Day 4 Last part Audio file #8 Renal 2 Penis Embryo: what is the embryology of hypospadias?

Opening on the undersurface (you pee and it goes on your shoes ! failure of closure of urethral fold Epispadias? Opening on upper surface (pee and goes in face " defect in genital tubercle Peyronies dz: li#e $upuytren%s contracture Priapism ! permanent erection& seen commonly in '($) bc of the R*(%s and sic#le cells trapped in the +ascular channels, MC cancer of the penis - squamous bc lac# of circumcision, .t is more commonly seen in an uncircumscribed pt ! they usually do not clean (poor hygiene predisposes ! the smegma is carcinogenic. Testic e (ryptorchid testis ! testicle doesn%t want to come down, /here are two phases in the decent of a testicle: transabdominal migration down to inguinal canal, 0.1 is responsible for this, /he second part of the trip is androgen dependent, /his includes testosterone and dihydrotestosterone, 'o& the first phase is from 0.1 and the second phase is androgen dependent, 2eed testicle down by two years of age bc if not& has a ris# of seminomas, 'till at ris# if you get it down, 3ets say you went in& and it loo# atrophic and other testicle loo#s normal& ha+e to ta#e normal one out& too bc it is also at ris#, 'o& must ha+e testes e4amines to ma#e sure you don%t ha+e a seminoma, !na ogy: in turners& they are infertile and ha+e menopause before menarche& bc by two years of ages& they ha+e no follicles in their o+aries& and this is called a strea# gonad, /his is an o+ary without any follicles, /his is analagous to cryptorchid testes: 5ust li#e the cryptorchid testes predisposes to seminomas (which is a germ cell tumor & so does the strea# gonad predispose to a

germ cell tumor ! howe+er& do not call them seminomas in women& but dysgerminomas, 'o& in pts d4%d with /urner%s syndrome& they surgically remo+e both o+aries bc of the great ris#, /hey don%t #eep them in there bc lead to cancer, "rchitis ! mumps Epididymitis ! less than 78 - 2 gonorrhea9chlamydia& greater than 78 pseudomonas #aricoce e ! on left side bc spermatic +ein connected to left renal +ein& wheras the spermatic +ein on the right is connected to the .:(" bc of this& the pressures increase& and a +aricocele on the left& leads to increased heat and is one of the most common causes of infertility ! ie what would happen if you bloc#ed the left renal +ein? ;ould de+elop a +aricocele, 'o& if you bloc# the left renal +ein& you will increase the pressure in the spermatic +ein and will lead to a +aricocele, Torsion ! spermatic cord twisting" when there is a torsion of the spermatic cord& it shortens it, /his means that the testicle will go up into the inguinal canal, /his is painful, <ou will lose your cremasteric refle4 (in normal male& if you scatch the scrotum& it will contract& which is lost in torsion of the testicle , $ydroce e ! persistence of tunica +aginalis" when you ha+e big scrotum& you don%t #now whether its big bc there is fluid in it& or its big bc there is a testicle in it, 'o& what do you do? /ransilluminate, .f it transilluminates& it is hydrocele, .f it doesn%t its cancer, d9d for painless enlargement of testicle : cancer& cancer& cancer== (why they don%t e+en do b4& 5ust remo+e %eminoma ! 0( (best prognosis " huge cells with lymphocyctic infiltrate, /hey are the counterpart of a woman%s dysgerminoma, /hese will melt with radiation& ha&e itt e 'eta hc(" met to paraortic lymph nodes ! why? *c they came from the abdomen& and that%s where they will go,

MC testicu ar tumor in chi d) *o + sac tumor" tumor mar#er? Alpha feto protein ,hat is -orst testicu ar cancer) choriocarcinoma . not the same prognosis of a gestationally deri+ed choriocarcinma in a woman ! you%re dead E4ample:: 28 yo male with unilateral gynecomastia and dyspnea, (hest 4ray re+eals multiple nodular masses in the lung, 'o& gynecomastia and mets d)& > what is the primary cancer? testicle ! choriocarcinoma, 'ource of gynecomastia: /$C( is i+e L$0 and therefore it stimu ates progesterone in the ma e0 -hich increases duct gro-th and 'reast tissue and eads to gynecomastia E4ample:: same scenario& but older man ! will lead to malignant lymphoma 'o& older pts get malignant lymphoma (not as primary d)& but from mets " the testes mets a lot & esp in leu#emia and lymphomas %ummary: ;orst - choriocacinoma 0( - 'eminoma 0( in #ids - yol# sac tumor 0( in old - mets malignant lymphoma Prostate ?yperplasia occurs in the periurethral portion of the prostate gland, /his is why you get dribbling and urinary retention as the most common symptom, @rostate cancer is in the periphery of the prostate gland within the periphery of your finger, 'o& when you press on it& you feel hardness, E4ample A8 yo man with urinary retention and bladder is up the umbilicus and has dribbling ! what is the most li#ely cause? 2O/ prostate cancer ! why? *c for prostate cancer to do that& it has to in+ade all the way through the prostate gland to the urethra9bladder nec#, /his is prostate ?<@ER@3A'.A bc it is already around the urethra& and this is the 0((& not cancer, ;hat male

hormone is totally responsible for prostate? $ihydrotestosterone ! in embryogenesis& this hormone fuses the labia to form a scotrum& e4tends the clitoris to form a penis and ma#es a prostate gland, 'o& prostate ?@< and cancer are 2O/ testosterone dep cancers& but dihydrotesterone dep cancers, .f you use a 8 alpha reductase inhibitor& that will increase testosterone, /his drug will decrease $.?<$RO/E'/O'/ERO2E 0( cancer in men - prostate cancer @roduces osteoblastic mets, Day 1 Audio file #6 Byn6 $irsutism and #iri ization ?irsutism - increased hair in normal hair bearing areas :irili)ation - hirstuism& plus male secondary se4ual characteristics ()its& acne& deeper +oice & clitoromegaly (pathognomonic /estosterone is predominantly synthesi)ed in the o+ary, 0ost testosterone in a woman is from the o+ary, $?EA sulfate is C8D from adrenals& and is an androgen, /herefore& if a pt has hirstuism& ha+e to get two tests ! get a testosterone le+el ! ha+e to fractionate it bc sometimes the total can be normal& but the free test can be increased& and you get a $?EA sulfate test, 'o& if testeterone is predominantly ele+ated& it is coming from the o+ary and if $?EA is ele+ated& it is coming from the adrenals, .f it is adrenal orgin& it consists of hydro4ylase def (adrogenital syndrome & (ushings& etc,, ?irstuism from the o+aries is a common phenomenon, 'o& when you are e+aluating hirsutism& loo# at $?EA le+els (adrenal origin and testosterone le+els(o+arian origin ,

One of the common causes of o+arian origin are polycystic o+arian syndrome, Po ycystic o&arian syndrome MCC hirstuism 2 po ycystic o&arian syndrome 3or idiopathic4 (Also due to stromal hyperplasia ! stroma of the o+ary can ma#e testosterone& or tumors others o+ary /his d) is a hypothalamic>pit abnormality where 1'? is suppressed and 3? is increased, .f you #now what 3? does& it ma#es the pathophys easy, .n a woman& 3? is responsible for synthesis of theca interna (which is around the de+eloping follicle , $uring the proliferati+e phase of the cycle& what is predominantly being synthesi)ed is the 6A #eto steroids $?EA and androstenedione, /he androstenedione is con+erted by o4ydoreductase into testosterone, /hen& the test goes across the membrane of the de+eloping follicle into the granulosa cells& where there is aromatase, 1'? is put in there, /hen& the aromatase in the granulosa cell con+erts test into estrodiol and this is where the woman gets her estradiol (from the aromati)ation process , 3? is responsible for synthesis of 6A #eto steroids and testosterone in the o+aries, /his is why we will see hirstuism in a woman with polycystic o+arian syndrome (bc increase of 6A #etosteroids& $?EA& androstendione& and testosterone , Obesity is a common correlation with this d), /his ma#es sense bc e4cess adipose - more aromatase& so the se4 hormones test and androstenedione can be con+erted to estrogens in these pts, Androstenedione is aromati)ed into estrone (a wea# estrogen , /estosterone is aromati)ed into estradiol& which is a strong estrogen, 'o& we ha+e a parado4 ! ha+e a woman with signs of e4cess androgens (hirsutism& acne ! not signs of +iruli)ation , At the same time& these are being con+erted to estrogens so will ha+e endometrial hyperplasia and therefore ha+e a ris# of endometrial caricinoma, 'o& there is a combo of increased androgens and increased estrogens, .t is the increased estrogens that causes suppression

of 1'? +ia negati+e feedbac#& while there is a @O'./.:E feedbac# on 3?, 'o& bc increased estrogens& pt is constantly suppressing 1'? and constantly increasing 3?& so the cycle repeats itself, 'o& you can brea# the cycle with an O(@ bc the progestin in it will bloc# 3?, 'o& why do they ha+e cysts? 1unctions of 1'? is to prepare the follicle, Also& they increase the aromatase acti+ity, .f the 1'? is constantly suppressed& the follicle degenerates and lea+es behind a cystic spaces where the follicle used to be, 'o& pt has @O3<cytic o+arian syndrome related to chronic 1'? suppression, (an feel these by pel+ic e4am and seen with ultrasound, Menstrua dysfunction Dysmenorrhea - painful menses (primary and secondary ! 0(( primary is too much @B1 ! a @B that increases contraction of the uterine musculature, /he 0( secondary cause is endometriosis , /here are also problems with dysfunctional uterine bleeding ! this is 2O/ a bleeding abnormality related to a bleeding9organic cause, 'o& in other words& it is not bleeding from an endometrial polyp& its not bleeding from a cancer" this type of bleeding is a hormone imbalance that causes abnormality in bleeding, 0(( abnormal bleeding in young lady from menarche to 2F yrs of age - ano+ulatory bleeding, 'o& if a young lady is bleeding& that is the usual cause, ;hat is occurring? /here is a persistent estrogen stimulation that is occurring on the mucosa& and not enough progesterone stimulation, 'o& they de+elop a lil hyperplasia& there is a build up of mucosa as the month progresses& and then e+entually the stroma sloughs off and leads to significant bleeding, 'o& its mainly an estrogen primed uterus& without the effect of progesterone and they do not o+ulate related to this, /his is the 0((,

!menorrhoea @rimary amenorrhea and secondary amenorrhea ;hen you thin# amenorrhea& it can be a prob with the hypothalamus9pituitary, .n other words& is the hypothalamus putting out BnR? or not? .s the pit putting out 1'?93? or not? 'o& is it a hypothalamic> pit abnormality? .s it an o+arian prob? 0aybe the o+ary is not ma#ing enough estrogen, .s its an end organ prob? /his is anatomically related ! maybe she doesn%t ha+e a +agina > 5o+itans+y67uster6$auser syndrome& or maybe she has an imperforate hymen ! she%s been ha+ing periods all along& and has blood built up behind it& or cer+ical stenosis ($E' e4posure ! these are all anatomical reasons for the amenorrhea, !shermans syndrome ! secondary amenorrhea& woman has repeated dilatation and curotoshes(? & where the stratum basalis is scraped away" ha+e to lea+e something behind from which you can proliferate endometrial mucosa ! if you scrape all the way down the the muscle& will not be able to menstruate again& and will scar e+erything off& leading to an infertile woman, 'o& amenorrhea is primary or secondary : hypothalamic>pit problem& o+arian prob& or end organ prob, 1'? and 3? le+els help in distinguishing those 7, .f pt has hypothalamic>pit prob& what would 1'? and 3? be? 3ow, .f had a primary o+arian problem& what would they be? ?igh, .f you ha+e an end organ defect& what would 1'? and 3? le+els be? 2ormal, ;hat is the first step in the wor#up of any case of amenorrhea? @regnancy test, Turners syndrome: @rimary cause of amenorrhea& webbed nec#& females 0a5ority are HO& therefore do not ha+e a barr body, $efects in lymphatics, (an ma#e d4 at birth +ia @E

! see swelling of hand and feet (lymphedema turners ;ebbed nec# is due to lymphatic abnormalities ! get cystic hygromas& which are dilated lymphatics in the nec# area and fill with lymphatic fluid and stretch the s#in ! bc they stretch the s#in& loo#s li#e webbing, ?a+e preductal coarctations, $o not ha+e 0R, some cases are mosaics ! HOHH and there is a remote possibility that they may be fertile, /here are also HOH<%s that are mosaic%s, ha+e menopause bE menarche, All of there follicles are gone by the age of 2& and this is the strea# o+aries (gonad , /herefore& they are susceptible to dysgerminomas (seminomas are in males are analogous , 8terine Disorders !denomyosis ! glands and stroma within the myometrium !+ery common cause of dysmenorrheal& dyspyrunia& menorragiah& hysterectomy" does 2O/ predispose to cancer, Endometriosis ! functioning glands and stroma outside the uterus (myometrium is .2'.$E " 0( location - o+ary& causes bleeding in the o+ary ! see chocolate cyst (endometroma%s > not cancer& 5ust endometriosis of the o+ary & tube& in pouch of $ouglas E4ample: good Iuestion to as# if pt has endometriosis: J$oes it hurt when you defecate ? <es, ?ow about when your period goes away?K 2o& it goes away ! this is endometriosis bc there is bleeding in the rectal pouch of the pouch of $ouglas (there is endometreosis there , /he rectum is filled with stools& and streches the pouch of $ouglas& leading to pain, 'o& pain on defecation during the period leads to endometriosis, Endometria $yperp asia 1rom unopposed estrogen, Always dangerous to ha+e unopposed estrogen& meaning no progesterone effect& bc then pt runs ris# for endometrial cancer,

0(( endometrial cancer - endometrial ?@< due to unopposed estrogen @ouch of $ouglas can collect seeding from o+arian cancer& pus from @.$& unclotted blood from ruptured ectopic pregnancy (low part of a woman%s pel+is includes: +agina& cer+ical os& uterus& bladder Endometria cancer: Early +s late menarche ! early is worse bc longer time for estrogen to circulate Early +s 3ate menopause ! late is worse bc more estrogen e4posure Obese +s not obese ! obese bc the estrogen factor in adipose (more aromatase & therefore& obese woman are more susceptible to cancers related to estrogen > breast cancer& endometrial cancer& o+arian cancer /ype .. diabetics are at increased ris# bc 8FD of type .. pts are obese (so& the obesity is the cause of increased ris# of endometrial cancer , Cancer and age 'rac+ets E8 - cer+ical 88 - endometrial G8 - o+arian 88 yo& postmenopausal is when you usually see endometrial carcinoma, Any woman that has been in menopause for o+er 6 yr& and then has rebleeding has endometrial cancer until pro+en otherwise, 6st step in management? Endometrial *4 Leiomyoma ! 0( bC tumor in a woman 3eiomyosarcoma ! mitosis prob" 0( sarcoma of the uterus" big bul#y tumors (as are all sarcomas " leiomyoma is 2O/ a precursor for leiomyosarcoma, E4ample: young woman sudden onset of se+ere lower abdominal pain ! must do a pregnancy 3 oo+ at 'eta .$C( e&e 4 test to ru e out ectopic pregnancy.

"&arian masses 'urface deri+ed ! deri+ed from the surface of the o+ary Berm cell types > dysgerminomas (men ha+e these& too 'e4 chord stromal tumors ! ma#e estrogens (ie granulosa cell tumors > therefore can ha+e hyperestrinism which leads to bleeding and endo carcinomas & some ma#e androgens (sertoli leydig cell tumors of the o+ary ! assoc with +iruli)ation and hirstuism , (males 5ust ha+e germ cell tumors 9o icu ar cyst MCC of o&arian mass in a young -oman 2 fo icu ar cyst 1ollicle that ruptured& not neoplastic& accumulates fluid and leads to peritonitis, .t is bad if its on the right side bc it can be either ruptured follicular cyst& appedicitus& ectopic pregnancy (ruptured & @.$" loo# at with ultrasound Lnder 78 yo& most o+arian masses are bC O+er 78 yo& most o+arian masses ha+e a greater potential of being malignant, %urfaced deri&ed (o+erall 0( 0( surfaced deri+ed - serous cystadenoma (*C " serous cystadenocarcinoma (malignant (these are the 0( o+erall bC and malignant o+arian tumors /hese are also the 0( that are bilateral& and the cystadenocarcinoma has psommoma bodies (bluish colored ! due to apoptosis& destruction of the tumor cell and replacement with dystrophic calcification , Also seen in papillary carcinoma of the thyroid and in meningioma%s E4ample:: G8 yo& bilateral o+arian enlargement (remem they tend to arise at this age Any woman that is o+er 88 and has palpable o+aries is cancer until pro+en otherwise bc a postmenopausal woman should be ha+e o+aries that are atrophying,

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E4ample:: G2 yo woman with o+arian mass on the right ! already #now its bad bc shouldn%t ha+e a palpable o+ary, Cystic teratoma /ooth& sebaceous glands& cartilage& s#in& thyroid&& 0( o+erall germ cell tumor& usually *C .f it is ma#ing thyroid& it is called struma o+ary %e: chord stroma tumors 0( - fibromas (*C 0eigs syndrome: o+arian fibroma& ascites& and right side pleural effusion ! goes away when you ta#e the o+ary out, Branulosa cell tumor of o+ary: low grade malignant tumor" what does the granulosa cell normally do? .t aromati)es androgens and estrogens& so a granulosa cell tumor is more than li#ely an estrogen producing tumor, 'ignet ring cells ! is this a primary cancer& or mets from another site? 'ite is from stomach ! called a #ru#enburg tumor" there is ;" primary o&arian cancer that has signet ring ce s. (estationa Disorders P acenta (horionic +illus ! outside layer syncytiotrophoblast& clear cells under the outside layer - cytotrophoblast" which is ma#ing hormones? 'yncytiotrophoblast, ;hat hormones is it ma#ing? *>hcB and ?uman @lacental 3actogen (?@3 ! growth hormone of pregnancy, ?as my4omatous stroma, :essels coalesce into umbilical +ein& which has the highest o2 content, ;eop asms of chorionic &i us: $ydatidiform mo e ! can be complete (EG& HH& both H c%somes come from father ! called androgenesis or partial (triploid& GC c%somes& can ha+e a fetus present /he complete moles ha+e a greater propensity to mo+ing on to choriocarcinoma,

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Causes of choriocarcinoma: 68D of choriocaricnomas are from pree4isting hyadiform mole 28D from spontaneous abortion 28D from normal pregnancy ?yatidiform moles are bC tumors of the chorionic +illus" choriocarcinomas are a malignancy of the trophoblastic tissue (do not see chorionic +illi , 3o+es to go to the lungs and responds well to chemotherapy (can e+en go away in the presence of mets

/reast
@icture a schematic with nipple& lactiferous duct& ma5or ducts& terminal lobules (where mil# is made & and the stroma 2ipple - @agets d) of the breast 3actiferous duct - .ntraductal papilloma (0(( of bloody nipple discharge of woman under 8F ! bC papillary tumor& if you press on it& blood will come out of the areola 0a5or ducts - where most of the cancers arise from ! in+asi+e ductal cancers& medullary carcinomas& mucinous carcinomas /erminal lobules (where mil# is made ! 0( tumor - lobular carnicoma& is famous be *.3A/ERA3 (so& lobular tumors are to the breast as serous tumors are to the o+ary in terms of their bilatterallity " mammography doesnt pic up o'u ar cancers. MCC of mass in 'reast of -oman under 1< 2 fi'rocystic change MCC of mass in 'reast of -oman o&er 1< 2 cancer: infiltrating ductal carcinoma (not intraductal ! this means that we are not pic#ing up the cancer early enough by mammography and pic#ing up in the intraductal phase& and our techniIues are insensiti+e ! so we are missing the ductal stage and we are pic#ing up the cancer when it has in+aded ! to pic# up early& need to get at 8mm or less , 'o& if they are intraductal& has a good prognosis

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E4ample: 78 yo woman with mo+able mass in breast that gets bigger as the cycle progresses fibroadenoma /hese are the most commons in terms of age and location 'lide: fi'rocystic change ! cysts& lumpy bumpy in breast& more painful as the cycle progresses bc they are hormone sensiti+e E4ample:: ductal hyperplasia ! cannot see" precursor lesion for cancer that are estrogen sensiti+e epithelial cells in the ducts (5ust li#e the endometrial glands are estrogen sensiti+e& the glands lining the ducts are estrogen sensiti+e , %c erosing adenosis ! in terminal lobules& bC part of fibrocystic change (see cysts 9i'roadenoma MC tumor that mo&es around in the 'reast in a -oman under =1 2 fi'roadenoma ! is the neoplastic components the glands or the stroma? .t%s the stroma ! as it grows& it compresses the ductstems& so they ha+e slit li#e spaces" +ery common, E+en if you #now it%s a fibroadenoma& still get a b4 /reast Cancer 'lide: ?ow do you #now its breast cancer? nipple is hard as a roc# ! when breast cancers in+ade the stroma& they elicit a fibroblastic and elastics tissue response& ma#ing it hard ! this is good bc it ma#es it palpable, This is -hy a -oman o&er 1<0 that has a pain ess pa pa' e mass0 its cancer. >f its painfu and under 1<0 its rare y cancer 3fat necrosis0 fi'rocystic change4. 'o& the magic word is painless, Outer Iuadrants of the breast are the 0( sites bc this is where most of the breast tissue is, /herefore& this would be the 0( site for breast cancer, /he 2nd 0( site is around the areola, 'lide: nipple being suc#ed in& whitish mass& stellate (classic for in+asi+e cancer " on mammography&

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see density with spicules coming out and has calcified, /his is highly predicti+e for cancer, ;hat is the first step in management of a palpable mass? 12A ! bc can ma#e a d4 and tell if its solid or cystic (this is also the first step in management of cold nodule in thyroid& not ultrasound , 'lide: intraductal cancer ! netli#e arrangement& called comedocarcinoma& 5un# that comes out (li#e caseous necrosis " has erb>2 oncogene (aggressi+e cancers , 'lide: in+asi+e cancer& see tumor cells in+ading stroma" see .ndian filing ! sign of in+asi+e lobular cancer" seen more often in infiltrating ductal carcinoma 'lide: ec)ematous d) around the nipple - pagets d) of the breast ! rash around nipple ! cancer of the duct that has spread to the s#in 'lide: inflammatory carcinoma ! worst& red& dimpled s#in bc the lymphatics are plugged with cancer underneath and the lymphatic fluid lea#ed out& but the ligaments are still attached& but increasing the fluid in the interstium& and as it e4pands out& it dimples ! p%doeu orange ! so& inflammatory carcinoma loo#s li#e that bc its lymphatic filled with tumor& and is the worst of the worst, 'lide: lobular carcinoma ! 0( cancer of the terminal cancer (at the end of the ducts " it is famous for bilaterality 'lide: lymphedema is a woman that is postradical masectectomy" when you are doing a modified radical mastectomy& what are you remo+ing? /he entire breast including a nipple& lea+ing behind pec ma5or& a4illary resection& and ta#ing pec minor, 0( complication - winged scapula (bc cut the long thoracic ner+e The umpectomy remo+es the underlying tumor with a good border of normal tissue around it& ta#e a few nodes from the a4illa (bc ha+e to use for

6E

staging bc they go to lower a4illary first & and then you do radiation of the breast (good for breast conser+ation ! same prognosis as mastectomy E4ample:: ERA>@RA - estrogen receptor9progesterone receptor assay ! what does it mean? Relationship betwn estrogen and its receptor synthesis, 'o& if you are in a reproducti+e period of your life when estrogen is abundant& the receptors will be downregulated, /his is why in women that are young& in the reproducti+e period of their life& ha+e breast cancer and are ER@RA negati+e bc this is what we would e4pect bc estrogen would down regulate receptor synthesis, ;hereas& if you are postmenopausal& it leads to up regulation of the receptors and those women are ER@RA positi+e, *ut what does this mean? .t means that the tumor is responding to estrogen and need to ta#e away that estrogen affect bc it is feeding the tumor, ?ow can you ta#e it away? /amo4ifen ! this is wea# estrogen& so it hoo#s into the receptor of breast tumors& so if there is any left behind& normal estrogen in a woman can%t get into it and won%t be able to feed the tumor, 'o& it%s a bloc#er of the receptor, (omplications? 0enopausal type symptoms" also& it is an estrogen so you ha+e the ris# of endometrial cancer, A benefit in the postmenopausal state with an ERA @RA pos woman is that it does pre+ent osteoporosis, 'o& cannot gi+e estrogen to a woman that is ERA @RA pos& but is a candidate for tamo4 and will prolong recurrence, Audio file $ay8 #2 Byn2 (wrong title it is Endoc Ch ??: Endocrine Disorders Primary &s %econdary &s Tertiary ?ashimotos - destruction of the thyroid gland @R.0AR< hypothyroidism (the gland screws up the hormone ?ypopituitarism and hypothyroidism 'E(O2$AR< hypothyroidism (no /'? to stimulate

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?ypothalamic $) - 'arcoidosis destroying /R?: /ER/.AR< (no /R? E4ample: adenoma on parathyroid producing @/? leading to hypercalcemia - primary hyperparathyroidism E4ample: ha+e hypocalcemia9+it $ def& and as#ed the parathyroid to undergo hyperplasia& that is called 'E(O2$AR< hyperparathyroidism E4ample: what if after a long time @/? #eeps being made - tertiary hyperparathryroidism (rare "&eracti&ity &s underacti&ity of g ands %timu ation test: if pt has underacti+e gland& would use stimulation test to see if the gland is wor#ing, %upression test: if pt has o+eracti+e gland& would use suppression test to see if gland will stop wor#ing, 0ost of the time& things that cause o+eracti+ity& we (A22O/ suppress them, /here are 2 e4ceptions where we suppress them& and they deal with o+eracti+ity in the pituitary gland ! 6 pro actinoma can be suppressed bc it can pre+ent the tumor from ma#ing prolactin" bromocriptine suppresses it (dopamine analog ! normally& women do not ha+e galactorrhea bc they are releasing dopamine& which is inhibiting prolactin (therefore dopamine is an inhibitory substance ! bromocriptine is also used for treating par#inson%s bc bromocriptine is a dopamine analog (which is what is missing in par#insons d) 2 Pituitary Cushings: bC tumor in the pitiuitary that is ma#ing A(/? ! you (A2 suppress it with a high dose of de4amethasone, /hese are the only two e4ceptions for a tumor ma#ing too much stuff, (/here is no way to suppress a parathyroid adenoma ma#ing @/?& or an adrenal ademona

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ma#ing cortisol& or a an adrenal tumor from synthesi)ing aldosterone ! these are AL/O2O0OL' E4ample: pt with hypocortisolism ! lets do an A(/? stimulation test ! will hang up an .: drip and put in some A(/?" collecting urine for 6A hydro4ycorticoids (metabolic end product of cortisol and nothing happens ! so what is the hypocortisol due to? Addison d) ! gland was destroyed ! therefore& e+en if you #eep stimulating it& you will not be ma#ing cortisol, E4ample: 3et%s say after a few days you see in an increase in 6A hydro4ycorticoids& then what is the cause of hypocortisolism? ?ypopituitarism ! in other words& it%s atrophic bc its not being stimulated by A(/?& but when you ga+e it A(/? o+er a period of time& it was able to regain its function, 'o& with that single test& you are able to find cause of hypocortisalism, (an also loo# at hormonal le+els ! ie Addison%s causing hypocortisalism& what would A(/? be? ?igh" if you ha+e hypopituitarism causing hypocortisalism& what would A(/? be? 3ow $ypopituitarism MCC in adu ts 2 nonfunctioning pituitary adenoma (within sella turcica ! in the sphenoid bone& hence surgery is transphenoidal surgery& where the e4panded sella turcica is , @it Adenoma ! usually nonfunctioning and destroys the normal pituitary o+er time as it grows& leading to hypopituitarism, %heehans 3postpartum necrosis4 E4ample:: ha+e a pregnant woman& has abruptio placenta and goes in to hypo+olemic shoc#& but get out" doing fine and breast feading baby at home& but suddently stops breast mil# production ! d4? @ostpartum necrosis ! therefore she has infarcted her pituitary (coagulation necrosis & and this is residual pitiuatary

6A

3This is not iquefacti&e necrosis 'c the pituitary is not part of the 'rain4. 0ech is ischemia and coagulation necrosis, @regnant woman ha+e a pituitary gland two times the normal si)e, @rolactin is being synthesi)ed ! but a pregnant woman does not ha+e galatorrhea bc the estrogen and progesterone inhibit release, 'o& the moment you gi+e birth& the inhibitory effect is released and start ha+ing galactorrhea, /his is the 2nd 0(( hypopit in adult, MC in +ids 2 craniopharnygioma Rath#e%s pouch origin ! this is part of the embryological de+elopment of the pituitary gland ! pieces of it remain and can become neoplastically transformed into a craniopharygioma, .ts not a malignant tumor& but a bC tumor in a bad place, .t is 0( supra>sellar ! (abo+e the sella ! and it goes down and destroys the pituitary& but li#es to go forward and bumps into optic chiasm& leading to 'itempora hemianopsia& leading to +isual field defect, E4ample:: child with headaches and +isual field defect ! do a schematic of it and will as# what the cause is ! craniopharyngioma ! tumor of rath#e%s pouch origin, (ro-th $ormone ;hen you ha+e a tumor that is e4panding in the sella turcica& different releasing factors (hormones decrease in a certain succession, /he first thing that is destroyed is gonadotropin, 'o& in a woman& what would happen? 'he would ha+e amenorrhea (secondary amenorrhea , ;hat if . were a man (what is the analogous condition ? .mpotence" impotence is to a male as amenorrhea is to a female, .mpotence - failure to sustain an erection during attempted intercourse, /he ne4t thing that goes is growth hormone (which has 2 functions: 6 increases aa upta+e and 2 in&o &ed in g uconeogenesis (hormone that produces bone and tissue growth is insulin li#e growth factor>6& which is present in the li+er ! a#a somatomedins" so& B? release will stimulate the li+er to release .B1>6 to cause growth of bones linearly and soft

68

tissue " an adult with the loss of growth hormone will not get smaller& but will ha+e the effects of lac# of growth hormone: will start to lose muscle mass and will ha+e fasting hypoglycemia bc B? is normally gluconeogenic, 'o& its not there and not contributing is func to glucogngeogenesis& leading to hypoglycemia, ;hat would you see in a child? @ituitary $warfism, ;ould see hypop asia (incomplete de+elopment of something , 'o& pit dwarfisim is an incompletely de+eloped child& but e+erything loo#s normal, ;hat is the best stimulation test to see if you are B? or .B1>6 defecient? 'leep, <ou grow when you sleep ! e4actly at 8 am (that%s when B? comes out , 'o& the best test is sleeping& then chec#ing blood at 8 am (if it isn%t your def ,;hy is histidine and arginine deficient? /hey are essential to normal growth of a child bc they stimulate growth hormone, /hese are basic aa%s, /his is why wt lifters buy arg9his supplements, 'o& best test is sleep& followed by measuring arg and his le+els, /he third hormone to go is /'?& which leads to hypothyroidism (therefore low /'? and low /E ! cold intolerance& brittle hair& fatigue& delayed refle4es , /he ne4t thing that goes is A(/? & leading to hypocortisalism, ;ill be fatigue will a low cortisol le+el, ;ill also lead to hypoglycemia bc cortisol is gluconeogenic, /hat last thing to lose is prolactin, Dia'etes >nsipidus (entral (lac#ing A$? +s 2ephrogenic (#idney doesn%t respond to A$? (entral: one of the common causes is car accident& leading to head trauma, /he head is shifted and stal# is se+ered, One of the first things that goes is A$? bc it is made in the supraopitic para+entricular nucleus of the hypothalamus, .n the same ner+e it is made in& it goes down the stal# and is stored in the @O'/ER.OR pituitary, 'o& if you se+er that stal#& you se+er the connection and leads to A$? def, Also def in all the releasing factors that are made in the hypothalamus that stimulate the pituitary& leading to hypopituitarism (e+entually ! but initially will ha+e s9s of $. - polyurea and thrist ,

6C

2ephrogenic: ha+e A$?& but doesn%t wor# on the collecting tubule to ma#e it permeable to free water, Other polyurea%s ($0 ! mech - osmotic diuresis& polydipisia ! mech - drin# too much water (psychological problem & hypercalcemia leads to polyurea , (onstantly diluting& but will ne+er be able to concentrate urine" '.A$? is the e4act opposite& where A$? is always there& and will constantly concentrating& and will not be able to dilute, .n $.& constantly diluting urine& losing free water& and will ne+er be able to concentrate the urine, 'o& you are losing all the water& and serum 2a will go up& correlating with an increased plasma osmolality (bc most of plasma osmolality is 2a , To test: restrict -ater ! in a normal person& if you restrict water& the plasma osmolality will go up to 2C2 (the upper limit of normal for the osmolality & A8F urine osmolality > what does that mean? @t is concentrating the urine, 'o& if you are depri+ing a normal pt of water& it should concentrate the urine" water is being retained get into the E(1 to get the serum 2a into normal range, E4ample: pt restricted water and ha+e a 76C and 762 plasma osmolality (which is ele+ated , 'o& they ha+e hypernatremia, .f you loo# at urine osmolality& it is 66F and C8, 'o you #now that ha+e $., 'o& how do you distinguish central from nephrogenic? Bi+e them A$? (a#a +asopressin , 'o& you gi+e it to them and see what happens to urine osmolality, >f it increases greater that 1<@ from the 'ase ine: then its centra . >t its ess than 1<@ its nephrogenic. 'o& ga+e A$? to first guy and it urine osmolality change to 88F& indicating that he has central $., 1or the second pt& A$? was gi+en& but only a lil increase in urine osmalality& indicated nephrogenic $., !cromega y ;hat is cheapest way for screening for acromegaly? As# for an old pic of the pt 6F years

2F

ago, Bigantism in #id bc epiphyses ha+en%t fused& therefore an e4cess in B? and .B1>6 lead to an increase in linear growth, *ad d) bc can die from cardiomyopathy, 'o& they ha+e e4cess B? and e4cess .B1>6, 'o& what if you%re an adult with acromegaly? ;ill not get taller bc the epiphyses ha+e fused& but bones will grow wider, One of the bones in the head that does that is the frontal bones& so they stic# out, 'o& get a gorilla li#e increase in the frontal lobe (bc it increases si)e of the sinuses & so the hat si)e will increase, <our hands get bigger& feet get bigger& and e+ery organ in the body gets bigger, Also& you produce a cardiomyopathy& which leads to death, (a actorrheaAPro actinoma 0en do not get galactorrhea bc we don%t ha+e enough terminal lobules to ma#e the mil#, 'o& if a male has a prolactinoma& do not e4pect him to ha+e galactorrhea, /his has many causes, ;hen woman comes in with it& ma#e sure you as# what drug they are on > bc there are many drugs that can stimulate prolactin synthesis, E4ample:: O(@%s& hydrala)ine& (a channel bloc#ers& psychotropic drugs, @rimary hypothyroidism can also be a cause& therefore get a /'? le+el, ;hy? *c if you ha+e hashimoto%s& not only is /'? increased& but you also ha+e increased /R?, /R? is used as a stimulation test for prolactin, 'o& you must rule out hypothyroidism in a woman with galactorrhea (so in this case& there is nothing wrong with the pituitary& but the thyroid& leading to galactorrhea , %o0 must rAo hypothyroidism, .f all this is ruled out and pt has high prolactin le+el& d4 is prolactinoma (any time there is a prolactin le+el o+er 2FF it is always a prolactinoma , ;hen pts ha+e prolactinoma& why do they de+elop amenorrhea? *c prolactin has a negati+e feedbac# on BnR?, 'o& this is a cheap birth control pill for the first three months after pregnancy bc mom is breast feeding& and the high prolactin le+els are feeding bac# on the pituitary on BnR?,

26

Thyroid /hyroid studies ! do 2O/ ha+e to #now resin /7 upta#e and /E inde4es" 7 things need to #now: /E& /'?& . 676 upta#e .f /'? is normal& the thyroid is normal, .f /'? is decreased& pt has hyperthyroidism or hypopituitarism, .f /'? is increased& ha+e high primary hypothyroidism, /hyroid binding globulin is the binding protein for thyroid hormone ;hat is the binding protein forM cortisol? /ranscortin" calcium? Albumin" 1e? /ransferrin" (u? (eruloplasmin" what D of binding sites occupied? 7FD , 7 of C binding sites on /*B are occupied by thyroid hormone, 1ree /E le+el, ;hen we measure total /E le+el& there is free /E and bound /E, /he free /E is the part that is metabolically acti+e and is con+erted to /7, /his part is doing all the wor# (that part that is bound is not , ;hat happens if you are on an O(@ with an increase of estrogen? /*B and transcortin increase, 'o& increased syn /*B& and is immediately 697 occupied (C sites on /*B& and 697 occupied by /E& so that is 7 /E%s , *c e+erything is in eIuilibrium& the thyroid senses that it lost 7 /E%s and replaces them immediatetly, 'o& has the 1REE /E altered? 2o, 'o what is the /'?? 2ormal, ;hat is the /E? .ncreased (but the free hormone le+el and /'? not altered , 'o& an increase /E with a normal /'? means the pt is on estrogens, /his is true for any woman on estrogen or any pregnant women, 'o& the total /E is ele+ated bc increased /*B (not be increased free hormone le+el and it automatically has 7 sites occupied by /E , 'ame is true for cortisol ! if pt is

22

pregnant or on O(@& cortisol is ele+ated but do not ha+e signs of cushings, ;hy? *c transcortin is increased bc estrogen increasing the synthesis of it& so there is more cortisol bound to it& but the free cortisol le+els are still normal, E4ample:: if football player9wt lifter& assume pt is on anabolics, /hey wor# the opposite, Anabolics brea# down proteins that you normally would use for other things to build up and put them into muscle, /he proteins it li#es to go after is binding proteins, 'o& when they are on anabolics& thyroid binding globulin is decreased bc the aa%s that you would ha+e used to ma#e the binding protein are instead utili)ed to ma#e muscles stronger, 'o& they won%t wor# if you are not wor#ing aa supplements, E4ample: pt on anabolics& so less /*B being synthesi)e bc proteins being used elsewhere (muscles , /he same number of site are occupied& but missing /*B, 'o& free /E is the same& but missing /*B, 'o& if a person has a low /E with a /'?& they are on anabolic steroids, .f a woman has a high /E and a normal /'?& what is she on? Estrogen, .f a person has high /E and low /'?& what do they ha+e? ?yperthyroidism, .f pt has low /E and increased /'?& what do they ha+e? Primary hypothyroidism, $o not need resin /7 upta#e to ma#e these d4%s, > B=B upta+e is a radioacti+e test (remember that thyroid hormone is tyrosine with iodine on it , (;hat are other things in+ol+ed with tyrosine? 0elanin& tyrosine tyrosinase& dopamine ! goes into the golgi apparatus and becomes melanin& phenylalanine& dopamine& dopa& 2E& epi (catecholamines & if you put iodides on tyrosine you ha+e thyroid hormone , 'o& with hyperthyroidism (ie gra+es & thyroid gland will be ma#ing more thyroid hormone, ;ould we need more iodide to do this? <es, 'o& if you ga+e a pt radioacti+e iodide& will there be increased upta#e of radioacti+e iodide in that o+eracti+e gland? <es, 'o& will ha+e increased .676 upta#e, ;hat if . were ta#ing e4cess thyroid hormone to lose weight ! what

27

would that do to my /'? le+el? 'uppress it, 'o& when that pt is ta#ing too much hormone& the gland has atrophied, 'o& if you ha+e a radioacti+e . 676& would there be an increased upta#e? 2o bc is has atrophied, 'o& radioacti+e . 676 is the main way to distinguish whether a person has true e+idence of hyperthyroidism (B3A2$ is ma#ing too much thyroid hormone +s someone that is surreptitiously9purposely9un#nowingly ta#ing too much thyroid hormone and producing hyperthyroidism, . 676 is the best test to distinguish these two types of hyperthyroidism, 'o& if its increased& pt has gra+es (gland is using it " if its decreased& pt is ta#ing thyroid hormone, E4ample:: pt from wt loss clinic ! they are ta#ing thyroid hormone& so they will lose wt at the e4pense of hyperthyroidism 'lide: midline cyst ! d4? Thyrog ossa cyst. Remember that the thyroid gland was originally at the base of the tongue and migrates down the midline to the current location, 'lide: cyst in anolateral portion of nec# ! d4? *ranchiocleft cyst (#now all branchiocleft deri+ati+es ! esp the one in the head area , Thyroiditis (inflammation of the thyroid /he only imp one is hashimoto%s (ra&es Dz ! e4ophalmos 8nique to (ra&es Dz ! e4cess BAB%s deposited in orbital fat& and pushing the eye out (pathonomognic for gra+es " apathetic gra+es O3$ people with gra+es d) ha+e heart prob with atrial fib, /hey get heart manifestations, 'o& any pt with atrial fib& must get a /'? le+el to rule out gra+es, sAs hyperthyroidism: heat intoleranc& sinus tachy& atrial fib& bris# refle4es& diarrhea& systolic ?/2& hypercalcemia& increased bone turno+er (all symptoms are adrenergic ! they are all catecholamine things !

2E

why? /E increases the synthesis of beta receptors (catecholamines are cousins of /hyroid hormone and they wor# together, All the symptoms are adrenergic, ;hat is the .2./.A3 R4 of gra+es? *eta bloc#ers (bloc#ing adrenergic response& then gi+e @/L to stop the gland from ma#ing it ! can stop all the symptoms with beta bloc#er e4cept one ! sweating so& thyroid studies on gra+es pt: /E is high& /'? is low& . 676 is ?.B? Audio 1ile $ay8 #7 Endoc >n hyperthyroidism0 want to always loo# at the face and will see periorbital puffiness& which is seen a lot bc of BAB%s (also in +ocal cords& leading to hoarseness& tibial area leading to nonpitting edema Mitra #a &e Pro apse also has an increase in BABs bc dermatan sulfate is responsible for causing e4cess and redudency of the +al+e , Also seen in ?ashimotos, Bra+es is due to .gB Ab against /'? receptor& causing it to synthesi)e too much, ;hat type of ?@< r4n is this? /ype .. (Ab against the receptor " 0B is also type .. ?@< (ha+e Ab against receptor which is destroying the receptor , .n hashimoto%s thyroiditis& they also ha+e an .gB against the receptor& e4cept instead of acti+ating the gland& it inhibits it, 'o& in ?ashimoto%s and Bra+es& these are both autoimmune d)%s but at opposite ends of the spectrum, One as stimulatory .gB while the other has an inhibibitory one, 'o& an o+erlying symptom that they both ha+e is pretibial my4edema and BAB deposition, ;here do you see a decrease in BAB%s (ie metabolism of BAB%s ? 3ysosomal storage d)s ! ?urlers& ?unters ! need lysosomal en)ymes for brea#ing down dermatan sulfate& etcN sAs hypothyroidism . wea#ness (0( bc all pts with hypothyroidism ha+e pro4imal muscle myopathy& so they cannot get up out of chairs & serum (O%s are ele+ated, Also ha+e

28

brittle hair& course s#in& slow mentation& periorbital puffiness& delayed refle4& diastolic ?/2 'lide: b4 of thyroid gland in ?ashimotos%s ! no follicle& but do see germinal follicle bc there is autoimmune destruction of the gland, /here are cytoto4ic / cells that destroying it& and are synthesi)ing Ab%s (.gB Abs& hence you see the germinal follicles & and therefore loo#s li#e a lymph node , ;ill see a low /E& high /'?& low . 676 (not necessary to do this test , E4ample: pt on estrogen ! what will happen to /E? .ncrease /'?? 2ormal (no need for . 676 ! this is bad bc babies thyroid would ta#e it up and its thyroid would ta#e it up and leads to cretinism thyroid hormone is responsible for brain growth in the first year& so it imp to do thyroid hormone screens to a+oid cretinism (will be se+erly 0R bc brain depends on thyroid hormone for de+elopment , E4ample: Bra+e%s d) ! /E high& /'?& low& . 676 high E4ample: pt on anabolic steroids ! /E low& /'? normal E4ample: ?ashimotos ! /E low& /'? high& . 676 low E4ample: factitious (ta#ing too much thyroid hormone and ha+e hyperthyroidism ! /E high& /'? low& . 676 low (main factor that distinguishes from gra+es (oiter Anytime thyroid is big, 3ots cysts, MCC goiter 2 >odine def 0ost often due to low iodide le+els& so they ha+e hypothyroidism or borderline hypothyroidism& so the glands are getting re+%d up& /E goes up and /'? goes down (so /'? will be stimulating it& then not& then it is& etc,, , R4 of choice ! thyro4ine

2G

'ometimes ha+e a nodule ! nodules that de+elop in the thyroid gland get hemorrhaged, /here is sudden increase in hemorrhage due to cyst, $4 with 12A, /hen& gi+e thyroid hormone and many times these things will get smaller, .n this country& we iodini)e salt& so don%t see much, ?owe+er& some places people ha+e iodine poor diets ! ie Breat 3a#es in (hicago area& *ritain" when they get gra+es d)& due to increase in /7 bc they are iodide def and do not ha+e enough iodine, Co d nodu e &s $ot ;odu e 0eans if nodule is ta#ing up . 676 or not, .f it does not& there is an area of lucency& and therefore cold, .f it is hot& there will be a blac# dot, ;hy? *c if the nodule is autonomously ma#ing thyroid hormone& what is the /'?? $ecreased, .f the /'? is decreased& would that suppress the normal portion of the thyroid? <es& so it undergo atrophy and not ta#e it up& leading to blac# dot (wouldn%t see anything else , ;hat is chance that a cold nodule is malignant in a woman? 68>2FD, 0ost cold nodules in an older woman are benign, 0ost are cysts, A small D is follicular adenoma, Any cold nodule in a 0A2 is cancer until pro+en otherwise, Any cold nodule in a child is cancer until pro+en otherwise, Any @ER'O2 that has been e4posed to radiation and has a cold nodule has (A2(ER (papillary carcinoma of the thyroid ! radiation e4posure in head9nec# area , Cancers of the thyroid 2eed to b4 (cannot tell if malignant 5ust by loo#ing at it ! this is true for follicular adenoma& something bC& multinodular goiter, $one with 12A, 6, Papi ary cancer would show up with a cold nodule& and has Psammoma 'odies. @apillary carcinomas mets to cer+ical lymph nodes ne4t to them, /hey commonly do this& and ha+e a good prognosis, /his is the only assoc with radiation, Annie orphan nuclei, 2, 9o icu ar cancer ! 2nd 0( type& in+ades +essels, $o not go to lymph nodes, 'pread hematogenously& therefore often go to lungs and bone,

2A

7, Medu ary carcinoma ! some cases are sporadic and other cases ha+e A$ relationship" assoc with 0E2 syndromes (multiple endocrine neoplasia .& ..a& ..b @in# stain ! stain with congo red and see polari)ed apple green birefringence amyloid A (which came from calcitonin " what is the tumor mar#er? (alcitonin (which is the screening test of choice E4ample: where would the cancer be located in the body where the tumor mar#er is con+erted into amyloid? Medu ary carcinoma of the thyroid ME; > ! pit tumor& parathyroid adenoma& pancreatic tumor (usually Polinger Ellison& leading to peptic ulcer , ME; >>a ! medullary carcinoma& pituitary & pheochromocytoma ME; >>' ! medullary carcinoma& pheochromocytoma& mucosal neuroma ?ow do you screen? Ret protooncogene (uniIue to coding for receptors in this syndrome , Prognosis 3'est to -orst4: Papi aryC9o icu arCMedu ary P!5!T$*5">D (L!;D @t can ha+e tetany with a normal total (a, (a is bound and free ! it%s the free (a that is metabolically acti+e (which is true for A2< hormone ! the part that is bound is totally metabolically inacti+e , 'o& who does (a interact with? @/? 'o& if (a is low& the @/? is high& and if (a is high& @/? is low, Roughly 697 of the binding sites in albumin are occupied by (a, 'o& in other words& roughly EFD of the total (a is bound to albumin, EAD is ioni)ed (a floating around and the rest is phosphate and sulfates, /he ioni)ed (a is the metabollicaly acti+e form, 0(( o+erall of hypocalcemia - hypoalbuminemia, ?a+e low albumin le+el& therefore decreased le+el& and less of albumin binds (a, 'o& before you loo# at @/?

28

le+els& loo# at albumin le+els ! if that is low& this is the cause of hypocalcemia, /his is not affecting the free hormone le+el& 5ust that albumin is decreased, /his the same as /*B being decreased& leading to decreased /E, ! +a osis 3resp or meta'o ic4: ha+e decreased ? ions& and p? is increased, ;hat are the acidic aa%s? Blutamate& Aspartate, ;hy are they acidic? ?a+e (OO? groups (as opposed to basic aa%s & which ha+e more basic 2? groups , /he reason why albumin is such a great binder of (a is bc it has the most negati+e charges in the body& bc it has the most acidic aa%s in it, 'o& if you ha+e an al#alotic state the (OO? groups become (OO J>J groups, *c if you ha+e less ? ions& its (OOK>J, 'o& albumin has 0ORE of a negati+e charge in an al#alotic state& which means it can bind more (a, 'o& where does it get it from? .oni)ed free (a (so a bunch of ioni)ed free (a binds to the the albumin , ?owe+er& we ha+e 2O/ altered the total& 5ust too# it, .t doesn%t affect the total& but it $OE' decrease the ioni)ed (a le+el& leading to /E/A2<, 'o& total is the same& but the ioni)ed le+el has decreased, ;hat is the mech of tetany? ?a+e threshold for the A@ before the ner+e is stimulated, /hen you ha+e a resting membrane potential, 'o& a decreased ioni)ed (a le+el will lower the threshold for acti+ating the ner+e and muscle, .f its >GF for normal threshold, @t is partially depolari)ed& therefore doesn%t ta#e a lot to acti+ate the muscle or the ner+e (which is the mech of tetany ! so you are lowering the threshold, .n hypercalcemia& the opposite occurs and you are increasing the threshold& so it ta#es more ioni)ed (a to acti+ate the ner+e, @/? on y a4is and (a in 4 a4is ! ht of sIuare @/? and width - (a Lo- serum Ca0 o- PT$ 2 primary hypoparathyroidism MCC 2 pre&ious thyroid surgery E4ample: pt goes in to remo+e thyroid cancer (these days they autotranplant it to the arm

2C

E4ample: newborn with cyanosis& irritable and 4ray of chest shows not anteriormediastinum shadow ! d4? $iBeorge ! hypoparathyroidism and no thymus E4ample: o- Ca0 high PT$ 2 secondary hypoparathyrodism ! so whate+er is causing the hypocalcemia is causing a compensatory increase in @/? (called secondary hypoparathyrodism ! the 0(( of this is renal failure bc these pts ha+e hypo+itaminosis $& which decreases (a and increases @/? , 'o& any decrease in (a with cause a compensatory increase in @/?, E4ample: high Ca0 high PT$ 2 primary hyperparathyroidism - gland is not obeying negati+e feedbac#, /his is 0(( hypercalcemia is a community" .f pt is in a hospital& 0(( hypercalcemia - mets to bone (malignancy induced , 0ost hypercalcemia pts are asmptomatic" if they ARE symptomatic& they ha+e stones ((a stones& which is the 0( symptomatic presentation for hypercalcemia , 3abs: increased (a& increased @/?& low phosphate (normally @/? increases (a reabsorption and decreased phophorus reabsorption , Almost always o+er 8F yo E4ample: high Ca0 o- PT$ 2 a other causes e:cept primary hyperparathyroidism. 0( due to malignancy, (an @/? li#e peptide cause hyper(a? <es (so if you measure @/? it will be normal , 'Iuamous cell of the lung& renal adenocacinoma& or mets to bone (brea#ing bone down & sarcoidsis (leading to hypercalcemia & multiple myeloma (leading to hypercalcemia all will ha+e 3O; @/?, 'o& what is the e)%est way to determine hyper(a in a pt? @/? le+el (if its high& its primary hyperparathyroidism" if its low& its all the causes ! ie malignancy , !D5E;!L (L!;D Cushing %yndrome @LR@3E striae& obesity& thin e4tremities

7F

0(( - pt on long term steroid therapy (ie pts with renal transplants& pt on immunosuppressant& 3upus .f this is e4cluded& need to thin# of 7 sources: pituitary (ushings& adrenal (ushings& ectopic (ushings, ;hich of the three will ha+e the highest A(/? le+els? Ectopic (small cell carcinoma , ;hich would ha+e the lowest A(/? le+els? Adrenal, ;hy? *c its ma#ing cortisol& which would suppress the A(/?, @it (ushings is usually a bC tumor ma#ing A(/?, /here are 2 good screening tests for (ushings (when you ha+e e4cluded the fact that they are not on steroids , /he screening tests are: 2E hr urine test for free cortisol, /his is loo#ing for cortisol in the urine& not attached to any protein (so it%s free , .t must mean that you ha+e a lot of e4cess of it to ha+e that much of it in your urine, /his is the *E'/ screening test for (ushings, /his test distinguishes (ushing%s syndrome from (ushingoid obesity, E4ample: see obese pt with (ushing%s symptoms and you thin# they ha+e (ushings" howe+er& get a 2E hr urine cortisol test and it%s normal, .f it%s increased& they truly ha+e (ushings ! in other words& they ha+e CCD sens and specificity, /hey will as# about de:meth suppression test (low +s high dose , ;hat is de4amethasone? .t%s a cortisol analog, .f you gi+e de4amethasone to a normal person& it will suppress A(/?, .f you suppress A(/?& the cortisol le+els with be low& indicating the cortisol le+els are suppressible, 'o& what happens when you gi+e a 3O; dose of de4amethasone in a pt with (ushings ! will you suppress their cortisol? 2o, 'o& you see a lac# of suppression, /herefore pt has cushing%s, ?owe+er the 3O; dose 5ust tells you pt has (ushings& not what #ind they ha+e& so it 5ust a screening test (if you did a 2E hr cortisol urine le+el& it would be positi+e , Remember that there are two endocrine d)%s that you (A2 suppress ! @./L./AR< (ushings and prolactinoma, 'o& if you gi+e high dose of de4amethasone& you are able to suppress

76

the A(/? release by the pituitary and cortisol goes down, .t will not be suppressed in adrenal and ectopic (ushings (small cell , QRead last sentence if you get a long IuestionR E4ample: for one of these& they will describe (ushings& and as# about de4meth suppression ! first thing to do is loo# at high dose suppression ! if its suppressed& its automatically pituitary cushings (not a hard Iuestion= 'o& why do the pts loo# li#e this? @t has hypercortisolism& which is gluconeogenic, 'o& need substrates for gluconeogenesis ! main substrate is aa from muscles, ;here are the muscles located? Arms and legs ! so pt will get a brea# down of muscle in the e4tremities& which is why they ha+e thin arms and thin legs, /hen will get alanine transaminated and get pyru+ate, 'o& will always ha+e thin arms and e4tremities, *c it is gluconeogenic& what will the glucose be? ?igh, ;hat does that do to insulin release? .ncreases it, ;hat does insulin do to fat? .ncreases fat storage, ;hat part of the body ha+e the most adipose? 1ace and trun#, 'o& you are getting an increase in deposition of /B in the face and trun# and bac#, 'o& the thin e4tremities is due to brea#ing down muscle for aa%s in gluconeogenesis, /he moon facies& buffalo hump and truncal obesity is due to increase in insulin and fat deposition, /he stretch mar#s are due to obesity& and they are purple bc cortisol decreases collagen synthesis, ;ill get structurally wea#er collagen, .ts li#e purpura within the stretch mar# (li#e senile purpura , *rea# down the +essels bc increase in cortisol, E4ample: Trousseaus sign ! sign of tetany" this pt has ?/2& hypernatremia& hypo#alemia& and metabolic al#alosis ! d4? @rimary aldosteronism, (ha+e tetany bc al#alosis ! neg charges on albumin are increased& and ionin)ed (a le+el decreases , A#a (onn%s syndrome !drena Medu a tumors MC in adu ts 2 pheochromocytoma 3bC& ?/2 (so& adult& ?/2& tumor in adrenal medulla - pheo "

72

ha+e unstable ?/2 ! an4iety& sweat a lot" get a 2E hr urine test for :0A and metenephrine (these are metabolic endproducts of 2E an Epi (so& an4ious& sweating& ?/2 , Are there assoc with pheochromocytoma? <es ! 0E2 ..a and 0E2 ..b& neurofibromatosis (ie pt with neurofibromatosis with ?/2 ! what test you get? :0A and metanephrine 2E hr urine& bc high assoc with pheo , 0( in #ids - neuroblastoma (0A3.B2A2/ *oth of these are from renal medulla& both are neural crest origin& both produce ?/2, @heo adults " neuro > #ids ,aterhouse 9riderichsen %yndrome 2, menigitidis E4ample:: 62 yo& gram J>J diploccocus& high fe+er& nuchal rigidity& spinal tap found neutrophils and gram J>J& #id then Scrashed% ! started to get petechial lesions all o+er the body& hypo+olemic shoc#& died& on autopsy both adrenal glands are hemorrhaged ! $4? ;aterhouse 1reidric#son MCC meningitis from B month to BD yrs of age 2 ; meningitidis. .t is the O23< meningitis with petechial lesions (and they always mention this , 'o& if they gi+e meningitis and petechia& #now is 2 meningitis, .f they are hypo+olemic& they hemorrhaged their adrenals and went into hyp+olemic shoc#& also& they ha+e no cortisol or mineralocorticoids, Cause of hypocortiso ism that is chronic 2 !ddisons dz 0(( Addisons - autoimmune destruction of the gland (used to be /* due to autoimmune destruction , /he entire adrenal corte4 is destroyed& therefore the mineralocorticoids and glucocorticoids are low, 'o& there is low cortisol with ?.B? A(/?, ;hat does that do to melanocytes? .ncreases them& leading to hypigmentation in the mouth and elsewhere, /here is 2O aldosterone, /here are 2 pumps (2a9O pump and proton9O pump , Are you gonna lose 2a? <es ! which will lead to hyponatremia and ?<@ER#alemia (pea#ed / wa+es , ;ill you be able to get rid of the protons in the urine? 2o !

77

therefore will ha+e metabolic acidosis, 'o& you ha+e hyponatremia& hyper#alemia& metabolic acidosis& hyperpigmentation, E4ample: ambiguous genetalia ! what is first step in management? (%some analysis ! ha+e to find out what the genetic se4 is, .t%s HH, 'o& pt has ambiguous genetalia& female& phenotypically cannot tell& so its fema e pseudohermaphrotide . (play odds ! adrenogenital syndrome due to ?B hydro:y ase def. 6A hydro4ylase is responsible for 6A #etosteriods (include $?EA& androstenedione& and are wea# androgens , Androstenedione can be con+erted into testosterone and testosterone into dihydrotestosterone, 6A hydro4ycorticoids are 66 deo4ycortisol and cortisol %o0 if you ha&e an increase in BE hydro:ycorticoids0 this is an increase in BB deo:ycortiso and cortiso >f you ha&e an increase in BE +etosteroids0 3BE0 7%4 its an increase in D$E! and androstenedione. ,hen you ha&e an enzyme def0 things pro: to the ' oc+ increase and things dista to the ' oc+ decrease ,ith ?B hydro:y ase def0 decrease mineralcorticoids and glucocortiocoids and increase androgens& lead to ambiguous genetalia (e4cess androgens & lose salt& high A(/?& therefore hyperpigmented ,ith BB hydro:y ase def ! decreased cortisol& decreased aldost& but increased 66 deo4ycorticosterone (wea# mineralcoricoid & increased 6A hydro4y%s and 6A #etos ! lil girl will ha+e ambiguous genitalia& lil boy will ha+e precocious puberty (e4cess androgens & ?/2 BE hydro:y ase def ! no androgens& increased in mineralocorticoids (?/2 & so if it%s a lil boy he won%t ha+e test and will loo# li#e a female bc no de+elopment (no e4ternal genitalia bc no 6A #eto%s&

7E

test& or dihydrotest , .n a lil girl ! she will be underde+oped, >s et ce tumors Only 2 to #now: .nsulinomas and PE syndrome PE: ma#ing too much gastrin& leads to peptic ulcers .nsulinoma: is pt in5ecting or do they really ha+e insulinoma? ;hen you brea# proinsulin down into insulin& you release ( peptide& so for e+ery insulin molecule that is released& there is ( peptide that is released with it, 'o& if you in5ect human insulin into yourself& and produce a low glucose le+el and ( peptide will be 'L@@RE''E$, .f you ha+e a islet cell tumor& glucose will be low& insulin will be high and ( peptide will be .2(REA'E$, E4ample: pts that ha+e access to insulin get this ($rs& nurses& pharmacists Audio file $ay8 #E 0usculos#eletal Dia'etes Me itus Type B Absolute insulin deficiency Antibodies against islet cells $OA ?3A relationship .nsulin used (always Type ? 1amily history of diabetes Obesity Amyloid in islet cells ?yperosmolar non>#etotic coma .nsulin used when e+entually pt get resistant to '1L @A/?OBE2E'.': 2 mechanisms: 6 "smotic Damage /issue has to ha+e aldose reductase: only 2 ha+e them:

78

i 3ens& glucose sorbitol& osmotic reacti+e& absorbs water into the lens Retinal +essels in lens get wea#& then destroyed due to microabsesses and can rupture and lead to blindness, ii 'cwann (ells: 0(( cause of peripheral neuropathy is $iabetes: 0E(?: osmotic damage 2 ;on6enzymatic ( ycosy ation Renders the *0 permeable to proteins: ?yaline arteriolosclorosis& diabetic nephrophathy ?bA6c: long term control of $0, 'lide: Retina in a diabetic>microaneurysms (red dots 'lide: Retina in a diabetic>neo+asculari)ation E4ample: 8F yr old& blurry +ision" gets a prescription from a optometrist& new glasses& one month later& blurry +ision again, Bets new prescr& one mth later& blurry +ision again, $4: $iabetes, Blucose is being con+erted to sorbitol>water is going in and changing the refracti+e inde4, (lassic Iuestion, ?A:E to get a 1A'/.2B *3OO$ B3L(O'E, 3ab: 1asting glucose T62G mg9dl on two separate occasions, E4ample: *eh 'c lin#: /he 1*' le+el has been decreased from 6EF mg9dl to 62G mg9dl, .s this increasing the specificity or the sensiti+ity of the test? A: ?.B? 'ensiti+ity, *y bringing it lower ie closer to the normal range& you are going to be able to pic# up more people with diabetes, ;hen it was 6EF& it was high sp: to eliminate false positi+es, 'o it was uneIui+ocally a diabetic if it was T 6EF, Blucose tolerance test& don%t worry about it,

7G

(estationa Dia'etes $ef: ;oman who did not ha+e diabetes& but after becoming pregnant de+elops diabetes, Ris# factors for baby: R$'& premature deli+ery ;omen with B$& are at a higher ris# for de+eloping diabetes later on, Amyloid in *eta islets: /ype 2 Antibodies against islets" inflammation: /ype6 ((o4ac#ie +irus implicated ?3A correlation: $L! D5= and D542Type BF propensity for de+eloping /ype 6& if certain en+ironmental factor comes in such as infection: (o4sac#ie& mumps& E*: ?3A*2A: An#ylosing 'pondylitis En+ factors: (hlamydeal .nfection Llcerati+e (olitis& 'higellosis @soriasis Muscu os+e eta %ystem 2eed to identify crystals in syno+ial fluid (out Pseudogout Rhomboid crystals in syno+ial fluid--pseudogout *ut @seudogout could also ha+e needle>shaped crystals (li#e those of mono>sodium urate in Bout which ma#es $$ difficult, 'o you use a special filter to ma#e the whole slide red and then the crystals are made to loo# yellow or blue, ;hen the color of the crystals is yellow when the plane of filter is parallel to the analy)er;egati&e y 'irefringent 2("8T

7A

East west direction: color is blue and parallel to analy)er-Positi&e y 'irefringent 2 P%E8D"("8T (calcium pyrophosphate !rthritis "steoarthritis @rogressi+e wearing down of articular cartilage 'ometimes leads to reaction to in5ury: '@LR formationMat the margin of the 5oint- ?eberden%s node: osteophyte in the 5oint 2ote the enlargement of the $.@ (?eberdenUs nodes and @.@ 5oints (*ouchardUs nodes & enlargements represent osteophytes, 5heumatoid !rthritis .nflammatory 5oint d)" enlarged 0(@ 5oints Rh factor sets up the inflammation: .g0 Ab against .gB, .gB is in syno+ial fluid, .g0>.gB form comple4es& acti+ate the complement system& damage the 5oint& syno+ial fluid gets inflamed& starts growing and growing& starts growing o+er the articular cartilage- @A22L'" hyperplastic syno+ial fluid, (different from /ophus Voints can get fi4ed& and an#ylosed and cannot mo+e, $on%t get fi4ing of the 5oint in OA, .f rheumatoids don%t #eep mo+ing their 5oints& and if it is not controlled using anti>inflammatory drugs then e+entually they cannot mo+e it at all, 'lide: Rheumatoid nodules, (an be seen in Rheumatic fe+er as well, E4ample: older pt ha+ing trouble eating and swallowing crac#ers& feels li#e there is sand in my eye all the time, On e4amination: eyes and mouth are dry, $4? %Gograns %yndrome. @t with RA and auto>immune destruction of lacrimal glands& sali+ary glands, Oeratocon5uncti+itis sicca

78

Rheumatoid nodules in lung W pneumoconiosis--(aplan 'yndrome /reatment of RA- 0ethotre4ate E4ample: @t with RA& de+elops a macrocytic anemia with hypersegmented neutrophils& neuro e4am is normal& interstitial fibrosis in lung, ;hat is the drug? 0ethotre4ate (out 2 podagra *ig toe& usually first one to be in+ol+ed" usually at night, 0onosodium urate crystals are precipitated and ta#en up by the neutrophils that phagocytose it and release chemicalsMinflammatory reaction, $on%t define Bout based on Lric acid le+el, Ele+ated uric acid does not necessarily lead to gout, About 28D of people might ha+e ele+ated uric acid, $4: ?A' to be by presence of uric acid crystals in the 5oint, /reatment: .ndomethacin to control inflammation, (ause: o+er production (R4-allopurinol: bloc#s Hanthine o4idase or under e4cretion of uric acid (TCFD of cases R4-uricosuric drugs li#e probenecid and 'ulfinpyra)one Chronic (out 2 tophus: deposition of monosodium urate in soft tissueMmalleolus :ery disabling as it erodes the 5oint, R4- allopurinol 'lide: /ophus that was polari)ed showing 0'L crystals 'lide: H>ray of digit showing erosion by tophus (enetics of (out: 0ultifactorial inheritance

7C

A:O.$ red meats (full of purines A:O.$ Alcohol, 0echanism: 0etabolic acidosis: uric acid has to compete with other acids for e4cretion in pro4imal tubule, Alcohol increases all the lactic acid& and beta hydro4yl butyric acids, 'o all these acids compete and win against uric acid& and get e4creted, Lric acid #eeps waiting and waiting" and builds up and causes gout, !n+y osing spondy itis 3!%4 ?3A*2A association 'lide: 2ote anterior fle4ion which often results in restricti+e lung disease, ?unched o+er& restricts mo+ement of chest ca+ity& blood gas abnormalities& 2F yr old& morning when he wo#e up& sudden pain in sacro>lumbar region, .nflammatory reaction seen on H>ray& as the day progresses pain decreases, E+entually& the inflammation spreads to the +ertebral column& and it fuses--K*amboo spineK Also de+elop: L+eitis& Aortitis& iridocyclitis& blurry +ision& e+entually go blind, E4ample: Benetic d) where degenerati+e arthritis in +ert col& on autopsy& blac# cartilage" urine on e4posure to air turns blac#, ! +optonuria Aut rec& homogentisic acid o4idase en)yme def 'lide: 2F yr old& dysuria& increased freI& urinalysisleucocyte esterase positi+e& sterile pyuria>>se4ually acti+e& had non>specific urethritis& con5uncti+itis& was treated, .t was (hlamydia trachomatis con5uncti+itis& but one wee# later& got sterile con5uncti+itis and tendonitis in Achilles tendon, 'o patient with non>infectious con5uncti+itis& pre+iously had (hlamydia trachomatis infection and then de+eloped con5uncti+itis and arthritis (?3A *2A positi+e : 5eiterHs syndrome

EF

!nother En& trigger in $L!/?E positi&e pt: Llcerati+e (olitis %eptic arthritis due to disseminated gonococcemia 2ote the hot #nee and the pustule on the wrist& on aspirating: gram negati+e diplococci '/$- 'e4ually /ransmitted $isease '-'yno+itis-5oints /- /enosyno+itis- 5oints in hands and feet $- $ermatitis-pustules 0(( of septic arthritis in L'- Bonorrhoea 1or it to become disseminated& need to be deficient in the final pathway of (omplement system: C16CI (some say (G>(C 'lide: 2ote the .4odes tic# (+ector of *orrelia burgdorferi and *abesia microti & note the erythematous rash in the bottom screen > the tic# bite is in the center of the rash and the rash e4tends out in concentric circles from that point& the rash is called erythema chronicum migrans (pebble thrown in water @athognomonic of LymeHs disease Early form R4: tetracycline Chronic Lymes Disease: Apart from disabling 5oint disease: myocarditis plus bilateral *ell%s palsy: (2 :.. in+ol+ed W pt will ha+e *abesiosis .diopathic: is usually Lnilateral *ell%s @alsy?erpes 'imple4 Abo+e @t de+elops ?emolytic anemia& what did he see in his peripheral blood smear? *abesia microti (ring form similar to @lasmodium falciparum 5emem'er: the >:odes tic+ has the reser&oir for /orre ia 'urgdorferi 3-hite tai ed deer that has /a'esia microti4 !;D /a'esia microti intra> erythrocytic parasite

E6

R4: (eftria4one

/one Disorders "steogenesis imperfecta 'lide: Oid with an eyeball& blue sclera: A$ disorder with defect in synthesis of type . collagen& note the blue sclera> loss of collagen in sclera allows bluish color of choroidal +essels to shine through: "steogenesis imperfecta (2O/ foreign body= Jbrittle bone diseaseK cant brea# bone down Xuestion: what%s the defect? $efecti+e synthesis of type 6 collagen Xuestion: what%s the mechanism of de+elopment of blue sclera? (ollagen in sclera& type 6 is defecti+e& so it is so thin& so you can see the underlying choroidal +eins that gi+es the blue color, "steopetrosis 2 Jmar' e 'one diseaseK $efect in too much bone: defect in osteoclasts "steoporosis 'lide: $ecreased width of inter +ertebral cartilage, 2ote the collapse of the +ertebra due to loss of bone mass: patients lose more bone than is replaced 'lide: $owager%s ?ump 0ech: @ostmenopausal osteoporosis is due to the loss of the inhibitory effect of estrogen on the release of interleu#in 6 from osteoblasts" not enough estrogen to stop the acti+ity of .nterleu#in>6 (osteoclast acti+ating factor from brea#ing your bone down, Osteoporosis: O+erall reduction in bone mass, *oth mineral A2$ organic component, ;?O3E mass of bone is reduced,

E2

Osteomalacia: $ecreased minerali)ation of bone: organic part of bone is normal, (artilage is o#& osteoid is o#" its not getting minerali)ed $4 of osteoporosis: $ual beam Absorptiometry: density of the bone in whole body is measured, 2on in+asi+e& +ery easy, MC fracture: compression fracture: lose stature& ?nd MC fracture: (olle%s fracture of distal radius, Xuestion: .s swimming a good e4ercise for pre+enting osteoporosis: 2O, *ecause no stress on bones, .t is great e4ercise for aerobics, *ut it does not pre+ent osteoporosis, ;al#ing is good, ;eight bearing is e+en better than wal#ing= ;al# with $umbells= Bet aerobics and inc in bone mass= ?A:E to stress bone to build it up, E4ample: .n space& lac# of gra+ity and astronauts are gi+en bisphosphonates& :it $ and calcium to get bone density bac#: because serious prob of osteoporosis in space, /ip: reproducti+e women need to: 6 E4ercise 2 68FF mg of (a e+eryday 7 EFF>8FF units of :it $ E :it pill that contains .ron /one Tumors E:ostosis 3osteochondroma4 2ote the cartilaginous cap on the surface of the bone, /his causes a protuberance of the bone, /his is the most common benign bone tumor, Chondrosarcoma of the hip MC ma ignant one "steogenic sarcoma 'lide: 2ote metaphyseal origin of the cancer and e4tension into the muscle& note the splinter of periosteum that is ele+ated which would correspond to (odmanUs triangle

E7

'lide: H>ray of pro4imal humerus showing the YsunburstY appearance of osteogenic sarcoma that is e4tending into the muscle& osteogenic implies that the cancer is ma#ing bone Adolescent& sun burst app& codmans triangle& #nee area--Osteogenic 'arcome %uppressor (ene re ationship: Rb suppressor (hromosome 67 Muscu ar Disorders Duchennes Muscu ar Dystrophy Bower%s maneu+er Ele+ated 'erum (O& Absence of dystrophin protein 'e4 lin#ed recessi+e& missing $ystrophin gene :ariant: *ec#er%s dystrophy: ma#e dystrophin but it is defecti+e Analogy: alfa 6 antitrypsin def: 0(( of ?(( in children Adults get panacinar emphysema: many diff sub types of alfa 6 anti>trypsin: 6 Absent alfa 6 anti>trypsin: get pan acinar emphysema, 2 Alfa 6 anti>trypsin is present but it cannot get OL/ of the hepatocytes: so get ?(( Audio file $ay 8 #8 '#in Myotonic dystrophy 6 MC adu t dystrophy0 !D /riplet repeat d) ! repetition of tri>nt%s (there are E d)%s with this abnormality ! ?$& 1ragile H ! ha+e macrorchidism (big testes in adolescents & 1riedrich%s ata4ia& 0yotonic dystrophy , .n future generations& d) gets worse ! anticipation, /herefore& can anticipate that in future d)%s it will get worse, 1or each generation& there are more

EE

triplet repeats added on& leading to a more defecti+e protein and the d) gets worse and worse, E4ample: genetic counselor telling couple that they ha+e a d)& where if are to ha+e children& the d) will be fatal in their children, /he couple didn%t listen to their counseler& had a child and the child died only after 6 month, ;hat was it and what is this: an ie triplet repeat disorder (anticipation 0uscle wea#ness in face (so mouth is drooped open , E4ample: pt with failure to release grip on golf stic# (or when sha#ing hand ! they cannot rela4 their muscle grip& diabetes& cardiac abnormality Myasthenia (ra&is AutoAb against Ach receptor ! it%s an .gB Ab& therefore is an E4ample: of type .. ?@<& li#e Bra+e%s& which is an .gB Ab against the receptor (by definition& this ma#es it type .. , ;hether you destroy the receptor or 5ust bloc# it is irrele+ant, Ach cannot hoo# into it and therefore there is muscle wee#ness, /he first muscles are the lids& which leads to lid lag, /hey also get double +ision bc muscles of the eye are messed up& leading to diplopia, E+entually& they get dysphagia for solids and liIuids (gets stuc# in upper esophagus& bc this is where there is '/R.A/E$ muscle , E+entually muscle d) pre+ails throughout, 1eel energi)ed in the morning and feel tired at night, /ensilon test positi+e, (an die, R4 is acetylcholinestrase inhibitors, *y gi+ing an inhibitor& bloc# the brea#down of Ach and build up Ach, ;ith few receptors you ha+e in there& there is a larger chance of hoo#ing up to the receptors and pt does well, ?owe+er& e+entually& no receptors there and it doesn%t matter how much Ach is there& so pt is screwed, /hen& her only option is a thymectomy, /he thymus is in the anterior mediastimun, /ric# Iuestion: they can as#& what is the pathology? /hey can describe 0B and as#& what do you e4pect to see in the mediastinum? $o 2O/ put thymoma, /his is a malignancy of the thymus and

E8

does occur in 68>2FD of cases& but isn%t the 0( pathology seen in the thymus in a pt with 0B, 'ee germinal follicles in the thymus (remember& this / cell country& not * cell country& so its abnormal to ha+e germinal follicles here ! they are the ones ma#ing the Ab causing the 0B, 'o& by doing a thymectomy for R4& you are remo+ing the Ab producing tissue, 697 pts get a complete cure, 697 get a partial cure& and 697 die bc they waited too long for thymectomy and R4 and didn%t ha+e receptors& anyway, 'o& * cell hyperplasia is the 0( thing you see& not thymoma, /his where the Ab is being made, Lupus *utterfly distribution on the face (malar rash Of all the autoimmune d)%s this one is the most li#ely one to ha+e a JWK A2A (CCD sensiti+ity , /he Ab%s you want to order to pro+e that its lupus are anti>'mith Ab (which has a 6FFD spec& therefore no false pos ! therefore 6FFD @@: for lupus& meaning that if you test JWK for this Ab& you ha+e 3upus, /he other Ab is anti !ds$2A ! this not only indicates that you ha+e lupus& but also that you ha+e O.$2E< d), /hat has a C8D spec& too, 'o& these are two good Ab%s to confirm lupus, 0orning stiffness is present in lupus (simulates Rh arthritis9photophobia & rash& pericarditis" 3E cell prep ! Anti ! $2A Ab%s are phagocytosed by neutrophils& and they ha+e altered $2A, 2ot specific for lupus (waste of time , Progressi&e %ystemic %c erosisAC5E%T /ight face& telangiectasia& Raynauds& dysphagia (solids and liIuids & dystrophic calcification& sclerodactly" if #idneys in+ol+ed& it is progressi+e systemic sclerosis& 2O/ (RE'/ (doesn%t in+ol+ed #idneys , Dermatomyositis Racoon eyes& ele+ated serum (O& rash o+er the @.@ (goutren% patches & highest assoc with underlying cancer, %Gogrens syndrome

EG

Assoc with rh arthritis& autoimmune ! Ab%s destroy sali+ary glands leading to dry mouth& lacrimal glands leading to dry eyes, E4ample: b4 of lower lip which is a confirmatory test ! its loo#ing to see if there is destruction of the minor sali+ary glands ! see lymphocytes (which is confirmatory d4 , Ab%s are anti>''a (a#a anti>Ro and anti>''b (a#a anti>3a ('' - '5ogren%s syndrome , Anti>ro can also be in lupus pts& and can cross the placenta and disrupts the baby%s conduction system (leads to complete heart bloc# ,

%+in
/asa ce carcinoma (upper lip %quamous ce carcinoma (lower lip Psoriasis ! sil+ery lesion that is red and raised, (an in+ol+e the hands& scalp ! pts thin# they ha+e dandruff (a#a seborreic dermatitis ! from malase)ia furfura & but they really ha+e psoriasis, On blac# person won%t see red lesion& will see sil+er one, Rash at pressure points ! esp the elbow, !topic dermatitis ! child with allergic diathesis starts d)" ha+e ec)ema (a#a atopic dermatitis " type . ?@<, Contact dermatitis ! ie to metal (nic#el " type .: ?@< E4ample: pathophys is eIualant to what? JWK @@$& bc both are type .: ?@< %e'orrheic Dermatitis $ue to Malassezia furfur (a fungus .( pt (ie A.$s /his is a preA.$s lesion Tinea capitis E4ample: pt with bald spot on head& fluouresces and seen with blac# light blac#light (L:>A light (an cause /inea capitis 3no- Trichophyton tonsurans is MCC4

EA

*c the fungus in+ol+es the inner portion of the shaft& there are no fluorescent metabolites& and is ,ood ight negati&e All the other superficial dermatophyte infections including Tinea corporis (ring worm E4ample: red outer edge and clear center& what is first step in wor#up? 'crape outside and do OO? prep& and see hyphae and yeast forms, ! other superficia dermatophyte infections 3e:cept Tinea capitis4 are due to trychophyton ru'ra. ;hat is the color around /inea capitis? Red (rubra (how to remember it , Mo uscum contagiosum 'andy li#e material in crater& children& self inoculate @o4+irus ma#es these ($2A +irus :olcano crater loo#& with sandy stuff in it Pityriasis 5osea E4ample: rash on butt ! non pruritic rash& 2O2 .21E(/.OL'" oblong loo#ing with red on outside and pale in middle, <ou thin# this is / corporis& but its oblong (and not circular , $o a OO? prep& find nothing" then put topical steroids and doesn%t go away" 7 days later comes bac# with rash in the line of langer in (hristmas tree li#e distribution" not an infectious d)& i+e a hera d rashF not a fungus Dysp astic ;e&us syndrome E4ample: precursor lesion for malignant melanoma" if you ha+e o+er 6FF ne+i all o+er body& you ha+e dysplastic ne+us syndrome :ery common 0ust go to dermatologist once a year bc need to loo# at dysplastic ne+i, (ould be a precursor lesion for malignant melanoma, 4 diff types of ma ignant me anoma ;hat is first step in management? E4cision E4ample: superficial spreading malignant melanoma (0( E4ample: on face of older pt ! 3entigo maligna melanoma" irregular border& corn colored& 3EA'/ li#ely to met of all malignant melanomas,

E8

E4ample: blac# pop%n do not get malignant melanomas bc the blac# pigment in the s#in pre+ents L: light damage and propensity for cancer, howe+er& there is one type of cancer they malignant melanoma they (A2 get: blac# pt with dyspnea& on 4ray find multiple mets all o+er body, *4 is done and pt has malignant melanoma& which part of the body would you e4amine to find the primary d)? Lnder the nails& palms or sole of the feet ! this is Acrolentiginous malignant melanoma (Sacro% means edge of9tip of ! this is the 0O'/ ABBRE''.:E of all the melanomas, /his has nothing to do with radiation, @agets d) loo#s similar E4ample: 2odular malignant melanoma ! also +ery aggressi+e, The most important thing affecting prognosis is depth of in&asion (#ey to prognosis ! magic # is , AG mm , .f its less than ,AG& its not gonna met, To:ins 2 poisonous spiders ! / ac+ -ido?as a neuroto4in ! causes spasm of the muscles in the upper thighs and abdomen so strong its almost li#e tetanus" pain muscle contractions& esp in the abdomen, /here is an anti+enom& painful bite E4ample: person went down into their cellar& lifted bo4es& felt sharp pric# on finger& and de+eloped contractures o+er a period of hrs ! due to blac# widow bite, /ro-n rec use spider (a#a +iolin spider @ainless bite& has a necroto4in& leading to ulcer 'o& neuroto4in for blac# widow& necroto4in for brown reclous ,here is receptors to androgens) %e'aceous g ands (this is why men get more )its than woman ! testosterone will release lipid rich material which gets into the hair follicle, /hen& if you ha+e proprionum acnei (anaerobe it has lipases that

EC

brea#down fat from the sebaceous gland and produces 1A%s that irritate the follicle and end up with acne, 'o& men more li#ely to get it bc they ha+e acne .t all occurs in the erector pili muscle of the s#in, 'o& there are androgen receptors sebaceous glands and erector pili muscle, Drug used to pre&ent hirsutism) %pirono actone (same drug used to bloc# aldosterone " this drug is good bc it bloc#s androgen receptors and therefore pre+ents hirsutism, (an also lead to gynecomastia,

C;%
'pinal fluid ! deri+es from choroid ple4us in the +entricles, .n the lateral& 7rd and Eth +entricles, .ts an ultrafiltrate of plasma, ;hat is the difference in serum and spinal fluid? ;ay more protein in spinal fluid bc it%s an ultrafiltrate, (ell? ?ardly any cells in spinal fluid (none , Blucose? 3ower in spinal fluid ! about GFD of what it is in serum (if the spinal fluid glucose le+el were low& then something is in there utili)ing it for energy such as bacteria or fungus or cancer cells , .s there anything 0ORE in spinal fluid than serum? (hloride (way higher in spinal fluid than serum > around 62F, /hese are imp bc there are in5uries to the head, E4ample: baseball that hits the eye in an orbital blowout fracture ! can potentially brea# cribriform plate& leading to dripping fluid out& which could be snot& serum& or spinal fluid, 'o& its imp to #now diff%s btwn the two, E4ample: wac#ed in the head ! fluid out of ear (otorrhea & hemorrhage leads to battle sign, /his is a fracture of the basilar plate and there is spinal fluid there, 0ost of the fluid comes out the aIueduct of syl+ius ! which is the 0(( of hydrocephalus in children bc it gets bloc#ed off until you get a build up of spinal fluid in the 7rd +ent and lateral +ent& which is a narrow area and leads to hydrocephalus, /hen& it

8F

comes to the fourth +ent and needs to get out bc it needs to get into the subarachnoid space, 'o& it goes through the foramen of 3usch#a and 0agendie& so fluid goes out, $ura means strong ! it%s tightly adherent to the periosteum, 'o& when pt has epidural hematoma (blood clot betwn bone and dura , /he only pressure that can split the periosteum away from dura is arterial pressure, 'o& this is the one -hen the midd e mengia artery ruptures& and can be done with arterial pressure (not +enous , .t gets into the subarachnoid space (to protect us ! a cushion against damage , Bet rid of spinal fliud in arachonoid granulation, QA tumor can arise from the arachnoid granulations ! meningioma,R .t goes through the arachnoid granulations& (there are 2O 3<0@?A/.(' .2 *RA.2 and the dural sinuses and conglomerate into the 5ugular +ein& which is emptied into the right side of the heart, 'o& when you do a +alsal+a and the nec# +eins distend& that pressure transmits all the way bac# to the dural sinuses& to the arachnoid granulations through the spinal fluid & and right down the the needle in the subarachnoid space at 3E and the pressure goes up, /his is called Iua#ens step maneu+er, .t is a great test for when you are doing a spinal tap to see if the entire subarachnoid space is patent, .f you don%t see that manometer go up& there is something bloc#ing the spinal fluid more pro4imally, E4ample: when you wt lift& you shouldn%t hold your breath bc the pressure are huge and and lead to a herniated dis#, Tentorium Cere'e i AFD of brain tumors in adults are supratentorial (in+ol+e cerebral corte4 AFD of brain tumors in #ids are infratentorial (cerebellar& cystic astrocytoma& medulloblastoma $ydrocepha us (ommunicating +s 2oncommunicating

86

(ommunication of spinal fluid in +entricles with subarchnoid space, ;oncommunicating 0( 'omething is pre+enting spinal fluid in the +entricles from getting into the subarachnoid space MCC 2 stenosed !queduct of %y &ius Or something going in the Eth +ent& ependymoma in #ids will bloc# it off& or meningitis in base of brain (/* & leads to scar tissue bc bloc#s foramen of magendie and lusch#a, Communicating 'till communicating& but still a build up of pressure, One cause could be tumor of choroid ple4us (papillary loo#ing , 'o& if you ha+e a tumor there& you ha+e a greater ultrafiltrate of plasma and would be ma#ing more plasma, Also& would be ma#ing more spinal fluid, /here would still be a communication with here& but the pressure would build up bc ma#ing more than you commonly do, 0ore commonly& what if you ha+e a subarachnoid bleed or meningitis? /hen pt has scarred off arachnoid granulations and ha+e no way of draining it out, 'o& still ha+e a communication& but cannot get rid of it (0( , !rno d Chiari Ma formation E4ample: pull down spinal cord, /his would bring the medulla into the cer+ical region and maybe a lil part of the cerebellum, 3eads to hydrocephalus and platybasia (flattening of the base of the s#ull Dandy -a +er syndrome (erebellar +ermis is not de+eloped $erniation ;hy would we herniate in the brain? *c there is cerebral edema and no other place to go, /he famous ones are tonsillar herniation through the foramen magnum, (from the cerebellum ! cerebellar herniation ! has been sIuee)ed into the foramen magnum& and has constriction, (an cause immediate death,

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Lncal herniation ! medial portion of the temporal lobe herniates through the tentorium cerebelli and pressing against midbrain& leads to hemorrhage (duret%s hemorrhage , Also an oculomotor ner+e that is gonna be compressed, 'o& this will lead to opthalomoplegia (3RG'OE& 7 & so e+erything inner+ated by (2 ... is paraly)ed, ;ith oculomotor ner+e palsy& it is down and out, (down and in is (2 E palsy ! if (2 G is paraly)ed& will loo# cross eyed , 3oo# at pupil, E4ample: 0R. of oribit& name muscles @arasympathetic constrict the pupil (normally & sympathetics dilate (normally 'o& if you mess up the parasympathetics& which normally constrict& it will lead to mydriasis, /he first sign of uncal herniation is mydriasis of pupil on side of herniation (so it dilates on that side , Also& posterior cerebral artery can get bloc#ed with uncal herniation& leading to post lobe infarction, 7no- 'rainstem and C;s and ho- it re ated to herniation Papi edema Any cause of increased incranial pressure :it A to4 3ead poisoning ! delta>aminole+ulinic acid ! leads to increased permeability Audio file $ay8 #G (2' $ydrocepha us 0(( - stenosis of the aIueduct of syl+ius 2oncommunicating, Bet hydrocephalus bc the sutures ha+e not fused if you miss hydrocephalus in adult and sutures ha+e fused& will lead to dilatation of the +entricles and e+entually o+er years& the pressure will turn bac# to normal bc the increased pressures #eep the choroid ple4us from ma#ing so much $ementia& ata4ia& urinary incontinence, A#a normal pressure hydrocephalus (bc pressures normali)e Tu'erous %c erosis

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!D ?amartomas (noneoplastic proliferation of things :entricles ha+e bumps called tubercles ! which are hamartomas which ha+e proliferation of astrocytes, /hey produce hamartomas that bulge into the +entricle& called candle stic# dripping, ?emartomas of the #idney called angiomyolipomas& 0R& cardiac tumors (rhabdomyomas & shagreen patches& areas of hypopigmentation& woods light shine out !nencepha y ;orst of neural tube defects Absent brain #erte'ra arch defects %pina 'ifida occu ta ! tufts of hair come out& +ert arches do not touch& no meninges come Meningoceo e ! meninges come out Meningomy oce e ! both meninges and spinal cord come out ?igh alpha feto protein le+els in blood of mother" decreased in downs syndrome ?a+e to be on folate to pre+ent neural tube defects (neural tube finished forming by 7F days& so ma#e sure she is on folate if she is trying to get pregnant , ;eurofi'romatosis Albright syndrome (precocious puberty& cafZ au lait& bone )its 'turge weber (afZ au lait (coffee colored non raised lesions spot& ple4iform neurofibromas& hyperpigmentation in the a4illa (a4illary frec#ling & neurofibromas A$ & therefore late manifestations (esp for neurofibromatosis & penetrance& +ariable e4pressi+ity (you are e4pressing the d)& but diff le+els of how se+ere the d) is E4ample: pt with $T; and pic& what test would you get? Relationship of neurofibroma with pheochromocytoma& therefore get a 2E hr urine for :0A and metanephrine, !coustic sch-annoma

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E4ample: pt with sensorinerual hearining loss ! bC tumor of 'chwann cells around (2 8 Meningiomas Optic ner+e gliomas %yringomye ia E4ample: pt that wor#s in factory and one of wor#ers says you are burning your hand and pt didn%t notice this& on e4am loss of musculature (loss of 302 in intrinsic muscles of the hand& loss of pain and temp in cape li#e distribution across bac#, (an%t feel pain (not A3' ! in A3'& first place of de+elopment of loss of muscles is here& so don%t confuse" but A3' is L02 and 302 loss& @LRE 0O/OR & so if pt has pain& ie& this is sensory and not A3' *ig cystic ca+ity #noc#ing off spinothalamic #noc#ing off pain and temp, can #noc# off the corticospinal tract and anterior horn cells& so it will be a (O0*O of sensory A2$ motor loss for syringiomyelia, >nfections Meningitis &s encepha itis 0eningitis ! inflammation of meninges and nuchal rigidity" if you mo+e your head or e4tend your #nee& you will stretch the meniges& leading to pain (stretching inflamed meninges , Encephalitis ! sleeping sic#ness ! they are always sleeping and drowsy" they ha+e mental status abnormalities (not nuchal rigidity @us at the base of the brain ! can possibly bloc# lush#a and ma5endie& leading to obstructi+e hydrocephaly and noncommunicating ;hen you R4 meningitis& use steroids and Abs, why? 'teroids pre+ent scar tissue formation and complications that arise with it (ie hydrocephalus , /his is standard /* meningitis R4 (/* in brain causes +asculitis and scarring $eafness is a complication of meningitis,

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5a'ies E4ample:: meningitis& cerebral abcess& Rabies (0(( in 'tates - s#un#s& dogs in 7rd world 2egri bodies (per#in5e cell inclusion CM# @eri+entricular calicifications E4ample: section of #id (brain > see white stuff going around +entricles 0( congental infection - (0: ;hat body fluid is best to culture from? Lrine Meningitis ;hat is 0( meningitis9sepis in first month of life? Broup * strep ! strep agalactae ! bc many women ha+e this organism in their +agina& so they are carriers, @remature ruptured membranes lets the organism get up& get an chorioamnionitis and into the bloodstream, 2nd 0(( is E coli 7rd 0(( is listeria monocytogenes (gram W rod with tumbling motility ! as does /richomonas +aginalis ;hat food should pregnant women a+oid? 'oft cheeses (ie feta cheese& but listeria is present , 0( in 6 month ! 68 yo - 2 meningitides (not ? influen)a bc +accination 0( in 68W - 'trep pn E4ample: 82 yo man& nuchal rigidity& tap shows increased protein& increased neutrophils and decreased glucose ! d4? 'trep pn, what is the gram stain? Bram W diploccus Cryptococcus .ndia in# ! see narrow based bud for (ryptococcus ;ho do you thin# this is in? .(%d pts ;hat is 0( immunodef in L'A? A.$s 0(( meningitis in A.$s pts? (ryptococcus Mucormycosis .n frontal lobe& therefore from a diabetic in #etoacidosis E4ample: special stain on A.$s pt with ($ E ct of 8F& (/ showed space occupying lesion $4? To:op asmosis

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E4ample: pig herder& and long time problem with focal epileptic sei)ures (dilating therapy ! multiple calcified and cystic lesions in brain ! d4? Cysticercosis E4ample: Vacob (ruet)feltds from prions (mad cow ! who is most li#ely to get? 2europathologists& neurosurgeons& beef& lettuce from Ari)ona (cow manure on it Traumatic esions Epidura hematoma (abo+e dura ! hit in head middle meningeal ! ha+e to fracture bone (under arterial pressures& can separate dura from periosteum , ;hen you get 8F mls of blood& you get uncal herniation and die, .e get him& say they are o#& G hrs later epidural hematoma and death %u'dura hematoma ! rupture of bridging +eins betwn dura and arachonoid membrane, .f you ha+e cerebral atrophy& then the space bwtn the dura and arachnoid membranes is bigger, *ridging +eins dangling& brea# and get a hematoma, 1luctuating le+els of consciousness, 3eft untreated lead to dementia, $o (/ to r9o epi and subdural hematoma (also for stro#es ! if its a hemorrhagic stro#e %tro+es 'lide: *rain: one side is bigger, Atherosclerotic stro#e" pale infarct of brain, At bifurcation& there is an atherosclerotic plaIue and thrombus, 2o blood flow to brain and it infracted& starts brea#ing down& no reperfusion& so it remains a pale infarct, .f the thrombus did brea# apart& and reperfusse the brain& the blood in the goes into the area of infarction and is called a hemorrhagic infarct, ?owe+er& this usually doesn%t occur and pale infarcts more common, .f no blood& and there is infarction& pt is a candidate for heparin therapy, O+er time& if pt sur+i+es& ends up with cystic space where there was infarction and this is called liIuefacti+e necrosis>>pale infarct& liIuefacti+e necrosis,

8A

'lide: hemorrhagic infarct ! blood is to edge of brain ! this is an embolic infarct& usually from left side of the heart, /he +essel it always goes to is middle cerebral artery, .t gets into the (ircle of ;illis and into the middle cerebral, .f you emboli)e down& will go into the superior mesenteric /he reason it is hemorrhagic is bc pt will get brea#down of fibrinolytic system of the embolus and leads to reperfusion, .nstead of being a pale infarct& it%s a hemorrhagic infarct, 'o& both a atherosclerotic stro#e and hemorrhagic stro#e are both infarcts ! one is pale and the other is hemorrhagic, 'lide: $T;& pressures cause lenticulostriate +essels to come up and supply this area of the brain, $eri+e from the middle cerebral aneurysms& called (harcot *ouchard aneurysm and it ruptures& leading to giant hematoma and blood clot, ?orrible prognosis, 'o& embolic stro#e goes to surface of the brain and if it%s in the basal ganglia& its a -ays an intrace'ra ' eed from $T;. E4ample: su'arachnoid hemorrhage mostly due to rupture congenital berry aneurysm, 0( at the 5unction ant comm branch of ant cerebral artery 3ess common cause of 'A?: !# ma formation 'turge ;eber ! on same side as s#in lesion of the face& there is an A: malformation Lacunar infarcts ! small areas on the brain" unusual bc they hit areas of the brain, $epending on where in the internal capsule& can ha+e a pure motor stro#e or pure sensory, 0( due to ?/2 Mu tip e %c erosis 3M%4 MC demye inating Dz 3autoimmune4 . M% % ide:demylinated: white matter has myelin it& grey doesn%t, .f you are destroying white matter& then you%ll see grey underneath, P aques of M%, 2 ways to demylinate

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6 #noc# off cell that ma#es myelin in the brain (oligodendrocytes in brain& schwann cell in @2' ! +iruses do this ! subacute sclerosis& progressi+e multifocal leu#oencephalopathy& ?@: ! they affect the oligodendrocyte" 2 can also ha+e Ab%s against myelin and not the oligodendrocyte& which is 0' paresthesias 2ystagmus& ata4ia& optic neuritis with blurry +ision (MCC of "ptic ;euritis2 M% bc demylination of optic ner+e >nternuc ear optha map egia (demylination of 031 > pathognomonic %pina tap -i sho- increased protein0 norma g ucose0 increase ymphs

$ydrocepha us E: #acuo 'e+ere atrophy of brain and +entricles loo# bigger than they should be $ementia ! zheimers Dz (lassic lesion: senile plaIue& neurit%s& amyloid (*eta== ! so beta amyloid is to4ic and the more you ha+e the more to4ic ! pathognomonic of al)heimers& on c%some 26& therefore seen in down%s& neurofib tangles (in any dementia and ?$ Al) ! probs in higer le+els ! dementia Only way to d4 is autopsy (confirmation ! see senile plaIues Par+insons Dz Resting tremor

8C