ob/gyn seminar

ob/gyn notes

angiongenesis

mural cells- specialized cells that surround blood vessels

-pericytes, smooth muscle

angiogenic factors

vegf's, notch ligands

wet macular degeneration caused by hypoxia and vessel overgrowth that clouds vision - using antiVEGF is good treatment, also used for diabetic retinopathy

vegf family tyrosine kinase receptor expressed on blood and lymphatic vessels

notch - regulates sprouting angiogenesis, ligand is tethered to another cell membrane (jagged, delta like),

all vegf receptors regulated by notch

notch4 and delta ligand 4, - important for determining whats an artery and vein, delta ligand for is strongly expressed in tip cells the beginning of angiogenesis

notch blocks sprout initiation, keeps a stalk a stalk and tip cell is notch off, ^notch ligand

notch downregu vegfr2 and upreg vegfr1 (inhibitory), tip cells vegfr2 increased expression to increases ligand expression and decreases notch expression

vegf induces delta ligand 4, turns on ligand stimulates notch in neigboring cell.

macrophages can be a source of VEGF and can guide angiogenesis

avasatin - vegf inhibitor approved for some cancers (colon 6-9months longer life than chemo alone, breast very good in shrinking size but doesn't increase survival time etc)

avastin side effects

gi perf ~10% of patients (thought that regeneration of gut depends on angiogenesis)

htn crises

chf

nephrotic syndrome

dii4 blocking antibodies lead to paradoxical hypersprouting but lumens are collapsed so blood cant flow

Pregnancy

2000-2030 incidence expected to double

nyc 530k have it

265k don't know it

1/2 hispanic children will get diabetes

ethnicity - non hispanic whites type1

asians/hispanics type ii predominance

obesity major risk factor, ^portions, sedentary lifestyle

type I 10%

tyep II 90%

gestational carb intolerance (gestation diabetes 2-8%)

secondary diabetes - from injury to pancreas, steroid induced

symptoms - polyuria, phagia, dipsia

blood sugar >200 anytime is diabetic

fast >126 diabetic

100>126 suspect

screen - )GTT

75gm two hour test - 110-126F

140-199 PP = impaired

in pregnancy

OCT - 50gms (don't need fasting) - 1 hour 130-140 abnormal just postive screen

done 24-28wks, high risk pt done at first visit at city hospitals

high risk patient

asian/hispanic, hx of macrosomia, stillbirth, fam hx, obese, glucosuria

if OCT+?

3 hour OGTT

fasting 100gm 1,2,3 hour tests

at least 2/4 have to be abnormal

95 fasting

180 1 hour

155 2nd hour

140 3rd hour

HAPO hyperglycemia and adverse pregnancy outcomes big study

75gm OGTT @ 28wks any of the following lead to adverse outcomes

F=92

1hr 180

2hr 153

capillary blood glucose is unreliable, glycosylated hemoglobin not used

White Classification 1949

A gestational in pregnancy, A1normal fasting high Postprandial, A2 elevated need treatment

B onset >20 yrs duration <10yrs

C- onset 10-20 duration 10-19yrs

D - onset <10>20yrs benign retinopathy

F - nephropathy >500mg 25 hrs

R - proliferative retinopathy

H - ASHD(athersclerotic heart disease)

T-prior renal transplant

Pregnancy - diabetogenic state, insulin resistance and hyperinsulinemia

contrainsulin hormones - HPL, prolactin, progesterone, cortisol - increase gluconeogenesis, come from placenta. ~24 wks when placenta big enough to make hormones on its own why test is done then

throwing up - ketoacidosis, increased insulin, hypoglycemia

PMR perinatal mortality rate (used to compare health of populations)= IUFD +NND neonatal death = 1-3% in general pop

3-5% in diabetes

congential anomalies in diabetes, TGA, VSD, CoA, PDA, ASK, TOF

caudal regression - extremely rare, low low survival

CNS- spina bifida

risk incresed 252fold

Pathophys

hyperglycemia - free radicals, reduces arachidonic acid, ketone bodies, shifts Oxyhb curve, somatomedin inhibiting factors,

yolk sac may be primary targe site (4-6 weeks gestation).

preeclampsia common in diabetics

polyhydramnios - baby is polyuric (just like adult, osmotic diuresis), another explanation is baby is big has big placenta and more fluid coming across

poly associated w/poorly controlled diabetes, control diabetes the fluid level can resolve

fetal demise - seen in both kinds of diabetes, big babies susceptible to fetal demise, mediated by fetal hypoxia

macrosomia - hard to deliver (shoulder dystocia), trunkal obesity, hyperinsulinemia causes IGF-1 big baby

neonatal complications

-resp distress syndrom

-hypoglycemia - when deliver diabetic do a heel stick and check sugar

-hypocalcemia - transport of calcium across cell membrane, mechanism unknown look for tetany

- hyperbilirubinemia due to hemolysis (earlier and more intense)

- polycythemia

A1c should be<6.5

fasting should be <95

2hr pp <120

monitoring -

glucometer

lab checks, bad because longer tube sits RBCs each sugar in tube,

glycosylated hemoglobin - very reliable

rbc life is 3months (half life is 6 weeks)

diet - 25-35kcal/kg

early dinner, ^fiber, no concentrate sugars, ^complex carbs, soluble fiber lowers lipids, keeps blood sugar steady

aim for glycemic index of 50%,

physical activity - walking is the safest activity, 15-30min 3x week, stair climbing is good

insulin treatment in pregnancy

NPH longer acting

R-regular short acting

0.7-0.9 units/kg, begin at half dose

newer one - lispro -very good because acts immediately

oral agents - not approved for pregnancy although used in clinics

glyburide - RCT on glyburide for GDM, used off label, starting in 3rd trimester, doesn't cross placenta

now initial agent, can be used in 1st trimester, no reports of teratogenesis

Metformin - used to treat PCOS and began to ovulate, less neonatal hypoglycemia, 1/2 need insulin as well, more preterms, FDA/ACOG not endorsed.

renal function -24hr urin, CrCl, protein, BP, retinal function, EKG

nodular glomerulosclerosis - kimmelsteil-wilson lesion (glycosylated protein), microalbuminuria

diabetes leading cause of dialysis/blindness

fetal surveillance

crown rump length, anomly scan/efw 3rd

msafp w/quad screen

fetal echo for pregestational diabetics

3rd tri nst and bpp because diabetes big cause of late term death (38-39 wks)

delivery timing and mode

deliver >38 wks if can

check L/S and PG if <38wks

may deliver earlier if big baby,

ripen cervix to avoid failed inductions

NPO no insulin that morning

IV fluids D5RL,10 u insulin

if active labor wont need insulin because muscle using it

SSI postparum, 6 weeks to go down pregestation levels

do a GTT if + residual diabetes, 50% will eventually get diabetes in 20yrs

IUDs in diabetics have higher risk of infection (intrauterine)

long term - GDM doesn't ^nephropathy, retinopathy, baby has increased risk of diabetes, ADHD, learning disabilities,