitis inflamm of pancreas that’s potentially ¥ Damage widespread enough to create ¥ Severe epigastric or mid abdominal pain that radiates to back serious → hospital, organ dysfunction or death systemic inflammation & appearance ¥ Serum amylase ↑ (disappears on late presentation), CRP ¥ Can be acute or chronic of SIRS, & shock or other organ level indicates severity ¥ Primary role of pancreas is exocrine gland delivering dysfunction like ARDS or ATN in Treatments digestive enzymes produced in acinar cells to kidneys occur ¥ Treatment directed at pain reduction, pancreas rest (NPO), & duodenum ¥ Fluid may migrate to abdominal cavity restoration of plasma volume w IV fluids to maintain BP ¥ Acinar cells generate proteolytic enzymes, amylase & cause ↓ blood volume w ¥ Pharmacological & lipases in nonactive forms that activate when they accompanying hypoperfusion o Meperidine hydrochloride (Demerol) helps w pain reach SI by trypsin once cleaved, so acinar cells also ¥ Lining of gut becomes dysfunctional instead of morphine bc ↓ incidence of spasm in pancreatic secrete trypsin inhibitor to keep them from being from damage & allows translocation duct sphincter activated right of intestinal bacteria into bloodstream o Fentanyl for pain bc less damaging to kidneys away leading to sepsis o Somatostatin (Octreotide) IV or SC to limit pancreatic ¥ Acinar cell injury Common Causes secretions → trypsin ¥ Most common gallstones or ¥ NG tube may be used to remove gastric fluids that irritate activation, alcoholism condition prematurely ¥ Other causes hypertriglyceridemia, ¥ IV fluids to restore blood volume & electrolyte balance activating drug induced, endoscopic retrograde ¥ Ultrasound or endoscopic retrograde enzymes & cholangiopancreatography (ERCP) cholangiopancreatogram (ERCP) to detect gallstones & causing from mechanical injury or sensitivity find cause autodigestion of to dye, abdominal trauma, ¥ CT scans to check for fluid accumulation & areas of necrosis pancreas tissues hypertriglyceridemia, idiopathic ¥ Cholecystectomy indicated for gallstones, surgical removal → inflam & ¥ Severity ↑ in obesity of necrosis (25-30% cases, pancreatitis reoccurs w/in 6- release of pro- ¥ Acute hemorrhagic pancreatitis 18wks if gallbladder not removed) inflammatory often d/t chronic pancreatitis from ¥ Critically ill patients on TPN, removal of lipids if pancreas cytokines & alcohol, genetic or autoimmune aggravated complement disease system activation Downloaded by Anjeza Haziri ([email protected])  lOMoARcPSD|40301475 Diabetes II Patho 2021/22 Exam Review DIABETES Complications Patient Teaching ¥ Acute triggered by concurrent illnesses & factors related to management of plasma glucose levels (noncompliance w diet or pharm ¥ Maintain therapy, pharm side effects) normoglycemia (A1C o Hypoglycemia 320) 6. Glycogenolysis & gluconeogenesis → Metabolic acidosis pH usually normal hyperglycemia (pH≤7.3 & ↓HCO3 38 (from hypothalamic DA receptor o Phenothiazines & receptors block), unstable BP, profuse sweating, dyspnea, muscle rigidity, incontinence, ↑ WBC & non-phenothiazines ¥ Atypical block several diff CPK (from ↑muscular activity & rhabdomyolysis) ¥ Atypical receptor types in brain including ¥ Atypical antipsychotics 2nd- D2 & alpha adrenergic receptors o Little-no EPS, weight gain & obesity & related risk factors, ↑prolactin levels→menstrual gen, broader spectrum acting as serotonin agonist which disorders, ↓libido, osteoporosis women, impotence men, require routine blood work (+ & -) w fewer EPS activates & mimics serotonin ¥ Extrapyramidal system part of motor system involved in coordination, differentiated from side effects effect ↑ serotonin → ↓ DA pyramidal system, involved in reflexes, locomotion, complex movements, postural control Downloaded by Anjeza Haziri ([email protected])