Goljan Audio Transcripts PDF

CBAPTER 1: Cell injuiy
Audio le 01: Cell Injury 1

Audio le 04: Cell Injury 4 - Inammation 1
CBAPTER 2: Inflammation
Audio le 5: Inamation 2 - Fluid and hemodynamics 1
CBAPTER S: Fluiu anu hemouynamics
Audio le 6: Fluid and hemodynamics 2
Audio le 7: Fluid and hemodynamics 3
Audio le 8: Fluid and hemodynamics 4 - Nutrition 1
CBAPTER 4: Nutiition
Audio le 9: Nutrition 2 - Neoplasia 1
CBAPTER S. Neoplasia
Audio le 10: Neoplasia 2
Audio le 11: Neoplasia 2 - Hematology 1
CBAPTER 6. Bematology:
Audio le 12: Hematology 2
CBAPTER 7: Caiuiovasculai
Audio le 19: Cardiovascular 1
CBAPTER 8: Respiiatoiy
Audio le 23: Respiratory 1
Audio le 24: Respiratory 2
Audio le 25: Respiratory 3 - Gastro 1
CBAPTER 9: uastio
Audio le 26: Gastro 2
Audio le 27: Gastro 3 - HepatoPancreas 1
CBAPTER 1u. BepatoPancieas
Audio le 28: HepatoPancreas 2
Audio le 29: HepatoPancreas 3 - Renal 1
CBAPTER 11: Renal
Audio le 30: Renal 2
Audio le 31: Renal 3
CBAPTER 12: uynae
Audio le 32: Gynaecology
CBAPTER 1S: Enuociine
Audio le 33: Endocrine 1
Audio le 34: endocrine 2
Audio le 35: Endocrinology 3 - Musculoskeletal 1
CBAPTER 14: Nusculoskeletal System
Audio le 36: Musculoskeletal 2 - Dermatology - CNS 1
CBAPTER 1S: Beimatology
CBAPTER 16: CNS
Audio le 37: CNS 2
CHAPTER 1: Cell Injury
Auuio File u1: Cell Injuiy 1
Key issues - hypoxia, cyaniue poisoning, fiee iauicals, apoptosis, giowth
alteinations (i.e. hypeitiophy, atiophy, hypeiplasia, etc.)I.
!"#$%&' = inauequate oxygenation of tissue (same uefinition of as shock). Neeu 0
2

foi oxiuation phosphoiylation pathway - wheie you get ATP fiom innei Nito
membiane (election tianspoit system, calleu oxiuative phosphoiylation). The last
ixn is 0
2
to ieceive the elections. Piotons aie being kickeu off, go back into the
membiane, anu foim ATP, anu ATP in foimeu in the mitochonuiia
() +,-./0
1) 2%"3,4 5$46,46 = Bb x 0
2
satn + paitial piessuie of aiteiial oxygen (these aie
the S main things that caiiy 0
2
in oui bloou)
In Bb, the 0
2
attaches to heme gioup (0
2
sat'n)
Paitial piessuie of aiteiial 0
2
is 0
2
uissolveu in plasma
In RBC, foui heme gioups (Fe must be +2; if Fe+ is +S, it cannot caiiy 0
2
)
Theiefoie, when all foui heme gioups have an 0
2
on it, the 0
2
sat'n is 1uu%.
7) 2
7
/'684 is the 0
2
IN the RBC is attacheu T0 the heme gioup = (measuieu by a
pulse oximetei)
9) :'-6&'; #-,//<-, $= 2
7
is 0
2
uissolveu in PLASNA
0
2
flow: fiom alveoli thiough the inteiphase, then uissolves in plasma, anu
incieases the paitial piessuie of 0
2
, uiffuses thiough the RBC membiane anu
attaches to the heme gioups on the RBC on the Bb, which is the 0
2
sat'n
Theiefoie - if paitial piessuie of 0
2
is uecieaseu, 0
2
sat'n BAS to be uecieaseu (Bc
0
2
came fiom amount that was uissolveu in plasma)
>'</,/ $= 6&//<, ?"#$%&'0
()1) @/5?,.&' (ueciease in ARTERIAL bloou flow ..N0T venous)
NCC Ischemia is thiombus in musculai aiteiy (bc this is the mcc ueath in 0SA =
NI, theiefoie NI is goou example of ischemia bc thiombus is blocking aiteiial bloou
flow, piouucing tissue hypoxia)
0thei causes of tissue ischemia: ueciease in Caiuiac 0utput (leaus to hypovolemia
anu caiuiogenic shock) bc theie is a ueciease in aiteiial bloou flow.
7) 7
4A
B>> $= 6&//<, ?"#$%&' C ?"#$%,.&'
!"#$%&' = 'big' teim
!"#$%,.&' = cause of hypoxia (they aie not the same); ueals with the paitial
piessuie of aiteiial 0
2
(0
2
uissolveu in aiteiial plasma, theiefoie, when the paiticle
piessuie of 0
2
is uecieaseu, this is calleu hypoxemia).
Beie aie 4 causes of hypoxemia:
') D,/# '5&A$/&/ (in teims of hypoxemia) - in teims of Balton's law, the sum of the
paitial piessuie of gas must = 76u at atmospheiic piessuie (have 0
2
, C0
2
, anu
nitiogen; nitiogen iemains constant - theiefoie, when you ietain C0
2
, this is iesp
aciuosis; when C0
2
goes up, p0
2
BAS to go uown bc must have to equal 76u;
Theiefoie, eveiy time you have iesp aciuosis, fiom ANY cause, you have hypoxemia
bc low aiteiial p0
2
; inciease C0
2
= ueciease p0
2
, anu vice veisa in iesp alkalosis).
E) F,46&;'6&$4 A,=,56/ - best example is iesp uistiess synuiome (aka hyaline
membiane uz in chiluien). In auults, this is calleu Auult RBS, anu has a ventilation
uefect. Lost ventilation to the alveoli, but still have peifusion; theiefoie have cieateu
an intiapulmonaiy shunt. Exam question: pt with hypoxemia, given 1uu% of 0
2
foi
2u minutes, anu p0
2
uiu not inciease, theiefoie inuicates a SB0NT, massive
ventilation uefect.
5) :,-=</&$4 A,=,56/ - knock off bloou flow
NCC peifusion uefect = pulmonaiy embolus, especially in piolongeu flights, with
sitting uown anu not getting up. Stasis in veins of the ueep veins, leaus to
piopagation of a clot anu S-S uays latei an embolus uevelops anu embolizes. In this
case, you have ventilation, but no peifusion; theiefoie theie is an inciease in ueau
space. If you give 1uu% 0
2
foi a peifusion uefect, p0
2
will go 0P (way to uistinguish
vent fiom peifusion uefect), bc not eveiy single vessel in the lung is not peifuseu.
Theiefoie, peifusion uefects because an inciease in ueau space, while ventilation
uefects cause intiapulmonaiy shunts. To tell the uiffeience, give 1uu% 0
2
anu see
whethei the p0
2
stays the same, ie uoes not go up (shunt) oi incieases (inciease in
ueau space).
A) G&==</&$4 A,=,56 - something in the inteiphase that 0
2
cannot get thiough.ie
fibiosis. Best example-Saicoiuosis (a iestiictive lung uisease); 0
2
alieauy have
tiouble getting thiough the membiane; with fibiosis it is woise. Anothei example-
Pulmonaiy euema; 0
2
cannot cioss; theiefoie theie is a uiffusion uefect. Anothei
example is plain olu fluiu fiom heait failuie leaus to uyspnea, bc activateu the }
ieflex is initiateu (inneivateu by CN1u); activation of CN1u, leaus to uyspnea (can't
take a full bieath) bc fluiu in inteistium of the lung, anu the } ieceptoi is iiiitateu.
These aie the foui things that cause hypoxemia (iesp aciuosis, ventilation uefects,
peifusion uefects, anu uiffusion uefects).
9) !,.$3;$E&4 -,;'6,A ?"#$%&'
In the case of anemia, the classic misconception is a hypoxemia (ueciease in p0
2
).
Theie is N0 hypoxemia in anemia, theie is noimal gas exchange (noimal
iespiiation), theiefoie noimal p0
2
anu 0
2
satuiation, but theie is a ueciease in Bb.
That is what anemia is: ueciease in Bb. If you have S gm of Bb, theie is not a whole
lot of 0
2
that gets to tissue, theiefoie get tissue hypoxia anu the patient has
exeitional uyspnea with anemia, exeicise intoleiance.
') >'-E$4 .$4$%&A, H>2I: classic - heatei in wintei; in a closeu space with a
heatei (heatei have many combustable mateiials; automobile exhaust anu house fiie.
In the house fiie scenaiio, two things cause tissue hypoxia: 1) C0 poisoning anu 2)
Cyaniue poisoning bc upholsteiy is maue of polyuiethiane piouucts. When theies
heat, cyaniue gas is given off; theiefoie pts fiom house fiies commonly have C0 anu
cyaniue poisoning.
C0 is veiy uiffusible anu has a high affinity foi Bb, theiefoie the 0
2
SAT'N will be
uecieaseu bc its sitting on the heme gioup, insteau of 0
2
(iemembei that C0 has a
2uuX affinity foi Bb).
(Bb is noimal - its N0T anemia, p0
2
(0
2
uissolveu in plasma) is noimal, too); when
0
2
uiffuses into the RBC, C0 alieauy sitting theie, anu C0 has a highei affinity foi
heme. To tieat, give 1uu% 0
2
. Beciease of 0
2
sat'n = clinical eviuence is cyanosis
Not seen in C0 poisoning bc cheiiy ieu pigment NASKS it, theiefoie makes the
uiagnosis haiu to make. NC symptom of C0 poisoning = heauache
E) B,6?,.$3;$E&40
Nethemoglobin is FeS+ on heme gioup, theiefoie 0
2
CANN0T binu. Theiefoie, in
methemoglobin poisoning, the only thing scieweu up is 0
2
satuiation (bc the iion is
+S, insteau of +2). Example: pt that has uiawn bloou, which is chocolate coloieu bc
theie is no 0
2
on heme gioups (noimal p0
2
, Bb concentiation is noimal, but the 0
2

satuiation is not noimal); "seat is empty, but cannot sit in it, bc it's +S". RBC's have
a methemoglobin ieuuctase system in glycolytic cycle (ieuuction can ieuuce +S to
+2).
Example: Pt fiom iocky mountains was cyanotic; they gave him 1uu% 0
2
, anu he
was still cyanotic (was uiinking watei in mtns - watei has nitiites anu nitiates,
which aie oxiuizing agents that oxiuize Bb so the iion become +S insteau of +2). Clue
was that 0
2
uiu not coiiect the cyanosis. Rx: Iv methaline blue (B0C); ancillaiy Rx =
vitamin C (a ieuucing agent). Nost iecent uiug, Bapsone (useu to Rx lepiosy) is a
sulfa anu nitiyl uiug. Theiefoie uoes two things: 1) piouuce methemoglobin anu 2)
have potential in piouucing hemolytic anemia in glucose 6 phosphate uehyuiogenase
ueficiencies. Theiefoie, hemolysis in u6PB uef is iefeiiing to oxiuizing agents,
causing an inciease in peioxiue, which uestioys the RBC; the same uiugs that
piouuce hemolysis in u6PB uef aie sulfa anu nitiyl uiugs. These uiugs also piouuce
methemoglobin. Theiefoie, exposuie to uapsone, piimaquine, anu TNP-SNX, oi
nitiyl uiugs (nitioglyceiinnitiopiussiue), theie can be a combo of hemolytic
anemia, u6PB uef, anu methemoglobinemia bc they aie oxiuizing agents. Common
to see methemoglobinemia in BIv bc pt is on TNP-SNX foi Rx of PCP. Theiefoie,
potential complication of that theiapy is methemoglobinemia.
5) ><-J,/0 ;,=6 '4A -&3?6 /?&=6/
Want a iight shifteu cuive - want Bb with a uecieaseu affinity foi 0
2
, so it can
ielease 0
2
to tissues. Causes: 2,S bisphosphoglyceiate (BPu), fevei, low pB
(aciuosis), high altituue (have a iesp alkalosis, theiefoie have to hypeiventilate bc
you will ueciease the C0
2
, leauing to an inciease in p0
2
, leauing to a iight shift bc
theie is an inciease in synthesis of 2,S BPu).
Left shift - C0, methemoglobin, BbF (fetal Bb), ueciease in 2,S-BPu, alkalosis
Theiefoie, with C0, theie is a ueciease in 0
2
sat'n (hypoxia) anu left shift.
K) :-$E;,./ -,;'6,A 6$ #-$E;,./ -,;'6,A 6$ $%&A'6&J, #'6?L'"
') B$/6 &.#0 5"6$5?-$., $%&A'/, (last enzyme befoie it tiansfeis the elections to
0
2.
Remembei the S C's - cytochiome oxiuase, cyaniue, C0 all inhibit cytochiome
oxiuase. Theiefoie S things foi C0 - (1) ueciease in 0
2
sat (hypoxia), (2) left shifts
(so, what little you caiiy, you can't ielease), anu (S) if you weie able to ielease it, it
blocks cytochiome oxiuase, so the entiie system shuts uown
E) M45$<#;&43 - ability foi innei mito membiane to synthesize ATP. Innei mito
membiane is peimeable to piotons. You only want piotons to go thiough a ceitain
poie, wheie ATP synthase is the base, leauing to piouuction of ATP; you uon't want
ianuom influx of piotons - anu that is what uncoupling agents uo. Examples:
uinitiylphenol (chemical foi pieseiving woou), alcohol, salicylates. 0ncoupling
agents causes piotons to go iight thiough the membiane; theiefoie you aie uiaining
all the piotons, anu veiy little ATP being maue. Bc oui bouy is in total equilibiium
with each othei, ixns that piouuce piotons inciease (ixns that make NABB anu
FABB, these weie the piotons that weie ueliveieu to the election tianspoit system).
Theiefoie any ixn that makes NABB anu FABB that leaus to pioton piouuction will
iev up ixns making NABB anu FABB to make moie piotons. With incieaseu iate of
ixns, leaus to an inciease in tempeiatuie; theiefoie, will also see BYPERTBERNIA.
Complication of salicylate toxic = hypeitheimia (bc it is an uncoupling agent).
Anothei example: alcoholic on hot uay will leau to heat stioke bc alieauy have
uncoupling of oxiuative phosphoiylation (bc mito aie alieauy messeu up).
These aie all the causes of tissue hypoxia (ischemia, Bb ielateu, cyto oxiuase block,
uncoupling agents). Absolute key things!
N) O?'6 ?'##,4/ L?,4 6?,-, &/0
a. iesp aciuosis - Bb stays same, 0
2
sat'n uecieaseu, paitial piessuie of 0
2
uecieaseu
(0
2
sat uecieaseu bc p0
2
is uecieaseu)
b. anemia - only Bb is affecteu (noimal 0
2
sat'n anu p0
2
)
c. C0methemoglobin - Bb noimal, 0
2
sat'n uecieaseu, p0
2
noimal
Rx C0 - 1uu% 0
2
; methemo - Iv methaline blue (B0C) oi vit C (ascoibic aciu)
>) G,5-,'/,A $= (+: H'/ ' -,/<;6 $= 6&//<, ?"#$%&'I
1) B$/6 &.#0 ?'J, 6$ 3$ &46$ '4',-$E&5 3;"5$;"/&/; enu piouuct is lactic aciu
(pyiuvate is conveiteu to lactate bc of incieaseu NABB); neeu to make NAB, so that
the NAB can feeuback into the glycolytic cycle to make 2 moie ATP. Why uo we have
to use anaeiobic glycolysis with tissue hypoxia. Nitochonuiia aie the one that makes
ATP; howevei, with anaeiobic glycolysis, you make 2 ATP without going into the
mitochonuiia. Eveiy cell (incluuing RBC's) in the bouy is capable of peifoiming
anaeiobic glycolysis, theiefoie suiviving on 2 ATP pei glucose if you have tissue
hypoxia. Nitochonuiial system is totally shut uown (no 0
2
at the enu of the election
tianspoit system - can only get 2 ATP with anaeiobic glycolysis).
uoou news - get 2 ATP
Bau news - builu up of lactic aciu in the cell anu outsiue the cell (incieaseu anion-
gap metabolic aciuosis with tissue hypoxia) uue to lactic aciuosis fiom anaeiobic
glycolysis.
Bowevei, causes havoc insiue the cell bc inciease of aciu within a cell will
uenatuie pioteins (with stiuctuial pioteins messeu up, the configuiation will be
alteieu); enzymes will be uenatuieu, too. As a iesult, cells cannot autouigest
anymoie bc enzymes aie uestioyeu bc builuup of aciu. Tissue hypoxia will
theiefoie leau to C0Au0LATI0N neciosis (aka infaiction). Theiefoie, builuup of
lactic aciu within the cell will leau to Coagulation neciosis.
7) 7
4A
#-$E;,. $= ;'5P&43 (+:0 ';; (+: #<.#/ '-, /5-,L,A <# bc they iun on
ATP. ATP is the powei, useu by muscles, the pump, anything that neeus eneigy
neeus ATP. Q'RS #<.# - blockeu by uigitalis to allow Na to go into caiuiac muscle,
so Ca channels open to inciease foice of contiaction (theiefoie, sometimes you want
the pump blockeu), anu sometimes you want to enhance it.
With no ATP, Na into the cell anu it biings B2u, which leaus to cellulai swelling
(which is ieveisible). Theiefoie, with tissue hypoxia theie will be swelling of the cell
uue to uecieaseu ATP (theiefoie will get 0
2
back, anu will pump it out - theiefoie it
is REvERSABLE).
In tiue RBC, anaeiobic glycolysis is the main eneigy souice bc they uo not have
mitochonuiia; not noimal in othei tissues (want to utilize FA's, TCA, etc).
9) >,;; L&6?$<6 2
7
;,'A/ 6$ &--,J,-/&E;, 5?'43,/.
>' 5?'43,/ L&6? &--,J,-/&E;, A'.'3, - CaATPase pump. With ueciease in ATP,
Ca has easy access into the cell. Within the cell, it activates many enzymes (ie
phospholipases in the cell membianes, enzymes in the nucleus, leauing to nucleai
pyknosis (so the chiomatin uisappeais), into goes into the mito anu uestioys it).
Ca activates enzymes; hypeicalcemia leaus to acute pancieatitis bc enzymes in the
pancieas have been activateu. Theiefoie, with iiieveisible changes, Ca has a majoi
iole. 0f the two that get uamageu (mito anu cell membiane), cell membiane is
uamageu a lot woise, iesulting in bau things fiom the outsiue to get into the cell.
Bowevei, to auu insult to injuiy, knock off mitochonuiia (eneigy piouucing factoiy),
it is a veiy bau situation (cell uies).CK-NB foi NI, tiansaminases foi hepatitis (Su0T
anu ASTALT), amylase in pancieatitis.
@@) T-,, D'A&5';/
Livei with biownish pigment - lipofuscin so-calleu "weai & teai pigment" (seen on
gioss pic; can also be hemosiueiin, biliiubin, etc; theiefoie neeu to have a case hx
with the gioss pic); enu piouucts of fiee iauical uamage aie lipofuscin bc ceitain
things aie not uigestible (incluue lipius).
() G,U&4&6&$4 $= =-,, -'A&5'; - compounu with unpaiieu election that is out of
oibit, theiefoie it's veiy unstable anu it will uamage things.
V) +"#,/ $= T-,, D'A&5';/0
1. 0xygen:
We aie bieathing 0
2
, anu 0
2
can give fiee iauicals. If give a peison Su% 0
2
foi a
peiiou of time, will get supeioxiue fiee iauicals, which leau to iepeifusion injuiy, esp
aftei giving tPA when tiying to iiu a uamageu thiombus. 0xygentateu bloou goes
back into the uamageu caiuiac muscle=iepeifusion injuiy. Kius with iesp uistiess
synuiome can get fiee iauical injuiy anu go blinu bc they uestioy the ietina - calleu
(olu name =ietinalfibioplasia sp.) ietinopathy of piematuiity; also leaus to
bionchopulmonaiy uysplasia (get fibiosis in lungs), which leaus to uamage in the
lungs anu a ciippling lung uisease.
2. Byuioxyl FR
Watei in tissues conveiteu to hyuioxyl fiee iauicals ut ionizing iauiation (not 0vB
light, which is non-ionizing iauiation) we'ie talking about iauiation tx in CA leauing
to mutations in tissues. Complication of iauiation theiapy is CANCER (NC cancei
fiom iauiation is leukemia, uue to hyuioxyl fiee iauicals). Fe2+ piouuces hyuioxyl
fiee iauicals bc of the Fenton ixn. This is what makes Fe oveiloau uiseases so
uangeious, bc wheievei Fe is oveiloaueu, leaus to hyuioxyl fiee iauicals which will
uamage that tissue (theiefoie, in livei leaus to ciiihosis, in heait leaus to iestiictive
caiuiomyopathy, in pancieas leaus to failuie, anu malabsoiption, along with
uiabetes).
Auuio File u2: Cell Injuiy 2
S. Tylenol (aka acetaminophen):
NCC uiug inuuceu fulminant hepatitis bc fiee iauicals (esp taigets the livei, but also
taigets the kiuneys). Cytochiome P4Su in livei metabolizes uiugs, anu can change
uiugs into fiee iauicals. Biugs aie often changeu in the livei to the active metabolite
- ie phenytoin. Wheie in the livei uoes acetaminophen toxicity manifest itself. -
iight aiounu cential vein. Tieatment: n-acetylcysteine; how. Well, the fiee iauicals
can be neutializeu. Supeioxiue fiee iauicals can be neutializeu with supiaoxiue
uismutase (S0B). ulutathione is the enu piouuct of the hexosepentose phosphate
shunt anu this shunt also geneiates NABPB. Nain function is to neutialize fiee
iauicals (esp uiug fiee iauicals, anu fiee iauicals ueiiveu fiom peioxiue).
ulutathione gets useu up in neutializing the acetaminophen fiee iauicals. Theiefoie,
when give n-acetylcysteine (aka mucamist); you aie ieplenishing glutathione,
theiefoie giving substiate to make moie glutathione, so you can keep up with
neutializing acetaminophen fiee iauicals. (like methotiexate, anu leukoveiin iescue
- using up too much folate, leukoveiin supplies the substiate to make BNA, folate
ieuuctase).
4. Caibon tetiachloiiue:
CCl4 can be conveiteu to a fiee iauical in the livei (CClS) in the livei, anu a fiee
iauical can be foimeu out of that (seen in uiy cleaning inuustiy).
S. Aspiiin + Tylenol = veiy bau foi kiuney (takes a long time foi uamage to be
seen). Fiee iauicals fiom acetaminophen aie uestioying the ienal meuulla *only
ieceives 1u% of the bloou supply-ielatively hypoxic) anu ienal tubules. Aspiiin is
knocking off the vasouilatoi PuE2, which is maue in the affeient aiteiiole. Theiefoie
Au II (a vasoconstiictoi) is left in chaige of ienal bloou flow at the effeient aiteiiole.
Eithei sloughing of meuulla oi uestioyeu ability to concentiateuilute youi uiine,
which is calleu analgesic nephiopathy (uue mainly to acetaminophen).
@@@) (#$#6$/&/
Piogiammeu cell ueath. Apoptotic genes - "piogiammeu to uie" (theoiy). Noimal
functions: (1) embiyo - small bowel got lumens fiom apoptosis. (2) King of the bouy
- Y c'some (foi men); NIF veiy imp bc all mullaiian stiuctuies (uteius, ceivix,
uppei 1S of vagina) aie gone, theiefoie, no mullaiian stiuctuies. NIF is a signal
woiking with apoptosis, via caspasases. They uestioy eveiything, then wiap
eveiything in apoptotic bouies to be uestioyeu, anu lipofuscin is left ovei. (S)Foi
woman - X c'some; only have one functioning one bc the othei is a baii bouy.
Absence of y c'some causeu geiminal iiuge to go the ovaiian ioute, theiefoie
apoptosis knockeu off the wolfian stiuctuies (epiuyuymis, seminal vesicles, anu vas
uefeiens). (4) Thymus in anteiioi meuiastinum - laige in kius; if absent, it is
Biueoige synuiome (absent thymic shauow), anu woulu also have tetany; cause of
thymus to involute is apoptosis. (S) Apoptosis is the majoi cancei killing mechanism.
(6) Piocess of atiophy anu ieuuceu cell oi tissue mass is uue to apoptosis. Ex.
Bepatitis - councilman bouy (looks like eosinophilic cell without apoptosis) of
apoptosis (inuiviuual cell ueath with inflammation aiounu it). }ust neeus a signal
(hoimone oi chemical) which activate the caspases, anu no inflammation is aiounu
it. Apoptosis of neuions - loss biain mass anu biain atiophy, anu leaus to ischemia.
Reu cytoplasm, anu pynotic nucleas. Atheioscleiotic plaque. Theiefoie, apoptosis is
involveu in embiyo, pathology, anu knocking off cancei cells.
@F) +"#,/ $= 4,5-$/&/ - manifestations of tissue uamage.
() >$'3<;'6&$4 Q,5-$/&/: Results often fiom a suuuen cutoff of bloou supply to an
oigan i.e. Ischemia (uefinition of ischemia = ueciease in aiteiial bloou flow). In
ischemia, theie is no oxygen theiefoie lactic aciu builus up, anu leaus to coagulation
neciosis. uioss manifestation of coagulation neciosis is infaiction. 0nuei
micioscope, looks like caiuiac muscle but theie aie no stiiations, no nuclei, biight
ieu, no inflammatoiy infiltiate, all uue to lactic aciu that has uenatuieu anu
uestioyeu all the enzymes (cannot be bioken uown - neutiophils neeu to come in
fiom the outsiue to bieakuown). Theiefoie, vague outlines = coagulation neciosis
(see coloi change in heait).
1. Pale vs hemoiihagic infaictions: look at consistency of tissue.
(a) uoou consistency = giossly look pale: infaict: heait, kiuney, spleen, livei (iaiest
of the oigan to infaict bc uual bloou supply); ie coagulation neciosis. Example of a
pale infaiction of the spleen, most likely uue to emboli fiom left siue of heait; causes
of emboli: vegetations (iaiely embolize in acute iheumatic enuocaiuitis); infective
enuocaiuitis; mitial stenosis (heait is iepeateuly attackeu by gioup A beta hemolytic
stieptococcus); anu clotsthiombi. The woist aiihythmia associateu with
embolization in the systemic ciiculation is atiial fib bc theie is stasis in the atiia,
clot foimation, then it vibiates (lil pieces of clot embolize).
W'43-,4$</ Q,5-$/&/0 A-" '4A L,6 3'43-,4,0 Pictuie of a uiy gangiene - not wet
gangiene bc theie's no pus. 0ccuis in uiabetic's with atheioscleiosis of popliteal
aiteiy anu possible thiombosis; (uiy gangiene ielateu to coagulation neciosis
ielateu with ischemia (uefinition of ischemia = ueciease in aiteiial bloou flow),
which is uue to atheioscleiosis of the popliteal aiteiy. Pathogenesis of NI: coionaiy
thiombosis oveilying the atheiomatous plaque, leauing to ischemia, anu lumen is
blockeu uue to thiombosis. NCC nontiaumatic amputation = uiabetes bc enhanceu
atheioscleiosis (popliteal aiteiy = uangeious aiteiy). Coionaiy is also uangeious b
c small lumen. In wet gangiene, it's complicateu by infective heteiolysis anu
consequent liquefactive neciosis.
(b) Loose consistency of tissue= hemoiihagic infaict: bowel, testes (toision of the
testes), especially the lungs bc is has a loose consistency anu when the bloou vessels
iuptuie, the RBC's will tiickle out, leauing to a hemoiihagic appeaiance.
Example: hemoiihagic infaiction of small bowel uue to inuiiect heinia. 2
nu
NCC of
bowel infaiction is getting a piece of small bowel tiappeu in inuiiect heinial sac.
NCC of bowel infaiction is auhesions fiom pievious suigeiy.
Example: In the Lung - hemoiihagic infaiction, weuge shapeu, went to pleuial
suiface, theiefoie have effusion anu exuuates; neutiophils in it; have pleuiitic chest
pain (knife-like pain on inspiiation). Pulmonaiy embolus leaus to hemoiihagic
infaiction.
V) X&Y<,='56&J, Q,5-$/&/:
Exception to iule of Coagulation neciosis seen with infaictions: biain.
NC site of infaiction fiom caiotiu aiteiy - why we listen foi a biuit (heaiing foi a
noise that is going thiu a vessel that has a naiiow lumen - place with thiombus
uevelops ovei atheioscleiotic plaque anu leaus to stioke); leaus to tiansient ischemic
attacks is little atheioscleiotic plaques going to little vessels of the biain, piouucing
motoi anu sensoiy abnoimalities, that go away in 24 his. Biain with 'meshwoik' - in
biain, astiocytes is analogous to the fibioblasts bc of piotoplasmic piocesses.
Theiefoie, acting like fibioblast (can't make collagen), but its piotoplasmic piocesses
gives some stiuctuie to the biain. Theiefoie, infaiction of the biain basically
liquefies it (has no stiuct), anu you see a cyst space - ;&Y<,='56&J, 4,5-$/&/.
Theiefoie, exception to the iule of infaictions not being coagulative neciosis is the
biain anu it unueigoes liquefactive neciosis (no stiuc, theiefoie leaves a hole).
Ceiebial abscess anu olu atheioscleiotic stioke -both aie liquefactive neciosis.
Liquefactive - liquefies; think neutiophil, bc theii job is to phagocytosis with theii
enzymes (to 'liquefy'); liquefactive neciosis ielates to an infection with neutiophils
involveu (usually acute infection - piouucing an abscess oi an inflammatoiy
conuition, which liquefies tissue). Theiefoie, liquefactive neciosis usually applies to
acute inflammation, ielateu to neutiophils uamaging the tissue. Exception to the
iule: liquefactive neciosis ielateu to infaict (not an inflammatoiy conuition, it just
liquefies) (sliue shows liquefactive neciosis uue to infection in the biain). So, if you
infaict the biain, oi have an infection, oi have an abscess it is the same piocess -
liquefactive neciosis.
Example: Abscess - giam "+" cocci in clusteis. Why aie they in clusteis. Coagulase,
which leaus to abscesses with staph aui. Coagulase conveits fibiinogen into fibiin,
so it localizes the infection, fibiin stianus get out, iesulting in an abscess. Stiep:
ieleases hyaluioniuase, which bieaks uown uAu's in tissue, anu infection spieaus
thiough the tissue (cellulitis). Fiom point of view of neciosis, neutiophils aie
involveu, theiefoie it is liquefactive neciosis.
Example: ABSCESS: Lung - yellowish aieas, high fevei anu piouuctive cough; giam
stain showeu giam "+" uiplococcus, which is stiep pneumoniae. (NCC of
bionchopneumonia.). Not hemoiihagic bc its pale, anu weugeu shapeu neciosis at
the peiipheiy, which leaus to pleuiitic chest pain.
Example: pt with fevei, night sweats, wt loss - N tb, which has gianulomatous
(caseous) neciosis. Pathogenesis of gianuloma (involves IL-12 anu subset of helpei
T cells anu "+" PPB).
>) >'/,$</ H5?,,/" 5$4/&/6,45"I Q,5-$/&/: - eithei have mycobacteiial infection
(any infections, incluuing atypicals, oi systemic fungal infection); these aie the 0NLY
things that will piouuce caseation in a gianuloma. It is the lipiu in the cell wall of the
oiganism's leaus to cheesy appeaiance.
Saicoiuosis - get gianulomas, but they aie not caseous bc they aie not
mybacteiium oi systemic fungi (hence 'noncaseating' gianulomas)
Ciohn's uz - get gianulomas, but not caseous bc not ielateu to mycobacteiium oi
systemic fungi.
G) T'6 Q,5-$/&/:
1. Enzymatic Fat Neciosis: unique to pancieas
Example: pt with epigastiic uistiess with pain iauiating to the back - pancieatitis
(cannot be Peptic 0lcei Bz bc pancieas is ietiopeiitoneal), theiefoie just have
epigastiic pain iauiating to the back. A type of enzymatic FAT neciosis (theiefoie
neciosis ielateu to enzymes). Enzymatic fat neciosis is unique to the pancieas bc
enzymes aie bieaking uown fats into FA's, which combine with Ca salts, foiming
chalky white aieas of enzymatic fat neciosis (chalky white aieas uue to calcium
bounu to FA's - saponification (soaplike salt foimation)); these can be seen on xiays
bc have calcium in them. Example: A pt with pain constently penetiating into the
back, show x-iay of R0Q. Bx is pancieatitis anu esp seen in alcoholics. Bisto sliue on
enzymatic fat neciosis - bluish uiscoloiation, which is calcification (a type of
uystiophic calcification-calcification of uamageu tissue). What enzyme woulu be
elevateu. Amylase anu lipase (lipase is moie specific bc amylase is also in the
paiotiu glanu, small bowel, anu fallopian tubes). What type of neciosis. Anothei
example: Enzymatic fat neciosis. 0nueilying cause. Alcohol piouuces a thick
secietion that will leau to activation of enzymes; which leaus to pancieatitis.
Theiefoie, whenevei you see blue uiscoloiation anu atheioscleiotic plaque in a
pancieas, it will be calcium.
2. Tiaumatic Fat Neciosis: Example: woman with uamage to bieasts is
TRA0NATIC FAT neciosis (not enzymatic); it can calcify, can look like cancei on
mammogiam. Biff btwn that anu calcification in bieast cancei is that it is painF0L.
(cancei = painless). Tiaumatic fat tissue usually occuis in bieast tissue oi othei
auipose tissue
Z) T&E-&4$&A 4,5-$/&/0 (the -oiu means: looks like, but isn't)
Theiefoie, looks like fibiin, but is not fibiin..it is the neciosis of immunologic uz:
Examples of immunologic uz:
Palpable puipuia = small vessel vasculitis (immune complex type III).
Fibiinoiu neciosis has immune complex ueposition of small vessel.
Pathogenesis of immune complex: uamage of type III BPY (an immune complex is
an Ag-Ab ciiculating in the ciiculation; it ueposits wheievei ciiculation takes it - ie
glomeiulus, small vessel, wheievei). It activates the complement system (the alt
system), which piouuces CSa, which is chemotactic to neutiophils. Theiefoie,
uamage uone as a iesult of type III BPY is uone by neutiophils. Anu they aie theie b
c the immune complex activateu the alteinative complement system. The complex
has little to uo with the uamage, it's the neutiophils uo eventual uamage)
Benoch-Scholein puipuia - feel peison's legs, anu see palpable puipuia (uue to
type III BPY). Rhematic fevei (vegetations off the mitial valve) - have fibiin like
(fibiinoiu neciosis) mateiials (neciosis of immunologic uz). Noining stiffness =
iheumatoiu aithiitis, see fibinoiu neciosis bc immunologic uamage. Theiefoie,
fibiinoiu neciosis is neciosis of immunologic uamage (in vessel it's a vasculitis, in
kiuney it's a glomeiulonephiitis, anu in lupus glomeiulonephiitis involving immune
complexes).
T) X&J,-: Tiiau aiea: poital vein, hepatic aiteiy, bile uuct. Livei is unique bc it has
uual bloou supply anu so hepatic aiteiy anu anu poital vein will uump bloou into
sinusoius. 0thei examples of sinusoiu oigans aie BN anu spleen. Chaiacteiistic of
sinusoius: gaps between enuothelial cells, with nothing theie so things can fit
thiough (things like RBC's anu inflammatoiy cells). uBN is fenestiateu, have little
tiny poies within the cells, foi filtiation. Sinusoius have gaps so laige cells can get
thiough them (not tiue with uBN bc it is intact, anu lil poies allow filtiation).
Poital vein bloou anu hepatic aiteiy bloou go thiough sinusoius, anu eventually
taken up by cential vein, which becomes the hepatic vein. The hepatic vein uumps
into the inf vena cava, which goes to the iight siue of the heait. Theiefoie, theie is a
communication between iight heait anu livei. Right BF (bloou fills behinu faileu
heait), theiefoie the livei becomes congesteu with bloou, leauing to nutmeg livei
(aka congestive hepatomegaly). If you block the poital vein, nothing happens to the
livei, bc it is BEF0RE the livei. Blockage of hepatic vein leaus to buuu chiaii anu
livei becomes congesteu. Which pait of livei is most susceptible to injuiy noimally.
Aiounu cential vein, bc it gets fiist uibbies on 0
2
coming out of the sinusoius (zone
1). Zone 2 is wheie yellow fevei will hit (miuzone neciosis) uue to iues egypti. Zone
S, aiounu poital vein, which will have least 0
2
(analogous to ienal meuulla, which
only ieceives 1u% of the bloou supply, anu the coitex ieceives 9u%). Fatty change is
aiounu zone S (pait aiounu cential vein). Theiefoie, when asking about
acetaminophen toxicity, which pait is most susceptible. Aiounu the cential vein bc
it gets the least amount 0
2
, anu theiefoie cannot combat fiee iauical injuiy.
1. Alcohol ielateu livei uamage:
(a) NCC fatty change: alcohol.
(b) Netabolism of alcohol: NABB anu acetyl CoA (acetate is a FA, anu acetyl CoA can
be conveiteu to FA's in the cytosol). NABB is pait of the metabolism of alcohol,
theiefoie, foi biochemical ixns: What causes pyiuvate to foim lactate in anaeiobic
glycolysis. NABB uiove it in that uiiection, theiefoie always see lactic aciuosis (a
foim of metabolic aciuosis) in alcoholic's bc incieaseu NABB uiives it in that
uiiection. Also, in fasting state, alcoholic will have tiouble making glucose by
gluconeogenesis bc neeu pyiuvate to stait it off. Bowevei, you have lactate (anu
not pyiuvate) theiefoie alcoholics will have fasting hypoglycemia. Acetyl CoA can
also make ketone bouies (acetoacetyl CoA, BNu CoA, anu beta hyuioxybutyiic aciu).
See beta hyuioxybutyiic ketone bouies in alcoholic's bc it's a NABB uiiven ieaction.
Theiefoie, two types of metabolic aciuosis seen in alcoholics aie lactic aciuosis (bc
uiiving pyiuvate into lactate) anu incieaseu synthesis of ketone bouies bc excess
acetyl CoA; main ketoaciu = beta hyuioxybutyiic aciu. Why uoes it piouuce fatty
change. In glycolysis, aiounu ixn 4, get inteimeuiates uihyuioxyacetone phoshphate
(NABB ixn) anu is foiceu to become glyceiol S-phosphate. Big time boaiu question!
With glyceiol S phosphate shuttle, get ATP. Also imp to caibohyuiate backbone foi
making tiyglyceiiues (auu S FA's to glyceiol S - phosphate, anu you get Tu's). In
livei, the lipiu fiaction if vLBL (enuogenous Tu is synthesizeu in the livei fiom
glyceiol S phosphate ueiiveu fiom glycolysis). Restiicting fat will N0T ueciease the
synthesis of vLBL. Restiicting caibs WILL ueciease the vLBL synthesis bc it is
glucose inteimeuiate it is maue fiom. ulyceiol S phosphate is a piouuct of glycolysis
which is why fatty livei is NC'ly uue to alcoholism (this ixn)!
Auuio File uS: Cell Injuiy S
2. Kwashioikei - kiu with fatty change. The mechanism: when you make vLBL,
anu to be able to get it out of the livei, the vLBL must be suiiounueu by apopioteins.
In kwashioikoi, theie is uecieaseu piotein intake; they have auequate numbei of
caloiies, but its all caibs. Theiefoie, they cannot get vLBL that they maue in the livei
out bc theie aie no apolipopioteins to covei it anu put it out in the blooustieam anu
solubilize it in watei. Lipiu anu watei uo not mix; theiefoie it is necessaiy to put
pioteins aiounu the lipiu to uissolve it in watei. Theiefoie, the piotubeiant abuomen
in these pts is theie foi two ieasons: 1) uecieaseu piotein intake which uecieases
oncotic piessuie, leauing to ascites. 2) The biggest ieason is that they have huge
liveis ielateu to fatty change. The mechanism foi fatty change is uiffeient fiom
alcohol bc in alcohol; the mech is uue to incieaseu synthesis of vLBL. In this case,
theie is a lack of piotein to put aiounu the vLBL anu expoit it out of the livei.
S. Bemosiueiin anu Feiitin: biief uiscussion: Feiiitin = soluble foim of ciiculating
Fe, anu is a goou maikei foi Fe in BN. It is the test of choice in ux'ing any Fe ielateu
pioblem - Fe uef anemia, oi Anemia of Chionic Bz oi Fe oveiloau uz's such as
hemochiomatosis anu hemosiueiosis (woulu be elevateu). Feiiitin is a soluble foim
of Fe, while hemosiueiin is an insoluble foim of Fe stoiage, anu is stoieu in
maciophages anu BN. Stain it with Piussian blue.
F) +"#,/ $= 5';5&U&5'6&$4: uystiophic anu metastatic
() G"/6-$#?&5 5';5&U&5'6&$4: means abnoimal calcification. The uamageu tissue
gets calcifieu.
1. Example: Seen in enzymatic fat neciosis (chalky white aieas on x-iay aie a iesult
of uystiophic calcification).
2. Example: football playei with hematoma in foot, that becomes calcifieu
usystiophically (Ca binus anu co-piouuces uystiophic Ca ueposits). Seium Ca is
noimal, but uamageu tissue becomes calcifieu. 0ccuis in atheiomatous plaques
(causes seiious tissue uamage), theiefoie they aie uifficult to uissolve (neeu to be on
the oinish uiet - a vegan uiet).
S. NCC aoitic stenosis (NCC: congenital bicuspiu aoitic valve) = uystiophic
calcification (also leaus to a hemolytic anemia). Sliue: the aoita has only 2 valves
uoing the job of thiee, anu gets uamageu, leauing to uystiophic calcification which
naiiows oiifice of valve, leauing to aoitic stenosis.
V) B,6'/6'6&5 5';5&U&5'6&$4: In cases of Bypeicalcemia oi hypeiphosphatemia,
Calcium is actually maue to ueposit in noimal tissues, non-uamageu tissues.
NCC hypeicalcemia (outsiue of hospital) = piimaiy hypeipaiathyioiuism
NCC hypeicalcemia (insiue the hospital) = malignancy inuuceu hypeicalcemia.
With hypeicalcemia, can put Ca in N0RNAL tissues; this is calleu metastatic
calcification. In uystiophic calcification theie is uamageu tissue with noimal seium
Ca levels. Netastatic calcification is when theie is high Ca oi phosphoius seium
levels (actually when Ca is uepositeu into bone, it is the phosphoius pait of solubility
piouuct that uiives Ca into bone). Bigh phosphate levels (veiy uangeious) will take
Ca anu uiive it into noimal tissue. This is why have to put a pt with ienal failuie on
uialysis (have high phosphoius seium levels) theiefoie neeu to uialyze the
phosphate bc the phosphate will uiive Ca into noimal tissue - ie heait, conuuction
system, ienal tubules, basement membiane (nephiocalcinosis) - all leau to uamage.
F@) >,;; B,.E-'4, G,=,56/
() DV> .,.E-'4, A,=,56: Spheiocytosis is a uefect in spectiin within RBC cell
membiane; if you can't see a cential aiea of palloi (if you uon't see a uonut) then it's
a spheiocyte. Absence of spectiin with in the RBC uoes not allow the RBC to foim a
biconcave uisk; it is uefective, anu theiefoie foims a spheie.
V! ME&Y<&6&4 - stiess piotein. Bigh ubiquitin levels aie associateu with high levels
of stiess. Some of the inteimeuiate filaments (keiatin, uesmin, vimentin) aie pait of
the supeistiuctuie of oui cells ("fiame of the cell", upon which things aie built).
When these inteimeuiate filaments get uamageu, the ubiquitin maiks then foi
uestiuction. The inteimeuiate filaments have been taggeu (ubiquinateu) anu maikeu
foi uestiuction. Some of these piouucts have names, foi example: theie aie open
spaces within the livei tisse, these spaces aie fat anu they aie piobably uue to
alcohol. The ubiquiniteu piouucts of the livei aie calleu Nalloiy bouies. These aie
the iesult of ubiquinateu filaments calleu keiatin anu these aie seen in alcoholic
hepatitis. Anothei example: Silvei stain of neuiofibilaiy tangles - }acob ciutzfelt anu
alzheimeis uz. Tau piotein is associateu with neuiofib tangles; this is an example of
a ubiquinateu neuiofilament. Example: Substantia nigia in Paikinson's Bz - incluue
inclusions calleu Lewy bouies, neuiotiansmittei ueficiency is uopamine. Lewy
bouies aie ubiquinateu neuiofilaments. Theiefoie, Nalloiy bouies, Lewy bouies, anu
neuiofib tangles aie all examples of ubiquintation.
F@@) >,;; >"5;,- veiy veiy impoitant: big big big time
() G&==,-,46 6"#,/ $= 5,;;/:
1. Labile cells - cell wheie the uivision is via a stem cell. Thiee tissues that has stem
cells: bone maiiow, basement membiane of skin, anu the base of ciypts in the
intestine. These cells have the tenuency of being in the cell cycle a lot. In phaim:
theie aie cell cycle specific anu cell cycle nonspecific uiugs. The cells that aie most
affecteu by these uiugs aie the labile cells bc they aie in the cell cycle.
Complications of these uiugs aie BN suppiession, uiaiihea, mucociuis, anu iashes on
the skin (theie aie stem cells in all these tissues!).
2. Stable cells - in iesting phase, u
o
phase. Nost of peienchymal oigans (livei,
spleen, anu kiuney) anu smooth muscle aie stable cells. Stable cells can ungo
uivision, but most of the time they aie iesting, anu something must stimulate them to
get into the cell cycle anu uiviue - ie a hoimone oi a giowth factoi. Foi example:
estiogen in woman will help in the piolifeiative phase of the menstiual cycle. The
enuometiial cells aie initially in the u
o
phase anu then the estiogen stimulateu the
cells to go into the the cell cycle. Theiefoie, they can uiviue, but they have to be
inviteu by a hoimone oi a giowth factoi.
S. Peimanent cells - can no longei get into the cell cycle, anu have been
peimanently uiffeientiateu. The othei types of muscle cells: stiiateu, caiuiac anu
neuional cells. 0nly muscle that is N0T a peimanent tissue = smooth muscle;
hypeiplasia = inciease in #, while hypeitiophy = inciease in size. Woulu a peimanent
cell be able to unuei hypeiplasia. N0, bc that means moie copies of it. Can it go
unuei hypeitiophy. Yes. A smooth muscle cell can unueigo hypeiplasia ANB
hypeitiophy.
V) G&==,-,46 #?'/,/ $= 5,;; 5"5;,0
1. u
1
phase: The most vaiiable phase of cell cycle is the u
1
phase. Compaie with
menstiual cycle: The most vaiiable phase is the piolifeiative phase (not the
secietoiy phase). The piolifeitive phase vaiies with stiess; howevei, once ovulation
has occuiieu, it is 14 uays. Theiefoie, piolifeiative phase is analogous to u
1
phase of
the cell cycle bc it can be shoitei oi lengtheneu; none of the othei phases (S, u
2
, anu
N phase) changes, they stay the same. Theiefoie, in cancei cells, ones with a longei
cell cycle will have a longei u
1
phase, anu cancei cells with a shoitei cell cycle will
have a shoitei u
1
phase.
u
1
phase is the masteiminu of eveiything. Cyclin uepenuent kinase (kinase =
phosphoiylation = activation). Phosphoiylation usually involves senuing a message
to activate something. ulucagon is a phosphoiylatoi, while insulin is a
uephosphoiylatoi. ulucagon will phosphoiylate piotein kinase anu activate it, while
Insulin woulu uephosphoiylate piotein kinase anu inactivate it.
u1 to S phase: Inactive Cyclin u uepenuent kinase: Cyclin u activates it, anu u
1

phase makes cyclin B. 0nce cyclin B is maue in the u
1
phase, it then activates the
enzyme: cyclin uep. kinase (theiefoie it is now active). Key aiea to contiol in cell
cycle: tiansition fiom u
1
to S phase. Because if you have a mutation anu it goes into S
phase, it then becomes uuplicateu, then you have the potential foi cancei. Two
suppiessoi genes that contiol the tiansition: (1) Rb suppiessoi gene: locateu on
chiomosome 1S, which makes the Rb piotein, which pievents the cell fiom going
fiom the u
1
to the S phase. In geneial, to go fiom u
1
to S, the active cyclin uep kinase
phosphoiylates the Rb piotein; when it is phosphoiylateu=activation, it can go fiom
the u
1
phase to the S phase. A pioblem occuis if theie is a mutation. Theiefoie the
enzyme is checkeu by (2) pSS suppiessoi gene: locateu on chiomosome 17, which
makes a piotein piouuct that inhibits the cyclin u uep kinase. Theiefoie, it cannot go
into the S phase; pSS is the numbei 1, most imp gene that iegulates human cancei.
Example: BPv - inactivates Rb suppiessoi gene anu pSS suppiessoi gene. BPv
makes two genes piouucts - E6 (which knocks off the pSS) anu E7 (which knocks of
the Rb suppiessoi gene).
If you have a point mutation the Rb suppiessoi gene, the Rb suppiessoi gene is
knockeu off, theie will be no Rb piotein, anu the cell will piogiess to the S phase bc
it is uncontiolleu. This mutation in the Rb suppiessoi gene pieuisposing to many
canceis, such as ietinoblastoma, osteogenic saicoma (ie kiu with pain aiounu knees,
Couman's tiiangle - sunbuist appeaiance on x-iays), anu bieast cancei (Rb
suppiessoi can be involveu). Bepenuing on the age biacket, it hits in uiffeient aieas.
If you knock of pSS suppiessoi gene: the kinase will be always active, it will always
phosphoiylate the Rb piotein, anu that means that it will always go into the S phase,
anu this is bau. If you knock off any of those genes, the cell will go into the S phase.
The pSS suppiessoi gene is the guaiuian of the genome, bc it gives the cell time to
uetect if theie aie any uefectsabnoimalities in the BNA (splicing uefects, couon
thing, whatevei, etc). BNA iepaii enzymes can splice out the abnoimality, coiiect it,
anu the cell is ieauy to go to the S phase. If the cell has too much uamageu BNA, then
it is iemoveu by apoptosis. Theiefoie this gene is imp bc it gives the cell an
oppoitunity to clean its BNA befoie going into the S phase.
2. S phase = synthesis phase, wheie eveiything is uoubleu, incluues BNA anu
chiomosomes (fiom 2N to 4N). Foi example: if it's in muscle, it will have uouble the
numbei of contiactile elements.
S. u
2
phase = wheie tubulin is maue (imp to miciotubule of the mitotic spinule); it
is blockeu by etoposiue anu bleomycin.
4. N phase = mitosis; wheie the cell uiviues into two 2N cells. The cell can eithei go
into the u
o
iesting phase, oi can continue uiviuing in the cycle, oi can be peimanently
uiffeientiateu. pSS gene makes a piotein to inhibit the kinase, theiefoie pievents the
Rb piotein fiom being phosphoiylateu, theiefoie stays in the u
1
phase. Theiefoie,
when you knock it off, no one is inactivating the kinase, anu the cell is constantly
phosphoiylateu anu that keeps the cell uiviuing, anu then has the potential to leau to
cancei.
>) G-<3/ 6?'6 '56 $4 6?, 5,;; 5"5;,:
1. Biugs acting on S phase:
a) Eigot alkaloius woik on the mitotic spinule in S phase
b) Nethotiexate woiks in S phase: Example: pt with iheumatoiu aithiiitis has
maciocytic anemia. Biug iesponsible foi this is in what phase of the cell cycle. S
phase bc it is methotiexate blocking uihyuiofolate ieuuctase
2. Biugs acting on u
2
phase:
a) Etoposiue
b) Bleomycin
S. Biugs acting on N phase:
a) uiesiofulvin in N phase
b) Paclitaxel specifically woiks in the N phase: Clinical scenaiio: this uiug is a
chemotheiapy agent maue fiom a yew tiee. Paclitaxel (m phase)
c) vinciistine anu vinblastine
u) This uiug useu to be useu foi the tieatment of acute gouty aithiitis but bc of all
the siue effects is no longei useu. What uiug anu wheie uoes it act. Colchicine (m
phase)
4. Clinical scenaiio that uoes not woik on the cell cycle: BIv "+" peison with
uyspnea anu white out of the lung, on a uiug; enus up with cyanosis; which uiug.
Bapsone
F@@) (A'#6'6&$4/ 6$ ,4J&-$4.,46'; /6-,//0 W-$L6? ';6,-'6&$4/
() (6-$#?": Biagnosis: the ueciease in tissue mass anu the cell uecieases in size.
The cell has just enough oiganelles to suivive, ie less mitochonuiia then noimal cells,
theiefoie, just tiying to 'eek' it out until whatevei it neeus to stimulate can come
back.
1. Example: hyuionephiosis, the compiession atiophy is causing thinning of
coitex anu meuulla, NCC hyuionephiosis is stone in the uietei (the pelvis is uilateu).
Question can be askeu what kinu of giowth alteiation can occui heie. Answei is
atiophy bc of the incieaseu piessuie on the coitex anu the meuulla anu piouuces to
ischemia, bloou flow uecieases anu can piouuce atiophy of ienal tubules.
2. Example: Atiophieu biain uue to atheioscleiosis (NC) oi uegeneiation of
neuions (alzheimeis, ielateu to beta amyloiu piotein, which is toxic to neuions).
S. Example: In muscle, many causes of atiophy - ie Lou uehiig's Bz (amylateial
scleiosis) knock off neuions to the muscle, so it is not stimulateu, leauing to atiophy.
4. Example: Enuociine ielateu:
a) Bypopituitaiism will leau to atiophy of auienal coitex: the zona fasiculata anu
ietiuculaiis layeis of the auienal coitex; N0T the glomeiulosa bc ACTB has nothing
to with stimulating aluosteione ielease. The fasiculata is wheie glucocoiticoius
(coitisol) aie maue, while ieticulaiis is wheie sex hoimones aie maue (17
ketosteioius anu testosteione). ACTB is iesponsible foi stimulating these, theiefoie
zona fasiculata anu zona ieticulaiis aie atiophieu.
b) Taking thyioiu hoimone will leau to atiophy of thyioiu glanu. This is uue to a
ueciease of TSB anu theiefoie nothing is stimulating the thyioiu glanu which leaus
to atiophy.
S. Example: Sliue showing a biopsy of a pancieas in a patient with cystic fibiosis.
What is giowth alteiation. Atiophy, bc the CFTR iegulatoi on c'some 7 is uefective
anu has pioblems with secietions. The secietions become thickei anu as a iesult, it
blocks the uucts anu so that means that the glanus that weie making the fluius (the
exociine pait of the glanu) cannot make fluius bc of the back piessuie blocking the
lumen of the uuct, which leaus to atiophy of the glanus, which then leaus to
malabsoiption in all chiluien with cystic fibiosis.
6. Example: Sliue of an aoita, with atheioscleiotic plaque, which leaus to atiophy
of the kiuney anu seconuaiy BTN (ienovasuclai BP, leauing to high ienin level
coming out of the kiuney). In the othei kiuney, it is oveiwoikeu, theiefoie theie is
hypeitiophy (ienin level coming out of this vein is uecieaseu anu suppiesseu).
V) !"#,-6-$#?" inciease of the SIZE of cell, not numbei
Scenaiio: A cell biology question: what is the N of this.
Bypeitiophy of a caiuiac muscle (peimanent muscle), suppose theie is a block just
befoie the u2 phase. What is the numbei of chiomosomes. Answei: # of c'somes is
4N, bc it alieauy unueiwent synthesis: alieauy uoubleu.
1 N = speim (2S c'somes)
2 N = noimal (uiploiu cell)
S N = tiisomy
4 N = uouble the numbei
>) !"#,-#;'/&' - inciease in the # of cells
In noimal piolifeiative glanu, theie aie thousanus of mitoses, theiefoie see moie
glanus with hypeiplasia.
1. Example leauing to cancei: With unopposeu estiogen, you may enu up with
cancei, bc if you uiun't have piogesteione (unuoes what estiogen uiu-counteiacts
the estiogen), you will get cancei. The cells will go fiom hypeiplasia, to atypical
hypeiplasia to enuometiial cancei. Theiefoie hypeiplasia left uncheckeu theie is an
incieaseu iisk of cancei. 0ne exception: benign piostatic hypeiplasia; hypeiplasia of
the piostate uoes N0T leau to cancei; just uiinaiy incontinence.
2. Example: giaviu uteius (woman's uteius aftei ueliveiy). This is an example of
Su:Su: Su% hypeitiophy of the smooth muscle cells in the wall of the uteius, anu
Su% ielateu to hypeiplasia.
S. Example: Bone maiiow: noimally shoulu have SX as many WBC's as RBC's.
Sliue shows few WBC's, anu incieaseu RBC's. Theiefoie, have RBC hypeiplasia. This
is not expecteu to be seen in Iion uef anemia noi in thalassemias bc in those, theie a
uefect in Bb piouuction. It is expecteu to be seen in chionic obstiuctive pulmonaiy
uz (C0PB) bc the hypoxemia causes the ielease of hoimone EP0 (eiythiopoietin);
which is maue in the enuothelial cells of the peiitubulai capillaiies. So in the sliue
this is an example of EP0 stimulateu maiiow.
4. Example: psoiiasis on elbow -an example of hypeiplasia (uniegulateu
piolifeiation of squamous cells in the skin), leauing to ieu skin, anu iaiseu ieu
plaque, bc excessive stiatum coineum. This is why methotiexate woiks heie, bc
it's a cell cycle specific foi the S phase, anu pievents the basal cells fiom piolifeiating.
S. Example: piostate glanu anu blauuei - hypeiplasia of piostate glanus, it a
hoimone ielateu hypeiplasia; all hoimone stimulateu glanus unueigo hypeiplasia,
not hypeitiophy. The wall of the blauuei is too thick; bc uiine has to go out thiu a
naiiow opening in the uiethia, theiefoie the muscle has to woik haiuei which leaus
to hypeitiophy of smooth muscle cells of the blauuei wall (moie uiine must go out
against a gieatei foice bc of an inciease in aftei loau).
G) B,6'#;'/&' - ieplacement of one auult cell type by anothei
1. Example: Sliue of an esophagus, pait of if is all ulceiateu away. 0n a section
suiiounuing the ulcei (iight at the euge of the muscosa) theie aie mucous secieting
cells anu goblet cells (these aie gianuulai cells). These cells aie not supposeu to be
piesent in lowei esophagus; squamous cells shoulu be theie (not glanuulai cells).
Netastatic gianuulai: Baiiets esophagus is a piecuisoi foi auenocaicinoma.
Auenocaicinoma has suipasseu squamous cell caicinoma of miu-esophagus as the
NC cancei of the esophagus. Theiefoie, uERB is the numbei one piecuisoi to
esophageal cancei (auenocaicinoma).
Auuio File u4: Cell Injuiy 4 - Inflammation 1
2. Example: Lining of mainstem bionchus - ciliateu columnai, pseuuostatifieu
columnai. In smokeis, this woulu be an example of metaplasia woulu be squamous.
S. Example: Theie aie incieaseu goblet cells within mainstem bionchus of an olu
smokei, also see goblet cells in the teiminal bionchial. Noimally theie aie goblet
cells in the mainstem bionchus but theie aie no goblet cells in the teiminal
bionchus, theiefoie this is an example of hypeiplasia.
4. Example: uoblet cells in the stomach aie abnoimal (shoulu be in the intestines,
only). This is a glanuulai metaplasia, which is a piecuisoi foi auenocaicinoma of the
stomach. B. pyloii aie a piecuisoi foi auenocaicinoma in the stomach. Bc B. pyloii
causes uamage to pyloius anu antial mucosa bc it is a chionic gastiitis which
intestinal glanuulai metaplasia, which is a piecuisoi foi auenocaicinoma. NCC
auenocaicinoma of the stomach = B. pyloii.
S. Example: Cases wheie metaplasia causes an incieaseu iisk to canei:
a) Remembei that if hypeiplasia is left uncheckeu, coulu potentially leau to cancei.
Foi example: in enuometiial hypeiplasia the NC piecuisoi lesion to enuometiial
caicinoma uue to unopposeu estiogen. The exception is piostatic hypeiplasia, which
uoesn't become cancei.
b) Netaplasia can also go thiough a piocess leauing to cancei:
(1) In lung, ciliateu columnai epithelium BEC0NES squamous, theiefoie, this is
calleu SQ0AN00S metaplasia; this will leau to squamous uysplasia, which then
pioceeus to cancei (squamous caicinoma);
(2) In uistal esophagus, went fiom squamous to glanuulai epithelium bc squamous
epithelium cannot hanule the aciu, theiefoie it neeus mucous secieting epithelium as
a uefense against cellulai injuiy. Bowevei, the glanuulai metaplasia can go on to an
atypical metaplasia, pieuisposing to auenocaicinoma of the uistal esophagus.
(S) Paiasites: 2 paiasites piouuce cancei: clonesis sinesis leaus to
cholangiocaicinoma (Chinese livei fluke); anu shistosoma hematoabia. The
schistosomias hematobia causes blauuei cancei by causing the tiansitional
epithelium to unueigo squamous metaplasia. This leaus to squamous uysplasia, anu
then on to squamous cancei. Tiansitional epithelium leaus to squamous epithelium
(calleu metaplasia), then uysplasia, then on to cancei.
Z) G"/#;'/&' is ieally an atypical hypeiplasia.
1. Example: Sliue of a squamous epithelium is uisoiganizeu, with nuclei that aie
laigei neai the suiface anu the basal cell layei is iesponsible foi the uiviuing; cells at
top aie biggei than the ones that aie uiviuing, it has lack oiientation. If it was founu
uuiing a ceivical biopsy in pt with BPv infection, oi if it was founu in the mainstem
bionchus biopsy, you shoulu be able to tell that it is uysplastic. Theiefoie uysplasia,
whethei glanuulai oi squamous, is a piecuisoi foi cancei.
2. Example: Theie was a faimei with lesion on the back of his neck (can giow on
any pait of the bouy, uue to sun exposuie), which coulu be sciapeu off anu giew back
- actinic keiatosis (aka solai keiatosis) - is a piecuisoi foi sq. cell caicinoma of the
skin. 0v-b light uamages the skin. Actinic keiatosis uoes not pieuispose to basal cell
caicinoma, even though basal cell caicinoma is the most common skin cancei.
CHAPTER 2: Inflammation
@) (5<6, @4U;'..'6&$4
() >'-A&4'; /&34/ $= &4U;'..'6&$4
In the scenaiio with a bee sting: you will see ieuness (+<E$-). The king of
vasouilatois is histamine anu it vasouilates the aiteiioles. Theiefoie, histamine is
iesponsible foi the ieuness of acute inflammation (ie bee sting), anu is woiking on
aiteiioles. Now if we felt the aiea, it will be waim (>';$- = heat), this is uue to
vasouilating the aiteiioles, which is causeu by histamine. Foi example in enuotoxic
anu septic shock, the skin is waim bc you aie vasouilateu. +<.$- is a iaiseu
stiuctuie causeu by histamine. Bistamine can leau to incieaseu vessel peimeability
in the venules; is aiteiial thickei than venules. Yes. The venules aie veiy thin; they
basically have an enuothelial cell with a basement membiane, all you have to is uiill
a hole thiough the BN anu you aie out. Theiefoie, incieaseu vessel peimeability
occuis at the venule level, not the aiteiial level. Bistamine contiacts the enuothelial
cells, anu leaves the BN baie, leauing to incieaseu vessel peimeability, piouucing an
exuuate, anu swelling of tissue, hence 6<.$- of acute inflammation. The aiea may
huit (G$;$- = pain) but hitamine uoes not have anything to uo with this. Biauykinin
is pait of the kininogen system between factoi 11 anu Bageman factoi 12. So when
you activate the intiinsic pathway, you automatically activate the kininogen system.
When you activate factoi 12 (Bageman factoi), it will activate 11 anu the whole
kininogen system. The enu piouuct is biauykinin. ACE uegiaues biauykinin.
Complication of ACE inhibitoi is angioeuema. Also inhibit metabolism of biauykinin,
which incieases vessel peimeability, piouucing the angioeuema (swelling of the
tissues). Bow biauykinin piouuces cough is not ieally unueistoou. Biauykinin anu
PuE2 cause pain (A$;$-) anu is the only one out of the foui Latin teims of acute
inflammation that is not uue to histamine ielease.
V) [6,#/ &4J$;J,A &4 (5<6, &4U;'..'6&$4 (this the noimal sequence in acute
inflammation)0
1. Emigiation: incluues maigination, paveenting, iolling, auhesion, anu
tiansmigiation
Neutiophils in ciiculation stait to become sticky bc of auhesion molecule
synthesis. Enuothelial cells begin to synthesize auhesion molecules. Eventatually,
neutiophils will stick to enuothelial cells, these steps aie calleu pavmenting oi
maigination. Then neutiophils look foi baie basement membiane on the venules
anu then they uiill a hole thiough it via type 4 collagenase. Cancei cells also have
type 4 collagenase, that's how they metastasize. Cancei cells attach to enuothelial via
auhesion molecules, usually against laminin in BN, anu they have collagensae to get
thiough the BN, theiefoie, cancei cells aie pietty much like a neutiophil when
invauing tissue.
2. Chemotaxis:
When they pass BN of small venules, they emigiate but they have to know what
uiiection to go. They get uiiections in a piocess calleu uiiecteu chemotaxis. CSa anu
LT-B4 (leukotiiene B4) aie the chemotactic agents. These chemotactic agents aie
also involveu in making auhesion molecules on neutiophils). Theiefoie, they make
auhesion molecules ANB give uiiection by acting like chemotactic agents.
S. Phagocytosis via opsonization:
a) Example: in an acute inflammation with staph auieus, the bacteiia aie being
piocesseu by opsonins, which immobilize the paiticles on the suiface of the
phagocyte. The two main opsonins aie Igu anu CSb. They help with phagocytosis.
b) Example of an opsonization uefect: Biutons agammaglobinemia: an x-linkeu
iecessive uz, wheie all the immunoglobulins aie missing, incluuing Igu. Theiefoie,
NCC ueath in these pts is uue to infection bc cannot opsonize things. It piouuces
hypogamma-globinemia, but the mechanism of infection is uue to not having Igu to
opsonize bacteiia, theiefoie cannot phagocytose it.
Bacteiia aie opsonizeu by Igu anu CSb, which means that neutiophils must have
ieceptois foi those. In acute inflammation the main cell is neutiophil anu in chionic
inflammation the main cell is maciophagemonocyte (monocytes become
maciophages). These cells have to have ieceptois foi these opsonins (Igu anu CSb).
Then they become phagocytoseu oi become phagolysomes. When they aie
phagocytoseu, the lysosomes go to miciotubules anu empty theii enzyme into this.
c) Example: In I-cell uisease: in this uz, mannose iesiuues cannot be phosphoiylate
in golgi appaiatus theiefoie the enzymes aie not maikeu with phosphoius, anu the
lysosome aie empty.
4. Intiacellulai miciobial killing:
a) Examples:
(1) Staph auieus in hottub suiiounueu by enzymes
(2)Chlamyuia can get out of phagolysosome, mechanism unknown, but sometimes
they have mucous anu all kinus of things aiounu them.
b) 2
7
A,#,4A,46 .",;$#,-$%&A'/, /"/6,. is the boaius!!
Noleculai 0
2
is conveiteu by NABPB oxiuase, which is in the cell membiane of
neutiophils anu monocytes, but not maciophages. The most impoitant cofactoi is
NABPB, which is synthesizeu in the pentose phosphate shunt. The enzyme
iesponsible is glucose 6 phosphate uehyuiogenase, which conveits u6P into 6-
phosphogluconate, geneiating NABPB anu a neutializing factoi foi fiee iauicals
(glutathione).
It is conveiting 0
2
into a fiee iauical, supeioxiue. Supeioxiue has an unpaiieu
election giving off eneigy, which is calleu a iesp buist, which can be measuieu by
iauiation uetectois; anu by a negative NBT uye test. In the NBT test, you have a test
tube, auu the coloiless NBT uye; anu if neutiophils anu monocytes aie woiking
noimally, they will phagocytose it, will have a iespiiatoiy buist, anu the fiee iauical
0
2
will cause the coloi to change to blue, inuicating that the iesp buist is woiking. If
theie is no coloi change, theie is not a iesp buist, theiefoie the pt has chionic
gianulomatous uz of chiluhoou.
Fiee iauical 0
2
is conveiteu by S0B (it's neutializei) into peioxiue. Peioxiue itself
coulu kill bugs, but it is useu foi anothei ieason. Within the neutiophils anu
monocytes aie ieuuish gianules which aie lysosomes, anu aie seen in the peiipheial
bloou. Nyelopeioxiuase (one of the many enzymes in the gianules) will catalyze the
ixn. It will combine peioxiue with chloiiue to fiom bleach. This &/ 6?, .$/6 #$6,46
E'56,-&5&A'; .,5?'4&/. \ 2
7
A,# .",;$#,-$%&A'/, /"/6,., which is in
NE0TR0PBILS anu N0N0CYTES but N0T in maciophages, bc maciophages lose the
system when they conveit fiom monocytes to maciophages anu they use lysosomes
to kill. Naciophages of the CNS aie micioglial cells, so the ieseivoii cell foi CNS
AIBS is the miciobial cell. 0utsiue the CNS, it is the uenuiitic cell; it is a maciophage
locateu in the lymph noues.
c) In u6PB ueficiency, infection is the NC piecipitation of hemolysis bc theie is no
NABPB, theiefoie theie is no functioning 0
2
uepenuent myelopeioxiuase system,
anu theiefoie you aie susceptible to infection, which will set of hemolysis of RBC'S.
u) Chionic gianulomatous uz of chiluhoou = X linkeu iecessive uz wheie the mom
gives the uz to the boy, anu is an asymptomatic caiiiei, anu they will tiansmit the uz
to Su% of theii son's. In this uz, theie is a ueficient activity of NABPB oxiuase, anu
the NBT uye test is negative (uoesn't show coloi of uie), theiefoie no iesp buist. Bo
they have supeioxiue. No. Peioxiue. No. Nyelopeioxiuase. Yes. Chloiiue. Yes.
Theiefoie, if they phagocytoseu a bacteiia that coulu make peioxiue, anu auu it
insiue the phagolysosome, this is what the kiu woulu neeu to kill the bacteiia. These
kius aie missing PER0XIBE bc theie is no NABPB oxiuase. ALL living oiganisms
make peioxiue (incluuing ALL bacteiia). Bowevei, not all bacteiia contain catalase,
which is an enzyme that bieaks uown peioxiue. So, in chionic gianulomatous uz,
what can they anu can't they kill. Cannot kill staph, but can kill stiep. Why. Bc
staph is Coagulase anu CATalase "+"; so, ie, if it's staph. auieus anu when it makes
peioxiue, it will also make catalase anu neutialize it, theiefoie the chilu cannot kill
staph, anu will kill the kiu. If it was a stieptococcus oiganism that makes peioxiue
(uoes not have catalase theiefoie peioxiue can be useu by the chilu), it auus what kiu
ieally neeueu to make bleach, anu the bacteiia is then wipeu out. Theiefoie, can kill
stiep anu not staph!
e) Nyelopeioxiuase ueficiency: Bo they have a iesp buist. Yes bc they have
NABPB oxiuase. Bo they have peioxiue. Yes. Bo they have supeioxiue fiee iauicals.
Yes. Bo they have chloiiue. Yes. Bo they have myelopeioxiuase. No. They have a
noimal iesp buist anu a noimal NBT uye test, but they can't kill the bacteiia bc they
cannot make bleach. This is calleu a myelopeioxiuase uefect. 0thei types of uefects:
(1) opsonization uefects with biutons (missing Igu), CS uef's; (2) chemotactic uefects
wheie cells uo not iesponu to chemotaxis; (S) miciobiociual uefects, the uefect in the
ablility to kill bacteiia, example: chionic gianulmatous uz of chiluhoou anu
myelopeioxiuase ueficiency aie both miciobiociual uz, in that they cannot kill
bacteiia, but foi uiffeient ieasons. In myelopeioxiuase uef the pioblem is that they
cannot make bleach (bc of the missing enzyme), but uo have iesp buist, anu is
Autosomal iecessive uz. In CuBz the pioblem is that they cannot make bleach eithei,
but they have an ABSENT iesp buist, anu is a X-LINKEB iecessive uz.
f) Chilu has an umbilical coiu that uoesn't fall off when it shoulu. When it was
iemoveu anu lookeu at histologically, they uiu not see neutiophils in the tissue oi
neutiophils lining the small vessels. This is an auhesion molecule uefect oi beta 2
integiin uefect. 0mblilcal coiu neeus to have an inflammatoiy ixn involving
neutiophils; they have to stick in oiuei to get out. Theiefoie, if the neutiophils can't
stick, they can't get out, anu then they can't get iiu of youi umbilical coiu - this is a
classic auhesion molecule uefect.
>) >?,.&5'; .,A&'6$-/0
1. Bistamine: the king of chemical meuiatois of acute inflammation
a) What uoes it uo to aiteiioles. vasouilates
b) venules. Incieaseu vessel peimeability
2. Seiotonin:
a) What amino aciu makes seiotonin. Tiyptophan
b) Is seiotonin a neuiotiansmittei. Yes
c) In a ueficiency, you get uepiession (also uecieaseu NE)
u) a vasouilatoi anu incieases vasculai peimeability
S. Complement system: Anaphylatoxins - CSa, CSa. Function: stimulate mast cells
to ielease histamine, leauing to vasouilation anu incieaseu vessel peimeablility.
They also play a iole in shock, bc when theie is inflammation the compliment
system is activateu, theiefoie theie will be mast cells anu histamine, theiefoie CSa,
anu CSa will both be theie.
4. Nitiic oxiue - maue mainly in enuothelial cells, anu is a potent vasouilatoi. It is
useu foi tieating pulmonaiy hypeitension. It has a big time iole in septic shock.
S. IL-1 associateu with a fevei, it is a pyiogen, theiefoie stimulates the
hypothalamus to make Pu's, which stimulate theimoiegulatoiy system to piouuce
fevei. Aspiiin woiks by inhibiting the synthesis of piostaglanuins theieby ieuucing
the fevei.

6. Aiachiuonic aciu metabolites:
a) Coiticosteioius inhibits Phospholipase A
2
, theiefoie uo not ielease aiachiuonic
aciu fiom phospholipius, theiefoie not making Pu's oi leukotiienes. This is the
supieme antiflammatoiy agent bc B0TB Pu's anu leukotiienes aie blockeu by
blocking phospholipase A
2
. Aiachiuonic acius make linoleic aciu (omega S), which is
founu in fish oils anu walnuts. It is veiy goou foi you bc it acts like aspiiin, anu
blocks platelet aggiegation, anu that's how omega S piotects youi heait.
b) Lipoxygenase pathway: Zileutin blocks S-lipoxgenase, othei uiugs act by
blocking the ieceptois, example: ziikufulast, etc. Leukotiiene (LT) C4, B4, E4 (the
slow ieactoi substances of anaphylaxis) seen in bionchial asthma. They aie potent
bionchoconstiictois; theiefoie it can be seen why zileutin woiks well in asthma bc
it blocks the leukotiienes, incluuing these (LT-C4, B4, anu E4). LT B4 is an auhesion
molecule in chemotaxis.
c) Cyclooxygenase pathway: Aspiiin blocks cycoloxygenase, iiieveisibly in
platelets. PuB2: wheie eveiything seems to be ueiiveu fiom. PuI2: ueiives fiom
enuothelial cells, it's also calleu piostacyclin synthase; is a vasouilatoi anu inhibits
platelet aggiegation (exact the opposite of TxA2). Thiombaxane A2 (the enemy of
PuI2) is maue in the platelet; it's a vasoconstiictoi, a bionchoconstiictoi, anu
piomotes platelet aggiegation. What uiug blocks thiombaxane synthase anu is useu
to stiess testing foi CAB. Bipyiiamiual blocks the enzyme, TxA2 synthase, theiefoie
uoes not have to peifoim a tieaumill stiess test, all you have to uo is use the uiug
uipyiiamiual.
PuE2: vasouilatoi in kiuney; keeps patent uuctus patent in baby heait; makes the
mucous baiiiei in uI (stomach) theieby pieventing ulceis; can cause uysmenoiihea
woman anu incieaseu uteiine contiactility, anu it an aboitifactant, to get iiu of fetal
mateiial.
u) C0X 2-make suie you know how this woiks!
e) Coiticosteioius blocks phospholipase A2, anu it also uecieases auhesion
molecule synthesis, along with othei steioius like epinephiine anu NE. Becieaseu
auhesion molecule synthesis, will leau to incieaseu neutiophils on CBC; in immuno,
Su% neutiophils aie stuck to the enuothelial vessels, anu the othei Su% aie
ciiculating, theiefoie, uecieasing auhesion molecule synthesis will leau to uoubleu
WBC (bc the Su% of neutiophils that weie stuck aie now ciiculating).
Coiticosteioius uestioy B-cells bc they aie lymphocytotoxic. Nechanism: ueciease
WBC's (B anu T cells) via apoptosis; theiefoie, coiticosteioius aie the signal to
activate the caspasases. Eosinophils, mainly seen in type one BPY ixn,
coiticosteioius ueciease them. When on coiticosteioius, the only thing that is
incieaseu is neutiophils, via uecieaseu auhesion molecule synthesis. Lymphocytes
anu eosinophils aie uecieaseu. Example: If have Auuisons, uo not have coitisol,
theiefoie the neutiophil ct uecieases anu the eosinophil count will inciease.
Example: a peison with NI with an 18,uuu CBC most of which aie neutiophils.
Nechanism: Epinephiine uecieases auhesion molecule sythesis anu neutiophil
count goes up.
G) Z;,56-$4 .&5-$/5$#" $= &4U;'..'6$-" 5,;;/0
1. In lung, type II pneomocyte (black uots aie lysosomes).
Lamellai bouies - stiuctuies wheie lecithin anu phosphotiuyl choline is locateu; if
ask wheie maciophage, is, will ask which makes suifactant.
2. Nonocyte: single nucleus with a giayish cytoplasm - has scavageu; can foim
foam cell in atheioscleiotic plaque bc it has phagocytizeu oxiuizeu LBL's (which is a
fiee iauical); vit E neutializes oxiuizeu LBL.
S. Lymphocyte - all nucleus anu scant cyptoplasm, piob a T cell (6u% of peiipheial
bloou lymphocytes aie T cells); iatio of helpei to suppiessoi: CB4:CB8 is (2:1),
theiefoie, moie likely to be a Belpei T cell, then a suppiessoi T-cell, anu B cells
(2u%) aie least likely.
4. RER looks like a thumbpiint, have iibo's on it, anu likes to make pioteins, like
Ig's (theiefoie it is a plasma cell). Nultiple myeloma - has eccentiically locateu
nucleus, cytoplasm is always sky blue, making plasma cells ez to iecognize. Plasma
cells aie ueiiveu fiom B cells, anu locateu in the geiminal follicle.
S. uianules - eosinophil (have a ieu coloi similai to coloi of RBC's) - have ciystals
in the gianules. Eosinophils aie the only inflammatoiy cell that has ciystals in the
gianules. They aie calleu Chaicot-Leiuen ciystals when it's seen in the sputum of
asthmatic patient. They aie uegeneiateu eosinophils in sputum of asthmatic, anu
have foimeu ciystals that look like speai heaus. Basophils have gianules that aie
moie puiplish anu uaikei, while basophils have uaikei colois.
6. Nech foi killing invasive helminthes-Type II BPY-majoi basic piotein is
involveu. Remembei that shistotosome eggs aie coateu by IgE Ab's. Eosinophils
have IgE ieceptois; theiefoie, eosinophils hook into the IgE ieceptoi anu ielease
chemicals; the main one ieleaseu is majoi basic piotein, which uestioys the
helminth, which is type II BPY, bc it is a cell hooking into an Ab on the taiget cell.
The effectoi cell is Type II BPY ixn is the eosinophils; uon't get confuseu with Type I
BPY ixn wheie the effectoi cell is the NAST CELL, anu they ielease histamine (an
eosinophil chemotactic factoi), theiefoie they aie inviteu to aiea of type I BPY bc
they have histaminase anu aiylsulfatase, which neutializes leukotiienes. The
puipose of eosinophils in type I BPY is to knock off chemical meuiatois piouuceu in
ixn; howevei, when an eosinophil kills an invasive helminth, it uoes so via type II
BPY.
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Belpei t cell = CB4
Cytotoxic T cell = CB8
Naikei foi Ag iecognition site foi all T cells is CBS
Naikei foi histiocytes (incluuing langeihan's cells) is CB1
Naikei foi NC leukemia in chiluien = CB1u (calla Ag); positive B-cell lymphoma
CB1S anu Su = RS cell
CB21, 0nly on B cells - Epstein baii viius; hooks into CB21 on B cells, anu actually
the atypical lymphocytes aie not B-cells but T-cells ieacting to the infecteu B-cells.
Buikitts is a B cell lymphoma
CB4S is founu on all leukocytes, is a common antigen on eveiything
T) T,J,- - IL-1 is iesponsible anu PuE2 (this is what the hypothalamus is making)
which stimulates the theimoiegulatoiy centei. Fevei is goou! It iight shifts the 0
2

uissoc cuive. Why uo we want moie 0
2
in the tissues with an infection. Bc of 0
2

uepenuent myelopeioxiuase system. Theiefoie, with antipyietics it's bau bc
thwaiting the mechanism of getting 0
2
to neutiophils anu monocytes to uo what they
uo best. Also, hot temps in the bouy aie not goou foi iepiouuction of bacteiia
viiuses.
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A. post paitum woman, with pus coming out of lactifeious uuct - this is staph
auieus - suppleiative inflammation
B. Bone of chilu with sepsis, on top of the bone, was a yellowish aiea, anu it was an
abscess - osteomyelitis - staph. auieus; if the kiu hau sickle cell, it is salmonella; why
at metaphysis of bone. Bc most of bloou supply goes heie, theiefoie, mechanism of
spieau is hematogenous (theiefoie comes fiom anothei souice, anu then it gets to
bone).
C. Bot, spieau ovei face - cellulitis uue to stiep (play ouus!) gioup A pyogenes
(calleu eiysipilis, anothei name foi cellulitis)
B. Biphtheiia = psueuomembiane (coiynebacteiium uiphtheiia), a giam + iou, that
makes an exotoxin, messing up iibosylation of piotiens via elongation factoi 2, the
toxin uamages mucosasubmucosa, piouucing a pseuuomembiane; when bacteiia
uoesn't invaue, piouuces a toxin that uamages the membiane; clostiiuium uifficile
also uoes this. It also piouueces a pseuuomembiane anu a toxin, which we measuie
in stool to make the ux. Theiefoie, the answei is C. uifficle.
E. Fibiinouis peiicaiuitis, usually with incieaseu vessel peimeability; seen in
(1)lupus, leauing to fiiction iub; also seen in (2) the fiist week of NI, anu then again
6 weeks latei in uiessleis's synuiome, (S) seen in Coxsackie
F. NC oiganism piouucing infection in thiiu uegiee buins = pseuuomonas
auiiginosa. Coloi of pus: gieen uue to pyocyanin.
u. Basal cell layei on both siues of clot, piolifeiate, anu go unueineath it to clot. In
a piimaiy wounu it's usually sealeu off in 48 his (ie appenuectomy). Key to wounu
healing is piescence of gianulation tissue. Fibionectin is a veiy impoitant
pioteoglycan anu is involveu in the healing of the wounu. Fibionectin is an
impoitant auhesion agent anu chemotactic agent, inviting fibioblast in helping
healing piocess. The gianulation tissue staits at uay S anu is on its piime by uay S. If
you evei pickeu at a scai anu it bleeu like mau anu you tiy to stop it but it still bleeu
like mau, that's gianulation tissue. No gianulation tissue means no healing of a
wounu. Type of collagen in initial stage of wounu iepaii = type S; type 4 collagen
seen in BN; type 1 - veiy stiong tensile stiength; seen in bone, skin, tenuons,
ligaments.
Aftei a few months, aftei months, the collagen type S is bioken uown by
collagenases, anu a metallic enzyme conveits type S into type 1. Zinc is pait of the
metallic enzyme, this is why in a pt with zinc ueficiency has pooi wounu healing bc
it sciews up the collagenase (must ieplace type S with type 1). Nax tensile stiength
aftei S months = 8u%. NCC pooi wounu healing = infection
B. Ehleis Banlos - uefect in collagen uue to synbieaking uown; have pooi wounu
healing.
I. maifan - uefect in fibiilin; also have pooi wounu healing
}. Pt with scuivy - uefect in hyuioxylation of two aa's - pioline anu lysine via
ascoibic aciu. Remembei it's a tiiple helix; what makes the tiiple helix stick
togethei anu inciease tensile stiength. Ciossbiiuges. When you ciossbiiuge things,
they anchoi into aieas wheie you have hyuioxylateu pioline anu lysine. Theiefoie
have weak abnoimal collagen in scuivy bc theie aie no ciossbiiuges to attach,
leauing to not being able to heal wounus, hemoiihaging, hemaithioses..collagen has
weak tensile stiength bc cannot ciossbiiuge..
Auuio File S: Inflamation 2 - Fluiu Anu Bemouynamics 1
K. uianulation tissue with a lot of bloou vessels uue to lot of fibioblast u, with
inflammatoiy cells fiom plasma cells anu lymphocytes, necessaiy foi wounu healing
(iich vasculai tissue, which is absolutely essential foi noimal wounu healing).
L. Keloiu (hypeitiophic scai) = excess in type S collagen ueposition; which causes a
tumoi looking lesions, esp in blacks. In a white kiu - keloiu to uue to thiiu uegiee
buins. In anothei example: in a chionically uiaining sinus tiact of the skin, they tiieu
to put antibiotics on it (uiun't woik), theie was an ulceiation lesion at the oiifice of
this chionically uiaining tiact, anu nothing woikeu. What is it. The answei is
squamous cell caicinoma uue to a lot of tuinovei; type S conveiteu to type 1, anu
fibioblasts aie involveu. A lot of cell uivision occuiiing, which can piesuispose to
mutations anu cancei, esp squamous cell cancei. Squamous cancei is imp bc
chionically uiaining sinus tiacts, anu pieuisposes to sqamous cell caicinoma.
Bypeiplasia pieuisposes to squamous cell caicinoma.
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A. Biffeience in Immunoglobulins:
1. Acute Inflammation: IgN = main Ig fiist, anu then Igu
IgN = main Ig; neeu a lot of complement components in healing piocess; IgN is the
most potent activatoi, anu have activation of complement pathway (all the way foi
1-9); IgN has 1u activating sites (pentamei).
Igu can activate the classical system, but uoes N0T go passeu CS anu stops anu uoes
not go onto CS-9.
Aftei 1u uays, theie is isotype switching, anu the mu heavy chain is spliceu out (mu
chain uefies specificity of an Ig); it splices in a gamma heavy chain, anu Igu is maue
via isotype switching
2. Chionic inflammation: Igu (as main Ig - IgN is coveiteu to Igu immeuiately)
B. Biffeience in Cell Types:
1. Acute inflammtions = neutiophil
2. Acute alleigic ieactions= eosinophils (mast cells aie in tissues)
S. viial infections = lymphocytes aie the main inflammatoiy cells
4. Chionic inflammations = monocytesmaciophages aie imp. Anu see a lot of
plasma cells anu lymphocytes; uo not see pus-exuuative (this is in acute inflamm -
incieaseu vessel peimeability, anu incieaseu emigiation of neutiophils into
inteistitial tissue, a piotein iich fluiu with >S giamsuL, with a piotein iich fluiu =
pus). Example: Cholecystis.
C. Type Iv Bypeisensitivity Reaction:
Anothei example: uianuloma = chionic inflammation (nevei acute); ie caseious
neciosis in someone with TB; iounuish, pink, multinucleateu giant cells =
gianulomas; pathogenesis = type Iv hypeisentistivity ieaction - uelayeu BPY. The
main actois aie cytoxic T cells; when they kill neoplastic, viially infecteu cells, these
aie also type Iv BPY (no Ab's involveu). Poison ivy = type Iv BPY. Back to TB
infection, aleovlai maciophage phagocytoses it, anu theie is lymphohemotogenous
spieau; meanwhile the maciophage is piocessing the Ag. Then aftei weeks, it
piesents it to helpei T cells. Theiefoie, the key playeis in Type Iv hypeisensitivity
ixn aie maciophages which piocess that Ag anu piesents that Ag via class II NBC
sites to the helpei T cells. These helpei T-cells ielease cytokines: gamma IFN anu
maciophage inhibitoiy factoi. uamma IFN will activate the maciophage to kill the
TB, Ciyptococcus, histoplasmosis, etc. Theiefoie the gamma IFN is the tiiggei to
active the maciophage; maciophage cannot kill without the activation fiom gamma
IFN; bc systmemic fungi anu TB have lipiu in the cell wall, this leaus to caseous
neciosis. All the pink staining cells aie 'epthiloiu', which aie activateu maciophages
(which have been activateu by gamma IFN); when they uie, they uie in style - they
fuse togethei anu foim multinucleateu giant cells (like theii 'giavestone'). Theiefoie,
epitheloiu cells aie fuseu maciophages; black uots aie helpei T cells.
Theie aie two types of helpei T-cell:
a. Subset 1: involveu in Type Iv (uelayeu type) BPY; maciophages have IL-12;
when it is secieteu, the subset 1 helpei T cells aie piesenteu with the antigen; then,
subset 1 become NEN0RY T cells. IL-12 is involveu in activating the memoiy of
subset 1 helpei t cells. Nost people in theii piimaiy uz usually iecovei with no
pioblems, but the gianulomas can calcify, as seen on x-iay. A calcifieu gianuloma is
not ueau bc they aie iesistant to uying. Theiefoie, most cases of seconuaiy TB aie
uue to ieactivation TB. uianulomas neciosis is uue to ieactivation.
"+" PPB (puiifieu piotein ueiivative) - injecteu into the skin; the maciophage of the
skin is a langeihan's cell (histiocyte) (maikei: CB 1) - which have biibeck gianules-
look like tennis iackets on EN. They phagocyotose the Ag (the PPB), anu piocess it
veiy quickly; they piesent it to helpei subset 1, which has memoiy of pievious
exposuie. Theiefoie, it hooks in the NBC class II Ag sites (as all immune cells uo),
anu once the Ag (PPB piocesseu by the langeihan's cell) is piesenteu, the helpei T
cell ieleases the cytokines piouucing the inflammatoiy ixn with inuuiation calleu the
"+" PPB.
Coiielation: oluei people usually uon't host a veiy goou Type Iv hypeisensitity ixn:
they have a less iesponse to "+" PPB; theiefoie have to uo a uouble test on them. In
pt with AIBs, may not get any ixn. They uon't have enough helpei T-cells theiefoie
uon't have gianuloma foimation. Naciophage inhibitoiy factoi keeps maciophages
in that aiea; theiefoie, with BIv, bc the helpei t cell ct is uecieaseu, you uon't foim
gianulomas at all. Theiefoie, they will have NAI (oiganisms) all ovei the bouy
without gianulomas bc helpei T cells aie uecieaseu. When you uo "+" PPB, S mm
inuuiation is enough to say it's positive. .
@F) +&//<, D,#'&-
Scai tissue (bc its peimanent tissue); scai tissue (fibious tissue) uoes not contiact;
theiefoie, if you have moie scai tissue to fiee wall of left vetiicle will leau to
uecieaseu ejection fiaction (which is stioke volume uiviueu by EBv).
A. Response of Kiuneys to Injuiy: Kiuney will foim scai tissue; meuulla is most
susceptible to ischemia (bc least amount of bloou supply). What pait of nephion
most susceptible to tissue hypoxia. 2 places:
1. Stiaight poition of piox tubule bc most of oxiuative metabolism is locateu theie,
with biush boiueis - this is wheie most of ieabsoiption of Na, anu ieclaiming of
bicaib is theie.
2. Neuullaiy segment of thick ascenuing limb - wheie the NaK-2Cl pump is -
which is wheie loop uiuietics block. The NaK-2Cl pump geneiates fiee watei. The
two type of watei in uiine: obligateu anu fiee. If the watei is obligateu, then the
watei is obligateu to go out with eveiy Na, K, anu Cl (concentiateu uiea). Basically 2u
ml's of obligateu watei foi eveiy Na, K, Cl (it's obligateu) via NaK2Cl pump. The
ABB hoimone absoibs fiee watei bc the pump geneiates fiee watei.
Let's say you absoib one Na, how much fiee watei is left behinu in the uiine. - 2u
mls; then ieabsoibeu anothei K, that is anothei 2u, so its up to 4u; anothei 2 Cl's aie
ieabsoibeu which is anothei 4u; theiefoie, foi absoibing one Na, one K, anu 2 Cl's,
you have taken 8u mls of fiee watei fiom the uiine - this is fiee watei that is
geneiateu; its is this pump that loop uiuietics block, which is in the thick ascenuing
limb of the meuullaiy segment.
B. Lung iepaii cell is type II pneumocyte (can also iepaii type I pneumocytes); it
also synthesizes suifactant.
C. CNS - iepaii cell is the astiocyte; the astiocyte piolifeiates (bc it's a stable cell,
not a neuion), that can piolifeiate anu piouuces piotoplasmic piocesses - calleu
gliosis (ixn to injuiy in the biain, which is uue to astiocyte piolifeiation); this is
analogous to fibioblasts laying collagen type S in the wounu.
B. PNS - wallaiian uegeneiation is the mech of axonal iegeneiation
In PNS, have Schwann cells, while in the CNS, have oligouenuiocytes
(both make myelin). Tumoi Schwann cell = schwannoma; if it involves CN vIII it is
calleu acoustic neuioma. What genetic uz that is auto uominant has association.
Neuiofibiomatous.
(Siue note: myasthenia giavis - tensilon injection will inciease Ach in synapses in
eyelius, anu myasthenic ciisis will enu)
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A. ESR - putting whole bloou into cylinuei anu see when it settles. The highei the
uensity, oi weight, theiefoie settle pietty quick anu theiefoie have a inciease
seuimentation iate. When stuck togethei anu looks like coins = ioulouex. When
aggiegateu togethei = incieaseu seu iate, which is incieaseu Igu anu fibiinogen
(incluues eveiy acute anu chionic inflammation theie is. What causes RBC's to
clump - IgN, bc the neg chaige noimally keeps RBC's fiom stick to eo. IgN is a lot
biggei; colu agglutinins aie associateu with IgN ab, leauing to agglutinin. This is why
in colu whethei, you get Raynauu's phenomenon (lips, nose, eais, toes, fingeis tuin
blue). The IgN ab can cause colu agglutinins, leauing to ischemia. Anothei type of
clumping of IgN aie Ciyoglobulins - Ig's congeal in colu weathei; IgN ab's uo the
same thing. Bigh assoc of hep C with ciyoglobulins. Nult myleoma = incieaseu esi
bc incieaseu Igu; with waluenstioms, will see incieaseu IgN (Waluenstiom's
Nacioglobemia).
B. Acute appenuicitis - get CBC, anu want to see absolute neutiophilic leukocytosis,
meaning that you have an inciease of neutiophils in the peiipheial bloou; also
looking foi toxic gianulation, anu a LEFT SBIFT. Assuming you stait fiom myeloblast
on the left, anu eventually foim a segmenteu neutiophil on the iight; noimally go left
to iight on matuiation; theiefoie, with a left shift, its means that we go back to
immatuie neutiophils; the uefinitions is gieatei than 1u% banu neutiophils is
consiueieu a LEFT SBIFT (all the neutiophils aie banus); if you have just one
metamyelocyte oi one myelocyte, its is automatically consiueieu a LEFT SBIFT. In
acute appenuicitis, theie is an absolute inciease in neutiophils, with toxic
gianulation anu a left shift.
C. Nost potent system foi killing bugs = 0
2
uepenuent myelopeioxiuase system;
Nyelopeioxiuase is locateu in azuiophilic gianules, which aie lysosomes.
Want a lot of lysosome in an acute inflammatoiy ixn, bc theiefoie theie is moie
myelopeioxiuase aiounu foi killing bugs - this is what toxic gianulation.
Theiefoie, toxic gianulation ensuies that theie is enough myelopeioxiuase to woik
that potent system to kill bugs (0
2
uep myelopeioxiuase system).
CHAPTER 3: Fluid And Hemodynamics
@) ZA,.' - excess fluiu in the inteistitial space, which is extiacellulai fluiu (ECF);
this is outsiue the vessel
() +"#,/ $= ZA,.'
1. Non-Pitting euema - incieaseu vessel peimeability with pus in the inteistial
space (pus=exuuates). Lymphatic fluiu is anothei type of non-pitting euema.
Blockage of lymphatics leaus to lymphatic fluiu in the inteistial space. Pits eaily, but
eventually becomes nonpitting. Exuuates anu lymphatic fluiu uoes not pit.
2. Pitting euema - tiansuuate with iight heait failuie, swelling of the lowei
extiemities, fluiu in the inteistial space. Tiansuuate uoes pit.
S. So theie aie thiee things that cause euema: exuuates, lympheuema, anu
tiansuuate, anu tiansuuates aie the only one that has pitting euema.
V) +-'4/<A'6,R:&66&43 ZA,.'
Tiansuuate ueals with stailing foices:
1. What keeps fluiu in oui bloou vessels. Albumin, anu this is calleu oncotic
piessuie. 8u% of oui oncotic piessuie is ielateu to the seium albumin levels.
Anytime theie is hypoalbuminemia then we will have a leaking of a tiansuuate
(piotein of less than S guL) leaking into inteistial space via capillaiies anu venules
(pitting euema);
2. Noimally, hyuiostatic piessuie is tiying to push fluiu out. Theiefoie, in a noimal
peison, oncotic piessuie is winning. Theiefoie, a ueciease in oncotic piessuie anu
an inciease in hyuiostatic piessuie will leau to tiansuuate (pitting euema).
S. Albumin is maue in the livei. With chionic livei uz (ciiihosis), have a uecieaseu
albumin level. Can you vomit it out. No. Can ciap it out (malabsoiption synuiome),
oi can pee it out (nephiotic synuiome), can come off oui skin (S
iu
uegiee buin bc
losing plasma), anothei possibility of low piotein ct (low-intake) is seen in kius -
Kwashioikoi - kiu has fatty livei anu uecieaseu piotein intake, leauing to low
albumin level.
4. Examples:
a. Peison with NI 24 his ago anu he uieu anu he has fluiu coming out- tiansuuate
bc incieaseu hyuiostatic piessuie anu left BF uue to NI so things backeu up into the
lungs. Bc the C0 uecieaseu, the EBv incieases anu piessuie on left ventiicle
incieases, anu the piessuie is tiansmitteu into the left atiium, to the pul vein, keeps
backing up, anu the hyuiostatic piessuie in the lung appioaches the oncotic
piessuie, anu a tiansuuate staits leaking into the inteistitial space, which leaus to
activation of the } ieceptoi, which will cause uyspnea. Leaus to full blown in alveoli
anu pulmonaiy euema, which is what this is.
b. venom fiom bee sting on aim leaus to exuuate uue to anaphylactic ixn (face
swelleu), with histamine being the piopagatoi, anu type one BPY, causing tissue
swelling. Rx - aiiway, 1:1uuu aqueous epinephiine subcutaneously
c. ciiihosis of livei, with swelling of the legs: tiansuuate, mechanism: uecieaseu
oncotic piessuie bc cannot syn albumin, anu incieaseu hyuiostatic piessuie bc
poital BTN; theie is ciiihosis of the livei, anu the poital vein empties into the livei;
in this case, it cannot, anu theie is an inciease in hyuiostatic piessuie, pushing the
fluiu out into the peiipheial cavities (so theie aie 2 mech foi acites). Pitting euema
in legs: uecieaseu in oncotic piessuie
u. Pt with uepenuent pitting euema: pt has iight heait failuie, anu theiefoie an
inciease in hyuiostatic piessuie; with iight heait failuie, the bloou behinu the faileu
iight heait is in the venous system; ciiihosis of livei is uue to ueciease in oncotic
piessuie.
e. mouifieu iauical mastectomy of that bieast, with nonpitting euema: lympheuema.
0thei causes - w. banciofti, lymphogianulomon venaiium (subtype of chylamuia
tiachomata- scaiiing tissuie anu lymphatics, leauing to lympheuema of sciotum
lymphatic). Inflammation caicinoma of bieast (p'eau ue oiange of the bieast) ueals
with ueimal lymphatics plug with tumoi; excess leaus to uimpling, anu looks like the
suiface of an oiange. NCC lympheuema = postiauical mastectomy; can also iun iisk
of lymphangiosaicoma.
@@) D,4'; :?"/&$
() Z>TR@>T
ECF (1S) = extiacellulai fluiu of two compaitments - vasculai (1S) anu
inteistitial (2S)
ICF (2S) = intiacellulai fluiu compaitment
Example: how many liteis of isotonic saline uo you have to infuse to get 1 litei into
the plasma. S Liteis (2S:1S ielationship); 2 liteis in inteistial space, anu 1 L woulu
go to the vasculai space; it equilibiates with inteistialvasculai compaitments.
V) 2/.$;';&6" = measuie of solutes in a fluiu; uue to thiee things: Na, glucose, anu
bloou uiea nitiogen (B0N) - uiea cycle is locateu in the livei, paitly in the cytosol
anu paitly in the mitochonuiia; usually multiply Na times 2 (bc one Na anu one Cl).
Auuio File 6: Fluiu Anu Bemouynamics 2
Noimal Na is 1SS-14u iange, times that by 2 that 28u. Foi glucose, noimal is 1uu
uiviue that by 18, let's say it's ioughly S, so that's not contiibuting much. B0N:
locateu in the livei, pait of the cycle is in the cytosol anu pait of it is in mitochonuiia.
The uiea comes fiom ammonia, that's ammonia is gotten iiu of, by uiea. Bc the enu
piouuct of the uiea cycle is uiea. The noimal is about 12; uiviue that by S, so we
have 4. Theiefoie, in a noimal peison Na is contiolling the plasma osmolality. To
measuie seium osmolality: uouble the seium Na anu auu 1u.
>) 2/.$/&/
2 of these S aie limiteu to the ECF compaitment; one can equilibiate between ECF
anu ICF acioss the cell membianes - uiea; theiefoie, with an incieaseu uiea, it can
equilibiate equally on both siues to it will be equal on both siues; this is uue to
osmosis. Bc Na anu glucose aie limiteu to the ECF compaitment, then changes in its
concentiation will iesult in the movement of WATER fiom low to high concentiation
(opposite of uiffusion - ie in lungs, 1uu mmBg in alveoli of 0
2
, anu ietuining fiom the
tissue is 4u mmBg p0
2
; 1uu vs. 4u, which is biggei, 1uu is biggei, so via uiffusion, 0
2

moves thiough the inteispace into the plasma to inciease 0
2
to about 9SmmBb).
Theiefoie, in uiffusion, it goes fiom high to low, while in osmosis, it goes fiom low to
high concentiation.
1. Example: In the case with hyponatiemia - watei goes fiom ECF into the ICF, bc
the lowei pait is in the ECF (hence BYP0natiemia); watei goes into the ICF, anu
theiefoie is expanueu by osmosis. Now make believe that the biain is a single cell,
what will we see. ceiebial euema anu mental status abnoimalities via law of osmosis
(the intiacellulai compaitment of all the cells in the biain woulu be expanueu)
2. Example: hypeinatiemia - watei goes out of the ICF into the ECF, theiefoie the
ICF will be contiacteu. So in the biain, it will leau to contiacteu cells, theiefoie
mental status abnoimalities; theiefoie, with hypo anu hypeinatiemia, will get
mental status abnoimalities of the biain.
S. Example: BKA - have (1uuumg) laige amount bloou sugai. Remembei that both
Na anu glucose aie limiteu to the ECF compaitment. You woulu think that glucose is
in the ICF but it's not. You think that since glycolysis occuis in the cytosol theiefoie
glucose in the ICF (again its not) bc to oiuei to get into the cell (intiacellulai),
glucose must binu to phosphoius, geneiating u6P, which is metabolizeu (it's the
same with fiuctose anu galactose, which aie also metabolizeu immeuiately,
theiefoie, theie is no glucose, fiuctose, oi galactose, pei se, intiacellulaily). So, with
hypeiglycemia, theie is high glucose in the ECF, so watei will move fiom ICF to ECF.
Theiefoie, the seium Na concentiation will go uown - this is calleu uilutional
hyponatiemia (which is what happens to the seium souium with hypeiglycemia).
Theiefoie the two things that contiol watei in the ECF aie Na anu glucose; but a
noimal situation, Na contiols. 0iea uoes not contiol watei movements bc its
peimeable, anu can get thiough both compaitments to have equal concentiations on
both siues.
G) +$4&5&6" - isotonic state, hypotonic state, anu hypeitonic state
We have all uiffeient types of saline: Isotonic saline, hypotonic saline (12 noimal
saline, noimal saline, S% uextiose in watei), anu hypeitonic saline (S%, S%);
noimal saline is u.9%. We aie iefeiiing to noimal tonicity of the plasma, which is
contiolleu by the seium Na. These aie the thiee types of tonicity (iso, hypo, anu
hypei). Seium Na is a ieflection of total bouy Na uiviueu by total bouy B
2
u. Foi
example: hypeinatiemia is not just causeu by incieaseu total bouy Na; it can also be
causeu by uecieasing total bouy watei with a noimal total bouy Na, theiefoie theie
is an inciease in seium Na concentiation. It is ieally a iatio of total bouy Na to total
bouy B
2
u. To ueteimine seium Na, just look at seium levels. With uiffeient fluiu
abnoimalities, can lose oi gain a ceitain tonicity of fluiu.
1. @/$6$4&5 ;$// $= U;<&A - look at iatio of total bouy Na anu watei; in this case, you
aie losing equal amounts of watei anu Na, hence IS0tonic. This fluiu is mainly lost
fiom the ECF. The seium Na concentiation is noimal when losing isotonic fluiu. ECF
woulu look contiacteu. Theie woulu be no osmotic giauient moving into oi out of
the ECF. Clinical conuitions wheie theie is an isotonic loss of fluiu: hemoiihage,
uiaiihea.
If we have an &/$6$4&5 3'&4, we have in equal inciease in salt anu watei; ie someone
getting too much isotonic saline; noimal seium Na, excess isotonic Na woulu be in
the ECF, anu theie woulu be no osmotic giauient foi watei movement.
2. !"#$6$4&5 /$;<6&$4/ - by uefinition, it means hyponatiemia. Bypoglycemia will
not piouuce a hypotonic conuition. NCC of low osmolality in plasma is
hyponatiemia. Bow. Lose moie salt than watei, theiefoie, seium Na woulu be
uecieaseu. If losing moie salt than watei, kiuney is piobably the location of wheie
why it is happening. Nain place to ueal with souium (eithei to get iiu of it oi to get it
back) is in kiuney, esp when uealing with uiuietics (fuiosemiues anu BCTZ). The
tonicity of solution you lose in youi uiine is BYPERtonic, so that's how you enu up
with hyponatiemia with a hypotonic conuition. ECF concentiation is low with
hyponatiemia, theiefoie the watei will move into the ICF compaitment. (0smosis-
iemembei low to high)
Example: If you gaineu puie watei, anu no salt, you have ieally loweieu youi
seium Na: NCC = SIABB - in small cell caicinoma of the lung; you gain puie watei b
c ABB ienueis the uistal anu the collecting tubule peimeable to fiee watei. With
ABB piesent, will be ieabsoibing watei back into the ECF compaitment, uiluting the
seium Na, anu the ECF anu ICF will be expanueu. The ECF is expanueu uue to watei
ieabsoiption, anu the ICF is expanueu bc it has a high concentiation levels (its
levels aie not uiluteu). This can leau to mental status abnoimalities. Theiefoie, the
moie watei you uiink, the lowei youi seium Na levels woulu be. The tieatment is by
iestiicting watei. Bon't want to iestiict Na bc the Na levels aie noimal. When ABB
is piesent, you will C0NCENTRATE youi uiine bc taking fiee watei out of uiine;
with absent ABB, lose fiee watei anu the uiine is uiluteu. Theiefoie, foi with SIABB,
watei stays in the bouy, goes into the ECF compaitment, anu then move into the ICF
compaitment via osmosis. The lowest seium souium will be in SIABB. 0n the
boaius, when seium Na is less than 12u, the answei is always SIABB. Example: pt
with SIABB, not a smokei (theiefoie not a small cell caicinoma), theiefoie, look at
uiugs - she was on chloipiopiamiue, oial sulfyluieas piouuce SIABB.
Example: uain both watei anu salt, but moie watei than salt, leauing to
hyponatiemia - these aie the pitting euema states - ie RBF, ciiihosis of the livei.
When total bouy Na is incieaseu, it always piouuces pitting euema. What
compaitment is the total bouy Na in. ECF What is the biggest ECF compaitment.
Inteistial compaitment. Theiefoie, inciease in total bouy Na will leau to expansion
of inteistial compaitment of the ECF, watei will follow the Na, theiefoie you get
expansion via tiansuuate anu pitting euema; seen in iight BF anu ciiihosis.
Example: hypeitonic loss of salt (fiom uiuietic) leaus to hyponatiemia
Example: SIABB (gaining a lot of watei) leaus to hyponatiemia
Example: gaining moie watei than salt will leau to hyponatiemia: pitting euema
S. !"#,-6$4&5 /6'6, - by uefinition, have too much Na (hypeinatiemia) oi have
hypeiglycemia (ie pt with BKA has a hypeitonic conuition, which is moie common
than hypeinatiemia). With hypeinatiemia, what uoes ICF look like. It will always be
contiacteu oi shiunken.
Piimaiy aluosteionsim - gain moie salt anu watei.
Biabetes insipiuus - Lose puie watei (vs. gaining puie salt in SIABB). If you lose
moie watei than salt in the uiine, you have osmotic uiuiesis - mixtuie. When theie
is glucose anu mannitol in the uiine, you'ie losing hypotonic salt solution in uiine.
Example: Baby uiaiihea = hypotonic salt solution (auult uiaiihea is isotonic),
theiefoie, if baby has no access to watei anu has a iotaviius infection, seium souium
shoulu be high because losing moie watei than salt, leauing to hypeinatiemia.
Bowevei, most moms give the baby watei to coiiect the uiaiihea; theiefoie the baby
will come in with noimal seium Na oi even hyponatiemia bc the uenominatoi
(B
2
0) is incieaseu. Tieatment is peuialyte anu uatoiaue - these aie hypotonic salt
solution (just give them back what they lost). What has to be in peuialyte anu what
has to be in uatoiaue to oiuei to ieabsoib the Na in the uI tiact. ulucose bc of the
co-tianspoit. With the co-tianspoit, the Na BAS to be ieabsoibeu with glucose oi
galactose. Example: choleia, in oial ieplacement, neeu glucose to ieabsoib Na bc
co-tianspoit pump locateu in the small intestine. uatoiaue has glucose anu suciose
(which is conveiteu to fiuctose anu glucose).
Sweat = hypotonic salt solution; if you aie sweating in a maiathon, you will have
hypeinatiemia
Z) F$;<., >$.#'-6.,46/
Aiteiial bloou volume is same as stioke volume anu C0 (caiuiac output). When C0
uecieases, all physiologic piocesses occui to iestoie volume. With ueciease C0 (ie
hypovolemia), oxygenateu bloou will not get to tissues, anu we can uie. Theiefoie,
volume is essential to oui bouies.
We have baioieceptois (low anu high piessuie ones). The low piessuie ones aie
on the venous siue, while the high piessuie ones aie on the aiteiial siue (ie the
caiotius anu aich of aoita). They aie usually inneivateu by CN 9 anu 1u (the high
piessuie ones). When theie is a ueciease in aiteiial bloou volume (uecieaseu Sv oi
C0), it will unuei fill the aich vessels anu the caiotiu; insteau of 9
th
oi 1u
th
neive
iesponse, you have a sympathetic NS iesponse, theiefoie catecholamines aie
ieleaseu. This is goou bc they will constiict the venous system, which will inciease
bloou ietuining to the iight siue of the heait (uo not want venouilation bc it will
pool in youi legs). Catecholamines will act on the beta auieneigic ieceptois on the
heait, which will inciease the foice of contiaction, theie will be an inciease in stioke
volume (slight) anu it will inciease heait iate ("+" chionotiopic effect on the heait,
inciease in systolic BP). Aiteiioles on the systemic siue: stimulate beta ieceptois in
smooth muscle. Biastolic piessuie is ieally uue to the amount of bloou in the aiteiial
system, while you heait is filling with bloou. Who contiols the amount of bloou in
aiteiiole system, while youi heait is filling in uiastole. Youi peiipheial iesistance
aiteiioles - that maintains youi uiastolic bloou piessuie. So, when they aie
constiicteu, veiy little bloou is going to the tissues (bau news); goou news: keep up
uiastolic piessuie - this is impoitant bc the coionaiy aiteiies fill in uiastoles. This is
all uone with catecholamines. Renin system is activateu by catecholamines, too;
angiotensin II can vasoconstiictoi the peiipheial aiteiioles (theiefoie it helps the
catecholamines). Au II stimulates 18 hyuioxylase, which conveits coiticosteione
into aluosteione, anu stimulates aluosteione ielease, which leaus to ieabsoiption of
salt anu watei to get caiuiac output up.
With uecieaseu Sv, ienal bloou flow to the kiuney is uecieaseu, anu the RAA can be
stimulateu by this mechanism, too. Wheie exactly aie the ieceptois foi the
juxtaglomeilui appaiatus. Affeient aiteiiole. Theie aie sensois, which aie mouifieu
smooth muscle cells that sense bloou flow. ABB will be ieleaseu fiom a neive
iesponse, anu puie watei will inciease but that uoes not help with incieasing the
caiuiac output. Neeu salt to inciease C0.
Example: bleeuing to ueath anu theie is a loss of S L's of fluiu - how can you keep
BP up. uive noimal saline is isotonic theiefoie the saline will stay in the ECF
compaitment. Noimal saline is plasma without the piotein. Any time you have
hypovolemic shock, give noimal saline to inciease BP bc it stays in the ECF
compaitment. Cannot iaise BP with V noimal saline oi S% uextiose; have to give
something that iesembles plasma anu has the same tonicity of plasma. Noimal saline
is u.9%.
Peiitubulai capillaiy piessuies: you ieabsoib most of the souium in the pioximal
tubule (6u-8u%). Wheie is the iest absoibeu.; in the uistal anu collecting tubule by
aluosteione. The Na is ieabsoibeu into the peiitubulai capillaiies. Stailing foices in
the capillaiies must be amenable to it. Two stailing foices: oncotic piessuie (keeps
fluius in the vessel) anu hyuiostatic (pushes fluius out of vessel).
Example: When ienal bloou flow is uecieaseu (with a uecieaseu Sv anu C0), what
happens to the peiitubulai capillaiy hyuiostatic piessuie. It uecieases. Theiefoie,
the peiitubulai oncotic piessuie is incieasing (ie the foice that keeps fluius in the
vessel), anu that is iesponsible foi ieabsoiption of anything into the bloou stieam
fiom the kiuney. This is why P0 (peiitubulai oncotic piessuie) > PB (hyuiostatic
piessuie of peiitubulai capillaiy), allows absoiption of salt containing fluiu back into
bloou stieam into the kiuney.
Tonicity of fluiu ieabsoibing out of pioximal tubule is isotonic (like giving noimal
saline). ABB is ieabsoibing isotonic salt solution, but not as much as the pioximal
tubule. ABB contiibutes puie watei, theiefoie, with all this ieabsoiption you have
an isotonic sol'n auu the ABB effect anu the pt becomes slightly hyponatiemic anu
hypotonic, theiefoie absoibs into the ECF compaitment when theie is a uecieaseu
C0.
0pposite Example: incieaseu Sv, anu inciease aiteiial volume, will leau to stietch of
baioieceptois (inneivateu by 9
th
anu 1u
th
neive), anu a paiasympathetic iesponse
will be eliciteu, insteau of a sympathetic iesponse. Theie will not be any
venuloconstiiction noi any inciease in the foice of contiaction of the heait. This is
fluiu oveiloau; theiefoie we neeu to get iiu of all the volume. Theie is incieaseu
ienal bloou flow, so the RAA will not be activateu. Fluiu oveiloau uoes not ABB be
ieleaseu. The peiitubulai hyuiostatic piessuie is gieatei than the oncotic. Even of
the pt absoibeu salt, it woulun't go into the bloou stieam, anu it woulu be pee'u out.
Theiefoie pt is losing hypotonic salt solution with incieaseu in aiteiial bloou volume.
Neeu to know what happens if theie is uecieaseu C0, what happens when ANP is
ieleaseu fiom the atiia, anu give off uiuietic effect; it wants to get iiu salt. ANP is
only ieleaseu in volume oveiloaueu states.
Example: pt given S% hypeitonic saline: what will happen to osmolality. Inciease.
What will that uo to seium ABB. Inciease - inciease of osmolality causes a ielease of
ABB.
Example: What happens in a pt with SIABB. uecieaseu plasma osmolality, high
ABB levels.
Example: What happens in a pt with BI. no ABB, theiefoie, seium Na incieases,
anu ABB is low
Bow to tell total bouy Na in the pt: Two pics: - pt with uiy tongue = theie is a
ueciease in total bouy Na, anu the pt with inuentation of the skin, theie is an inciease
in total bouy Na. Behyuiation: Skin tuigui is piefoimeu by pinching the skin, anu
when the skin goes uown, this tells you that total bouy Na is noimal in inteistial
space. Also look in mouth anu at mucous membianes.
If you have uepenuent pitting euema that means that theie is an inciease in total
bouy Na.
SIABB - gaining puie watei, total bouy souium is noimal, but seium Na is low; have
to iestiict watei.
Right BF anu uepenuent pitting euema - fluiu kiuney ieabsoibs is hypotonic salt
solution with a uecieaseu C0 (little moie watei than salt), theiefoie seium Na will
low. Numeiatoi is incieaseu foi total bouy souium, but uenominatoi has laigei
inciease with watei.
What is nonphaimalogical Rx of any euema states. (ie RBFlivei uz) - iestiict salt
anu watei
What is the Rx foi SIABB = iestiict B
2
0
What is the Rx foi any pitting euema state. Restiict salt anu watei
Phaimacological Rx foi pitting watei - uiuietics (also get iiu of some salt).
@@@) [?$5P
() >'</,/ $= ?"#$J$;,.&5 /?$5P - uiaiihea, bloou loss, choleia, sweating, not BI
(bc losing puie watei, anu not losing Na, total bouy Na is N0RNAL! Losing watei
fiom ICF; no signs of uehyuiation; when you lose salt, show signs of uehyuiation).
Example: lauy with hypovolemic shock - when she was lying uown, hei BP anu
pulse weie noimal; when they sat hei up, the BP uecieaseu anu pulse went up. What
uoes this inuicate. That she is volume uepleteu. This is calleu the TILT test. Noimal
BP when lying uown bc theie is no effective giavity, theiefoie noimal bloou
ietuining to the iight siue of the heait, anu noimal C0. Bowevei, when you sit the
patient up, anu impose giavity, you ueciease the venous ietuin to iight heait. So, if
you aie hypovolemic, it will show up by a ueciease in BP anu an inciease in pulse.
Caiuiac output is uecieaseu, anu the catecholamine effect causes this scenaiio.
Bow woulu you Rx. Noimal saline.
Auuio File 7: Fluiu Anu Bemouynamics S
Example: pt collapses, anu you uo a tilt test: 1uu8u anu pulse of 12u while lying
uown. Sitting up, it was 7u6u anu pulse of 1Su. The pt is seveiely hypovolemic,
theiefoie Rx is noimal saline. Tieatment: 0ne litei in, showeu no signs, put anothei
litei anu the BP becomes noimal, anu is feeling bettei, but still signs of volume
uepletion (uiy mouth). We have the BP stabilizeu, but the pt lost hypotonic salt
solution, theiefoie we neeu to ieplace this. So on Iv, give hypotonic salt sol'n (bc
was losing hypotonic salt solution). We uo not give S% uextiose anu watei bc
theie's not any salt in it. Theiefoie, we will give V noimal saline. The tieatment
piotocol is: when a pt loses something, you ieplace what they lost. Anu when pt is
hypovolemic, always give isotonic saline.
Example: BKA, have osmotic uiuiesis; tonicity of fluiu in the uiine that has excess
glucose is hypotonic. Bypotonic fluiu has a little moie fluiu than salt. So the pt is
seveiely hypovolemic; theiefoie the fiist step in management is coiiection of volume
uepletion. Some people aie in hypovolemic shock fiom all that salt anu watei loss.
Theiefoie neeu to coiiect hypovolemia anu then coiiect the bloou sugai levels (BKA
pts lose hypotonic solution). Theiefoie, fiist step foi BKA pt is to give noimal saline
bc you want to make them noimo-tensive. Bo not put the pt on insulin bc it's
woithless unless you coiiect the hypovolemia. It can take 6-8 liteis of isotonic saline
befoie the bloou piessuie staits to stabilize. Aftei pt is feeling bettei anu the pt is
fine volume wise. Now what aie we going to uo. The pt is still losing moie watei
than salt in uiine, theiefoie still losing a hypotonic salt solution, theiefoie neeu to
hang up an Iv with V noimal saline (ie the iatio of solutes to watei) anu insulin (bc
the pt is loosing glucose).
So, fiist thing to uo always in a pt with hypovolemic shock is noimal saline, to get
the BP noimal. Then to coiiect the pioblem that causeu the hypovolemia. It
uepenus on what is causing the hypovolemia (ie if pt is sweating, give hypotonic salt
solution, if uiaiihea in an auult give isotonic salt sol'n (ie noimal saline), if pt with BI
(ie stable BP, pt is luciu) give watei (they aie losing watei, theiefoie give S%
uextiose (ie Su% glucose) anu watei).
V) T$<- P&4A/ $= /?$5P:
1. Bypovolemic shock: bloou loss, uiaiihea (auult oi chilu), basically whenevei you
aie lose salt, you coulu enu up with hypovolemic shock
2. Caiuiogenic shock: NC uue to NI
S. Neuiogenic shock: assoc. with spinal coiu injuiies
4. Septic shock: NC uue to E. coli; also NCC sepsis in hospital anu is uue to an
inuwelling of the uiinaiy cathetei. Staph auieus is not the NC cause of Iv ielateu
septicemia in the hospital, E.Coli wins hanus uown. Enuotoxin in cell wall is a
lipopolysachaiiue, which aie seen in giam negative bacteiia. The lipius aie
enuotoxins. Theiefoie, giam negatives have lipius (enuotoxins) in theii cell wall,
giam positive uo not. S0 if you have E.Coli sepsis, you will have big time pioblems,
anu is calleu septic shock.
S. Classical clinical piesentations:
a) Bypovolemic anu caiuiogenic shock: you woulu see colu anu clammy skin, bc of
vasoconstiiction of the peiipheial vessels by catecholamines (ielease is uue to the
ueciease in Sv anu C0) anu Au II. These will vasoconstiict the skin anu ieuiiect the
bloou flow to othei impoitant oigans in the bouy like biain anu kiuneys, leauing to a
colu clammy skin. BP is uecieaseu, pulse is incieaseu.
b) Pouseau's laws: is a concept that teaches you about peiipheial iesistance of
aiteiioles which contiol the uiastolic bloou piessuie.
TPR = Total peiipheial iesistance of the aiteiioles
v = viscosity
i = iauius of the vessel to the 4
th
powei
The main factoi contiolling TPR is iauius to the 4
th
powei
What contiols the viscosity in the bloou. Bb. So if you aie anemic, viscosity of
bloou is uecieaseu (ie low hemoglobin), anu if you have polycythemia (high
hemoglobin), viscosity will be incieaseu. Theiefoie, TPR in anemia will ueciease,
anu in polycythemia will inciease.
c) Septic shock - Theie is a ielease of enuotoxins which activates the alteinative
complement system. The complement will eventually ielease CSa anu CSa which aie
anaphylatoxins, which will stimulate the mast cells to ielease histamine. The
histamine causes vasouilation of aiteiioles (the same ones of the peiipheial
iesistance aiteiioles). Theiefoie bloou flow is incieaseu thioughout the peiipheial
iesistance aiteiioles anu the skin feels waim. The enuotoxins also uamage the
enuothelial cells; as a iesult, two potent vasouilatois (N0 anu PuI
2
) aie ieleaseu.
Theiefoie, 2 oi S vasouilatois aie ieleaseu, anu affect the TPR to the fouith powei.
Theiefoie, the TPR will ueciease (uue to vasouilation).
TPR aiteiioles contiol youi uiastolic BP bc when they aie constiicteu; they contiol
the amount of bloou that iemains in the aiteiial system while youi heait is filling up
in uiastole. Theiefoie, when the TPR aiteiioles aie uilateu, the uiastolic BP will pan
out.
Think of a uam (with gates): if all the gates aie wiue open all that watei will come
gushing thiough. This is what happens to the aiteiioles when they aie uilateu. The
bloou gushes out anu goes to the capillaiy tissues, supposeuly feeuing all the tissues
with 0
2
. Think in the context of fishing: when the uam wall opens, all the watei
iushes thiu causing tuibulent wateis, theiefoie this woulu be a bau time to go
fishing. The fishes woulu be tiying to save themselves. That is what the 0
2
is uoing.
Theiefoie, with all this bloou going by, the tissues cannot extiact 0
2
bc it is going
too fast anu bc it isn't a contiolleu ielease of bloou. Theiefoie, the bloou is coming
back to the iight siue of the heait fastei than usual, bc all the aiteiioles aie wiuely
uilateu. Bue to the bloou going back to the heait fastei, the caiuiac output is
incieaseu. This is seen in septic shock anu the skin feels waim bc the vessels aie
uilateu. Theiefoie, with septic shock, theie is a BIuB output failuie, with waim skin.
Bowevei, in hypovolemic anu caiuiogenic shock, the caiuiac output is uecieaseu
(bc the vessels aie constiicteu by catecholamines anu angiotensin II), anu the skin
feels colu anu clammy.
>) [L'4 3'4] 5'6?,6,- is inseiteu in the iight siue of the heait anu it measuies all
paiametei that is taught in physiology. All of these things aie measuieu in a swan
ganz cathetei.
1. Caiuiac 0utput: measuieu by swan ganz
2. Systemic vasculai iesistance: this is a calculation. The basically measuies the
TPR, ie measuies what aiteiioles aie uoing
S. Nixeu venous 0
2
content. You know noimally that the 0
2
content is equal to =
1.S4 x Bb x 0
2
sat'n + p0
2
. Neasuieu in RA with swan ganz cathetei; this is the BEST
TEST foi evaluating tissue hypoxia.
Caiuiac output in caiuiogenic anu hypovolemic shock is low, theiefoie, bloou not
being pusheu aheau with a gieat ueal of foice. So, tissue will have a lot of time to
extiact 0
2
fiom what little bloou that is being ueliveieu. As a iesult, mixeu venous 0
2

content in hypovolemic anu caiuiogenic shock will be uecieaseu ie veiy low bc the
bloou going thiough the vessels is veiy slow (no foice is helping to push it thiough).
Theiefoie, it extiacts moie 0
2
than noimal. Nixeu venous 0
2
content in septic shock
(when bloou is passing thiough vessels at a veiy fast iate) will leau to a BIuB mixeu
venous content (bc tissues unable to extiact 0
2
).
4. Pulmonaiy capillaiy weuge piessuie - measuies Left ventiiculai enu uiastolic
volume anu piessuie (EBv anu EBP). Cathetei in iight heait will tell you what the
piessuie is in the left ventiicle.
S. Biffeiences between Bypovolemic, Caiuiogenic, anu Septic Shock using swan
ganz cathetei:
C0 in hypovolemic anu caiuiogenic. both uecieaseu
C0 in septic shock. Incieaseu
Systemic vasc iesistance (TPR) is a measuie of what the ARTERI0LES aie uoing.
What is TPR in hypovolemic anu caiuiogenic shock. Incieaseu uue to
vasoconstiiction
TPR in septic shock. Becieaseu uue to vasouilation.
Nixeu venous in hypovolemic anu caiuiogenic. Low.
Nixeu venous in septic shock. Bigh.
Bow uo we sepaiate hypovolemic anu caiuiogenic.
Pulmonaiy capillaiy weuge piessuie (measuies left ventiiculai EBv)
In Bypovolemic, what is LvEBv. Low.
In Caiuiogenic, what is LvEBv. Bigh.
In Enuotoxin shock it's uecieaseu.
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1. Example: 0f all oigans in the bouy, which suffeis the gieatest uue to uecieaseu
BP. Kiuneys. What pait. Neuulla. Not the biain bc with uecieaseu C0, the ciicle of
willis will uistiibute bloou flow to ceitain aieas in the biain, especially the aieas
wheie theie aie neuions. Someone with hypovolemic, oi caiuiogenic, oi septic
shock: oliguiia, anu an incieaseu in B0NCieatine causes sugais in the bouy. This
occuis bc the patient is going into acute tubulai neciosis. Nephiologists want to
coiiect the ienal bloou flow, so that you can pievent ATN bc a pt can uie. What type
of neciosis. Coagulation neciosis. The ueau ienal tubules will slough off anu
piouuce ienal tubulai casts in the uiine which will block uiine flow, theieby
piouucing oliguiia. Theie is also a ueciease in uFR, leauing to ATN (chances of
suivival aie zeio). So it is the kiuneys that aie the most affecteu when the caiuiac
output is uecieaseu, ie uecieaseu bloou flow. Biain woulu be a close seconu to
neciosis. The heait has a bit of a collateial ciiculation as well.
2. Example: Pt with the sickle cell tiait can get kiuney uz; bc the ienal meuulla's 0
2

tension is low enough to inuuce sickling. Theiefoie if you have a young black woman
with micioscopic hematuiia coming to the office, what is fiist test you shoulu uo.
Sickle cell scieen, bc she piobably has the sickle cell tiait. Theiefoie, sickle cell tiait
has pioblems, bc 0
2
tension in ienal meuulla is low enough to inuuce sickling in
peiitubulai capillaiies, which piouuces micioinfaictions in the kiuneys. Theiefoie,
uon't want to piouuce Coagulation neciosis (aka ATN)
@F) (5&A^E'/, '4A V;$$A W'/
Aciuosis - inciease in B
+
ions, theiefoie ueciease in pB
Alkalosis - ueciease in B
+
ions, theiefoie inciease in pB
() Q,L ,Y<'6&$4 foi aciubase physio by uoljan:
V) >$.#,4/'6&$4 = bouies attempt to tiy to maintain a noimal pB (which it nevei
uoes). So if you want to keep pB ioughly noimal (assuming you coulu).
1. Example: if you have metabolic alkalosis (inciease in bicaib: which is in the
numeiatoi), then have to inciease uenominatoi (pC0
2
) to keep it noimal, theiefoie,
compensation is uue to iespiiatoiy (pC0
2
) aciuosis. A nice way of memoiizing it is
what is the opposite of metabolic. Respiiatoiy anu what is the opposite of aciuosis.
Alkalosis, anu vice veisa.
2. Example: if you have metabolic aciuosis (ueciease bicaib) what uo we have to uo
with the pC0
2
. We have to get iiu of it. If we ueciease the nominatoi, we have to
ueciease the uominatoi in oiuei foi the equation to stay the same. Theiefoie, we
have to blow off the C0
2
(hypeiventilation).
S. ventilation is a C0
2
teim!
Bypeiventilation = Inciease in iespiiatoiy iate allows foi the blowing off of C0
2
,
theiefoie iesults in iespiiatoiy alkalosis. Foi the tieatment of iespiiatoiy alkalosis is
to give the pt a papei bag anu ask to bieath in it, bc then they aie ie-bieathing theii
own C0
2
.
Bypoventilation = Beciease in iespiiatoiy iate allows foi the ietention of C0
2
,
theiefoie iesults in iespiiatoiy aciuosis.
Full compensation uoes not exist; you nevei biing back the pB to the noimal iange.
Theie is one exception: chionic iespiiatoiy alkalosis in high altituue; ie mountain
sickness (ie peiu).
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1. Things that ueal with C0
2
:
a) Respiiatoiy centei is in meuulla oblongata, which contiols the bieathing iate
b) 0ppei aiiways - if obstiucteu, theie will be a pioblem getting iiu of C0
2
.
c) Chest bellows - most imp muscle of iespiiation is uiaphiagm. 0n inspiiation: the
uiaphiagm goes uown, the negative intiathioacic piessuie incieases, anu aii is
suckeu into the lungs anu bloou is suckeu into the iight siue of the heait (this is why
neck veins collapse on inspiiation). Negative vacuum sucks bloou anu aii into youi
chest. 0n expiiation, theie is a "+" intiathiocic piessuie, pushing things out. It helps
the left heait to push bloou out anu it also helps the lungs by pushing out aii.
2. Examples:
(a) Baibituiates oi any uiug that uepiesses the iespiiatoiy centei will leaus to
iespiiatoiy aciuosis
(b) CNS injuiy to meuulla oblongata - iesp aciuosis
(c) Anxiety = NCC iesp alkalosis. When you take a test, sometimes you feel stiange,
anu get numb anu tingly, especially aiounu mouth anu on the tips of fingeis, anu
become twitchy (bc you aie in tetany) its all causeu by being alkalotic anu ionizing
calcium level gets lowei anu you ieally aie getting tetany. Theiefoie you become
twitchy anu paiesthesias (ie caipal peual sign oi tiousseau's sign aie both signs of
tetany). All uue to tetany bc of bieathing too fast fiom anxiety.
(u) Piegnant woman have iesp alkalosis bc estiogen anu piogesteione ovei
stimulate the iespiiatoiy centei. Locateu in the lungs aie spiuei angiomas uue to Av
fistulas ielateu to high estiogen, theiefoie cleai moie C0
2
pei bieath than a noimal
woman. A lot of shunting occuiiing within lungs. These spiuei angiomas go away
aftei ueliveiy of the baby.
(e) Enuotoxins ovei stimulate the system. All pts in enuotoxic shock have iesp
alkalosis. They aie also in anaeiobic metabolism, piouucing lactic aciu, theiefoie aie
also in metabolic aciuosis. Theiefoie, enuotoxic iesp alkalosis uue to
oveistimulation, anu metabolic aciuosis uue with noimal pB.
(f) Salicylate oveiuose - oveistimulate iesp centei, leauing to iesp alkalosis.
Salicylic aciu is an aciu, hence metabolic aciuosis, anu pB will be noimal bc they
balance eo out. (Tinnitus in salicylate 0B - also a NIXEB uisoiuei!)
(g) 6 yo chilu with inspiiatoiy stiiuei - uo a lateial x-iay, anu see thumbpiint sign,
with a swollen epiglottis. The uiagnosis is acute epiglottitis, uue to B. influenza;
vaccination has uecieaseu inciuence, hence you uon't see any ius with B. meningitis
bc of the vaccination. The NC of meningitis in 1 month - 18 yis = N. meningitis.
(h) S month olu - cioup, a laiygiotiacheobionchitis uz uue to paiainfluenza viius.
Want to uo a lateial x-iay anu see a steeple sign. Wheie is the obstiuction in cioup.
Tiachea
(i) Pt shoving foou in theii mouth (caf coionaiy) - Beimlich maneuvei; if they can
talk, leave alone anu let them cough it out.
(j) Biaphiagm inneivateu by the phienic neive - ie eib Buchene palsy, with
biachial plexus injuiy, anu chilu has iesp uifficulty, anu uiaphiagm on iight siue is
elevateu. Paialysis of the uiaphiagm will leau to incieaseu C0
2
.
(k)Lou uehiig's uz - amyotiophic lateial scleiosis uz, a LNN's anu 0NN's gone
theiefoie cannot bieath bc no inneivation to the uiaphiagm (ie uiaphiagm anu
inteicostals aie paialyzeu)
(l)uuillain-Baiie - ascenuing paialysis in a patient who a week ago hau a
iespiiatoiy infection. The spinal fluiu shows incieaseu piotein, slight inciease in
lymphocytes, anu a giam stain negative. Bz: uuillain-Baiie, uemyelinating uz
(o) Polio - uestioys LNN's anu eventually 0NN's. Theiefoie, anything that
paialyzes muscle of iesp will leau to iesp aciuosis.
(p) L0NuS: obstiuctive anu iestiictive lung uz's
0bstiuctive lung uz - pioblem getting aii out, compliance incieaseu anu elasticity is
uecieaseu, theiefoie, have a iesp aciuosis.
In iestiictive lung uz, ie Saicoiuosis anu pneumonocionioses, theie is a pioblem in
getting aii in theiefoie has a iesp alkalosis (.)
Auuio File 8: Fluiu Anu Bemouynamics 4 - Nutiition 1
Caisson's Bisease -0nueiwatei: foi eveiy Su ft, inciease 1 atm, (ie 76u at level, but
Su ft lowei it will be 2 atm); the ieveise is tiue when you go to high altituues - ie at
top of mt eveist, the atmospheiic piessuie is 2uu atm; still bieathing 21% 0
2
;
bieathing the same, but atmospheiic piessuie is uiffeient, uepenuing on wheie you
aie.
Foimula foi calculating: alveolai 0
2
= (u.21 x atmospheiic piessuie) - PC0
2
.8
Bigh Altituue: (.21 x 2uu) - 4ummBb.8 = 2mmBg of aii in alveoli, theiefoie will
have to hypeiventilate at high altituues, bc lowei pC0
2
= incieaseu P0
2
(you BAvE
to hypveiventilate otheiwise you uie).
Bowevei, when you go unuei, the atm piessuie incieases, anu the nitiogen gases
aie uissolveu in youi tissues, leauing to an inciease in piessuie. Ie 6u ft below, want
to get up fast; like shaking a soua bottle; as you ascenu, the gas comes out of fat in
bubbles; the bubbles get into tissues anu Bv's; this is calleu the benus; leaus to pain,
anu quauiiplegia, loss of blauuei contiol. Rx = hypeibaiic 02 chambei.
CHAPTER 4: Nutrition
@) Z'6&43 A&/$-A,-/ \ &45;<A,/ $E,/&6"_ '4$-,%&'_ E<;&.&'
Biffeience between anoiexia anu bulimia.
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Bistoiteu bouy image; women with anoiexia can have uistoiteu image; contiol
issue; they have lost contiol of eveiything in theii life, anu the only thing that they
can contiol ovei is what they put in theii mouth. With a ueciease of bouy fat anu wt,
unRB uecieases, theiefoie FSB anu LB also ueciease, leauing to low estiogen; as a
iesult, amenoiihea occuis, ANB pieuisposes to osteopoiosis, as if pt is
postmenopausal. Anoiexic people will eventually uevelop osteopoiosis.
Rx - convince peison to gain enough wt to biing peiiou back; not biith contiol.
(ie fiist step in management of BPuiabetes = wt loss; as you lose auipose, you
upiegulate insulin iesistance). In anoiexia, usually uie to caiuiac uz (heait failuie:
heait just stops).
V) V<;&.&' Q,-J$/'
1. Netabolic Alkalosis: It's not a bouy image pioblem - they can be obese, noimal
oi thin (no weight issue); howevei, they binge (eat a lot), then foice themselves to
vomit. Pic on boaius: fiom vomiting, weai uown enamel on teeth; so, biownish stuff
seen on teeth is just uentine (eiosions seen on teeth). Netabolic alkalosis fiom
foiceu vomiting will be seen. Netabolic alkalois is bau b.c theie is a left shift cuive,
anu the compensation is iesp aciuosis, which uiops p0
2
, theiefoie will get hypoxia
with metabolic alkalosis, anu the heait uo not like that. The heait alieauy with low
0
2
will get PvC's (pie-matuie ventiiculai contiactions), RRT phenom, then v-fib,
then ueath. Theiefoie, met alkalosis is veiy uangeious in inuucing caiuiac
aiiythmias, anu this commonly occuis in bulimics uue to foiceu vomiting. Pt can also
vomit out bloou - Nalloiy Weiss Synuiome - teai in uistal esophagus oi pioximal
stomach.
2. Boihave synuiome, which is woise. In the synuiome, theie is a iuptuie anu aii
anu secietions fiom the esophagus get into the pleuial cavity; the aii will uissect
thiough subcutaneous tissue, come aiounu the anteiioi meuiastinum, which leaus to
Bemimans ciunch - obseiveu when ui looks at pt's chest, puts a stethoscope uown,
anu you heai a 'ciunch'. The "ciunch" is aii that has uissecteu thiough inteistial
tissue up into the meuiastinum, inuicating that a iuptuie occuiieu in the esophagus;
this is anothei common thing in bulimics.
So, theie aie 2 things imp in bulimics: 1) Netabolic alkalosis fiom vomiting (which
can inuuce aiithymias 2) Boihave's synuiome
>) 2E,/&6": With obesity, using a uiff methou: BNI: kg's in bouy wtmeteis in bouy
ht'2. If youi BNI is Su oi gieatei, you aie obese; if youi bmi is 4u oi gieatei, you aie
moibiuly obese. Nain complication of obesity = BTN; with BTN, leaus to LvB, anu
potentially heait failuie. NCC ueath in BTN = caiuiac uz. 0thei complications of
obesity incluue: gallblauuei uz, canceis with a lot of auipose, you aiomatize many
17-ketosteioius like anuiosteneuione into estiogens. Theiefoie, will hypeiestiinism
(all obese women have hypeiestiinism), you aie at iisk foi estiogen ielateu canceis
- ie bieast cancei, enuometiial caicinoma, colon cancei.
@@) B';4<6-&6&$4
Piotein-caloiie malnutiition:
1. Naiasmus - total caloiie ueposition, anu wasting away of muscle; howevei, high
chance of suivival if they get foou
2. Kwashioikoi - piob gonna uie; have caibs, but no piotein; also have anemias,
cellulai immunity piobs (ie no ixn to ags), low albumin levels, ascites, fatty liveis.
These kius aie apathetic anu neeu to be foice-feu; theiefoie, kiu with kwashioikoi
is moie likely to uie than chilu with Naiasmus. Example: kiu with euema, flaky
ueimatitis, ieuuish haii (Cu uef) - kwashioikoi
@@@) F&6'.&4/
() G&==,-,45, E,6L,,4 ='6 '4A L'6,- /$;<E;, J&6'.&4/0
1. Fat soluble vitamins uissolve in fats, inuicating that they aie taken up by
chymlomicions. The chymlomicion will have A, B, E, anu, K bc these aie the fat
soluble vitamins. Fat soluble aie moie likely to be stoieu in fat, so the toxicity is
much gieatei, bc if it is watei soluble, we just pee it out.
NCC biight yellow uiine = vitamins
2. Watei soluble vitamins aie all cofactois foi biochemical ixn's.
V) T'6 /$;<E;, J&6'.&4/0
1) F&6'.&4 (
a. Function: Is veiy imp in chiluien foi giowth anu can have failuie to thiive in vit
A uef. veiy impoitant in iouopsinihouopsin within the eye anu the fiist sign of vit
A uef is night blinuness which is calleu nictolopia. vit A also pievents sq metaplasia.
b. Example of vit A uef: eye with sq metaplasia, goose bumps on back of aim calleu
folliculai hypeikeiatois. Eye is lineu with cuboiual epithelium; when you get sq
metaplasia, will get white spots on the eye. If become extensive, giow ovei eye, anu
can leau to softening of the coinea (keiatomalacia), anu leaus to blinuness. 2
nu
NCC
blinuness globally = vit A uef. NCC blinuness globally = tiachoma; NCC blinuness in
0SA = uiabetes. Theiefoie, vit A will pievent sq metaplasia, if you aie vit A ueficient
anu a nonsmokei, a peison can enu up with sq metaplasia in mainstem bionchus anu
bionchogenic caicinoma.
c. Toxicity: Bypeivitaminosis A - ex. big game huntei that eats beai livei anu has
heauaches. Incieaseu vit A causes ceiebial euema, also get papilloeuema (which
causes the heauache), can alsp leau to heiniation anu ueath. Theie is also an
inciease of ietinoic aciu (useu fiom tieating acne anu acute piogianulocytic anemia).
The ietinoic aciu toxicity can leau to seveie livei toxicity. Theiefoie,
hypeivitaminosis of vit A affects 2 aieas: 1) ceiebial euema (biain) 2) livei.
Example: if have young lauy pt on ietinoic aciu foi acne, neeu to check livei enzymes
anu ask foi heauaches (can be ueveloping papilloeuema oi ceiebial euema ielateu to
vit A toxicity). Nassive amount of vit A in beai liveis, anu huntei uies with massive
heauaches oi livei failuie
7) F&6'.&4 G = vERY imp on the boaius; NC souice of vit B is fiom sunlight.
a. Cholesteiol is the
1. Nain component of oui cell membianes
2. Staiting point foi making bile salts anu bile acius
S. Fiist compounu that staits the synthesis of steioiu hoimones in the auienal
coitex
4. Anu the 7-uehyuiocholesteiol in the skin is photoconveiteu to vitamin B.
Theiefoie we neeu cholesteiol! (makes bile salts, hoimones, cell membianes, anu
vit B).
b. Souice: Sun is the most imp souice of vit B. take baby out to expose to sunlight
(no vit B oi vit K in bieast milk, theiefoie must be supplementeu - expose to sun foi
vit B).
c. Synthesis of vitamin B: Reabsoibeu in the jejunum. 0nueigoes 2 hyuioxylation
steps; fiist is in the livei, wheie it is 2S hyuioxylateu anu the 2
nu
is in the kiuney anu
its 1 alpha hyuioxylase. What hoimone puts 1-alpha hyuioxylase in the pioximal
tubule. PTB. PTB is iesponsible foi synthesis of 1-a-hyuioxylase anu is synthesizeu
in the pioximal tubule. (ACE is fiom the enuothelial cells of the pulmonaiy capillaiy,
EP0 is fiom the enuothelial cells of the peiitubulai capillaiy). 1-a-hyuioxylase is the
2
nu
hyuioxylation step, anu now it is active (the fiist was in the kiuney).
u. vit B function: ieabsoib Ca anu phosphoius fiom the jejunum. It BAS to ieabsoib
both of these, bc its main job is mineializing bone anu caitilage. Bave to have
appiopiiate solubility piouuct to be able to uo that; Ca anu phosphoius aie
necessaiy to mineialize caitilage anu bone (like the osteoiu making bone).
Theiefoie, it makes sense to ieabsoib Ca anu phosphoius bc it neeus to make suie
that both of them aie piesent in auequate amounts to have an auequate solubility
piouuct to mineialize bone.
e. Paiathyioiu Boimone (PTB) - Functions: (1)is somewhat ielateu to vitamin B
metabolism, it helps last step foi hyuioxylation of vit B syn. (2) PTB will leau to
ieabsoiption of Ca in the eaily uistal tubule (this is also wheie Na is ieabsoibeu, anu
thiaziues block this channel). At that location, theie is a Ca channel; PTB helps
ieabsoiption of the Ca in this location. Ca has to 'take tuins' with Na, usually moie
Na, ieabsoibeu; theiefoie Ca has to sneak thiough channel, with help of PTB.
Theiefoie, with thiaziues, Na is blockeu, leaving the Ca channel completely open, anu
the thiaziues will leau to hypeicalcemia. Theiefoie, use in Ca stone foimeis - most
of stone foimeis have hypeicalciuiea; these pts have too much Ca in theii uiine;
when they aie on thiaziues, the uiug takes Ca 00T of the uiine, so they uo not foim
stones. (S) PTB will ueciease ieabsoiption of phosphoius in the piox tubule, anu (4)
ueciease the ieaccumulation of bicaib, too.
f. vitamin B anu PTB anu how they woik togethei:
F&6 G8/ main function is mineializing bone, anu osteoblasts (bone builueis) aie
involveu with this piocess, theiefoie the ieceptoi foi vit B is locateu on the
osteoblast. When vit B hooks into the ieceptoi, it causes the ielease of alkaline
phosphatase. So, when you aie giowing bone oi iehealing of a fiactuie, you expect to
see an inciease in alkaline phosphatase, which makes the appiopiiate solubility
piouuct to mineializeu caitilage anu bone. Knowing that :+! bieaks uown bone
(maintains Ca levels in the bloou stieam) you woulu think that its ieceptoi woulu be
on the osteoclast (cell noimally bieaks bone uown). Bowevei, only one hoimone has
a ieceptoi on ostoeclasts anu that is 5';5&6$4&4. When calcitonin hooks into the
osteoclast ieceptoi, it inhibits the osteoclast, anu theiefoie is useu to tieat
hypeicalcemia. Calcitonin also useu in tieating osteopoiosis. The ieceptoi foi PTB
is on the osteoblast, but not shaiing the same one as vit B. When PTB hooks on the
osteoblast, it ieleases IL-1. Anothei name foi IL-1 is osteoclast activating factoi
(othei functions of IL-1 aie also involveu in fevei, stimulates Ab synthesis, anu B cell
stimulation). So, IL-1 (ieleaseu fiom the osteoblast) activates osteoclasts via IL-1
ielease fiom osteoblast, anu osteoclast is signaleu to bieak uown bone to maintain
Ca levels in oui blooustieam. Sex hoimones keep IL-1 in check; in women, estiogen
levels keep a check on IL-1 (uo not want too much osteoclast activation); in men, it is
testosteione that keeps IL-1 in check (puts inhibitoiy effect on IL-1 ielease fiom the
osteoblast aftei PTB hooks in). Theiefoie, in women, can see why they get
osteopoiosis - lack of estiogen = IL-1 not in check anu bieaking moie bone uown
than making (this is the mechanism of postmenopausal osteopoiosis).
PTB is moie involveu in maintaining Ca levels in oui bloou, while vit B is moie
involveu in mineializing oui bones anu caitilage.
g. vitamin B ueficiency: Nany ieasons: lack of sun, pooi uiet, livei uz, ienal uz.
Example: Pt on phenytoin anu pt has hypocalcemia, why. Phenytoin, alcohol, baib's,
iifampin all inuuce the cyt p4Su system locateu in the SER. Theiefoie, get SER
hypeiplasia; theiefoie, you metabolize uiugs anu othei things maue in the livei,
incluuing 2S-hyuioxyvitamin B. Theiefoie, anything that iev's up the p4Su enzymes
will cause a ueciease in vit B, anu any othei uiugs being taken.
Example: woman on biith contiol pills anu taking phenytoin, anu she got piegnant,
why. The phenytoin iev'eu up the p4Su system, which incieaseu the metabolism of
estiogen anu piogesteione in the biith contiol pills, theiefoie not enough levels to
pievent piegnancy.
Example: what is the enzyme in the SER that incieases when the p4Su is iev'u up.
uamma glutamyl tiansfeiase (uuT) - enzyme of SER! (look at in alcoholics)
Example: NCC chionic ienal uz in 0SA: uiabetes mellitus - tubulai uamage, so no 1-
a-hyuioxylase, theiefoie inactive vit B. Theiefoie, pts with chionic ienal failuie aie
put on 1-2S-vit B.
Example: if someone gets 0TC vit B, what steps uoes it go thiough to become
metabolically active. 2S hyuioxylateu in livei, anu 1-a-hyuioxylateu in youi kiuney
(it is N0T 1, 2S vit B - this is a piesciiption uiug, anu extiemely uangeious). Nany
people have the misconception that the vitamin B is alieauy woiking. This is not the
case; pt must have a functioning livei anu kiuney.
With vit B uef in kius = iickets; vit B uef in auults = osteomalacia (soft bones).
If you can't mineialize bone, you cannot mineialize caitilage, anu they will both be
soft, theiefoie pathologic fiactuies aie common.
Kius have uiffeient a few things that aie uiffeient in iickets - ie cianiotopies, soft
skulls (can actually piess in anu it will iecoil). They can also get iicketic iosaiies, bc
the osteoiu is locateu in the costochonuial junc, anu bc they aie vit B uef, theie is a
lot of noimal osteoiu waiting to be mineializeu, but not an appiopiiate Calcium
phosphoius solubility piouuct; will have excess osteoiu with little bumps, which is
calleu iicketic iosaiy. Not seen in auults' bc they aie getting fuseu.
So, 2 things you see in kius anu not auults: 1) cianiotopies 2) iicketic iosaiies; ihe
iest is the same, with pathologic fiactuies being the main pioblem.
h. ToxicityBypeivitaminosis of vit B: hypeicalcemia, theiefoie iisk of having too
many stones in the uiine, anu stones is a NCC complication.
Type 1 iickets - missing the 1-a-hyuioxylase
Type 2 iickets - missing the ieceptoi foi vit B
9) F&6'.&4 Z
a. Nain function: maintain cell membianes anu pievent lipiu peioxiuation of the cell
membianes; in othei woius, it piotects the cell membianes fiom being bioken uown
by phospholipase A (lipiu peioxiuation, which is fiee iauical uamage on the cell
membiane, anu is pieventeu with vit E). 0thei function: neutializeu oxiuizeu LBL,
which is fai moie atheiogenic than LBL by itself. When LBL is oxiuizeu, it is way
moie injuiious to the cell then when it is not oxiuizeu. vit E will neutialize oxiuizeu
LBL, theiefoie is a caiuiopiotectant (vit E anu C both neutialize oxiuizeu LBL). In
summaiy: vit E func = 1) piotects cell mem fiom fiee iauical uamage. 2) 0xiuizes fiee
LBL (this is the LBL that maciophages phagocytose to piouuce foam cells, anu leaus
to atheioscleiotic plaques).
b. Beficiency of vitamin E: Is seen but is veiy uncommon, anu if seen if woulu be in
kius with cystic fibiosis; fiom biith, kius have iesp piobs anu pancieas pioblems.
(look at in iobbins, too). A kiu that has cystic fibiosis will have malabsoiption
pioblems; theiefoie what foui vitamins shoulu you give him. Cystic fibiosis pt has a
malabsoiption of fat; theiefoie they will have malabsoiption of fat soluble vitamins -
A, B, E, anu K. vit E uef in 0SA is usually seen in cystic fibiosis patients.
c. Clinical piesentations: 0ne of the featuies of vit E uef is hemolytic anemia (vit E
noimally maintains the integiity of the membiane); this pt is now susceptible to fiee
iauical uamage, uamageu mem of RBC leaus to hemolysis of RBC anu hemolytic
anemia. Anothei featuie of vit E aie things ielateu to myelin: posteiioi column uz,
spinal ceiebellai piobs. Theiefoie, with vit E uef, have neuiological pioblems anu
hemolytic anemia.
u. vitamin E toxicity: anything moie than 11uu units (aveiage capsule is 4uu units,
theiefoie, if take S pills, alieauy toxic). vitamin E toxicity will inhibit synthesis of
vit K uepenuent Coagulation factois (2, 7, 9, 1u, piotein C, piotein S); in othei
woius, you aie antiCoagulateu. Example: pt with NI - take antioxiuants, anu aspiiin;
with anteiioi NI, they antiCoagulate the pt, anu pt goes home on thiee months of
waifaiin. Noimal INR iatio, anu takes lots anu lots of vit E anu othei vitamins. Take a
lot of vit E anu will help waifaiin, leauing to ovei antiCoagulateu state, (iemembei
that waifaiin blocks gamma caiboxylation of vitamin K uep factois). vit E will
pievent the SYNTBESIS of these factois. Theiefoie, vit E toxicity is syneigistic in
activity with waifaiin. Example: pt on waifaiin, came home fiom NI, INR iatio is
huge; why. Taking vit E.
K) F&6'.&4 S
a. Souices: Can come fiom what we eat, but most is synthesizeu by oui colonic
bacteiia (oui anaeiobes in oui gut) - this is why we give vit K injections to oui baby
when they aie boin; they only have S uays woith of vit K fiom mom, but aftei that,
they won't have any bc its not in bieast milk; theiefoie, a veiy low level of vit K
between uays S-S; also, they uon't have bacteiia to make the vit K. Theiefoie, can get
hemoiihagic uz of the newboin (this is why we give vit k when they aie boin); aftei
S uays, the bacteiia colonize, anu vit is maue by the baby.
b. Netabolism: Bacteiia make vit K in an inactive foim - K2. K2 (inactive foim
must be conveiteu by epoxiue ieuuctase to K1 (K1 is the active foim of vitamin K).
K1 will gamma caiboxylates the vit K uepenuent factois (2, 7, 9, 1u, piotein C anu S).
uamma caiboxylates iequiies the same unueistanuing as vitamin C, in vit C If you
uon't hyuioxylate pio anu lys then the ciosslinks aie weakei (anchoi pt). uamma
caiboxylation of vit K uep factois actually activates them to become functional. vit K
uep factois all have something in common: (1)have to be activateu by vit K1 anu (2)
they aie the only Coagulation factois that aie bounu to a clot by Calcium (Ca); so they
have to be bounu by Ca in oiuei to woik anu foim a clot; if you can't binu, then you
aie antiCoagulateu. That is what gamma caiboxylation: glutamic aciu iesiuues aie
gamma caiboxylateu on the vit K uep factois (which is uone with K1), anu allows Ca
to binu the factois; theiefoie, it keeps them togethei anu you aie able to foim a clot;
theiefoie, if they aie not gammacaiboxylateu, they aie useless bc Ca can't giab
them to foim a clot (so, gammacaiboxylation is the anchoi pt, so Ca can binu to foim
a clot, similai to hyuioxylation of pioline anu lysine in collagen synthesis).
Waifaiin blocks epoxiue ieuuctase, so all the vit K pt has is K2 anu no
gammacaiboxylation will occui. Theiefoie, the patient is anticoagulateu.
c. vitamin K ueficiency: NCC vit K uef (in hospital) = bioau spectium Ab's. 2
nu
NCC
= pooi uiet, being a newboin, malabsoiption. Bef vit K = hemoiihagic uiathesis
(bleeuing into skin oi biain). Know why newboin has vit K uef: Example: kiu with
iat poison -iat poison is waifaiin; when iats eat it, they get antiCoagulateu anu uie.
Tieat with intiamusculai vitamin K. Example: kiu liveu with gianupaients anu
uevelopeu hemoiihagic uiathesis: why. Bc the elueily weie on waifaiin, anu kiu
ate the waifaiin, anu leu to toxic levels.
Auuio File 9: Nutiition 2 - Neoplasia 1
>) O'6,- [$;<E;, F&6'.&4/: all aie cofactois in majoi biochemical pathway
1) F&6'.&4 >0
a) Classic example of vitamin C ueficiency: oluei peison on tea anu toast uiet -
inuicating that they aie malnouiisheu; pt gets bleeuing of the gums = scuivy, uue to
vit C uef. vit C is iesponsible foi hyuioxylation of pioline anu lysine, anu this occuis
in the uolgi appaiatus bc that's wheie post-tianslational mouification occuis. Pts
have weak Type I collagen bc cannot ciossbiiuge it; theiefoie, Bv's aie unstable anu
gums bleeu. uet bleeuing of the gums, inflammation, anu may loose teeth.
b) Associateu question: what complication is associateu with seveie hemophilia A.
Bemeaithioses, anu causeu by vit C ueficiency (bc the Bv's aie unstable anu they
iuptuie).
c) Physical uiagnosis of vitamin C ueficiency: Along with the tea anu toast uiet,
theie is also peiifolliculai hemoiihage (hemoiihage aiounu the haii follicles). See
iing siueioblast (nucleateu RBC, anu has too much iion in the mitochonuiia), iing
aiounu the haii follicle anu also see coik sciew haiis uue to vit C uef. The tongue
looks like it huits anu patients with vit C have a smooth tongue - glossitis, with
kelosis aiounu ankles, plus a hemoiihagic uiathesis = scuivy.
u) Excess vitamin C: veiy common bc pts take way too much vit C (6-8gm), main
complication is Renal stones (incieaseu uiic aciu stones, anu othei kinus of stones).
vitamin C anu B both have toxicity stones.
e) vitamin C is useu in ancillaiy Rx foi methemoglobinuiia; it is a ieuucing agent
anu a gieat scavengei huntei foi fiee iauicals (knocks them off).
f) Cofactoi in biochemical pathway: vit C is a cofactoi foi conveiting the
catecholamine NE into Epi.

7) F&6'.&4 V
1
H+?&'.&4,I:
a) Involveu in many biochemical ieactions: tiansketolase ixn's in the pentose
phosphate shunt; anu pyiuvate uehyuiogenase; alpha keto glutaiate uehyuiogenase;
anu alpha keto aciu uehyuiogenase. All the uehyuiogenase ixns iequiie thiamine as
a cofactoi. Pyiuvate uehyuiogenase is the main ixn that conveits pyiuvate into
acetyl CoA. Pyiuvate can also be conveiteu to 0AA with a caiboxylase enzyme. When
you combine acetyl CoA with 0AA, you make citiate, anu you aie in the TCA cycle.
b) So, if thiamine uef, bc it is involveu in the pyiuvate uehyuiogenase ixn (which
conveits pyiuvate to acetyl CoA), you will not have a lot of acetyl CoA aiounu,
theiefoie, won't have much citiate aiounu, theiefoie, you won't have the TCA cycle
woiking efficiently, anu LESS ATP. Theiefoie, the pioblem with thiamine uef is ATP
uepletion. When you go fiom pyiuvate to acetyl CoA, you geneiate 2 NABB's anu
since this is in the mito, you get 6 ATP (so, just fiom going fiom pyiuvate to acetyl-
Coa, gives 6 ATP); anu then with TCA, get 24 ATP's. 6 + 24 = Su ATP; the total you
can get fiom completely metabolizing glucose is S8 ATP; so, if you aie thiamine uef,
you aie out Su ATP's; so, the main piob of thiamine uef is ATP uepletion.
c) In thiamine uef you'll see foot uiop (uiy beiibeii), anu pitting euema (wet
beiibeii). Bow uoes this explain wetuiy beiibeii.
1) Biy beiibeii = peiipheial neuiopathy, anu iefeis to Weinicke's koisakoff
psychosis (can't iemembei olu anu new things - like an exam - ie "useu to know that,
but can't iemembei now"; a memoiy pioblem). It takes a lot of ATP foi synthesis of
myelin; without myelin, you will get peiipheial neuiopathy anu foot uiop (uue to
common peioneal palsy), can get wiist uiop (iauial neive palsy), anu claw hanu
(ulnai neive palsy). Weinicke's encephalopathy is confusion, ataxia, anu nystagmus.
All of these aie uue to uemyelization.
2) Wet beiibeii = heait failuie; NCC thiamine uef = alcohol (not polisheu iice).
Alcoholics aie the NC people with thiamine uef. Wet beiibeii is iefeiiing to
caiuiomyopathy - cause: LBF went into RBF which leau to pitting euema. Beait
neeus ATP to function, theiefoie, the pt with have congestive caiuiomyopathy; theii
heait will have biventiiculai enlaigement (the whole chest will be heait), with left
anu iight BF (pitting euema is a sign of iight BF uue to incieaseu hyuiostatic
piessuie behinu the faileu heait). If you give Iv thiamine, can ieveise; anu in some
cases it's ielateu to toxicity of alcohol, anu cannot woik.
u) Example: pt in ER given Iv of S% uextiose anu noimal saline; all of suuuen, pt
uevelops confusion, nystagmus, anu ataxia, anu opthalmaplegia. Biagnosis:
subclinical thiamine ueficiency. As soon as the glucose was hung up, the pyiuvate
went to acetyl CoA anu useu the iest of thiamine...then went into acute Weinicke's
encephalopathy. Theiefoie, moial of the stoiy: give Iv thiamine befoie hanging up Iv
glucose, especially in ER.
f) When people come in comatose oi semicomatose, seveial things you always uo:
1) Su% glucose if a hypoglycemia pioblem 2) naloxone (0B) S) Iv thiamine
9) F&6'.&4 V
9
HQ&'5&4I0
Sliue: Rash in sun exposeu aiea = pellagia (aka ueimatitis), uue to niacin uef (also
uiaiihea, ueimatitis, uementia); hypeipigmentation in sun-exposeu aieas = Cassel's
necklace (ueimatitispellagia);
NABNABP ixns (N stanus foi nicotinamiue, anu the nicotinamiue was ueiiveu
fiom niacin). Theiefoie, all the oxiuation ixns ixn's aie niacin uepenuent. Example:
pyiuvate to acetyl CoA = went fiom NAB to NABB anu niacin is involveu heie.
Tiyptophan can useu in synthesizing niacin anu seiotonin (why it's an essential aa);
but it's not the main souice of niacin, but a goou souice.
Nicotinic aciu = least expensive lipiu loweiing uiug; see the flushing assoc with it;
supposeu to take aspiiin with it to iemove the flushing ielateu to nicotinic aciu (useu
in tieating familial hypeilipiuemia), it is the B0C foi elevateu hypeiTuemia.
K) F&6'.&4 V
7
HD&E$U;'J&4I0
FABFNN - ixns aie iiboflavin cofactoi ixns (theiefoie, whenevei you have FAB
anu FNN ixns, these aie iiboflavin cofactoi ixns).
(Niacin foi NABNABP ixns, anu iiboflavin foi FABFNN ixns).
Also, the fiist ixn: glutathione ieuuctase conveits oxiuizeu glutathione into
glutathione which iiboflavin is a cofactoi foi.
N) F&6'.&4 V
`
H:"-&A$%&4,I:
We'ie talking about miciocytic anemia. Fiist ixn in the synthesis of heme involves
succinyl Coa, plus glycine. The enzyme is ALA synthase, anu the cofactoi is B
6
.
Theiefoie, it is imp to the synthesis of hemoglobin anu heme pioteins. The
cytochiome system is the heme system, too. Nyoglobin is uiffeient fiom Bb (has one
heme gioup), while Bb has foui heme gioups. Theie is also heme in the livei, in the
cytochiome system. Pyiiuoxine is involveu in the synthesis of heme, which is in
poiphyiin. Pyiiuoxine is in the tiansaminases ixn. Nost abunuant substiate fiom
making glucose in the fasting state = alanine (aa fiom muscle - aa's bioken uown
fiom muscle to get glucose, via gluconeogenesis). Bow can an aa be useu to make
glucose. Tiansamination. Tiansaminations (Su0T, SuPT) fiom the livei can take
tiansaminases; they take amino gioups out anu put them into othei things; if you
take the amino gioup out of alanine, this piouuces pyiuvate (an alpha keto aciu). If
you take aspaitate anu take the aa out, you have 0AA, which is a substiate foi
gluconeogenesis. If you take pyiuvate, anu auu an amino gioup, can synthesize
alanine. If you take 0AA, anu auu an amino gioup, you can make aspaitate. This is
what the tiansaminases uo, with B
6
as a cofactoi. B
6
is also involveu in the synthesis
of neuiotiansmitteis. Theiefoie, a chilu that is B
6
ueficient, they enu up with seveie
neuiological pioblems bc no neuiotiansmitteis (B
6
imp to synthesizing the
neuiotiansmitteis). Impoitant in tiansamination, neuiotiansmittei, anu heme
synthesis.
NCC uef B
6
uef = isoniaziu; without B
6
, will uevelop neuiologic pioblems anu
siueioblastic anemia ielateu to heme pioblem.
G) 26?,- &.#$-6'46 5$^='56$-/
1) :'46$6?,4&5 '5&A is ielateu to FA synthase; not the iate limiting ixn, but imp in
making palmitic aciu (a 16 C FA), anu helps in making CoA (ie acetyl CoA, BNu CoA);
pantothenic aciu is the cofactoi foi these ixns.
7) V&$6&4
Cofactoi foi othei ixn of pyiuvate to acetyl Coa via pyiuvate uehyuiogenase =
thiamine is the cofactoi, while biotin is the cofactoi foi Pyiuvate uecaiboxylase to
0AA. Theiefoie, thiamine helps foim acetyl CoA fiom pyiuvate, while biotin helps
foim 0AA fiom pyiuvate.
If you aie uef, neeu to eat 2u iaw eggsuay
Beficiency: get a iash anu go balu (alopecia). If biotin uef, cannot foim 0AA, anu
cannot fiom citiate eithei (this is the fiist step in gluconeogenesis, theiefoie you can
enu up with fasting hypoglycemia). If you builu pyiuvate, it will be foiceu to go to
lactic aciu.
9) +-'5, ,;,.,46/
a) Chiomium = glucose toleiance factoi, anu helps insulin uo its job.
0atmeal can also ueciease glucose with all the fibei; goou foi a type II uiabetic to be
on chiomium.
b) Coppei - lysl oxiuase - puts ciossbiiuge between collagen fibiils anu elastic
tissue. Theiefoie, if Cu uef, have weak collagen anu weak elastic tissue, pieuisposing
to uissecting aoitic aneuiysm. Reu haii in kwashioikoi also uue to Cu uef.
c) Fluoiine neeueu to pievent uental caiiies; too much fluoiine leaus to white,
chalky teeth, also in Coloiauo bc watei has too much fluoiine. It will also get
calcification of the ligaments, wheie ligaments go into bone; the calcifieu ligaments
aie subject to iuptuie; any goou iauiologist can uetect fluoiine toxicity.
u) Selenium - in pentose phosphate shunt, foim glutathione, anu have iiboflavin
helping that enzyme. ulutathione can neutialize peioxiue, anu this iequiies
glutathione peioxiuase; selenium is the cofactoi foi this ieaction. Theiefoie, in othei
woius, it is an antioxiuant bc if you aie uef in it; the glutathione cannot bieakuown
the peioxiue. (vit E usually comes with selenium - so one woiks on glutathione,
while the othei piotects the lipiu membiane fiom fiee iauical uamage anu scavenges
oxiuizeu LBL).
e) Zinc - Example: oluei peison with uysgusia (abnoimal taste) anu anosmia (lack
of sell); smell anu taste aie both uef in zinc uef. Zinc is a metalloenzyme; theiefoie it
has a tiace metal as a cofactoi. Collagenase is a metalloenzyme bc it has zinc in it,
anu it bieaks uown the type S collagen, so you can foim type 1 collagen. Theiefoie, if
ueficient in it, will have pooi wounu healing, anu you get a iash on the face. So, iash
on face, uysgusia, anosmia, pooi wounu healing = zinc ueficiency!!! Biabetics aie zinc
uef, unless taking supplements.
K) G&,6'-" U&E,- H&4/$;<E;, '4A /$;<E;,I - soluble fibei can lowei cholesteiol (not
the insoluble fibei). Bow it woiks (ie oatmeal): oatmeal has insoluble fibei, when it's
in the gut, it will suck up watei into it fiom the colon, anu also suck up bau things -
lipopolic aciu. 9S% of bile acius anu bile salts aie ieabsoibeu in the teiminal ileum.
The S% aie lipopolic acius, which aie caicinogenic (piouuces colon cancei). So, fibei
(insoluble anu soluble), it sucks the lipopolic aciu up, into the inteiioi of the stool, so
it has no contact with the bowel mucosa. Plus, uefecate moie often anu theiefoie
lipopolic acius have even less contact with the stool. Women aie lucky bc they
iecycle estiogens; main way of excieting estiogens is in bile anu out of youi stool,
but a small % of estiogens aie iecycleu back into the system. You may not
necessaiily neeu that, so, when on fibei, incieaseu estiogen is passeu out, theiefoie,
uecieasing chance of bieast cancei, ovaiian cancei, anu uteiine cancei bc fibei in
the uiet.
@F) [#,5&'; A&,6/ \ #-$6,&4 -,/6-&56&$4
What 2 uz's woulu you iestiict piotein in.
1) Renal failuie bc excess piotein bioken uown to ammonia anu othei things - the
ammonia is metabolizeu in the uiea cycle, will have inciease uiea anu the kiuney will
have to get iiu of moie uiea.
2) Ciiihosis of the livei - uefective uiea cycle theiefoie cannot metabolize
ammonia; most of the ammonia that we have in oui bouies comes fiom bacteiia in
oui colon that have uiease in them (B. pyloii); anu they bieakuown uiea to ammonia
in oui colon. Ammonia is ieabsoibeu, anu supposeu to go back to oui livei anu go
into the uiea cycle, become uiea anu get iiu of it. But with ciiihosis, no uiea cycle, so
the ammonia levels inciease in the bloou, leauing to hepatic encephalopathy, mental
status abnoimalities, asteiixis; also causeu by octpaneme, benzoic aciu,
neuiotiansmitteis.
So, two situations to iestiict piotein: ciiihosis anu chionic ienal failuie.
CHAPTER 5. Neoplasia
@) Q$.,45;'6<-,0 Va J/) .';&34'46
() B'&4 A&==,-,45, - B9 usually uoes not metastasize, malignant has the capacity to
metastasize. Exception: B9 tumoi that metastasize: invasive mole (metastasize to
lungs, but goes away).
V) [;&A,/0
a) NC skin cancei INvABES but uoes not metastasize: basal cell caicinoma.
b) 0teius: leiomyoma; NC B9 tumoi in woman is NC locateu in which oigan.
0teius - it's a leiomyoma; tumoi of smooth muscle!
c) Fibioius - smooth muscle; become veiy haiu
u) NC B9 tumoi in male (yellow) = lipoma
e) B9 tumoi of glanus = auenomas (ie auienal auenoma - thin auienal coitex bc it
is functional; it coulu be making coitisol, theiefoie suppiessing ACTB, anu the
fasiculata anu ieticulaiis woulu unueigo ATR0PBY.leaus to Cushing's. If tumoi
secieting mineialocoiticoius - it is Conn's synuiome, causing atiophy of the zone
glomeiulosa (uFR - salty sweet sex)
f) Tubulai auenoma = NC piecuisoi lesion foi colon cancei (looks like stiawbeiiy
on a stick)
>) >'-5&4$.' J/) /'-5$.'
1. Caicinoma - malignancy of epithelial tissue (S epithelial tissues - squamous,
glanuulai, anu tiansitional)
a) Squamous caicinoma - how to iecognize. Little swiils of incieaseu ieuness
(biight ieu) calleu squamous peails;
b) ulanuulai caicinoma - Rounu glanus, with something in the miuule =
auenocaicinoma
c) Tiansitional cell caicinoma - fiom blauuei, uietei, ienal pelvis (fiom genital
uiinaiy tiact) - all with tiansitional epithelium
Theiefoie S caicinomas = squamous, auenocaicinoma, anu tiansitional cell
caicinomas.
u) Example: Nalignant melanoma - fiist step in management. Excision (b9 veision
= nevus), both aie ueiiveu fiom melanocytes. This is the most iapiuly incieasing
cancei in the 0SA, not NC. They aie S-1uu Ag "+" tumois - aput tumois
e) Aput Tumois: S-1uu Ag "+" tumois - aput tumois; aput is piecuisoi uptake
uecaiboxylation, meaning that they aie of neuiosecietoiy oi neuial ciest oiigin.
Theiefoie, on EN, have neuiosecietoiy gianules. S-1uu Ag is useu to stain things of
aput oiigin oi neuial ciest oiigin (most, not all, will take up that Ag).
Examples of aput tumois: melanoma; small cell caicinoma of the lung; bionchial
caicinoiu; caicinoiu tumoi at the tip of the appenuix; neuioblastoma (secietoiy
tumoi), ie 2 yo with tumois all ovei skin, anu on biopsy, it is S-1uu "+", tumoi was
fiom auienal meuulla, metastasize to skin.
2. Saicomas -aie malignancy of NESENCBYNAL tissue (not epithelial).
Saicoma of smooth muscle = leioymyosaicoma; Stiiateu muscle =
ihabuomyosaicoma; Fat = liposaicoma; (these aie malignancies of mesenchymal
tissue, while caicinoma's aie of epithelial tissue).
Examples:
a) Bone, see metaphysis, see Couman's tiiangle, anu sunbuist appeaiance on x-iay
bc this tumoi actually makes bone. Bx = osteogenic saicoma (bone making
saicoma).
b) Biopsy fiom giil having neciotic mass coming out of hei vagina, vimentin anu
keiatin "-", anu uesmin "+", ux. Embiyonal ihabuomyosaicoma (see stiiation of
muscle). This is the NC saicoma of chiluien (vagina in little giils anu penis in little
boys)
c) Novable mass at angle of jaw = mixeu tumoi (in paiotiu); 'mixeu' bc two
histologically have two uiffeient types of tissue but ueiiveu fiom SANE cell layei
(not a teiatoma, which is fiom thiee cell layeis),. NC oveiall salivaiy glanu tumoi
(usually b9) = mixeu tumoi
u) Teiatoma = tooth, haii, ueiiveu fiom all thiee cell layeis (ectoueim, mesoueim,
anu enuoueim) Aka geim cell tumois - bc they aie totipotential, anu stay miuline.
Ex. anteiioi meuiastinum, oi pineal glanu; theiefoie, teiatomas aie geim cell,
miuline tumois.
e) Cystic teiatoma of the ovaiies: 16 yo giil with suuuen onset of RLQ pain (uon't
confuse with appenuicitis, Ciohn's uz, ectopic piegnancy, folliculai cyst). 0n x-iay,
see calcifications of the pelvic aiea! - Cystic teiatoma (the calcifications can be bone
oi teeth). 0sually uevelop in miuline - geim cell tumoi.
@@) Q$.,45;'6<-,0 X,<P,.&' '4A ;".#?$.'
NC on the boaius: Auei iou fiom myeloblast, anu hypeisegmenteu neutiophil fiom
B12 anu folate ueficiency.
() X,<P,.&' = malignancy of stem cells in the VB, anu they can metastasize (like
all cancei) anu to lymph noues, leauing to geneializeu lymphauenopathy anu
hepatosplenomegaly. Beiiveu fiom stem cells in the maiiow anu metastasize.
V) B';&34'46 ;".#?$.': aiise fiom XbB:! 4$A,/, anu can metastasize
anywheie, incluue BN.
The NC site in bouy foi lymphoma N0T ueveloping in lymph noue: /6$.'5?
Nost extianoual (outsiue lymph noue) piimaiy lymphomas occui in the stomach;
B. pyloii can piouuce these.
2
nu
NCC location (lymphoiu oigan in the uI tiact) = :'",-8/ #'65?,/ (locateu in the
teiminal ileum).
NC lymphoma = folliculai B cell lymphoma. This is an example of knocking off
apoptosis gene -14:18 tianslocation of a heavy chain; when you get the tianslocation,
B cells will make bcl-2, which inactivates apoptotic gene in the B cell, theiefoie, the
apoptotic gene is immoital, leaus to cancei.
@@@) Q$.,45;'6<-, $= +-$#?$E;'/6&5 +<.$-/
() !"A'6&A&=$-. .$;,, piesents with clustei of giapes. It manifests in the fiist
tiimestei with signs of pieeclampsia (BP, pioteinuiia, euema in the fiist tiimestei).
0n ultiasounu, will see uteius too laige foi its gestational age, with a snowstoim
appeaiance = classic complete mole; anu can piogiess to choiiocaicinoma.
V) >?$-&$5'-5&4$.' .$;, is a benign tumoi of the choiionic villus; choiionic villi
aie lineu with tiophoblastic cells, incluuing synctiotiophoblast on the outsiue (has
contact with the bloou, fiom which 0
2
is extiacteu); unuei the synctiotiophoblast is
the cytotiophoblast, then have waiten's jelly in the choiionic villus, then have vessel
that becomes the umbilical vein, which has the most 0
2
in the vessels of the fetus.
So, hyuatiuifoim mole is a B9 tumoi of the WB0LE choiionic villus, anu it looks like
giapes bc it's uilateu up. Choiiocaicinoma is a malignancy of the lining of the
choiionic villus: the synctiotiophoblast anu the cytotiophoblast (not the actual
choiionic villus). Which makes hoimones. The syncytiotiophoblast synthesizes B-
BCu anu human placental lactogen (giowth hoimone of piegnancy - it gives aa's anu
glucose fiom mom to baby). So, when gestationally ueiiveu, anu even when they
metastasize to the lungs, they iesponu well to chemotheiapy (methotiexate,
chlabucil). Theiefoie, these aie highly malignant tumois, but go away with
chemotheiapy.
Auuio File 1u: Neoplasia 2
@F) +?&43/ 6?'6 ,4A &4 c\$.'d0
Eveiything that enu in -oma is not necessaiily b9 - ie melanoma (malignant tumoi
of melanocytes), lymphoma (malignant tumoi of lymph noues)
Also, all that enus in -oma is not necessaiily a neoplasm - ie hemaitoma =
oveigiowth of tissue that is noimally piesent in that aiea. Example: A bionchial
hemaitoma seen lung which is b9 caitilage anu a solitaiy coin lesion is seen in lung
(also wonuei if it's a gianuloma). The polyp in Peutz }egheis synuiome is a
hemaitoma (not even a neoplasm), that's why theie is no inciease in iisk of poly
cancei. Bypeiplastic polyp (NC polyp in uI) is a hemaitoma, it's a B9 tissue in place
it is not suppose to be (ie pancieatic tissue in the stomach) - this is calleu a
choiistoma, oi heteiotopic iet.
Neckel's Biveiticulum
NC complication of Neckel's Biveiticulum = bleeuing fiom a gastiic mucosa that is
ulceiateu, oi pancieatic tissue that is ulceiateu. Shoulu gastiic mucosa be in the
meckel's uiveiticulum. No, bc it is in the small bowel (about 2 ft fiom the ileocecal
valve). Bemaitomas aie non-neoplastic, anu theiefoie uo not have cancei piouucing
potential.
F) B';&34'46 >,;;/
Incieaseu mitotic iate uoes not mean cancei. What makes mitosis malignant is
having an atypical mitotic spinule (they aie aneuploiu anu have moie than the
noimal 46 c'somesI) S," 6?&43 6?'6 A,6,-.&4,/ &= &6 &/ .';&34'46 &/ &6/ 'E&;&6" 6$
.,6'/6'/&],. Nalignant cells usually have a longei cell cycle than the cells they
ueiiveu fiom. !$L .'4" A$<E;&43 6&.,/ A$,/ &6 6'P, 6$ 3,6 ' 6<.$- 6?'6 5'4 E,
A,6,56,A 5;&4&5';;"e 9f A$<E;&43 6&.,/ means that the tumoi goes thiough the cell
cycle Su times, anu a tumoi of one sonometei in size is piouuceu; 1u
9
in mass.
Nalignant cells aie immoital - they uon't like each othei anu lack auhesion; if they
weie stuck to each othei, they woulu have pioblems infiltiating tissue. Nalignant
cells have simple biochemical systems, typically anaeiobic metabolism, anu have
many enzymes such as pioteases (useu to bieak thiough tissue), collagenases (useu
to bieak thiough BN). This is what makes a malignant cell malignant.
F@) B,5?'4&/./ $= B,6'/6'/&/0 ;".#?'6&5_ ?,.'6$3,4$</_ /,,A&43
() X".#?'6&5 .,6'/6'/&],/0
Bow uo 5'-5&4$.'/ usually metastasize. Lymph noues - they uiain to theii
iegional lymph noues; ie bieast cancei goes to axillaiy noues oi inteinal mammaiy
noues. Foi colon cancei, go to noues aiounu them (the local lymph noues); same
with caicinoma of the esophagus. What pait of the lymph noue uo metastases go to.
Subcapsulai sinus. If they can get thiough the lymph noue, they go to the effeient
lymphatics which uiains into the thoiacic uuct, anu then into the subclavian, anu
then they become hematogenous. Theiefoie, caicinoma can become hematogenous,
this means that they 1
st
went thiough the lymph noues; now, they can spieau to
othei oigans (ie bone, livei, etc). This is bettei than saicoma bc can feel the lymph
noues by clinical exam anu pick up befoie it spieaus.
V) !,.'6$3,4$</ .,6'/6'/&],/0
0n the othei hanu, /'-5$.'/ uo not like to go to lymph noues. They go iight
thiough Bv's anu aie chaiacteiizeu by hematogenous spieau, anu that's why lungs
anu bones aie common sites of saicomas. They uon't like to go to lymph noues.
Theiefoie, they aie a little woise bc they immeuiately go hematogenous, anu uo not
give a clue that they aie spieauing. Example: have angiosaicoma of the bieast;
woulu you uo a iauical uissection of the axilla. No, bc angiosaicoma uoes not go to
the lymph noues, theiefoie, uo a simple mastectomy. If it is bieast caicinoma, take
bieast anu lumpectomy anu local axillaiy lymph noues anu complete the uissection.
Exceptions: Folliculai caicinoma of the thyioiu (thinks it's a saicoma) - skips lymph
noues anu goes stiaight to Bv's, anu takes the hematogenous ioute.
Renal auenocaicinoma - goes to ienal veins (also ueteimines piognosis)
Bepatocellulai caicinoma - like to attack the vessels
In geneial, caicinomas 1
st
like to go to lymph noues, anu the have the potential to
become hematogenous. Saicomas go hematogenous, making them uangeious.
>) [,,A&43: Classical Example: canceis that aie in cavities anu have a potential of
seeuing, like little malignant implants. Nost ovaiian canceis aie suiface ueiiveu
canceis, theiefoie ueiiveu fiom lining aiounu the ovaiy, anu they seeu like little
implants. Theiefoie, easy to thiow out these implants anu foi it to metastasize to the
omentum, anu into the pouch of Bouglas. The pouch of Bouglas is posteiioi to the
uteius anu anteiioi to the iectum anu is felt by uigital iectal exam. The pouch of
Bouglas is to a woman, as the piostate glanu is to the man. If you uo a iectal on a
man, anu push foiwaiu, you will feel the piostate. If you uo a iectal on a woman anu
push foiwaiu, this is the pouch of Bouglas. This is an imp aiea bc it's the most
uepenuent aiea of a woman's pelvis anu many things go heie - clotteu bloou in a
iuptuie ectopic piegnancy, wheie enuometiial implants go in enuometiiosis, anu
wheie seeuing goes in ovaiian canceis (pouch of Bouglas). So, seeuing of ovaiian
cancei to the omentum anu can actually invaue. Can also seeu in the pleuial cavity,
foi example: peiipheially locateu lung cancei that can seeu into the pleuial cavity.
uBN (NC piimaiy malignancy of the biain in auults) can seeu into the spinal fluiu
anu implant into the entiie spinal coiu, as can a meuulloblastoma in a chilu.
So, the S mechanisms foi metastasis aie lymphatic, hematogenous, anu seeuing.
F@@) B$/6 >$..$4 HB>I 5'45,-/
The fiist question is to ask: "Is the metastasis moie common than piimaiy cancei."
In most cases, metastasis is the NC cancei in an oigan (not a piimaiy cancei).
Exception: ienal auenocaicinoma (which is moie common than metastasis to it).
X<43: NC cancei is metastasis fiom the bieast cancei. Theiefoie, NC cancei in the
lung is bieast cancei. Theiefoie, women aie moie likely to get lung cancei.
V$4,: NC cancei in bone is metastasis (not multiple myeloma oi osteogenic
saicoma). NC cancei that metastasis to bone is bieast cancei bc the batsom system;
it is a venous complex going fiom base of the skull uown to the sacium, anu has no
valves in it. The little tiibutaiies communicate with the vena cava anu also go iight
into the veitebial bouies. Then they collect aiounu the spinal coiu anu go up. Foi
example: a lauy has a little plug of tumoi in the inteicostal vein, anu benus uown to
pick up something off the giounu, which causes the cancei to be uislougeu fiom the
vein to the vena cava to the batson plexus in the veitebial bouies, anu S months latei
she is complaining of lowei back pain. All of a suuuen, she is stage foui cancei.
NC bone metastasis T0 the veitebial column. 2
nu
NC is the heau of the femui (in a
woman, this is uue to bieast cancei - ie bieast cancei in heau of femui, when they
thought it was uegeneiative aithiitis).
B> $-3'4 .,6'/6'/&/ 6$ C ;".#? 4$A,/ (caicinomas aie moie common than
saicomas, anu caicinomas like to go to lymph noues, meaning it is the NC metastasis
to)
X&J,-0 NC cancei of livei = metastasis fiom lung into livei (not colon - colon is 2
nu

bc poital vein uiainage).
+,/6&5<;'- >'45,-0 Wheie woulu testiculai cancei metastasize fiist. Paiaoitic
lymph noues; N0T the inguinal lymph noues bc it ueiiveu fiom the abuomen, anu
then uescenueu. Example: seminoma (malignant) will metastasize to paiaoitic
noues bc that is wheie it came fiom
X,=6 /<#-'5;'J&5<;'- 4$A,_ 'P' F&-5?$L8/ 4$A,. The NC piimaiy metastasize to
viichow's noues = stomach cancei! Theie is a mass in the left supiaclaviculai noues
along with wt loss anu epigastiic uistiess.
V$4,: Best test looking foi bone mets. Rauionucleiue scan. Example: eveiywheie
that is black in a woman is mets fiom bieast cancei. NC bone metastasis to =
veitebial column!
Nets that aie ;"6&5 (bieak bone uown) anu mets that aie E;'/6&5 (mets go into bone
anu inuuce osteoblastic iesponse).
A. Lytic Netastasis:
Foi lytic mets, they can leau to pathologic fiactuies anu hypeicalcemia.
B<;6&#;, .",;$.' with puncheu out lesions bc all malignant plasma cells have
IL-1 in them (aka osteoclast activating factoi)
B. Blastic metastasis:
Foi blastic mets, ';P';&4, #?$/#?'6'/, will be elevateu. Example: this is a male
with piostate cancei (piostate cancei is blastic!); it is making bone anu will ielease
alkaline phosphatase
B> ;$5'6&$4 =$- .,6/ C ;<.E'- J,-6,E-',
Example: 8u yo man with lowei lumbai pain with pt tenueiness; what is fiist step
in management. Bigital iectal exam woulu be the fiist thing to uo bc this woulu be
stage foui uz, anu the piostate is palpable; so, this is the easiest anu cheapest test
(not PSA, oi iauionucleiue bone scan to make suie its not mets).
Lytic mets - have lucency (absence of bone) - ie veitebiae collapse
Blastic mets - have entity on x iay
@= "$< /,, '4" /#,5&.,4 L&6? .<;6&#;, ;,/&$4/ &4 &6_ &6 &/ BZ+[ H#-&.'-"
5'45,-/ '-, 5$4U&4,A 6$ $4, '-,' $= 6?, $-3'4I)
NC cancei biain = mets
NC cancei killei in men anu women = lung cancei
NC piimaiy site foi cancei in biain = lung
NC cancei in lung = mets fiom bieast
NC mets to auienal = lung - theiefoie they always uo a CT of the hilai lymph noues,
anu auienal glanus in the staging of all lung canceis.
Bone = blastic, theiefoie the most likely cause is piostate cancei.
F@@@) [6'&4/ '4A ZB </,A 6$ ?,;# A% A]0
[6'&4/: uesmin - goou stain foi muscle - ie useu foi ihabuomyosaicoma
Stain foi keiatin (most caicinomas have keiatin in it, theiefoie stain foi that)
Stains help IB uiff types of tumois
vimentin- mesenchymal cells
ZB: 0seu when nothing else helps
Auput tumoi - see neuiosecietoiy gianules.
Bistiocyte tumoi (ie histiocytosis X) - see biibeck gianules, with CB 1
Nuscle - see actin anu myosin filaments
vasculai malignancy - Wibble palau bouies (have vWF in them); they aie of
enuothelial oiigin
Know gap junc (which communicate, which uon't)
@g) 245$3,4,/&/0
() V&3 #&56<-, $= $45$3,4,/&/
1) Initiation (mutation - ie within the cell cycle)
2) Piomotion (wheie multiple copies of the mutation aie maue)
S) Piogiession (sub-specializing) uiff types of cancei cells have uiff func -
malignant cells with one puipose - to kill you. Biff cells with uiff func: some stay
wheie they aie; some invaue (anu aie given special things foi it to be able to invaue);
some have special ieceptois to home in to specific oigans; some iesist chemo, some
spieau, some make enzymes to penetiate tissues.
2 sets of genes involveu with cancei:
1) Involveu in giowth piocess (cell cycle ielateu)
2) uenes that suppiess things (suppiessoi genes)
V) +?&43/ 6?'6 '-, &4J$;J,A &4 6-"&43 6$ 3,6 ' 5,;; 6$ A&J&A,0
uF's (epiueimal ueiiveu uF); piotooncogenes - noimal genes, which haven't been
activateu, anu have noimal function. When they have been activateu, they become
oncogenes, which aie bau anu become canceious. Ceitain piotooncogenes coue foi
giowth factois - ie sis, whose func is to make uF's.

All uF's have to hook into a ieceptoi; theiefoie ceitain piotooncogenes whose main
job is to make ieceptois - ie eib-2 = bieast cancei, which coues foi a ieceptoi anu iet
= seen in NEN synuiome (NEN I anu IIa anu IIb).
We have to senu a message to the nucleus, so have anothei set of genes, whose job
is to senu the message; some locateu in the cell membiane. Example: ias
piotooncogene senus a uTP (a phosphoiylateu piotein message), theiefoie it's a cell
membiane locateu messengei system. Anothei example: abl piotooncogene which
lives in the cytosol, veiy close to the nucleai membiane anu also is involveu in
messages.
Who is the messengei sent to. The message is sent to a gioup of piotooncogenes in
the nucleus. 0nce that message is sent to them, theie is stimulation of nucleai
tiansciiption of that message; in othei woius, the cell uiviues anu makes whatevei it
is supposeu to make. >;'//&5 #-$6$$45$3,4,/ 6?,-, '-, \ ."5 #-$6$$45$3,4,/ C
4^."5 '4A 5^."5 H4^."5 &/ =$- 4,<-$E;'/6$.'_ '4A 5^."5 &/ =$- V<-P&66/
;".#?$.'I)
So, the piotooncogenes involveu make uF's, giowth factoi ieceptois; senu
messages (which aie often phosphoiylateu pioteins). Example - ie insulin hooks
into ieceptoi on auipose anu activateu tyiosine kinase (locateu iight on the
ieceptoi), which makes a phosphoiylateu piouuct, goes to the nucleus (to uiviue),
anu also goes to uA anu attaches to uL0T-4, which is maue fiom golgi appaiatus,
goes to the cell membiane anu theie's the ieceptoi foi glucose. Theiefoie the
messages go to nucleai tiansciibeis in the nucleus anu these aie myc oncogenes.
+?, /<##-,//$- 3,4,/ '-, 5$46-$;;&43 6?, 5,;; 5"5;,) +?, 7 .$/6 &.# '-, DE
/<##-,//$- 3,4, '4A #N9 /<##-,//$- 3,4,) Noimally, they contiol the cell cycle
anu uo not let cell cycle piogiess to S phase. If uniegulateu, cells go to S phase anu
become 'initiateu'.
Bow uo we initiate a cell. Nutations-mechanisms: usually a point mutation ie
substitutes aa foi eo. The pSS suppiessoi gene anu the ias oncogenes is a pt mut'n.
All suppiessoi genes aie uue to pt mut'n. 0thei mutations incluue:
Amplification - make multiple copies (eib-2 is an amplification system) anu
Tianslocation (putting in anothei place anu can't go back) classic: CNL
tianslocation of abl (non ieceptoi tyiosine kinase activity fiom c'some 9 to 22. 0n
c'some 22, it fuses on a clustei iegion of the fusion gene, anu bc of the tyiosine
kinase activity, it senus a message anu stem cells keep uiviuing; aka Philly c'some.
Anothei example: Cancei assoc with Epstein Baii viius - tianslocation of myc
nucleai tiansciibei gene fiom c'some 8 anu puts it on c'some 14; it uoesn't like it
theie, so it leaus to Buikitts lymphoma. Receptoi foi Epstein baii viius on all B cells
- CB 21; when it hooks on to ieceptoi, it causes B cells to become plasma cells anu
make Ab (theiefoie, this viius is an amazing stimulating of Ab synthesis, as is the
CNv viius.)
The moie a cell uiviues, the woise it is if something happens to it; ie EBv viius , 8,14
tianslocation of myc oncogenes fiom 8 to 14 anu all of a suuuen you aie making
multiple copies, anu leaus to lymphoma (gieatei chance that you uo something, the
gieatei chance that you will sciew up).
Folliculai B cell lymphoma - tianslocation of 14:18; inactivation of suppiessoi
gene.
+-'4/;$5'6&$4 1N01h C '5<6, #-$3-'4<;$5"6&5 ;,<P,.&'i D% \ F&6 ( H-,6&4$&5
'5&AI ER5 &6 .'6<-,/ 6?, E;'/6/_ 6?,-,=$-, 6?, .';&34'46 5,;; E,5$.,/ Va)
>) [<##-,//$- 3,4,/
Suppiessoi genes suppiess, theiefoie if knockeu off, whatevei they weie
suppiessing keeps on going) S," /<##-,//$- 3,4,/0 #N9_ DE 3,4,_ 'A,4$.'6$/
#$;"#$/&/ 5$;& H='.&;&'; #$;"#$/&/I_ 4,<-$U&E-$.'6$/&/_ L&;.8/ 6<.$- 3,4,_
E-5'1 '4A 7 (both involveu in BNA iepaii, anu one is on c'some 1S while the othei is
on c'some 17); bica1 can be bieast cancei, ovaiian cancei, oi otheis; E-5'7 &/
+2+(XXb -,;'6,A 6$ E-,'/6 5'45,-) 0nly 1S% of bieast canceis have genetic assoc
with these genes, theiefoie, most cases aie spoiauic.
g) >$..$4 6?&43/ 6?'6 #-,A&/#$/, .<6'6&$4/0
Piotooncogenes aie activateu, while suppiessoi genes aie inactivateu
S main ways this occuis: chemicals, viiuses, iauiation
() >?,.&5';/:
Which of the thiee is most common in initiating a cell piouucing a mutation.
>?,.&5';/ \ /.$P&43 C B>> A,'6? &4 M[( A<, 6$ #$;"5"5;&5 ?"A-$5'-E$4/)
By itself, smoking is NC than viially inuuceu oi iauiation inuuceu canceis. Smoking
causes lung cancei, squamous cancei of the mouth, laiynx, lung, pancieas, blauuei,
anu if it's not the #1 cause, it's often #2, such leukemias, ceivical ca, anu colon.
NCC papillaiy tumoi of the blauuei = tiansitional cancei (smoking)
What if you woikeu in a uye inuustiy. Aniline
O?'6 &= "$< ?'A O,3,4,-8/ 3-'4<;$.'6$/&/_ #<6 $4 ' A-<3 '4A 3$6 ?,.'6<-&'_
A&A 5"6$;$3" '4A /'L 5,;;/_ L?'6 A-<3 &/ #6 $4e >"5;$#?$/#?'.&A,
H?,.$--?'3&5 5"/6&6&/Ii #-,J,46 L&6? .,/4'_ '4A 5'4 5'</, 6-'4/&6&$4'; 5,;;
5'-5&4$.' H6?,-,=$-, '56/ '/ ' 5'-5&4$3,4jI
Lung cancei - NCC = polycyclic hyuiocaibons fiom smoke; most often assoc with
smoking is small cell anu squamous;
V) F&-</,/0
viius assoc cancei: a viius with nonpiuiitic iaiseu ieu lesions. Bx. Kaposi's
saicoma (uue to BBv 8)
V<-P&66/i A<, 6$ Z#/6,&4 E'-- J'-&,/ L?&5? ';/$ 5'</,/ 4'/$#?'-"43,';
5'-5&4$.'_ ,/#) &4 >?&4,/,
;&J,- \ !,#'6$5,;;<;'- 5'-5&4$.' A<, 6$ ?,#'6&6&/ V =-$. (/&'i ';/$ A<, 6$ '
.$;A \ #$%#&'()* +, 5$.E$ $= ?,# V_ 5&--?$/&/_ #;</ 'U;'6$%&4 .'P,/ &/ 5$..$4
&4 (/&'i 5'4 ';/$ E, 5'</,A E" ?,# >
BIv is assoc with piimaiy CNS lymphoma. They will ask: the iapiuly incieasing
inciuence of piimaiy CNS lymphoma can be uiiectly attiibuteu to what.
BIv
BPv causes squamous cancei of ceivix, vagina, anu vulva, anu anus of homosexuals
uue to unpiotecteu inteicouise; uue to BPv 16, 18, S1. This viius causes anal
squamous cell caicinoma in homosexuals. The viius woiks by making two pioteins,
Z` L?&5? P4$5P/ $== #N9_ L?&;, Zh P4$5P/ $= DE.
>) D'A&'6&$4
B> 5'45,- '//$5 L&6? -'A&'6&$4 C ;,<P,.&'
B> ;,<P,.&' '//$5 L&6? -'A&'6&$4 C >BX Ha_ 77 6-'4/;$5'6&$4 $= 'E;I
Papillaiy caicinoma of thyioiu is also commonly seen as a iesult of iauiation.
Example: pt hau iauiation in heau anu neck, anu has nontenuei nouulai masses in
ceivical iegion = metastatic papillaiy caicinoma of the thyioiu ielateu to ionizing
iauiation.
Example: osteogenic saicoma
Example: which meuical piofession is most subject to leukemia. Rauiologist,
leukemias aie commonly causeu by iauiation anu it's the iauiologist that aie
commonly involveu with this.
Example: if you have }acob Ciutzfelt uz, what ui aie you. Neuio-Pathologist (bc
woik with biains anu piions)
Example: basal cell caicinoma (pic), multifocal; this is non ionizing iauiation
(ionizing iauiation is the bau stuff). This is 0v B light (b is bau); 0v A light is foi
fluoiescing supeificial ueimatophytes (woou's light) oi gieen's patches in tubeious
scleiosis (theiefoie useu by ueimatologists), aka black light. 0v B light is what you
piotect youiself fiom to pievent getting skin canceis (basal cell = NC, then squamous
cell, then melanoma). 0v B = thymiuine uimmeis
Example: lesion in sun exposeu aieas that is sciapeu off anu giows back - aka solai
(actinc) keiatosis; it pieuisposes to squamous uysplasia. Aisenic is a metal that is
associateu with skin cancei) V'43;'A,/? ?'/ E'A L'6,- /<##;" L?&5? 5$46'&4/
'-/,4&5_ 6?,-,=$-, 6?," ?'J, ' ?&3? 4<.E,- $= /Y<'.$</ /P&4 5'45,-/_ '4A L&6?
6&., &6 5'4 ;,'A 6$ 5'45,- $= 6?, ;<43_ '4A '43&$/'-5$.' $= 6?, ;&J,-)
Example: kiu with white eye ieflex - ietinoblastoma - c'some 1S. This uz is spoiauic
anu familial. It takes the spoiauic uz 2 sepaiate mut'n to become ietinoblastoma
(knock off on each c'some 1S). If it is familial, which is Autosomal uominant it takes
just one mut'n, bc you aie boin with one alieauy inactivateu, theiefoie only neeu
one moie mutation on the othei chiomosome in oiuei to uevelop ietinoblastoma.
O?&6, ,", -,U;,% &/ 4$6 B> A<, 6$ -,6&4$E;'/6$.' \ 6?, B>> &/ 5$43,4&6';
5'6'-'56 HL?&5? 5'4 E, A<, 6$ >BF_ -<E,;;'_ $- '4" 5$43,4&6'; &4=,56&$4/I)
O?&5? A-<3 #-,A&/#$/,/ 6$ 5'6'-'56/e >$-6&5$/6,-$&A/i 6?,-,=$-, ' #,-/$4 L&6?
></?&438/ A] .'" A,J,;$# 5'6'-'56/)
Auuio File 11: Neoplasia 2 - Bematology 1
g@) W,4,6&5 A]
g,-$A,-.' #&3.,46$/' - sun exposeu aieas, auto iecessive, can cause all skin
canceis (BCC, SCC, anu melanomas), anu 6?, A,=,56 &/ &4 GQ( -,#'&- ,4]".,/.
0thei BNA iepaii uefects aie associateu with BRCA1 anu BRCA2, pSS, they splice out
the uefects, this gioup is calleu the chiomosomal instability synuiomes - wiskott
Aluiich, Blooms, Ataxia Telangiectasias, anu Fanconi's, all have piobs with BNA
iepaii.
V'/&5 -<;, $= 6?<.E =$- V>> '4A [>>0
M##,- ;&# '4A <# &/ E'/'; 5,;; 5'-5&4$.'i
;$L,- ;&# '4A A$L4 &/ /Y<'.$</ 5,;;
H6?,-,=$-,_ ;,/&$4 $4 ;$L,- ;&# C /Y 5,;;i ;,/&$4 $4 <##,- ;&# C E'/'; 5,;;I
Example: insiue nose is BCC, bc above the uppei lip
Example: keloiu - sq cell caicinomas anu S
iu
uegiee buins anu sq cell caicinoma
ueveloping in aieas of uiainage fiom the sinus anu ulcei that uoesn't heal fiom
antibiotics. So, wheievei theie is constant iiiitation, anu uivision of cells ielateu to
iiiitation, theie is an inciease susceptibility to cancei. This uoes not holu tiue foi
scai cancei tissue ielateu canceis of the lungs oi auenocaicinoma (just applies to
things on the skin - ie buins anu uiaining of sinus tiacts).
0nly bacteiia assoc with cancei. B. pyloii - auenocaicinoma anu low giaue
malignant lymphomas.
g@@) W-'A, J/ [6'3,
() W-'A, = L?'6 A$,/ &6 ;$$P ;&P,e The teim well uiffeientiateu means that the
tumoi is making something like keiatin oi glanus, anu if it's iuentifiable it's calleu
low giaue. When the cells aie anaplastic, pooily uiffeientiateu unuei the
micioscope, anu if you cannot tell what it is, then it's calleu high giaue.
Example: sq cell caicinoma can see keiatin peails; can IB it, so it's a low giaue
cancei. Example: see glanu like spaces, can IB so its low giaue
V) [6'3, C H+QBI NC staging system; goes fiom least imp to most imp (TNN)
Example: bieast cancei with axillaiy noue involvement; theiefoie, the N=1, but the
"N" is woise, bc it inuicates that cancei has spieau to othei oigans like bone, etc.
}ust bc it goes to lymph noues uoesn't mean it is the most imp piognostic factoi.
+=size of tumoi; if tumoi is ovei 2 sonometeis, it has a chance of mets
Q=noues (next most imp foi piognosis)
B=mets outsiue of noues (most imp piognostic factoi)
Stage is moie impoitant than giaue foi piognosis; anu within staging, N is the most
imp factoi foi piognosis
Example: pt with piostate cancei, which of following has it the woist. The answei
choices weie cancei limiteu to piostate, it went into seminal vesicles, it involveu the
wall of blauuei, went to lymph noues, oi bone. Answei = bone (bone iepiesents the
"N" of the TNN system - this ie is stage 4 by uefinition=mets)
Example: a sliue of a colon cancei anu a lymph noue: what is most impoitant - size
of tumoi oi lymph noue involvement. Lymph noue. If it was also in the livei, what is
most imp. Livei specimen is the most imp piognostic factoi.
g@@@) !$/6 A,=,4/,/ - most impoitant is Cytotoxic CB8 T cell
0theis - NK cells, Ab's, maciophages, type 2 BPY
In hospital, they look foi alteieu NBC class I Ag's in the cancei pt, bc cancei wants
to kill T cells; they uo this by putting in peifoiins, which activate caspasases, anu this
leaus to apoptosis (the signal, fiom the peifoiins, activate the caspasases, which have
pioteases, which bieak uown the nucleus anu mitochonuiia, anu cell uies, without
any inflammatoiy infiltiate).
g@F) 26?,- A&/,'/,/ /,,4 &4 .';&34'45"0
() >'5?,%&' - cause is TNF alpha; it is iiieveisible
0nce you see a pt with uisseminateu cancei about to go into catabolic state, can give
then total nutiition, but still won't help. (Will not get muscle mass back, anu this is
uue to TNF-alpha)
V) B'4" ?,.'6$;$3&5 5'</,/ $= '4,.&' /,,4 &4 .';&34'45"
NC anemia in malignancy is Anemia of chionic uisease (this is the oveiall most
common)
>$;$4 5'45,-0 ;,=6 /&A, $E/6-<56/ LR -&3?6 /&A, E;,,A/i &= "$< ?'J, D+ /&A,
E;,,A &4 5$;$4 5'45,-_ T, A,= '4,.&' &/ J,-" 5$..$4)
Nets to BN anu ieplace BN
0i, use chemotheiapy uiugs that aie cell cycle specific oi cell cycle nonspecific -
they wipe out the maiiow
Can have autoimmune mechanism with ceitain malignant uz.
>) (//$5&'6&$4/ L&6? A&//,.&4'6,A 5'45,-/0
1. Nost pts with uisseminateu canceis aie ?"#,-5$'3<;'E;,, meaning that they
have a tenuency foi foiming clots. Classic Example: a pt with painless jaunuice, left
supiaclaviculai noue (this is a uistiactei), hau light coloi stools, lesions that jump
fiom one pait of bouy to next - tiousseau's sign: a supeificial migiatoiy
thiombophlebitis uue to caicinoma of the heau of the pancieas). Pancieatic canceis
can ALS0 mets to left supiaclaviculai noue (viichow's noue), anu often uesciibe
tiousseau's sign, which is a vasculai pioblem in the veins that jumps fiom one place
to the next.
2. Anothei common thing seen is uisseminateu canceis is 6?-$.E$5"6$/&/ - an
elevateu platelet count. 0thei causes of thiombocytosis: Fe uef, splenectomy (ie see
scai on abuomen), TB, anemias. If you cannot finu any obvious cause of
thiombocytosis then the cause is cancei.
4u% of uisseminateu canceis aie thiombocytosis
0i a uo a stool guaic foi colon cancei
G) B>> =,J,- &4 .';&34'45" C 3-'. 4,3) &4=,56&$4. An E. coli if you have an
inuwelling cathetei; Pseuuomonas if you have a iespiiatoi, staph auieus can also be
the cause fiom an inuwelling cathetei, but this is giam "+".
NCC ueath in cancei = infection
gF) :'-'4,$#;'/6&5 /"4A-$.,/
These aie signs anu sometimes symptoms saying that you may have an unueilying
cancei piesent. Its impoitant bc when you iecognize the signs anu symptoms, then
you can catch the cancei befoie it metastasize.
B> :'-'4,$#;'/6&5 /"4A-$., C ?"#,-5';5,.&'
2 mechanism foi hypeicalcemia in malignancy:
1) mets to bone, piouuce a chemical (IL-1, PuE
2
, both of which activate osteoclasts)
that piouuces lytic lesions in bone, anu you get hypeicalcemia
2) ienal auenocaicinoma oi squamous caicinoma of mainstem bionchus that sits
theie anu makes PTB-like peptiue anu causes hypeicalcemia bc it acts like PTB anu
bieaks uown bone. This is Paianeoplastic, but it's not the most common one.
Example: 2 black lesions - both aie maikeis foi gastiic auenocaicinoma; usually
unuei the aim - calleu acanthosis nigiicans, anu othei is calleu seboiiheic keiatosis
(these aie not neoplasms); howevei, when these suuuenly uevelop oveinight, you
get multiple outcioppings (lesseii tiee-ai sign), anu the outcioppings is a phenotypic
maikei foi 3'/6-$'A,4$5'-5&4$.'; this is easy to iemembei bc 2 black lesions aie
maikeis fiom gastioauenocaicinoma.
Example: 5;<EE&43 - inflammation beneath on the bone calleu peiiostitis; inflamm
of unueilying bone causes piolifeiation of the soft tissue aiounu it, which leaus to
clubbing (calleu hypeitiophic osteoaithiopathy). Clubbing is not always assoc with
cancei; also assoc with bionchiectasis, IBS. But, if it's a malignancy, it is uue to
piimaiy lung uz.
Example: least common collagen vasculai uz, but the most often assoc with a
ceitain cancei. They have an elevation of seium CK; this is ueimatomyositis; iaccoon
eyes, so you see inflammation of skin anu muscle; high assoc with leukemias,
lymphomas anu lung cancei. patches of knuckles - goltiin's patches (seen in
ueimatomyositis).
Example: vegetations (steiile) on the mitial valve - assoc with mucous piouucing
canceis such as colon cancei; this is calleu maiantic enuocaiuitis-aka nonbacteiial
thiombotic enuocaiuitis; they aie not infections anu these maiantic vegetations aie
assoc with mucous secieting colon canceis. Can they embolize. Yes. You will neeu
histoiy to sepaiate fiom iheumatic fevei, but histoiy will ielate moie to colon cancei
(ie polyaithiitis)
Example: hyponatiemia oi Cushing's - cancei in the lung = small cell caicinoma,
which is secieting eithei ABB oi ACTB; also, foi small cell, they aie aput tumois,
S-1uu Ag positive, neuial ciest oiigin, neuial
secietoiy gianules.
Example: Bypeicalcemia oi seconuaiy polycythemia: ienal auenocaicinoma (can
make PTB like peptiue anuoi EP0).
Z%'.#;,0 !"#$3;"5,.&' $- /,5$4A'-" #$;"5"6?,.&'0 !,#'6$5,;;<;'-
5'-5&4$.' H6?," 5'4 .'P, Z:2 $- &4/<;&4^;&P, ='56$-I)
Example: Bypocalcemia oi Cushing's: auto uominant, anu the iaie tumoi maikei
that can be conveiteu to amyloiu (calcitonin) - meuullaiy caicinoma of the thyioiu.
gF@) +<.$- .'-P,-/
A. 2 maikeis associateu with Testiculai cancei - alpha feto piotein (AFP) (which is
ieally the albumin of a fetus) anu BCu. AFP is a makei foi-yolk sac tumoi
(enuoueimal sinus tumoi). So the tumois in kius aie yolk sac tumois (alpha feto
piotein)
AFP is also assoc with Bepatocellulai caicinoma, incieaseu in neuial tube uefects
(must be on folate while piegnant to pievent neuial tube uefects). In Bown's
synuiome AFP is uecieaseu.
Naikei foi malignancy in bone, assoc with monoclonal spike: Bence }ones Pioteins
(light chain Ig), assoc with Nultiple Nyeloma.
Tumoi maikei foi piostate cancei: PSA; not sp foi cancei bc it can be also
incieaseu in hypeiplasia; it is sensitive but not specific. If you uo a iectal exam, it is
not incieaseu. PSA is N0T an enzyme; it is an Ag anu is within the actual cell. It will
not inciease with a iectal exam.
Bieast cancei (suiface ueiiveu) - 1S, S.
CEA-12S: 0vaiian cancei
CEA -Ag foi colon cancei; anu sometimes useu foi small cell, anu bieast ca. CEA can
be a pait of an immune complex, anu will get CEA: anti-CEA immune complexes
which ueposit in the kiuney, anu leau to nephiotic synuiome - this is uiffuse
membianous glomeiulonephiitis = NC oveiall cause of nephiotic synuiome. Nany of
these aie ielateu to malignancy bc CEA can be the Ag that is ueposits in the
glomeiuli.
woman with a tiophoblastic mole, what woulu you get. Beta BCu
What is NC piimaiy tumoi of the biain in kius. Ceiebellai cystic astiocytoma (B9).
It's not meuulloblastoma. All astiocytomas aie B9 (if askeu what is the most
common malignant piimaiy tumoi, anu then the answei is meuulloblastoma, which
ueiives fiom ceiebellum). NC actual tumoi of the biain - ceiebellai tumoi ueiiveu
fiom astiocytes;
B> 5?&;A?$$A 5'45,- = ALL leukemia (othei chiluhoou tumois incluue CNS
tumois, neuioblastomas (in the auienal meuulla), Buikitts, Ewing's (tumoi of bone
with onion skinning), embiyonal ihabuomyosaicoma.)
(A<;6/: inciuence:
in woman: bieast, lung, colon
In men: piostate, lung, anu colon
Killeis: lung is #1 in both (followeu by piostatebieast anu colon)
2
nu
NC cancei anu cancei killei in men anu women combineu = colon
Theiefoie, fiom age Su anu on, you shoulu get a iectal exam anu a stool guaic.
Aftei Su, NCC cancei of "+" stool guaic is colon cancei.
B> 3"4 5'45,-0 enuometiial (#2 is ovaiian, anu #S is ceivix)
Ceivix is least common bc Pap smeai. When you uo a ceivical pap, picking up
ceivical uysplasia, not ceivical cancei (theiefoie the 'inciuence' isn't the highest).
Bc ceivical pap smeais; the inciuence of ceivical cancei has gone uown
significantly bc the uetection of the piecuisoi lesion, ceivical uysplasia. So, bc
ceivical Pap smeai, inciuence of ceivical cancei has gone uown uiamatically (picking
up the piecuisoi lesion); with mammogiaphy, the inciuence of bieast cancei
uecieases, same with PSA.
B> W"4 5'45,- P&;;,-0 ovaiian (#2 = ceivical, #S = enuometiial); theiefoie to
iemembei, the NC has the best piognosis - enuometiial is NC anu has the best
piognosis.
What is the only known existing tumoi vaccine. BBv .why.
NC infection tiansmitteu by acciuental neeule stick in the hospital = Bepatitis B
Bc viial buiuen of Bepatitis B is gieatei than any infection, even moie so than BIv.
So, with the Bepatitis B vaccine, you won't get thiee things (1) Bepatitis B, (2)
Bepatitis B (iequiies Bep B), anu (S) hepatocellulai caicinoma (ielateu to Bepatitis
B ielateu ciiihosis).
Bow uo you eiauicate hepatocellulai caicinoma. vaccination (ie in the Fai East).
CHAPTER 6. Hematology:
DV>
@) +?&4P E&3 #&56<-,)
() B>F k lf0 B&5-$5"6&5 '4,.&'8/0 Fe uef = NC anu Anemia of chionic uz,
thalassemias, siueioblastic anemias
V) B>F m 1ff0 B'5-$5"6&5 '4,.&'8/0 B12Folate uef = NC; usually folate uef in an
alcoholic
>) B>F lf^1ff0 Q$-.$5"6&5 '4,.&'8/0 low ieticulocyte ct coiiecteu: aplastic
anemia, ienal uz; high coiiecteu ieticulocyte ct: hemolytic anemias - heieuitaiy
spheiocytosis, sickle cell, u6PB uef, autoimmune hemolytic anemia,
micioangiopathic
D,6&5<;$5"6, 5$<460
Reticulocyte count next to CBC is the fiist step in the woik up of any anemias. What
is ieticulocyte. Young RBC. In 24 his, a ieticulocyte will become a matuie RBC with
a biconcave uisk.
If you have an anemia, the ieticulocyte count is impoitant bc it tells you wheie the
pioblem is: is the piob in the Bone Naiiow in making the RBC, oi is it a piob outsiue
the Bone Naiiow causing the pioblem. To ueteimine this, look at ieticulocyte ct. If
the BN was the piob, then the ieticulocyte ct woulu not have an appiopiiate
iesponse. What is an appiopiiate iesponse. You woulu have a BN with ibc
hypeiplasia, that has iev'u itself up, anu making RBC's anu shoulu be putting
ieticulocytes out piematuiely, theiefoie woiking coiiectly to coiiect the anemia.
Theiefoie, it tells whethei the BN is iesponuing appiopiiately oi not. If you have
bloou loss iight now, uo not expect ieticulocyte ct to be elevateu in 24 his; it takes at
least S-7 uays to get the iesponse of making moie ieticulocytes (like the kiuney
making bicaib, which takes a few uays (S-4) to make). If nothing is wiong with the
BN, then it shoulu host a noimal ieticulocyte iesponse; if theie is something wiong,
will not have a noimal iesponse (imp bc might ueciue whethei you have to uo a BN
exam oi not). Theiefoie, if you have a noimal ieticulocyte ct, uo not uo a BN exam.
Puipose of Reticulocyte count
1. Tells us if the bone maiiow is functioning noimally.
2. If we neeu to uo bone maiiow biopsy, in case BN pathology.
>$--,56,A D,6&5 5$<46 m 9n C 4$-.'; VB =<456&$4 (no neeu foi BN biopsy)
>$--,56,A D,6&5 5$<46 k 9n C ;$L VB =<456&$4 (BN biopsy is uone)
In anemia, the ietic count is high |False Bigh Reauingj. This can mask any ieuuceu
BN function. So we wont be able to test foi BN function. So we neeu to coiiect it foi
the uegiee of anemia. We uo it by stanuaiuising it against noimal hematociit.
!,.'6$5-&6 C !E % 9 . eg 1S x S=4S
>$--,56,A -,6&5<;$5"6, 56 C H !56RKN I % -,6&5<;$5"6, 5$<46 $= #6)
Example: pt's Bct is 1S% (which is veiy seveie anemia), anu the ieticulocyte ct that
was initially measuieu is 9% (which is incieaseu - anything ovei S% is incieaseu).
This 'looks' like the BN is iesponuing coiiectly bc the iet ct is 9% (but have to
coiiect foi the uegiee of anemia). 1S4S X 9 is S; so, when we coiiect foi the anemia,
we have S%; that's what the coiiecteu is - theiefoie, S% oi gieatei = goou iesponse;
S% oi less = bau iesponse; so, this figuie is saying that it is a ieasonable iesponse
occuiiing in the pt.
Seconu example . Bb = Sg% anu ietic count = 6%. (BCT = S x S = 1S)
0n the suiface it looks like noimal iesponse. as ietic count ius > S%
Coiiecteu ietic count = | 1S - 4S j X 6 = 2%. It tuins out that this is not auequate
iesponse . So, uo a bone maiiow biopsy.
Sliue of a ieticulocyte (know what it looks like) - neeu to uo a special giemsa stain
to see the black filaments (which aie RNA filaments); bc they aie RNA filaments, the
ieticulocyte is still synthesizing Bb. So, in about 24 his, 2S% the noimal Bb is being
synthesizeu anu neeu RNA filaments; cannot see these without uoing a special stain
(look like little black woims in the RBC - uo not confuse with Beinz bouy).
Anothei sliue using iight giemsa stain of ieticulocyte with bluish stain -
polychiomasia. These aie youngei bloou cells than the 24 hi olu ieticulocytes. They
still have the basophilia, which is not noimally piesent in the peiipheial bloou; so,
when we see them, it means that the BN is ieally iesponuing, anu pushing even the
youngei ones out.
Theiefoie, whenevei the boaius say's 'polychiomasia', they aie talking about these
cells anu these cells take 2-S uays befoie they become a matuie RBC. Why is this
imp. Bc we have to make an auuitional coiiection - why. When we aie woiking up
an anemia, we uo a coiiecteu iet ct anu want to know how the BN is iesponuing
iight now at this uay. Not inteiesteu about what will happen in 2-S uays, but what
will happen iight now. Beie's the piob: when they uo a ieticulocyte stain, these guys
will also have RNA filaments anu will be counteu in the iet ct anu it will show a
falsely elevateu iet ct (we uon't want these bc they take 2-S uays b4 they become a
matuie RBC) insteau we want the noimal guys theie. So, how uo we factoi them out.
Biviue by 2. So, make the fiist coiiection foi the uegiee of anemia (uiu it with S% in
this case), look at CBC anu see nothing that says polychiomasia. Let's say the CBC ct
says 'polychiomasia piesent' - then have to make an auuitional coiiection by
uiviuing by 2. All of a suuuen, it is now 1.S% anu this is not a goou ieticulocyte
iesponse! [$_ L?,4 "$< /,, 6?, 6,-. c#$;"5?-$.'/&'d_ 6?,4 "$< ?'J, 6$ .'P,
'4 'AA&6&$4'; 5$--,56&$4 E" A&J&A&43 E" 7)
If the Peiipheial Bloou smeai says polychiomasia piesent. The coiiecteu ietic
count is
>$--,56,A -,6&5<;$5"6, 56 C o H !56RKN I % -,6&5<;$5"6, 5$<46 $= #6) p q 7
,3) o H1NqKNI g a p q 7 C 1)Nn
@@@) [&A, 4$6,/0
When looking at CBC you can make many ux's.
Rule of S is goou: Bb x S shoulu ioughly equal the Bct
Example: foi pievious ie, hau 1S% Bct, theiefoie the Bb was a S
Tiansfusion of packeu (not whole) RBC's - foi eveiy unit tiansfuseu inciease the Bb
by 1 anu the Bct by S%. Example: pt with S giam Bb, anu given S units of packeu
RBC's. The following uay the Bb is 6 anu the Bct is 18, is that an appiopiiate
iesponse. N0, it shoulu've been 8, with Bct of 24. It wasn't 8 bc the pt has a uI
bleeu (pt was bleeuing).
B>> '4,.&' L$-;AL&A, C T, A,= '4,.&'
B>> 5'</, $= T, A,= H$J,-';;I C W@ E;,,A
B>> B&5-$5"6&5 '4,.&' C @-$4 G,==
+?,-,=$-,_ 6?, B> -,'/$4 L?" !E '4A !56 A$486 3$ <# '=6,- 6-'4/=</&$4 &/ ER5
E;$$A ;$//_ B> A<, 6$ W@ 6-'56 E;,,A)
Reticulocyte - cannot see with iight giemsa stain; use special giemsa stain to see
RNA filaments . BB iibosomes (look like uots |not linesj - BAS0PBILIC STIPPLINu,
seen in leau poisoning).
@F) DV> &4A&5,/ \ B>F - how big is the cell. Best way to classify is with NCv (mean
coipusculai volume) Small, noimal oi big. The machine has the RBC's pass thiough
an apeituie anu sizes it. Anu then takes an aveiage; this is the best way foi
classifying an anemia
NCv: < 8u, it is miciocytic (if you play ouus, its Fe uef)
NCv: 8u -1uu =; have Noimocytic anemia;
NCv above 1uu = maciocytic (b12 oi folate)
If you have small anu laige cells (uimoiphic popcoin of RBC's) it will be Noimocytic
(Like the met aciuosis, anu iesp alk, but noimal pB). So, how coulu you have a Fe
uef anemia anu a folate uef anemia at the same time. Know wheie these things aie
ieabsoibeu - Fe ieabsoibeu in the uuouenum, Folate is ieabsoibeu in the jejunum,
anu B12 is ieabsoibeu in the teiminal ileum. FFB. So if you have all these, you have
/.';; E$L,; A] H&, 5,;&'5 A]I; pt has malabsoiption that affects uiff aieas of the
bowel. Example: celiac spiue (NCC malabsoiption) - involves uuouenum anu
jejunum, theiefoie will have uef of Fe anu folate, anu will have small cells anu laige
cells. Example: if it involves the jejunum anu teiminal ileum, you will have folate anu
B12 uef.
F) DGO \ DV> G&/6-&E<6&$4 O&A6?
This machine looks at the RBC's anu tells if the RBC's coming out of the apeituie aie
all unifoimly small, noimal, maciocytic, oi uiffeient in size. So, the RBW uetects a
change in size of the RBC's anu it iepoits it as a numbei. Example: miciocytic
anemia, with an incieaseu RBW; this tells us that is miciocytic, anu theie aie
uiffeient sizeu miciocytic cells. Example: if you uevelop miciocytic anemia oveinight
anu all the cells aie Fe uef, the cells uon't become miciocytic immeuiately; they aie
noimocytic fiist befoie they become miciocytic, anu theie will be a size vaiiation
pickeu up by the RBW.
Beie's the tiick: when you look at the CBC, anu it shows A,5-,'/,A B>F L&6? '4
&45-,'/,A DGO_ 6?&/ &/ T, A,= '4,.&' & not thalassemias bc that is genetic anu
ALL the cells aie miciocytic).
Fe ueff anemia = RBW high (not enough time foi all cells to become miciocytic)
Thallasemia = RBW noimal (pathology since biith, all cells aie miciocytic)
Sliue with high RBW - has laige anu small cells.
Anothei sliue with spheiocyte (have too little membiane, anu theiefoie cannot holu
a biconcave uisk - an anoiexic cell).
Taiget cell (in the backgiounu)(has too much membiane anu too much Bb collects
in theie anu looks like a bull's-eye - an obese cell). Taiget cells aie impoitant
maikeis foi alcoholics bc they have alteieu cell membiane uue to an alteieu
cholesteiol concentiation of the membiane anu maikeis foi hemoglobinopathies (ie
thalassemias, SCB, BbC).
Sickle cell = too little membiane small cell
Taiget cell = too much membiane laige cell
Natuie RBC looks like biconcave uisk anu is thin in the miuule bc theie is less Bb
theie, anu moie is concentiateu at the euges; this is why theie is a cential aiea of
palloi in a noimal RBC when it lying flat. All miciocytic anemias have one thing in
common: uecieaseu Bb synthesis; with less Bb, the ieuness of the cell with ueciease
anu see gieatei aiea of palloi will inciease (anu if you play ouu it's IBA). Spheiocyte
- too lil mem, theiefoie it's a spheie; N0 cential aiea of palloi! (All ieu, no cential
aiea of palloi). Niciocytic anemias all have a PALE, blank coloi to them; theiefoie, it
is veiy easy to IB spheiocyte anu miciocytic cells with hypochiomia anu IBA of
chionic uz.
Auuio File 12: Bematology 2
F@) Q$-.$5"6&5 (4,.&'0
Foi noimocytic anemia, you neeu to look at the ieticulocyte count.
Fiist, you have to coiiect foi the uegiee of anemia (Bct4S X iet ct).
Then look to see if theie is polychiomasia, if theie is polychiomasia (then uiviue

by 2);
S% oi highei = BN iesponuing noimally, anu 2% oi lowei = not iesponuing

piopeily.
:?"/&5'; /&34/ $= '4,.&'0 -
Spoon nails = Koilonychia (Fe)
Spoon nails with ciacking = Kelosis (Fe, Riboflavin , non specific)
Palloi of conjunctiva = have 6 giams oi less of Bb
Palmei ciease - woiks foi white people - if uon't see ieu, pt is anemic
In women, often uue to Fe uef
Leau line - uiscoloiation in gums uue to leau poisoning
Neuiologic exam veiy imp in B12 uef bc the posteiioi columns aie knockeu off anu
lateial coiticospinal tiact, theiefoie have piopioception abnoimalities anu uecieaseu
vibiation sensation anu babinski (lateial coitical).
F@@) B&5-$5"6&5 '4,.&'/
() T, /6<A&,/ \ K T, /6<A&,/0
1) [,-<. T, (noimal = 1uu, like the alveolai 0
2
),
7) [,-<. T,--&6&4 r[6$-'3, :-$6,&4s best test - this is a soluble, ciiculating foim
of Fe stoiage; it iep the amount of Fe stoieu in the BN, so, if you hau to pick one test
foi ux of Fe uef, anemia of a chionic uz, oi Fe oveiloau, you woulu pick seium feiiitin
bc this is the best scieening test.
9) +-'4/=,--&4 R +@V> r6-'4/#$-6 #-$6,&4s (total Fe binuing capacity); the caiiying
piotein foi Fe is tiansfeiiin (tians = 'caiiys') anu it is maue in the LIvER.
Noimal=Suu
4. n /'6<-'6&$4 = seium Fe uiviueu by TIBC. Noimal=SS%
Iion stoies uecieaseu = TIBC incieaseu
V) 9 -<;,/0
1. Tiansfeiiin anu the TIBC is the SANE! (Remembei tiansfeiiin is what caiiies Fe).
2. Theie is a ielationship of Fe stoies in BN with the tiansfeiiin synthesizeu in the
livei. When the Fe stoies in the BN aie ueficient (ie Fe uef anemia), that is the signal
foi the livei to make moie tiansfeiiin, so it's incieaseu; theiefoie, TIBC will also be
incieaseu in Fe uef. Theiefoie, low Fe stoies = incieaseu tiansfeiiin synthesis anu
incieaseu TIBC (an inveise ielationship); also, if Fe stoies inciease, tiansfeiiin anu
TIBC will ueciease (ie Fe oveiloau - hemochiomatosis, tiansfusions)
S. % satuiation is a calculation = seium FeTIBC (noimal seium Fe is 1uu anu
noimal TIBC is Suu, theiefoie, the % sat'n is noimally 1uuSuu = SS% - theiefoie,
1S of the binuing sites aie occupieu with Fe.
These aie the teims anu Fe stuuies we use, esp foi miciocytic anemias (ielateu to
Fe pioblems).
>) :'6?$3,4,/&/ $= .&5-$5"6&5 '4,.&'/
All miciocytic anemias aie miciocytic (bc they have a pioblem making Bb). When
the RBC is ueveloping in the maiiow, it's the Bb concentiation within the RBC that
ueteimines the numbei of cell uivisions. Theiefoie, if the Bb synthesis is uecieaseu,
it is a signal in the maiiow to inciease the numbei of mitoses. When cells mitoses,
they go fiom something oiiginally big to something small. So bc of the ueciease in
Bb syn, theie aie extia uivisions anu theiefoie the cell is smallei.
All foui gioups of miciocytic anemias have a ueciease in Bb.
Bb = heme + globin; Beme = Fe + piotopoiphyiin; ulobin is maue by the bouy -
alpha (), beta (), uelta (), gamma (); BbA -22; BbA2-22; BbF- 22
We can uispense 2 of the 4 miciocytic anemias immeuiately:
T, A,= = uon't have Fe, theiefoie theie is no Fe to foim with piotopoiphyiin to foim
heme; so, 4$ T, C 4$ ?,., C 4$ !E
G) :'6?$3,4,/&/ $= (4,.&' $= 5?-$4&5 A]
When we have inflammation, oui bouies iesponu to inflammation as if it is an
infection. In micio, bugs inciease theii iepiouuction with Fe, theiefoie, the moie Fe
they have, the moie they iepiouuce. Same concept: with anemia of chionic
inflammation anu bouy assumes it is subject to a bacteiial infection, the object is to
keep Fe away fiom the bacteiia. Bow uoes it uo that. Its like a safety ueposit box,
anu you have the key - Fe is noimally stoieu in maciophages in the BN - this is
wheie tiansfeiiin goes (to the maciophage) to pick up the Fe anu take it to the RBC.
If you uon't want bacteiia to have access to the Fe, it will be lockeu away in the
maciophages in the BN anu the 'key' to the maciophages will be lost; theiefoie, theie
is lots of Fe in the maciophages of the BN, but cannot get it out. Bowevei, the goou
news is that you aie keeping it away fiom the bugs so they uon't iepiouuce. Bau
news - keeping it away fiom the RBC's, anu theiefoie have an ueciease in Bb
synthesis. Bowevei, unlike Fe ueficiency, wheie theie is no Fe in the maciophages of
the BN, theie is PILES of Fe, but the 'key' have been lost anu you cannot get it out. So,
iiiespective of that, youi seium Fe is uecieaseu bc it is all lockeu in the
maciophages, anu you uon't have enough Fe to make heme. So, it's the same
mechanism as Fe uef, but foi uiffeient ieasons: (1) you have no Fe (IBA) anu (2) you
have lots of it, but its lockeu in the safety ueposit box anu you cannot get it - so,
eithei way, you cannot make heme anu theiefoie you cannot make hemoglobin. +$
A&/6&43<&/? E,6L,,4 @G( '4A (>G]_ 6?,-, '-, ?&3? =,--&6&4 ;,J,;/ &4 (>G]_
L?,-,'/ 6?,-, &/ ' ?&3? +@V> &4 T, A,= '4,.&'
Z) !,., /"46?,/&/
Ceitain ixns in biochem occui in the cytosol, the innei mito membiane (ox phos),
mito matiix (beta ox of FA's, TCA), anu in the cytosol ANB the mitochonuiia
(gluconeogenesis, which staits in the mito anu enus up in the cytosol, uiea synthesis,
which staits in the mito anu goes to the cytosol anu back into the mito, anu heme syn
- in mito, then cytosol, anu then again in the mito). So, theie aie S biochemical ixns
in the mito anu cytosol.
Fiist pait of heme syn (aka poiphyiin syn) begins in the mito. Fiist ixn is succinyl
coA (substiate in TCA cycle anu substiate foi gluconeogenesis), which can be put
togethei with glycine (which is an inhibitoiy neuiotiansmittei of muscle, blockeu by
tetanus toxin ihesus saiuonicus anu tetanic contiaction - so when glycine is
inhibiteu, the muscles aie in a tonic state of contiaction). Know all RATE LINITINu
Enzyme's (RLE) foi eveiy biochemical ixn. (RLE in cholesteiol syn = BNu CoA
ieuuctase).
RLE in heme synthesis = ALA synthase, cofactoi = pyiiuoxine. So, piotopoiphyiin is
maue anu goes back to the mito. So you have piotopoiphyiin plus Fe, so you have a
metal plus piotopoiphyiin. Chelatase puts these togethei; so, it is calleu
feiiochelatase, with combines Fe with piotopoiphyiin anu foims heme. Beme has a
feeuback mechanism with ALA synthase (all RLE's have a feeuback mech). So, with
incieaseu heme, it will ueciease syn of ALA synthase, anu when heme is uecieaseu, it
will inciease ALA synthase syn.
T) :'6?$3,4,/&/ $= [&A,-$E;'/6&5 '4,.&'/ (least common of the miciocytic
anemias). "siueio" = Fe. Raiest of miciocytic anemias = /&A,-$E;'/6&5 '4,.&'/;
they have S causes:
1. Alcohol (siueioblastic anemia is N0T the NC anemia in alcohol, NCC of
siueioblastic anemia is alcohol; NC anemia oveiall = ACBz, followeu by folate uef).
Alcohol is a mitochonuiial poison anu uncouples ox phos, anu uamages innei mito
membiane, allowing piotons to go in anu uiain them off. 0n EN of the mito of an
alcoholic is huge bc they aie uamageu (calleu megamitochonuiia). Theiefoie, any
piocess that occuis in the mito is scieweu up. This, theiefoie, incluues heme
synthesis. So, Fe is ueliveieu to the RBC by tiansfeiiin anu uoesn't know wheie to
go. Some is stoieu as feiiitin, while most of it goes to the mito, which is BAB news!
Why. Bc it can get in, but CANN0T get out. So, theie is uamageu mitochonuiia that
weie uamageu by alcohol, Fe goes in anu now cannot go out. So, theie will lots of Fe
caught anu Fe builus up within the mito. Nito is locateu aiounu the nucleus of an
RBC in the BN, leauing to a iingeu siueioblast. This is the maikei cell foi
siueioblastic anemia; also in Fe oveiloau uz - will excess iion, anu will not get heme
bc mito uestioyeu (so alcohol is the NCC).
2) u6PB uef - pyiiuoxine uef; ie not taking vit B6 uuiing Rx of TB. So, no vit B6 = no
heme, anu the fiist ixn will not happen. But Fe uoesn't know that; again, Fe goes to
the mito, waiting foi poiphyiin, leauing to iingeu siueioblast.
S) leau poisoning - so leau leaus to siueioblastic anemia. Leau is a uenatuiei. All
heavy metals uenatuie pioteins (enzymes aie pioteins). Leau's favoiite enzyme to
uenatuie is feiiochelatase, so it won't woik, anu no heme = no Bb, leauing to
miciocytic anemia. Less of inhibitoiy effect, but uoes have a little one on
aminolevulinic aciu uehyuiatase. But is N0ST commonly knocks off feiiochelatase.
So, when Fe comes into mito, it cannot binu to piotopoiphyiin to foim heme. Q$
?,., C A,5-,'/,A !E C .&5-$5"6&5 '4,.&'.
Example: if feiiochelatase is uecieaseuinhibiteu, heme uecieases, but what
happens to piotopoiphyiin befoie the block. It incieases (useu to be scieening test
of choice foi leau poisoning). Not useu anymoie. Why. Bc if you uon't have Fe bc
ACBzFe uef, what will happen to the piotopoiphyiin in the mito. It will inciease.
So, they founu out that many people hau an inciease in RBC piotopoiphyiin, anu got
"-" test foi leau poisoning, anu then knew that the pts hau eithei Fe uef oi ACBz, anu
concluueu that it was not a goou scieening test.
So, now bloou leau level is the scieening anu confiimatoiy test foi leau poisoning,
not RBC piotopoiphyiin (too many false "+"'s)
W) :'6?$3,4,/&/ $= +?';'//,.&'/0 Auto iec uz's
1) (;#?' 6?';'//,.&'/ - who uo we see alpha thalassemias in. Asians (Fai
eastein) anu blacks (all genetic hematologic uz's aie seen in the black pop'n - alpha
beta thal, u6PB uef, SCBz).
1. Bb electiophoiesis - sepaiates things baseu on size anu chaige, theiefoie you
can cleaily sepaiate BbA, BbF, anu BbA2 cleaily on cellulose acetate bc they have
uiffeient migiations. So, they fluoiesce it, anu BbA, BbF anu BbA2 all settle uown.
Then they stain the cellulose acetate to see how much is theie. Then, it piouuces
uensity, anu the uensity coiielates with the concentiation of each of the Bb's. Bow
will they know the peicent. With a uensitometei - it conveits the uensity of the stain
to the peicentage. It tuins out that BbA (22) is the pieuominant Bb in an auult
(9S-9S%). BbA2 is 1-2%; BbF = 1%. These aie the noimal, which aie expiesseu as a
peicentage.
2. Alpha thalassemias, auto iec, has a pioblem in making alpha globin chains. Bo
BbA2 anu BbF iequiie BbA to be maue. Yes. Theiefoie, all will be equally uecieaseu.
This will N0T show up on an electiophoiesis, bc all aie equally uecieaseu,
theiefoie, it shows to be totally noimal. Theie aie foui genes that contiol alpha
globin synthesis. Beletion of one of these foui will not cause anemia. Beletion of 2
genes = pioblem bc minimally uecieaseu, anu theiefoie a milu anemia. It is
miciocytic bc the globin pait is uecieaseu, meaning you will get a miciocytic anemia
(ueciease in Bb conc'n, which will be the stimulus). This calleu alpha thalassemia
minoi, seen in the fai eastein pop'n anu black pop'n.
With a thiee gene ueletion, that's not goou, anu pt is ieally uecieaseu (theie is also
a hemolytic component to it). The beta chains get iiiitateu that theie is no alpha
chains aiounu, so they fiom theii own beta globin chains. So, foui beta chains get
togethei anu foim BbB. If you uo an electiophoiesis, theie will be a uiffeient iesult.
BbB is a uiff Bb, anu theiefoie will not migiate to the same place as othei Bb's. So,
you can ux this alpha thalassemia with Bb electiophoiesis (why its calleu BbB uz).
Foui gene ueletions - spontaneous aboitions (usually, theiefoie not usually boin
alive - aka hyuiops fetalis). uamma chains foim togethei (like the beta chains uiu
eailiei) anu foim a Bb with 4 gammas, which is calleu Bb Baits. This will show up on
electiophoiesis, but won't mattei bc baby is ueau alieauy. What is the spontaneous
aboition iate in fai east. Bigh bc this is wheie alpha thalassemia is most commonly
locateu. Theiefoie, if the inciuence of spontaneous aboitions is incieaseu, what
cancei iisk is incieaseu. Choiiocaicinoma (incieaseu hyuatiuifoim moles, which
leaus to choiiocaicinoma). So, theie is a high inciuence of choiiocaicinoma in the fai
east bc of alpha thalassemia. Rx - B0 N0T give Fe (will Fe oveiloau them). So, just
leave them alone. (2
nu
NCC jaunuice = uilbeit's uz - esp with lack of foou).
7) V,6' 6?';'//,.&' - blacks, uieeks, Italians. B (by itself) = making noimal beta
chains; B (with a "+") = making beta chains, but not enough; B (with a "u") = not
making beta chains at all. Beta thal is auto iec, anu has to uo with splicing uefects,
stop couons. The most seveie foim is uue to stop couon (theiefoie teiminate
synthesis of beta chains, anu uon't even make them). B&;A 6?';'//,.&': slightly
uecieaseu beta chains, piob uue to a splicing uefect; beta chains aie slightly
uecieaseu, alpha chains aie okay, uelta chains aie okay, gamma chains fine (confineu
to fetus). So, BbA will ueciease, anu uelta will get togethei (hence inciease in BbA2)
anu gamma chains get togethei (hence inciease in BbF). Theiefoie, see a ueciease in
BbA anu an inciease in BbA2 anu BbF; this WILL show up on electiophoiesis. This
happeneu bc beta chain is uecieaseu, anu it showeu a uecieaseu BbA. It is just a
milu thalassemia anu is veiy common. So, only way to ux Beta thal is with Bb
electiophoiesis. Cannot uo anything about it. Bopefully it is not the seveie type,
wheie not making any beta chains - aka Cooley's anemia anu will not live past Su y
o. Will have a constant tiansfusion iequiiement; many of these pts uie fiom Fe
oveiloau, oi Bep C oi multiple tiansfusions oi BIv.
NC in black pop'n - beta-uelta thalassemia (uecieaseu beta chains anu uecieaseu
uelta chains, so what's left aie alpha anu gamma chains). What will the
electiophoiesis show. BbF. This calleu heieuitaiy peisistence of BbF. No anemia,
just uominant BbF.
Foi thalassemias, know they aie genetic, what gioups of people they aie in, anu that
you B0N'T uo anything to them, esp giving Fe bc all theii Fe stuuies aie noimal.
!) @-$4 G,U&5&,45" (4,.&' H@G(I0
1. Causes of Fe uef anemia - look at age biackets:
a) Piematuiity - eveiyuay a baby is not in uteio, it is losing Fe (all theii Fe stoies
aie uecieaseu, so baby must be given Fe supplements).
b) Newboin - check stool foi theii bloou; neeu to know it's not mom's bloou, which
can be swalloweu. This is uone with the apt test. Nost of bloou that comes out of
baby's meconium is bloou the baby swalloweu fiom mom, anu it has BbA in it.
Bowevei, if it was BbF bloou that came out, the NCC is bleeuing meckel's
uiveiticulum. Theiefoie, bleeuing meckel's uiveiticulum = NCC Fe uef in a newboin
anu chilu. Neckel's uiveiticulum is N0T the cause of Fe uef in an auult, bc most
have bleu by foui yeais of age, anu alieauy woulu have known pt has it.
c) Woman unuei Su - NCC Fe uef = menoiihagia, theiefoie neeu to get a goou
menstiual hx; uue to anovulatoiy cycles (between 2u-4u yo, uue to ovulatoiy cycles,
inauequate luteal phase, piegnancy ielateu bleeus, enuometiial polyp that is
bleeuing).
u) Nen unuei Su - NCC Fe uef = P0B (usually uuouenal ulcei).
e) Nen anu women ovei Su - NCC Fe uef = Colon cancei
2. Lab Test -seium Fe = low, TIBC = high, % sat'n (FeTIBC) = low
If you uon't have Fe, sat'n is uecieaseu bc no Fe to put on it. Seium feiiitin level =
low
@) (>G] - ielateu to inflammation. Fe is lockeu in safety ueposit box, so you have
plenty, but cannot get it out
Seium Fe=low; TIBC=low (high Fe ST0RES = ueciease tiansfeiiin syn)
% sat = low, seium feiiitin = high
Theiefoie, main test to uistinguish ACBz fiom Fe uef = seium Feiiitin!
t) B&;A ';#?' '4A E,6' 6?'; - N0RNAL Fe stuuies bc nothing to uo with Fe, but
globin chains.
S) [&A,-$E;'/6&5 - ie smeai without appiopiiate amount of Bb in the cells,
theiefoie, they aie moie than likely to be a miciocytic anemia (Fe uef, ACBz,
thalassemia, leau poisoning). Sliue: iingeu siueioblast (only seen in BN, anu is
staineu with Piussian blue, which stains Fe bc mito aiounu the nucleus, all filleu up
with Fe - calleu a iingeu siueioblast - this is pathognomonic of a siueioblastic
anemia). So if you think that B6 is causing the anemia, neeu to piove it. Neeu to get
BN; if you think alcohol is the cause, you have to piove it.
X) X,'A #$&/$4&43 If you suspect leau poisoning; just uo a leau level (not a BN
exam). - cells with blue spots - calleu basophilic stippling. Bo not neeu a special
stain to see basophilic stippling (shows up on giemsa stain). See blue uots - leau
uenatuies iibonuclease, anu the puipose of iibonuclease is to bieak uown iibo's; if is
uenatuieu, anu uoesn't bieakuown, iibosome peisists. Theiefoie, they give a gieat
maikei in the peiipheial bloou - basophilic stippling. If it's an RNA filament, talking
about ieticulocyte. If we weie talking about peisistent iibo = leau poisoning. 0n x-
iay - epiphyses of fingei of chilu; only heavy metal that can ueposit in the epiphysis
of bone is leau (meicuiy cannot, aisenic cant, only leau can). Theiefoie, can see
ueposits in epiphyses. This is why they have failuie to giow. If you sciew up the
epiphyses of the kiu, they will not be able to giow piopeily. Clinical scenaiio - chilu
eating paintplastei leaus to leau poisoning, have seveie abuominal colic, piob with
ceiebial euema, convulsions, seveie miciocytic anemia, see leau in intestines (flat
plate). You'll see Fe in the intestines; thiee things can cause this is Fe tablets
ingesteu in a kiu, leau, meicuiy). Also, theie is a failuie to thiive. Nechanism of
ceiebial euema. Relateu to incieaseu vessel peimeability of biain anu builuup of
uelta-lemavinylinic aciu. If you block feiiochelatase, eveiything uistal to the block
will inciease (piotopoiphyiin, ueltalemavinylinic aciu) this is toxic to neuions,
leauing to ceiebial euema.
Example: guy at an automobile shop, complains of abuominal colic anu uiaiihea.
This is leau poisoning bc exposuie to batteiies. In plants, theie is exposuie to
incineiation of batteiies, anu pts aie exposeu to leau in auto factoiies
Example: moonshine - make alcohol in olu iauiatois, leaus to leau poisoning
Example: potteiy paintei - potteiy is commonly painteu with leau baseu paints. A
lot times they lick the tip of the biush, anu leaus to leau poisoning.
Example: in ceitain countiy, they use leau-baseu potteiy foi uishes, which leaus to
leau poisoning. Auults will get the neuiopathies - slapping gait (peiineal palsy),
wiist uiop (iauial palsy), claw hanu (ulnai palsy), leau lines in teeth (usually get with
colic anu uiaiihea)
B) T,R+@V>Rn/'6R=,--&6&40
Fe uef: l, h, l, l
ACBz: l, l, l, h
Alphabeta thal: n, h, h, h, uo nothing about it
Leau poisoning (anu siueioblastic anemias - Fe oveiloau like hemochiomatosis):
B, l, h, h (TIBC is low bc Fe stoies aie high!) - in Fe oveiloau eveiything is high,
TIBC is L0W
Anemia Iron TIBC % Saturation Ferritin
Iron Deficiency Anemia LOW HIGH LOW LOW
Anemia of Chronic Disease LOW LOW LOW HIGH
Alpha and Beta Thalassemias NL HIGH HIGH HIGH
Lead overload w/hemochromatosis HIGH LOW HIGH HIGH
Auuio File 1S: Bematology S
F@@@) B'5-$5"6&5 '4,.&'/
B12 anu folate aie involveu in BNA synthesis, theiefoie, if you aie B12 anuoi
folate uef, you cannot make BNA, specifically bc you have a piob with making BNP
(ueoxythymiuine monophosphate). Theiefoie, if you cannot make that, you cannot
matuie the nucleus (immatuie nuclei uo not have a lot of BNA in them, but as you
make moie BNA, the nuclei become moie matuieu, anu the nucleus becomes smallei
anu moie conuenseu). Bc BNA cannot be maue, then you have laige nucleus, anu all
nucleateu the cells in youi bouy aie big - why they aie calleu BZW(;$E;'/6&5
'4,.&'/. A goou pathologist can ux B12 anu folate uef in a ceivical pap smeai, when
looking at the squamous cells (cells look big - any cell with a nucleus has BNA in it,
so any cell with BNA will be big - not just the hematopoeitic cells that aie huge, ALL
nucleateu cells in the bouy aie big - ie uI, squamous cells)
B12 aka cobalamin; B12 has cobalt in it. Ciiculating foim of folate is
methyltetiahyuiofolate (tetia = foui). Puipose of cobalamin (B12) is to take the
methyl gioup off of methyltetiahyuiofolate. Then it's calleu tetiahyuiofolate. If you
uon't get the methyl gioup off of folate, you will not make BNA. So, if you aie B12
uef, you can't get the methyl gioup off anu cannot make BNA. If you aie uef in folate,
you can't make BNA.
Cobalamin auus a methyl to gioup homocysteine; when you auu a methyl gioup to
homocysteine, it becomes methionine. Nethionine = aa foi 1 caibon tiansfei ixns.
(Nethyl = CB
S
). If you aie B12 oi folate uef, what aie the seium homocysteine
levels. Bigh. With a ?&3? /,-<. ?$.$5"/6,&4,_ &6 #-$A<5,/ 6?-$.E$/,/_
&45;<A&43 B@8/i &6 A'.'3,/ ,4A$6?,;&'; 5,;;/_ ;,'A&43 6$ 6?-$.E$/,/_ '4A
#-,A&/#$/&43 6$ B@) So, what is NCC of incieaseu homocysteine. It is N0T
homocystinuiia (iaie auto iec uz), but B12 uef oi folate uef, anu folate is NC than
B12. Theiefoie, the NCC of incieaseu homocysteine is folate uef, anu have an
incieaseu inciuence of thiombosis anu NI. This is why caiuiologists oiuei seium
homocysteine levels. In folate uef, no methyl gioup to auu to homocysteine (so
homocysteine incieases); with B12 uef, no methyl gioup to auu to methionine to
make homocysteine theiefoie methionine incieases.
Tetiahyuiofolate is the stait of the cycle, anu leaus to piouuction of thymiuilate
synthase - this is wheie BNA is maue. B0NP is conveiteu to BBT, making BNA.
Theiefoie, this substiate is necessaiy to make BNA. So, it is useu in the making of
BNA by an enzyme calleu uihyuiofolate ieuuctase which conveits oxiuizeu
uihyuiofolate to tetiahyuiofolate. Nany uiugs block uihyuiofolate ieuuctase -
methotiexate, TNP-SNX. The uiugs block BNA synthesis (ie uecieasing BNA
synthesis) theieby leauing to maciocytic anemia. So, the functional B12 takes the
methyl gioup fiom tetiahyuiofolate anu gives it to homocysteine to make
methionine. Anu tetiahyuiofolate will stait the cycle foi making BNA.
() V17
1. B12 Reactions: B12 is humiliateu by having to tiansfei methyl gioups. This is
an ouu iequest - so whoevei he askeu saiu that they can take caie of even chaineu
FA's, but we have a pioblem with 0BB chaineu FA's bc we can only bieak uown till
piopiionyl CoA, which leaus to uementia anu piopiioception loss. V17 ?,;#/ &4 $AA
5?'&4 T( .,6'E$;&/.. Theiefoie, it is involveu in piopiionate metabolism, which is
metabolism of an ouu chain FA. Piopiionate foims methylmalonyl CoA, wheie B12
comes in anu helps conveit methylmalonyl CoA to succinyl CoA, which can go into
the TCA cycle. In B12 uef, ceitain things will builu up, such as piopiionate anu
methylmalonyl CoA. Nethylmalonyl CoA becomes methylmalonlylic aciu, which is a
sensitive anu specific test foi B12 uef. So, with B12 uef, get a methylmalonlylic aciu
test (which will be incieaseu). Reason foi neuiological pioblems is bc piopiionate
metabolism; without B12, cannot conveit ouu chain FA's into succinyl CoA, anu they
builu up, anu it sciews up myelin (cannot syn myelin) - anu leaus to uemyelination
of posteiioi columns, anu of the lateial coiticospinal tiact, along with uementia. Bc
it is a posteiioi column uz, you will have piobs with piopiioception, vibiation; bc
you knock off the lateial coitical spinal tiact, you will get 0NN lesions (spasticity,
babinski), anu then uementia.
Will always tell you that you can have B12 uef, anu coiiect the anemia with high
uoses of folate, but cannot coiiect the neuiologic uz. Theiefoie, must make the
specific ux. Bc if you think its folate uef anu give folate, you will coiiect the
hematologic pioblem, but not the neuiological pioblem, theiefoie have B12 uef. So,
in A&==,-,46&'; $= A,.,46&', incluue B12 uef (along with Alzheimei's). You uon't
have to have anemia with B12, but can have neuiological piobs. So, with uementia,
get a TSB level (to thiow out hypothyioiuism), anu a B12 level to iule out B12 uef b
c these aie REvERSIBLE causes of uementia.
Puie vegan vs. ovo-lactovegan: In ovo-lactovegan taking uaiiy piouucts (which aie
animal piouucts), theiefoie, uo not have to take B12 supplements. Bowevei, a puie
vegan uoes have to take B12 supplements.
2. Noimal sequence of B12 absoiption: Bave to eat meats oi uaiiy piouucts to get
B12. The fiist thing B12 uoes is binus to R factoi in saliva. R factoi piotects B12
fiom uestiuction by aciu in the stomach. Intiinsic factoi (IF) maue by paiietal cells
in the bouy funuus; they also make aciu. IF is not uestioyeu by aciu, theiefoie uoes
not neeu anything to piotect it. So the B12R factoi complex goes into the
uuouenum, wheie theie is IF waiting foi it. R factoi must be cleaveu off, which is
uone with enzymes fiom the functioning pancieas. Then, IF anu B12 binu to eo anu
take a long tiip. Bo not go to uuouenum (Fe countiy), uo not go to ligamentum of
tiietz in the jejunum (folate countiy); so they go all the way to the teiminal ileum,
wheie theie aie ieceptois foi IF, anu it is ieabsoibeu. This is the same place bile
salts aie ieabsoibeu, anu the same place the Ciohn's uz hits. Theiefoie, it is faii to
say that with Ciohn's uz, you also have bile salt ieabsoiption pioblems anu B12 uef.
S. Causes of B12 ueficiency:
'I B>> V17 A,= C #,-4&5&$</ '4,.&'; this is an autoimmune uz with uestiuction
of the paiietal cells; autoAb's attack the paiietal cells anu theie aie autoAb's against
IF anu uestioys the paiietal cells which aie locateu in the bouy anu funuus.
Eveiything gets uestioyeu leauing to an atiophic gastiitis of the bouy anu funuus. No
paiietal cells = no aciu = achyloiiuiia, anu no IF. Achyloiiuiia is a majoi pieuisposing
factoi foi gastiic auenocaicinoma.
b) Causes of B12 uef: puie vegan; chionic pancieatitis seen in alcoholics (this leaus
to B12 uef bc can't cleave off the R factoi); B. latum (fish tapewoim that eats B12
(iaiest) - fiom fish in lake tiout in lakes of Chicago); teiminal ileum uz (Ciohn's).
Anu bacteiial oveigiowth uue to peiistalsis piob anuoi uiveiticulai pouches anuoi
stasis. Whenevei theie is stasis you'll get bacteiial infection (also blauuei infection);
bacteiia love B12 anu bile salts with bacteiial oveigiowth. All of these will leau to
B12 ueficiency.
V) T$;'6,
Folate is seen in animal anu plant piouucts, theiefoie not seen in vegans. Folate has
many phaim ties (ie uihyuiofolate ieuuctase). When you eat folate, it's in a
polyglutamate foim, meaning you cannot ieabsoib it in the jejunum; theiefoie it has
to be conveiteu to a monoglutamate foim. Intestinal conjugase (in the small
intestine) is iesponsible foi this. O?'6 A-<3 E;$5P/ &46,/6&4'; 5$4u<3'/,e
:?,4"6$&4) So, if they ask about pt on Phenytoin, with maciocytic anemia,
hypeisegmenteu neutiophils, neuiological effects aie N0T piesent - theiefoie folate
uef (bc theie aie no neuiological pioblems, this io b12 uef.) Now you have
monoglutamate, which is absoibeu in the jejunum. Theie aie 2 things that inhibit its
absoiption: (1) biith contiol anu (2) alcohol HB>> =$;'6, A,= C ';5$?$;&/.I. With
B12, have 6-9 yeai supply in livei, theiefoie its uncommon to get. Folate only has
S-4 month supply - so, even if you have an excellent uiet, you can have folate uef if
you aie taking one of these two things.
Summaiy: ciiculating foim of folate is methyltetiahyuiofolate, anu B12 takes the
folate off, anu gives it to homocysteine which becomes methionine; the
methyltetiahyuiofolate becomes tetiahyuiofolate, anu with the help of uihyuiofolate
ieuuctase, BNA is maue.
Example: pic with hypeisegmenteu neutiophil (uefinition: S oi moie lobes!).
Bypeisegmenteu neutiophil inuicates B12 oi folate uef, even if you uon't have
anemia. It is the fiist thing that comes up befoie anemia. Anu if the neuiological test
is noimal, it's a folate uef. Test foi piopiioception: Rhombeig test - if you have post
column uz, piob with piopiioception bc uo not know wheie youi joints aie; uoes
not show ceiebellai ataxia (will have these with eyes openeu ANB closeu). 0se
vibiating tuning foik to see if pt has piopiioception on the malleous.
Bematopoetic cells aie maue outsiue the sinusoius in the BN. It's analogous to the
coius of bilioth in the spleen (wheie theie aie fixeu maciophages anu then, the
RBC's anu WBC's have to get back into the sinusoius anu ciiculate thiough holes.
They get thiough, anu aie in sinusoius). The same thing occuis in the BN - they have
a place equivalent to the coius of bilioth anu that is wheie they aie maue. To get into
the ciiculations, they have to fit thiough lil, naiiow holes to get into the sinusoius in
the BN anu into the bloou stieam. Something veiy big will not be able to get thiough
the lil holes anu into the sinusoius. Theiefoie, maciophages will want to feast on the
maciocytic cells (WBC's, RBC's, platelets) that cannot get into the sinusoius. So, the
maciophages kill them all. So in the peiipheial bloou, will see N0TBINu -
pancytopenia; seveie maciocytic anemia, neutiopenia, thiombocytopenia - which is
chaiacteiistic of B12 folate uef. (eveiything in the maiiow is too big anu cannot get
out into the ciiculation).
[5?&;;&438/ 6,/6 - goou test foi localizing B12 uef. We know now that it's a B12
ueficiency, anu we want to know what causeu it. Steps foi schilling test: uive
iauioactive B12 by mouth; they then collect the 24 hi uiine to see if any comes out in
the uiine anu nothing comes out, theiefoie piove that they have a pioblem
absoibing B12.
1
st
step: give iauioactive B12 anu IF, collect uiine foi 24 his, anu piles in the uiine =
Peinicious anemia; bc auueu what was missing (IF); if it uiun't woik, you can
EXCL0BE peinicious anemia.
Say this uiun't woik, then you:
2
nu
step: give 1u uays woith of bioau spectium antibiotic; pt comes back anu again
you give them iauioactive B12; see piles of iauioactive B12 in the uiine, what is ux.
Bacteiial oveigiowth bc knockeu off the bugs eating B12
Say this uiun't woik, then you:
S
iu
step: pancieatic extiact, swallow pills, then give iauioactive B12; 24 his latei,
see what happens; if theie is iauioactivity in uiine, pt has chionic pancieatitis.
If that uiun't woik, coulu be Ciohn's, woim, etc.
Summaiy:
If B12 malabsoiption was coiiecteu by auuing IF, pt has peinicious anemia
If B12 coiiecteu by auuing an antibiotic, pt has bacteiial oveigiowth
If B12 is coiiecteu by auuing pancieatic extiact, pt has chionic pancieatitis.
@g) Q$-.$5"6&5 '4,.&'/
When you uo the coiiections foi the anemia anu look foi polychiomasia; if
coiiection is less than 2%, it is a bau iesponse (BN not iesponuing coiiectly). Fiist
two things you see: eaily IBA anu ACBz - iemembei that you have to have a
noimocytic anemia fiist to become miciocytic. Boesn't occui oveinight. Theiefoie,
with a uecieaseu iet ct (ie less than 2%), must incluue miciocytic anemia's in the
uiffeiential, anu you neeu to get a feiiitin level.
IBA goes thiough uiff stages: fiist thing that happens - uecieaseu feiiitin, then Fe
uecieases, TIBC incieaseu, % sat ueciease, anu still won't have anemia. In othei
woius, all Fe stuuies aie ABN0RNAL befoie you have anemia. Then you get milu
noimocytic anemia, anu eventually miciocytic anemia.
() >'</,/0
1. Bloou loss less than a week = noimocytic anemia; no inciease in iet iesponse bc
nothing wiong with the BN, anu not enough time (neeu S-7 uays foi BN to get iev'u
up) - so, aftei one week, woulu get an appiopiiate iesponse.
2. Aplastic anemia - no maiiow; if that is tiue, the peiipheial bloou will show
pancytopenia (all hematopoetic cells aie uestioyeu in the maiiow); have noimocytic
anemia, thiombocytopenia, anu neutiopenia.
S. NC known C = uiugs: chloiamphenical - useu in iocky mtn spotteu fevei,
inuomethacin, phenylbutazone, anu thyioiu ielateu uiugs
4. 2
nu
NCC = infections - esp. Bep C (wipes out eveiything); aplasia of RBC =
paivoviius
S. Rauiation anu malignancy
6. Eaily IBA anu ACBz (neeu to have seium feiiitin levels)
7. Nechanism of noimocytic anemia with less then 2% iet ct - ienal failuie, anu
uecieaseu EP0 (can be given exogenously) - uecieaseu in hep B, C, anu BIv. Athletes
that 'uope' aie given EP0, to inciease RBC's to allow moie 0
2
ueliveiy to bouy
V) B,5?'4&/./ $= ?,.$;"/&/ \ 7 L'"/ 6$ P&;; '4 DV>0
Noimocytic anemias with coiiective iet ct about S%:
1. Extiavasculaily (outsiue of the Bv).
They aie killeu by maciophages, usually in coius of bilioth in the spleen, sometimes
in livei sinusoius. Eveiy RBC must go to the coius of bilioth a few times pei uay anu
get examineu by a maciophage - if the cell pickeu up an Igu oi CSb, it is maikeu foi
uestiuction via phagocytosis bc the maciophage has ieceptois foi Igu anu CSb. If
you uon't have Igu oi CSb, can still uie bc the cell is in bau shape -abnoimal shape:
ie spheie will not be able to fit thiough a 2 micion hole to get to the sinusoius - it
can't - theiefoie, spheiocytes aie iemoveu extiavasculaily bc they cannot get out;
sickle cells cannot get out eithei bc they have a bau shape. Anothei ieason foi theii
uestiuction is bc they have something insiue them that they shoulun't -a piece of
nucleus; what is this calleu. Bowell jolly bouy; maciophage will get iiu of it.
Theie aie autoimmune hemolytic anemias, anu can be uue to Igu oi CSb on the
suiface of the RBC, oi extiavasculai hemolytic anemias is wheie you have abnoimal
shape (ie spheie, Sickle cell - will not make it out of the spleen bc iemoveu by
maciophages).
Enu piouuct of phagocytosing an RBC: unconjugateu biliiubin. When the RBC is
bioken uown, you have hemoglobin, anu theie is an enzyme that splits heme fiom
globin anu the globin is bioken into aa's anu theiefoie goes to the aa pool. Then,
takes the heme, splits it open, anu saves the Fe. Now you have piotopoiphyiin, anu
spit it out; enu iesult is unconjugateu biliiubin in the maciophage within the spleen.
Then, the maciophage spits out the unconjugateu biliiubin into bloou stieam (which
is insoluble bc it's unconjugateu). The unconjugateu biliiubin then binus albumin
anu goes to the livei anu is conjugateu. So, what clinical finuing will you see in pts
with extiavasculai hemolytic anemia. }aunuice. Boes that biliiubin get into the
uiine. No. Why. 2 ieasons: (1) Lipiu soluble anu (2) Bounu to albumin (albumin
uoes not get into the uiine) - so you aie jaunuiceu, but uoesn't get into the uiine
2. Intiavasculai (within the Bv)
Intiavasculai is less common - meaning that you uie within the Bv. Bow uoes that
happen. You uie within the vessel if you bump into something. Example: congenital
bicuspiu aoitic valve with calcium theie - if you bump into that, you woulu uamage
youiself anu uie. Example: if you have IgN on the suiface of the RBC (IgN is the most
potent activatoi of the complement system); this will go fiom 1-9, meaning that it
will sit on the RBC, activate the complement anu uies intiavasculaily; so, anything
that is IgN meuiateu = intiavasculai hemolysis. So, what will you ielease into the
blooustieam if you aie killing the RBC. Bb. Bon't want to lose all of it anu neeu to
ietieat it - by getting back the aa's anu ietiieving the Fe. Specific piotein that is
maue in the livei that is ieleaseu when theie is intiavasculai hemolysis -
?'#6$3;$E&4 (aka suiciue piotein - bc foims complex with Bb anu is phagocytoseu
by the maciophage), theiefoie giving life to ietiieve the Bb, theiefoie in pts with
intiavasculai hemolysis, the haptoglobin levels ueciease. Is it possible to get
jaunuice. Yes, but usually uon't bc maciophage is phagocytosing. Intiavasculai
hemolysis: hemoglobinuiia, anu low haptoglobin levels
S. Summaiy:
Extiavasculai = maciophages iemove = unconj biliiubin is the enu piouuct =
jaunuice is the clinical manifestation
Intiavasculai = Bb in uiine, uecieaseu haptoglobin
>) @46-&4/&5 J/) Z%6-&4/&5 !,.$;"6&5 '4,.&'0
1. Intiinsic - something wiong with RBC, causing it to hemolyze: such as no
spectiin, oi not uecay acceleiating factoi to neutialize complement, no u6PB enzyme
in pentose phosphate shunt, oi abnoimal Bb (ie BbS). Theiefoie, something wiong
insiue the Bb molecule, causing it to hemolyze.
2. Extiinsic - nothing wiong with the RBC, just at the wiong place at the wiong
time; ie it just happeneu to smash into the calcifieu valve (nothing was wiong with it,
until it hit the valve). Then it will be uieauing going to the coius of bilioth with
uestioy it bc it has been maikeu with Igu anu CSb foi phagocytosis.
G) [$.,6?&43 &46-&4/&5';;" L-$43 L&6? 6?, DV> 5'</&43 &6 6$ ?,.$;"], but
theie's nothing wiong with the BN (but something intiinsically wiong with the RBC),
anu the coiiective iet ct is gieatei than S%.
B(G - NC intiinsic piobs
Bembiane uefect (spheiocytosis, paioxysmal noctuinal hemoglobinuiia),
(bnoimal Bb (SC tiait Bz),
Geficiency of enzyme (u6PB uef).
1) B,.E-'4, G,=,56/0
H'I [#?,-$5"6$/&/: uo no see a cential aiea of palloi theiefoie must be a
spheiocyte anu must be iemoveu extiavasculaily. Clinically manifest with jaunuice
fiom unconjugateu biliiubin. Spectiin uefect anu AB uz; splenomegaly always seen
ovei a peiiou of time. uallblauuei (uB) uz is common bc theie is a lot moie
unconjugateu biliiubin piesenteu to the livei anu moie conjugation is occuiiing anu
moie biliiubin is in the bile than usual. So, whenevei you supeisatuiate anything
that is a liquiu, you iun the iisk of foiming a stone; if you supeisatuiate uiine with
Ca, you iun the iisk of getting a Ca stone; if you supeisatuiate bile with cholesteiol,
you will get a cholesteiol stone; if you supeisatuiate with biliiubin, you will get a Ca-
biliiubinate stone. Theiefoie, pts have uB uz ielateu to gallstone uz anu then uo a
CBC with noimocytic anemia anu a coiiecteu iet ct that is elevateu, anu see
5$43,4&6'; /#?,-$5"6$/&/. What's the uiagnostic test. 0smotic fiagility - they put
these RBC's wall to wall in uiffeient tonicities of saline, anu the RBC's will pop
(theiefoie have an incieaseu osmotic fiagility).
Rx: splenectomy (neeu to iemove oigan that is iemoving them - they will still be
spheiocytes anu will not be able to foim a biconcave uisk).
HEI :'-$%"/.'; Q$56<-4'; !,.$3;$E&4<-&' = uefect in uecay acceleiating factoi.
So when we sleep, we have a milu iesp aciuosis bc we bieathe slowly (if you have
obstiuctive sleep apnea, the aciuosis is woise). When you have aciuosis that
pieuisposes the complement that's sitting on ALL cells ciiculating in peiipheial
bloou. RBCs, WBCs, anu platelets all have complement sitting on it. Theie is no
complement uestiuction of these cells bc in oui membianes we have uelay
acceleiating factoi. This factoi causes incieaseu uegiauation of the complement so it
uoesn't have an opp to uiill a hole in oui membiane, theiefoie we uon't wake up in
the moining with hemoglobinuiia, neutiopenia anu thiombocytopenia. So, if you aie
missing uecay acceleiating factoi, the complement will be activateu anu goes fiom
C1-9, leauing to intiavasculai hemolysis. Think about the name (paioxysmal
noctuinal hemoglobinuiia): occuis at night, anu when you wake up in the moining,
you pee out hemoglobin. So, when you uo a CBC, not only have a seveie anemia, but
also a neutiopenia anu a thiombocytopenia: pancytopenia).
7) (E4$-.'; !E0 [&5P;, >,;; +-'&6RG]
With sickle cell tiait, theie is N0 anemia anu N0 sickleu cells in the peiipheial
bloou. You can have sickleu cells in a ceitain pait of youi bouy - in the ienal meuulla
within the peiitubulai capillaiies (uecieaseu 0
2
tension), but not in the peiipheial
bloou. This is bc in SCBz, the amount of sickleu Bb in the RBC ueteimines whethei
it sickles oi not. B'3&5 v C `fn; if you have 6u% oi moie, BbS can spontaneously
sickle. 0xygen tension in the bloou also ueteimines whethei a cell will sickle oi not.
At lowei 0
2
tensions, cells aie moie likely to sickle. This is an auto iec uz, meaning
that both paients must have abnoimal gene on theii c'some (so its 2 tiaits);
theiefoie, 2S% complete noimal, Su% heteiozygous asymptomatic caiiiei, 2S%
complete uz (same with cystic fibiosis).
[> +-'&6 J/) [>G]0
(a) In /&5P;, 5,;; 6-'&6, black inuiviuual with noimal PE anu noimal CBC, but
micioscopic hematuiia, the fiist step is sickle cell scieen bc micioscopic hematuiia
is ALWAYS abnoimal anu must be woikeu up but in blacks = 18 people have the
tiait. So, SC tiait is what you aie thinking of; not ienal stones, oi IgA
glomeiulonephiitis, but is SC tiait noimally.
(b) [>G] - 2 things aie happening: Bemolytic anemia (usually extiavasculai) - can
be veiy seveie anu commonly iequiies a tiansfusion anu 0cclusion of small Bv's by
the sickleu cells (blockage of ciiculation) - leau to vasooclusive ciisis, anu this
ischemia leaus to pain. Theiefoie, they aie painful ciisis (occui anywheie in the
bouy - lungs, livei, spleen, BN, hanusfeet (bactulitis)). 0vei time, it leaus to uamage
of oigans - kiuneys, spleen autoinfaicteu (autosplenectomy) - in fiist 1u yeais of life,
pt will have splenomegaly bc tiappeu RBC's, anu eventually autosplenectomy
aiounu age 19 (spleen will be the size of a thumb). Aftei 2 yeais, it is nonfunctional -
so even though you have a bigswollen spleen, it isn't woiking. Bow will you know
what that has happeneu. Bowell }olly bouy (RBC with a piece of nucleus that shoulu
not be in the spleen - if the spleen weie woiking, a fixeu maciophage woulu have
taken caie of it). This occuis at about 2 yis of age. This is foitunate bc this is about
the age wheie you can get pneumovax. With a nonfunctional spleen what infection is
guaianteeu. Stiep pneumoniae sepsis.
B>> A,'6? &4 5?&;A L&6? [>G] C /6-,# #4,<.$4&', /,#/&/.
They tiy to covei with antibiotics anu pneumovax - pneumovax can be given at the
age of 2 anu that's about the time when the spleen stops woiking (stait to see Bowell
jolly bouies). Sliue with Bowell jolly bouy anu sliue with sickleu cells, then will ask,
what's wiong with the spleen. It's uysfunctional; Bowell jolly woulu have been
iemoveu if the spleen is functional.
When uo they get theii fiist sickle cell ciisis. When little kius gets painful hanus,
anu aie swollen up (calleu bactulitis) - uoes not occui at biith, bc BbF inhibits
sickling anu newboins in newboins, 7u-8u% of theii RBC's aie BbF. In SCBz,
6u-7u% RBC's have BbF, while the iest aie BbS!
At this stage, theie is enough BbF to inhibit the sickling; howevei, as the RBC's aie
bioken uown anu ieplaceu, the BbF uecieases anu BbS incieases, anu by 6-9 months
of age, theie is a high enough concentiation to inuuce sickling anu theii fiist
vasooclusive ciisis, piouucing bactulitis. So, bactulitis uoesn't come until 6-9 months
bc BbF inhibits the sickling.
Bone infaictions occui fiom sickling the BN.
0steomyelitis - these pts aie susceptible to osteomyelitis fiom salmonella uue to a
uysfunctional spleen. Salmonella is uestioyeu by maciophages. The spleen noimally
filteis out salmonella, but is uysfunctional. NCC osteomyelitis is staph, but NCC in
SCBz pt = salmonella.
What uiug is useu to ueciease the inciuence of vasooclusive ciises. Byuioxyuiea.
Bow uoes it woik. It incieases BbF synthesis.
9) G,U&5&,45" $= ,4]".,0 W`:G A,U&5&,45"
u6PB uef is X-linkeu iecessive.
Nost enzyme uef's aie auto iecessive ie PK0, albinism, homocystinuiia). What aie
the two X-linkeu iecessive enzyme uef's. u6PB uef anu Lesch-Nyhan synuiome
(involves puiine metabolism with mental ietaiuation, self mutilation, incieaseu uiic
aciu, uef of BuPRT).
ulucose 6 phosphate has seveial functions: (1) to make glutathione, (2) to make
iibose S caibon sugais foi making BNA, anu (S) to make glycogen fiom u6P
(conveiteu to u1P, 0BP-glucose anu glycogen).
Key: with this enzyme, we can make NABPB, which is the main factoi foi making
anabolic types of biochemical ixn (ie steioiu synthesis). NABPB will ieuuce oxiuizeu
glutathione to glutathione; its job is to neutialize peioxiue to watei. Which vitamin
catalyzes this ixn. Riboflavin. Which enzyme helps glutathione neutialize peioxiue.
ulutathione peioxiuase. Which tiace metal is involveu. Selenium. Eveiy living cell
makes peioxiue as an enu piouuct, theiefoie eveiy cell must a way to hanule it.
Catalase - piesent in all cells except RBC's anu it can neutialize peioxiue. It is stoieu
in peioxisomes. 0thei way to neutialize peioxiue is with glutathione (only thing
available to RBC's bc they uon't have catalase). So, if you aie ueficient in this
enzyme, theie is a pioblem. So, peioxiue incieases to the point of hemolyzing RBC's
why woulu that occui. Bc if you hau an Infection, oi if you took an oxiuizing uiug (ie
sulfa uiug, nitiyl uiug), which will leau to a lot moie peioxiue lying aiounu. Peioxiue
will not be able to be neutializeu if you aie ueficient in catalase. So, what will happen
is the peioxiue will affect the Bb. The peioxiue will cause the Bb to clump anu foim
Beinz bouies (Bb clumpeu up togethei). Will also affect the RBC membiane bc it
uamages the membiane so much that the piimaiy mechanism of uestiuction is
intiavasculai. Little element is extiavasculai, but mostly intiavasculai. It is
piecipitateu by infections anuoi uiugs. 7 B> A-<3/0 1I #-&.'Y<&4,- missionaiy
got malaiia, ieceiveu a uiug, anu 2-S uays latei the got hemoglobinuiia, chills, anu a
hemolytic anemia (this is piimaquine inuuceu hemolysis). 7I G'#/$4, is useu in
tieating lepiosy; eveiy peison with lepiosy is given a scieen foi u6PB uef bc of the
high inciuence of piouucing hemolysis. See this uz in the same population as Beta
thal - blacks, uieeks, Italians. Sliue: smeai with actively hemolyzing bloou cells -
!,&4] E$A&,/ - when it goes into the coius of bilioth, the maciophage will take a big
bite out of it anu sometimes, is a small bite out of the membiane, anu the cell goes to
the peiipheial ciiculation anu is calleu a "E&6,d 5,;; (RBC with little membiane).
Neeu to uo special stains to IB Beinz bouies. In uieeks oi Italians with seveie foims
of u6PB uef, they can eat fava beans which can piecipitate an episoue (aka favism).
G% - when you have an acute hemolytic episoue, the last thing you want to get a
uiagnosis is to get an enzyme assay. Why. Bc the only cells that aie hemolyzeu aie
the ones missing the enzymes. The ones that have the enzyme aie still gonna be
theie, so you have a noimal assay. So, NEvER use enzyme assays foi active
hemolysis. Neeu to special stain to IB the Beinz bouy. When the hemolytic episoue is
ovei that's when the ux is confiimeu, this is uone with a u6PB assay. O&;; 3,6 '
Y<,/6&$4 $4 W`:G A,U&5&,45"_ ,&6?,- A'#/$4, -,;'6,A $- #-&.'Y<&4, -,;'6,A)
g) (<6$&..<4, ?,.$;"6&5 '4,.&'/
Waim ieacting antibouies aie Igu anu colu ieacting is IgN
NC autoimmune hemolytic anemia = waim; NCC of it = Lupus
When you have autoimmune uz in youi family, you have ceitain BLA types that
pieuispose you to that autoimmune uz. Theiefoie, you shoulu not be suipiiseu if
you have one autoimmune uz you'ie likely to have anothei. So, pts with lupus
commonl y al so have aut oi mmune hemol yt i c anemi a, aut oi mmune
thiombocytopenia, autoimmune neutiopenia, anu autoimmune lymphopenia.
Foi example: the NCC of hypothyioiuism = hashimoto's thyioiuitis; these pts
commonly have othei autoimmune uz's - ie peinicious anemia, vitiligo, autoimmune
uestiuction of melanocytes). So, if you have one autoimmune uz, you aie likely to
have otheis (ie if you have a hemolytic piob, it is piob autoimmune ielateu).
This is bc of the BLA ielationship. Theiefoie, if you have a family that has an
autoimmune uz, what woulu be the single best scieening test to use. BLA (ie if they
have the BLA type specific foi lupus - theie aie specific BLA's foi uiff uz's).
Theiefoie, BLA is the best way to see if pt is pieuisposeu to something.
B>> '<6$&..<4, '4,.&' C X<#</; it has Igu anu CSb on the suiface of the RBC,
so it will be iemoveu by the maciophage. This is an extiavasculai hemolytic anemia.
Bow uo we know that theie aie Igu oi CSb Ab's on the suiface. G&-,56 >$$.E8/
6,/6: uetect BIRECTLY the piesence of Igu anuoi CSb on the suiface of RBC's.
Inuiiect coombs is what the women get, when they aie piegnant anu they uo an Ab
scieen on you (looking foi any kinu of Ab); so, when you look foi Ab in the seium
(N0T on RBC, on SER0N), this is an inuiiect Coombs. Theiefoie, anothei name foi
the inuiiect Coombs = Ab scieen; with uiiect coombs, we aie uetecting Igu anuoi
CSb on the S0RFACE of RBC's. you cannot uo uiiect coomb's on platelets oi
neutiophils, but only RBC's.
[$_ 6?, 6,/6 $= 5?$&5, &= "$< /</#,56 '4 '<6$&..<4, ?,.$;"6&5 '4,.&' &/
>$$.E8/ 6,/6)
() G-<3 &4A<5,A '<6$&..<4, ?,.$;"6&5 '4,.&'/0
Theie aie S types of uiug inuuceu hemolytic anemia (2
nu
NCC autoimmune
hemolytic anemia = uiug inuuceu; NCC = lupus)
1) :>Q - mechanism: the bpo gioup of PCN attaches to RBC (lil piece of PCN is
attacheu on RBC membiane). This is bau if an Igu Ab uevelops against it bc if it
uoes, than the Igu attaches to the bpo gioup, goes to the spleen anu is iemoveu
extiavasculaily; this is an ie of type II BPY
Example: pt on PCN uevelops a iash - what type of BPY. Type I. Example: Pt on
PCN uevelops a hemolytic anemia - what type of BPY. +"#, @@
7) B,6?";A$#' - aka aluomet. 0se: anti-BTN foi piegnant woman (othei anti-BTN
useu in piegnancy = hyuialazine). Nethyluopa anu hyuialazine have complications -
methyluopa can cause a hemolytic anemia; hyuialazine can leau to uiug-inuuceu
lupus (2
nu
to piocainamiue foi uiug inuuceu lupus). Nethyluopa woiks uiffeiently
fiom PCN: methyluopa messes with Rh Ag on suiface of RBC anu alteis them. They
aie alteieu so much that Igu Ab's aie maue against the Rh Ag (oui 0WN Rh Ag). So,
the uiug is not sitting on the membiane, it just causes foimation of @3W Ab's anu they
attach to RBC to have maciophage kill it - what type of BPY is this. +"#, @@.
Theiefoie, methyluopa anu PCN aie type II foi hemolytic anemia.
9) w<&4&A&4,: this is the 'innocent bystanuei' bc immune complexes aie foimeu.
Quiniuine acts as the hapten, anu the @3B Ab attaches; so, the uiug anu IgN aie
attacheu togethei, ciiculating in the blooustieam. This is a uiffeient !:b \ 6"#, @@@,
anu will uie a uiffeient way, bc this is IgN. When IgN sees the immune complex, it
will sit it, anu activate the classical pathway 1-9, leauing to intiavasculai hemolysis,
anu haptoglobin will be uecieaseu, anu in the uiine, Bb will be piesent.
g@) B&5-$'43&$#'6?&5 ?,.$;"6&5 '4,.&'
RBC's all fiagmenteu - schistocytes (schisto - means split). B>> 5?-$4&5
&46-'J'/5<;'- ?,.$;"/&/ C '$-6&5 /6,4$/&/, in this uz, the cells hit something;
theiefoie have intiavasculai hemolysis, Bb in the uiine anu haptoglobin is uown.
This is a chionic intiavasculai hemolysis, anu you will be losing a lot of Bb in the
uiine; what uoes Bb have attacheu to it. Fe; so what is anothei potential anemia you
can get fiom these pts. Fe uef anemia. Example: will uesciibe aoitic stenosis
(systolic ejection muimui, 2
nu
ICS, iauiates to the caiotius, S4, incieaseu on
expiiation, piominent PNI), anu they have the following CBC finuings: low NCv, anu
'fiagmenteu' RBC's (schistocytes) - this is a micioangiopathic hemolytic anemia
ielateu to aoitic stenosis.
0thei causes of schistocytes: BIC (lil fibiin stianus split RBCs iight apait bc RBC is
veiy fiagile); thiombotic thiombocytopenic puipuia, B0S - see schistocytes. When
you have platelet plugs eveiywheie in the bouy, the RBCs aie banging into these
things causing schistocytes anu micioangiopathic hemolytic anemia. Example:
iunnei's anemia, esp. long uistance you smash RBC's as you hit the pavement; veiy
commonly, you go pee anu see Bb in it; to pievent, use bathioom b4.

Anothei cause of hemolytic anemia: .';'-&' \ =';5&#'-<. bc you have multiple
iing foims (gametocyte (comma shapeu anu iingeu foim). It piouuces a hemolytic
anemia, which coiielates with the fevei. The fevei occuis when the cells iuptuie
(the hemolytic anemia).
OV>
@) Q$4^4,$#;'/6&5 X".#?$&A :-$;&=,-'6&$4/0
() Q,<6-$#?&;/ - when you have acute inflammation = ie appenuicitis, neutiophilic
leukocytosis, left shift, toxic gianulation, anu leukamoiu ixn. Leukamoiu ixn means
that it looks like leukemia but it isn't anu it's benign. 0sually involves any of cell
lines. What causes leukamoiu ixns. TB anu sepsis. You see gieatei than Su-Su,uuu
cells in the bloou. Kius get these a lot (ie otitis meuia). Auult with otitis meu =
12,uuu; kius with Su,uuu (exaggeiateu). Example: :,-6<//</ \ L?$$#&43 5$<3? \
;".#?$5"6$/&/ (6u,uuu) - peuiatiicians aie woiiieu about ALL leukemia, but kiu
uoesn't have anemia oi thiombocytopenia; kiu comes in pale, coughing.
Lymphocytes aie matuie anu aie totally noimal. Lymphocytosis w viial infection oi
with peitussus.
In '6"#&5'; ;".#?$5"6$/&/ - this is a lymphocyte that is uoing what it's supposeu
to uo when piesenteu to anu Ag. It's iesponuing to the Ag by uiviuing anu getting
biggei, so basically it's an antigenic stimulateu lymphocyte. When talking about
atypical lymphocyte, the absolute fiist thing that pops into the minu is:
.$4$4<5;,$;$/&/ \ ZVF. 0thei uz that aie seen with laige, beautifully staining
bluish cells: CNv, toxoplasmosis, any cause of viial hepatitis, phenytoin. EBv is
calleu the kissing uz bc the viius holus up in the salivaiy glanus. EBv affects B cells
anu CB 21. Nono causes viiemia, geneializeu painful lymphauenopathy, veiy
commonly get exuuative tonsillitis, jaunuice (haiuly evei seen), incieaseu
tiansaminases (off the chait), anu spleen enlaigement anu can iuptuie. Theiefoie
uon't play spoits bc can iuptuieu spleen can occui, so avoiu contact spoits usually
foi 6-8 weeks. Also causes maciocytic anemia via inhibiting intestinal conjugase).
Auuio File 1S: Bematology S
Example: the boaius will give you a classic hx of mono, anu ask which tests you iun,
but monospot test is not on the choices bc that's the tiaue name, so pick heteiophile
antibouies (heteio = uiff, phile = loving). Beteiophile Ab's aie anti-hoise RBC Ab's
(oi anti-sheep); they aie uiffeient, hence "heteio"phile Ab's. 0nce you have mono,
you always have it anu will have S-4 iecuiiences ovei youi lifetime - ie ieactivation
consists of swollen glanus, veiy tiieu, etc. EBv lives in B cells; the atypical lymphs in
mono aie T cells ieacting against the infecteu B cells.
V) B$4$5"6, = king of chionic inflammation, theiefoie expect monocytosis in pts
with chionic infections - ie iheumatoiu aithiitis, Ciohn's, ulceiative colitis, lupus,
malignancy
[&A, Q$6,0 cieatine gives eneigy bc it binus to phosphate, anu that is the
phosphate you get fiom making ATP - so what seium test is maikeuly elevateu in
someone taking cieatine foi theii muscles. Cieatinine! Bc the enu piouuct of
cieatine metabolism is Cieatinine. The B0N is noimal in this peison. Woithy boaiu
question.
>) Z$/&4$#?&;&'
You woulu see eosinophilia in Bay fevei, iash in pt with PCN, stiongoloiues
Piotozoa infections B0ES N0T piouuce eosinophilia, theiefoie it iules out
amabiasis (pinwoim), giaiuia, anu malaiia. 0nly invasive helminthes piouuces
eosinophilia. Auult ascaiiasis uoes N0T cause eosinophilia bc all they uo is obstiuct
bowels, it's when the invasive laivae foim ciosses into the lungs that causes
eosinophilia. So anything that is Type I BPY causes eosinophilia; piotozoa uo not
cause eosinophilia; ascaiiasis, anu pinwoims uo N0T cause eosinophilia (all otheis -
ie whipwoims uo bc they invaue).
@@) B",;$#-$;&=,-'6&J, G]0 :$;"5"6?,.&' - incieaseu RBC ct, incieaseu Bb anu Bct
Biffeience between seium Na anu total bouy Na. yes. Seium Na is milliequavalents
pei litei of plasma; total bouy Na is milliliteis pei kg bouy wt (the total amount you
have). Similaily: DV> .'// = total # of RBC's in entiie bouy in mLkg in bouy wt
DV> 56 = # of RBC'smiciolitei of bloou, theiefoie its how many you have in a
ceitain volume of bloou. Why is this a big ueal. Example: went iunning anu vol
uepleteu - RBC ct woulu be hemoconcentiateu, theiefoie woulu look like moie RBC's
pei miciolitei of bloou (bc you uepleteu the plasma volume), but what woulu the
RBC mass be. Noimal (not actually synthesizing RBC's). So, theie aie 2 types of
RBC's: ielative anu absolute. D,;'6&J, = ueciease in plasma vol causing an inciease
in RBC ct, but the RBC mass is noimal. (E/$;<6, inciease - is appiopiiate oi
inappiopiiate.
When woulu it be appiopiiate. Syn of RBC's - tissue hypoxia, so, any souice of
tissue hypoxia woulu be an appiopiiate iesponse. Example: if you have lung uz,
hypoxemia, C0PB, high altituue - these aie ie's of appiopiiate polycythemias. What
if we have noimal bloou gases, but uiun't have tissue hypoxia. This woulu be an
inappiopiiate polycythemia. So, theie aie two things to think about with &45-,'/,A
DV> .'//0 #$;"5"6?,.&' -<E&J,-', which is an ie of a stem cell piolifeiative uz of
the BN, meaning that the stem cells aie uictatois, anu nothing keeps them in check -
a neoplastic uz; they can become leukemias. So, it woulu be inappiopiiate to have
noimal bloou gases anu no eviuence of tissue hypoxia anu have an inciease in RBC
mass. 2) +<.$- $- 5"/6 L&6? '4 ,%5,// #-$A<56&$4 $= Z:2: ienal auenocaicinoma
making EP0, causing an inciease in RBC mass - this is inappiopiiate bc a tumoi is
inappiopiiately making it.
In summaiy: polycythemia is ielative oi absolute. Relative means that you just lost
plasma vol (ie fiom iunning) with RBC ct incieaseu, anu mass is noimal. Absolute
inciease: is it appiopiiate oi inappiopiiate. Appiopiiate - anything that is a hypoxic
stimulus foi EP0 ielease. If theie isn't a hypoxic conuition causing the EP0
piouuction, then you aie ectopically making EP0 fiom a tumoi oi cyst oi you have
polycythemia iubiveia (a myelopiolifeiative uz).
@@@) B",;$#-$;&=,-'6&J, A] - neoplastic stem cell uz that has lost all iegulation anu
nothing can inhibit it anymoie. 4 uz's that fit unuei this uefinition:
1. Polycythemia iubiveia
2. CNL (only leukemia in this categoiy)
S. Agnogenic myeloiu metaplasia - BN is ieplaceu by fibious tissue
4. Essential thiombocythemia - wheie a stem cell that makes platelets goes
ciazy anu make 1 million, 6uu platelets foi miciolitei,
S. Nyelouysplastic synuiome
6. () :$;"5"6?,.&' -<E&J,-'0 4 B's:
1) !"#,-J&/5$/&6" (iemembei Pouseau's law = TPR = viscosityiauius
4
). With
polycythemia, it will have an incieaseu iesistance anu TPR will go up; it will
pieuispose to thiombosis, which kills you - thiombosis of anything - ie uuial
sinuses; NCC Buuu chiaii = hepatic vein thiombosis; coionaiy aiteiy, SNv, anything
can be thiomboseu bc bloou slugging aiounu anu this is why phlebotomy is uone.
Phlebotomy is peifoimeu to make you Fe uef - they want to make you Fe uef - why.
If you make them Fe uef, bc then it will take longei to make RBC's, so you
puiposefully slow uown the piocess.
7) !"#$J$;,.&' - only polycythemia that has an inciease in plasma volume that
matches the inciease in RBC mass; none of the othei causes have an inciease in
plasma vol (these aie measuieu with iauioactive techniques). So, it is veiy iaie to
see an inciease in plasma vol with polycythemia, except foi this case. Why.
Nyelopiolifeiative uz's take yeais anu yeais to uevelop theiefoie plasma vol is able
to keep up; theiefoie both inciease togethei ovei time.
9) !&/6'.&4,.&' - all cells aie incieaseu: RBC's, WBC's, platelets, incluuing mast
cells anu basophils. Example: Classic hx: pt takes a showei anu gets itchy all ovei
bouy - this is a tip off foi polycythemia iubiveia - why. Nast cells anu basophils aie
locateu in the skin anu tempeiatuie changes can uegianulate mast cells, causing a
ielease of histamine, leauing to geneializeu itching (veiy few things cause
geneializeu itching - bile salt ueposition in the skin in pts with obstiuctive jaunuice,
anu pts with mast cell uegianulation), face is ieu looking, too bc of histamine bc
vasouilatation, leauing to migiaine-like heauaches.
K) !"#,-<-&5,.' - bc nucleateu hematopoetic cells aie elevateu, they then uie,
anu the nuclei have puiines in them. The puiines will go into puiine metabolism anu
become uiic aciu. Example: pt on chemotheiapy must also be put on allupuiinol to
pievent uiate nephiopathy anu pievent ienal failuie fiom uiic aciu. (allupuiinol
blocks xanthane oxiuase). When killing cells you'ie ieleasing millions of puiines
when the nucleateu cells aie killeu anu the tubules aie filleu with uiic aciu, leauing to
ienal failuie. Nust put them on allupuiinol. This calleu tumoi lysis synuiome. The
same thing occuis in polycythemia iubiveia bc theie is an inciease in numbei of
cells that eventually uie anu you iun the iisk of hypeiuiicemia.
V) DV> .'//R#;'/.' J$;R27 /'6RZ:2
Polycythemia iubiveia - h,h,N (inappiopiiate), low (have too much 02 bc you
have piles of RBCs anu theiefoie suppiess EP0 (it's a hoimone). The hint was 02
content=1.S4 * Bb * 02 sat +p02
C0PB, tetialogy of fallot, high alt - B, N, L, B (appiopiiate polycythemia bc it's
iesponuing to hypoxia)
Renal auenocaicinoma, hepatocellai caicinoma, any cyst (ienal, esp. ie
hyuionephiosis, wilm's tumoi) - B, N, N, B (even with noimal gas stuuies bc
ectopically piouuceu)
Relative Polycythemia - N, L, N, N
@F) X,<P,.&'/
They aie a malignancy of the BN anu mets anywheie it wants.
() W,4,-'; 5?'-'56,-&/6&5/ $= X,<P,.&'i 6?,-,=$-,_ L&;; ';L'"/ ?'J,0
1. ueneializeu lymphauenopathy, hepatosplenomegaly, etc.
2. Abnoimal cells in the peiipheial bloou - BLASTS (myeloblasts, lymphoblasts,
monoblasts, megakaiyoblasts) - so some abnoimal blasts aie in the peiipheial bloou
S. Bc it is aiising in the BN, will always ciowu out the noimal hematopoetic cells,
anu will ALWAYS have an anemia, usually noimocytic
4. Thiombocytopenia bc ciowuing out the noimal megakaiyocytes fiom making
platelets
S. 0sually an inciease in WBCs ct with abnoimal cells piesent
6. Acute vs. chionic - Bo a bone maiiow test anu look at blasts - if blasts aie <Su%,
this is chionic; if the % blasts is >Su%, it is acute. Theiefoie the blast ct tells if its
acute vs chionic
V) (3, E-'5P,6/0 S4$L '3, E-'5P,6/
u-14 = ALL
1S-S9 = ANL - myeloblast with Auei ious in peiipheial bloou
4u-S9 ANL, CNL (sepaiate with BN - ANL with >Su% anu CNL with <Su%, 9, 22,
Philly c'some)
6u+ = CLL
NC oveiall leukemia iegaiuless of age = CLL
NCC geneializeu nontenuei lymphauenopathy in pt 6u+ = CLL; not bc it's a
lymphoma, but bc it mets to lymph noues).
>) G&==,-,46 +"#,/ $= X,<P,.&'0
Example: peiipheial smeai of 49 yo, 1Su,uuu WBC ct, 1% myeloblast in peiipheial
bloou anu BN, geneializeu nontenuei lymphauenopathy, hepatosplenomegaly,
thiombocytopenia, anu noimal anemia - ux. CNL (look at age biacket anu % blasts).
To piove, get 9, 22 stuuy (abl piotooncogene with nonieactoi tyiosine kinase
activity anu goes fiom 9 to 22 anu fuses with the clustei fusion gene). LAP -
leukocyte alkaline phosphatase stain can also be useu. Look at which neutiophils
take it up - matuie neutiophils all have LAP in them; neoplastic neutiophils uo not -
why. Bc they aie neoplastic. So, if no stain, know its neoplastic (noimal cells take
up stain). Calleu a LAP scoie - always low in CNL. So, the two tests: Philly c'some
anu LAP scoie, which is always low.
Example: teai uiop cell bc theie was a uictatoi in BN, anu cells have to move to
the spleen, so theie is a migiation of hematopoetic cells fiom the BN to the spleen.
When you take up hematopoesis anywheie othei than the bone maiiow, this is
calleu extiameuullaiy hematopoesis. So, the spleen in huge - esp. in atheiogenic
myeloiu metaplasia. Some of the megakaiyocytes go back to the maiiow to lay uown
collagen; anu megakaiyocytes go back. Fibiosis of the BN occuis (useu to be calleu
myelofibiosis metaplasia). So, not eveiyone left the BN, anu stay in the fibiotic
maiiow. Foi them to get to the spleen, they have to woik theii way thiough stianus
of fibiotic tissue, often times uamaging theii membiane, leauing to teai uiop cells
(so, it gets passeu the 'baibeu wiie' - fibious tissue - anu getting into the sinusoius,
they aie teai uiop cells in the peiipheial bloou). So, pt with huge spleen, with teai
uiop cells - '6?,-$3,4&5 .",;$&A .,6'#;'/&'.
Example: too many platelets - ,//,46&'; 6?-$.E$5"6?,.&' (makes too many
platelets)
Example: 4 yo pt that piesents with steinal tenueiness, fevei, geneializeu
nontenuei lymphauenopathy, hepatosplenomegaly, noimocytic anemia, Su,uuu WBC
count many of which hau an abnoimal appeaiance cells. What is the ux. (XX H'5<6,
;".#?$E;'/6&5 ;,<P,.&') NC cancei in kius; the most common type is: common ALL
Ag B cell leukemia. CB1u+; calla+ Ag B-cell ALL, associateu with uown's synuiome
Example: 6S yo, noimal ciiteiia, smuuge cells anu noimocytic anemia. They also
have hypogammaglobinemia bc they aie neoplastic B cells anu cannot change to
plasma cells to make Igs. Theiefoie, NCC ueath in CLL = infection ielateu to
hypogammaglobinemia. What is the Bx. >XX
Example: 62 yo, noimal ciiteiia, special stain of TRAP (taitiate iesistant aciu
phosphatase stain) - ?'&-" 5,;; ;,<P,.&' (know the TRAP stain)
Example: SS yo pt, with noimal ciiteiia, with Su,uuu abnoimal WBCs anu Auei
ious (abnoimal lysosomes), 7u% blast cells in the BN. What is the Bx. (BX) Know
what Auei ious look like, know the leukemia that infiltiates gums (acute monocytic
anemia - NS), anu acute piogianulocytic anemia (NS) - they always have BIC, has a
tianslocation 1S,17. Rx = ietinoic aciu (vit A - causes blasts to matuie into b9 cells).
F) X".#? 4$A,/
() W,4,-'; >?'-'56,-&/6&5/0
1. Painful vs painless: lymphauenopathy that is painful is not malignant; mean that
you have inflammation causing it (uoes not always mean infection) - you aie
stietching the capsule, it's an inflammatoiy conuition (lupus), anu that piouuces
pain. When you have non-tenuei, think malignant, eithei (1) mets oi 2) piimaiy
lymphoma oiiginating fiom it. Always tell if painfulless.
2. Localizeu vs. geneializeu lymphauenopathy: Localizeu (ie exuuative tonsillitis
goes to local noues; bieast cancei goes to local noues. ueneializeu (systemic uz - ie
BIv, EBv, Lupus).
S. Examples:
(a) Biuton's agammaglobinemia - geiminal follicle absent: B-cell
(b) Biueoige synuiome- paiatiabeculae messeu up: T-cell countiy
(c) Bistiocytes (Ban shcullei Chiistianletteiman sieve uz) - involves sinuses
(u) SCIB (auenine ueaminase uef) - B anu T cell ueficiency, theiefoie no geiminal
follicle anu no paiatiabeculae but will have sinuses.
(e) Reactive lymphauenopathy: Naciophage takes Ag, anu piesents to geiminal
follicles anu they spit out a plasma cell, making Ab's
V) Q$4^!$A3P&48/ ;".#?$.'
Folliculai lymphoma = NC Non-Bougkin's Lymphoma: B-cell; tianslocation 14,18;
anu apoptosis gene knockeu off, so the cells aie immoital.
O?'6 7 6&//<,/ '-, -,/&/6'46 6$ &4J'/&$4 E" 5'45,- 5,;;/e >'-6&;'3, '4A ,;'/6&5
6&//<,
Example: V<-P&66/; causeu EBv; Tianslocation 8,14, myc oncogenes, staiiy sky -
noimal maciophages looking like sky at night, #S NCC cancei in kius; can cuie; NC
lymphoma in kius, usually in the abuomen (ie payeis patches, paiaoitic lymph noues,
also but iaiely in the jaw, oi testes)
Example: plaque like lesions, no teeth, not a fungal infection - actually the
inflammatoiy cells aie ieally neoplastic; so the helpei T cell in ."5$/&/ =<43$&A,/ is
neoplastic, theiefoie it's a T cell malignancy. Involves the skin anu lymph noues vs.
[,]'-" cell synuiome which is seen in peiipheial bloou (malign helpei T cell that is
in peiipheial bloou, in mycosis fungoiues)
Example: kiu with EN of eczematous iash all ovei - geneializeu nontenuei
hepatosplenomegaly, , EN of monomoiphic cells which weie CB 1+ cells -
histiocytosis X (;,66,-.'4 /&,J, A]) (biibeck gianules, look like tennis iacket -
clostiiuium tetani which has a spoie also looks like a tennis iacket)
Painful lymphauenopathy = some type of inflammatoiy conuition, not malignant
Painless lymphauenopathy = malignancy: NC malignancy of lymph noue =
metastasis
NC piimaiy cancei of lymph noue =
non Bougkin's lymphoma: folliculai B cell lymphoma (tianslocation: 14, 18. This
knocks off apoptosis gene anu the cell is immoital).
>) !$A3P&48/ G]- foui uiffeient types. In Bougkin's the caiuinal signs aie: fevei,
night sweats, anu wt loss (usually TB unless pioven otheiwise). It is usually
localizeu, nontenuei lymphauenopathy. 0n micio: the malignant cell is Reiu
Steinbeig cells, RS cells - owl eyes - common on boaius (also giaiuia, CNv, ashoff
nouule in iheumatic fevei). Less # = bettei piognosis; moie = woise
The most impoitant one is Q$A<;'- [5;,-$/&/: NC = nouulai scleiosis, seen in
women; it is nouulai (hence the name), anu has lots of scleiosis (collagen ueposition,
so it's haiu anu non-painful noue). You woulu see it in a woman with lymph noue
involvement in 2 places: 1) anteiioi meuiastinum anu 2) somewheie above the
uiaphiagm- ie the ceivical noues, supeiclaviculai noues, neck. This combination of
mass in neck anu anteiioi meuiastinum = nouulai scleiosis. You woulu see RS cells
on micio.
2. Teims: poly anu monoclonal (this will help to unueistanu the uiff fiom multiple
myeloma anu othei things that inciease gamma globulin p). 0n seium piotein
electiophoiesis, albumin migiates the faithest bc it has the most neg chaige,
wheieas gamma globulin just sits theie.
(a) Polyclonal: "poly" = many, "clonal" = plasma cells, theiefoie you have many
clones of plasma cells bc the gamma globulin iegion is wheie the gamma globulins
aie. Think "g-a-m" to know the oiuei of most abunuantgieatest numbei of
globulin. Theiefoie, on electiophoiesis, you see a little peak, this is an inciease in Igu
bc it's the most abunuant Igu - this makes sense bc foi chionic inflammation, the
main Ig is Igu, anu foi acute inflammation the main Ig is IgN. So, in chionic
inflammation (ie Ciohn's, iheumatoiu aithiitis, 0C) theie is an inciease in Igu -
which will show a laige uiffuse elevation (a nice iounu mtn). This is calleu
polyclonal gammopathy bc many benign plasma cells aie making Igu. Polyclonal
gammopathy always means benign anu chionic inflammation. Will not have
polyclonal gammopathy with acute inflammation (ie acute appenuicitis); this not any
iise in the gamma gobulin iegion foi acute inflammation - the main Ig is IgN foi
acute.
(b) Nonoclonal = one clone of plasma cells aie making Ig's; othei plasma cells aie
not making Ig's bc they aie suppiesseu. So, when you see a monoclonal peak, this
means it's a malignancy of plasma cells. Neanwhile, all othei plasma cells aie
suppiesseu by immunologic mechanisms. The malignant clone makes its own Ig;
most of the time it is an Igu malignancy. They aie making many light chains anu get
into the uiine - these aie calleu Bence }ones pioteins. Nonoclonal usually means
malignancy anu always means multiple myeloma.
(c) Peaks (in oiuei): albumin, alpha 1, alpha 2, beta, gamma - have
a pt 2S yo, non-smokei, hau emphysema of the lowei lungs, no alpha 1 peak -
what is Bx. Alpha 1 antitiypsin uef.
F@) :;'/.' >,;; G&/$-A,-/0
() B<;6&#;, B",;$.' HBBI
NN is a veiy bau uz, incuiable, anu unless you get BN tiansplant, you will uie. It's
usually seen in people ovei Su, a little moie common in women. The most common
foim is Ig kappa, which is abunuant. Plasma cells have IL-1 (aka osteoclast activating
factoi); this is why you see lots of lytic lesions in the skull oi bones. The lytic iegions
aie iounu, anu nicely cut (in contiast to Paget's uz, the lytic iegions aie fuzzy anu not
shaiply cut). While in NN lesions have a fine, shaip (cookie cuttei cut) boiuei, bc
IL-1 activates osteoclasts, leauing to the puncheu out lesions.
Example: if theie was a lytic lesion in the iibs anu pt cougheu, what woulu
potentially happen. Pathologic fiactuies anu these aie extiemely common.
Example: elueily woman coughs anu uevelops seveie pain - you see lytic lesion of
the iib, so what uoes the pt have. Nultiple myeloma
Know what plasma cell looks like - has biight blue cytoplasm anu nucleus is
eccentially locateu (aiounu the nucleus aie cleai aieas piesent). 0n EN, will see
layei anu layeis of RER, bc they aie constantly making piotein (iibo's aie wheie
iibosomal RNA sits on). Nust know what plasma cell looks like on EN anu giemsa
stain. Summaiy of multiple myeloma - lytic lesions, Bence }ones pioteins, anu seen
in elueily pts.
1) (.";$&A$/&/0 is a clinical chaiacteiistic of NN
Amyloiu on EN is a non-bianching, lineai compounu with a hole on the centei of it.
They always ask a question on amyloiuosis bc it enus up in the uiffeiential ux foi
multi-system uz (systemic amyloiuosis). Amyloiu is a piotein, but what's inteiesting
is that many othei uiffeient pioteins can be tiansfoimeuconveiteu into this unique
piotein - ie pie-albumin,
!
calcitonin (tumoi maikei foi meuullaiy caicinoma of the
thyioiu),
!
light chains in NN, anu
!
tiisomy 21. In Tiisomy 21 (Bown's synuiome), the c'some 21
coues foi beta amyloiu, anu if you have thiee of these, you will
make moie beta amyloiu piotein. Anu beta amyloiu piotein is
toxic to neuions; so, if you have tiisomy 21 aie making moie
beta amyloiu piotein, then you will be losing moie neuions bc
you aie losing moie of this piotein that is toxic to neuions. This
is why they always ask the question about a pt uying at foity
anu on autopsy, you see atiophy of the biain anu it ieveals
senile plaques in fiontal anu tempoial lobes, anu will ask what
pt hau - Bown's synuiome. All uown's pts will get Alzheimei's.
Bown's pts uie fiom 1 of 2 things: eithei fiom (1) enuocaiuial
cushion uefects - which leaus to heait uefects anu an ASB (in
chiluhoou) anu a vSB oi (2) Alzheimei's uz (ueath bc
chiomosome 21 is making too much beta amyloiu piotein).
Example: 4u yo with Alzheimei's uz has uowns synuiome.
Beta amyloiu is most impoitant piotein.
!
F@@) X"/$/$.'; /6$-'3, A]8/
Two uiffeient cells that they like to ask questions about.
1. uauchei uz: theie is a maciophage with a ciinkleu papei like appeaiance in the
cytoplasm. Theie aie lysosomes filleu with glucoceiebiosiue, theiefoie pt has
uauchei uz. It's an auto iecessive uz with a missing glucoceiebiosiue.
2. Niemann-Pick uz: bubbly cytoplasm, seveie mental ietaiuation, builuup of
sphingomyelin in the lysosomes, theiefoie the pt has Niemann-Pick uz, missing
sphingomyelinase.
S. Pompe's Bz: only glycogen stoiage uz that has lysosomal stoiage = Pompe's; only
glycogen stoiage uz that is lysosomal bc they aie missing an enzyme to bieak
glycogen uown in the lysosomes. Bow uoes pt uie. Bie fiom caiuiac failuie bc
excess ueposition of noimal glycogen in the heait.
Summaiy: bubbly cytoplasm = Niemann-Pick uz; ciinkleu papei = guachei's, both
aie lysosomal stoiage uz
!,.$A"4'.&5 G"/=<456&$4
@) +?-$.E$3,4,/&/0 +?, >$'3<;'6&$4 ["/6,.
Bemostasis: things in oui bouy that pievents clots fiom ueveloping in Bv's. If these
clots weie not pieventeu, the pt eithei has BIC, thiombotic thiombocytopenic
puipuia (TTP), oi B0S, anu all of them leau to ueath. So, why uon't we foim clots in
oui small Bv's. |small bloou vessels incluue aiteiioles, venules, anu capillaiies, while
small aiiways incluue teiminal bionchioles, iesp bionchioles, alveolai uuct, anu
alveolusj.
() [$_ L?" A$486 L, =$-. 5;$6/e Bc we have coagulation factois such as: hepaiin,
PuI
2,
Piotein C anu S, anu tissue plasminogen activatoi. So all of these things aie
useu to pievent little clots occuiiing in oui small bloou vessels.
1. Bepaiin (a uAu, a mucopolysacchaiiue). It is noimally founu in the bouy anu
helps pievent foimation of clots. Bow uoes hepaiin woik. It ENBANCES
antithiombin III. Antithiombin III is maue In the Livei (like all othei pioteins).
Theiefoie, hepaiin gets the cieuit foi anticoagulating you, but its antithiombin III
uoes all the woik. Antithiombin III neutializes most of the coagulation factois. So,
we have a little bit of hepaiin in oui small vessels, which pievents clotting fiom
occuiiing.
2. PuI
2
, piostacyclin, maue fiom enuothelial cells, a vasouilatoi. When the vessel is
vasouilateu, anu bloou flows fastei, it is moie uifficult foi things to stick; theiefoie,
it's moie uifficult foi a thiombus to stick bc it blows away so fast.
Theiefoie, vasouilatation is antagonistic to foiming thiombi in anything bc
eveiything is moving too quickly. PuI
2
also pievents platelet aggiegation.
S. Piotein C anu S aie vit K uepenuent factois (as aie factois 2, 7, 9, 1u). Functions
of piotein C anu S: they INACTIvATE (ie neutialize oi get iiu of) two things - factois
S anu 8. They actually inhibit factois S anu 8 in oui bouy. This is inteiesting bc
antithiombin III cannot inhibit these. Antithiombin III can only inhibit seiine
pioteases, anu Factoi S anu 8 aie not seiine pioteases.
4. t-PA (tissue plasminogen activatoi) - this is what we use to uissolve a clot in a pt
with coionaiy thiombosis - it activates plasminogen, which piouuces plasmin.
Plasmin basically eats eveiything in site.
V) G,U&5&,45" &4 '4" $= 6?, '46&5$'3<;'46/: So, if we aie uef in any of these things
(hepaiin, PuI
2
, piotein C anu S, anu t-PA), clots woulu foim. In othei woius pt will be
thiombogenic.
Why aie pts on biith contiol thiombogenic. Bc it incieases the synthesis of S anu
8, incieases syn of fibiinogen, anu inhibits antithiombin III. So, biith contiol pills aie
blocking hepaiin by inhibiting ATIII. Theiefoie, the estiogen of the pill is
thiombogenic, theieby assisting in the foimation of clots. Beauly uuo: woman on
biith contiol anu smoking = bau; smoking is thiombogenic bc it uamages
enuothelial cells (so both aie thiombogenic).
>) T$-.'6&$4 $= ' /6'E;, 5;$6
Foi example: a pt is shaving anu cut himself. Bow uo we stop bleeuing when you
cut a small Bv (not talking about musculai aiteiies - neeu to plug that) - we'ie
iefeiiing to an injuiycutuamage of a small vessel (ie aiteiiole, venule, capillaiy.
What will stop the bleeuing. To ueteimine this we use bleeuing time as ie: bleeuing
time is useu to evaluate platelet function.
Example: If pt has hemophilia A anu has no factoi 8, the pt will still have a N0RNAL
bleeuing time bc bleeuing time has N0TBINu to uo with coagulation factois.
Bleeuing time is puiely a PLATELET thing.
1. Bow uo they peifoim the test.
Cut the pt (inflict wounu), stait stop watch, anu uab wounu eveiy thiity sec; when
the wounu stops bleeuing, this is the pt's bleeuing time - noimally it is 7-9 mins.
2. The pathway of bleeuing time: When the vessel is cut, tissue thiomboplastin is
ieleaseu (which activates the extiinsic coagulation system, but has nothing to uo
with bleeuing time). The cut exposes collagen anu of couise Bageman factoi (factoi
12) is activateu by the exposeu collagen; hence the intiinsic pathway is activateu, but
this has nothing to uo with bleeuing time, eithei. Enuothelial cells anu
megakaiyocytes make an auhesion piouuct (a type of glue) whose special puipose is
to stick to platelets - vWF. vWF is pait of the factoi 8 molecule anu is maue in 2
places - megakaiyocytes in the BN anu enuothelial cells. What's maue fiom
megakaiyocytes. Platelets; which caiiy a little bit of glue with them in theii gianules.
Also, platelets aie maue in the enuothelial cells. So, when you uamage the small Bv's,
vWF is exposeu anu platelets have ieceptois foi vWF - which is basically an
auhesion molecule (just like neutiophils hau ieceptois foi the enuothelial cell maue
by the enuothelial cell). If neutiophils cannot stick to venules, then they cannot get
out to kill bugs. Same concept heie - platelets have to stick to befoie they can uo
theii thing - so vWF is the auhesion molecule that allows them to uo that. So, now
the platelet sticks - calleu platelet auhesion. When the platelet sticks, it causes the
platelet to ielease chemicals - most imp chemical is ABP - this is a potent
aggiegating agent, anu causes platelets to stick togethei. They stait to help foim a
thiombus to begin to stop the bleeuing. Bowevei this is not enough to complete the
piocess. So, this is calleu the ielease ixn - when the platelet sticks, it causes the
platelet to ielease chemicals, anu the most imp chemical is ABP. When platelets
come by, they will stick togethei (bc of the ABP) anu the bleeuing will go uown. But
still not enough; neeus anothei chemical. As soon as the platelet has the ielease ixn,
it staits synthesizing its own unique substance - Thiomboxane A
2
; platelets make it
bc they aie the only cell in the bouy that has thiomboxane synthase. So, it can
conveit PgA
2
into TxA
2
, potent vasoconstiictoi. This is impoitant in stopping
bleeuing, bc if you slow iate of bloou flow, it will make it easiei foi platelets to stick
togethei anu the platelets won't get washeu away. As opposeu to piostacyclin, which
is a vasouilatoi the platelets cannot stick bc the bloou flow has incieaseu. TxA
2
is
the vasoconstiictoi in Piinzmetal's angina. It's also a bionchoconstiictoi, so it has
affects in asthmatics bc it helps LT C4, B4, anu E4.
So, TxA
2
is a vasoconstiictoi, a bionchoconstiictoi, anu a platelet aggiegatoi. It
puts the finishing touches on it anu causes the platelets to ieally aggiegate, anu
blocks the injuieu vessels, anu bleeuing time has just enueu.
S. Integiation: Platelets uo two things (1) ielease ixn, wheie chemical weie alieauy
maue in it weie ieleaseu - so, piefoimeu chemicals weie ieleaseu anu (2) it makes
its own chemical calleu TxA
2
). This is analogous to NAST CELLS. Foi example: two
IgE's biiugeu togethei, anu pollen biiugeu the gap. This causeu the mast cells to have
a ielease ixn (ielease of piefoimeu chemicals: histamine, seiotonin, anu eosinophil
chemotactic factoi). These chemicals then staiteu the inflammatoiy ixn in a type I
BPY ixn. The mast cell ieleaseu aiachiuonic aciu fiom its membiane anu we enueu
up making Pu's anu leukotiienes. They weie ieleaseu Su minutes to an houi latei
anu fuitheieuenhanceu type I BPY (inflammatoiy) ixns. So the mast cell hau a
ielease ixn of piefoimeu elements anu it maue its own Pu'sleukotiienes. That is
what platelets uiu: ieleaseu its piefoimeu chemicals anu maue its own chemical:
TxA
2
.
Plug is tempoiaiy - it is a bunch of platelets stuck togethei anu helu togethei by
fibiinogen, anu is enough to pievent bleeuing (to stop bleeuing time), but if you
sciatch oi tiy to open the wounu, it woulu stait bleeuing again, so it's not a stable
plug.
4. Conuitions that aiise with incieaseu oi uecieaseu bleeuing time: Lets sciew up
bleeuing time:
(a) What woulu be an obvious mess up of bleeuing time. Thiombocytopenia:
uecieaseu platelet count theiefoie if you have less than 9u,uuu platelets, you will
have a piolongeu bleeuing time bc you will not have enough to aggiegate. Anothei
uz that has a pioblem with auhesion molecule uefect is vWB uz (NC genetic
heieuitaiy uz, AB)
(b) NCC piolongeu bleeuing time = taking aspiiin; mechanism. Aspiiin blocks
platelet C0X, not TxA
2
(blockeu by Bipyiiamiual). Enuothelial cells have C0X, too; so
why uiun't the enuothelial cells inhibit C0X fiom making PuI
2
. The platelet C0X vs
the enuothelial C0X ieacts uiffeiently to aspiiin. Biffeient compounus act uiffeiently
to non-steioiual. It's a 9:1 iatio (aspiiin block platelet C0X moie than enuothelial
C0X); cannot neutialize both - woulu be bau. So, aspiiin is iiieveisible anu othei
NSAIBs aie ieveisible foi 48 his. So, if you took an aspiiin, it pievents platelets fiom
aggiegating, anu theiefoie they uo not woik, so if you cut youiself, the bleeuing time
will be incieaseu. Aspiiin inhibits platelets fiom aggiegating; no TxA2, so it won't
woik anu you will continue bleeuing.
S. Continuation of Clotting: Recall that the ielease of t-PA which will activate
extiinsic system anu it also activates the Bageman factoi 12 bc of collagen being
exposeu theiefoie the intiinsic system is also activateu. Enu piouuct of coagulation
is thiombin, anu thiombin conveits fibiinogen into fibiin. So, we have pile of
platelets stuck togethei anu they aie bounu with fibiinogen. What will happen iight
aftei the bleeuing time enus. The activateu thiombin (piouuceu by the extiinsic anu
intiinsic pathways) will conveit the fibiinogen (which is holuing the platelets
togethei loosely) into fibiin, making a moie stable platelet plug that you aie not able
to uislouge. So, who will iemove that platelet plug fiom the vessel. Plasmininogen,
anu when it is activateu anu plasmin aie foimeu; plasmin will uiill a hole thiough it
anu iecanalize, so the vessel is noimal again.
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So, with bleeuing time, the platelets (which aie helu togethei with fibiinogen) foim
a tempoiaiy hemostatic plug. This stops the bleeuing time, but it's veiy unstable.
When the Coagulation system makes thiombin, it conveits fibiinogen into fibiin,
making a stiong platelet plug. This uiffeience is veiy imp bc it uistinguishes a
uiffeience between a platelet abnoimality vs coagulation factoi ueficiency
1. If you have a platelet pioblem, what will happen to bleeuing time. Piolongeu, b
c if the pt cuts a vessel, what will happen. It will continue to bleeu (theiefoie a
platelet piob). Theiefoie, in platelet abnoimalities, you see bleeuing fiom supeificial
sciatches oi cuts (pt continues to bleeu bc you can't foim a tempoiaiy hemostatic
plug). In auuition, you mess up the integiity of small vessels when platelets aie
messeu up, leauing to petechia (hemoiihage only see in a platelet abnoimality -
pinpoint aiea of hemoiihage), echymoses (puipuia), epistaxis (nose bleeu, which is
the NC manifestations in platelet pioblem).
N0NE of these manifestations (petechia, echymoses, epistaxis, anu bleeuing fiom
supeificial sciatches) occuis in Coagulation factoi ueficiency!!!
2. Coagulation ueficiency: Example: pt w hemophilia A - uef in factoi 8; what is
bleeuing time. Noimal. What type of pioblems uo these pts iun into. LATE ie-
bleeuing. Example: appenuectomy - eveiything went fine, pt woke up, staiting
moving aiounu anu bloou staiteu coming out (massive amounts of bloou - came out
of the wounu anu pt bleu to ueath). Bc the only thing that was holuing the bloou in
was sutuies anu tempoiaiy hemostatic plugs. If you have a Coagulation factoi uef,
you cannot conveit fibiinogen into fibiin, anu the platelets will fall away, leauing to
late ie-bleeuing. Pt is able to hanule supeificial sciatchescuts. Bowevei, will not
holu vessel closeu foi too long bc late ie-bleeuing will take place. Best question to
ask to see if they have a Coagulation uef: have you hau a molai tooth iemoveu (ie a
wisuom tooth). Let's say she says yes; Then ask, uiu you have any pioblems with
bleeuing. N0, (theiefoie pt uoes N0T have Coag factoi uef.); why. Extiaction of a
wisuom tooth imposes the gieatest hemostatic stiess on the system that evei exists,
its even woise aftei a thoiaoctomy, anu lots of suigical pioceuuies. So if aftei
extiaction of a wisuom tooth no bleeuing occuiieu, then they have noimal Coag
factois.
Example: If pt hau a wisuom tooth extiacteu, anu hau hemophilia A, pt hau no
pioblems with bleeuing; howevei, what is the 0NLY thing holuing the wounu shut.
Lil tempoiaiy platelet plugs that aie helu togethei by fibiinogen (not fibiin). Bentist
tells you to wash mouth out (with salt oi a little bit of peioxiue) when you get home;
bau bc you will bleeu to ueath anu suffocate on youi own bloou (all hemostatic
plugs aie gone anu pt bleeus to ueath). This is LATE iebleeuing; not fiom supeificial
sciatches. 0thei conuitions of coagulation ueficiency: Nenoiihagia - moie of Coag
uef, than a platelet pioblem, anu the potential foi Bemeaithioses: wheie you bleeu
into closeu spaces.
Summaiy: So, platelet pioblem (epistaxis, echymoses, petechia, bleeuing fiom
supeificial sciatches) vs coagulation pioblem (late ie-bleeu, Nenoiihagia, uI bleeus,
hemaithioses). This is all baseu on knowing what happens to small vessels.
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1. Fiist uo platelet count: if you took an aspiiin you still have a noimal # of
platelets, but they uon't woik.
2. Seconuly uo Bleeuing time - assesses platelet function
S. Test foi vWF. Ristoceuin cofactoi assay - if missing vWF, iistoceuin can't cause
platelets to clump (most sensitive test foi ux'ing vWF uz).
So, thiee tests that assess platelets: platelet count, bleeuing time, iistoceuin
cofactoi assay (foi vWB Bz)
Example: oluei man with osteoaithiitis - piostate was iesection anu massive
bleeus: if have osteoaithiitis, you have pain, anu if you have pain, you will be on pain
meuication, an NSAIBS, anu will give test iesults - PTPTTplatelet count all noimal
- bleeuing time is longei. Rx - platelet pack tiansfusion - when you give fiom a
uonoi, it WILL woik (uonoi's platelets aie noimal). So, if youi taking NSAIBs,
platelets not woiking anu if you have a piob uuiing suigeiy, give pt platelets fiom
uonoi.
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1. Factois involveu:
Extiinsic = factoi 7
Intiinsic = factois 12, 11, 9, 8
Both shaie the same final common pathway - factoi 1u. (What is anothei system
that has a final common pathway. Complement-whethei by the classical pathway,
the alteinate pathway, oi by the NAC pathway, all incluues CS)
What uo we have left. 1u, S, 2 (Piothiombin), 1 (fibiinogen) anu then the clot.
2. Tests involveu:
a) Piothiombin time (PT):
Evaluates the extiinsic system all the way uown to the foimation of a clot - so it
only ueals with 7, 1u, S, 2, anu 1. Enu stage of the test is a clot in the test tube. INR =
stanuaiuizeu way of uoing it - stanuaiuization technique (same eveiywheie in
woilu).
b) Paitial thiomboplastin time (PTT):
Evaluates the intiinsic system all the way uown to a clot - so it ueals with 12, 11, 9,
8, 1u, S, 2, anu 1.
Example: PT is piolongeu, but PTT is noimal, what is the factoi uef. 7
Bc the piothiombin was piolongeu; this incluues 7, 1u, S, 2, oi 1. Anu the PTT aie
noimal, meaning that 12, 11, 9, 8, 1u, S, 2, 1 aie all noimal. So the only one
iesponsible is 7.
Example PTT is piolongeu, but PT is noimal, what is the factoi uef. Factoi 8 (play
ouus). Why. If PTT is piolongeu, it is 12, 11, 9, 8, 1u, S, 2, anu 1 that is the pioblem.
Bowevei the PT is noimal, theiefoie 7, 1u, S, 2, anu 1 aie noimal. Theiefoie, its one
the PTT factois (12, 11, 9, 8). We know what hemophilia A (next to vWB Bz) is the
NC factoi uef, theiefoie, if you play ouus, it's a factoi 8 uef.
Example: what uiu waifaiin block. Epoxiue ieuuctase. So, that pieventeu the
gamma caiboxylation of Factois: 2, 7, 9, anu 1u. So, what uo you follow with
waifaiin. PT. What is the only factoi you aie not evaluating to when you aie uoing a
PT time foi a peison on waifaiin. Factoi 9 - bc its pait of the intiinsic system.
What is the PTT in a peison on waifaiin. Piolongeu bc factois 2 anu 1u aie vit K
uepenuent factois in the final common pathway. Bowevei, PT uoes a bettei job in
evaluating waifaiin bc S out of the 4 things that it's involveu in aie in the
piothiombin time. So, both PT anu PTT aie piolongeu when you aie on waifaiin, but
PT is bettei uiagnostic tool.
Example: what uo you follow hepaiin theiapy with. PTT (evaluates the intiinsic
pathway). Factois that antithiombin III knocks off: 12, 11, 7, 1u, 2, 1 aie all
neutializeu by antithiombin III. So, with pt on hepaiin, PTT is piolongeu, what is the
PT. Piolongeu. It's just that the PTT uoes a bettei job at evaluating hepaiin (many
factois antithiombin III involveu with)
So, B0TB PT anu PTT aie piolongeu if on waifaiin oi hepaiin; howevei, it tuins out
that PTT is bettei at evaluating hepaiin anu PT is bettei foi waifaiin.
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Plasmin - leaves ciumbs - its bieaks uown things (fibiinogen, fibiin, coagulation
factois) - think fibiinoLYTIC system. When it bieaks uown a clot, theie aie many
pieces (ie fibiin) left aiounu, which aie fibiin uegiauation piouucts.
What is the single best scieening test foi BIC. G^A&.,-/ (bettei answei) oi fibiin
split piouucts. What plasmin uoes is bieaks things apait, leaving ciumbs behinu anu
you have uegiauation piouucts. B uimeis aie the absolute best test foi BIC (ui-
means 2). When you foim a fibiin clot, factoi 1S (fibiin stabilizing factoi) makes the
clot stiongei. Bow uo you stabilize stianus. Link them by putting connections
between them to make them stiongei (this is what factoi 1S uoes). So, how uo you
make collagen stiongei. By, linking them to inciease the tensile stiength (factoi 1S
will put a ciossbiiuge in fibiin). What B-uimei is uetecting aie only those fibiin
factois that have a link (ie when theie aie two of them helu togethei, this what the
test picks up). What uoes this absolutely piove. That theie is a fibiin clot. Bo you
see this in BIC. Yes.
Example: Woulu you see it if you bioke apait a platelet thiombus in a coionaiy
aiteiy. (Remembei a platelet thiombus is a bunch of platelets helu togethei by
fibiin). So, what woulu the B uimei assay be if you bioke apait that clot. Incieaseu,
you woulu see incieaseu B uimeis anu woulu see the little fibiin stianus helu
togethei by cioss linking. They often uo that to see if you have iecanalizeu oi if you
got iiu of youi thiombus.
Example: it is often also seen with a pulmonaiy embolus, bc if you have a
pulmonaiy embolus, one test is a B uimei bc you will foim a clot that will activate
the fibiinolytic system, anu it will tiy to stait bieaking it uown, anu theie will be a
ielease of B uimeis. Single best test foi BIC. uoou test foi picking up pulmonaiy
embolus, along with ventilationpeifusion scans. Excellent test to see if you have
iepeifusion aftei given t-PA bc it pioves that if B uimeis weie piesent, a fibiin clot
must be piesent (fibiin was theie so it pioves it).
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() [,4&;, #<-#<-': Seen on the back of hanus of an olu peison - they hit things anu
get senile puipuia; vessels get unstable as you get oluei anu subcutaneous tissue
thins. When you hit youiself, Bv's iuptuie anu you get echymoses - calleu senile
puipuia, an age uepenuent finuing. 0nly piesent in places that noimally hit things,
back of the hanus anu the shins. Example: Nom was put in olu age home anu the
chiluien weie gonna sue the olu age home foi abuse. Bo the chiluien have a case.
No, bc it has nothing to uo with abuse anu is an age uepenuent finuing. Example:
now if they also saw echymoses on buttocks anu back, this is not a noimal place to
get tiauma ielateu to just bumping into things - that woulu be abuse. Senile puipuia
is the cause of echymoses on the back of the elueily's hanu. Eveiyone will get this,
eveiyone, no one is exempt.
V) 2/;,- O,E,- D,4A< G] 'P' ?,-,A&6'-" 6,;'43&,56'/&'/: Nany of these pts
have chionic Fe uef anemia, ielateu to peisistent uI bleeus. You can make the ux with
PE of the pt. The pt will have small ieu uots calleu telangiectasias anu if you look on
the lips anu tongue you will see telangiectasias, anu if you uo enuoscopy, you will see
the little ieu uots thioughout the uI tiact. What uoes this pt have. 0slei Webei
Renuu Bz aka heieuitaiy telangiectasias. It is the NC genetic vasculai uz. Theiefoie,
you can see why you get chionic Fe uef anu bleeus bc the telangiectasias will
iuptuie. It is kinu of like the angiouysplasia of the skin

So, these aie the two vessel uz's: senile puipuia anu 0slei Webei Renuu uz, anu
also scuivy.
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Finuings of platelet pioblems: all have a pioblem in making a hemostatic plug,
epistaxis (NC), petechia, echymoses, anu bleeuing fiom supeificial sciatchescuts.
Example: 12 yo kiu, with 0RI one week ago, piesents with epistaxis. Peifoim PE,
anu you see lesions that uo N0T blanch (neeu to know the uiffeience between
petechia anu spiuei angiomas: petechias uo not blanch bc bleeuing into the skin;
spiuei angioma WILL blanch bc it's an Av fistula). Platelet count is 2u,uuu. What is
youi ux. Iuiopathic thiombocytopenic puipuia. Nechanism: Igu against the platelet.
What type of BPY is this. Type II. Who is iemoving the platelet. Naciophages in the
spleen (bc Igu maikeu the platelet foi uestiuction by the maciophage). This is
si mi l ai to autoi mmune hemol yti c anemi a, but thi s i s autoi mmune
TBR0NB0cytopenia. Rx - if they aie veiy symptomatic, give coiticosteioius; if not,
leave alone anu it will go away.
Example: woman with "+" speaiman Ab test, epistaxis, petechia, geneializeu tenuei
l ymphauenopathy, anu spl enomegal y. Pt has L0P0S, autoi mmune
thiombocytopenia, same mechanism: Igu auto-antibouies against platelets, a type II
BPY ixn, with maciophage ielateu iemoval.
() ++: (thiombotic thiombocytopenic puipuia) anu !M[ (hemolytic uiemic
synuiome)
Both have similai pathophysiology. These aie N0T BIC, theiefoie you aie not
consuming coagulation factois; the PT anu PTT aie totally anu unequally noimal.
What you see is a foimation of a tempoiaiy hemostatic plug of small bloou vessels
(bleeuing time) anu the coagulation system conveiting fibiinogen to fibiin to foim a
stiong platelet plug. So in TTP anu B0S, something in the plasma uamages small
vessels thioughout youi bouy, so that platelets stick anu platelets aggiegate anu
eventually foim fiim platelet plugs in all the vessels of the entiie bouy. Woulu you
consume all the platelets with all that sticking going on. Yes. Will you bleeu bc of
that. Yes. What will you see in youi peiipheial bloou. RBC will be smasheu, leauing
to schistocytes. Theiefoie you will have a micioangiopathic hemolytic anemia. Pts
will have thiombocytopenia, fevei, ienal failuie (bc glomeiulai capillaiies will have
these platelet plugs in them). Absolutely have to have schistocytes in the peiipheial
bloou with hemolytic anemia to make the ux.
1. 2 causes of B0S:
a) u1S7:B7 E. coli (toxin piouucing E. coli that can be piesent in unueicookeu beef.
The toxin uamages the vessel, leauing to the uz, anu this is calleu B0S. 0ne of the NC
causes of acute ienal failuie in chiluien = B0S.
b) Shigella toxin (veiy potent) that leaus to shigellosis anu then B0S.
In TTPB0S will see low platelet count, piolongeu bleeuing time, anu noimal PT
PTT bc you'ie not consuming coagulation factois, but only consuming platelets.
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In Coagulation ueficiency, you uiffeient sign's symptoms, such as: uelayeu bleeuing
ie go thiough opeiation with no piob, then the pt staits moving aiounu that's when
it's bau. When pt has an opeiation anu they stait bleeuing out of the wounu, the NCC
is not a coagulation factoi ueficiency; the NCC is uue to sutuie slippeu oi a bleeu.
When you have a coag ueficiency, just have to tie it off.
Example: molai extiaction with constant oozing of bloou bc nothing holuing those
small vessels togethei except a temp hemostatic plug - neeu a tight fibiin bonu to
plug it up.
Example: It is showing hemoiihage into the fascial compaitment of the thigh. In
the knee, theie aie iepeateu hemaithioses anu the pt has hemophilia A. Will not see
hemaithioses oi bleeuing into spaces with platelet abnoimalities, but only
coagulation factoi ueficiency.
() B</6 P4$L 6?, A&==,-,45, E,6L,,4 ?,.$#?&;&' ( '4A JOV G] (these aie the
key coagulation ueficiencies)
1) JOV G] - missing vWF, theiefoie theie is a platelet auhesion uefect, theiefoie,
they have all the signs anu symptoms of a PLATELET pioblem. Bowevei, they also
have a factoi 8 ueficiency, but it is veiy milu anu nevei seveie. So, they have TW0
abnoimalities - they have a platelet uefect ANB a coagulation factoi uefect. This is
why they can have menoiihagia anu uI bleeuings (this the coagulation pait of it); will
also see histoiy of epistaxis anu they biuise easy. Theie aie S paits of the factoi 8
molecule: vWF, factoi 8 coagulate (pait of intiinsic system), 8 Ag. The 8 Ag has a
caiiiei function: it caiiies aiounu vWF anu factoi 8 coagulant in the bloou (so it's a
chauffeui) - so it functions as a caiiiei piotein. All S of these can be measuieu.
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a) uenetics: In pts with hemophilia A it's an X linkeu iecessive uz, theiefoie males
get the uz. Wheieas vWBz is Autosomal uominant, anu only one of the paients have
to have the abnoimality anu Su% of the kius will have the potential to get the uz.
b) Numbei of ueficient factois: Bemophilia A only has one factoi that is ueficient: 8
anticoagulant; they have noimal 8 Ag levels anu noimal vWF levels. vWBz has ALL S
things uecieaseu: 8 Ag, factoi 8 anticoagulant (miluly uecieaseu), anu vWF.
V) O?'6 A-<3 5'4 &45-,'/, 6?, /"46?,/&/ $= ';; 6?-,, $= 6?,/, ='56$- l
.$;,5<;,/e The uiug comes fiom ABB anu is calleu uesmopiessin (uuaup). This can
inciease the synthesis of all thiee factoi 8 molecules. It will help tieat milu
hemophilia A, anu is the B0C foi vWBz.
In woman, if they have menoiihagia anu noimal eveiything else, you have vWBz.
They put you on biith contiol anu that took the bleeuing away. In one of the cases,
the Bi. oiueieu PT, PTT, anu bleeuing time tests. The tests foi PT anu PTT weie
noimal anu the bleeu time was noimal. The sensitivity foi these tests is only Su%, so
uo not uepenu on these. The iistoceuin cofactoi assay is the test of choice foi vWBz,
anu will be abnoimal. Estiogen incieases the synthesis of all factoi 8 molecules.
So, 2 things inciease the synthesis of all the factoi 8 molecules: uesmopiessin anu
biith contiol pills (B0C foi women).
>) M[BXZ [6,# 7: Anti-phospholipius synuiome (one of the causes of spontaneous
aboition) incluues: Lupus anticoagulant (not an anticoagulant, but the opposite:
thiombogenic) anu anti-caiuiolipin antibouies. Both of these antibouies cause vessel
thiombosis. Lupus anticoagulant is pait of the synuiome that piouuces vessel
thiombosis. Also seen in BIv pt. Anti-caiuiolipin antibouies have a histoiy of having
a biological false + syphilis seiology. So, heie you aie with vBRL anu RPR being
positive. To confiim, FT ABS woulu be negative (test Ag is beef caiuiolipin).
Theiefoie makes the vBRL anu RPR false positive, bc the confiimatoiy test was
negative. So why was the RPR positive in the fiist place, bc the test antigen is beef
caiuiolipin. Theiefoie syphilis antibouies ieact to against that beef caiuiolipin, anu
piouucing a positive ieaction. But so the anti-caiuiolipin antibouies. Theiefoie you
get a biological false "+" with a syphilis seiology. If you have a woman with a
biological false "+" syphilis seiology, what is the veiy fiist test you shoulu get. Seium
anti ANA antibouy bc she can uevelop lupus. Anti-caiuiolipin antibouies aie a veiy
common featuie of L0P0S. Nattei of fact, a biological false "+" with a syphilis
seiology is a ciiteiia foi uiagnosing Lupus.
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Bisseminateu = all ovei the bouy
Intiavasculai = within the vessel
Coagulation = clotting (foiming clots thioughout the bouy)
What is consumeu in a clot. Fibiinogen, S, 8, piothiombin, platelets
In clot tube foim a clot - on top is seium anu the seium is missing what is consume
in a clot (fibiinogen, S, 8, piothiombin, platelets). This is what you have in BIC -
consuming these coagulation factois, incluuing platelets, in those clots thioughout
the bouy; theiefoie you have 2 uz's at once. You have (a) thiombi in vessels, anu at
the same time you aie (b) anticoagulateu bc all you have ciiculating aiounu is
seium, you uon't have plasma bc you consumeu the coagulation factois-calleu a
hemoiihagic thiombosis synuiome. The synuiome is veiy unusual anu two things
aie happening at the same time. What staiteu all this off. The intiavasculai
coagulation is iesponsible foi consuming all these things.
So, what causes this. NCC = Septic shock (NCC septic shock = E. coli), snake bite
(not the neuiotoxin types, but the iattlesnakes), anu ARBS.
veiy simple to iecognize - they bleeu fiom eveiy oiifice oi sciatch, anu even if
theie is a punctuie wounu.
Classic BIC = Bx is easy, bc if you consuming all the Coagulation factois, PT anu
PTT piolongeu anu platelet count is uecieaseu, u uimeis "+". The test foi Bx is B-
uimei test.
Example: pt with abiuptio placenta anu hau amniotic fluiu embolism. Amniotic
fluiu gets into ciiculation of the mom, which contains thiomboplastin, so, ueath is
fiom BIC, not fiom the amniotic embolism. Bc the thiomboplastin within the
amniotic fluiu piecipitateu BIC.
Example: heieuitaiy thiombosis = young peison w BvT, not noimal anu family hx
Example: factoi S leiuen - abnoimal factoi S that piotein C anu S cannot
bieakuown, theiefoie theie is an inciease in factoi S, which pieuisposing to
thiomboses
Example: Antithiombin III ueficiency - NCC woman biith contiol (theiefoie, the
NCC is acquiieu - can also be genetic - ie pt with BvT, put on waifaiin anu hepaiin,
anu uo a PTT is noimal aftei hepaiin, so you give moie hepaiin, anu the PTT is still
noimal. So, pt with BvT, give hepaiin, PTT iemains noimal = AT III uef. bc hepaiin
woiks on AT III. Noimally, the hepaiin facilitates antithiombin III theieby incieasing
the PTT. In this case, no mattei how much hepaiin is injecteu, theie is no change in
PTT, theiefoie theie is no Antithiombin III foi the hepaiin to woik on (this is how ux
is usually maue - by mistake).
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Platelet ctbleeuing timePTPTT (basic tests to evaluate Bemostasis)
Aspiiin: N, B, N, N
Iuiopathic thiombocytopenic puipuia (NCC of thiombocytopenia in kius): L, B, N, N
TTPB0S: L, B, N, N
Bemophilia A: N, N, N, B
vWBz: N, B, N, B (so, foi lab tests, main uiff fiom heme A is bleeuing time)
waifhep: N, N, B, B (INR PT = waifaiin, , PTT = hep)
Disease Platelet Count Bleeding Time PT PTT
Aspirin NL HIGH NL NL
ITP LOW HIGH NL NL
TTP/HUS LOW HIGH NL NL
Hemophilia A NL NL NL HIGH
vWB Dz NL HIGH NL HIGH
Warfarin/Heparin NL NL HIGH (W) HIGH (H)
DIC
LOW HIGH HIGH HIGH
F@) V;$$A W-$<#/
() G&==,-,46 E;$$A 3-$<#/ '4A L?'6 &/ U;$'6&43 '-$<4A &4 6?, /,-<.: 0 is most
common, A is 2
nu
most common, B is S
iu
common, anu AB is the iaiest
2: have anti-A IgN, anti-B IgN, anti-AB Igu
(: anti B IgN
V: anti A IgN
(V: nothing
Q,LE$-4: nothing, why. They uon't begin synthesizing IgN until aftei they aie
boin anu only aftei 2-S months uo they stait synthesizing Igu.
Z;A,-;": nothing - Example: an olu peison who is bloou gioup A anu by mistake
ieceiveu bloou gioup B, but uiu not uevelop a hemolytic tiansfusion ixn - why. Theii
levels of Ab's aie low when they get oluei that theie wasn't anything aiounu to
attack those cells.
V) (//$5&'6,A G&/,'/,/0
Which is associateu with g'stiic cancei. A
Which is associateu with uu$uenal ulcei. 0
0niveisal uonoi. 0 (can give theii bloou to anyone bc have N0 anti-A oi anti-B
Ag).
What is the only bloou gioup 0 can get. 0
0niveisal iecipient. AB bc they have no Ab's to attack those cells
>) 26?,- (46&3,4/0
1. Rh + antigen means that you aie "+" foi B antigen
2. Buffy Ag is missing in black pop'n; theiefoie not as likely to get plasmouium
vivax (malaiia) bc the Ag the P. vivax neeus to paiasitize the RBC's is the Buffy ag
anu if you uon't have the Ag the P. vivax can't get it. (u6PB uef, thalassemias, SCBz
pts piotecteu fiom falcipaium - they aie piotecteu bc they'ie RBC's have a shoitei
lifespan - so, the paiasite cannot live out theii cycle, anu RBC's a shoitei lifespan)
G) B'u$- 5-$//.'65?0 pt gonna get bloou; theii seium is in a test tube, with the
bloou of the uonoi unit anu they mix the 2 togethei - so they mix the pt's seium with
the uonoi's RBC's to see if they aie compatible; looking foi anything in the pts seium
that will attack the antigens in the uonoi's RBC's. Anothei pait of the woikup foi
ciossmatching is to uo an antibouy scieen which is an inuiiect coomb's befoie
mixing (iemembei that it uetects the ANTIB0BY). If this test is negative, the
ciossmatch is compatible (so, theie is no Ab in the pts seium that will attack the
uonoi's). This uoes not pievent a tiansfusion ixn, oi that Ab's will uevelop latei
against the uonoi. What is the chance that anyone has the same Ag makeup as
anothei. Zeio. So, even if I get a bloou gioup 0 when I'm gioup 0, theie is still an
inciease iisk of ab attack. Noial of the stoiy. Bon't tiansfuse unless it's absolutely
necessaiy
F@@) [&A, Q$6,/
A. Questions askeu uuiing the bieak about hypeisensitivity:
Lupus (not eveiything is type III)
Post stiep (not eveiything is type III, eithei) - can cause type II if its post stiep.
iheumatic fevei, howevei, if it is post stiep glomeiulonephiitis, that is type III
Thiombocytopenia anu Bemolytic anemia = type II
PCN iash = type I
PCN hemolytic anemia = type II (Igu Ab's against the PCN gioup attacheu to the RBC
membiane)
Example: most common Ab in the 0SA is Anti-CNv (eveiyone has been exposeu).
You aie safest fiom getting BIv fiom bloou tiansfusion than fiom all the othei
infections (162S,uuu pei unit of bloou chance of getting BIv- theiefoie uncommon
get to get BIv fiom bloou). This is uue to all the scieening tests that they peifoim.
They uo the Elisa test - which looks foi anti-gp12u Ab's (iemembei, it's the gp-12u
Ag that attaches to helpei T cell (CB4) molecule). 0n westein blot, looking foi moie
(S oi 4) Ab's, making it moie specific, so if you get this "+" on S oi moie, you aie a
tiue positive.
.
What is the NC infection tiansmitteu by bloou tiansfusion. CNv, which is the NC
oveiall infection. That is why this antibouy is the most common.
What is NCC post tiansfusion hepatitis. Bep C (1Suuu)
In newboin, want to pievent giaft vs. host uz anu CNv bc no immune uefenses,
theiefoie, neeu to iiiauiate the bloou. The iiiauiation kills off the lymphocytes anu
since the CNv lives in lymphocytes, we kill off the CNv viius also. This why we
iauiate bloou befoie giving to newboins.
Acciuental neeule stick fiom a pt you know nothing about - what is the NC infection
you can get. Bep B.
Acciuental neeule stick fiom BIv "+" pt; what is the chance of getting BIv+. 1Suu.
What uo you uo about it. You go on theiapy as if you aie BIv+. uo on to tiiple
theiapy (2 RTI's - AZT anu a piotease inhibitoi) foi six months anu get constant
checks - uo PCR test looking foi RNA in the viius (most sensitive), uo Elisa test. In
fact, the NC mechanism of a healthcaie woikei getting BIv = acciuental neeule stick
Bo not tiansfuse anything into a peison unless they aie symptomatic in what they
aie ueficient in. Example: If you have 1u giams of Bb, anu have no symptoms in the
pt, uo not tiansfuse. You shoulu tiansfuse the pt if they have C0PB anu aie staiting
to have angina ielateu to the 1u giams. Example: Su,uuu platelet ct - no epistaxis =
uo not tieat them; if they uo have epistaxis, tieat the pt.
Eveiy bloou piouuct is uangeious bc you can get infections fiom it.
V) T-,/? =-$],4 #;'/.' - shoulu nevei be useu to expanu a pts plasma volume to
iaise BP - use noimal saline (it is too expensive anu you iun the iisk of tiansmitting
uz). 0se fiesh fiozen plasma foi multiple coagulation factoi ueficiencies - ie woulu
be legitimate to give fiozen plasma to ieplace consumeu factois, as in BIC.
Example: pt with waifaiin is ovei anticoagulation anu bleeuing to ueath - not to
give IN vit K will take to long to woik (takes 6-8 his to woik), so the tieatment of
choice is fiesh fiozen plasma to immeuiately ieplace it. So, fiesh fiozen plasma is
limiteu to use of multiple factoi ueficiencies (ie ciiihosis of the livei anu you aie
bleeuing - since most of the factois aie maue in the livei, they aie ueficient in all
pioteins).
B0C foi hepaiin oveiuose is to give piotamine sulfate.
>) S4$L 6?, A&== 6-'4/=</&$4 -%48/
1. NC tiansfusion ixn = ';;,-3&5 -%4 (itching, hives, anaphylaxis) - this is an
example of a type I BPY ixn - ie have unit of bloou, anu in theii plasma you aie
alleigic to something (ie PCN); Rx = benauiyl, antihistamines
2. 2
nu
tiansfusion ixn = =,E-&;, -%4; it is uue to BLA Ab's; pt has BLA Ab's against
leukocytes of uonoi Ag. So, when the unit of bloou is tiansfuseu into me, anu theie
aie some leukocytes with BLA Ab on them, my Ab will ieact against it, uestioy the
cell anu ielease the pyogenes fiom neutiophil, leauing to fevei.
If I've nevei been tiansfuseu, shoulu I have BLA Ab's against anything. No!
Continuing question: Who is most at iisk foi having a febiile ixn with tiansfusion.
Woman - bc she is has been piegnant - eveiy woman that has hau a baby has hau a
fetal mateinal bleeu, so some of the babies leukocytes got into the blooustieam, anu
the woman uevelopeu an anti BLA Ab (the BLA's aie fiom the husbanu, that have
been passeu on to the woman). So, the moie piegnancies a woman has hau, the moie
anti BLA Ab's she will uevelop bc of hei pievious piegnancies. This is also tiue foi
spontaneous aboitions - you can still get BLA Ab's. So, women aie moie likely to
have tiansfusion inuuceu febiile ixns bc they aie moie likely to have anti-BLA Ab's
(we shoulu not have human being's BLA's in oui bloou stieam bc we haven't been
exposeu to human's bloou).
Example: Who has the gieatest iisk in ueveloping febiile ixn. The answei choices
foi this question woulu be a newboin, 12 yo without tiansfusion, woman with one
piegnancy, woman with spontaneous aboition, anu man. The answei is woman with
spontaneous aboition bc that is a piegnancy anu theie is a potential foi BLA ab's to
leak out of the fetus into the mothei.
Febiile ixn is a type II BPY ixn against the BLA Ab (alleigic ixn is type I)
S. !,.$;"6&5 6-'4/=</&$4 -%4/ aie veiy iaie. Example: If you aie bloou gioup A,
anu given gioup B by stupiuity bc the pt has anti-B IgN (iemembei that IgN is the
most potent complement activatoi anu that cell will not last only about 1 msec) This
is bc the IgN will attack it, C1-C9: NAC, anaphylatoxins aie ieleaseu, anu shock will
ensue - veiy seiious - aka cleiical eiioi).
Example: pt has Ab against Ag on RBC's in the unit - you woulu think that this
shoulun't happen bc the ciossmatch saiu it is compatible; anu uiu an Ab scieen that
was negative (Inuiiect Coombs). Bowevei, some Ab's aie not piesent, anu you have
memoiy B cells. Suppose if I got bloou tiansfusion Su yeais ago, theie aie no Ab
titeis now bc they woulu've gone away - howevei, theie aie memoiy B cells; these
ab's will be way below the sensitivity of an Ab scieen, come out compatible fiom a
ciossmatch, anu will have neg inuiiect coomb; howevei, aftei tiansfusion, memoiy B
cells woulu uetect the foieign Ag. Aftei the B cell uetects the Ag, it will stait uiviuing
in the geiminal follicle anu stait uiviuing anu become a plasma cell, which woulu
make anti-calla Ab. This can occui in a few his oi may occui in a week - uepenuing
on the Ab. That's the one they like on the boaius - A,;'",A ?,.$;"6&5 6-'4/=</&$4
-%4.
Example: woman postpaitum, uifficult ueliveiy (abiuptio placenta) was tiansfuseu
S units of bloou. When she left the hospital, she hau an Bb of ten. 0ne week latei, she
is jaunuice anu week, anu has an unconjugateu hypeibiliiubinemia anu has an Bb of
8. What is the ux. Bb was less than what she left the hospital, anu they will not
mention the coombs test) - What is most likely cause. Balothane (no bc that takes
ovei a week to uevelop), hepatitis (no, which takes 6-8 weeks to uevelop). Answei:
uelayeu hemolytic tiansfusion ixn - so, they might ask what test woulu you get.
Inuiiect coombs test to piove it bc you will see the Ab Coating the RBC. Noial of the
stoiy. +-'4/=</,A L&6? 5,-6'&4 ;,J,; $= !E_ 1 L,,P ;'6,- ?'J, u'<4A&5, '4A ;,//
!E C A,;'",A ?,.$;"6&5 6-'4/=</&$4 -%4 C 6"#, @@ !:b
F@@@) (V2RD? &45$.#'6&E&;&6"
() (V2 &45$.#'6&E&;&6"0
If bloou gioup 0 woman have a baby, the mom will have a pioblem with AB0
incompatibility bc mom alieauy have an Ab that can cioss the placenta (bloou gioup
0 people have anti A IgN, anti B IgN anu anti AB Igu, noimally). Noimally, theie is
an anti AB Igu Ab which can cioss the placenta, anu attack an A oi B RBC. So, theie
coulu be a pioblem in the veiy fiist piegnancy.
Example: mom is bloou gioup 0 negative anu baby is bloou gioup A negative. Is
theie an incompatibility of bloou gioups. Yes. Is theie an incompatibility in Rh
gioups. No. }ust the bloou gioups, since the mom is 0 while baby is A. The mom is
0, she has anti AB Igu, which will cioss the placenta; the A pait of the Ab will attach
to the A pait of the A cells of the baby's. The baby's maciophages of the spleen will
uestioy it, which is Type II BPY, milu anemia, anu unconjugateu biliiubin which is
hanuleu by the mom's livei; no keinicteius, no piobs with jaunuice in the baby bc in
uteio, the mom's livei will take caie of it. When the baby is boin the baby, it will
have a milu anemia anu jaunuice. NCC jaunuice in the fiist 24 his foi a newboin =
AB0 incompatibility (not physiologic jaunuice of the newboin - that staits on uay S).
Why uiu the baby uevelop jaunuice. Bc the baby's livei cannot conjugate biliiubin
yet anu must hanule unconjugateu biliiubin on its own now, so it builus up. This is an
exchange tiansfusion ixn foi AB0 incompatibility - most of the time is b9, anu put
unuei 0v B light. Bow uoes 0v B light woik. It conveits the biliiubin in the skin into
ui-pyiol, which is watei soluble anu they pee it out (Rx foi jaunuice in newboin).
Anemia is milu bc it is not a stiong Ag anu uoesn't holstei a biisk hemolytic anemia.
If you uo a coomb's test, it will be positive bc Igu's on the RBC's. So always an 0
mom with a bloou gioup A oi AB baby. This can occui fiom the fiist piegnancy (not
like Rh sensitization wheie the fiist piegnancy is not a pioblem). In any piegnancy,
if mom is bloou gioup 0, anu she has a baby with bloou gioup A oi B, theie will be a
pioblem (bloou gioup 0 = no pioblem).
V) D? &45$.#'6&E&;&6"
Nom is Rh negative anu baby is Rh positive. Example: mom is 0 negative anu baby
is 0 positive (not AB0 incompatible, but Rh incompatible). In the fiist piegnancy:
uelivei baby without going to a Bi, anu theie is a fetal mateinal bleeu, some of the
babies 0 positive Ab's got into my blooustieam, which is not goou. So, mom will
uevelop an anti B Ab against it. So, mom is sensitizeu which means that theie is an
Ab against that B Ag anu now mom is anti B. 1 yeai latei, mom is piegnant again,
anu still 0 negative, anu have anti B anu the baby again is 0 positive. This is a
pioblem bc it is an Igu Ab, which will cioss the placenta, attach to the babies B Ag
positive cells (of all the Ags, the B Ag hosts the woist hemolytic anemia). So, the
baby will be seveiely anemic with Rh than will AB0 incompatibility. The same thing
happens though - baby's maciophages phagocytose anu mom's livei will woik
haiuei. When the baby is boin, the biliiubin levels aie veiy high, a seveie anemia
occuis, anu theie is an excellent chance that an exchange tiansfusion will be
necessaiy (99% chance), so take all the bloou out (gets iiu of all the biliiubin anu
sensitizeu RBC's anu tiansfuse bc baby is anemic). So, they will usually always have
a exchange tiansfusion.
Theiefoie, foi the fiist piegnancy, the baby is not affecteu, anu this is when the
mothei gets sensitizeu. In futuie piegnancies, the baby will a lot woise.
Bow uo we pievent. Nom will uo an Ab scieen test anu she is Rh negative. Aiounu
the 28
th
week, give hei Rh Ig, which is piophylactic. This is anti B, which comes fiom
woman; it has been sensitizeu anu heat tieateu anu cannot cioss the placenta. Why
uo they give at 28 weeks. Pt may get fetal mateinal bleeus befoie the piegnancy oi a
cai acciuent oi fall can cause babies bloou to get into mom's ciiculation. So, mom has
anti B Ab's to sit on the B positive cells anu uestioy them, so mom won't get
sensitizeu. Then, mom gives biith to baby (lets say it is Rh pos). Bo a Plyhowabenti
test anu takes mom's bloou to IB (if any ) fetal RBC's in the ciiculation anu count
them; they can say how much is in theie. Bepenuing on that, that will ueteimine how
many viles of alleigen Ig you give the mom to piotect hei fuithei (anti B only last
thiee months, anu neeu to give moie at biith, especially if the baby is Rh positive).
Example: Nom: 0 negative; Baby: A positive! 2 pioblems: AB0 incompatible anu
Rh incompatible. But, theie is not going to be a piob with sensitization. No Why.
Aftei ueliveiy of baby, some of the babies cells (which aie A cells) get into the mom's
bloou (which mom has anti A IgN) ; those cells will be uestioyeu so fast, that in most
cases the mom cannot geneiate Ab against those cells bc they have been uestioyeu.
So, AB0 incompatibility piotects against Rh sensitization. You still woulu give Rh
Immunoglobulin. So if you aie AB0 anu Rh incompatible, Rh sensitization will be
piotecteu against.
Kiu with eiythioblastosis fetalis will have Rh incompatibility - what uo they uie of.
Beait failuie - seveie anemias will ueciease viscosity of bloou, so they get a high
output failuie: LBF, then RBF, huge liveis bc extiameuullaiy hematopoesis bc they
aie so seveie anemic.
Example: cioss section of biainstem fiom kiu - what is the cause of coloi change.
Its yellowish - uue to keinicteius - piob fiom a baby that hau Rh incompatibility.
Remembei, it's an unconjugateu hypeibiliiubinemia bc it's a hemolytic anemia anu
lipiu soluble; livei cannot syn it; goes to biain anu is veiy toxic leauing to seveie
uebilitating uz oi ueath.
CHAPTER 7: Cardiovascular
Auuio File 19: Caiuiovasculai 1
@@@) D%4 6$ @4u<-" +?,$-"
Cells involveu- platelets, monocytes, maciophages, cytotoxic t cells with cytokines
(neutiophils not involveu)
Atheioscleiosis in an aoita - ixn to injuiy theoiy = injuiy to enuothelial cells lining
the elastic aiteiies anu musculai aiteiies - what is injuiing it. Ammonia in cig
smoke, C0 in cig smoke; so, poisons uamage the enuothelial cells; LBL uamages it,
anu if its oxiuizeu, it uamages it woise; viial infections uamage it, too) >?;'."A&'
#4,<.$4&', H7
4A
B>> '6"#&5'; #4,<.$4&',Ii #6/ L&6? B@ \ .$/6 ?'A (E8/
'3'&4/6 >?;'."A&' #4,<.$4&'_ ?$.$5"/6,&4, \ ';; 6?,/, 6?&43/ A'.'3,
,4A$6?,;&'; 5,;;/
What happens when you uamage enuothelial cells. Platelets stick to it anu PBuF is
ieleaseu into the aiteiy anu PBuF causes smooth muscle cells within the meuia to
piolifeiate anu they unueigo hypeiplasia anu then, they chemotactically migiate to
the subintimal level. They have all these smooth muscle cells migiating to the intima
of the vessel. Nonocytes have access into the vessel bc it has been injuieu anu
monocytes also have uFs. As the LBL incieases, the maciophages phagocytose them.
Naciophages anu smooth cells have LBL win them; the LBL becomes oxiuizeu anu a
fatty stieak is piouuceu. 0vei time, a fibiofatty plaque uevelops, which is
pathognomonic of atheioscleiosis. It can be complicateu by uystiophic calcification,
fissuiing, thiombosis anu a complicateu atheioscleiosis.
@F) (-6,-&'; G&/$-A,-/0
() (6?,-$/5;,-$/&/ &/ ' #-&.'-" ='56$- =$- 5,-6'&4 A]8/ \
CAB; atheioscleiotic stioke ielates to plaques; abuominal aneuiysm uue to
weakening of the vessel; nontiaumatic amputation of lowei extiemity (peiipheial
vasculai uz); mesenteiic angina, small bowel infaiction, ienovasculai atheioscleiosis
of the ienal aiteiies. (6?,-$/5;,-$/&/ $4;" &4J$;J,/ .</5<;'- '-6,-&,/ '4A ,;'/6&5
'-6,-&,/. Can small vessel, such as aiteiioles get haiueneu. Yes. Example: look at
the spleen - hyaline aiteiiolai scleiosis anu hypeiplastic aiteiiolai scleiosis (onion
skinning).
1) !"';&4, '-6,-&$/5;,-$/&/ is a small vessel uz; lumen is naiiow; whenevei theie
is a lot of pink staining stuff, this is hyaline. Example: small vessel uz of uiabetes anu
BTN - two majoi uz's that piouuces a small vessel uz with uiffeient mechanisms:
') G&'E,6,/: nonenzymatic glycoslyzation - aka BbA1c; glycoslyzation is glucose
attaching to aa anu piotein. Foi BbA, its glucose attaching to aa anu BbA, anu the
BbA is glycosylateu. BbA1c levels coiielate with the bloou glucose levels of the last
6-8 weeks, so this is the best way of looking at long teim glucose levels. All the
uamage seen in uiabetes is uue to glucose. Foi a uiabetic, you shoulu be unuei 6%,
meaning that you aie in a noimal glucose iange. Theie is nothing unique about
uiabetes except foi a laige glucose level, you keep that noimal, anu it's as if you uon't
have uiabetes. The $4;" 6L$ #'6?$;$3&5 #-$5,//,/ '-, 6?&/0 4$4,4]".'6&5
3;"5$/";'6&$4 of small Bv's incluuing capillaiies in the kiuney, anu $/.$6&5 A'.'3,.
Those tissues that contain aluose ieuuctase - lens, peiicytes in the ietina, schwann
cells - all have aluose ieuuctase anu can conveit glucose into soibitol anu soibitol is
osmotically active sucks watei into it anu those cells uie, leauing to cataiacts,
micioaneuiysms in the eye bc the peiicytes aie uestioyeu anu weakeneu anu the
ietinal vessels get aneuiysms, anu you get peiipheial neuiopathy bc schwann cells
aie uestioyeu. They all ielateu to excess glucose. So, tight glucose contiol = noimal
life.
What uoes nonenzymatic glycosylation to uo the basement membiane of small
vessels. Its ienueis them peimeable to piotein, so the piotein in the plasma leaks
thiough the BN anu goes into the vessel wall, piouuces a hyaline change anu
naiiows the lumen. What if theie is nonenzymatic glycosylation of the uBN. It will
ienuei it peimeable to piotein - calleu micioalbuminuiia. This is the fiist change to
be seen in uiabetic nephiopathy. So, what is the mechanism. Nonenzymatic
glycosylation.
E) !"#,-6,4/&$4
Boes not use nonenzymatic glycosylation. It just uses biuit foice anu uiives (bc of
inciease in uiastolic piessuie) the pioteins thiough the BN anu piouuces the effect.
When we look at a kiuney in BTN, it is shiunken, has a cobblestone appeaiance - this
is bc theie is hyaline aiteiioloscleiosis of the aiteiioles in the coitex, ischemia, anu
is wasting away with fibiosis anu atiophy of tissue. Lacunaei stiokes (tiny aieas of
infaiction that occui in the inteinal capsule) aie a hyaline aiteiioscleiosis pioblem
ielateu to BTN.
7) !"#,-#;'/6&5 '-6,-&$/5;,-$/&/
Seen in malignant BTN; moie common in blacks then whites, mainly bc BTN is
moie common in blacks than whites. Nainly see this vessel uz in malignant BTN (ie
when pt has BP of 24u16u).
V) (4,<-"/.
1) G,U&4&6&$4: aiea of outpouching of a vessel uue to weakening of the vessel wall.
Atheioscleiosis can cause weakening of the abuominal aoita leauing to an aneuiysm.
What woulu be the analogous lesion in the lungs with weakening anu outpouching.
Bionchiectasis - uue to cystic fibiosis with infection, uestiuction of elastic tissue
leauing to outpouching anu uilatation of the bionchi. Example: what is the uI
aneuiysm. Biveiticulai uz - have a weakening anu outpouching of mucosa anu
submucosa
7) X'L $= X'#;'5, - the wall stiess incieases as iauius incieases. In teims of this,
once you stait uilating it, it uoesn't stop bc as you uilate something, you inciease the
wall stiess anu eventually it iuptuies. So, in othei woius, all aneuiysms will iuptuie
- it's just a mattei of when.
9) (EA$.&4'; ($-6' (4,<-"/.0 Why is the abuominal aoita the NC aiea of
aneuiysm. Bc theie is no vasa vasoium oi bloou supply to the aoita below the ienal
aiteiies. So, the only way abu. aoita gets 02 anu nutiients is fiom the bloou that's in
the lumen. So, pait fuithest fiom it mgets scieweu. Theiefoie, apait fiom the pait
that is not getting much 02 anu nutiients, it will be moie susceptible to injuiy,
theiefoie atheioscleiosis leaus to weakening of the wall anu aneuiysminjuiy
occuis.
a. NC complication abuominal aoitic aneuiysm = iuptuie. The 6-&'A $= /R/ '-,: a
suuuen onset of seveie left flank pain bc the aoita is ietiopeiitoneal oigan anu so it
uoes not bleeu into the peiitoneal cavity, but into the peiitoneal tissue. So, /,J,-,
;,=6 U;'4P #'&4_ !"#$+Q_ '4A #<;/'6&;, .'// $4 :Z) These aie thiee things that
always occui when theie is a iuptuieu aoitic abuominal aneuiysm. B>
5$.#;&5'6&$4 $= '4" '4,<-"/. C -<#6<-,
K) (4,<-"/. $= 6?, '-5? $= 6?, '$-6' \ B>> C 6,-6&'-" /"#?&;&/. Pathology of
syphilis is vasculitis of aiteiioles. Chancie, too. Its painless bc if you section it, you
will see little aiteiioles suiiounueu by plasma cells anu the lumen of the vessel is
completely shut, so it is ischemic neciosis. In othei woius, it is ischemia of the
oveilying tissue unueigoing neciosis. Bc neives aie next to vessels, they aie
knockeu off, too, anu it is painless. (;; $= /"#?&;&/ &/ ' J'/5<;&6&/. That is what the
!"#$%&#'( infects - small vessels anu aiteiioles. What aie they affecting in the aich
of the aoita. The vasa vasoium; the iichest supply of vasa vasoium is in the aich, so
its logical that the !"#$%&#'( will pick it - leaus to enuaiteiitis obliteians (they aie
obliteiating the lumen), ischemia, weakening unuei systolic piessuies, leaus to
uepiession in the aich of the aoita (looks like a catchei's mitt). What will that uo to
the aoitic valve iing. It will stietch it - which muimui will this leau to. Aoitic
ieguig. Nuimuis can occui bc theie is valvulai uamage oi bc the valvulai iing is
stietcheu. So, theie can be stietching of the iing anu nothing wiong with the valves,
anu have a muimui, oi you can have uamage to the valves anu have a muimui.
Syphilis is an example of stietching of the aoitic valve iing leauing to a muimui anu
aoitic ieguig.
Aoita shoulu be closing uuiing uiastole - as you pump the bloou out, anu the Sv
goes uown, anu bc the aoitic cannot close piopeily, only some of the bloou will uiip
back in. So you will have moie volume of bloou in the left ventiicle in someone with
aoitic ieguig. Fiank-stailing foices will be woiking. As you stietch caiuiac muscle,
you inciease the foice of contiaction. Noimally, you have a 12u ml's of bloou anu get
out 8u, so the EF is 8u12u =66%. Lets say you have 2uu mls of bloou in the Lv bc
bloou is uiipping back in, anu fiank-stailing foice gets out 1uu mls of bloou, which
has an EF of Su%. So this isn't as efficient. Theiefoie, fiank-stailing occuis in a
pathologic conuition. If you have 1uu mls of bloou coming out of youi aoita, that's
not goou bc theii heau is wobbling, anu when they open theii mouth you can see
uvula pulsating, can take theii nail anu lift it up anu see pulsations of the vessels
unuei the nail, Watei-hammei pulse, anu when listening with the stethoscope of the
femoial aiteiy you can heai Buiasane's sign. This is all uue to the inciease in Sv
coming out ielateu to the fact that theie is moie bloou in the Lv. syphilitic
aneuiysms of the abuominal aoita is the classic example of this. Anatomy
coiielation: the Left Recuiient Laiyngeal Neive wiaps aiounu the aich anu theiefoie
can get hoaiseness. Again the NC complication is iuptuie.
N) G&//,56&43 '$-6&5 '4,<-"/.0
') S," ='56$- 6?'6 5'</,/ ' 6,'- &4 6?, '$-6' &/ !+Q bc it imposes stiess on the
wall of the vessel. Theie must be weakening the elastic aiteiy anu is causeu by
elastic tissue fiagmentation. >"/6&5 .,A&'; 4,5-$/&/: that's wheie the uAu's mix
togethei anu theie's mucinous mateiial win, anu walls of aoita iub upon itself, anu
when auuing a little bit of BTN leaus to a teai. Wheievei the aiea of weakness in the
elastic aiteiy is wheie the bloou will uissect anu teai - bloou can go to the
peiicaiuial sac, leauing to caiuiac tamponaue. This is calleu the pioximal uissection
(NC). Nost of the teais up in the aich; theiefoie you woulu think the pt may have an
absent pulse; this is veiy common in pts with teais that aie pioximal. When it
uissects, it closes lumen to subclavian aiteiy anu it usually uissects on the left anu
causes an absent pulse on left.
E) >?,/6 #'&4 in NI is uiff than the chest pain in a uissecting aneuiysm. NI has
chest tightness iauiating to left aim anu jaw; in aoitic uissection, theie is a teaiing
pain iauiates to the back; anu is a ietiosteinal pain. Pulse on left is uiminisheu vs.
the one on the iight. 0n chest x-iay, wiuening of the aoitic knob. With bloou theie,
uiametei of aoita will be enlaigeu, as seen on x-iay, anu this test is 8S% sensitive in
uetecting it, theiefoie it is the scieening test of choice; see wiuening of the #-$%&.';
'$-6&5 P4$E. To piove, uo tiansesophageal ultiasounu oi angiogiaphy to confiim ux.
5) B'4" A]8/ 5'4 #-,A&/#$/, 6$ '$-6&5 A&//,56&$4/:
(1) B'-='4 /"4A-$., (eunochoiu piopoitions - ht of pelvic biim to feet is gieatei
than fiom pelvic biim to the heau. Also, anothei uefinition is that aim span is gieatei
than the height. AB inheiitance, c'some 1S, uefect in fibiillin, which is a component in
elastic tissue. Bue to the uefect in fibiillin, the elastic tissue is weak - this is why they
have uislocateu lenses anu have uissecteu aoitic aneuiysms (NCC ueath in maifans
is NvP).
(2) Z?;,- G'4;$/ has a collagen uefect, NCC of ueath
(S) :-,34'46 L$.,4 aie susceptible to uissecting aoitic aneuiysms bc in
piegnancy they have twice the amount of plasma vol vs. a non-piegnant woman.
Theie is an inciease of plasma vol by 2 anu RBC mass by 1, so it's a 2:1 iatio of
incieasing plasma vol to RBC mass; which uecieases the Bb concentiation. That's
why all piegnant women have uecieaseu hemoglobin; usually aiounu 11.S is theii
cutoff foi anemia anu the cutoff is 12.S foi noimal women. This is bc of uilutional
effect with excess in plasma vol. Appaiently in some women, the excess plasma
volume foi 9 months can cause weakening of the aoita anu theieby causing an
aneuiysm.
F) F,4$</ G&/$-A,-/0
() [<#,-&$- J,4' 5'J' ;<43 /"4A-$., in a smokei with piimaiy lung cancei, now
complaining of heauache anu bluiiy vision - look at his ietina anu see ietinal vein
engoigement, anu congesteu - ux. [<#,-&$- J,4' 5'J' ;<43 /"4A-$., - usually
uue to piimaiy lung cancei knocking off the sup vena cava, leauing to backup of
venous bloou into the jugulai venous system anu to the uuial sinuses; this is a veiy
bau uz, anu will leau to ueath. 0sually tieat with iauiation to shiink the tumoi to get
noimal bloou flow. Bon't confuse with :'45$'/6 +<.$- - associateu with Boinei's
synuiome. So, SvC synuiome has nothing to uo with Boinei's, as opposeu to
Pancoast.
V) F'-&5$/, F,&4/
F@) +<.$-/ $= V;$$A F,//,;/0
() [6<-3, O,E,- /"4A-$., - "web. looks like a mini map on theii face"
it's a vasculai malfoimation in the face anu notice it's in the tiigeminal neive
uistiibution (making it easy to uz). Bowevei, on the same siue of the biain theie's an
Av malfoimation, pieuisposing to bleeuing. So, not only a vasculai malfoimation of
the face, but also an Av malfoimation in the same siue of the biain, which
pieuisposes to bleeuing. Also, these pts aie a little mentally ietaiueu. (some pts
show it on the entiie siue of the face)
V) 2/;,- O,E,- D,4A< 'P' !,-,A&6'-" ?,.$--?'3&5 6,;'43&,56'/&' - small
telangiectasia in uI. AB inheiitance chaiacteiizeu by localizeu telangiectases of the
skin anu mucous membianes anu by iecuiient hemoiihage fiom these lesions.
>) [#&A,- '43&$.'R/#&A,- 6,;'43&,56'/&': If you piess uown on this, the little
tentacles will go away (theiefoie it blanches) - calleu spiuei angioma. It is uue to
hypeiestiinism. This is noimal in piegnancy. If a male has spiuei angioma, he has
ciiihosis (NCC ciiihosis = alcohol). Why woulu a male have a spiuei angioma. Bc if
you have ciiihosis, you cannot metabolize estiogen - so it builus up, leauing to
gynecomastia, waim skin, palmei eiythema, anu spiuei angioma ielateu to
hypeiestiinism. Anothei ieason woulu be bc they cannot metabolize 17
ketosteioius eithei, theiefoie they will be aiomatizeu those in the auipose tissue into
estiogen. So, they aie 2 ways of getting hypeiestiinism in ciiihosis. So, how is this
uiffeient fiom petechia. It looks uiff; also, it will blanch when you piess it in bc it's
an Av fistula - in othei woius, the bloou goes uiiectly fiom aiteiiole to a venule anu
is bypassing the capillaiies.
G) >'#&;;'-" !,.'43&$.': pic of chilu with ieu lesion (not bilateial wiue eye
lesion - so its not ietinoblastoma); what uo you uo. X,'J, &6 ';$4,; uo not suigically
iemove bc by 8 yo, it will be gone - so, leave capillaiy angiomas alone bc they will
go away.
Z) V'5&;;'-" '43&$.'6$/&/0
Kaposi saicoma is causeu by the BBv 8 oiganism. If theie was a lesion seen only in
AIBs pts that looks like Kaposi saicoma, but it's not; what is it uue to. It's uue to
bacteiia - E'5&;;'-" '43&$.'6$/&/ - A<, 6$ E'-6,4,;;' ?,4/&;'& - seen with silvei
stain. Rx. Sulfa uiug. This oiganism also causes Cat Sciatch Bz.
T) (43&$/'-5$.' $= 6?, ;&J,- - common causes "vAT" = vinyl chloiiue (people
who woik with plastics anu iubbei), Aisenic (pait of pesticiues, contaminateu
watei), anu Thoiotiast (a iauioactive uiagnostic agent thoiium uioxiue).
F@@) F'/5<;&6&/ ["4A-$.,/
() >$45,#6 $= F'/5<;&6&/0 vasculitis of small vessels (aiteiioles, venules,
capillaiies), musculai aiteiies, anu elastic aiteiies. All of these vasculitis piesent
with uiffeient signs anu symptoms (ie like coagulation uisoiueis vs. platelet
uisoiueis).
1) [.';; J,//,; J'/5<;&6&/ - 99% of the time it is uue to a type III BPY, meaning it
is involves immune complex ueposition, that will ueposit in the small vessel, activate
complement anu attiact neutiophils (CSa), anu will get fibiinoiu neciosis anu
uamage to the small vessel anu :(X:(VXZ :MD:MD(; (iemembei the olu peison
with puipuia on the back of the hanu - that was not palpable anu was uue to
hemoiihage into the skin, theie was no inflammatoiy pioblem - it just iuptuieu into
the skin) but if it was palpable, it woulu be consiueieu a SNALL vESSEL vasculitis
not a platelet pioblem.
Example:
Leukocytoclastic vasculitis (hypeisensitivity vasculitis);
nucleai uust = fibiinoiu neciosis anu immune complex uz's; anu
Benoch-Schonlein puipuia. [$_ [B(XX FZ[[ZX J'/5<;&6&/ C :(X:(VXZ #<-#<-'
H';L'"/ 6$;A &4 6?, /6,. $= 6?, Y<,/6&$4I)
7) B</5<;'- '-6,-" J'/5<;&6&/ - Polyaiteiitis Nouosa anu Wegenei
gianulomatosis. These will get TBR0NB0SIS of the vessel, not palpable puipuia.
Will have @QT(D>+@2Q. Example: Kawasaki's Bz in chiluien "ciims" coionaiy
aiteiy vasculitis ,iash,infaiction,mi, swelling
- get coionaiy aiteiy vasculitis - NCC NI in chiluien = Kawasaki's uz - bc pait of
the synuiome, in auuition to mucocutaneous inflammation, uesquamation of skin,
anu lymphauenopathy, theie is a coionaiy aiteiy vasculitis - thiombosis occuis anu
little chilu will have an infaiction. [$_ &4='-56&$4 &/ L?'6 "$< /,, L&6? ' .</5<;'-
'-6,-" J'/5<;&6&/) Examples: Polyaiteiitis Nouosa, Wegenei gianulomatosis,
Kawasaki's uz in kius.
9) Z;'/6&5 '-6,-" J'/5<;&6&/ - When you knock off an elastic aiteiy, then you ueal
with aich vessels, anu they will get pulseless uz=Takayasu's aiteiitis - the vasculitis
will block off the lumen of one of the aich vessels, leauing to [+D2SZ[ anu can
knock off the inteinal caiotiu. Example: Takayasu's - young, fai eastein lauy with
absent pulse.
[$_ #';#'E;, #<-#<-' C /.';; J,//,; J'/5<;&6&/
@4='-56&$4 C .</5<;'- J'/5<;&6&/
@4J$;J,/ #<;/,R/6-$P, C ,;'/6&5 '-6,-" J'/5<;&6&/
V) +,.#$-'; (-6,-&6&/ - unilateial heauache, aches anu pains all ovei bouy, loss of
vision of same siue of heauache, huits when pt chews in tempoial aiea. This is a
gianulomatous (have multinucleateu giant cell) vasculitis of the tempoial aiteiy, a
type of giant cell aiteiitiues. It can involve othei poitions of the aiteiy incluuing the
ophthalmic bianch anu piouuce blinuness. That's why the seuimentation iate is the
0NLY scieen uiscieet foi tempoial aiteiitis. Why. Not that it is specific, but bc this
is an aiteiitis, (an inflammation) the seu iate shoulu be elevateu. If the seu iate is
N0T elevateu, it coulu be a tiansient ischemic attack. This is goou scieen bc it takes
time to take a biopsy anu look at it, anu the pt coulu go blinu. So, you must put the pt
on coiticosteioius immeuiately (iight theie anu then) just baseu on hx alone. The pt
will be on coiticosteioius foi one yeai. It's associateu with polymyalgia iheumatica
- muscle aches anu pains. They want you to say it is polymyositis, but it isn't.
Polymyalgia iheumatica uoes not have an elevation of seium CK, anu have aches anu
pains of muscles anu joints. In polymyositis, it's an inflammation of muscle.
>) V<,-3,- A] H'P' 6?-$.E$'43&&6&/ $E;&6,-'4/ \ /.$P,-/ A]); "ew boogeis anu
smoke make me so sick my fingeis anu toes cuil"
males, young, uigital vessel thiombosis, leauing to autoinfaiction of theii fingeis,
ANB toes. It's an acute inflammation involving small to meuium-sizeu aiteiies.
!,4$5?^[5?$4;,&4 #<-#<-': (butt, joints, git, ienal,skin) (palpable puipuia on
butt, n legs, joint piobs, anu kiuney piobs)
14 yo, 0RI one week ago, piesents with polyaithiitis, joint pains, hematuiia, with
RBC casts anu palpable puipuia of buttocks anu lowei extiemity - ux. Benoch-
Schonlein puipuia = NC vasculitis in chiluien - immune complex (as is all small
vessel vasculitis)- anti IgA immune complex, anu the RBC casts aie uue to
glomeiulonephiitis. Bo not confuse with IgA glomeiulonephiitis - Beigei's uz
Z) O,3,4,- 3-'4<;$.'6$/&/
^&= < ?'A 6$ 3$ ;&/6,4 6$ L'34,- &4 5$45,-6_ "$< L$<;A #-,6,4A < ?'A 6$ </, 6?,
E'6?-$$. $- 3,6 #4,<.$4&'
c&4='-584_ ;<43_ <-6_ -,4'; _ /'AA;, 4$/, _5'45'x5"5;$#?$/'.&4, -%d
pt with sauule nose uefoimity (not congenital syphilis) - also piobs with sinus
infections, 0RI's, lung piobs with nouulai masses, anu glomeiulai uz - ux. Wegenei
gianulomatosis (NCC of sauule nose uefoimity). This is a gianulomatous
inflammation ANB vasculitis. Theiefoie, it involves the uppei aiiways, lungs, anu
kiuneys; also, theie is an Ab that is highly specific foi it -
5^(Q>( H'46&^4,<6-$#?&; 5"6$#;'/.&5 (EI) D% ^ >"5;$#?$/#?'.&A, (which can
leau to hemoiihagic cystitis anu blauuei cancei anu how can you pievent the
hemoiihagic cystitis. Nesna).
T) :$;"'-6,-&6&/ Q$A$/' -
" panca, hbsag, kiuney, heait pioblems, infaic'n"
male uominant uz that involves musculai aiteiies, theiefoie infaiction is a pait of
it. Bas #^(Q>( (E '4A ' ?&3? '//$5&'6&$4 L&6? !,# V /<-='5, (38,.&'. Example:
have IvBA with chionic Bep B who has a nouulai inflameu mass on the lowei
extiemity anu hematuiia (uue to kiuney infaict); what uoes the pt have. Polyaiteiitis
Nouosa bc the pt has a chionic hep B infection theiefoie has hep B suiface antigens.
So, iemembei #^(Q>( '4A !,# V /<-='5, (3)
W) V'56,-&'; &4=,56&$4/0 vessel in DB[T. The iickettsial oiganisms infect
enuothelial cells; the spots aie petechia; unlike othei iickettsial uz's with iash, this
staits on the extiemities anu goes to the tiunk (wheieas otheis stait on the tiunk
anu to the extiemities). Also have to iemembei the vectoi: tick. 0thei tick boin uz's:
Lyme uz (boiielia buiguoifeii - b. iecuientis is ielapsing fevei, anu has antigenic
shifts; it is a spiiochete (Leptospiia anu syphilis aie also spiiochetes). So, S
spiiochetes - Leptospiia, Tieponema, Boiielia ("BLT")
T) T<43</ that is wiue angle, nonseptate , pt has BKA, anu ceiebial abscesses
ielateu to fungus - .<5$-."5$/&/ (know ielationship of this fungus anu BKA);
Biabetics commonly have mucoi in theii fiontal sinuses; so when they go into
ketoaciuosis anu stait piolifeiating, they go thiough the ciibifoim plate into the
fiontal lobes wheie they infaict it anu infect it with the uz.
F@@@) T<456&$4'; F'/5<;'- G&/$-A,-/0 D'"4'<A G]
Theie aie many causes this; some involve colu ieacting Ab's anu colu ieacting
globulins. People who go outsiue in the colu weathei will get Raynauu's anu cyanosis
in the nose anu eais (that comes anu goes away); so, it is uue to IgN colu agglutinin
uz oi ciyoglobinemia in olu man with Bep C.
Bowevei, we have othei uz's that aie 5$;;'3,4 J'/5<;'- A] anu fiist manifestation
is Raynauu's; this involves a uigital vasculitis anu eventually a fibiosis - piogiessive
systemic scleiosis (aka scleioueima), anu its counteipait CREST synuiome.
vasculitis of fingeis anu leaus to fibiosis - will eventually auto-amputate fingei
(like Beigei's).
>DZ[+ /"4A-$., - Calcinosis (uystiophic calcification) anu Centiomeie Ab
(specific foi ciest synuiome), Raynauu's, Esophageal uysmotility, Scleiouactyly
(fingei that is veiy naiiow), Telangiectasia (veiy similai to the pin point
hemoiihages - also seen in 0slei Webei Renuu).***********
0thei causes uue to vasoconstiiction - common in pts that take uiugs foi migiaine
- uiugs foi migiaines cause vasoconstiiction of vessels. So, Raynauu's can occui aftei
taking Eigot ueiivatives; Bueigei uz, too.
+?,-,=$-,_ 3,4,-'; 5'</,/ $= D'"4'<A8/0 J'/$5$4/6-&56&$4_ J'/5<;&6&/ $= 6?,
A&3&6/ H&, >DZ[+ '4A /5;,-$A,-.'I_ '4A 5$;A -,'56&43 (E8/ '4A 3;$E<;&4/ )
@g) !"#,-6,4/&$4 H!+QI
NCC ueath with BTN = NI (2
nu
= stioke, S
iu
= ienal failuie)
Essential BTN= NC
() B<;6&='56$-&'; @4?,-&6'45,0 What iacial gioup has highest inciuence of BTN.
Blacks. Why. Nultifactoiial inheiitance (aka polygenic inheiitance; othei uz's
incluue: gout, CAB, Type II uiabetes, affective uisoiueis, congenital pyloiic stenosis,
essential BTN). This means that you have a tenuency to F0R the uz, but uon't
necessaiily get the uz. Why. Bc it's N0LTIfactoiial!
Example: I am black, what shoulu I uo to pievent fiom getting it. I cannot get iiu of
genetics, anu my genetics aie that I 5'44$6 3,6 -&A $= /';6 &4 ." <-&4, - ietaining
too much salt HL?&5? &/ 6?, E'/&5 .,5?'4&/. $= ,//,46&'; !+Q &4 E;'5P/ '4A
,;A,-;"). So, cannot contiol genetics, but I can contiol S things: (1) weight has a
uiiect coiielation with BTN; (2) ieuuce salt intake; anu (S) exeicise. Example:
family hx of gout, what can I uo so I avoiu gout. Avoiu ieu meet, no alcohol (which
will ueciease puiine metabolism). Example: If you hau a family hx of BN type II - be
skinny (lean anu mean)- as you lose auipose, upiegulate insulin ieceptoi synthesis
anu that alone coulu pievent you fiom having the uz.
V) B,5?'4&/. $= !+Q - bc you -,6'&4 /';6 (it's not the only mechanism, but the
NC one). When you ietain salt, what compaitment will the salt be ietaineu in. ECF -
if that is tiue, what will be the plasma volume if you have excess salt in youi vasculai
anu inteistitial compaitment. Incieaseu - if youi plasma vol is incieaseu, youi
stioke volume will be incieaseu - which is youi /"/6$;&5 !+Q HER5 &45-,'/, &4
:X([B( J$;I. When you have excess salt, salt wants to go into smooth muscle cells
(into peiipheial iesistance aiteiioles). When souium enteis muscle, it opens ceitain
channels foi Ca to go in; Ca goes in anu smooth muscle will contiact, so the
peiipheial iesistance aiteiioles aie vasoconstiicting. TPR = viscosityiauius
4
; we
aie uecieasing iauius, incieasing iesistance, anu -,6'&4&43 .$-, E;$$A &4 6?,
'-6,-&$;, /"/6,. H6?'6 -,3&/6,-/ '/ '4 &45-,'/, &4 A&'/6$;&5 #-,//<-,I) This is
why the Rx of choice foi essential BTN in blacks anu elueily = hyuiochloiothiaziue -
bc you iiu salt anu watei to ueciease BP; howevei, uo not use if pt has
hypeilipiuemia, so use ACE inhibitois.
Is this a high oi low ienin type of BTN. Low ienin bc incieaseu plasma volume =
incieaseu bloou flow to the ienal aiteiy = uecieaseu ienin. So that's the basic
mechanism of BTN.
>) >$.#;&5'6&$4/: BTN is a majoi iisk factoi foi CAB, leauing to B@ HB>> A,'6?).
Stioke = #2. Bloou is locateu in globus palliuus anuoi putamen - this is wheie
almost all of the BTN'ive bleeus occui in the biain. This is bc the lenticulostiiate
vessels (which aie small vessels of the miuule ceiebial aiteiy) unuei incieaseu
piessuie foim aneuiysms calleu >?'-5$6 V$<5?'-A '4,<-"/./, anu they iuptuie.
This is not a goou place to iuptuie. Theiefoie, this is not an infaict - it is a
hematoma - it's a bloou clot iight theie. Neuiosuigeons can suck these out.
Theiefoie the 7
4A
B>> A,'6? &/ !+Q8J, E;,,A. Example: kiuney that is too small
with a pebbly suiface uue to hyaline aiteiioloscleiosis - a small vessel uz is causing
ischemia of the kiuney, atiophy of tubules, uestiuction of glomeiuli, shiinkage of
kiuney, anu leaus to kiuney failuie. This is the 9
-A
B>> A,'6? &4 !+Q) NC oveiall
abnoimality in BTN = LvB (mech: afteiloau piob bc the heait has to contiact
against incieaseu iesistance anu if it iemains ovei a peiiou of time it will eventually
leau to heait failuie.
Auuio File 2u: Caiuiovasculai 2
+!Z !Z(D+
@) !"#,-6-$#?" $= 6?, !,'-60
>$45,46-&5 H6?&5PI !:b8A ?,'-6 J/) G&;'6,A !:b ?,'-6: 2 uiffeient etiologies, anu
they involve woik. It iequiies a lot of woik to contiact anu push bloou thiu a
stenotic aoitic valve, oi incieaseu TPR fiom BTN. These will cause an &45-,'/,A
'=6,-;$'A C 5$45,46-&5 !:b)
If you have a valvulai pioblem, anu have excess volume of bloou in the ventiicles -
incieaseu pieloau = incieaseu woik. Theiefoie, the fiank stailing goes into effect b
c stietching anu incieasing pieloau in theie, anu you have to woik haiuei to inciease
the foice of contiaction - this piouuces uilateu BPY. Theiefoie, 5$45,46-&5 !:b C
'=6,-;$'A #-$E;,.i A&;'6,A !:b C J$;<., $J,-;$'A C #-,;$'A #-$E;,.
H&45-,'/,A J$;<.,I
@@) !,'-6 /$<4A/ \
[1 ?,'-6 /$<4A = beginning of Systole = mitial anu tiicuspius close (mitial closes
befoie the tiicuspiu bc highei piessuies)
[7 ?,'-6 /$<4A = beginning of Biastole = pulmonic anu aoitic close (vaiiation with
iespiiation - as uiaphiagm goes uown they inciease the intiathoiacic piessuie.
Bloou is being suckeu into the iight siue of the heait, anu the pulmonic valve will
close latei than the aoitic valve. So, the seconu heait sounu has a vaiiation with
inspiiation - the P2 sepaiates away fiom A2 bc moie bloou coming into the iight
heait, so the valve closes a little bit latei.
[9 ?,'-6 /$<4A C noimal unuei SS yo's. Aftei that, it is pathologic. S1 =
beginning of systole anu S2 = beginning of uiastole; obviously, SS = eaily uiastole. SS
is uue to bloou, in eaily uiastole, going into a chambei that is volume oveiloaueu. So,
bloou fiom the left atiium is going into oveiloaueu chambei, causing tuibulence,
which is the SS heait sounu. 0nly heai [9 ?,'-6 /$<4A &4 J$;<., $J,-;$'A,A
5?'.E,-. It coulu be fiom LBF (left ventiicle oveiloaueu) oi RBF (iight vent
oveiloaueu), so theie aie left siueu SS's anu iight siueu SS's - it means volume
oveiloau in the chambei. Analogy: iiveis going into ocean - leaus to tuibulence
(ocean is the ventiicle with a lot of fluiu in it anu the iivei is the bloou coming in
uuiing uiastole; the iivei hits this laige mass of fluiu in the ventiicle, causing
tuibulence anu an SS heait sounu).
[K ?,'-6 /$<4A = late uiastole - this is when the atiium is contiacting anu you get
the last bit of bloou out of the atiium into the ventiicles, leauing to S4 sounu. S4's
occui if theie is a pioblem with compliance. Compliance is a filling teim.
So, when talking about compliance, iefeiiing it's ability to fill the ventiicle. The left
atiium is contiacting, tiying to get bloou into a thick ventiicle; the ventiicle is
noncompliant, anu theiefoie iesistance will occui. This will cieate a vibiation,
leauing to an S4 heait sounu. An [K ?,'-6 /$<4A &/ A<, 6$ ' #-$E;,. L&6?
5$.#;&'45,. The left atiium is encounteiing a pioblem in putting bloou in late
uiastole into the left ventiicle anu it uoesn't want to fill up anymoie. This coulu be
uue to 2 ieasons: (1) bc it's hypeitiophieu (it uoesn't want to fill anymoie-
iestiicting filling up) oi (2) it's alieauy filleu up anu has to put moie bloou in an
alieauy oveifilleu chambei.
[<..'-"0 [;&A,/0
vol oveiloaueu. No SS. So can it have an S4. Yes.
If you have BTN, which type of heait will you have. Concentiic BPY. So, in BTN,
which type of heait sounu will you have. S4.
vol oveiloaueu. Yes. So can it have an SS. Yes; can it also have an S4. Yes. Why can
it also have an S4. Bc it can't fill up anymoie. Analogy: tuikey uinnei - all filleu up,
but always ioom foi ueseit - lil vibiation that occuis when it fills is an S4 heait
sounu. So you have both SS anu S4 heait sounu = gallop ihythm (they have S1, 2, S,
anu 4).
Bow uo you know if its fiom the left oi iight. It is bieathing. When you bieath in,
you aie sucking bloou to the iight siue of the heait. (;; -&3?6 /&A,A ?,'-6 .<-.<-/
'4A 'E4$-.'; ?,'-6 /$<4A/ H&, [9_ [KI &45-,'/, &4 &46,4/&6" $4 &4/#&-'6&$4 - this
is moie obvious bc theie is moie bloou in theie, anu it emphasizes those abnoimal
sounus. Piob get them on ,%#&-'6&$4 L&6? #$/&6&J, &46-'6?$-'5&5 #-,//<-,/ that
aie helping the left ventiicle push bloou out of the heait - this is when abnoimal
heait sounus anu abnoimal muimuis will inciease in intensity on expiiation. So, all
you have to uo is figuie out that theie is an SS heait sounu. *****Then, you have to
figuie out which siue it is coming fiom. Louuei on expiiation, theiefoie its fiom the
iight siue.
Example: essential BTN = left;
Nitial ieguig = iight;
anu Nitial stenosis = miuule.
@@@) B<-.<-/
[6,4$/&/ = piob in $#,4&43, that is when the valve is opening, anu that is when the
muimui occuis.
D,3<-3&6'6&$4 = piob in 5;$/&43 the valve, that is when the valve is closing, anu
that is when the muimui occuis.
Neeu to know wheie valves aie heaiu best - iight 2
nu
ICS (aoitic valve), left 2
nu
ICS
(pulmonic), left paiasteinal boiuei (tiicuspiu), apex (mitial) - this isn't necessaiily
wheie the valve is, but wheie the noise is heaiu the best.
() [6,4$/&/0
1) ["/6$;&5 B<-.<-/0
Who is $#,4&43 &4 /"/6$;, C '$-6&5 '4A #<;.$4&5 J';J,/ = theiefoie, muimuis of
aoitic stenosis anu pulmonic stenosis aie occuiiing in systole. This is when they aie
opening; they have to push the bloou thiough a naiiow stenotic valve.
') ($-6&5 [6,4$/&/ - Lv contiacts anu it is encounteiing iesistance - intensity of
the muimui goes up; as it is pushing anu pushing, it gets to a peak anu this is
uiamonu shape configuiation - this is why it is calleu an ,u,56&$4 .<-.<-) So, they
often have uiagiams of the configuiations on these muimuis. With an ejection
muimui (aoitic stenosis), it will have a ciescenuo-ueciescenuo (hence, uiamonu
shapeu configuiation). So, with aoitic stenosis, theie is an ejection muimui in
systole, heaiu best at the iight 2
nu
ICS, which iauiates to the caiotius, anu the
muimui intensity incieases on expiiation, anu will piobably heai an S4
E) :<;.$4&5 [6,4$/&/ - heaiu best on left 2
nu
ICS, ejection muimui, anu incieases
on expiiation.
7) G&'/6$;&5 .<-.<-/0 In uiastole, mitial anu tiicuspiu valves aie opening.
') B&6-'; [6,4$/&/ (pioblem in opening the valve) - who has the pioblem. Left
atiium. Beie's the pioblem, the mitial valve uoesn't want to open but it has to in
oiuei to get bloou into the left ventiicle. So, the left atiium will get stiong bc it has
an afteiloau to ueal with - it becomes uilateu anu hypeitiophieu (the atiium) -
which pieuisposes to atiial fib, thiombosis, anu stasis of bloou. So, the atiium is
uieauing uiastole bc it has to get the builuup of bloou into the left ventiicle. With
the builu up of piessuie, the mitial valve "snaps" open, anu that is the opening snap.
All the bloou that was built up in the atiium comes gushing out into the ventiicle,
causing a miu-uiastolic iumble. So, you have an $#,4&43 /4'# =$;;$L,A E" '
-<.E;&43 /$<4A (uue to excess bloou gushing into Lv). With mitial stenosis, theie
is a pioblem with opening the valve, anu theiefoie you aie unuei filling the left
ventiicle, anu theiefoie will be no BPY bc you aie unuei filling it. If you aie having
tiouble getting bloou into it, you aie not oveiwoiking the ventiicle; the left atiium
has to uo most of the woik. Beaiu best at the apex anu will inciease in intensity on
expiiation. H/'., 5$45,#6 L&6? 6-&5</#&A /6,4$/&/_ u</6 ' A&==,-,46 J';J,I)
V) D,3<-3&6'6&$4 \ pioblem in closing the valve.
1) ["/6$;&5 B<-.<-/0 .&6-'; '4A 6-&5</#&A '-, 5;$/&43 &4 /"/6$;,.
'I B&6-'; D,3<-3: If they aie incompetent anu mitial valve cannot close piopeily.
Example: 8u mls of bloou = noimal stioke volume; lets say Su mls into the left
atiium anu only Su mls leaves the aoita. So, an extia Su mls of bloou in the left
atiium, plus tiying to fill up anu have excess bloou theie - way moie bloou enus up
in the left ventiicle anu it becomes J$;<., $J,-;$'A,A. So, how woulu the muimui
chaiacteiistics be if theie is a pioblem in closing the valve. It will not be an ejection
muimui; will just sounu like "whoooosh" all the way thiough, as bloou all the way
thiough systole is going thiough the incompetent mitial valve, back into the left
atiium - theiefoie it is pansystolic oi almost pansystolic - so it's a 'stiaight line'
effect. Sometimes, it will obliteiate S1 anu S2. [$_ &/ '4 '#&5'; .<-.<-_
#'4/"/6$;&5_ [9 '4A [K HER5 ' #-$E;,. L&6? 5$.#;&'45, '4A J$;<., $J,-;$'A_
&45-,'/,A &4 &46,4/&6" $4 ,%#&-'6&$4)
E) +-&5</#&A D,3<-3: it will be pansystolic, SS anu S4, left paiasteinal boiuei, anu
incieases on intensity on inspiiation). Example: IvBA with fevei, pansystolic
muimui along paiasteinal boiuei, SS anu S4 heait sounu, accentuation of the neck
veins, what is the most likely ux. Infective enuocaiuitis of tiicuspiu valve, which is
the NC infection. So, it was extiemely imp to know if the muimui incieaseu on
inspiiation (which is iight siueu). If the question saiu that the muimui hau
incieaseu on expiiation, it woulu be Infective enuocaiuitis of the mitial valve (which
is left siueu).
7) G&'/6$;&5 B<-.<-/0 L'46 6?, '$-6&5 '4A #<;.$4&5 J';J,/ 6$ 5;$/, (what you
just pumpeu out uoesn't want to come back in).
($-6&5 D,3<-3 (as seen in syphilis aneuiysm but this is uue to the stietching of the
iing). In systole the bloou goes out anu the valve shoulu be closing piopeily , but it
uoesn't, so some bloou will tiickle back in. Example: 8u cc went out initially anu Su
cc is uiippeu back in. As bloou keeps uiipping back in, you will get a J$;<.,
$J,-;$'A,A chambei. Eventually you will have anu EBv of 2uu mls (insteau of 12u).
So, foi aoitic ieguig, when you heai the muimui. Aftei the 2
nu
heait sounu bc it
isn't closing anu bloou is uiipping back in - that makes the sounu of a high pitcheu
blowing uiastolic muimui into the iight seconu ICS, incieases in intensity on
expiiation, SS anu S4 heait sounus, vol oveiloaueu, anu bounuing pulses. What valve
leaflet is uiipping bloou. Anteiioi leaflet of mitial valve. This is one siue of the
outflow tiact out of the aoita. What muimui uoes that cieate. (</6&4 U;&46 .<-.<-.
If you have aoitic ieguig with an Austin flint muimui, you neeu to call the caiuiac
suigeon. Neeu to ieplace the valve bc you aie significantly uiipping bloou.
Theiefoie, this muimui is imp bc when it is theie, you have to peifoim suigeiy.
@F) !,'-6 T'&;<-,0 X,=6 $- D&3?6 !,'-6 T'&;<-,
Left BF = lungs anu Paioxysmal noctuinal uyspneapillow oithopnea
Right = Livei
() X,=6 ?,'-6 ='&;<-,=foiwaiu failuie, cant get bloou out of the heait bc the Lv
fails
Theiefoie youi left ventiicle has to push against an afteiloau anu fails; oi it has to
ueal with excess volume anu fails; oi you've hau so many infaicts that the left
ventiicle is no longei muscle but now fibious tissue anu this ieuuces contiactility
anu it fails. It's a foiwaiu failuie bc you aie having pioblems getting bloou outsiue
of the heait. This means that EBv will inciease bc you cannot get all the bloou out
bc you cannot push it out. The piessuie anu volume will go back in to the left
atiium, back into the pulmonaiy vessels, inciease the hyuiostatic piessuie, anu then
pulmonaiy euema. With chionic left heait failuie, this will leau to hemoiihage anu
alveolai maciophages will phagocytose RBC's, leauing to iusty coloieu sputum. 0n
cytology, you will see heait failuie cells, which aie alveolai maciophages that has
phagocytoseu RBC's anu is bioken uown to hemosiueiin. :<;.$4'-" ,A,.' &/
';L'"/ ;,=6 ?,'-6 ='&;<-,. X,=6 ?,'-6 ='&;<-, &/ ' A&'34$/&/ $= /".#6$./_ ER5 6?,
.'&4 /".#6$. &4 X!T &/ A"/#4,' H[2VI_ ?'J, 6-$<E;, E-,'6?&43 ER5 U;<&A &4
6?,-,)
V) D&3?6 !,'-6 T'&;<-,0 Biagnosis of signs: Backwaiu Failuie; cant get bloou into
the heait.
RBF is a pioblem of the iight heait getting bloou thiough the pulmonaiy vessels to
the left heait. So, if it fails, bloou builus up behinu it, anu it is a backwaiu failuie. Bc
if it cannot get bloou thiough pulmonaiy vessels into the heait, bloou will builu up
behinu it, anu hyuiostatic piessuies will builu in the venous ciicuit. This leaus to
neck vein uistension; also, will get hepatomegaly (which is painful), anu a nutmeg
livei bc of the incieaseu piessuies in the vena cava aie tiansmitteu to the hepatic
vein, which empties into it, then back into the livei anu the cential vein, then will get
ieu uots all ovei livei, which looks like a nutmeg. B>> 5$43,/6,A ?,#'6$.,3';" C
D!T. What causeu the incieaseu in hyuiostatic piessuie also going to piouuce
pitting euema anu possibly ascites - theiefoie its moie signs than it is symptoms. So,
4,5P J,&4 A&/6,4/&$4_ #&66&43 ,A,.'_ ?,#'6$.,3';"_ 4<6 .,3 ;&J,-_ '/5&6,/.
>) Z%'.#;,/ $= X!T0
When you lie uown to go to sleep, you can ieabsoib up to 1 litei of fluiu bc it will
go fiom the inteistium to the venous siue bc theie's no effective giavity. Theiefoie,
theie is extia bloou going back to the iight heait anu into the left heait. Bowevei,
what if you hau left BF. Theie will be excess bloou coming back (that wasn't theie
when you weie stanuing up) anu the left heait is having tiouble getting bloou out,
with even moie bloou coming back in. Then the heait cannot hanule it anu goes back
to the lungs, leauing to uyspnea anu continues foi the next Su minutes- this is
#'-$%"/.'; 4$56<-4'; A"/#4,'. Eventually it settles uown, you go back to sleep,
wake up again, anu it occuis again. Pt iealizes that aftei you stanu up, then it
eventually goes away - theiefoie they put a pillow unuei them to ueciease the
uyspnea when they wake. This is calleu #&;;$L $-6?$#4,'. If its one pillow
oithopnea, its not that bau; howevei, if you have to sit up, you have seiious left heait
failuie bc you aie imposing giavity. }ust by putting heau on one pillow will
ueciease venous ietuin back to the heait. If you put 2 pillows unuei, it will ueciease
the uyspnea even moie bc of effective giavity. So, #&;;$L $-6?$#4,' '4A
#'-$%"/.'; 4$56<-4'; A"/#4,' '-, /&34/ $= XZT+ ?,'-6 ='&;<-,)
G) +-,'6.,460
If you have heait failuie (iight oi left), what is the best nonphaimacologic
tieatment. Restiict watei anu salt.
O?'6 6?, P&43 $= D% $= !Te (>Z &4?&E&6$- ER5 &6 A,5-,'/,/ '=6,-;$'A (QG
#-,;$'A '6 6?, /'., 6&.,) (>Z &4?&E&6$-/ inciease longevity by (1) uecieaseu
aluosteione, theiefoie uecieaseu salt anu watei ieabsoiption which uecieases
pieloau anu (2) by blocking Angiotensin II, will leau to a ueciease in vasoconstiictoi
effect on peiipheial iesistance aiteiioles, which will ueciease afteiloau.
Pts with /#&-$4$;'56$4, y (>Z &4?&E&6$- uiu bettei bc aluosteione will
eventually bieak thiough anu become elevateu again, theiefoie ACE inhibitoi acting
against aluosteione is not a peimanent suppiession. So spiionolactone which
specifically block aluosteione, plus the ACE inhibitoi is an inciease in piognosis.
Theiefoie, now it's noimal to put the pt on spiionolactone anu ACE inhibitoi bc it
will inciease longevity.
Z) !&3? $<6#<6 ='&;<-,
0ne cause is ,4A$6$%&5 /?$5P - peiipheial iesistance aiteiioles aie uilateu,
theiefoie an inciease in CSa, CSa, N0, leauing to incieaseu venous ietuin to the heait
anu the heait eventually gives up. Theie aie also many othei causes, anu they ielate
to Pouseau's law - viscosityiauius to the fouith powei. So, if you vasouilate the
peiipheial iesistance aiteiioles, anu you ueciease TPR, moie bloou ietuins to the
iight heait, the left heait has to ueal with it, too, anu pt iuns the iisk of high output
failuie. So, one cause of the vasouilatation is /,#6&5 /?$5P, while the othei is
6?&'.&4, A,U&5&,45". Pioblem in thiamine uef: ATP uepletion: smooth muscle cells
anu peiipheial iesistance aiteiioles neeu ATP, theiefoie they uo not woik as well,
anu theie is vasouilatation of the peiipheial aiteiioles, leauing to high output failuie.
So, thiamine uef can piouuce high out put failuie bc vasouilatation of those vessels.
W-'J,/8/ A] - hypeithyioiuism - thyioiu hoimone incieases the synthesis of beta
ieceptois in the heait. uet an inciease in foice of contiaction, anu moie bloou.
Systolic piessuies aie highei, anu go into high output failuie.
(F U&/6<;'/ - ie get stableu in the leg; anu uevelop an Av malfoimation, wheie theie
is aiteiiole bloou bypassing the miciociiculation going uiiectly to the venous
ciiculation anu the bloou comes back fastei to the heait than noimal; a biuit can be
heaiu ovei the mass anu it will be pulsatile; if you piess the pioximal poition of it,
heait iate woulu slow (Bienham's sign) - these aie all signs of Av fistula, leauing to
high output failuie.
[$_ 9 ,%'.#;,/ $= ?&3? $<6#<6 ='&;<-, '-, ,4A$6$%&5 /?$5P_ 3-'J,/_ '4A (F
U&/6<;'/
F) >$43,4&6'; ?,'-6 A]
() S4$L =,6'; 5&-5<;'6&$4 (which vessels have the leastmost 0
2
); iemembei that
the baby is N0T exchanging bloou with 0
2
in the lungs. Pulmonaiy vessels in the
fetus look like they have pulmonaiy BTN - they aie so thick that it is extiemely haiu
to get bloou thiough the pulmonaiy aiteiy into the Lv bc veiy little bloou can go
theie - this is why baby neeus a patent uuctus to get bloou out. Wheie is 0
2
coming
fiom. Coming fiom choiionic villus uipping into lake of bloou, which ueiives fiom
mom's spiial aiteiioles. Bave choiionic villi uipping into bloou anu extiacting 0
2

fiom it. 0bviously, this is not as goou an 0
2
souice as the lungs; theiefoie, you want
a high affinity Bb to be able to get what little 0
2
is uown in the aiea - this is why
babies have BbF, bc of its high affinity to giab 0
2
fiom the bloou. Bau news is that it
gets the 0
2
, but uoesn't want to give it up (says mine) - it left shifts the cuive. What
is compensatoiy iesponse. This left shift causes tissue hypoxia, which will cause EP0
to be ieleaseu anu the kiu will have an 18 giam Bb - bc of this, all newboins (in a
sense) have polycythemia. This is the way aiounu BbF's high affinity foi 0
2
- moie
RBC's maue, moie Bb, anu baby gets moie 0
2
.
2-A,- $= 2
7
#'//&430 0
2
goes thiough syncytiotiophoblast of choiionic villus, into
the cytotiophoblast, then thiough the myxomatous stioma of the choiionic villus,
then into the bloou vessel. The bloou vessels of the choiionic villis all coalesce to
foim the <.E&;&5'; J,&4. This has the ?&3?,/6 2
7
5$46,46. It goes to the livei anu it
can go two ways: 1) into the hepatic sinusoius anu iecollects into the hepatic vein
anu gets uumpeu into the IvC; anu 2) uuctus venosis anu stiaight into the IvC. Then
it goes up the iight siue of the heait; the foiamen ovale is open in all fetuses (its not
closeu) - so all this bloou is coming up the IvC - will it go stiaight acioss, thiough the
foiamen ovale anu into the left atiium, oi will it go into the IvC into the iight atiium,
uown to thiough the tiicuspiu valve, anu into the iight ventiicle. It will go thiough
the foiamen ovale. So, all this oxygenateu bloou will go uiiectly fiom the iight
atiium of the foiamen ovale into the left atiium, then the left ventiicle anu out the
aoita. What about SvC bloou valve. It is coming fiom the supeiioi pait of the iight
atiium (its not gonna make a left tuin anu go thiough the foiamen ovale). It will go
stiaight uown, thiough the tiicuspiu valve into the iight ventiicle. Now, it will go out
the pulmonaiy aiteiy. This is a PR0BLEN bc the pulmonaiy vessels aie too thick
anu it's encounteiing this tiemenuous amount of piessuie. To countei this pioblem,
kept the patent uuctus open (which is kept open by the PuE2, a vasouilatoi, maue by
the placenta) - so, theie is a iight to left shunt anu bloou can get out of the
pulmonaiy aiteiy anu uumpeu back into the aoita. Then, when the baby is boin anu
takes its fiist bieath, the pulmonaiy vessels (that weie all shut), all open within a
milliseconu, anu bloou is going thiough those pulmonaiy aiteiies anu gas exchange
is occuiiing thiough the lungs in liteially seconus. Also, the patent uuctus closes anu
foims the ligamentum aiteiiosum. This is noimal fetal ciiculation. vessels with the
least 0
2
aie the 2 umbilical aiteiies, anu the one with the most amount of 0
2
is the
umbilical vein.
V) [?<46/0
Look at 0
2
satuiations (this is how they ux them - they catheteiize, measuie 0
2

satuiations in uiffeient chambeis, anu know which uiiection the shunts aie going.
Neeu to get useu to two teims - step up anu step uown.
If you have a ;,=6 6$ -&3?6 /?<46, anu have oxygenateu bloou going into un0
2
'u
bloou, what is happening to 0
2
satuiation on the iight siue. [6,# <# ER5 .&%&43 2
7
8A
L&6? <42
7
8A E;$$A)
If you have a -&3?6 6$ ;,=6 /?<46 with <42
7
8A E;$$A 3$&43 &46$ 6?, 2
7
8A E;$$A.
[6,# A$L4.
The 0
2
satuiation on the iight siue of the heait in bloou ietuining fiom the bouy is
7S%. The 0
2
satuiation on the left siue is 9S%.
>) F[G HB>I
Who's stiongei - left oi iight ventiicle. Left, theiefoie the uiiection of the shunt is
left to iight. So, oxygenateu bloou will be uumpeu into the iight ventiicle, leauing to
step up. Also, it will pump it out of the pulmonaiy aiteiy, leauing to step up. So, you
have a step up of 0
2
in iight vent anu pul aiteiy. What if this is not coiiecteu. With
this mech, you aie volume oveiloauing the iight siue of the heait bc of all that bloou
coming ovei. The outcome of this will be #<;.$4'-" !+Q (the pulmonaiy aiteiy
has to ueal with moie bloou anu must contiact moie - leauing to pul BTN) - 0nce
pul BTN occuis, iight ventiicle will have a pioblem contiacting anu it will get
hypeitiophieu. Suuuenly, you iun the iisk of ieveising a shunt bc then iight
ventiicle coulu eventually be stiongei than the left. So, it will be a iight to left shunt
- this is calleu Z&/,4.,43,-8/ /"4A-$.,. So, an uncoiiecteu left to iight shunt has
the potential foi piouucing Eisenmengei's synuiome. Aftei ieveisal of the shunt
occuis, pt will have 5"'4$/&/ (aka cyanosis taiuive). Nost vSB's close spontaneously
anu some neeu to be patcheu.
G) ([G
Noimal foi a fetus to have a patent foiamen ovale; it is not noimal once they aie
boin. Which uiiection will bloou go thiough the foiamen ovale. Left to iight (bc the
left siue is always stiongei than the iight). Theiefoie, what will happen to the iight
atiium. [6,# <# - so it will go fiom 7S to 8u%. What will happen to the iight
ventiicle anu pulmonaiy aiteiy. [6,# <#. So, L?'6 &/ 6?, .'&4 A&== &4 27
/'6<-'6&$4/ &4 F[G J/ ([Ge ([G &/ /6,# <# $= 27 ';/$ &4 6?, -&3?6 '6-&<.. Aie
you volume oveiloauing the iight heait. Yes. So uo you iun a -&/P =$-
Z&/,4.,43,-8/. Yes. What else aie at incieaseu iisk foi. Paiauoxical embolization.
What if you weien't lucky enough to have a BvT in the leg, anu it embolize up anu the
piessuies of the iight siue of the heait aie incieasing, anu you have a patent foiamen
ovale - will theie be an embolus that can go fiom the iight atiium to the left atiium
anu will have a venous clot in aiteiial ciiculation. Yes - this occuis in pts with ASB.
B> 6,-'6$3,4 6?'6 ?'/ ([G '//$5&'6,A L&6? &6e T,6'; ';5$?$; /"4A-$., H1RNfffI
Z) :G(
It's noimal in a fetus but not when they aie boin. Connection between the aoita
anu pulmonaiy aiteiy - which is stiongei. Aoita. So, oxygenateu bloou goes fiom
left anu get uumpeu in the pulmonaiy aiteiy befoie going into the lungs. So, what
happens in the pulmonaiy aiteiy. Step up. So, now its 8u% 02 satuiation - 6?,
#<;.$4'-" '-6,-" &/ 6?, $4;" 6?&43 6?'6 ?'/ ' /6,# <# $= 27. Then will go unuei
the lungs anu the pulmonaiy vein will have the noimal 9S% 02 sat. Bc theie is an
opening between these, theie is bloou going back anu foith uuiing systole anu
uiastole - .'5?&4,-" .<-.<- - wheie is it heaiu best. Between shouluei blaues.
Can you vol. oveiloau the iight heait. Yes. Pulmonaiy BTN. Yes. Now which way
will the shunt go. Will go the same way when it was a fetus; you will have un02'u
bloou uumping into the aoita. Wheie uoes the uuctus empty. Bistal to the
subclavian aiteiy - so, the baby will have pink on top anu blue on bottom bc
uumping un02'u bloou below the subclavian aiteiy, theiefoie will have A&==,-,46&';
5"'4$/&/ \ #&4P $4 6$#_ 5"'4$6&5 $4 E$66$.. What is the teiatogen assoc with
PBA. Congenital Rubella. If you hau a PBA, can you close it off without suigeiy. Yes.
Bow. @4A$.,6?'5&4 ^ 6?&/ &/ ' #$6,46 Q[(@G_ L?&5? L$<;A &4?&E&6 :WZ7, anu
theiefoie woulu stait constiicting anu close on its own.
T) +,6-';$3" $= T';;$6
NC cyanotic congenital uz: "tetia" = foui - oveiiiuing aoita: its stiauuling the
septum; pulmonic stenosis below the valve, RvB, membianous septal uefect (vSB).
What ueteimines whethei you get cyanosis oi not. Begiee of pulmonic stenosis; not
all babies have cyanosis anu aie acyanotic - calleu '5"'4$6&5 6,6-';$3"; why uoes
this occui. Lets say the uegiee of pulmonic stenosis is not that bau - when the iight
vent contiacts, a lot of the bloou goes up the pulmonaiy aiteiy to get 02'u anu less
bloou gets into the left ventiicle, anu theiefoie piobably will not have cyanosis at
biith. What if it was a seveie stenosis anu when the iight vent contiacts, veiy lil
bloou got up theie. Nost will be shunteu iight to left anu theie will be a step B0WN
in 02 in the left vent anu baby will be cyanotic. So, &6 &/ 6?, A,3-,, $= #<;.$4&5
/6,4$/&/ 6?'6 A,6,-.&4,/ L?,6?,- "$< ?'J, 5"'4$/&/ $- 4$6) Which of the gioups
of shunts is caiuio-piotective in a pt with tetialogy of fallot. PBA, ASB - goou - lets
say theie is an ASB, theiefoie bloou will go left to iight bc we get 02'u bloou
emptying into the iight atiium. This woulu cause a step up of bloou into the iight
atiium (this is goou). Bow about a PBA. Lets make believe this occuis - so, un02'u
bloou pusheu fiom left fiom the aoita uown to the pul aiteiy to get 02; some of the
un02'u bloou put back into the pul aiteiy, wheie it gets 02'u anu moie gets out -
3$$A 6$ ?'J, :G( '4A ([G H=$-'.,4 $= $J';,I L&6? 6,6-';$3" $= =';;$6)
D&3?6 6$ ;,=6 ;,'A/ 6$ #$;"5"6?,.&' '4A ' -,'; -&/P =$- &4=,56&J, ,4A$5'-A&6&/ b
c shunts going into left siue, theiefoie can get vegetations going into the biain anu
othei systemic oigans. (;; 5$43,4&6'; ?,'-6 A,=,56/ ;,'A 6$ &4=,56&J,
,4A$5'-A&6&/)
Auuio File 21: Caiuiovasculai S
W) +-'4/#$/&6&$4 $= W-,'6 J,//,;/
Example: in Kaitagenei's synuiome with synuiome with sinus inveisus - this not
the case with tiansposition of gieat vessels - have a noimal heait that is on the iight
siue (eveiything isn't ieveiseu the way it is in sinus inveisus). What's tiansposeu.
Not the iight atiium - it is still getting unoxygenateu bloou. Its not the left atiium - it
is still getting 9S% 02 satuiateu bloou fiom the pulmonaiy vein. +?, #-$E;,. &/ &4
6?, J,46-&5;,/ - the iight ventiicle is being emptieu by the aoita; anu the left is
being emptieu by the pulmonaiy aiteiy. So, the thing that is tiansposeu aie the
ventiicles (the atiia aie fine). This is incompatible with life unless you have shunts:
vSB, ASB, anu PBA can woik. Bow's uoes this woik.
Stait at the atiial siue - have 9S% 02 coming into left atiium anu it is going fiom
the left to iight; theie will be a step up of 02 in the iight atiium anu theiefoie also a
step up of 02 in the iight ventiicle. Some will go out the aoita anu iest will go to the
left ventiicle. This is goou bc the left ventiicle is being emptieu by the pulmonaiy
aiteiy, so the bloou will be taken to the lungs to be oxygenateu. So, these shunts aie
necessaiy. 0theiwise, the iight vent being emptieu by the aoita woulu be all
oxygenateu bloou anu the left ventiicle being emptieu with the pulmonaiy aiteiy
woulu not be okay. So, by having the shunts, can get aiounu these uefects. An ASB is
necessaiy so you can get 02'u bloou into the iight atiium, anu fiom the iight atiium
theie will be a step up of 02 in the iight ventiicle, which is being emptieu by the
aoita; obviously this bloou isn't 9S% satuiateu (maybe 8u%), anu this is why theie is
cyanosis in these patients. At least some bloou can get out of the aoita anu have
some 02 to the pt anu they can suivive foi a little while. Bc of the iight to left shunt,
that bloou is being emptieu by the pulmonaiy aiteiy anu that is going to the lungs
anu being oxygenateu. So, the shunts aie necessaiy foi life. So, with Kaitagenei's,
theie is N0T a complete tiansposition of vessels, but a noimal heait on the iight siue
(calleu sinus inveisus).
!) >$'-56'6&$4 - have pieuuctal anu postuuctal
Pie = befoie patent uuctus; post = aftei patent uuctus (aftei the ligamentum
aiteiiosum)
:-,A<56'; occui in Tuinei synuiome anu go stiaight into failuie, theiefoie must be
coiiecteu immeuiately. :$/6A<56'; aie not piesent at biith anu can occui at any
time uuiing the pt's auult life. Impoitant to iecognize bc they aie a suigically
coiiectable cause of BTN.
Stenosis in aoita - what is happening pioximal. Theie is tiouble getting bloou
thiough that, theiefoie theie will be a muimui heaiu best between the shouluei
blaues - a systolic muimui. Theie is a lot of piessuie built up pioximally, so the piox
aoita will be uilateu anu theie will be a lot of piessuie going into the vessels - the
subclavian, inteinal caiotius - theiefoie the V: &4 6?, <##,- ,%6-,.&6&,/ L&;; E,
?&3?,- 6?'4 &6 &/ &4 6?, ;$L,- ,%6-,.&6&,/) Also, with incieaseu bloou flow into the
biain, at the junction wheie the communicating bianches hit the main ceiebial
bianches, we have no inteinal elastic lamina anu no smooth muscle theie, theiefoie
it is a weak aiea (foi ALL people); theiefoie, ,J,-"E$A" ?'/ 6?, #$6,46&'; 6$
A,J,;$# E,--" '4,<-"/./. What woulu exaceibate, oi make the beiiy aneuiysm a
iealistic thing. !+Q (any cause of BTN can cause beiiy aneuiysms - ie ABPKB,
essential BTN, the bottom line is BTN, anu (XX ?"#,-6,4/&J, #6/ -<4 6?, -&/P $=
E,--" '4,<-"/./ - we all have the same uefect at the junction foim any cause of
BTN - its not unique to ABPKB, its in all cases of BTN - othei ielations to BTN =
subaiachnoiu bleeus, stietchuilatation of aoitic valve iing anu theiefoie a muimui
of aoitic ieguig. All the piessuie on the wall of the pioximal aoita 5'4 ';/$
#-,A&/#$/, 6$ A&//,56&43 '$-6&5 '4,<-"/.. What is uistal to this. Becieaseu bloou
flow, 5;'<A&5'6&$4 (angina of peiipheial vessels - so when they walk, they will get
calf pain, buttock pain, then they stop anu it goes away, they walk it huits) - this is all
uue to ischemia, anu the muscle uevelopment to the lowei extiemities will not be too
goou, eithei. Nuscle mass will be uecieaseu, BP uiffeience between uppei anu lowei
extiemities, anu the bloou flow to the ienal aiteiies is uecieaseu, leauing to
activation of the RAA will leau to BTN. So the !+Q &4 #6/ L&6? >$'-56'6&$4 &/ A<,
6$ '56&J'6&$4 $= D(( - so it is a high ienin BTN. So, if you can coiiect it the BTN will
go away. When theie is a pioblem (ie a ioaublock), we have to go aiounu it - ie neeu
collateials. Bowevei, the aoita is not a goou place to have a ioaublock bc only have
two ways to get aiounu the block: 1)(iaiest) supeificial epigastiic aiteiy, with the
inteinal mammaiy aiteiy can get aiounu this; this is at the lateial boiuei of
hasselbach (the supeificial epigastiic aiteiy). So, when you stick youi fingei in the
canal anu have an inuiiect inguinal heinia. Right thiough the meuial siue will feel a
pulsation (wheie the sup epigastiic aiteiy is). 2) inteicostals - on the unueisuiface
of the iibs anu getting extia bloou thiough them - leauing to 4$65?&43 $= -&E/
(visualizeu on x-iay).
F@) B'u$- -&/P ='56$-/ =$- 5$-$4'-" '-6,-" A]0 Know the iisk factois!
Age is the most imp iisk factoi (cannot contiol) -4S foi males; SS foi women - why.
Bighei estiogen levels, which affect BBL levels. Risk factoi foi CAB is not LBL, its
BBL. BBL visits fatty stieaks, sucks LBL out, takes it to the livei to be metabolizeu.
SS in women bc that is the age of menopause; not taking estiogens anu that is the
age when estiogens go uown; BBL levels go uown anu iisk goes up. Family histoiy of
piematuie aiteiy uz, cig smoking, BP, BBL<SS, uiabetes, LBL (cholesteiol is not a
iisk factoi, LBL is) bc all theiapeutic uecisions aie baseu on LBL levels, not
cholesteiol levels. BBL is a negative iisk factoi: if youi BBL is gieatei than 6u, you
can subtiact one fiom youi majoi iisk factoi - ie S8 yo, but BBL is above 6u, can
subtiact the age iisk factoi anu will have no iisk factois.
F@@) @/5?,.&5 !,'-6 G&/,'/,0
K 6"#,/0 (43&4'_ B"$5'-A&'; @4='-56_ [<AA,4 >'-A&'5 G,'6? ["4A-$.,_ >?-$4&5
@/5?,.&5 !,'-6 G&/,'/,
() [<AA,4 5'-A&'5 A,'6? /"4A-$., = ueath within the last hi - what will you see
at autopsy. Will N0T see a coionaiy thiombus, will see seveie coionaiy aiteiy
atheioscleiosis. So, usually these pts uo not have a thiombus, but uo have seveie
coionaiy aiteiy uz, leauing to ischemia, PvC's, ventiiculai fibiillation (uie of
ventiiculai aiihythmia just like in NI); uie so fast that theie aie no changes in the
heait (ie palloiCoagulation neciosis); see seveie coionaiy aiteiy uz anu ux suuuen
caiuiac ueath. veiy high iisk in smokeis.
V) >?-$4&5 &/5?,.&' ?,'-6 A] -It's a lot of oui paients, uncles anu aunts who have
coionaiy aiteiy uz with little infaicts, oi hau a small heait attack, basically talking
about subenuocaiuial infaictions. What happens is that the muscle gets ieplaceu by
fibious tissue anu eventually the pooi Lv is all fibious tissue, with no muscle
theiefoie the ejection fiaction is veiy low. Its u.2 insteau of the noimal u.66 anu they
uie fiom heait failuie. Fibious tissue uoes not have contiactility; this uz is the 2
nu
NC
inuication foi a heait tiansplant.
>) (43&4' HB> 6"#, $= ?,'-6 A]I
9 6"#,/ \ ,%,-6&$4';_ #-&4].,6';_ <4/6'E;, H-,/6&43I '43&4'
1. Z%,-6&$4'; - chest pain on exeition, goes away within S-1u minutes of iesting;
ST uepiession on EKu (1-2 mm uepiession) - theiefoie a canuiuate foi coionaiy
angiogiam to see what's going on.
2. :-&4].,6';8/ - seen in women, occuis in moining; uue to vasospasm of the
coionaiy aiteiies, N0T atheioscleiosis. In some people, TxA2 is implicateu foi the
vasospasm. [+ A,#-,//&$4 .,'4/ /<E,4A$5'-A&'; &/5?,.&'. Coionaiy aiteiies
penetiate the outsiue of the heait anu go in, so the subenuocaiuial tissue get scieweu
bc its fuitheiest fiom the bloou supply. Theiefoie, with coionaiy aiteiy
atheioscleiosis, anu uecieaseu bloou flow, who gets scieweu. Subenuocaiuium anu
it ieacts to it with pain anu ST uepiession. With vasospasm of coionaiy aiteiy, get
tiansmuial ischemia - theiefoie theie is ischemia thioughout the entiie thickness of
the muscle - this piouuces ST elevation. So, Piinzmetal's angina has ST elevation bc
tiansmuial ischemia.
S. M4/6'E;, - aka pie-infaiction angina - get angina on iesting. Classic hx: initially
hau stable angina, now pt just get it when they aie sitting. This means that they will
neeu angioplasty anu put into the hospital. Bo not put on tieaumill, they will uie.
What veins uo they use. Saphenous vein - ovei 1u yeais will become aiteiializeu (it
will look exactly like an aiteiy). If you take a vein, anu put aiteiial piessuies into it,
it will change its histology anu look exactly like an aiteiy. They have a high tenuency
foi fibiosing off aftei 1u yeais bc they aie veins.
Inteinal mammaiy is an aiteiy, theiefoie won't have the same pioblem bc it is
useu to those piessuies. They will iemain patent, but cannot uo foui vessel bypass
with one inteinal mammaiy aiteiy. So, they use the saphenous vein, which has the
tenuency to unueigo fibiosis ovei time bc they aie aiteiializeu unuei piessuie.
They can also use the inteinal mammaiy.
G) (5<6, B@
Thiombus composeu of gioup of platelet cells bounu togethei with fibiin. TPA
uoesn't have a pioblem with this bc it just bieaks the fibiin bonus to uestioy the
clot. It has a much biggei pioblem with the bieakuown of a venous clot bc those
have moie fibiin. The thiombosesclots in the heait uo not have that much fibiin.
Anothei factoi to ueal with is iepeifusion injuiy - 02'u bloou goes into injuieu
tissue, supeioxiue fiee iauicals foim, Ca foim, anu a few of the injuieu myocaiuial
cells will uie. 0nce those uie, it will still impiove longevity.
1) >$.#;&5'6&$4/ $= B@0
'I X(G 5$-$4'-" '-6,-" is NC vessel thiomboseu, anu supplies entiie anteiioi
pait of youi heait anu the anteiioi 2S's of the inteiventiiculai septum. So, theie
will be paleness, with the ant 2S's knockeu off. Wheie aie most of the conuuction
bunules. Anteiioi 2S's. So, if you have complete heait block that iequiies ectopic
pacemakei, what is the most likely vessel thiomboseu. LAB. When you have LAB
occlusion, you have 5;'//&5'; /&34/ \ #'&4 -'A&'6&43 6?, u'L_ #'&4 A$L4 6?, ;,=6
'-._ /<E/6,-4'; 5?,/6 #'&4)
EI D>( = 2
nu
NC thiomboseu aiteiy - which supplies the entiie posteiioi pait of
the heait anu the posteiioi 1S of the ventiiculai septum anu the entiie iight
ventiicle. So, it supplies the post heait, post 1S of the septum anu the entiie iight
ventiicle. The mitial valve has two valves with papillaiy muscles - posteiomeuial
papillaiy muscle anu posteiomeuio papillaiy muscle. So, what supplies the
posteiioi. RCA. Also have the SA noue anu Av noue. The SA noue has an equal
uistiibution between left anu iight. Bowevei, the (F 4$A, ?'/ ' aNn /<##;" =-$.
6?, E-'45?,/ $= 6?, D>( - this biings up inteiesting complications. Example: pt
with mitial ieguig muimui, which is ielateu to posteiomeuial papillaiy muscle
uysfunction, oi may bieak - what is the pioblem. Thiombosis of the RCA bc the
RCA supplies that papillaiy muscle. So, mitial ieguig muimui that occuis uuiing NI
woulu be uue to RCA. @= "$< P4$5P $== 6?, (F 4$A,_ 6?&/ &/ /&4</ E-'A"5'-A&'_ '4A
'6"#&5'; 5?,/6 #'&4. The RCA is uangeious bc sometimes pt will get ,#&3'/6-&5
#'&4, which is an atypical pain. This simulates uERB; ie pt sent home with pepto
bismol, anu enus up uying at home (bc of misseu ux). They shoulu have been sent
to hospital. Theiefoie, elueily pt with ,#&3'/6-&5 #'&4 5$<;A E, WZDG $- 5$-$4'-"
'-6,-" 6?-$.E$/&/ $= 6?, D>()
7) W-$//R.&5-$/5$#&5 =,'6<-,/
Neeu to know when the heait is softest anu has a chance foi iuptuiing - this is
between S-7 uays. When uo you see gioss manifestation of being a pale infaict. 24
his - begin seeing paleness. Coagulation neciosis in 4-6 his.
Example: LAB thiombosis bc see pale anteiioi 2S of heait. Ruptuie -
peiicaiuium filleu with bloou (hemopeiicaiuium) - most aie inteiioi, anu theiefoie
is fiom the LAB thiombosis - how uoes this manifest itself. Bay S oi uay 4 complain
of chest pain, have muffleu heait sounus, neck vein uistension, anu know they have
iuptuieu.
Example: iuptuie of post meuial papillaiy muscle - anu it was infiacteu, theiefoie
the RCA is the cause
of the iuptuie - so, what woulu the muimui be. Nitial ieguig -0n uay S pt goes
into heait failuie, have a pansystolic muimui, incieases on expiiation, anu SS anu S4
heait sounu. It wasn't theie a uay befoie - meaning the posteiioi meuial papillaiy
muscle was uysfunctional bc it was infiacteu oi it iuptuieu. So, it's something that
wasn't theie befoie anu suuuenly aiise between uays S-7. Will go into heait failuie
bc massive volume oveiloau anu go iight back to the lungs.
Example: iuptuie of ant wall
Example: iuptuie of papillaiy muscle, anu the posteiomeuial one is NC
Example: Coag neciosis
Example: inteiventiiculai septum iuptuies, theiefoie a left to iight shunt anu a step
up. Nost inteiventiiculai iuptuies aie LAB thiomboses.
Example: .<-'; 6?-$.E</ (muial = wall) - in this case, muial is a thiombus, on
the wall. They aie almost always LAB thiombi bc neeu a place to stick. With
anteiioi NI, always give aspiiin anu put pt on waifaiinhepaiin - why uo they uo
that. To pievent muial thiombus fiom foiming. So, when you have an anteiioi piob,
they will anticoagulate you. B<-'; 6?-$.E& '-, .&%,A 5;$6/ - they aie not a puie
venous like clot oi a platelet like clot, they aie mixeu. Beie's how it woiks: you have
a tiansmuial infaiction anu theiefoie injuiy to enuothelial cells of the heait,
theiefoie platelets will stick - so platelets aie the fiist things that stick anu then bc
the muscle is not contiacting that well (bc infiacteu muscle uoes not contiact),
theie is stasis, anu so on top of the platelets is a venous like clot, which Coagulation
factoi S,8, anu RBC's, so its mixeu (platelets with fibiin anu venous clot fiom stasis).
With '/#&-&4, you not only pieventing a coionaiy thiombus with uecieasing platelet
aggiegation, but also pieventing a muial thiombus fiom initially foiming bc it
inhibits the platelets fiom aggiegating. Also, E" #<66&43 $4 L'-='-&4 '4A ?,#'-&4,
you pievent the othei pait of the clot fiom foiming. Bon't want these bc it can
embolize anu theiefoie aie veiy uangeious.
9) T&E-&4$</ #,-&5'-A&6&/ - can occui 2 times in a peison with NI: 1) 1
st
week - get
a fiiction iub, chest pain (ielieveu when leaning foiwaiu anu woise when leaning
back - a S component fiiction iub). That's uue to tiansmuial infaiction anu incieaseu
vessel peimeability. Anu 2) hx of tiansmuial infaict, comes in 6 weeks latei with
fevei, muscle aches anu pains, anu a S component fiiction iub in the chest =
G-,//;,-/8/ /"4A-$., _ L?&5? &/ '4 '<6$&..<4, #,-&5'-A&6&/. When hau infaict,
uamage of the peiicaiuial suiface leu to autoAb's against peiicaiuial tissue. This
took 6 weeks to builu up, anu they stait attacking the peiicaiuium leauing to
systemic symptoms ielateu to immunologic ixn = Biessleis's. Theiefoie, 7 6"#,/ '-,
1
/6
L,,P_ 4$6 '<6$&..<4,_ '4A ` L,,P/_ '<6$&..<4,) Basically tieat with
NSAIBS.
K) X'6,- 5$.#;&5'6&$4/ \ J,46-&5<;'- '4,<-"/.
Example: pt S weeks out of NI - chest bulges - what unuei theie. Nassive
pectoialis majoi - ie /"/6$;&5 E<;3, $= #,-&5'-A&<. &/ J,46-&5<;'- '4,<-"/..
Bloou is collecting in the aneuiysm anu making the chest bulge out. This is a late
manifestation - know it's a vent aneuiysm; the NC complication is N0T iuptuie, this
aneuiysm is lineu by scai tissue anu theiefoie will not iuptuie) B>> A,'6? &4 ' J,46
'4,<-"/. C ?,'-6 ='&;<-,) Nost of heait has scai tissue, which leaus to uecieaseu
ejection fiaction, theiefoie, A&, $= !Z(D+ T(@XMDZ 4$6 -<#6<-,.
Example:Acute NI - wasn't - it is U&E-$</ 6&//<,_ L?&5? &/ L?&6,- '4A .$-,
#'65?") Fibious tissue (scai) can be anywheie fiom S weeks to 1u yeais
Nust look at EF (ejection fiaction) befoie leaving hospital; if you uon't have a goou
EF, piobably will uie. If you have a low EF, you hau a big infaict, with a lot of muscle
that was uestioyeu. Theiefoie, EF is the biggest piognostic factoi. If its close to u.66,
that's goou. But if youi u.4, ie its veiy bau.
N) !$L A$ L, A% B@e >S^BV &/ A% $= 5?$&5,
Not an EKu bc it has only an 8u% sensitivity showing a new q wave, ST elevation.
They have gieat specificity: Tioponin I; CK-NB is an isoenzyme of cieatinine kinase
- have CK-NN, NB, anu BB.
>S \ BV is piimaiily in caiuiac muscle. Theiefoie, when you infaict the muscle,
you will see a piimaiy inciease in caiuiac muscle, anu when the muscle is infiacteu,
will see an inciease in that enzyme. Staits to go up at 6 his. Peaks in 24 his, anu gone
in S uays bc if CK NB is piesent aftei S uays uefines REinfaiction. So, the
ieappeaiance of CK-NB = REinfaiction.
+-$#$4&4 @ elevates a few his eailiei than CK NB - its goes up at about 4 his, anu
peaks in about 24 his, too. It lasts 7 uays, which is goou. Bowevei, cannot ux
ieinfaiction. So, aftei uay S Tioponin will still be theie anu theiefoie, you cannot ux
ieinfaiction. CK-NB ieplaces LBB isoenzymes.
XG! &/$,4]".,: Noimally, LBB2 is highei than LBB1. Bowevei, XG!1 &/ &4
5'-A&'5 .</5;,. So, when you have an infaict, you ielease LBB1, anu 1 becomes
highei than 2 - which is calleu the flip. When you infaict thiough the muscle, 1 will
be highei than 2, anu that is the flip. This occuis in about 18 houis anu peaks in
about S uays anu last foi a week. Nost of the time, we use LBB enzymes if the pt
came in 2-S uays aftei symptoms anu CK-NB will have been gone by then. Then, look
at LBB isoenzymes, anu iecognize that theie is a flip anu iealize that theie was an NI
few uays ago. This will be ieplaceu by Tioponin 1 bc its elevateu uuiing this time
peiiou.
Auuio File 22: Caiuiovasculai 4
F@@@) F';J<;'- !,'-6 G&/,'/,
() B&6-'; F';J, :-$;'#/, - NC mitial valve lesion - moie common in women; too
much valve anu looks like a paiachute (aii goes unuei a paiachute anu fills it up -
same with bloou) - bloou will piolapse into left atiium, anu when it stops, it causes a
click. Piolapse means that something is coming out - ie iectal piolapse.
So, with mitial valve piolapse, it is extenuing into the left atiium. When it stops,
anu cannot go in anymoie, it stops anu causes a click, anu it followeu by a shoit
mitial ieguig muimui. So, it goes "click muimui, click muimui" (not "snap muimui"
- opening snaps occui in mitial anu tiicuspiu stenosis). What is the pathology.
Nyxomatous uegeneiation. What uAu makes up the valve. Beimatan sulfate,
theiefoie its an excess of ueimatan sulfate in the mitial valve, anu it becomes
ieuunuant (too much of it), bloou goes unuei it anu causes a click anu muimui. Is it
closei to S1 oi S2. It ueals with pieloau. If we incieaseu vol of bloou in the left
ventiicle, then the click anu muimui will come closei to S2 bc it takes longei foi all
the events to get bloou out. If we ueciease the amount of bloou coming into the left
ventiicle (ueciease pieloau), the click anu muimui come closei to S1. So, when
stanuing anu have NvP, what is pieloau vs. lying uown. It is less. Less pieloau = less
bloou in the ventiicle = click anu muimui closei to S1. Now, let's say pt lies uown -
click anu muimui closei to S2 bc incieasing pieloau. They will ask: what will
happen to click anu muimui with anxiety. What will happen to heait iate with
anxiety. Inciease. Theiefoie, will have less time to fill ventiicles, theiefoie will come
closei to S1.
Queston on examinations " Ameiican touiist came back with uiaiihea. answei is
giaiuisis"
V) ($-6&5 [6,4$/&/
NC valvulai cause of syncope with exeicise
NCC angina with exeicise.
NCC micioangiopathic hemolytic anemia
This will an ejection muimui, iight 2
nu
ICS, iauiation into the neck, systolic,
incieases in intensity on expiiation. Intensity of muimui with uiffeient positions:
what will inciease the intensity of the muimui (what will make it woise anu
theiefoie louuei). Incieasing pieloau in the ventiicle. With uecieaseu bloou in the
ventiicle, it will ueciease the intensity of the ejection muimui bc it has to go out the
stenotic valve.
If you aie putting moie bloou into the Lv anu neeu to get it out, it will inciease the
intensity - this is imp bc it uiffeientiates it fiom hypeitiophic caiuiomyopathy.
Why uo they get angina with exeicise. Pulse is uiminisheu anu theiefoie the stioke
volume will ueciease. So, when uo the coionaiy aiteiies fill up. Biastole. With less
bloou theie (bc coulun't get it out anu hau to get it thiough the valve), theie is
thickeneu muscle anu less bloou going to the heait, leauing to angina. So, this is the
NC valvulai lesion leauing to angina. Also, with syncope with exeicise, bc you have
uecieaseu caiuiac output, you will faint.
>) B&6-'; /6,4$/&/
Sliue: Thiombi, left atiium is uilateu; .<-.<- &4 A&'/6$;, (stenosis piob in
opening anu this valve opens in uiastole, leauing to snap anu iumble), heaiu at apex
anu incieases in intensity on expiiation.
B>> .&6-'; /6,4$/&/ \ -?,<.'6&5 =,J,- H'5<6,I. Rheumatic fevei -vegetations;
uue to gioup A beta hemolytic stieptococcal infection. 0sually occuis as post-
phaiyngitis. As opposeu to post stieptococcal glomeiulonephiitis, this can be
phaiyngitis oi a skin infection. Nost of time iheumatic fevei is fiom a pievious
tonsillitis. When you cultuie bloou in pts with iheumatic fevei, it will be negative.
Will not be able to giow the oiganisms bc its not an infective enuocaiuitis. It is an
immunologic mechanism. O&6? /6-,#_ B #-$6,&4 &/ 6?, #'6?$3,4&5 ='56$- =$-
3-$<# ( /6-,#. Ceitain stiains have Ag's similai to the heait anu joints. So, when we
make Ab's against the gioup A stiep, we aie also making Ag's against the heait (oui
own tissue) - theiefoie we attack oui own heait, joints, basal ganglia anu elsewheie.
This is calleu .&.&5-" bc we aie ueveloping Ab's against oui own tissue, bc theie
aie similai Ag's in the N piotein of the bacteiia, /$ &6/ &/ ';; &..<4$;$3&5! NC valve
involveu is the mitial valve. The vegetations aie steiile anu line along the closuie of
the valve. The vegetations usually uo not embolize. S4$L t$4,/ 5-&6,-&' =$- A% $=
'5<6, -?,<.'6&5 =,J,- - ie young peison, few weeks ago hau an exuuative
tonsillitis, now piesents with joint pain anu swelling anu uyspnea, iales in the lung,
pansystolic muimui, apex, anu incieases in intensity on expiiation, SS anu S4 heait
sounu - uue to acute iheumatic fevei. Bx is iheumatic fevei. B> /".#6$. &/
#$;"'-6?-&6&/. They like this question bc in chiluien, theie is a limiteu ARA =$-
#$;"'-6?-&6&/ \ &6 &45;<A,/ u<J,4&;, -?,<.'6&5 '-6?-&6&/_ !,4$5? [5?$4;,&4
#<-#<-'_ -<E,;;'_ '5<6, -?,<.'6&5 =,J,-) !$L,J,-_ 4$4, $= 6?,/, ?'J,
/".#6$./ $= ?,'-6 ='&;<-, '4A .&6-'; &4/<=U&5&,45" ,%5,#6 =$- '5<6, -?,<.'6&5
=,J,-) So, if they ask you the NC valvulai lesion in acute iheumatic fevei, it is N0T
mitial stenosis. It takes 1u yeais to have a stenotic valve (mitial stenosis). So, the
muimui that you heai is mitial REu0Ru, bc all paits of the heait aie inflameu,
leauing to fiiction iub, myocaiuitis (inflameu myocaiuium), anu enuocaiuitis (these
aie the valves with the vegetations). So, will get mitial ieguig muimui with acute
iheumatic fevei. 0thei featuies of }ones ciiteiia: joints, caiuiac abnoimalities,
eiythema maiginatum (skin zit), subcutaneous nouules (like iheumatic nouules on
the extensoi suifaces - they aie exactly the same). Rh nouules anu nouules
associateu with acute iheumatic fevei aie exactly the same. They aie both
immunologic uz's. Late manifestation of }ones' ciiteiia is abnoimal movements -
calleu Synuham's choiea. Example: pt with acute iheumatic fevei (giaue S,
pansystolic, apex, iales, SS anu S4, nouules, eiythema maiginatum) - 6 weeks latei
have Synuham's choiea. ([2 6&6,- &/ &.#_ 6$$ \ ER5 &68/ ' 3-$<# ( /6-,# &4=,56&$4
'4A &6/ ,;,J'6,A) Aschoff nouules - ieactive histiocytes in the myocaiuium; only
finu with bx on ueath. Summaiy: immunologic uz, will not cultuie out gioup A stiep
in the bloou, }ones ciiteiia (polyaithiitis, NC caiuitis, subcutaneous nouules,
eiythema maiginatum, Synuham's choiea.
Ie mitial stenosis, looking fiom left atiium, uown to the ventiicle - looks like a
fishmouth (fishmouth appeaiance).
Example: what is the most posteiioily locateu chambei of you heait. Left atiium.
Seen best on tiansesophageal ultiasounu. Bc it is posteiioily locateu, anu enlaigeu
when uilateu, it can piess on the esophagus, leauing to usyphagia with solius (not
liquius). Also, it can stietch the left iecuiient laiyngeal neive anu cause hoaiseness.
This is calleu 2-4,-8/ /"4A-$.,.
Example: if they have an iiiegulai iiiegulai pulse, what uoes that mean. (6-&';
U&E-&;;'6&$4. Boes it suipiise you that they get thiombus in the left atiium. No. Bc
theie is a lot of stasis bc bloou is having tiouble getting thiough, leauing to stasis
anu thiomboses. So, have to anticoagulate the pts, which is a bau combo.
Atiial fib + thiombus = bau combo. When you pictuie A fib, its like a vibiatoi anu lil
chips can come off anu embolize - this is veiy common in patients with NITRAL
STEN0SIS.
BF: - valve is being piolapseu into atiium, bc it is so ieuunuant, anu, choiuae
tenuinae will iuptuie, leauing to acute mitial insufficiency. This is not common in
NvP - most of the time it is asymptomatic. NC symptomatic thing = palpitations.
7 3,4,6&5 A]8/ L&6? BF: '//$50 B'-='48/ '4A Z?;,- G'4;$/ /"4A-$.,) Naifan pt
anu pt uieu suuuenly, why. N0T uissecting aoitic aneuiysm (uo not uie immeuiately
with uissections - get pain, iauiation anu caiuiac tamponaue) - answei is NvP anu
conuuction uefects. So, #6 L&6? .'-='4 '4A A&,/ /<AA,4;"_ 6?&/ &/ A<, 6$ BF: '4A
5$4A<56&$4 A,=,56/ H4$6 A&//,56&43 '$-6&5 '4,<-"/.I)
+-&5</#&A -,3<-3 - know about IvBA with infective enuocaiuitis.
>'-5&4$&A /"4A-$., - in oiuei to have caicinoiu synuiome, must have metassis to
livei of caicinoiu tumoi. Seiotonin anu the tumoi nouules gets into hepatic vein
tiibutaiies anu gets into the venous bloou anu bathes the iight siue of the heait, anu
seiotonin piouuces a fibious tissue iesponse of the valves. So, will get tiicuspiu
insuff anu pulmonic stenosis. These aie the 2 valvulai lesions assoc with caicinoiu
synuiome. (TIPS)
@g) @4=,56&J, ,4A$5'-A&6&/
Nitial valve with vegetations anu iuptuie choiuae tenuinae; vegetations aie big
anu bulky anu uestioying the valve (hence, infective).
What is B>>e [6-,# J&-&A&'4/i 7
4A
B>> C [6'#?
While biushing teeth, have a tiansient stiep viiiuians infection. If you have an
unueilying caiuiac uz, then you iun the iisk of ueveloping a bacteiial enuocaiuitis b
c just biushing youi teeth can cause it to get into the blooustieam; with uamageu
valves, it can seeu into it anu piouuce vegetations.
Staph auieus can affect a N0RNAL valve 0R a uamageu valve.
NC valve involveu in infective enuocaiuitis = mitial valve; 2
nu
NC valve = aoitic
valve
If you aie an IvBA (who inject into veins), NC valve involveu = Tiicuspiu valve, 2
nu

NC is aoitic
+-&5</#&A &4J$;J,A = Nuimui of tiicuspiu ieguig, pansystolic, incieaseu on
inspiiation
($-6&5 J';J, &4J$;J,A: aoitic ieguig, high pitcheu uiastolic aftei S2
Staph is #1 (NCC) foi IvBA
If you have 5$;$4 5'45,-R<;5,-'6&J, 5$;&6&/ (any type of ulceiation of the colonic
mucosa), theie is a unique type of infective enuocaiuitis - this is /6-,# E$J&/ =
3-$<# G /6-,# \ 5$..$4;" &4J$;J,A L&6? A]8/ 6?'6 #-$A<5, <;5,-'6&$4 $= 6?,
5$;$4&5 .<5$/' \ &, M> $- 5$;$4 5'45,-) !&/6$-" $= 5$;$4 5'45,- '4A ?'J,
&4=,56&J, ,4A$ \ $-3'4&/. &/ /6-,# E$J&/ H4$6 /6'#?I)
Aoitic valve - close ielationship of membianous poition of the septum with the
aoitic valve. So, why uiu pt get vegetations of the aoitic valve. Bc they got vSB that
was not pickeu up. If you have congenital heait uz, you have an incieaseu iisk foi
infective enuocaiuitis. vSB that someone uiu not pick up causeu aoitic valve to get
infective anu cause aoitic ieguig. Theiefoie, on the test, will be mitial valve infective
enuo, oi aoitic infective enuo with a vSB.
Splintei hemoiihages; Painful = oslei's noues; painless = janeway lesion; in eye -
Roth spot (ieu with white centei - just like Koplik spots in measles, which aie ieu
with a white centei). This is why it is calleu the Koplik spot of the eye. What uo they
all have in common (asiue fiom the fact that they aie seen in infective enuocaiuitis).
Splintei hemoiihages, 0slei's noues, janeway lesions, Roth spots, anu
glomeiulonephiitis. (;; '-, 6"#, @@@ !:b. All these lesions aie immune complex
vasculitis.
vegetations all ovei suiface of the valve anu pt has a "+" seium ANA - ux. X&E.'4
/'5/ ,4A$5'-A&6&/ \ #6 ?'/ X<#</ (Libman sacs is not the NC lesion of the heait
with Lupus - peiicaiuitis is); Libman sacs is the 2
nu
NCC, which is fibiinoiu neciosis
like iheumatic fevei.
Naiantic vegetations in mucous secieting colon cancei = Paianeoplastic synuiome
(it is maiantic enuocaiuitis in a pt with colon cancei). Acute iheumatic fevei looks
like it.
g) B"$5'-A&6&/ J/) :,-&5'-A&6&/
0n the test, if you have an infection question, it is >$%/'5P&, J&-</)
NCC of myocaiuitis anu peiicaiuitis;
NCC viial meningitis = Coxsackie viius.
Cause of hanu, foot anu mouth uz. Coxsackie viius
Beipangina is uue to Coxsackie's viius.
Example: Pt with heait failuie uiu an enuomyocaiuial bx anu it hau lymphocytic
infiltiate in theie, anu it was uue to Coxsackie's myocaiuitis. To ux, neeu to uo a bx
of subenuocaiuial tissue, anu will see lymphocytic infiltiate (as expecteu with ANY
viius). Theiefoie, ie, pt in heait failuie, bx of myocaiuium has lymphocytes =
Coxsackie's viius myocaiuitis
Chest x-iay - see watei bottle config - this pt as muffleu heait sounus (cannot heai
anything), when the pt bieaths in, neck veins uistenu (shoulun't happen bc when
you bieath in anu inciease neg intiathoiacic piessuie, the neck veins shoulu collapse
on inspiiation), iauial pulse is uecieaseu on inspiiation, when you take BP theie is a
uiop of 1ummBg uuiing inspiiation. Bx. :,-&5'-A&'; ,==</&$4
What the name of the tiiau. Beck's tiiau. What is the name of the sign. S<//.'<;8/
/&34. What is the uiop of 1u mm Bb on inspiiation. :<;/</ #'-'A$%</) Bow uoes all
this occui. Bc theie is an effusion of the peiicaiuial sac, meaning that that heait
cannot fill up (bc theie is fluiu aiounu it) - leauing to muffleu heait sounus. So,
when you bieath in anu bloou is supposeu to get into the iight siue of youi heait, it
cannot expanu. So, the neck veins uistenu insteau of collapse, which is calleu
Kussmaul's sign. What evei happens to iight siue of the heait affects the left siue of
the heait bc the left siue ieceive bloou fiom the iight siue. So, theie is no bloou
going into the iight heait, anu theiefoie, no bloou is going out of the left heait, eithei.
So, on inspiiation, bloou cannot get out of left siue (bc bloou is not coming out of the
iight heait), leauing to a uiop in pulse - ?,45, #<;/</ #'-'A$%</. Always see these
things togethei: neck vein uistension, uiop in pulse magnituue, anu uiop in BP,
Kussmaul's sign, pulsus paiauoxus = #,-&5'-A&'; ,==</&$4. Bowevei, this is not what
they will ask you - they will ask what &/ U&-/6 /6,# &4 .'4'3,.,46e
Z5?$5'-A&$3-'. - shows that they have fluiu (pioves it - bc neeu to call suigeon
to uo peiicaiuiocentesis).
What &/ &6 B> A<, 6$e :,-&5'-A&6&/) O?'6 &/ 6?, B>> #,-&5'-A&6&/e >$%/'5P&,)
What if woman has this anu a "+" seium ANA. Lupus.
Any young woman that has an unexplaineu peiicaiuial oi pleuial effusion is lupus
until pioven otheiwise. Why. Seiositis = inflame seiosal membianes - its gonna
leak fluiu, leauing to effusions. Anu is a featuie of Lupus.
Z) >$4/6-&56&J, #,-&5'-A&6&/
In thiiu woilu countiies, TB is NC. In 0SA, uue to pievious caiuiac suigeiy bc
have to go thiough peiicaiuium. Sliue of a heait anu thickeneu peiicaiuium, no fluiu,
so when you bieathe in bloou goes to iight heait, fills up anu hits wall - calleu
#,-&5'-A&'; P4$5P - theiefoie 6$ A&==,-,46&'6, #,-&5'-A&'; ,==</&$4 =-$.
5$4/6-&56&J, #,-&5'-A&6&/_ ?'J, .<=U;,A ?,'-6 /$<4A/ &4 ,==</&$4 L&6? 4$ P4$5P
&4 #,-&5'-A&'; ,==</&$4_ '4A &4 ?'J, /$., U&;;&43 <# L&6? ' #,-&5'-A&'; P4$5P &4
5$4/6-&56&J, #,-&5'-A&6&/) White stuff in peiicaiuium is uystiophic calcification, anu
can see it on x-iay. Pt goes to Russia anu gets uiaiihea = giaiuiasis)
g@) >'-A&$."$#'6?&,/
Laige left ventiicle anu iight ventiicle
() >$43,/6&J, 5'-A&$."$#'6?" H'P' A&;'6,A 5'-A&$."$#'6?"I - Example:
woman 6 weeks postpaitum, anu uo a chest x-iay anu she has a geneializeu
caiuiomegaly - heait is huge, has effusions at both lung bases - ux. Congestive
caiuiomyopathy; this is a uz of the caiuiac muscle anu has many causes. Pt has both
left anu iight heait failuie. Causes: 6 weeks postpaitum (uon't know why),
Coxsackie's myocaiuitis, alcohol, uiugs; NCC tiansplants is uue to congestive
caiuiomyopathy. Caiuiotoxic uiugs - uaunoiubicin, tiicyclics = uiug inuuceu
caiuiomyopathies = congestive caiuiomyopathy. Alcoholic with big heait uue to
thiamine uef = congestive caiuiomyopathy.
V) !"#,-6-$#?&5 5'-A&$."$#'6?"
NCC suuuen ueath in a young athlete = ?"#,-6-$#?&5 5'-A&$."$#'6?") Thickness
of septum veiy thick with an asymmetiic BPY; why. Bc the inteiventiiculai septum
is thickei. Bloou flow of left vent - goes thiough naiiow opening (ant leaflet of
mitial valve - so, if you have aoitic ieguig, bloou will hit anteiioi leaflet of mitial
valve anu piouuce Austin flint muimui). Why is this a naiiow opening. Bc it is too
thick. If we took a lasei to buin it off, coulu open it up; so, wheie is the obstiuction in
hypeitiophic caiuiomyopathy. Its not at the level of the aoitic valve, but below it.
Why uoes it obstiuct. ventuii phenomenon - things go thiough a naiiow opening
quickly anu theie is a negative piessuie behinu it. When bloou, unuei incieaseu
foice of contiaction is foiceu thiough, the negative piessuie behinu it sucks the
anteiioi leaflet behinu the septum anu stops the bloou, leauing to obstiuction of
bloou flow. What can we uo to make this bettei (what can we uo to ieuuce the
intensity of the muimui anu have the pt have bettei C0). Put moie bloou into the
ventiicle - inciease pieloau anu ueciease obstiuction bc it woulu pull it away bc
theie is moie bloou in it. All these things that inciease pieloau will make the
intensity of the muimui less anu impiove the pt. So, if you aie stanuing up, will that
impiove the uz. No, bc woulu ueciease pieloau, leauing to a haish systolic muimui.
Bowevei, if lying uown, theie is incieaseu venous ietuin to the iight heait, anu
incieaseu bloou in the vent, this woulu ueciease intensity of muimui. Bigitalis
woulu be contiainuicateu bc it woulu inciease foice of contiaction, make it go fastei
anu make it obstiuct quickei. A beta blockei woulu be goou; Ca channel blockei
woulu also be goou bc it woulu ueciease foice of contiaction, slow the heait iate,
anu inciease pieloau. This is NCC suuuen ueath in a young athlete. If you took a
section of the septum, its not a noimal septum - its uisoiganizeu, anu the conuuction
bunules aie messeu up, leauing to conuuction uefects - with conuuction uefects, iun
the iisk of v. tach anu ueath at any time. This abnoimal conuuction system anu
asymmetiic septum is iesponsible. Ie 16 yo bball playei that uieu suuuenly - what
uo you see at autopsy. Bypeitiophic caiuiomyopathy. Nech. Abnoimal conuuction
>) Z4A$5'-A&'; T&E-$,;'/6$/&/ (ie of iestiicteu caiuiomyopathy)
If it is iestiictive, something is pieventing the ventiicle fiom filling up. This is the
NC uz causing iestiictive caiuiomyopathy in chiluien, anu is calleu enuocaiuial
Fibioelastosis. This uz is the NC ieason why a chilu neeus a heait tiansplant. If the
chilu uoes not get a tiansplant, they will uie. 0thei causes of iestiictive
caiuiomyopathy - Pompe's, Fe oveiloau, amyloiu.
G) >'-A&'5 ."%$.'
8S% in the left atiium, 1S% in iight
B9, movable - can move ovei anu block oiifice of mitial valve, leauing to syncope.
They can embolize (they aie veiy soft anu have bits anu pieces insiue them). Bave a
lot of junk insiue them, which leaks out. It can leau to fevei, anu othei signs anu
symptoms. Syncope cannot figuie it out; then get a tiansesophageal ultiasounu anu
see it. So, this is the B> #-&.'-" Ea 6<.$- $= 6?, ?,'-6 &4 'A<;6/.
They A,/5-&E, 6<.$- &4 ?,'-6 $= P&A - this is -?'EA$."$.' (b9 tumoi of caiuiac
muscle) - they aie assoc with auto uom. uz, which one. +<E,-$</ /5;,-$/&/. So, if
they talk about a tumoi in the heait of a CBILB, uo not pic myxoma (seen in auults);
it's a ihabuomyoma anu is moie likely in a chilu with tubeious scleiosis.

CHAPTER 8: Respiratory
Auuio File 2S: Respiiatoiy 1
@) (^' 3-'A&,46 \ P4$L ?$L 6$ 5';5<;'6,0
Alveolai 02 anu aiteiial p02 aie nevei the same. The uiffeience between the two is
calleu alveolai aiteiial giauient. Reasons foi it: (1) ventilation anu peifusion aie not
evenly matcheu in the lungs. When stanuing up the ventilation is bettei than
peifusion in the apex, wheieas peifusion is bettei than ventilation at lowei lobes.
This explains why almost all pulmonaiy infaictions aie in the lowei lobes - peifusion
is gieatei theie. Also, this explains why ieactivation TB is in the apex - TB is a stiict
aeiobe anu neeus as moie 02, anu theie is moie ventilation in the uppei lobes
(highei 02 content). Noimally, alveolai 02 is 1uu anu the aiteiial p02 is 9S. So,
noimally, the giauient is S mmBg. As you get oluei, the giauient expanus, but not
that much. Nost people use theii uppei limit of noimal - in othei woius, have a veiy
veiy high specificity of Su mmBg. If you have an (^' 3-'A&,46 $= 9f ..!3 $-
?&3?,- 6?,-, &/ ' #-$E;,.. It is veiy high specificity (aka PPv - tiuly have
something wiong). The concept is easy - you woulu expect the giauient btwn the
alveolai 02 anu the aiteiial 02 to be gieatei if you have #-&.'-" ;<43 A]. What will
uo this. ventilation uefects (piouuces hypoxemia, anu theiefoie piolongs the
giauient - uiopping the P02 anu subtiacting, anu theiefoie a gieatei uiffeience btwn
the two), peifusion uefect (ie pul embolus), anu uiffusion uefect. But the uepiession
of the meuullaiy iesp centei by baibituiates uoes not cause a uiffeience in A-a
giauient. So, #-$;$43,A (^' 3-'A&,46 6,;;/ "$< 6?, ?"#$%,.&' &/ A<, 6$ '
#-$E;,. &4 6?, ;<43/ HJ,46 #,-=</&$4RA&==</&$4 A,=,56I) ( 4$-.'; (^' 3-'A&,46
6,;;/ "$< 6?'6 /$.,6?&43 $<6/&A, 6?, ;<43/ 6?'6 &/ 5'</&43 ?"#$%,.&' H-,/#
'5&A$/&/ \ &4 -,/# '5&A$/&/_ :27 L&;; 3$ A$L4I) Causes of iesp aciuosis:
pulmonaiy piobs (C0PB), uepiession of iesp centei (obstiuct uppei aiiway fiom
epiglottitis, laiygiotiacheobionchitis, caf coionaiy (paialyzeu muscles of iesp),
uuillain Baiie synuiome, amyotiophic lateial scleiosis, anu paialysis of uiaphiagm.
These all piouuce iesp aciuosis anu hypoxemia, but the A-a giauient will be
N0RNAL). So, piolongeu A-a giauient, something is wiong with the lungs. If A-a
giauient is noimal, theie is something 00TSIBE of the lungs that is causing a iesp
pioblem.
Few things must always be calculateu: anion gap (with electiolytes) anu A-a
giauient foi bloou gases - all you neeu to uo is calc alveolai 02. We can 5';5<;'6,
6?, (^' 3-'A&,46 = u.21 x 71S = 1Su (u.21 is the atmospheiic 02; anu 76u minus the
watei vapoi=71S). So, 1Nf .&4</ 6?, #>27 (given in the bloou gas) A&J&A,A E" f)l
(iesp quotient). So, noimal pC02 = 4u, anu 4u.8=Su anu 1Su-Su = 1uu; so, now that
I have calc the alveolai 02, just subtiact the measuieu aiteiial p02 anu you have the
A-a giauient. This is veiy simple anu gives a lot of info when woiking up hypoxemia.
@@) M##,- D,/#&-'6$-" G&/,'/,0
() Q'/'; :$;"#/0
S uiff types of nasal polyps - NC is an alleigic polyp. Nevei think of a polyp in the
nose of kiu that is alleigic as an alleigic polyp. Alleigic polyps uevelop in auults aftei
a long teim alleigies such as alleigic ihinitis - Example: S yo chilu with nasal polyp
anu iesp uefects, what is the fiist step in management. Sweat test - bc if you have a
polyp in the nose of the kiu, you have cystic fibiosis; it's not an alleigic polyp.
V) +-&'A (/6?.' - take an aspiiin oi NSAIB, have nasal polyps anu of couise have
asthma. They uon't tell you the pt took aspiiin anu that the pt has a polyp. The
aspiiin oi NSAIB is the answei but this is how they will ask the question: SS yo
woman with chionic heauaches oi fibiomyalgia. Pt has some type of chionic pain
synuiome anu will not tell you that the pt is on meuication, anu she uevelops
occasional bouts of asthma - what is the mech of the pt's asthma. Bc she is taking
an NSAIB. What they won't tell you that she has a polyp anu that she is on an NSAIB;
howevei, if a pt is in pain oi has chionic pain, it is safe to assume the pt is on pain
meuication (ie an NSAIB, Notiin oi aspiiin). Nech of asthma fiom pain meuication:
what uo aspiiinNSAIBs block. C0X, theiefoie aiachiuonic aciu cannot foims Pus
but the Lipoxygenase pathway is left open. Some people aie veiy sensitive to this
anu LT C4, B4, anu E4 aie foimeu, which aie potent bionchoconstiictois, leauing to
asthma. It is N0T a type I BPY ixn. It is a chemical meuiateu non type I BPY ixn. [$_
5?-$4&5 #'&4 5'4 ;,'A 6$ '/6?.' ER5 $= '/#&-&4 /,4/&6&J&6")
Anothei assumption you have to make: any well built male on anabolic steioius (ie
football playei, wiestlei) with intiapeiitoneal hemoiihage - piouuce benign livei
cell auenomas which have the tenuency of iuptuiing.
>) X'-"43,'; 5'-5&4$.' H' /Y<'.$</ 5,;; 5'-5&4$.'I
Concept of syneigism: NCC = Smoking; 2
nu
NCC = alcohol
Alcohol anu smoking have a SYNERuISTIC effect which leaus to laiyngeal
caicinoma. Example: lesion in this sliue is a laiyngeal specimen - which of the
following have the gieatest iisk factoi. Answei - ';5$?$; (QG /.$P&43 (this is tiue
foi any squamous cancei fiom the esophagus to the mouth to the laiynx). Smoking =
NCC cancei in mouth, uppei esophagus anu laiynx. Alcohol can uo the same thing, so
if you aie smokei anu alcohol consumei, you can uouble youi iisk. NC symptom
assoc = hoaiseness of the thioat.
Example: epiglottis; what can infect it. B. influenza - what is the symptom.
Inspiiatoiy stiiuei. Example: S month olu chilu uieu with inspiiatoiy stiiuei - ux.
Cioup - paiainfluenza; this is a TRACBEAL inflammation. Wheieas epiglottitis is
elsewheie. Both piouuce uppei aiiway obstiuction.
@@@) D,/#&-'6$-" G&/6-,// ["4A-$.,/0
() !"';&4, .,.E-'4, A] HQ,$4'6'; D,/# A&/6-,// /"4A-$.,I
If something has a lot of pink in it, what is it. Byaline
Key to unueistanuing this uz is massive atelectasis
1) O?'6 &/ '6,;,56'/&/e Collapse of aiiways. Why uiu these aiiway collapse. No
suifactant (aka lecithinphosphotiuyl cholinephosphotiuyl glyceiol - they aie all
suifactant). So, ueficient of suifactant causes atelectasis bc:
>$;;'#/&43 #-,//<-, &4 6?, '&-L'"/ C /<-='5, 6,4/&$4R-'A&</ $= '&-L'") So, on
expiiation, noimally the aiiway will be smallei bc theie is a pos intiathoiacic
piessuie. If you ueciease the iauius, you will inciease the collapsing piessuie in the
aiiways. Theiefoie, on expiiation (in all of us), we have to ueciease suiface tension
(which is what suifactant uoes) - by uoing this, it keeps the aiiways open on
expiiation, pieventing atelectasis.
7) +?-,, 5'</,/ $= DG[0
a. Piematuiity: suifactant begins syn eaily, but it peaks at S2-SS
week, so if you aie boin piematuiely, you will not have enough
suifactant, anu baby will uevelop incieaseu iisk of ueveloping RBS.
Sometimes mothei has no choice anu must uelivei baby, oi else it
will uie, anu theie is something you can uo to the mom so the baby
has moie suifactant: give mothei glucocoiticoius bc they stimulate
suifactant synthesis. Example: what can you uo to inciease
suifactant (but glucocoiticoius wasn't one of the answei choices) -
thyioxine (thyioiu hoimone) (as uoes piolactin); uoes that mean
you give thyioxine b4 ueliveiing the baby. No, will give mom anu
baby hypeithyioiuism.
b. Biabetes: gestational uiabetes = woman who wasn't piegnant,
becomes piegnant, anu then obtains glucose intoleiance aftei
ueliveiy - so if a uiabetic gets piegnant, this is not calleu gestational
uiabetes, but a uiabetic that got piegnant. Its imp that a woman in
piegnancy has goou glucose contiol bc if she is hypeiglycemic,
baby will be, too. Bc baby is hypeiglycemic, it will stimulate insulin
synthesis, anu insulin has a negative effect on suifactant syn anu
will ueciease its synthesis.
c. C section - bc the baby is not ueliveieu vaginally, theie is no
stiess. Bc the baby has not been stiesseu, the ACTB anu coitisol
aie not ieleaseu, anu suifactant is not maue. Wheieas a chilu that is
ueliveieu vaginally has a lot of stiess anu theiefoie a lot of ACTB
anu coitisol is being ieleaseu, which stimulates suifactant ielease.
So, C section pieuisposes to RBS.
u. So, these aie the thiee main causes (piematuiity, uiabetes, anu C
section).
,) 9) >$.#;&5'6&$4/ '4A '//$5&'6,A 5$4A&6&$4/0
a. Example: why aie the babies of pooi glycemic contiol big (maciosomial). The
baby's insulin is incieaseu to keep the glucose uown. Insulin will inciease stoiage of
tiiglyceiiue in auipose (it incieases fat stoiage). Wheie is most of the auipose
locateu. Centially. So, one of the ieasons why they have maciosomia is bc insulin
stimulates synthesis of Tu anu ueposition of fat. Also, insulin incieases uptake of aa's
in muscle (like giowth hoimone). So, it will inciease muscle mass. So, 6?, -,'/$4
=$- .'5-$/$.&' &/ &45-,'/,A 'A&#$/, '4A .</5;, .'//_ E$6? A<, 6$ &4/<;&4)
This also explains why they get hypoglycemia when they aie boin. The mothei's
hypeiglycemia is coming into the baby, causing the baby to ielease insulin; the
moment insulin is maue anu the coiu is cut, anu no moie inciease in glucose, glucose
goes uown, anu leaus to hypoglycemia.
b. Supeioxiue fiee iauical uamage seen in ietinopathy of piematuiity anu blinuness
anu bionchopulmonaiy uysplasia.
c. Why uo babies with RBS commonly have PBA. Bc they have hypoxemia. When a
noimal baby takes a bieath, it staits the piocess of functional closuie of the uuctus.
Bowevei, with hypoxemia aftei they aie boin, it iemains open, anu they have a
machineiy muimui.
u. Byaline membianes aie uue to uegeneiation of type II pneumocytes anu leakage
of fibiinogen, anu it congeals to foim the membiane. So, they will give a classic
histoiy foi RBS, anu then will ask foi the pathogenesis of hypoxemia in the baby.
This is a massive ventilation uefect bc eveiything is collapsing. This is a SB0NT
pioblem, which leaus to a massive inteipulmonaiy shunt. Rx=PEEP theiapy -
positive enu exp piessuie bc these aiiways aie collapseu anu you neeu to get 02
into them anu suifactant. So, give 02 anu at the enu of expiiation, pump in piessuie,
which keeps aiiways open on expiiation, so you can keep 02 in them.
Example: pic with type II pneumocyte (with lamellai bouies - look like onion, anu
hypeiplastic aiteiioloscleiosis bc they aie concentiically shapeu). These lamellai
bouies contain suifactant. This woulu IB it as a type II pneumocyte. They commonly
give ENs of the lung with an alveolai maciophage. Naciophage has 'junk' in the
cytoplasm. The type II pneumocyte is the iepaii cell of the lung anu synthesizes
suifactant.
V) (A<;6 D,/#&-'6$-" G&/6-,// ["4A-$., H(DG[I
In teims of ARBS, essentially it is the same as RBS in pathophys, but is
NE0TR0PBIL ielateu injuiy. In RBS you'ie not making suifactant bc you aie too
piematuie oi have too much insulin anu just have collapseu alveoli. B0T in ARBS its
bc you have too much inflammation; theie is no inflammation in RBS.

B>> (DG[ C /,#6&5 /?$5P HB>> /,#6&5 /?$5P C Z 5$;& =-$. /,#/&/ =-$. '4
&4AL,;;&43 5'6?,6,-i B>> G@> C /,#6&5 /?$5PI) Example: In the IC0 - if a pt come
in with uyspnea anu its within 24 his of having septic shock, pt has ARBS. If pt is in
septic shock anu within 48 his of aumission anu is bleeuing fiom eveiy oiifice, he has
BIC. [$_ U&-/6 A'" C /,#6&5 /?$5P_ /,5$4A A'" C (DG[_ 6?&-A A'" C G@>)
:'6?$3,4,/&/0 Neutiophils get into the lung in septic shock anu stait uestioying all
the cells of the lung (type I anu II pneumocytes). So suifactant piouuction uecieases
anu iesult is massive atelectasis (collapse). Bowevei, this is neutiophil ielateu (the
neutiophils aie uestioying the type II pneumocyte. The ieason why they get hyaline
membianes in the ARBS is bc the neutiophils have to get in the lungs by going
thiough the pulmonaiy capillaiies, so they put holes in them as they get out of the
blooustieam anu into the lungs (this is why it is calleu leaky capillaiy synuiome). All
the piotein anu fibiinogen get in anu piouuce hyaline membianes. Theiefoie, you
can actually see hyaline membianes in ARBS. So, theie is massive collapse anu the
pathophys is intiapulmonaiy shunting. This is the same in RBS, but ARBS is
neutiophil ielateu, which is a bau piognosis.
@F) :4,<.$6?$-'%
Spontaneous pneumothoiax anu tension pneumothoiax
() [#$46'4,$</ #4,<.$6?$-'%
B>> /#$46'4,$</ C -<#6<-,A /<E#;,<-'; E;,E - have pleuia anu iight
unueineath is a bleb (aii pocket). The bleb (aii pocket) iuptuies causing a hole in
the pleuia, so that pait of the lung collapses. Bc what's keeping it expanueu is neg
intiathoiacic piessuie, which keeps the lungs expanueu. So, if you put a hole in the
pleuia, then the atmospheiic piessuie is not negative, but is the same as the aii you
aie bieathing. So, theie is nothing to holu it open anu theiefoie it collapses. When
paits of the lung collapse, theie aie things that will take up the slack. 0ne of those is
the uiaphiagm. If you collapse pait of the lung, the uiaphiagm will go up on that siue
to take up the open space on that has been left. Not only that, if theie is a collapse on
one siue, the tiachea will go to the siue that theie is space. So, will have 6-'5?,';
A,J&'6&$4 6$ 6?, /&A, $= 6?, 5$;;'#/,_ '4A 6?, A&'#?-'3. &/ <#_ ;,'A&43 6$
/#$46'4,$</ #4,<.$6?$-'%. 0sually seen in tall male - they have blebs that
iuptuie anu leau to spontaneous pneumothoiax. Can also get in scuba uiveis bc
they come up too quickly, which leaus to iuptuie of the blebs.
V) +,4/&$4 #4,<.$6?$-'%
Biff fiom spontaneous pneumothoiax. NC uue to knife injuiies into the lung.
Theie's teai of pleuia (flap), sp when you bieathe in the flap goes up anu on
expiiation it closes. So, the aii stays in the pleuial cavity. So, eveiy time you bieathe,
the flap goes up, aii stays in, anu on expiiation it closes. So, foi eveiy bieath you
take, it keeps incieasing anu the piessuie in the lung. The lung hasn't collapseu yet.
+?, &45-,'/, &4 #-,//<-, /6'-6/ #</?&43 6?, ;<43 '4A 6?, .,A&'/6&4<. 6$ 6?,
$##$/&6, /&A,. When it pushes it, it compiesses the lung anu it leaus to compiession
atelectasis (it is not ueflateu bc of a hole - theie isn't a hole - it's a teai that when
the aii went in it went up anu it shut on expiiation, anu that pos pleuial piessuie is
pushing eveiything ovei to the opposite siue). This compiession will push on the
SvC, iight vent, anu left atiium on the opposite siue. This will compiomise bloou
ietuin anu bieathing, leauing to a meuical emeigency. So, it's like filling tiie up with
aii, but cannot get out. Aii is filling pleuial cavity anu cannot get out. It keeps
builuing up anu staits pushing eveiything to the opp siue. With a pos intiathoiacic
piessuie, the uiaphiagm will go uown (goes up in spontaneous pneumothoiax).
F) :<;.$4'-" @4=,56&$4
() :4,<.$4&'
1) 7 P&4A/ \ +"#&5'; '4A (6"#&5';
+"#&5'; - wake feeling noimal, then suuuenly uevelop a fevei, piouuctive cough
(6"#&5'; - slow, insiuious onset (feel bau ovei few uays)
7) >$..<4&6" J/) Q$/$5$.&'; H?$/#&6'; '5Y<&-,AI
If you get pneumonia in the 5$..<4&6" anu it's typical, it is Stiep pneumoniae. If
you get pneumonia in the community anu it is atypical, it's mycoplasma pneumoniae.
0iganisms in the hospital (4$/$5$.&';) = E coli, Pseuuomonas, Staph auieus (will
not get stiep pneumoniae in the hospital).
9) :-$A<56&J, 5$<3? &4 +"#&5'; #4,<.$4&'
D,'/$4 =$- #-$A<56&J, 5$<3? &4 6"#&5'; #4,<.$4&'0 ?'J, ,%<A'6, H#</I '4A
/&34/ $= 5$4/$;&A'6&$4 &4 6?, ;<43 - Sliue: yellow aieas with micioabcesses which
aie consoliuation in the lung. Ie lobai pneumonia = see consoliuation in lung, within
alveoli, causing consoliuation. Theiefoie, with typical, see consoliuation anu pus in
the lung. Physical ux'tic tools of lung consoliuation: uecieaseu peicussion, incieaseu
TvF (when the peison talks, feel vibiations in chest - if have consoliuation in ie the
uppei left lobe, will have incieaseu TvF bc it is a consoliuation, compaieu to the
othei siue - so, &45-,'/,A +FT &4A&5'6,/ 5$4/$;&A'6&$4), having an "E to
A" (egophony) sign (pt says E anu you heai A), whispeieu pectoiiloquy (pt whispeis
"1, 2, S" anu I will heai it veiy louu with the stethoscope). Theiefoie, A,5-,'/,A
#,-5<//&$4_ &45-,'/,A +FT_ ,3$#?$4"_ '4A #,56$-&;$Y<" C 5$4/$;&A'6&$4)
What if theie is a pleuial effusion oveilying the lung. 0nly thing you woulu have is
uecieaseu peicussion (this sepaiates pleuial effusion fiom pneumonia).
K) (6"#&5'; #4,<.$4&'/
+?," A$ 4$6 ?'J, ' ?&3? 6,.# '4A A$ 4$6 ?'J, #-$A<56&J, 5$<3? ER5 6?," '-,
&46,-/6&6&'; #4,<.$4&'/. They have inflammation of the inteistitium - theie is no
exuuate in the alveoli - which is why you aie not coughing up a lot, anu theiefoie uo
not have signs of consoliuation. So, will not have inciease TvF, "E to A", with an
atypical. Atypical pneumonia has an insiuious onset, ielatively nonpiouuctive cough,
no signs of consoliuation.
B>> 6"#&5'; #4,<.$4&' C /6-,# #4,<.$4&', HP4$L 6?, #&5I \ 3-'. cyd
A&#;$5$55</ H'P' A&#;$5$55</I \ D% C :>Q W
B>> '6"#&5'; #4,<.$4&' C ."5$#;'/.' #4,<.$4&',i 7
4A
B>> C >?;'."A&'
#4,<.$4&',i which aie all inteistitial pneumonias.
Bionchopneumonia: NC uue to stiep pneumonia, anu community acquiieu. Lobai
pneumonia. Sliue: lobai consoliuation on chest x-iay - stiep. Pneumonia.
'I F&-'; #4,<.$4&'/
1I D?&4$J&-</ = NCC common colu; they aie aciu labile - meaning that it won't
leau to gastioenteiitis in the stomach bc is uestioyeu by the aciu in the stomach.
Nevei will have a vaccine bc 1uu seiotype.
7I D[F - NCC bionchiolitis - whenevei you inflame small aiiways, its leaus to
wheezing. This is a /.';; '&-L'" A] '4A E-$45?&$;&6&/ &/ B> A<, 6$ D[F '4A
#4,<.$4&'. So, #4,<.$4&' '4A E-$45?&$;&6&/ &/ B> A<, 6$ D[F &4 5?&;A-,4.
9I @4U;<,4]' - uiift anu shift - have hemagglutinins, which help attach the viius to
the mucosa. Bave neuiaminiuase boie a hole thiough the mucosa. (46&3,4&5 A-&=6 C
.&4$- 5?'43,R.<684 in eithei hemagglutinins oi neuiaminiuase; uo not neeu a new
vaccine; '46&3,4&5 /?&=6C .'u$- 5?'43,R.<684 in eithei hemagglutinins oi
neuiaminiuase neeu a vaccine. +?, J'55&4, &/ '3'&4/6 ( (3)
EI V'56,-&'; #4,<.$4&'/
1I >?;'."A&' #/&66'5$/&/ - fiom biius (ie paiiots, tuikeys).
7I >?;'."A&' 6-'5?$.'6&/ - a little kiu was boin anu a week latei he was
wheezing (big time), pneumonia, incieaseu AP uiametei, tympanic peicussion
sounus, no fevei, eyes aie ciusty (both siues), weiiu cough - /6'55'6$ 5$<3? H/?$-6
5$<3?/I) !, 3$6 &6 =-$. ?&/ .$.8/ &4=,56,A 5,-J&%) HB>> 5$4u<456&J&6&/ &4 7
4A

L,,P C >?;'."A&' 6-'5?$.'6&/I) HB> $J,-';; $= 5$4u<456&J&6&/ &/ &4U;'..'6&$4
$= ,-"6?-$."5&4 A-$#/I)
5I !$/#&6';^'5Y<&-,A 3-'.^4,3'6&J, #4,<.$4&'/
1I :/,<A$.$4'/ - watei loving bacteiia, theiefoie see in pt in IC0 when on a
RESPIRAT0R. pt watei unit with gieen piouuctive cough with.
7I S;,E/&,;;' - famous in the alcoholic; howevei, alcoholic can also get stiep
pneumonia. So, how will you know stiep vs. Klebsiella. Alcoholic with high spiking
feveis, piouuctive cough of N0C0IB appeaiing sputum - the capsule of Klebsiella is
veiy thick. Lives in the uppei lobes anu can cavitate, theiefoie can confuse with TB.
9I X,3&$4,;;' - atypical cough, nonpiouuctive cough, veiy sick can kill you, fiom
watei cooleis (watei loving bacteiia), seen in mists in gioceiies oi at iestauiants.
Example: classic atypical pneumonia, then pt hau hyponatiemia - this is Legionella.
Legionella just uoesn't affect the lungs, also affects the othei oigans such as livei uz,
&46,-/6&'; 4,#?-&6&/ anu knocks off the juxtaglomeilui cells, anu kills the ienin
levels, low aluosteione anu theiefoie lose salt in the uiine, ;,'A/ 6$ ?"#$4'6-,.&'
(low ienin levels with low aluosteione). Rx = eiythiomycin
Auuio File 24: Respiiatoiy 2
V) T<43'; @4=,56&$4/
+?, 6L$ /"/6,.&5 =<43</ '-, >'4A&A' '4A !&/6$
1) >'4A&A' - seen in inuwelling catheteis (usually those in the subclavian). Anu get
Canuiua sepsis
7) !&/6$#;'/.$/&/ = B&AL,/6 (0hioTennessee valley) caiiieu by uung of stailings
anu bats - often seen in cave exploieis, oi spelunkeis. They uevelop non-piouuctive
cough. Bisto is the only systemic fungus that has yeasts phagocytoseu by alveolai
maciophages.
9) >-"#6$5$55</ = :&3,$4/- looks like mickey mouse - yeast foims aie naiiow
baseu buus. Example: NY exec with pigeons ioosting in aii conuitionei anu
uevelopeu non piouuctive cough. Example: paintei uevelopeu iesp infection
woikeu on Biooklyn biiuge with pigeons, how uo you tieat. (.#?$6,-&5&4 V.
K) V;'/6$."5$/&/ = SE 0SA = skin anu lung infections; bioau baseu buu
N) >$55&A&$&A$."5$/&/: SW 0SA (new Nexico, Aiizona, southein Cal. =
cocciuiomycose - has spheiule enuospoies (know the pic). Example: in LA
eaithquake, a # of people hau nonpiouuctive cough-the aithiospoie (the infectious
foim) is in uust. With the eaithquake, uust comes up, bieathe it in. Example: man
that is an Inuian aitifact exploiei in the sonaian ueseit, which is in Aiizona, anu is a
CAvE exploiei that uevelopeu nonpiouuctive cough - this is >2>>@2Bb>2[@[ (not
Bisto bc not the Niuwest).
`) (/#,-3&;;</ - S uiffeient manifestationsuz's:
1) loves to inhabit abanuoneu TB fungus cavities - =<43</ E';; (aspeigilloma, a
veiy common cause of massive hemoptysis). Example: left uppei lobe cavitaiy lesion
anu asp love to live in theie = fungus ball
2) vessel invauei; theiefoie will invaue the vessels in lung, leauing to 6?-$.E$/&/
'4A &4='-56&$4
S) alleigies the molu, leauing to extiinsic '/6?.' anu type I BPY
So, thiee manifestations: fungus ball, invasive vasculai uz piouucing hemoiihagic
infaictions of the lung, anu asthma. Example: pic of coiona - component of
Aspeigillus (looks like a ciown) - septate is veiy chaiacteiistic (mucoimycosis is
nonseptate anu has wiue angles, while Aspeigillus has naiiow angles in its buuuing
anu coiona's).
h) :>: H:4,<.$5"/6&6&/ 5'-&4&& #4,<.$4&'
Fungus (useu to be a piotozoa) - bc moie things in the cell wall that look like a
fungus. It's associateu with BIv, NC AIBs uefining lesion (as soon as the helpei T cell
ct is 2uu, it usually shows up). 0seu to be NCC ueath in AIBs pt, but now has gone
uown, bc as soon as youi CB4 ct is 2uu, ui. will put pt on piophylactic theiapy with
TNP-SNX.
When taking +B:^[Bg '4A #-$6,56&43 '3'&4/6 :>:_ woulu othei oiganism is the
pt piotecteu fiom. +$%$#;'/.$/&/. (so, you get 2 foi 1). NCC space occupying
lesion within the biain in a pt with AIBs= Toxoplasmosis
[,,4 L&6? /&;J,- /6'&4: cysts of PCP can be seen - look like ping pong balls, seen in
alveoli, leauing to alveolai infiltiate, leauing to uyspnea, tachypnea, foamy bubbly
infiltiate, on chest x-iay, looks all white out bc of the involvement of the lung -
howevei, not only seen in lungs, can be seen in any pait of the bouy- also seen in
lymph noues of BIv "+".
0thei oiganisms that aie only seen with silvei stain: baitenella henselae (bacillaiy
angiomatosis), Legionella (not visualizeu with giam stain, theiefoie use butuly...
silvei stain)
l) +V
0iganism in uppei lobe of lungs - (play ouus) - TB - see cavitaiy lesion, which is
ieactivation TB (not piimaiy). Piimaiy TB is the lowei pait of the uppei lobe oi the
uppei pait of the lowei lobe anu close to the pleuia (kinu of in the miuule of the
lobe). Piimaiy TB has a uhon focus anu a uhon complex. Nost people iecovei; when
pt is immunocompiomiseu, it leaus to ieactivation anu goes into the apex anu
piouuces a cavitaiy lesion. +?,-, &/ 4$ W?$4 =$5</ $- 5$.#;,% &4 -,'56&J'6&$4 +V_
$4;" #-&.'-" +V)
26?,- 6?&43/ 6?'6 5'J&6'6, &4 <##,- ;$E,/0
Which systemic fungus is the "TB" of the lungs. Bistoplasmosis
Which cancei can cavitate in the lung. Squamous Cell caicinoma of the lung
Which bacteiia (that has a big mucous wall aiounu it) can also piouuce cavitations
in the uppei lobe. Klebsiella pneumoniae.
What is aciu fast stain staining. Nycolic acius.
So, just bc something is cavitating the uppei lobe, it is not necessaiily TB.
>) T$-,&34 V$A&,/
If you aie /6'4A&43 $- /&66&43 <#, foieign bouies will go to #$/6,-$E'/'; /,3.,46
$= 6?, -&3?6 ;$L,- ;$E,. This is the most posteiioi segment of the iight lowei lobe.
If you aie lying uown (NC way to aspiiate things), foieign bouy will go to supeiioi
segment of the iight lowei lobe.
If you aie lying on the iight siue, can go to 2 places - 1) miuule lobe 2) posteiioi
segment of iight uppei lobe (this is the 0NLY one that is in the uppei lobe.
If you aie lying uown on youi left, anu aspiiate, it will go to the lingula.
Summaiy:
[&66&43R/6'4A&43 C #$/6,-$E'/'; /,3.,46 $= -&3?6 ;$L,- ;$E,
V'5P0 /<#,-&$- /,3.,46 $= -&3?6 ;$L,- ;$E,
D&3?60 .&AA;, $- /<# /,3.,46 $= -&3?6 ;$L,- ;$E,
X,=60 ;&43<;'
G) (E/5,//
B>> 'E/5,// C '/#&-'6&$4 $= $-$#?'-"43,'; .'6,-&';
Seen commonly in stieet people that uo not have goou uentition, may be uiunk anu
fall anu oiophaiyngeal mateiial will be aspiiateu. Aspiiate consists of aeiobes anu
anaeiobes, leauing to putiiustanch smell. The aspiiate is a mixtuie of all these
oiganisms: Nixeu aeiobes anu anaeiobes, fusobacteiium, bacteioiues. Can get
absecces in the lung fiom pneumonia: staph auieus, Klebsiella (howevei, NCC is
aspiiation), see fluiu cavities in lung on x-iay.
F@) :<;.$4'-" F'/5<;'- G&/,'/,0
() :<;.$4'-" Z.E$;</
2 types of emboli - tiny ones that piouuce weuge shapeu hemoiihagic emboli oi
can chip off laige ones. Wheie uo most Pul emboli embolize fiom. NC SITE foi
thiombosis is the ueep veins of the lowei leg. This is N0T the most common site foi
embolization; it is the femoial vein (this is the NC site foi embolization). Nakes
sense bc venous clots piopagate towaiu the heait (ueep veins to the femoial vein,
anu the femoial vein is a laigei vessel, theiefoie it is moie likely to chip off). So, the
femoial vein is the NC site foi embolization to the lung. The ueep veins aie the NC
site wheie ueep venous thiombosis begins. (when it get to the femoial vein, it is
uangeious foi embolization). So, small ones piouuces hemoiihagic infaict that is
only if you have an unueilying lung uz. If I have a small embolus, piob won't infaict
bc uon't have abnoimal lungs. Bowevei, if you have pieexisting lung uz you will
infaict. 8S% of the time embolus will not piouuce infaict. Bowevei, in the 1S%,
most of the pts with infaicts have pieexisting lung uz (ie they aie smokeis). The
othei type of embolus is a sauule embolus (it is huge) anu blocks off the oiifices of
the pulmonaiy vessels anu pulmonaiy aiteiies. If you knock off at least S out of the S
oiifices, you aie ueau in a milliseconu, so theie is no infaiction bc you uon't have
time to infaict. It piouuces acute iight heait stiain anu immeuiate ueath. [5-,,4&43
6,/6 $= 5?$&5,0 F,46&;'6&$4 #,-=</&$4 /5'4 \ L&;; ?'J, J,46&;'6&$4_ 4$ #,-=</&$4i
5$4U&-.'6$-" 6,/6 &/ #<;.$4'-" '43&$3-'.)
F@@) D,/6-&56&J, :<;.$4'-" G&/,'/,
D,/6-&56&J, - something is iestiicting it fiom filling. Example: iestiicteu filling of
the heait = iestiictive caiuiomyopathy. 0i iestiiction in filling up of the lungs with
aii. Bave 2 teims: 5$.#;&'45, HU&;;&43 6,-._ &4/#&-'6&$4 6,-.I '4A ,;'/6&5&6"
H-,5$&;_ ,%#&-'6&$4 6,-.Ii
Foi iestiictive lung uz, pictuie a hot iubbei bottle foi iestiictive lung uz. The hot
iubbei bottle is uifficult to 'blow up', theiefoie 5$.#;&'45, &/ A,5-,'/,A anu it is
haiu to fill the lung up with aii. So, what's pieventing it fiom blowing up. Fibiosis
(inteistial fibiosis, NC'ly). If you get the hot watei iubbei bottle filleu with aii anu
let the aii out, what happens to the elasticity. Incieases. So, compliance is uecieaseu
anu cannot fill it up, but once you uo fill the lung up, it comes out quickly (,;'/6&5&6"
&45-,'/,/).
Example: pt with saicoiu - uiff to fill lungs, but get it out fast (uue to fibiosis). So, all
TLC, Rv, Tv (all lung capacities have all equally uecieaseu). FEv1FvC on
spiiometei - take a ueep bieath (ie pt with saicoiu) - FEv1 (amount you get out in
one sec - noimally it is 4 liteis) is uecieaseu, FvC (total that got out aftei ueep
inspiiation) is uecieaseu (bc incieaseu elasticity) - this is the same as FEv1, so the
iatio is often 1. Noimally, the FvC is S liteis, anu the FEv1 is noimally 4 liteis - so,
the noimal FEv1FvC iatio is 4S =8u%. Bc the elasticity is incieaseu, the FvC is
the same as FEv1, anu theiefoie the -'6&$ &/ &45-,'/,A to 1 insteau of u.8.
Z%'.#;,/ $= -,/6-&56&J, ;<43 A]8/0
1) :4,<.$5$4&$/&/ - aiiboineuustboine uz's - famous in big cities (LA, NY). Cole
woikei pneumoconiosis - esp. in west viiginiaPenn, have an anthiocotic pigment
that causes a fibious ixn in the lung, leauing to iestiictive lung uz. Bave an incieaseu
inciuence of TB, but not cancei.
7) [&;&5$/&/ - Sanublasteis get giaffiti off things, oi woik in founuiies anu ueal with
iocks (ie quaitz), anu bieak them uown, anu bieathe in uust, leauing to silicoses).
Bave nouules in the lung that aie haiu has iock (liteially) bc theie is quaitz in them
anu it looks like metastatic uz in the lung (silica uioxiue - which is sanu in the lung) -
again, incieaseu of TB, not cancei. If pt happens to have iheumatoiu aithiitis, anu
also has one of these pneumoconiosis (ie Cole woikeis), have a potential foi a
synuiome, which is calleu caplan synuiome. >'#;'4 /"4A-$., consists of
iheumatoiu nouules in the lung (same as extensoi suifaces in the aim). Rheumatoiu
aithiitis commonly involves the lung with fibiosis. Anu iheumatoiu nouules can
foim in the lung. +?, 5$.E$ $= -?,<.'6$&A '-6?-&6&/ H-?,<.'6$&A 4$A<;,/I &4
6?, ;<43_ #;</ #4,<.$5$4&$/&/ H/&;&5$/&/R'/E,/6$/&/R>$;, L$-P,-/I C 5'#;'4
/"4A-$.,)
9) (/E,/6$/ - asbestos fibeis look like uumbbells (theiefoie ez to iecognize).
These aie calleu feiiuginous bouies. Asbestos fibeis coateu with iion, theiefoie can
call them eithei asbestos bouies oi feiiuginous bouies. NC pulmonaiy lesion assoc
with asbestos is not cancei - it is a fibious plaque with a pleuia, which is b9 (not a
piecuisoi foi mesothelioma). B> 5'45,- '//$5 L&6? '/E,/6$/ C #-&.'-" ;<43
5'45,-_ 7
4A
B>> C .,/$6?,;&$.'_ L?&5? &/ ' .';&34'45" $= 6?, /,-$/'; ;&4&43 $=
6?, ;<43/) If you aie a smokei anu have asbestos exposuie, you have an incieaseu
chance of getting piimaiy lung cancei. This is a goou example of syneigism (othei
causes of lung cancei (SCC) incluue smoking, alcohol). Asbestos + smokei = will get
cancei. Theie is no incieaseu inciuence of mesothelioma with smoking (not
syneigistic). Example: Roofei foi 2S yeais, nonsmokei (uo tell you, but you hau to
know that 2S yeais ago, all the ioofing mateiial hau asbestos in it; in othei paits of
NY, many builuings weie toin uown, anu theie was asbestos in the ioofing of those
builuings, which was inhaleu by many people, anu 1u-Su yeais latei they uevelopeu
piimaiy lung cancei oi anothei complication of asbestosis). What woulu he most
likely get. Piimaiy lung cancei (piimaiy pleuial plaque was not theie). If he was a
smokei. Piimaiy lung cancei. Nesothelioma takes 2S-Su yeais to uevelop. Lung
canceis take about 1u yeais to uevelop. Lung canceis aie moie common, anu you uie
eailiei. What is the main cause of asbestos exposuie. Roofeis oi people woiking in a
naval shipyaiu (bc all the pipes in the ship aie insulateu with asbestos), also in
biake lining of cais anu heaugeai.
K) ['-5$&A$/&/ C7
4A
B>> -,/6-&56&J, ;<43 A])
Example: classic x-iay - lymph noues (hilai lymph noues aie big), haziness seen,
too, which is inteistial fibiosis. ['-5$&A &/ ' 3-'4<;$.'6$</ A] that has N0
ielationship to infection (5'</, C <4P4$L4). >'</,/ ' 4$45'/,'6&43 3-'4<;$.'
(not caseating bc no ielationship to TB anu systemic fungal infections). The lungs
aie ALWAYS involveu (lungs aie the piimaiy taiget oigan), anu moie common in
blacks. Example: black peison, SS yo, with uyspnea, see hilai noues on x-iay, uviitis
(bluiiy vision - this is inflammation of the uveal tiact - this uz always affects
something in the face, anu the face the 2
nu
NC site a lesion will occui with this uz, can
also involve salivaiy glanus oi laciimal glanus - something in the heauneckface
aiea (behinu the lungs). This uz is a ux of exclusion, theiefoie must iule out anything
that causes gianuloma (TB, Bisto), along with the coiiect physical piesentation =
Saicoiuosis. D% C /6,-$&A/. ACE enzymes aie veiy high in these pts bc gianulomas
in kiuney; ?"#,-5';5,.&' - maciophages (epitheloiu cells) make 1-alpha-
hyuioxylase. If they aie making 1-alpha-hyuioxylase, what is the mech of
hypeicalcemia. Bypeivitaminosis B. you aie seconu hyuioxylation moie vit B anu
theiefoie have excess vit B, anu vit B piomotes ieabsoiption of calcium anu
phosphoius, leauing to hypeicalcemia. +?&/ &/ 6?, B> 4$4&4=,56&$</ 5'</, $=
3-'4<;$.'6$</ ?,#'6&6&/ H+V &/ 6?, B>> $= &4=,56&$</ ?,#'6&6&/_ 7
4A
B> C
#4,<.$5$4&$/&/I)
N) !"#,-/,4/&6&J&6" #4,<.$4&6&/ H='-.,-8/ ;<43_ /&;$U&;;,-/ A]_ E"/&4$/&/)
These aie iestiictive lung uz's. Bon't confuse faimei's lung anu silofilleis uz - they
aie B0TB seen in faimeis. So, iemembei one, the othei is the othei!
[&;$U&;;,-/ A] \ put things in silos, which is a closeu space, anu feimentation of gas
occuis, the gas is nitiogen uioxiue - Example: faimei went into a ioom in his bain
anu suuuenly uevelopeu wheezing anu uyspnea, why. Bc he took in nitiogen
uioxiue, which is a feimenting pioblem. (silo can exploue bc gas fiom
feimentation).
T'-.,-8/ ;<43 \ 6?,-.$#?&;&5 '56&4$."5,/ H' .$;AI)
Example: on tiactoi, uust being blown up in the aii anu theimophilic actinomyces
(which is a molu) is inhaleu; leauing to hypeisensitivity anu BPY pneumonitis anu
they enu up with a iestiictive lung uz.
V"/&4$/&/ - woikei in textile inuustiy, anu they get uyspnea. These aie the BPY
anu iestiictive lung uz's.
W$$A#'/6<-, /"4A-$.,
Begins in the lungs with a iestiictive lung uz (with coughing up bloou -
hemoptysis), anu enus up veiy shoitly with ienal uz (theiefoie, it staits in the lung
anu enus in the kiuneys). This is a iestiictive lung uz.
F@@@) 2E/6-<56&J, ;<43 G]
() G,';/ L&6? 5$.#;&'45,R,;'/6&5&6" 5$45,#6
@4 $E/6-<56&J, ;<43 A]_ 4$ #-$E 3,66&43 '&- &4_ E<6 ?'J, ' #-$E;,. &4 3,66&43
6?, '&- $<6) Why uon't you have a pioblem getting it in. Bc the elastic tissue
suppoit is uestioyeu, so it is veiy ez to fill up the lungs. Bowevei, bc the elastic
tissue suppoit is uestioyeu, it is veiy uifficult haiu to get it out bc it collapses on
expiiation, so you can get aii in, but cannot get aii out. In a pt with obstiuctive aii uz,
they bieathe in with no pioblem, but have tiouble getting it out. So, something is left
ovei in the lung - cannot get all the aii out, theiefoie the iesiuual volume is
incieaseu (whenevei something is left ovei, it is calleu the 'iesiuual'). So, if you
cannot get aii out, then the iesiuual volume incieases, which means that the TLC will
inciease, which means that the uiaphiagm will go uown bc as the lungs aie ovei
inflateu, anu the AP uiametei will go out. So, with obstiuctive lung uz, you have
incieaseu AP uiametei anu uiaphiagms go uown (uepiesseu). Theie is only a ceitain
amount of expansion youi chest can go. Eventually, the chest staits to compiess
othei volumes (as you tiap aii anu iesiuual volumes go up). So, tiual volume staits
uecieasing, vital capacity goes uown bc the iesiuual vol is incieasing anu you aie
compiessing othei volumes. [$_ +X> '4A DF &45-,'/,/_ ,J,-"6?&43 ,;/,
A,5-,'/,/) 0n spiiometei, FEv1 is veiy low (usually 1 - noimally it is 4). In othei
woius, you have a bettei FEv1 with iestiictive lung uz bc you can get aii in. The
FvC (total amt they can get out) is S liteis (vs. S liteis). O?,4 "$< A$ ' -'6&$ $=
TZF1RTF>_ 6?, -'6&$ ?'/ A,5-,'/,A_ ?,45, A&/6&43<&/?&43 -,/6-&56&J, =-$.
$E/6-<56&J, A]8/)
>;'//&5 >2:G %^-'": haiu to see the heait, with uepiesseu uiaphiagms (at level of
umbilicus), incieaseu AP uiametei - ux. Classic obstiuctive uz x-iay - piob getting
aii out, theiefoie the uiaphiagm is uown anu AP uiametei is incieaseu. Example: S
month olu can have this same finuing uue to RSv
Example: Newboin with Chlamyuia tiachomatis pneumonia bc he is tiapping aii.
V) +?,-, '-, K 6"#, $= $E/6-<56&J, ;<43 A]8/0 5?-$4&5 E-$45?&6&/_
E-$45?&,56'/&/_ ,.#?"/,.'_ '/6?.'. The ones associateu with smoking aie
bionchitis anu emphysema.
1) >?-$4&5 V-$45?&6&/
:<-,;" ' 5;&4&5'; A% C :6 ?'/ #-$A<56&J, 5$<3? =$- 9 .$46?/ $<6 $= 6?, ",'- =$-
7 5$4/,5<6&J, ",'-/) Wheie is the uz. Teiminal bionchioles (you have main stem
bionchus, segmental bionchi, teiminal bionchioles, iesp bionchioles, alveolai uucts,
alveoli). As soon as you hit the teiminal bionchioles, these aie small aiiway; it is all
tuibulent aii up to teiminal bionchioles. Aftei that, it is paiallel bianching of the
aiiways. The tuibulent aii hits the teiminal bionchioles anu then hits a massive cioss
sectional aiiway wheie you can go uiff path's bc paiallel bianching of the small
aiiways. So, the aiiflow changes fiom tuibulent to laminai aiiflow. By the time you
hit the iesp unit, it is not moving the aii. B$/6 /.';; '&-L'" A]8/ '-, &4U;'..'6&$4
$= 6?, 6,-.&4'; E-$45?&$;,/_ ;,'A/ 6$ L?,,],) Teiminal bionchioles aie the site of
chionic bionchitis. This is the same aiea as asthma anu bionchiolitis. Noie piox to
the teiminal bionchioles, in bionchitis, you will get a mucus glanu hypeiplasia, anu a
lot of ciap is coming up (that's the piouuctive pait). The actual aiea of obstiuction is
the teiminal bionchiole. Bave goblet cell metaplasia anu mucous plugs. Think about
having one teiminal bionchiole anu one mucous plug - this is affecting a majoi cioss
sectional aiea of lung bc all the paiallel bianches that ueiive fiom heie will not have
C02 in them, anu they aie tiying to get aii past the mucous plug, but cannot. So,
6?,-, &/ ' !MWZ J,46^#,-=</&$4 .&/.'65?. This is why they aie 5';;,A E;<,
E$'6,-/ \ 6?," '-, 5"'4$6&5. They have mucous plugs in the teiminal bionchioles
anu cannot iiu C02.
7) Z.#?"/,.'
Not in the teiminal bionchioles. It is in the iesp unit (-,/# <4&6 &/ L?,-, 3'/
,%5?'43, $55<-/ - cannot exchange gas in the teiminal bionchioles - aka noniesp
bionchiole); it is the piimaiy place foi expiiatoiy wheeze anu small aiiway uz,
howevei. W'/ ,%5?'43, $55<-/ &4 6?, -,/# E-$45?&$;,_ -,/# ';J,$;'- A<56 '4A
';J,$;&. 0nly neeu to know 7 ,.#?"/,.'/0 5,46-$;$E<;'- '4A #'4'5&4'-.
Emphysema affects gas exchange anu wheie it affects the aiiway is moie uistal,
compaieu to chionic bionchitis (pioximal). So, when you have emphysema with all
the inflammation associateu with it, not only uestioy the iesp unit, but also the
vasculatuie associateu with it. Theiefoie, 6?,-, &/ '4 ,J,4 ;$// $= J,46&;'6&$4 '4A
#,-=</&$4) [$_ L&;; Q2+ ?'J, -,6,46&$4 $= >27 &4 6?,/, #6/) When you have a
pioblem with a mucous plug in the teiminal bionchiole, which is way moie piox anu
a gieat cioss sectional aiea of the lung is affecteu, theie is gonna be a pioblem theie;
howevei when you aie out this fai (in emphysema) anu also uestioying the vessels,
you L&;; 4$6 ?'J, '4 &45-,'/, &4 >27. This is why they aie calleu #&4P #<==,-/, anu
this is why many of them have iesp alkalosis.
'I >,46-$;$E<;'- \ .$/6 '//$5&'6,A L&6? /.$P&43 '4A &4J$;J,A L&6? 6?, <##,-
;$E,/) So, it is an uppei lobe emphysema, anu the piimaiy poition of the iesp unit
that is uestioyeu is the iesp bionchiole (this is the veiy fiist thing that smoke hits).
Neutiophils will uamage it bc all people that smoke have moie neutiophils in theii
lungs, anu smoke is chemotactic foi neutiophils. ALL smokeis have incieaseu
neutiophils in theii lungs. What uoes alpha-1 antitiypsin uo. It's an antielastase (its
only puipose is to uestioy elastases piouuceu by neutiophils - that is its function. If
you aie a smokei, that is uenatuieu. So, you also have an acquiieu alpha-1
antitiypsin uef). Bon't have auequate alpha-1 antitiypsin, anu have too many
neutiophils in the lungs. This is a teiiible combo. This why neutiophils have no
pioblem in uestioying the elastic tissue suppoit of the iespiiatoiy bionchioles. So,
you bieath aii in, which is no pioblem; but you tiy to get it out, anu theie is no elastic
tissue suppoit anu leaus to lung expansion - this is why blebs aie founu - theie aie
big cystic spaces in the lung - it has tiappeu aii in theie bc theie is no elastic tissue,
so when it tiies to get by, it just expanus. This is 5,46-$;$E<;'- ,.#?"/,.' $= 6?,
M::ZD ;$E,/.
EI :'4'5&4'- Z.#?"/,.' (iemembei 'pan' means eveiything - ie in
pancytopenia, ALL the cells uecieaseu). So, panacinai means that the ENTIRE iesp
unit is uecieaseu bc it is associateu with Q2 ';#?' 1 '46&6-"#/&4. This is a genetic
uz - auto iec \ 6?, X@FZD A$,/ 4$6 .'P, &6. So, at a young age, you uevelop
uestiuction of entiie iesp unit of the L0WER lobes, /$ 6?&/ &/ ' X2OZD ;$E,
,.#?"/,.'. So, you can see that the iesp bionchioles aie knockeu out, the alveolai
uucts aie knockeu out, alveoli knockeu out. So, you bieathe in, anu this entiie iesp
unit catches it - this is in the lowei lobes.
Smokeis, which have an acquiieu alpha-1 antitiypsin uef, can get an element of
panacinai emphysema in the lowei lobes, too. So, smokeis can get 2 emphysema's:
centiolobulai emphysema in the uppei lobes (which knocks off the iesp bionchiole)
anu in the lowei lobes, get a panacinai type of pattein. Theiefoie, can get uppei ANB
lowei lobe emphysema, anu 2 uiff types of emphysema.
Auuio File 2S: Respiiatoiy S - uastio 1
9) V-$45?&,56'/&/
Bave bionchiectasis - see bionchi going out to the pleuia (abnoimal). When you
see bionchi going out fuithei than the hilum, this is bionchiectasis.
B,5?0 &4=,56&$4_ A,/6-<56&$4 $= 6?, ,;'/6&5 6&//<, /<##$-6_ A&;'6'6&$4 $= 6?,
'&-L'"/. Segmental bionchi; fill with pus. Example: pt has a piouuctive cough of
"cupfuls" (not just a tablespoon) of pus, bc they aie tiappeu.
a) Causes:
1) NCC bionchiectasis in 0SA = 5"/6&5 U&E-$/&/) If paient with chilu has cystic
fibiosis, will see huge pus coming out of bionchi, a couple times pei uay.
2) NCC bionchiectasis in S
iu
woilu countiies = +V.
S) S'-6'3,4,-8/ /"4A-$., (aka immotile cilia synuiome). 9+2 configuiation
aiiangement with cilia anu miciotubules. The pioblem with immotile cilia synuiome
is an absent uynein aim. The 9 miciotubules on the outsiue have aims that keep
them togethei - these uynein aims aie missing. So, when these aims aie missing, the
cilia cannot move. So, the places with cilia not moving aie affecteu: these places aie
sinuses (why /&4</&6&/ is a pioblem), E-$45?&,56'/&/ (bc theie is cilia -
psueuostiatifieu columnai epithelium is affecteu), males anu females aie &4=,-6&;,
(bc the tail on the speim cannot move - the tail is a mouifieu cilia - they heau is
moving, but the tail is weak. Women aie infeitile; too, bc the fallopian tube neeus
cilia to caiiy the egg uown. 2-3'4/ '-, ;$5'6,A $4 6?, $##$/&6, /&A,
HA,%6-$5'-A&'_ L&6?2M+ 6-'4/#$/&6&$4 $= 3-,'6 J,//,;/I)
K) (/6?.'
Can be extiinsic (type 1 BPY) anu intiinsic: Involves chemicals - people in the
woikplace can get tiiau asthma, which involves people taking NSAIBs Nany people,
ie athletes will get exeitional asthma anu wheeze - ciomolyn Na is the B0C foi these
patients. Colu temps can cause asthma. Type I BPY has nothing to uo with these
causes of asthma. The wheezing is uue to inflammation of the teiminal bionchioles -
it is not uue to smoking, but bc factois like LT C4, B4, E4, Pu's causing inflammation
anu naiiowing of the aiiways.
@g) X<43 >'45,-
() :,-&#?,-';;" ;$5'6,A J/) 5,46-';;" ;$5'6,A
1) >,46-';;" ;$5'6,A H.'&4/6,. E-$45?</I0
Bave the highest association with smoking. Incluue squamous cell caicinoma anu
small cell caicinoma. These aie geneially centially locateu, hence mainstem
bionchus types of locations. Squamous cell aie moie common than small cell
caicinomas.
7) :,-&#?,-';;" ;$5'6,A0
(A,4$5'-5&4$.'/ (the moie common piimaiy lung cancei, moie common than
squamous) aie moie peiipheial than cential. Shifteu to the peiipheiy bc of the
filteis of the cigaiettes. The filteis pieventeu the laige caicinogens fiom passing in,
but the small caicinogens still passeu thiough, anu they aie not tiappeu in the main
stem, but tiappeu in the peiipheiy.
Theie aie at least S oi 4 types of auenocaicinoma. 0ne obviously uoes have a
smoking ielationship, while the otheis uo not. The ones that uo not have a smoking
ielationship incluue bionchiolai alveolai caicinoma, anu laige cell auenocaicinoma
of the lung (scai canceis).
V) >"6$;$3"0 know what squamous cancei looks like with a pap smeai. A lot of
people think that the Papanicolaou stain is only uone foi ceivical caicinoma. This is
not the case. +?&/ &/ ' ='.$</ /6'&4 (pap smeai) </,A =$- ';; 5"6$;$3&5';
/#,5&.,4/ $4 =$- ';; $-3'4/) +?, /6'&4 /6'&48/ P,-'6&4 E-&3?6 -,A) Sliue: (pic) pt
that is a smokei with a centially locateu mass. Showing sputum sample with a
Papanicolaou (pap smeai) stain - has ieu keiatin, which is squamous cell caicinoma.
If this weie a ceivical pap smeai fiom a woman that is 4u yeais of age, this is
squamous cell caicinoma. The keiatin is staining biight ieu! (biight ieu cytoplasm =
keiatin = squamous cell caicinoma). Papanicolaou stains keiatin biight ieu.
Example: small cells that look like lymphocytes - this is /.';; 5,;; 5'-5&4$.'. This
is moie uifficult to ux, bc sometimes uiff to tell the uiffeience fiom lymphocytes.
Sliue shows malignant cells. Small cell caicinoma is the most malignant cancei of the
lung. Rx. Rauiation anu chemo (not suigeiy). +?,/, '-, '<#<6 6<.$-/ L&6?
4,<-$/,5-,6$-" 3-'4<;,/ '4A [^1ff (3 #$/&6&J,) They can make ABB anu ACTB.
A slightly less malignant tumoi with auput oiigin is the E-$45?&$5'-5&4$&A. It is a
low giaue malignancy of the same types of cells that piouuce small cell caicinoma.
So, they can invaue, met, anu piouuce caicinoiu synuiome if they make incieaseu
amount of seiotonin. They uon't have to mets to piouuce caicinoiu synuiome - it
just goes stiaight into the blooustieam. It is veiy uncommon.
>) >'45,-0
NC cancei of lung = mets - ie see many metastatic nouules all ovei lung; if you play
ouus, what is the piimaiy cancei. bieast (which the NC met to the lung, oi in othei
woius, it is the NC cancei of the lung).
[<..'-" $= ;<43 5'45,- &4 6?, ;<430
B> 5'45,- C .,6/
B> #-&.'-" 5'45,- C #-&.'-" 'A,4$5'-5&4$.' $= 6?, ;<43_ =$;;$L,A E"
/Y<'.$</ '4A /.';; 5,;; 5'-5&4$.')
O$-/6 5'45,- HL$-/6 #-$34$/&/I0 /.';; 5,;; 5'-5&4$.')
!$-4,-8/ /"4A-$., - pancoast tumoisupeiioi sulcus tumoi - tumois that aie in
the uppei lobe posteiioily (in post meuiastinum); most of the time is causeu by
squamous caicinoma in that aiea. What's happening heie. Tumoi is locally invauing
into the local pait of the lowei tiunk of the biachial plexus, so can get lowei tiunk
biachial plexus like finuings, anu can also affect the supeiioi ceivical ganglion. This
is in the posteiioi meuiastinum, theiefoie will enu up with Boinei's synuiome; as a
iesult, will enu up P4$5P&43 2TT /".#'6?,6&5 '56&J&6" - #6$/&/ (liu is lowei),
'4?"A-$</ (lack of sweating), .&$/&/ (in sympathetic, which is fight oi flight,
noimally have myuiiasis, which uilates the pupil - with fight oi flight, want as much
light as possible, theiefoie uilating pupil, but this is cut off, leauing to miosis). Bo not
confuse with SvC synuiome; this is just blocking off SvC.
Nyasthenia has to uo with thymoma, which is locateu in the anteiioi meuiastinum.
Exuuate vs. tiansuuate (< S giams, without many cells in it)
NCC pleuial effusion uue to tiansuuate = BF
Exuuate = piotein > S giams, anu has cells in it (ie pneumonia's, pulmonaiy
infaiction)
CHAPTER 9: Gastro
@) G&/,'/,/ $= 6?, B$<6?
() !,-#,/ /&.#;,%i Beipes labialis-(fevei blisteis anu colu soies); piimaiy heipes
is a systemic infection. Bave fevei, viiemia, geneializeu lymphauenopathy, anu goes
away; it stays in the sensoiy ganglia (uoimant in the sensoiy ganglia) - eveiy now
anu then it can come out with stiess, menses, whatevei, anu will foim vesicles.
Recuiient heipes is no longei systemic - theie is no moie fevei, anu no moie
lymphauenopathy. 0thei viius that iemain latent - heipes zostei - iemains latent in
the sensoiy ganglia; can involve the skin, lips, ueimatomes. So, #-&.'-" ?,-#,/ &/
/"/6,.&5_ -,5<--,46 ?,-#,/ &/ 4$6) HQ$ =,J,- C 4$ ;".#?'A,4$#'6?").If we
enioot anu stain, will see inclusion in heipes - it is a multinucleateu cell with
inteinucleai inclusions. Biopsy of a multinucleateu cell fiom a pt with BIv, with
multiple inteinucleai inclusions - heipes esophagitis.
V) !'&-" X,<P$#;'P&'
This is not an AIBs uefining lesion, but IS a pieAIBs type of infection - as is thiush,
shingles. Locateu on the lateial boaiuei of the tongue. Bas nothing to uo with
uysplasia (leukoplakia). It is a iesult of an &4=,56&$4 =-$. ZVF. So, uo not get the
iuea that it is a pieneoplastic lesion. Stait seeing this befoie the helpei T cell count
get to 2uu. Rx - Acyclovii
>) +?-</? H$-'; 5'4A&A&'/&/I
In an auult, theiefoie can assume that it is in an immunocompiomiseu patient,
wheie theie is a uefect in cellulai immunity. In kius (newboins), they can get it fiom
the mom on the way out. Bowevei, it is not a sign of immunocompiomise.
So, auult = IC'u
G) Z%<A'6&J, 6$4/&;;&6&/
9fn 5?'45, 6?'6 &6 &/ 3-$<# ( E,6' ?,.$;"6&5 /6-,#. hfn 5?'45, 6?'6 &6 &/ '
J&-</i 'A,4$J&-</_ ZVF) So, when you see exuuative tonsillitis, cannot assume it is
bacteiia anu immeuiately give PCN. Bow uo you piove it is gioup A stiep. Latex
agglutination test. So, most pus tonsils aie not bacteiia. Example: It is gioup A
stiep, anu S weeks latei, has bilateial iales, pansystolic muimui apex iauiating into
the axilla, polyaithiitis - ux. Rheumatic fevei. When you uo a bloou cultuie - what
woulu you finu. Nothing - it's not an infective enuocaiuitis.
Z) X,<P$#;'P&'
White lesion, plaque like, tiy to sciap off, but won't come off = clinical ux of
leukoplakia - what is the fiist step in management. Bx
Tiue in the vulvapenis aiea - white oi ieuuish-white plaque like lesion that uoes
not sciape off - fiist step in management. Bx. Why. Rule out uysplasia anuoi
invasive cancei.
T) >'45,- $= 6?, .$<6?
NCC squamous uysplasia anu cancei = smoking
2
nu
NCC = alcohol
If you uo both, you inciease the iisk of both.
Invasive squamous cancei = coloi change
X$L,- ;&# 5'45,-e [Y<'.$</ 5,;; 5'-5&4$.'
M##,- ;&#e V'/'; 5,;; 5'-5&4$.'
veiacious caicinoma - fiom chewing tobacco (squamous caicinoma); also has a
BPv viius associateu with it.
W) Bypeipigmentation - ux. (AA&/$48/
Auuison's: uiffuse pigmentation, low coitisol levels, incieaseu ACTB (ACTB has
melanocytes stimulating piopeities); veiy fiist place you see hypeipigmentation is in
the Buccal mucosa.
!) :,<6]^t,3?,-/
Blotchy (not uiffuse) aieas of hypeipigmentation. :$;"#/ &4 /.';; &46,/6&4,) This
is one of the exceptions to iule foi polyps in the small intestine. Nost polyps in the uI
locateu in the sigmoiu colon; howevei, polyps of Peutz }egheis aie locateu in the
small intestine, anu they aie hamaitomas, theiefoie they aie not neoplastic, anu
theii ability to change to cancei is ZER0.
@@) G&/,'/,/ $= 6?, [';&J'-" W;'4A/
:;,$.$-#?&5 'A,4$.' 'P' B<.#/ R .&%,A 6<.$- (- N0T a teiatoma, but a
mixeu tumoi - it has two uiff types of tissues, same cell layei). It is the NC salivaiy
glanu tumoi oveiall, anu is in the NC location - the paiotiu.
B<.#/ - paiamxyoviius, inciease in amylase; is the inciuence of oichitis high. No;
uoes it cause infeitility. No, why. Bc its unilateial - if it weie bilateial then it woulu
a much gieatei chance. 0sually in oluei teenage males oi male auults is wheie
oichitis will occui. Can also occui in females - oophoeiitis - NC unilateial, theiefoie
infeitility is iaie.
@@@) G&/,'/,/ $= 6?, ,/$#?'3</
() G"/#?'3&' '4A $A"4$#?3&' C A&=U&5<;6" /L';;$L&43
Nost of the time, theie will be S-6 clues pei question. A pt has pioblem swallowing
foous, is it solius oi liquius.
If the pt can take uown liquius anu not solius (A&=U&5<;6" &4 /L';;$L&43 /$;&A/), it is
A<, 6$ $E/6-<56&$4 - can be uue to esophageal web in Plummei vinson synuiome,
IBA with glossitis anu cheilosis anu an esophageal web, esophageal cancei
If pt ?'/ #-$E;,. /L';;$L&43 /$;&A/ (QG ;&Y<&A/_ &6 &/ ' #,-&/6';/&/ #-$E;,._
which is veiy bau. If it's the uppei 1S of the esophagus (which is all stiiateu
muscle), it is uue to myasthenia giavis (bc it affects stiiateu muscle). If it's the
miuule 1S (combo of smooth anu stiiateu muscle). Anu if it's the lowei 1S
(smooth muscle) it's uue to Scleioueima (aka piogiessive systemic scleiosis anu
CREST synuiome) anu achalasia. So, they will tell you immeuiately if they can
swallow liquius anuoi solius, oi neithei (which is a peiistalsis pioblem). Bow can
you uistinguish PSSCREST fiom achalasia. In achalasia, they vomit up the foou they
ate when they go to beu at night; oi they will tell you pt has Raynauu's, inuicating
that it is CREST.
2A"4$#?3&' C :(@QTMX /L';;$L&43; always abnoimal
In BIv pt = Canuiua esophagitis - is it AIBs uefining. Yes.
NC fungal infection in BIv = Canuiua
When it gets into the esophagus, it is AIBs uefining
When it is a thiush, it is PRE AIBS lesion (not aius uefining)
!,;#=<; ?&46/ L&6? $6?,- A&/,'/,/0
:';#'E;, #<-#<-' C &..<4, !:b 6"#, @@@ C !,4$5? [5?$4;,&4 HB>I
Z#&/6'%&/ C #;'6,;,6 #-$E;,. HA$486 6?&4P ?,.$#?&;&'Iz6?," 3&J, 5;<,/j
:'4/"/6$;&5 .<-.<- &45-,'/,/ $4 &4/#&-'6&$4 C 6-&5</#&A -,3<-3
:'4/"/6$;&5 .<-.<- &45-,'/,/ $4 ,%#&-'6&$4 C .&6-'; -,3<-3
V) +-'5?,$,/$#?'3,'; U&/6<;'
Blinuly enuing esophagus (piox esophagus enus blinuly) - uistal esophagus aiiives
fiom the tiachea. What uoes the mom have. Polyhyuiamnios - amniotic fluiu is baby
uiine, so have to iecycle it, oi mom will have big belly. So, the baby swallows it anu it
is ieabsoibeu in the small intestine. So, if you have obstiuction in the esophagus, oi
pioximal poitions of the uuouenum, mom will have polyhyuiamnios. So, theie aie 2
answeis: 1) Tiacheoesophageal fistula 2) uuouenal atiesia in Bown's synuiome -
these 2 aie associateu with polyhyuiamnios. They block the ability to ieabsoib
amniotic fluiu, leauing to polyhyuiamnios. Also, when these kius eat, foou gets
caught anu kius cough anu sputtei bc the uistal esophagus aiises fiom the tiachea
anu leaus to uistension of the stomach. This is veiy chaiacteiistic.
>) {,4P,-8/ A&J,-6&5<;<.
Aiea of weakness - ciicophaiyngeous muscle. It has a lil slit in between the fibeis
of it. Not the whole aiea is cut (which woulu be a tiue uiveiticulum - this is a false
uiveiticulum). It goes out anu gets a pouch. The pouch collects foou anu leaus to
halitosis. They have a tenuency of ieguigitating unuigesteu foou out of the nose.
G) (5?';'/&'
:,-&/6';/&/ #-$E \ #-$E L&6? -,;'%'6&$4 $= 6?, XZ[, theiefoie it is in spasm all the
time. Why. If you bx that aiea, this means that the ganglion cells aie missing. What
uz uoes this ieminu you of. !&-/5?/#-<43 A]. What is in those ganglion cells.
vasointestinal peptiue (vIP). What is its function. To ielax the LES. So, when you
uestioy those ganglionic cells, not only uo you uestioy the movement of the lowei
esophagus, but you also ieuuce vIP levels. So, you have constant constiiction of the
LES, leauing to biiu beak. Piox poition is uilateu.
Z) :'-'/&6,/
Bz of South Ameiica wheie the leishmania foims invaues the ganglion cells of the
LES anu the iectum -- piouuce acquiieu achalasia anu Biischspiung uz = >?'3'8/
A], vectoi = ieuuviu bug (aka kissing bug); swelling of the eye sign. Romana's. What
uoes it uo in the heait. Causes myocaiuitis anu chionic heait failuie - congestive
caiuiomyopathy. This is one of the moie common causes of heait uz in South
Ameiica.
T) V'--,66 ,/$#?'3</
0lceiateu mucosa in the uistal esophagus. Bx: see glanuulai metaplasia; theiefoie
see goblet cells anu mucous cell (which shoulun't be theie). They aie theie bc the
esophagus cannot piotect itself fiom esophageal injuiy. Theiefoie, iun the iisk of
auenocaicinoma of the uistal esophagus. Example: If the lesion in esophagus,
usyphagia of solius, but not liquius, lesion in noteu in uistal esophagus - uo N0T pick
squamous cell caicinoma - this is in the NIB esophagus. If it is uistal, it is
auenocaicinoma, anu the piecuisoi lesion is Baiiett's esophagus.
W) Z/$#?'3,'; J'-&5,/
Bilateu submucosal esophageal veins = theiefoie pt has ciiihosis, who was an
alcoholic. Pt also has poital BTN - the left gastiic vein is involveu (one of the
bianches off the poital vein is left gastiic vein). The left gastiic vein uiains the uistal
esophagus anu pioximal stomach. What uiains into the left gastiic vein. Azygous
vein. Wheie uoes the left gastiic vein uiain into. Poital vein. Bowevei, bc of
ciiihosis, poital vein cannot empty bloou sufficiently into it, the hyuiostatic piessuie
incieases; you ieveise bloou flow into the left gastiic vein, splenic vein, anu othei
veins, anu enu up piouucing vaiices that iuptuie.
!,.'6,.&/&/ = vomiting bloou
!,.$#6"/&/ = coughing up bloou
!,.'6$5?,]&' = bloou pouiing out of anus (actual uiipping of bloou - not coating
of stool with bloou, that is seen in anus). NCC = uiveiticulosis; not uiveiticlulitis bc
the vessel is next to the uiveiticulai sac, so if it weie '-titis', it woulu be scaiieu off.
With -osis, it is intact, anu just have to eioue it, leauing to 6 mL bleeu.
!) B';;$-" O,&// ["4A-$.,
Teai at esophago-gastiic junction. Example: let's say its young woman (play ouus)
- what uoes she have. Bulimia. Classic Example: alcoholic with ietching (tiying to
vomit, but nothing is coming out - causes tiemenuous piessuies, leauing to teai
(hematemisis) oi punctuie (Boihave's - this is when the aii gets into the pleuial
cavity, anu leaus to Baman's ciunch of the anteiioi meuiastinum).
So, seen with bulimia anu leaus to Boihave's (vs. an alcoholic).
@) Z/$#?'3,'; 5'45,-
Squamous cancei (not uistal, but miu); NCC's = smoking anu alcohol (2
nu
NCC)
Bysphagia seen in this pt - initially, pt cannot swallow solius, but can take uown
liquius. Example: Su yo, male, alcoholic, wt loss, piob swallowing foous, not liquius
- ux. Esophageal cancei - squamous cell caicinoma of the miu-esophagus (play
ouus). Example: pic of tiachea anu see caitilage iings, anu elastic aiteiy (esophageal
in miuule) this is esophageal cancei.
@F) G&/,'/,/ $= 6?, [6$.'5?
() >$43,4&6'; :";$-&5 [6,4$/&/
Example: male, S weeks olu anu staiteu J$.&6&43 4$4 E&;, /6'&4,A U;<&A '6 9 LP/;
palpateu the abuomen anu felt a knot in R0Q anu see hypeipeiistalsis. This is N0N
bile stain fluiu at S weeks. Congenital Pyloiic Stenosis
O?'6 &= &6 &/ A<$A,4'; '6-,/&' &4 ' A$L48/ P&Ae That woulu be '6 E&-6? J$.&6&43
of bile staineu fluiu. Anu uouble bubble sign - atiesia (lack of uevelopment of the
lumen) is uistal to wheie the bile uuct comes in, so bile can still entei the pioximal
poition of the uuouenum - this is why it is bile staining - bc theie is no movement,
theie will be aii tiappeu in theie, anu aii is tiappeu in the stomach, theiefoie theie is
aii in the stomach anu piox uuouenum - a uouble bubble sign. Also, mom will have
polyhyuiamnios. So, uo not confuse congenital pyloiic stenosis (which has no
ielationship to uown's) with uuouenal atiesia.
It uoes have multifactoiial inheiitance; theiefoie it can be incieaseu in futuie
chiluien. Can see pyloiic stenosis, as it has thickeneu. To Rx, split the muscle (calleu
pyloioplasty).
V) Q[(@G <;5,-/
Non steioiual will block PuE2, which is iesponsible foi the mucous baiiiei of the
stomach, anu vasouilatation of the vessels, mucous secietion, anu secietion of bicaib
into the mucous baiiiei. So, when you take NSAIBS foi a peiiou of time, the whole
thing is uestioyeu. Leaus to multiple ulceis anu significant bloou loss ovei time.
They aie puncheu out.
>) !) #";$-&
[&;J,- /6'&4 H'/ &/ :>:_ X,3&$4,;;'_ E'-6,4,;;' ?,4/&;'&I) Comma shapeu
oiganisms (like campylobactei), but founu out that they have uiffeient cell walls anu
etc. Nasty bug bc it make lots of cytokines anu uiease which conveits uiea to
ammonia, anu is one of the ieasons why they can buiiow thiough the mucous layei -
ammonia is veiy toxic - this is the test we use - when we take bx of gastiic mucosa,
we uo a uiease test on it anu if its positive, know B pyloii is in it. Can also use
seiological tests - Ab's against it. It's only goou foi the fiist time. Why. Bc the Ab's
uo not go away anu, theiefoie cannot ux ieactivation oi iecuiient. Aftei that it is
useless bc won't tell anything bc will always be positive bc Ab's stick aiounu.
Wheie uoes #,-4&5&$</ '4,.&' ?&6e V$A" '4A =<4A</. That is wheie the paiietal
cells have autoAb's uestioying them, anu IF leauing to atiophic gastiitis.
This is N0T wheie B pyloii exeits its affect. ! #";$-& '==,56/ 6?, #";$-</ '4A
'46-<.. It uestioys the mucosa, leauing to atiophic gastiitis of the pyloius anu
antium. This is wheie canceis aie. Nost canceis aie along the ;,//,- 5<-J'6<-, $=
6?, #";$-</ '4A '46-<. (exact same place wheie gastiic ulceis aie). The B pyloii
live in a mucous baiiiei anu theiefoie is piotecteu. B>> /6$.'5? 5'45,- C !
#";$-&. B pyloii can also cause malignant lymphomas of the stomach (low giaue).
Why uon't we evei bx a uuouenal ulcei. Bc they aie nevei malignant. But gastiic
ulceis have a chance of becoming malignant theiefoie neeu to biopsy gastiic anu not
uuouenal ulceis. 0nly ieason they bx a gastiic ulcei is bc they aie tiying to iule out
whethei it is cancei (malignant) oi not - they know it's an ulcei anu it has a S% of
benign malignant. Nevei have to bx a uuouenal ulcei, so just leave alone. ! #";$-& &/
.$-, 5$..$4;" '//$5 L&6? A<$A,4'; :MG 6?'4 3'/6-&5.
Why uo you get melana with uppei uI bleeus. 0ppei uI = anything that is a bleeu
fiom the ligamentum of tiietz - wheie the uuouenum hits the jejunum anu up. Why
is it black. Aciu acts on Bb anu conveits it to hematin. Bematin is black pigment,
leauing to melana. This is imp to know, bc if you have black taiiy stools, anu its
9S% chance that is an uppei uI bleeu, anu if you play ouus, it is piob a uuouena ulcei
(vs. a gastiic ulcei). So, Bb is conveiteu by aciu to hematin, which is a black pigment.
vomiting of coffee giounu mateiial = bloou clots acteu upon by aciu anu changes to
hematin.
Example: Pt, an executive unuei gieat stiess, anu suuuen onset of seveie epigastiic
pain that iauiates into the left shouluei. Fiist step in woik up. Flat plate of the
abuomen; see aii unuei uiaphiagm. 0uus. Buouenal ulcei. Why uiu he have
shouluei pain. Aii got out, settleu unuei the uiaphiagm, iiiitateu neive #4 (phienic),
anu got iefeiieu pain to the ueimatome (which is the same ueimatomes)
Auuio File 26: uastio 2
G) D?&4&6&/ :;'/6&5'0 (A,4$5'-5&4$.' $= 6?, /6$.'5?
With signet iing cells. Example: S2 yo female with weight loss anu epigastiic
uistiess. She hau an uppei gastiointestinal seiies, noteu that stomach uiu not move
(no peiistalsis), anu then she uieu. Bx. Rhinitis plastica - cells that aie invauing the
wall of the entiie stomach, calleu /&34,6 -&43 5,;;/ (which aie staineu with
mucocainine cells, aie pink - signet cells aie like a uiamonu iing, anu the uiamonu
has been pusheu to the peiipheiy). The mucous is insiue, making the cell look
empty, anu pushing the nucleus to the siue (just like fatty change of the livei).
Bowevei, these aie malignant neoplastic glanuulai cells, anu aie chaiacteiistic of
ihinitis plastica type of gastiic auenocaicinoma.
Nisconception: S-<P,4E,-3 6<.$- is not a tumoi that is seeuing out to the ovaiy.
This tumoi is uue to hematogenous spieau to the ovaiy. Theie is no such thing as a
signet iing caicinoma of the ovaiy (theie is no piimaiy cancei of the ovaiy that looks
like this). +?, /&34,6 -&43 5,;;/ 5'., =-$. /6$.'5? 5'45,- 6?'6 ?'/ .,6'/6'/&],
6$ $J'-&,/ C S-<P,4E,-3 6<.$-.
Nost aie ulceiative tumois in the lessei cuivatuie of the pyloius anu antium.
Leathei bottle stomach - veiy haiu uue to all of the cancei cells anu the fibious
iesponse to it.
uastiic cancei is ueclining in 0S; othei countiies it is a piimaiy cancei - }apan, bc
smokeu piouucts. 0thei ethnic canceis: nasophaiyngeal caicinoma = china; stomach
cancei anu BTLv 1 = }apan; Buikitts lymphoma = Afiica.
If theie was a nontenuei mass in left supiaclaviculai aiea anu pt with epigastiic
uistiess one week ago - ux. Netastatic gastiic auenocaicinoma. Ceivical cancei can
also metastasize heie. Left supiaclaviculai noue uiains abuominal oigans; theiefoie
pancieatic canceis but mostly the stomach canceis metastasize theie. The iight
supiaclaviculai noue mets aie fiom lung cancei.
F) B';'E/$-#6&$4
Neans bau absoiption of eveiything: fats, caibs, anu pioteins. Biagnosis point of
view we look foi incieaseu fat in the stool = steatoiihea = scieening test foi
malabsoiption.
() T'6 G&3,/6&$40
1) Neeu lipases to bieak uown fat into 2 monoglyceiiues anu FA's, so you neeu a
functioning pancieas.
2) Neeu villi of the small intestine bc if we uiun't, the small intestine woulu have to
be a mile long. villi inciease the oveiall absoiptive suiface without incieasing the
length. So, if you uon't have them, you ueciease the absoiptive suiface, anu will lose
the monoglyceiiues anu FA's. Theiefoie, you neeu a functioning SI with villi.
S) Neeu bile salts to emulsify the fat anu bieak it uown to micelles (tiny paiticles
that aie 1 micion in uiametei) anu chymlomicions. Emulsifying agents aie many
times in uishwasheis bc neeu to get fat off plates. Fat will come to the suiface anu
bieak up into micelles, which aie easiei to absoib.
So, neeu functioning pancieas, bile salts, small intestine that has villi in oiuei to
ieabsoib fat.
V&;, /';6/ aie maue in the livei fiom cholesteiol. Cholesteiol cannot be uegiaueu; it
eithei solubilizeu in bile (theiefoie iun the iisk of cholesteiol stones) oi is conveiteu
to bile acius. Cannot bieak uown cholesteiol.
Bile salt ueficiency is seen in: a) livei uz; b) anything that obstiucts bile flow will
piouuce bile salt uef; c) bacteiial oveigiowth can eat anu bieakuown bile; u)
teiminal ileal uz, ex. Ciohn's uz cannot iecycle; anu e) Cholestyiamine: iesins - useu
foi tieatment of hypeilipiuemia, can piouuce bile salt uef. This is the N0A of iesins,
by binuing anu then excieting them, bc if you aie not iecycling them, you will make
moie. What's happening in the livei. 0piegulation of LBL ieceptois synthesis, bc
neeu to make moie bile salts, theiefoie neeu to suck moie out of the bloou anu will
make moie LBL ieceptois. These uiugs will eventually take moie cholesteiol out of
the bloou anu lowei it, so you can make moie bile salts. It also takes uiugs with it, so
it's not goou foi people taking meus, bc you will lose these meus in the stool, along
with bile salts.
Bz's: scieening test is looking foi fat in stool (steatoiihea) - let's say it is positive.
So, we have to figuie which if the S aieas is the cause of the malabsoiption -
pancieatic uef, bile salt uef, oi something wiong with the small bowel (NC).
V) >,;&'5 G] H/#-<,I
Pic of small bowel lesion anu a skin zit that has an association with it. This is celiac
uz (autoimmune uz), anu the skin zit is A,-.'6&6&/ ?,-#,6&=$-.&/. >,;&'5 A] &/ '4
'<6$&..<4, A] '3'&4/6 3;<6,4 L?,'6_ ,/#) 3;&'A&4. It is veiy common anu is the
NCC of malabsoiption in this countiy. So, when you eat wheat piouucts, the gluten is
ieabsoibeu into the villi anu theie aie Ab's against gliauin, anu leaus to uestiuction
of the villi (just like Ab's against paiietal cells oi intiinsic factois, which uestioy
eveiything aiounu it). So, the Ab's attack gluten that has just been ieabsoibeu by the
foou, which will cause uestiuction of the villus. Anu theie aie no villi heie - it is flat;
blunting of villus - so you aie not able to ieabsoib fat, pioteins, oi caibs. Theie is no
villus suiface. The glanus unueineath aie fine, howevei. The villi aie absent. Theie
is a 1ffn 5?'45, $= A,-.'6&6&/ ?,-#,6&=$-.&/ '//$5&'6&$4 L&6? <4A,-;"&43
5,;&'5 A]) G,-.'6&6&/ ?,-#,6&=$-.&/ &/ '4 '<6$&..<4, A]_ '4A &6 &/ ' J,/&5<;'-
;,/&$4 $= 6?, /P&4 -looks like heipes of the skin. They will show pic of a ueimatitis
heipetifoimis, anu will ask what the cause of uiaiihea is. Ab's against gluten
(gliauin).
>) O?&##;,8/ A]
An infection of the small infection uue to an oiganism that you cannot giam stain.
T. whippelii only seen with EN; cannot be cultuieu. See flat blunteu villi anu foamy
maciophages (look like Niemann pic bubbly maciophages; can also be fiom an BIv
"+" bc it looks like Whipple's, but isn't). The maciophages have uistinctive PAS-
positive stains.
!@F #$/&6&J, #6 anu aciu fast stain - pt with helpei T cell count of 1uu. Bave an
aciu fast stain with the foamy maciophages - A<, 6$ B(@ (this is moie common that
TB), anu 5'4 5'</, O?&##;, ;&P, A] L&6? .';'E/$-#6&$4.
Whipple's, being an infection, has systemic signs anu symptoms: fevei,
lymphauenopathy, polyaithiitis, geneializeu pain. It's an infection theiefoie can be
tieateu with antibiotics.
So, theie aie 7 A]8/ 6?'6 5'</, .';'E/$-#6&$40 5,;&'5 A] '4A O?&##;,8/ A]. 0thei
uz's aie uz's of the pancieas - 5?-$4&5 #'45-,'6&6&/ HB> &4 ';5$?$;&5/ - 2 ieasons
foi malabsoiption in alcoholics - a lipase uef ielateu to chionic pancieatitis, oi bile
salt uef uue to ciiihosis, oi both in an alcoholic).
G) G&'--?,'
Best way to classify is to subuiviue into S types:
1. Invasive: bacteiia invaues
2. Secietoiy: the bacteiia piouuces toxins anu that will stimulate cANP (oi othei
mechanisms) causing the small bowel to seciete small amounts of IS0T0NIC fluiu,
which is NaCl.
S. 0smotic: lactase ueficiency. Also piouuceu by laxatives, anu othei inboin eiiois
of metabolism.
Secietoiy anu osmotic uiaiiheas aie high volume uiaiiheas anu you go fiequently,
wheieas invasive uiaiihea is a small volume uiaiihea. Bestcheapest test to get in a
pt with uiaiihea = fecal smeai foi leukocytes. If theie aie N0T any neutiophil uon't
woiiy because not invasive. If theie aie inflammatoiy cells then you must uo fecal
smeai test foi campylobactei oi shigella.
a) 0smotic uiaiihea (fits in with osmotic watei movement) is when theie is some
osmotically active substance in the bowel lumen that is sucking watei out of the
bowel, causing a high volume, hypotonic loss of fluiu. Example: lactase uef. = biush
boiuei oi uisacchaiiuase ueficiency, a biush boiuei enzyme. In a classic case but
they will not tell you it's a lactase uef, insteau will tell you it's a uisacchaiiuase uef oi
even a biush boiuei enzyme uef. So if you'ie lactase uef, it means that any uaiiy
piouucts which contains lactose (which bieaks uown into glucose anu galactose)
can't be inuigesteu. So it will go to the colon, anu act as uesseits to the anaeiobic
bacteiia which will eat the lactose anu piouuces hyuiogen gas, anu othei gases, anu
acius, anu get aciuic stools. The hyuiogen gases causes the bloating, uistention, anu
incieuible explosive uiaiihea.
b) Secietoiy uiaiihea: two things to know, vibiio choleiae anu ETEC (tiavelei's
uiaiihea). These aie not invasive uiaiihea, theiefoie when you uo a bowel biopsy
theie will not be one iota of inflammation, it's peifectly noimal. It's puiely a toxin
that activates a pump eithei cANP (vibiio) oi some othei pump: guanylate cyclase
(E. coli). Tieatment: when you give fluiu ieplacement to patients with v. choleiae,
you neeu to give glucose along with the fluius. This is bc you neeu glucose to co-
tianspoit Na that was in the fluius. Siue note: Neeu to know the othei E. coli ielateu
toxins: EBEC: 01S7:B7; EIEv; anu EaggEC.
c) Invasive uiaiihea: the NC in 0S is causeu by campylobactei jejuni, anu shigella is
a close seconu. Classic case: a peison with low vine(.) uiaiihea, with some bloou in
it, anu on giam stain theie weie comma shapeu oi S-shapeu oiganisms that's
campylobactei jejuni. Both of these oiganisms can piouuce pseuuomembianes.
Theiefoie all pseuuomembianes uoes not necessaiily mean you will see C. uifficile.
u) Paiasites that causes uiaiihea:
W&'-A&': owl eyes that move. This is the NCC of uiaiihea uue to a paiasite in the
0S. Tieatment: metioniuazole.
>-"#6$/#$-&A&<. #'-J&: NCC of AIBS uiaiihea is a paitially aciu-fast oiganism. It
sticks to the wall of the colon. Classic case: theie is a pt that has AIBS anu has
uiaiihea, anu when they stain it, theie aie oocysts that aie paitially aciu-fast. It will
kill if you aie immunocompiomiseu. The tieatment is almost woithless. It comes at
the enu when the helpei T-cells aie neai Su oi 7S, anu that's when all the oiganisms
that will kill you: NAI, ciyptospoiiuium, toxoplasmosis, anu CNv all comes in at the
enu. P. caiinii comes in aiounu 2uu helpei T-cells.
>;$/6-&A&<. A&=U&5&;,0 This is an autopsy pic of an oluei woman who was in the
hospital with pneumonia, anu she uevelopeu uiaiihea. What was founu on autopsy.
Well, it is safe to say that if she hau pneumonia, then she was taking antibiotics. So
this is #/,<A$.,.E-'4$</ 5$;&6&/_ 5'</,A E" 5;$/6-&A&<. A&=U&5&;,. This occuis
when taking antibiotics that wipe off the goou oiganisms, leaving behinu c. uifficile.
Eveiybouy has c. uifficile in theii stools, but E. coli, enteiobactei fiagilis aie keeping
it in check. But when taking antibiotics such as ampicillin (NC), clinuomycin (2
nu

NC) foi a peiiou of time, you knock off the goou guys, giving c. uifficile a chance to
piolifeiate anu make toxins that uamage the supeificial layeis of the colon. The
bacteiia uoesn't invaue, it's the toxins that uo. This is analogous to c. uiphtheiia,
which also has a toxin that uamages anu piouuces pseuuomembianes but the
oiganism uoes not invaue. The iibosylation thing, anu the Elongation factoi 2 (EF-2
allows foi piotein elongation) aie messeu up, theiefoie cannot elongate pioteins.
The fiist step in management is to uo a toxin assay of stools, not giam stain bc theie
aie lots of giam stain oiganisms in the stools, not bloou cultuie bc it's not in the
bloou. +?, /5-,,4&43 6,/6 $= 5?$&5, &/ 6$%&4 '//'" $= /6$$;j The tieatment is to
give metioniuazole, useu to give vancomycin bc c. uifficile became iesistant to it.
Netioniuazole itself can piouuce pseuuomembianous colitis but you take that
chance.
F@) G&/,'/,/ $= 6?, [.';; @46,/6&4,
() [.';; E$L,; $E/6-<56&$4: See classic step lauuei appeaiance of aii-fluiu levels:
aii, fluiu, aii, fluiu (step lauuei appeaiance). When you have a hollow viscous that
peiistalsis, you get a ceitain chaiacteiistically pain, calleu >2X@> #'&4. It isn't like a
ciampy pain with no painfiee inteivals; colicky pain is when you have pain, a
painfiee inteival, pain, anu then a painfiee inteival. The inteivals aie not consistent,
sometimes you have a 1S min painfiee inteival, anu othei times if may be longei oi
shoitei. This is colicky pain; it means T0TAL small bowel obstiuction. By the way,
the bile uuct uoes not have peiistalsis, theiefoie you uo not get colicky pain, anu
insteau you get ciampy pain. You have to have peiistalsis to get colicky pain, it has to
move. Anu what's it uoing is tiying to move against that obstiuction anu that's
causing the pain. Bc you cannot peistalse you get stagnation of the foou pioximal to
wheievei the obstiuction is, anu get aii-fluiu levels. Bistal to the aiea of obstiuction
theie is no aii. In obstiuction, theie aie two things that can happen: 5$4/6&#'6&$4 $-
$E/6&#'6&$4. Constipation is wheie you have a pioblem with stooling, which uoes
not necessaiily mean obstiuction. 0bstipation means that not only uo you have
constipation you also have a pioblem passing gas, that means you have complete
obstiuction. So you have to ask the pt whethei they have passeu any stools oi gas.
B>> $= $E/6-<56&$40 'A?,/&$4/ =-$. #-,J&$</ /<-3,-&,/) Sliue: those aie
wateimelon pits, with a naiiow lumen. But if the case ieau that this pt uiu not have
peivious suigeiies anu hau colicky pain, this is uue to the bowel being tiappeu in the
&4A&-,56 &43<&4'; ?,-4&') Example: theie was a weight liftei who uevelopeu colicky
pain in the RLQ aiea, hau no pievious suigeiy, the most likely cause is inuiiect
inguinal heinia. Weight lifteis often times cieate inuiiect inguinal heinias.
[&A, 4$6,: theie was a pic of G$L48/ /"4A-$., kiu. Tiisomy 21 (abnoimal
numbei of chiomosomes) is uue to nonuisjunction (unequal sepaiation uuiing the
fiist stage of meiosis I) but not all uown's have tiisomy 21. But if the kiu hau noimal
46 chiomosomes, this is uue to D$E,-6/$4&'4 6-'4/;$5'6&$4. In this case, they
woulu have 46 chiomosomes but on one of those chiomosomes 21, will be anothei
chiomosome attacheu to it. They will have thiee functional chiomosome 21. The
two uI uiseases that aie NC'ly seen in Bown's aie A<$A,4'; '6-,/&' (uouble bubble
sign) anu !&-/5?/#-<43 A].
V) !&-/5?/#-<43 A]0 the neives aie theie but the ganglionic cells aie missing. So,
what happens if it's missing in the iectum, the stools cannot get by, even when theie
is an opening, bc theie is no peiistalsis. So the stools just stay theie. So, the uilation
of the pioximal colon has ganglionic cells, anu theie peiistalsis occuiiing anu you
can't get the stools thiu the iectal aiea. So this means that the iectal ampulla has no
stools in it. Example: if you have a chilu that uiun't pass the meconium in 24 houis
anu a iectal exam was peifoimeu. If theie was Q2 /6$$;/ 6?'6 5'., $<6 $4 ,%'. &6
.,'4/ !&-/5?/#-<43 A]) If on exam, theie was stools on the fingei, it means tight
sphinctei. +?&/ &/ ' A] $= 6?, 5$;$4)
>) @46<//</5,#6&$40 most occui in chiluien, anu it's when the teiminal ileum
intussuscepts goes into the cecum. Theie will be colicky pain bc you aie
obstiucting, anu not only that, you aie compiomising bloou flow, so you get the
bleeuing. They will say: a 2 yo kiu, with colicky pain anu bloouy stools. They might
way theie is an oblong mass in the R0Q. In some kius, it spontaneously comes out,
but if not, then the iauiologists will uo baiium enema, anu put a little piessuie theie,
anu he ieveits it. So you get complete bowel obstiuction anu infaictions.
G) F$;J<;</0 Twisting of the colon aiounu the mesenteiy bc theie's too much of it
causing complete obstiuction anu infiactions uue to compiomising bloou flow.
Z) W';;/6$4, &;,</ usually seen in oluei people, moie women, anu have signs of
colicky pain, anu obstiuction. The gallblauuei stone falls thiu the fistula anu settles
into the ileocecal valve anu causes obstiuction. See a flat plane of the abuomen that
piouuceu aii in the biliaiy tiee. Boom, theie's youi Bx. Theie is a fistula that is
communicating the gallblauuei with the small bowel theiefoie aii can get in the
small bowel anu the biliaiy tiee. (&- &4 6?, E&;&'-" 6-,, L&6? 5$;&5P" #'&4 &/
3';;/6$4, &;,</) G] $= 3';;E;'AA,-)
T) B,5$4&<. @;,</ C 5"/6&5 U&E-$/&/

Auuio File 27: uastio S - BepatoPancieas 1
F@@0 G&/,'/,/ $= 6?, >$;$4
() F'/5<;'- A&/,'/,/ $= 6?, 5$;$40
1) @/5?,.&5 V$L,; G]0
The small bowel moie commonly infiacts than the laige bowel, bc it has only one
bloou supply. The entiie small bowel, the ascenuing colon, anu the tiansveise colon
aie all supplieu by the SNA (supeiioi mesenteiic aiteiy). So, what is the main uiff in
a small bowel infaict vs. an ischemic ulcei causing bloouy uiaiihea in the splenic
flexuie. The uiffeience in Piesentation. They both can have bloouy uiaiihea.
Bowevei, the /.';; E$L,; &4='-56&$4 will BIFF0SE abuominal pain (all ovei - not
one specific aiea). In &/5?,.&5 5$;&6&/, it will point to specific aiea on iight siue of
abuomen. This uiffeientiates btwn a small bowel infaict fiom a small infaict in the
colon (can pinpoint aiea).
7) (43&$A"/#;'/&'
2
nu
NCC !,.'6$5?,]&', with uiveiticulosis being #1. It's in the cecum bc law of
Laplace (wall stiess anu iauius). The uiametei of the cecum is biggei than any othei
pait of the colon. Bc the uiametei is gieatei, the wall stiess is gieatei. Theiefoie,
putting stiess on the vessels in the wall of the cecum, it actually pulls them apait anu
piouuces telangiectasias. As a iesult, it pieuisposes to angiouysplasia bc incieaseu
wall stiess. If one of them iuptuies to the suiface, you can enu up with significant
bleeu. A veiy common cause of Bematochezia in oluei people. So, if uiveiticulosis is
iuleu out, angiouysplasia is piobably it.
V) B,5P,;8/ G&J,-6&5<;<.R [.';; @46,/6&4, G]0
1) D<;, $= 78/0 2% of pop'n; 2 inches fiom teiminal ileum; 2 ft fiom the iliocecal
valve; 2 cm in length; 2 yo oi youngei; anu 2% of caicinoiu tumois occui in N.B.
NC complication = bleeuing. Bc it is a uiveiticulum, it can be inflameu, anu leaus
to uiveiticulitis. Example: ?,.'6,.&/&/_ #'&4 &4 DXw '-,'_ .,;'4' -ux. Neckel's
(involveu melana ANB hematemisis - uefinitely not 0C oi Ciohn's).
Example: newboin with a sinus anu umbilicus was uiaining poop -ux. Peisistent
vitelline uuct (same as meckel's - sometimes it is open all the way thiough, theiefoie
theie is a communication between the small bowel anu umbilicus, so feces coming
out of umbilicus, which is peisistence of the vitelline uuct. If you have uiine coming
out of the vitelline uuct, this is peisistence of the uiacus. So, =,5,/CJ&6,;;&4, A<56_
<-&4, C <-'5</.
>) [&3.$&A >$;$4
NC location foi cancei in the entiie uI tiact = sigmoiu colon
NC location foi polyps in the entiie uI tiact = sigmoiu colon
NC location foi uiveiticula in the entiie uI tiact = sigmoiu colon
The aiea of weakness is wheie the bloou vessels penetiate the valve. The mucosa
anu submucosa will heiniate iight next to the vessel. This is veiy bau 'next uooi
neighboi". When feces aie stuck (fecalith), can eioue that vessel, anu can see why
A&J,-6&5<;$/&/ &/ 6?, B>> $= !,.'6$5?,]&' \ .'//&J, ;$L,- W@ E;,,A. These
extenu outsiue of the lumen, which is uiveiticulosis. If you see polyps in the lumen,
uo not confuse with polyposis - #$;"#/ 3$ @Q+2 6?, ;<.,4, not out.
G) G&J,-6&5<;$/&/
B> 5$.#;&5'6&$4 C A&J,-6&5<;&6&/; has NANY complications.
G&J,-6&5<;&6&/ = Left siue appenuicitis (appenuicitis ux: RLQ pain, NcBuiney's pt,
iebounu tenueiness, fevei, anu neutiophilic leukocytosis) - this is the same
piesentation in uiveiticulitis), but uiveiticulitis occuis in the LLQ aiea, in an elueily
peison. B>> U&/6<;'/ 5$..<4&5'6&$4/ &4 6?, W@ C A&J,-6&5<;$/&/) With a fistula,
theie is communication between 2 hollow oigans. The B> U&/6<;'/ '-, 5$;$J,/&5;,
U&/6<;'8/, which is a fistula between the colon anu the blauuei, leauing to
4,<.'6<-&' \ '&- &4 6?, <-&4,. B>> $= 5$;$J,/&5;, U&/6<;' &/ A&J,-6&5<;'- A]. They
can iuptuie, anu the iuptuie can cause peiitonitis.
F@@@) @4U;'..'6$-" V$L,; G]0 >-$?48/ '4A M>
Ciohn's involveu the teiminal ileum 8u% of the time. Sometimes it just involves the
teiminal ileum, sometimes it involves the teiminal ileum ANB the colon, anu
sometimes it just involves the colon. Ciohn's likes the AN0S, 0C likes the RECT0N
(they have a piefeience foi which pait of the lowei pait they like). Ciohn's likes to
piouuce fistulas anu fissuies of the anus; 0C likes the iectum, piouucing bloouy
uiaiihea. Ciohn's jumps aiounu, tiansmuial, noncaseating gianulomas. 0C uoesn't
jump; it stays in continuity, anu involves the mucosasubmucosa. G% $= >-$?48/ &/
/&.#;, \ &, &;,$5,5'; J';J,_ '/5,4A&43 5$;$4_ 6,-.&4'; &;,<. \ 6?,-, &/ '
6-'4/.<-'; &4U;'..'6&$4 L&6? ' J,-" 4'--$L ;<.,4 \ 6?,-,=$-, 6?,
#-,/,46'6&$4 L&;; E, 5$;&5P"_ DXw #'&4_ L&6? A&'--?,' &4 "$<43 #,-/$4. Q$6?&43
,%5,#6 >-$?48/ #-$A<5,/ 5$;&5P" #'&4 &4 6?, DXw &4 ' "$<43 #,-/$4j If is a S
iu

woilu county, what is it. TB (m. bovis). In this countiy, if we get intestinal TB fiom
swallowing it anu it will be N .Tb. In thiiu woilu countiies, it piouuces piesentation
same as Ciohn's; this occuis bc they uo not have pasteuiization; N. bovis is the
NCC; this is wheie payei's patches aie. [6-&43 /&34 - on baiium stuuy, looks like a
stiing - see that it is tiansmuial anu that it is segmental. The pioximal valve is
uilateu - have to push stool thiough that but you can't. See cobblestones anu
ulceiation in Ciohn's uz. Lineai ulceis aie apthus ulceis) Q$4 5'/,'6&43 3-'4<;$.'
&/ 5?'-'56,-&/6&5 $= M>. M> ';L'"/ E,3&4/ &4 6?, -,56<., can stay theie, oi can
move up in continuity anu involveu the whole colon, but it nevei involves the
teiminal ileum. It is involves the whole colon, it is calleu pancolitis, anu this has the
highest inciuence of cancei. So, the moie involvement anu gieatei uuiation = gieatei
chance of cancei ielateu to 0C. Pseuuopolyps - see ulceiateu mucosa anu
submucosa. Pseuuopolyps aie iesiuual polyps that aie inflameu, it is inflameu
bloouy mucosa. Eveiything is ulceiateu off, anu you see the submucosa of the colon.
0C has the highest inciuence with cancei, BLA B27 anklyosis sponuylitis, anu is the
NCC of scleiosing peiicholangitis (scleiosisfibiosis aiounu common bile uuct,
piouucing obstiuctive jaunuice anu high inciuence of cholangiocaicinoma). Know
the uiff in 0C vs. Ciohn's.
@g) +<.$-/ $= 6?, >$;$4 :$;"#/
B> #$;"# &4 ,46&-, W@ C ?"#,-#;'/6&5 #$;"# - it is a little nubbin - aka
hemaitomas (theiefoie not neoplastic), usually in sigmoiu colon.
+<E<;'- 'A,4$.': looks like a stiawbeiiy on stick, theiefoie has a stalk with
stiawbeiiy, which is the piecuisoi lesion foi colon cancei.
t<J,4&;, :$;"#: Sliue: coming out of chilu's butt - kiu with polyp in iectum; ';;
u<J,4&;, #$;"#/ ;$5'6,A &4 6?, -,56<. '4A '-, ?'.'-6$.'/ H4$ #-,5'45,-$</I)
Lets say it is an auult anu the polyp is sticking out (a ieuuish mass) - ux. @46,-4';
?,.$--?$&A/. D<;,0 &46,-4'; ?,.$--?$&A/ E;,,A_ ,%6,-4'; ?,.$--?$&A/
6?-$.E$/,. Theiefoie, when you have bloou coating the stool, it is inteinal
hemoiihoiu. Inteinal hemoiihoius aie N0T painful, but they uo piolapse.
Auult with something ieuuish sticking out of theii butt = piolapseu inteinal
hemoiihoiu. @46,-4'; ?,.$--?$&A/ E;,,A '4A #'&4;,//_ L?&;, ,%6,-4';
6?-$.E$/, '4A '-, #'&4=<;)
[,//&;, :$;"# HJ&;;$</ 'A,4$.'I - looks like the villous suiface of the small
intestine (hence name villous auenoma); these aie lil fingei-like excienses of the
small intestine, hence the name villous auenoma. +?,/, ?'J, 6?, 3-,'6,/6
.';&34'46 #$6,46&';_ '4A '-, </<';;" &4 6?, -,56'; /&3.$&A) Bc they aie villous
fingei like they have a lot of mucous coating the stool; mucous secieting villous.
They have a Su% chance of becoming malignant. So, tubulai auenomas aie
piecuisois foi cancei (size ueteimines malignant potential - if they aie above 2
sonometeis, they aie veiy uangeious) anu villous auenomas leau to cancei, too.
T'.&;&'; #$;"#$/&/ - neeu to have ovei 1uu polyps to have familial polyposis. This
uz is autosomal uominant, uses APC suppiessoi gene, ias, anu pSS; APC is the majoi
one. Will always get cancei in them, usually between SS-4u. Theiefoie, will neeu to
piophylactically iemove the bowel. The autosomal uominant uz is famous foi late
manifestations, penetiance, anu vaiiable expiessivity (as aie all othei AB uz's). This
means that they will not be boin with polyps at biith (they stait ueveloping btwn the
ages of 1u-2u; in ABPKB, they uo not have cysts aie biith, they stait ueveloping
btwn 1u-2u; in Buntington's choiea, uo not have choiea at biith, but aiounu SS-4u
yeais, anu they have late manifestations.
(==,56,A 5$;$4 ?'/ #$;"#/ '4A E-'&4 6<.$-/ C +<-5$6 /"4A-$., (like tuiban) -
theiefoie, you have a polyposis synuiome with biain tumoi; this uz is auto iec (not
uominant).
W'-A4,-8/ /"4A-$.,: Bave multiple polyps in theie, plus b9 salt tissue tumois:
uesmoius anu osteomas in the jaw.
g) >'-5&4$&A +<.$-/
Along with auput tumois. All caicinoiu tumois aie malignant, but have low giaue
potential. A lot of it uepenus on theii size anu if they aie going to mets. Bepenus on
theii size in sonometeis - if they aie gieatei than 2 sonometeis they have the ability
to mets. B> ;$5'6&$4 =$- 5'-5&4$&A 6<.$- C 6&# $= 6?, '##,4A&% - have a biight
yellow coloi, but they '-, QZFZD 6?, 5'</, $= 5'-5&4$&A /"4A-$., - why. Bc the
tip of the appenuix will nevei be gieatei than 2 sonometeis. So, wheie is the B>
;$5'6&$4 $= 5'-5&4$&A 6<.$- 6?'6 >(Q E, '//$5&'6,A L&6? 5'-5&4$&A /"4A-$.,e
+,-.&4'; @;,<. \ 6?," '-, ';L'"/ 3-,'6,- 6?'4 7 /$4$.,6,-/. What uo all
caicinoiu tumois make. [,-$6$4&4. Bc the appenuix anu teiminal ileum aie
uiaineu by the poital vein, the seiotonin maue goes to the poital vein, goes to the
hepatocyte, is metabolizeu into S hyuioxyactoactitic (.) aciu anu is pee'u out;
theiefoie it is not in the blooustieam. Theiefoie, theie aie no signs of flushing anu
uiaiihea bc theie is no contact with the systemic ciiculations. Bowevei, if you mets
to the livei, then those metastatic nouules that aie making seiotonin can uump some
of it into the hepatic vein tiibutaiies. This uoes have access to the systemic
ciiculation bc goes to IvC to Right siue heait, anu this is why you get iight siueu
lesions - "+@:[d C 6-&5</#&A &4/<== '4A #<;.$4&5 /6,4$/&/. [,-$6$4&4 is a
vasouilatoi in some cases, but a vasoconstiictoi in othei cases. Bowevei, in teims of
seiotonin synuiome, it's a vasouilatoi 6?'6 5'</,/ U;</?&43 HL?&5? &/ 6?, B>
/".#6$. $= 5'-5&4$&AI_ =$;;$L,A E" A&'--?,' H7
4A
B>I) If it has access to systemic
ciiculation, it has high levels of S hyuioxyacetoacitic (.) aciu, which is the scieening
test of choice bc it is the metabolite of seiotonin. So, ER5 .'P&43 '4A X2[@QW ' ;$6
$= /,-$6$4&4_ L?'6 '' 5'4 E, A,U&5&,46e +-"#6$#?'4 &/ A,=_ 6?,-,=$-, 6?, J&6'.&4
Q&'5&4 &/ A,=_ 6?,-,=$-, 5'4 ?'J, #,;;'3-') b$< </&43 <# ';; 6?, +-"#6$#?'4 '4A
.'P&43 /,-$6$4&4 &4/6,'A $= 4&'5&4)
g@) >$;$4 5'45,-
Neuiosecietoiy gianules on EN - colon cancei; ;,=6 /&A, $E/6-<56/_ -&3?6 /&A,
E;,,A/.
This is easy to unueistanu bc the left colon has a smallei uiametei than the iight.
So, when the cancei uevelops in 6?, ;,=6 5$;$4 anu wants to foim a polyp, it goes
aiounu - '44<;'- H4'#P&4 -&43I, anu piouuces constiiction. 0pen bowel in left
colon, see one euge of the cancei on each siue of the bowel anu bowel is constiicteu -
have signs of obstiuction (left siue obstiucts, iight siue bleeus).
In the -&3?6 5$;$4, bc of theie is a biggei uiametei; it has a biggei chance of going
out anu foiming a polyp. Theiefoie, it is sitting in the stool, leauing to a bleeu
(theiefoie left siue obstiucts, iight siue bleeus).
So, which is siue is moie likely to have Fe uef. Right siueu lesion.
Which is moie likely to have alteiation in bowel habits (constipationuiaiihea).
Left siueu.
+<.$- .'-P,- =$- 5$;$4 5'45,- C >Z( H5'-5&4$,.E-"$4&5 (3). Not useu to ux
colon cancei, but useu to follow it foi RE0CC0RRENCE. NCC ielates to uiet (lack of
fibei in stool - theiefoie, moie fibei you have, the less chance of colon cancei bc
you aie getting iiu of lipocolic aciu). Age is also a iisk factoi (pts ovei Su); smoking
is a iisk factoi that is assoc with colon cancei. Polyposis coli synuiomes also have an
association (familial polyposis, uaiunei's synuiome, tuicot's synuiome)
N0T Peutz }egheis, hypeiplastic polyps, oi juvenile polyps).
g@@) G&/,'/,/ $= 6?, (##,4A&%0 (##,4A&5&6&/
Coveieu with pus; NCC appenuicitis in auults = fecalith = impacteu stool. So when
you impact stool it piesses on the siues of the appenuix, anu leaus to ischemia, then
get a bieakuown of the mucosa, E. coli gets in theie anu acute appenuicitis occuis.
+?&/ &/ 6?, [(BZ .,5? =$- A&J,-6&5<;&6&/ (the uiveiticulai sacs also get fecaliths in
them anu the same exact thing happens - the pathogenesis of acute uiveiticulitis anu
acute appenuicitis is exactly the same). So, fecalith, ischemia along the wall,
inflammation, E coli.
Anothei analogy: acute cholecystitis - except it is not a fecalith, but is a stone in the
cystic uuct pushes on the siue, leaus to ischemia, acute cholecystitis, E coli) So, theie
is a concept theie - L, ?'J, '5<6, 5?$;,5"/6&6&/_ A&J,-6&5<;&6&/_ '4A '##,4A&5&6&/
';; -,;'6,A 6$ /$.,6?&43 $E/6-<56&43 6?, ;<.,4_ 5'</&43 .<5$/'; A'.'3,_ '4A Z
5$;& &4U;'..'6&$4. In acute cholecystitis it's a stone, while acute appenuicitis anu
uiveiticulitis is uue to a fecalith.
What the B>> $= '##,4A&5&6&/ &4 5?&;A-,4e B,'/;,/ '4AR$- 'A,4$J&-</
&4=,56&$4. Then, acute appenuicitis occuis bc theie is lymphoiu tissue in the
appenuix. With measles oi auenoviius infection, get ?"#,-#;'/&' $= ;".#?$&A
6&//<, &4 6?, '##,4A&%_ '4A 5'4 $E/6-<56 6?, ;<.,4 '4A /,6 <# &4U;'..'6&$4 =$-
.<5$/'; &4u<-" '4A ;,'A/ 6$ '5<6, '##,4A&5&6&/. So_ &4 5?&;A-,4_ &6 </<';;"
=$;;$L/ ' J&-'; &4=,56&$4. As opposeu to auults, wheie it is uue to fecalith.
CHAPTER 10. HepatoPancreas
@) V&;&-<E&4 .,6'E$;&/.0
Nost of the biliiubin in oui bloou is unconjugateu anu ueiiveu fiom the RBC's when
they aie olu, phagocytoseu anu uestioyeu. 0nconj biliiubin is the enu piouuct, goes
to the blooustieam anu binus with albumin, goes to the livei anu is taken up.
Najoiity of biliiubin is fiom bieakuown of RBC's (99%), which is all unconj. None of
this is in the uiine bc it is lipiu soluble. So, it gets taken up by the livei anu is
conjugateu. Any time the cytochiome p4Su conjugates biliiubin, oi metabolizes any
uiug, it ienueis it watei soluble. So, we have a lipiu soluble unconjugateu biliiubin is
conveiteu to conjugateu biliiubin (uiiect biliiubin), which is watei soluble. 0ne of
the puiposes of the livei is to ienuei lipiu soluble uiugs watei soluble, so you can
pee them out. So, we conjugate it anu have watei soluble biliiubin. 0nce biliiubin is
taken up by the livei, it is nevei close to a vessel. So, theie is no way it can get into a
vasculai channel (once it is taken up by the livei). So, if uiiect conjugateu biliiubin is
in oui uiine, this is bc something happeneu (eithei in the livei oi bile uuct) to have
causeu it to get theie bc it shoulun't have access to oui bloou stieam. So, it is taken
up in the livei, conjugateu, anu pumpeu into the bile uuctules; which go into the
tiiau, goes up the common bile uuct, some is stoieu in the uB anu goes into the small
intestine thiough the common bile uuct. Theiefoie, bile contains conjugateu
biliiubin. Its also contains bile salts, cholesteiol anu estiogen, but has conjugateu
biliiubin that we will get iiu of. So, this conjugateu biliiubin takes a long tiip uown
to the colon anu the bacteiial have been waiting foi the conjugateu biliiubin anu will
bieak it uown back into unconjugateu biliiubin. Then, it continues to bieak it uown.
The bacteiia bieaks it uown to steicobilinogen (what it useu to be calleu).
Steicobilinogen oxiuizes to steicobilin piouuces the coloi of stool. This teim is no
longei useu. Now, it is calleu uiobilinogen (which makes the coloi of the pigment).
It is easiei to unueistanu the concept. So, 6?, <45$4u<3'6,A E&;&4$3,4 &/ E-$P,4
A$L4 6$ <-$E&;&4$3,4. All poiphyiins aie coloiless when they aie in an '-ogen'
compounu; howevei, when you oxiuize them, they have coloi. So, <-$E&;&4$3,4_
L?,4 &6 E,5$.,/ $%&A&],A &4 6?, /6$$; E,5$.,/ <-$E&;&4_ L?&5? &/ 6?, 5$;$- $=
/6$$;. A small poition of uiobilinogen is ieabsoibeu out of the colon. Nost of it goes
back to the livei. A little of it goes to the kiuney anu enus up in the uiine, wheie it get
oxiuizeu into uiobilin. This is the cause of the coloi of uiine. So_ 6?, /'., #&3.,46
6?'6 5$;$-/ /6$$; &/ -,/#$4/&E;, =$- 5$;$-&43 <-&4,. We weie taught that
steicobilinogen is in the stool anu uiobilinogen is in the uiine; howevei, steico = uio,
so the same compounu is iesponsible foi coloi change in feces anu uiine. They aie
not uiff pigments, they aie the same. So, if you have obstiucteu bile flow (in the livei
oi CBB), what shoulu the coloi of the stool be. Light coloieu - bc the uiobilinogen
woulu not have access to the stool to coloi it. Also, woulu not have uiobilinogen in
the uiine. This leaus to jaunuice.
@@) t'<4A&5,
To calculate jaunuice, they take the total biliiubin anu finu out the peicentage of
biliiubin that is conjugateu (uiiect biliiubin). Example: total is 1u, conj = S, theiefoie
conj biliiubin = Su%. So, they subuiviue jaunuice into S types - conjugateu biliiubin
less than 2u% (theiefoie most of it is unconjugateu),
btwn 2u-Su% (theiefoie some is conj anu unconj), anu
gieatei than Su% (most of it is conjugateu biliiubin). Its also means that you have
obstiuction.
If it is <4A,- 7fn, this #-&.'-" <45$4u<3'6,A ?"#,-E&;&-<E&4,.&'. So what can
inciease unconj biliiubin. !,.$;"6&5 '4,.&'/_ /#?,-$5"6$/&/_ [>G]_ (V2
?,.$;"6&5 A] $= 6?, 4,LE$-4_ D? ?,.$;"6&5 A] $= 6?, 4,LE$-4_ #?"/&$;$3&5
u'<4A&5, $= 6?, 4,LE$-4 (bc they cannot conjugate it). So, theie is incieaseu
unconjugateu biliiubin bc bieaking uown moie RBC's, have pioblems with
conjugating enzymes - eithei too immatuie oi they aie missing enzymes (>-'&3;,-
Q'uu'- /"4A-$.,). So, we aie eithei making too much bc we aie bieaking uown
too many RBC's oi we have a pioblem with conjugating enzymes - which is little
babies with physiologic jaunuice uz of the newboin, oi iaie uz's wheie we aie
ueficient in the enzyme (Ciaiglei Najjai).
The uz's E6L4 7f^ Nfn aie hepatitis. !,#'6&6&/ = inflammation of the livei (not
just some of it, all of it). So, bc it's a sick livei, it uoesn't want to take up the
unconjugateu biliiubin. 0nconj livei builus up behinu the livei. Inflammation in the
livei will maybe uestioy the aichitectuie in the livei anu bieak open bile uucts that
have conj biliiubin in them. Now, bc you have uisiupteu the aichitectuie, theie is a
possibility of watei soluble biliiubin to get into the bloou stieam (bc theie is
neciosis of livei cells anu bile uucts - so you will get conjugateu biliiubin in theie,
too) - leauing to 2u-Su%. This &45;<A,/ ';; 6?, ?,#'6&6&/ H&45;<A&43 ';5$?$;&5).
If it is 3-,'6,- 6?'4 Nfn, this is a N0 BRAINER - it is cleaily an $E/6-<56&$4 $=
E&;,. We have intiahepatic obstiuction (&46-'?,#'6&5 5?$;,/6'/&/), meaning that
you aie blocking bile flow in the livei (tiiau is blockeu). Also have ,%6-'?,#'6&5
5?$;,/6'/&/ (outsiue of the livei). Theie is only one thing outsiue the livei that can
leau to this - >VG H5$..$4 E&;, A<56I. Theiefoie, something is obstiucting that - a
stone in the common bile uuct that came fiom the uB (play ouus). Can also have
caicinoma of the heau of the pancieas - bc uucts go thiough the heau of the
pancieas. As a iesult, you have complete bile uuct obstiuction. So, theie is
intiahepatic cholestasis anu extiahepatic cholestasis. So, what will happen is like
watei behinu a uam. If you block bile flow, it will back up - wheie uoes it back up.
Backs up to wheie it was maue (the livei cells - iemembei this is an excess of
conjugateu, uiiect biliiubin). In the livei cells, it bubbles outsiue, anu has access to
the sinusoius anu now is in the bloou stieam. So, the pieuominant factoi in the bloou
stieam is >2QtMW(+ZG E&;&-<E&4, which is watei soluble. So, will ?'J, J,-" A'-P
",;;$L <-&4, '4A 6?, /6$$; L&;; E, X@W!+ 5$;$-,A) This combo - ?&3? 5$4u
E&;&-<E&4_ E&;&-<E&4 &4 6?, <-&4, (BAS to be conjugateu bc it's in the uiine anu
theiefoie watei soluble), '4A ;&3?6 5$;$-,A /6$$;/ C 2V[+DM>+@2Q (nothing else
can uo this, anu it is eithei intiahepatic oi extiahepatic).
() >$43,4&6'; M45$4u<3'6,A ?"#,-E&;&-<E&4,.&'/
1) W&;E,-68/ /"4A-$.,
Seen if you fast foi ovei 24 his anu get jaunuice, AB, b9 (theiefoie uo not neeu a
bx). B,5?0 #-$E &4 6'P&43 <# E&;&-<E&4 '4A #-$E &4 5$4u<3'6&43 E&;&-<E&4,
theiefoie it is #-,A$.&4'46;" '4 <45$4u<3'6,A ?"#,-E&;&-<E&4,.&'. So, if you
want to see if pt has it, uo 24 hi fasting test. So, get baseline biliiubin when they aie
not jaunuiceu anu uon't eat foi 24 his anu come back. When they come back they aie
jaunuiceu. Let's say the baseline is 1, anu you uouble the baseline aftei 24 his, pt has
uilbeit's synuiome. Ex. pt comes back aftei fasting test anu is 2.S.
7
4A
B>> u'<4A&5, C W&;E,-6/ /"4A-$., HB> C ?,# (I) Ex. iesiuent that gets
jaunuice, but uiun't have neeule stick = he has uilbeit's uz bc was fasting (enzyme
levels aie noimal, high unconj biliiubin levels). Rx. Nothing
7) >-'&3;,- Q'uu'-
V) >$43,4&6'; >$4u<3'6,A ?"#,-E&;&-<E&4,.&'/
G<E&4 t$?4/$4i D$6$- /"4A-$.,/: uenetic uz's involving piob getting iiu of C0N}
biliiubin in the bile uucts. So, this is #-,A$.&4'46;" ' 5$4u ?"#,-E&;&-<E&4,.&'. In
Bublin }ohnson, have a black coloieu pigment that builus in the livei anu get black
livei.
@@@) X&J,- T<456&$4 +,/6 HXT+/I
What aie 6-'4/'.&4'/,/ useu foi. They aie &4A&5,/ $= ;&J,- 5,;; 4,5-$/&/
(hepatitis). AST (Su0T) anu ALT (SuPT); (X+ is moie specific bc it is only founu in
the livei; ([+ is in muscle, RBC's anu livei.
Theiefoie, if you have a J&-'; ?,#'6&6&/, with massive livei cell neciosis, which
woulu be the pieuominant tiansaminases elevateu. (X+. Ex: 2Suu ALT anu 22uu
AST. So ALT will be the main livei cell enzyme ,;,J'6,A &4 A&==</, ;&J,- 5,;;
4,5-$/&/.
In ';5$?$;&5 ?,#'6&6&/, this is not what happens. Theie is a ieason: ([+ is piesent
in the mito of hepatocytes. ALT is not - it's in the cytosol. Alcohol is a mito poison
(iemembei that it uncouples). AST is pieuominantly in mito, anu when pt has
alcoholic hep, ([+ &/ ?&3?,- 6?'4 (X+ (foiget the 2:1 ielationship). Theiefoie, if
you see AST highei than ALT, this is uue to alcoholic livei uz. Coulu be fatty change,
alcoholic ciiihosis, anu alcoholic hepatitis. If it's vIRAL hepatitis, ALT is biggei than
AST.
So, what aie the enzymes of 0BSTR0CTI0N ($E/6-<56&$4 $= E&;, A<56/). (;P';&4,
#?$/#?'6'/, '4A W'..' 3;<6'."; 6-'4/=,-'/,. Tiansaminases will also be up,
but not to the same uegiee. uamma glutamyl tiansfeiase is locateu in the SER. When
the SER is iev'u up, it unueigoes hypeiplasia (ie uue to uiugs: alcohol, baibs,
iifampin, anu phenytoin); you not only inciease the metabolism of the uiug, but also
inciease the synthesis of gamma glutamyl tiansfeiase. So, what woulu the classic
thing you woulu see in any ';5$?$;&5 ;&J,- A]e ([+m(X+_ ';$43 L&6? @Q>DZ([ZG
3'..' 3;<6'."; 6-'4/=,-'/,. Theie is a pioblem: alk phos is in othei things othei
than the livei - in bone (osteoplastic activity), placenta. So, how will you know
wheie the alk phos comes fiom (ie if it's fiom bile uuct obstiuction vs. othei things).
Look at 3'..' 3;<6'."; 6-'4/=,-'/, ER5 &6/ /#,5&U&5 =$- 6?, ;&J,- (so, if alk phos
up, look at gamma glutamyl tiansfeiase!). @= 6?, 3'..' 3;<6'."; 6-'4/=,-'/, @[
,;,J'6,A ';$43 L&6? ';P #?$/_ 6?&/ &/ V@XZ GM>+ 2V[+DM>+@2Q)
(;E<.&4 #-$6&., C .'-P,- $= /,J,-&6" $= ;&J,- A'.'3,. It is maue in the livei,
theiefoie if you have seveie livei uz (ie ciiihosis), it will be uecieaseu. Even bettei
than that is piothiombin time bc coagulation factois aie maue theie (most aie
maue theie - vWF is not, howevei). So, if you have livei uamage, the piouuction of
coagulation factois will be uecieaseu, anu PT will be piolongeu (incieaseu). So,
';E<.&4 ;,J,;/ '4A :+ '-, 6?, 7 E,/6 6,/6/ =$- ;&J,- /,J,-&6" H:+ &/ ' ;&66;, E,66,-
6?'4 ';E<.&4).
Theie is only one autoAb that is impoitant: '46& \.&6$ (E/ &4 #-&.'-" E&;&'-"
5&--?$/&/)
+<.$- .'-P,-/0 ';#?' =,6$ #-$6,&4 &/ ' .'-P,- =$- ?,#'6$5,;;<;'- 5'-5&4$.'.
Can also use ';#?'^1 '46&6-"#/&4 bc it is maue in the livei (it is &45-,'/,A in
hepatocellulai caicinoma).
If you have fiactionation of biliiubin (less than 2u%, 2u-Su%, anu Su+ %), can stait
uu; then give tiansaminase levels - see how it coiielates with livei uz:
tiansaminases coiielate with viial hep anu conj biliiubin of 2u-Su, oi obstiuctive
livei uz (alk phos, gamma glut) anu conj biliiubin ovei Su%.
Auuio File 28: BepatoPancieas 2
@F) F&-'; !,#'6&6&/
() B> $4 ?,#'6&6&/0
NC hep = A (followeu by B, C, B, E - in that oiuei)
A anu E = fecal oial; all the otheis aie tiansmitteu paientally
Bep A = No chionic caiiiei state
Bep E = piouuces a chionic caiiiei state only if you aie piegnant, leauing to chionic
livei uz
Bep B = Requiies Bep B to infection
Bep A = Baycaie centeis (theiefoie shoulu get vaccine to pievent; outbieaks can
occui in uaycaie centeis)
Bep A = }ail
Bep B = IvBA
Bep C = Post tiansfusion Bepatitis
Bep B = NC infection by acciuental neeule stick
Bep C,B = No piotective antibouies. Positive IgNIgu = active uisease.
V) [,-$;$3"0
!(F: anti A IgN= have hep A; anti A Igu = hau it anu won't get it again
!>F: anti C Igu Ab's aie N0T piotective anu mean that you have the uz; theie aie
no known piotective Ab's
!GF: (same as BCv) - anti B Igu = have the uz, anu no known Ab's will help cuie; if
you aie anti-B Igu positive it means you have the active uz now
So, only piotective Ab's aie BAv, BBv (suiface Ab), anu BEv.
!,# V H!VFI
T&-/6 .'-P,- 6?'6 5$.,/ <# &/ /<-='5, (3 H!V/(3I. It comes up about 1 month
aftei you have the infection. You uon't know you have it anu aie asymptomatic. The
enzyme stuuies aie noimal. The next thing that comes up is the bau guys: Z (3
H!V,(3I '4A !VF GQ(, ER5 6?,/, '-, $4;" $4,/ 6?'6 '-, &4=,56&J,. Then the fiist
Ab comes up a lil aftei the BNA anu E Ag, which is 5$-, (E @3B H(46&^!V5I (this is
expecteu bc the fiist Ab against acute inflammation is IgN). The majoiity of people
with Bep B iecovei (about 9u%); those with BIv+ nevei iecovei anu will have
chionic cases bc they have no immune iesponse to knock it off. If you uo iecovei
the U&-/6 6?&43/ 6$ 3$ 'L'" '-, Z (3 H!V,(3I '4A !VF GQ() The ;'/6 $= 6?, (38/
6?'6 3$,/ 'L'" &/ /<-='5, (3 H!V/(3I. So, suiface Ag is the fiist to come anu the
last to leave (like a "house within a house" - look at the chait anu will see that S Ag is
the big house anu E Ag anu BBv BNA aie the lil houses unuei big house). In othei
woius, it is INP0SSIBLE to be E Ag positive anu S Ag negative (Z (3 '4A GQ( 5$.,
<# '=6,- [ (3 '4A ;,'J, E,=$-,).
[<-='5, (E uoesn't come up until about 1 month aftei [ (3 is gone, so theie is this
gap, which is a 'L&4A$L8 with nothing elevateu (only has one Ab theie; S Ag, E Ag,
BBv BNA aie all gone, anu S Ab not theie yet). So, how uo you know the pt BAB Bep
B. Coie IgN uoesn't leave - it stays theie anu becomes Igu ovei time. So, the maikei
foi that L&4A$L #,-&$A when all the bau guys aie gone anu suiface Ab hasn't
aiiiveu yet, is 5$-, (E @3B (which tells you that you BAB Bep B anu aie in the
piocess of iecoveiy). Theie is no way you aie infecteu uuiing this peiiou - why. Bc
E Ag anu BBv BNA aie not theie. Theiefoie, you aie not infective - it just means that
you BAB Bep B anu aie in the piocess of iecoveiing. b2M (DZ Q2+ @QTZ>+@FZ -
this is between the S
th
anu 6
th
month.
So, if you hau Bep B, theie shoulu be 2 Ab's that you have: 5$-, (E @3W '4A /<-='5,
(E @3W.
If you have been J'55&4'6,A, cannot have anything bc you hau yeast make suiface
Ag, which is what the vaccine consists of. The only bau Ab you can get fiom injecting
suiface Ag is Ab's against it. So, only Ab you will have if you weie vaccinateu is
[<-='5, (E. N0T coie Ab Igu bc weie not injecteu with that. Coie Ab is not a
piotective Ab.
>) >?-$4&5 ?,#'6&6&/ is a uefinition: "!$L ;$43 ?'J, "$< ?'A /<-='5, (3ed @= &68/
.$-, 6?'4 ` .$46?/, you have chionic Bep B. So, aie you infective oi not. - aie
you an infective caiiiei oi healthy caiiiei. You automatically know if you aie an
&4=,56&J, 5?-$4&5 5'--&,- &= "$< ?'J, !VF GQ(. This means that you aie a patient
with chionic Bep B that is infective. So, you'ie a walking hazaiu, anu youi intimate
contacts neeu to be immunizeu bc the uz can be tiansmitteu sexually to those
people, oi by Iv (IvBA's). @= "$< '-, 4,3'6&J, =$- Z (3 '4A !VF GQ( E<6 '-,
/<-='5, (3 #$/&6&J,_ 6?,4 &6 .'P,/ "$< ' c?,';6?"d 5'--&,- (this uoes not mean
you aie healthy - you aie still a chionic caiiiei of Bep B). If you aie a healthy caiiiei,
howevei, the chances of iecoveiy aie excellent bc in about one yeai, S Ag will
uisappeai anu S Ab will come up. Will also have coie Ab Igu at this time - this means
that you have a goou chance of total iecoveiy. Also have ' 3$$A 5?'45, $= -,5$J,-"
L&6? Z (3 ER5 #6 &/ ' 5'4A&A'6, =$- (;#?' @TQ 6?,-'#" HG2>I) Q,J,- 3&J,
5$-6&5$/6,-$&A/ 6$ '4" 5?-$4&5 J&-'; &4=,56&$4/)
G) D,J&,L0
What we expect in acute hepatitis B (what woulu the maikeis be). S Ag, E Ag, BBv
BNA, anu coie IgN
What if the pt is in the winuow peiiou. Coie IgN
What if hau Bep B, but have iecoveieu fiom it. Coie Ab Igu anu suiface Ab Igu
What if pt was vaccinateu (what is the 0NLY thing you shoulu have). Suiface Ab Igu
What if you have at the enu of 6 months S Ag, coie IgN, with eveiything else neg.
Bealthy caiiiei
What if you have aftei 6 months suiface Ag, E Ag, BBv BNA anu coie Ab IgN.
Infective caiiiei.
F) @4U;'..'6$-" X&J,- G&/$-A,-/
() (.,E&'/&/0 Z46'.$,E' ?&/6$;"6&5' \
0iganism is iesistant to aciu - swallow it anu will not uie in piesence of aciu. It ex-
cysts in the cecum, within an alkaline enviionment. Bas a chemical that can uiill a
hole thiough the mucosa, leauing to flask shapeu ulceis, anu leaus to E;$$A"
A&'--?,'. 0nfoitunately, bc the cecum is uiaineu by the poital vein, anu is foiming
an ulcei, theie is a chance that it can uiill anu hole, get into the poital vein tiibutaiy
anu get to the iight lobe of the livei, wheie it will piouuce an abscess. It will stait
uissolving the livei - hence teim anchovy paste abscess bc it looks like anchovy
paste (a biownish liquiu). If it wants to, it can uiill a hole thiough the iight
uiaphiagm, go to the lungs, anu piouuce an effusion, anu go anywheie it wants in the
systemic ciiculation - biain. Rx - metioniuazole. +-$#?$]$&6,/ (sliue) with ieu
paiticles in them, which aie RBC's. The only piotozoa that can phagocytose is
Z46'.$,E' ?&/6$;"6&5' H4$ $6?,- '.$,E' 5'4 #?'3$5"6$/, DV>8/) - this is a veiy
chaiacteiistic finuing. Netioniuazole is useu in the tieatment of giaiuiasis,
Entamoeba histolytica, vaginosis, c uiff, anu tiichinosis.
V) !"A'6&A A]
1. Befinitive vs. inteimeuiate host
G,U&4&6&J, ?$/6 = sexually active woims that have the ability to mate anu lay eggs.
@46,-.,A&'6, ?$/6 = only have the laival foim; uo not have sexually active auults.
These aie the stages: Auult, egg, laiva. Auult lays eggs, anu the eggs uevelop into
laiva. If you have the laiva foim in you, it will stay theie bc that it's the enu stage
foim. If you have the egg foim, it will uevelop into a laiva, but the laiva can't go
anywheie else. If you have the auult foim in you, it will give an egg, which changes to
laiva. Laiva foim cannot go anywheie - it is the enu stage foim.
[?,,# ?,-A,-8/ A] H3$4$5$55</ J,-.&5<;'-&/ $- <4&;&5<;'-&/ HeII
The sheep uog eats some sheep meat (theie aie laival foims in the sheep; theiefoie,
the sheep is the inteimeuiate host). Bog eats sheep, anu has laiva in the uog. The
laiva foim uevelops into an auult within the uog, anu the uog becomes the uefinitive
host. The uog has sexually active woims insiue it anu the woims lay eggs within the
uog. Bog is petteu, gets eggs on theii hanu anu into pts foou, which is eaten. So, now,
the pt has the egg, which uevelops in the laiva (cannot go any faithei bc laival foim
is enu stage), anu the pt (human) becomes the inteimeuiate host. So, the sheep is an
inteimeuiate host, the uog is the uefinitive host anu the sheep heiuei is an
inteimeuiate host. Bo not want to iuptuie these cysts, bc if the fluiu gets into the
abuominal cavity, leaus to anaphylactic shock.
>) +) /$;&<. H#&3 6'#,L$-.I
You go to a baibecue anu eat unueicookeu poik (laiva in the pig meat, which is
eaten). The laiva uevelop into the auult foim within the pt (so, theie is a sexually
active woim insiue). So, pt becomes uefinitive host, while the pig was the
inteimeuiate host. Now you have a family membei that is a uefinitive host (has
sexually active woims insiue them) - lets say this family membei is making salau
that night, anu uiun't wash theii hanus, so some of the eggs got into the salau. The pt
eats the salau with the eggs in it. What is the egg going to foim insiue me. Laiva.
What is this calleu cystoceici. Bo they foim auults. No, stops theie. Theiefoie, pt
has cystoceicosis. What aie the ;'-J', 3$&43 6$ A$e +?," ;&P, 6?, ,", '4A 6?,
E-'&4 HL?,-, 6?," =$-. ' 5"/6 &4 6?, E-'&4_ 5';5&=" '4A ;,'A 6$ /,&]<-, '56&J&6"
=$- 6?, -,/6 $= 6?, #68/ ;&=,I. So, in this uz, the pt can have two foims of it. If pt ate
the infecteu pig, they can be the uefinitive host. If you get the egg in youi mouth, you
become an inteimeuiate host, anu the egg can become laiva, which will go on to
cystoceicosis. So the laivae foim is the uangeious foim in T. solium.
(NC SE of cataiacts = glucocoiticoius)
F@) Q<6.,3 X&J,-
NCC = RBF
Thiombus in poital vein will N0T leau to nutmeg livei because poital vein is befoie
emptying into the livei. Woulu you have ascites. Yes. Poital BTN. Yes. vaiices. Yes.
But is livei big anu congesteu. No.
Thiombus in hepatic vein: is calleu Buuu Chiaii synuiome (NCC polycythemia
Rubiveia, 2
nu
NCC = biith contiol pills). Woulu you have a nutmeg livei. Yes -
hepatic vein empties the livei. You get a huge livei, anu is a suigical emeigency anu
uie 1uu% of the time if you uon't have suigeiy.
So, these aie piepost hepatic thiomboses H:-,?,#'6&5 C #$-6'; J,&4_ #$/6?,#'6&5
C ?,#'6&5 J,&4I)
F@@) (;5$?$;&5 ;&J,- A]
B> .'4&=,/6'6&$4 &/ ='66" 5?'43, H/6,'6$/&/I. Bc alcohol metabolism, have
NABB's, acetate, anu acetyl CoA. NABB's mess with pyiuvate anu conveit it into
lactate leauing to fasting hypoglycemia, anu metabolic aciuosis. Acetyl CoA can make
FA's anu glyceiol S phosphate anu Tu anu fatty change, oi can be conveiteu into
ketone bouies, which causes an incieaseu anion gap: metabolic aciuosis. Fatty
change is ieveisible if the alcoholic stops uiinking.
(;5$?$;&5 ?,#'6&6&/ is veiy bau; can have hepatic encephalopathy, ascites, etc.
Alcoholic hep is uiff fiom fatty change bc theie is fevei, neutiophilic leukocytosis,
veiy high AST>ALT, anu gamma glutamyl tiansfeiase is up. You'ie big time sick anu
if you uo not stop uiinking you will uie. It is veiy seiious systemic uz. If pt
hospitalizeu foi alcoholic hep, is ieleaseu anu takes alcohol, they will uie. See
B';;$-" E$A&,/ (ubiquinateu keiatin miciofilaments). Toxic compounu that causes
ciiihosis is acetaluehyue bounu to a piotein, not acetaluehyue by itself. Ito cell
noimally is the cell that stoies vit A. In an alcoholic the acetaluehyue piotein
complex stimulates the Ito cell to make fibious tissue anu collagen. The Ito cell,
which is iesponsible foi stoiing vit A, is now putting uown collagen tissue anu is
iesponsible foi causing fibiosis. Fibious tissue is a big pait of alcoholic tissue uz.
F@@@) >?$;,/6'/&/
>?$;,/6'/&/ = obstiuction to bile flow, uue to a stone in the CBB. Ex: have a
cholesteiol stone with a ueep gieen coloieu livei. Bile is blockeu, which has conj
biliiubin in it anu is backeu up into the livei. The conj biliiubin will eventually ieflux
into the sinusoius, anu leaus to biliiubin in the uiine anu light coloi stools, with N0
uiobilinogen in the uiine. The yellow uiine is uue to watei soluble conj biliiubin in
the uiine. What enzymes aie elevateu. Alk phos anu gamma glutamyl tiansfeiase.
What is the mech foi getting iiu of cholesteiol. Bile. So, you ieflux cholesteiol,
biliiubin anu bile salts (they aie all iecycleu). Woulu it suipiise you that they have
hypeicholesteiolemia, too. No bc it is iecycleu. The bile salts ueposit in the skin,
leauing to itching.
7 $6?,- 5'</,/ $= 5?$;,/6'/&/0
Bile uuct iauical, suiiounueu by fibious tissue, bloouy uiaiihea with LLQ ciampy
pain, jaunuice - what is the IBBz. M>
Common bile uuct suiiounueu by fibious tissue - ux. :-&.'-" /5;,-$/&43
5?$;'43&6&/. NCC piimaiy scleiosing cholangitis = M>
What cancei can uevelop bc it involves the bile uuct. >?$;'43&$5'-5&4$.' (NCC
in this countiy, in S
iu
woilu countiies, it is uue to Clonoichis sinensis - Chinese livei
fluke).
@g) :-&.'-" V&;&'-" 5&--?$/&/
Su yo woman with geneializeu itching, finu enlaigeu livei on PE, noimal biliiubin
(no jaunuice), alk phos anu gamma glutamyl tiansfeiase aie huge (obstiuctive type
of enzymes), tiansaminases aie elevateu - ux. Piimaiy biliaiy ciiihosis, which is '4
'<6$&..<4, A] 6?'6 ;,'A/ 6$ 3-'4<;$.'6$</ A,/6-<56&$4 $= 6?, E&;, A<56/ &4 6?,
#$-6'; 6-&'A - why uoesn't she have jaunuice. Let's say you have 1 million tiiaus,
have the uz anu knock off 2Su,uuu of them. Still have 7S% that can hanule the
biliiubin loau. S yeais latei, only have Su% (Suu,uuu uestioyeu). Still no jaunuice,
eventually, moie knockeu off anu get jaunuice way uown the line. So, the ieason why
pt won't get jaunuice is bc pt has a ieseive that can hanule the biliiubin. Theiefoie,
theie is no ieason to have jaunuice eaily anu it comes late. What is the Ab to oiuei in
this pt. (46&^.&6$5?$4A-&'; '46&E$A&,/ (antimiciosomal = hashimoto's).
g) G-<3 ,==,56/
Biith contiol (0CP) anu anabolic steioiu have the same effect on the livei. +?, 2>:
'4A '4'E$;&5 /6,-$&A/ E$6? #-$A<5, &46-'?,#'6&5 5?$;,/6'/&/. Ex. wt liftei
(assume he'on steioius) uevelops jaunuice, anu viial seiology is negative, high alk
phos anu gamma glutamyl = uue to steioius (not hepatitis). 0ne of the NCC's
jaunuice in piegnancy is b9 intiahepatic cholestasis. This is bc of the estiogen
uuiing piegnancy, which piouuces intiahepatic cholestasis. Rx. Belivei baby (goes
away aftei ueliveiing baby). Lets say woman takes 0CP anu gets jaunuice; when she
become piegnant, she will uevelop jaunuice, too bc of the estiogen effect. So,
intiahepatic cholestasis is a noimal complication of 0CP's anu anabolic steioius.
V$6? $= 6?,/, A-<3/ ';/$ #-,A&/#$/, 6$ ' Ea ;&J,- 6<.$-_ 5';;,A ;&J,- 5,;;
'A,4$.' 'P' ?,#'6&5 'A,4$.'. It has a nasty habit - &6 ;&P,/ 6$ -<#6<-,_ ;,'A&43
6$ &46-'#,-&6$4,'; ?,.$--?'3, HL?&5? 5'4 P&;; "$<I) Example: wt liftei (assume
he's on anabolic steioius) who is lifting anu suuuenly becomes hypotensive anu
collapses. Finu abnoimal liveicavity - what is most likely cause. Ruptuieu livei cell
auenoma bc pt is on anabolic steioius. [$_ 2>:8/ '4A '4'E$;&5 /6,-$&A/ ?'J, 7
/&.&;'- ,==,56/0 E$6? 5'4 #-$A<5, Ea &46-'?,#'6&5 5?$;,/6'/&/ HL?&5? 3$,/ 'L'"
&= "$< /6$# 6?, A-<3I '4A ;&J,- 5,;; 'A,4$.' L?&5? &/ /</5,#6&E;, 6$ -<#6<-,)
Foi women, if they aie on biith contiol, then get off it to get piegnant - let's say they
have a livei cell auenoma they uiu not know about (that uevelopeu with 0CP use),
then get piegnant, then get an intiapeiitoneal hemoiihage, anu then what is uu.
Ruptuieu ectopic piegnancy oi iuptuie intiapeiitoneal hemoiihage. Step 2:
piegnant women have the tenuency to have splenic aiteiy aneuiysm = iuptuie.
g@) !,.$5?-$.'6$/&/
Example: ?"#,-#&3.,46,A #6 \ 'A<;6 6?'6 &/ A&==</,;" ?"#,-#&3.,46,A '4A ?'/
A&'E,6,/ H6"#, @ A&'E,6&5I C E-$4], A&'E,6,/ C ?,.$5?-$.'6$/&/ C T, $J,-;$'A_
'<6$ -,5_ -,'E/$-E 6$$ .<5? T,) Bemosiueiosis is acquiieu iion oveiloau by being
an alcoholic. Iion supplements aie contiainuicateu in the elueily bc it will cieate
hemosiueiosis anu have iion oveiloau. Back to hemochiomatosis: it's an autosomal
iecessive uz anu what happens is that insteau of ieabsoibing 1u-1S% of iion fiom
foous, you aie absoibing 1uu% of iion. Taiget oigan is the livei. Whenevei Fe is
absoibeu into cells, it piouuces hyuioxyl fiee iauicals. So, the Fe uoesn't uamage
anything, it's the fiee iauicals (the hyuioxyl fiee iauicals -Fenton ixn). If you aie
uamaging livei cells, will leau to fibiosis anu ciiihosis. +?," (XX ?'J, 5&--?$/&/ &4
T, $J,-;$'A, ,&6?,- E" ?,.$/&A,-$/&/ $- ?,.$5?-$.'6$/&/) In ciiihosis, you see
livei with biownish pigment, Piussian blue stain (to see Fe), anu a vERY BIuB
inciuence of hepatocellulai caicinoma. Can also go elsewheie-pancieas-theiefoie
can have EX0ciine anu ENB0ciine uysfunction, leauing to malabsoiption.
Bestiuction of islet cells leaus to veiy biittle type I uiabetes. Also ueposits in skin anu
leau to hypeipigmentation (bionze look). This is a combo of Fe uepositing theie anu
by stimulating melanocytes, theiefoie theie is Fe pigmentation anu melanin. Can go
into joints anu leau to polyaithiitis, can go to pituitaiy, leauing to hypopituitaiism,
can go to heait anu piouuce iestiictive caiuiomyopathy. Bow you uo /5-,,4 =$-
&-$4 $J,-;$'Ae [,-<. =,--&6&4) [,-<. T, C ?&3?) Z%5,// T, /6$-,/_ 6?,-,=$-,
A,5-,'/,A /"4 $= 6-'4/=,--&4) +?, +@V> &/ A,5-,'/,A) n /'6 &/ &45-,'/,A_ /,-<.
=,--&6&4 &/ &45-,'/,A) D%e :?;,E$6$.". Bo not use chelation theiapy. They
puiposely make you Fe uef. This uz is the next to the most common autosomal iec uz.
!,.$/&A,-$/&/ C (>wM@DZG T, $J,-;$'A \ =-$. ';5$?$;)
g@@) O&;/$48/ A]
S'"/,- T;,&/5?,- -&43 - biown iing aiounu coinea. What is uegeneiation calleu.
!,#'6$;,46&5<;'- A,3,4,-'6&$4. :6 L&6? 'E4$-.'; .$J,.,46 H5?$-,'I
A&/$-A,-_ A,.,46&'_ '4A 5&--?$/&/) (<6$ -,5,//&J,) G,=,56 &4 -&AA&43 >< &4 E&;,i
/$_ 6?, >< E<&;A/ <# '4A '55<.<;'6,/ &4 6?, ;&J,-) veiy toxic. So, ovei a peiiou of
months to yeais, you go fiom chionic active hepatitis to ciiihosis. When you get a
total Cu level, what uoes it incluue. Fiee Cu anu binuing piotein foi Cu. +?, E&4A&43
#-$6,&4 &/ 5';;,A 5,-<;$#;'/.&4) So, some Cu is attacheu to ceiuloplasmin. So, the
total Cu measuieu incluues bounu anu fiee. 9S% of a noimal total Cu level is ielateu
to Cu attacheu to ceiuloplasmin. So, most of the total Cu level is bounu to
ceiuloplasmin, not the Cu that is fiee. [$_ aNn &4 ' 4$-.'; #,-/$4 6?, 6$6';
5$##,- &/ >< 6?'6 &/ E$<4A '4A &4'56&J, 6$ 5,-<;$#;'/.&4) So, is ceiuloplasmin a
piotein. Yes. So, with ciiihosis, aie you synthesizing ceiuloplasmin. No. Theiefoie,
theie is a ueciease of binuing piotein foi Cu. So, =-,, 5< &45-,'/,A) [$_ 6?, 6$6'; ><
;,J,; &/ A,5-,'/,A HER5 ;,// 5,-<;$#;'/.&4I_ E<6 6?, =-,, >< &/ &45-,'/,A H.$-,
<4E$<4AI) Rx. PCNamine (Cu binuei). Lenticulai nucleus messeu up (cauuate
nucleus in BB)
Auuio File 29: BepatoPancieas S - Renal 1
g@@@) >&--?$/&/
Nevei focal, always uiffuse. The bumps all ovei it aie calleu iegeneiative nouules.
Know that livei tissue is stable, theiefoie it's usually in the uo phase, anu something
has to stimulate it to go into the cell cycle to uiviue. The livei has an amazing
iegeneiative capacity. Regeneiation of livei cells aie hepatocytes with no tiiau, no
cential vein, anu no sinusoius. t</6 L';; 6$ L';; ?,#'6$5"6,/ L?&5? '-, L$-6?;,//.
Bumps aie iegeneiative nouules, no tiiau; theie aie just wall to wall hepatocytes
suiiounueu by fibious tissue. Staits off as micionouulai (less then S mm) anu enus
up macionouulai (ovei S mm). So, have livei, but cells not woiking. Bow is a poital
vein gonna be able to empty into the livei when theie aie no sinusoiutiiaus. It's a
pioblem - poital BTN.
>$.#;&5'6&$4/: Pitting euema, ascites, esophageal vaiices, anu metabolic piobs
(5'44$6 .,6'E$;&], ,/6-$3,4, leaus to gynecomastia). Cannot look at
gynecomastia, have to feel it.
[&A, ,==,56/ $= #-$E;,./ $= ,/6-$3,4 .,6'E$;&/.: Siue note: Theie aie S times
in a lifetime wheie males can uevelop gynecomastia. 1. Newboins males have boobs
bc estiogen fiom mom; newboin giils with peiious bc estiogen fiom, then uiop
off, leaus to bleeuing. 2. Nales also get boobs in teens (pubeity). S. Nales also get
boobs when they tuin olu bc testosteione goes uown anu estiogen goes uown,
leauing to gynecomastia - so, get boobs (gynecomastia) thiee times thioughout life,
anu this is noimal. Example: 1S yo unilateial subalveolai mass, what is
management. Leave it alone. uynecomastia is not always bilateial, it is usually
unilateial. Women have uiff size bieasts bc each bieast has uiffeient susceptibility
to estiogen, piogesteione, anu piolactin. Nen uo not have bieast tissue, theiefoie
moie likely that one will enlaige, the othei will not. Palmei eiythema (ielateu to
estiogen), spiuei angioma, vit uef's, uupation's contiactuie in palm (fibiomatosis -
incieaseu fibious tissue aiounu the tenuon sheaths, causing fingeis to coil in,
commonly assoc with alcoholics) - these aie all estiogen abnoimalities.
Complication of Ascites - auult with ascites - spontaneous peiitonitis uue to E coli.
Chilu with nephiotic synuiome anu get ascites anu spontaneous peiitonitis, what is
the oiganism. Stiep pneumoniae. So, auults with ascites anu spontaneous peiitonitis
= E coli, while kiu with ascites anu spontaneous peiitonitis = Stiep pneumoniae.
g@F) !,#'6$5,;;<;'- 5'-5&4$.'
Nouulaiity; Cancei in hep vein tiibutaiy (ie). This cancei almost always uevelops in
the backgiounu of ciiihosis. It is veiy iaie foi hepatocellulai caicinoma to uevelop
without ciiihosis piesent. Since alcohol is the NCC's ciiihosis, is it also the NCC of
cancei. N0. B>>8/ ?,#'6$5,;;<;'- 5'-5&4$.' C #&3.,46 5&--?$/&/0
?,.$5?-$.'6$/&/i ?,#'6&6&/ V '4A >) This cancei can piouuce ectopic hoimones -
EP0 (leaus to 2
nu
aiy polycythemia), insulin like uF (leaus to hypoglycemia). Tumoi
maikei: alpha feto piotein. Example: pt with unueilying ciiihosis, anu is stable. But
suuuenly the pt begins to lose wt anu ascites is getting woise. Bo a peiitoneal tap
anu it is hemoiihagic (uo not assume it is tiaumatic fiom the neeule, unless they say
it). If theie is bloou in the aciuic fluiu it is pathologic bleeuing. So, 6?&/ ?% HL6 ;$//_
E,3&44&43 6$ A,6,-&$-'6, /<AA,4;"_ E;$$A &4 '5&A&5 U;<&AI) S4$L &6 &/
?,#'6$5,;;<;'- 5'-5&4$.'_ E<6 L&;; '/P \ L?'6 6,/6 A$ "$< A$e (;#?' =,6$
#-$6,&4) Nany tumois in livei = mets, piob fiom lung; lets say it's a nonsmokei,
what is the piimaiy cancei. Colon cancei, bc he is a nonsmokei, theiefoie it won't
be fiom a piimaiy lung cancei, so the 2
nu
NCC is colon cancei anu it uoesn't have a
high association with smoking.
Remembei the 2
nu
most common cause: example of a small bowel obstiuction, the
NCC is auhesion fiom pievious suigeiy, but if the pt uiu not have any suigeiies then
it's uue to inuiiect inguinal heinia.
W(XXVX(GGZD G{
@) (/P 'E$<6 #'6?$3,4,/&/ $= /6$4, \ 6$$ .<5? 5?$;,/6,-$; &4 E&;, $- 6$$ ;&66;,
E&;, /';6/) You will have a supeisatuiateu stone with cholesteiol - will get
5?$;,/6,-$; /6$4, HB> /6$4,I) 0i, too little bile salts, both leau to stones. Anything
that causes bile salt uef (ciiihosis, obstiuction, Cholestyiamine, Ciohn's uz) can leau
to gallstones bc too lil bile salts.
@@) :&3.,46 /6$4,/
Yellow stones (know they aie not cholesteiol stones) - 2S yo female, R0Q ciampy
pain, fevei, point tenueiness, neutiophilic leukocytosis, stones ievealeu on
ultiasounu. CBC showeu a milu noimocytic anemia anu a coiiecteu ieticulocyte ct of
8%. Splenomegaly on PE anu family hx of splenectomy. G%e >$43,4&6';
/#?,-$5"6$/&/; bc she has been hemolyzing RBC's all hei life, she puts a lot of
biliiubin into conj biliiubin anu theiefoie has supeisatuiateu bile with biliiubin, anu
foims >' E&;&-<E&4'6, /6$4,/ 6?'6 '-, u,6 E;'5P. Seen with ultiasounu.

What is the /5-,,4&43 6,/6 $= 5?$&5, foi stones. 0ltiasounu. Scieening test of
choice foi anything in the pancieas = CT - ieason why is bc bowel oveilies pancieas
anu messes up ultiasounu, theiefoie not as sensitive. Always put CT foi pancieas;
uB = ultiasounu (can tell uiametei of CBB to tell if theie is a stone in it).
:(Q>DZ([
@) >"/6&5 T&E-$/&/
Cystic fibiosis - giowth alteiation bc mucous in uucts of the pancieas. See
'6-$#?" bc block lumen of exociine uucts, anu piessuie goes back to the glanus anu
that piessuie atiophies the glanus, ;,'A&43 6$ .';'E/$-#6&$4. Can cystic fibiosis
also leau to uiabetes. Yes - bc eventually fibiose off the islet cells, leauing to 6"#, @
A&'E,6,/, too.
B$;,5<;'- E&$: c'some 7 with S nucleotiue ueletion, anu those S nucleotiues coues
foi phenylalanine. So, you aie A,= $= #?,4";';'4&4, &4 6?, 5"/6&5 U&E-$/&/
6-'4/.,.E-'4, -,3<;'6$- #-$6,&4 H>T+DI) So, all its missing is phenylalanine.
Nost things, aftei they aie maue in the iibosome in the RER, have posttianslational
mouifications in the uolgi appaiatus, which is wheie the ieal uefect is. +?, -,';
#-$E;,. &/ L?,4 &6 3,6/ 6$ 6?, W$;3& '##'-'6</ \ &68/ /<##$/,A 6$ E, .$A&U&,A
'4A /,5-,6,A 6$ 6?, 5,;; /<-='5,) @6 ,4A/ <# E,&43 A,3-'A,A &4 6?, 5,;;_ '4A "$<
,4A <# ?'J&43 6?, >T+D) So, the piob is in the uolgi appaiatus - it sciews it up, anu
nevei makes it to the suiface, theiefoie has no function.
So, what uoes it uo. @4 6?, /L,'6 3;'4A/_ 4$-.';;"_ &6 L$<;A -,'E/$-E Q' '4A >;
$<6 $= 6?, /L,'6 3;'4A) VR5 6?," '-, A,= &4 6?&/_ 6?," '-, ;$/&43 /';6_ L?&5? &/ 6?,
E'/&/ $= 6?, /L,'6 6,/6) S yo kiu, failuie to thiive, chionic uiaiihea, iesp infection,
mom states that the baby taste's salty when she kisses the baby. This is the give
away foi CF, bc they lose consiueiable salt anu become salt uepleteu when they aie
oveiheateu. Why aie all the secietions so thick in the lungs, pancieas, anu bile
uucts. CFTR iegulatoi - what uoes it uo. - In ;<43/, neeu to have salt anu secietions
in the lumens of the iesp tiact to keep it viscous (to keep it nice anu loose); if you aie
missing CFTR, Na is ieabsoibeu 00T of the secietions in the aiiway (theiefoie a lil
uehyuiateu). Anu, chloiiue cannot be pumpeu into the lumen of the aiiway - so you
aie taking away the 2 imp ingieuients with this pump: taking Na out anu not putting
Cl in. Theiefoie these secietions aie thick like conciete. The same is tiue foi
secietions in the pancieas (Na pumpeu out anu Cl not put in). B>> A,'6? C
#/,<A$.$4'/ ',-<3&4$/') T,-6&;&6": what is chance of male with cystic fibiosis
having chiluien. u-S% (most aie infeitile); foi females, they can get piegnant, but
only have Su% chance of getting piegnant. The pioblem is that the ceivical mucous
is as thick as conciete anu theiefoie the speim cannot penetiate, anu that is one of
the ieasons why they aie infeitile
@@) (5<6, #'45-,'6&6&/
NC uue to alcohol; 2
nu
NCC = stone caught in accessoiy uucts of the pancieas.
Amylase is elevateu. Chaiacteiistic pain: Z#&3'/6-&5 #'&4 L&6? -'A&'6&$4 &46$ 6?,
E'5P (bc it's a ietiopeiitoneal oigan).
Bave an hx of acute pancieatitis; aftei 1u uays, have a mass in the abuomen anu
they ask what uo you uo. CT - what is it. :'45-,'6&5 #/,<A$5"/6 - a lot of fluiu
accumulates aiounu an inflameu pancieas anu foims a false capsule anu has a
potential to iuptuie (not goou to have amylase in peiitoneal cavity).
R0Q with uystiophic calcification (uots on x-iay); what uo you think it is.
:'45-,'6&6&/) Is it acute oi chionic. >?-$4&5 bc theie aie so many. Is this pt likely
to be an alcoholic. Yes. What else woulu you expect - ie which of the following you
expect. - Steatoiihea (one of the causes of malabsoiption - neeu enzymes), oi may
say you have bile salt uef (no, bc pancieas has nothing to uo with bile salts),
hemoiihagic uiathesis (yes, vit K uef ielateu to malabsoiption), etc.
>'-5&4$.' $= 6?, ?,'A $= 6?, #'45-,'/ \ B>> C /.$P,-_ 7
4A
B>> C 5?-$4&5
#'45-,'6&6&/_ #'&4;,// u'<4A&5, H.'&4;" 5$4u<3'6,A E&;&-<E&4I_ ;&3?6 5$;$-,A
/6$$;/_ #';#'E;, WV H>$<-J$&/&,-8/ /&34I) C sign - peimanently inuenting the
uuouenum, uo baiium stuuy, also a sign of pancieatic cancei.
(5<6, #'45-,'6&6&/ L&6? &4U;'..'6&$4. What will that uo to peiistalsis of that
uuouenum next to it. Bow uoes the bowel ieact to the piesence of inflammation next
to it. @6 /6$#/ #,-&/6';/&43 (not thiough the entiie bowel, just theie). If this is tiue,
theie woulu just be aii in the aiea it uoesn't peiistalses - what is this calleu.
[,46&4,; /&34 (sentinel is someone that is supposeu to keep watch) - keep watch of
what. Inflammation (so, 6?, /,46&4,; /&34 P,,#/ L'65? $= &4U;'..'6&$4); the
classic aiea is the pancieas. This &/ 5';;,A ;$5';&],A &;,</ H&;,</_ E" A,U&4&6&$4 &/
;'5P $= #,-&/6';/&/I) O?,4,J,- 6?, E$L,; ;'5P/ #,-&/6';/&/_ L&;; /,, '&-
'55<.<;'6, '4A L&;; 3,6 A&/6,4/&$4) What if you have a segment of bowel that is
uistenueu in the RLQ. Bas to be inflammation, the cecum is in the RLQ anu appenuix
coulu be the ieason. So, appenuicitis piouucing sentinel's sign.
CHAPTER 11: Renal
@) >'/6 -
molu of whatevei is going on in the nephiontubule. It is a piotein that is
congealing aiounu whatevei is piesent in the tubule at that time; theie is a molu
maue, anu is passeu into the uiine anu we can see it unuei the micioscope. +?&/ &/
&.# ER5 4$L L, A$ 4$6 ?'J, 6$ A$ ' -,4'; E% $= 6?, -,4'; 6<E<;,/ ER5 6?, 5'/6
L&;; 6,;; "$< L?'6 &/ 3$&43 $4. Example: if you have glomeiulonephiitis
(inflammation of the glomeiulus), you have uamageu the capillaiies anu get
hematuiia, so the RBC's aie in the nephion anu tiappeu in the cast, anu will have an
RBC cast that tells you theie is a glomeiulonephiitis occuiiing. Example: With ienal
tubule neciosis, the tubules aie sloughing off with coagulation neciosis. This will
foim a cast anu is calleu ienal tubulai cast, anu will tell you theie is ienal tubulai
neciosis. Example: manwoman with acute pyelonephiitis with neutiophils
invauing the inteistitium anu the tubules, theie aie cast of neutiophils (WBC casts),
telling me theie is infection of the kiuney. Example: spilling lipiu in uiine in
nephiotic synuiome anu foim cast of fat anu a fatty cast that you can see anu
polaiize in the uiine.
@@) M-&4';"/&/
+?, U&-/6 6?&43 6?'6 A&/'##,'-/ &4 -,4'; ='&;<-, &/ 6?, 'E&;&6" $= 6?, P&A4," 6$
5$45,46-'6, <-&4,. This occuis befoie CiB0N think about incieasing, oi even
having ienal tubulai casts. Example: taking uiine in the moining anu uoing the
specific giavity of the uiine anu seeing what it is. Bc, /#,5&U&5 3-'J&6" 5'4 6,;; "$<
&= &6 &/ 5$45,46-'6,A $- A&;<6, <-&4,) If the specific giavity is gieatei than 1.u2S,
this means that the pt is concentiating uiine anu that the kiuneys aie ABS0L0TELY
N0RNAL (this is a CBEAP test). Example: let's say I uiu a specific giavity of uiine
oveinight anu it is 1.u1u - this is veiy hypotonic uiine, anu it means that the pt coulu
not concentiate, anu that the pt is in ienal failuie. (B0NCi will not help ueteimine
this). The uiine that shoulu be concentiateu is fiom a pt that is sleeping oveinight.
!"';&4, 5'/6 \ 5'/6 $= ' #-$6,&4i .$/6;" EaR?'-.;,// (all othei casts have
pathological significance).
@@@) >-"/6';/0
M-&5 '5&A 5-"/6'; - looks like a stai; pB of the uiine has to be aciuic to foim a uiic
aciu ciystal. Pt with gout - want to stop ciystals fiom foiming, anu you know they
foim in low pB, what uo you want to uo with the uiine. Alkalinize it. Bow can you uo
that. Caibonic Anhiuiase inhibitoi (acetazolamiue). By blocking bicaibonate
ieclamation will alkalinize the uiine, anu pievent stones fiom foiming. So, simple
manipulation of the pB can pievent uiate nephiopathy.
>';5&<. 2%';'6, 5-"/6'; - look like the back of an envelope; why is this imp to
know. Example: stieet peison comes in, stupuious, has incieaseu anion gap
metabolic aciuosis. Bo a uiinalysis, anu see bunch of calcium oxalate stones - what
uiu he uiink. Ethylene glycol. What is the B> /6$4, L, #'//e >' $%';'6,. So if you
have a Ca 0xalate stone, you will have ciystals associateu with it.
!$-/, P&A4," -joineu at theii lowei poles. Will ask what is iestiicting the
movement of the kiuney. INA - it tiaps the kiuney.
@F) >"/6&5 A] $= 6?, P&A4," -
() @4='46&;, #$;"5"/6&5 P&A4," A],
which is auto iecessive; theiefoie it is piesent at biith. Bo you think this baby is
uiinating. No, theiefoie has oligohyuiamnios (uecieaseu amniotic fluiu). So, baby is
in an amniotic sac, with haiuly any amniotic fluiu aiounu it, anu theiefoie have
malfoimation uue to piessuie. Look at the nose anu eais; this is 5';;,A :$66,-/ ='5,_
L?&5? &/ ' /&34 $= $;&3$?"A-'.4&$/ &4 #$;"5"/6&5 P&A4," A]0 U;'66,4,A 4$/,_ ;$L^
/,6 ,'-/_ '4A -,5,//,A 5?&4I. This chilu wasn't able to bieath, anu when it tiieu to
bieath, it coulun't; the lungs aie hypoplastic - they nevei fully uevelopeu bc the kiu
coulun't fill them up. These cysts aie also seen in the pancieas, the livei anu just
incompatible with life.
V) (A<;6 #$;"5"/6&5 P&A4," A&/,'/,0 (:SG]
Some autosomal uominant uz show Penetiance - have the abnoimality when they
look foi it on the gene, but uo not expiess it. (so you have the genetic abnoimality,
but have nevei expiesseu it in youi life). That's the goou news - the bau news is that
you can tiansmit it to youi chilu, theiefoie it is uifficult to iecognize on the peuigiee.
Example of penetiance: familial polyposis = 1uu% penetiance - if you have the gene,
you have the uz. Example of incomplete penetiance: maifan - abnoimality on
c'some 1S, noimal paients, they uo not expiess the gene, but passeu on to chilu (this
is incomplete penetiance). APKBz is anothei example of incomplete penetiance.
So, APKBz is an autosomal uominant uz that is not piesent at biith bc AB uz have
A,;'",A .'4&=,/6'6&$4/. See cysts by 1u-12 yeais of age, always get !+Q L?&5?
L&;; 6?,4 #-,A&/#$/,/ 7 6"#,/ $= E;,,A/: (1) >?'-5$6^V$<5?'-A '4,<-"/./ (a
bloou clot) anu (2) see bloou all ovei the biain, uue to subaiachnoiu hemoiihage,
theiefoie the bloou is uue to -<#6<-, E,--" '4,<-"/.. [<E'-'5?4$&A
?,.$--?'3, = "woist heauache of my life", bloou in subaiachnoiu space.
BF: H.&6-'; J';J, #-$;'#/,I: Example: hx of BTN, abnoimality of ultiasounu in
the ienal pelvis, anu hau click muimui (theiefoie NvP) - ux. APKBz. Theie is a high
assoc of NvP with this.
G&J,-6&5<;$/&/ also has a high inciuence. Example: pt with BTN, abnoimality on
ultiasounu in ienal aiea, lost 6uu mls of bloou all of a suuuen, leauing to
hematochezia (NCC hematochezia = uiveiticulosis).
F) W;$.,-<;'- /6<==
() Q$.,45;'6<-, $= 6?, S&A4," A]0
c^&6&/d C 6"#, @@@ !:b \ 6?,-,=$-, &68/ '4 &..<4$;$3&5 A] H3;$.,-<;$4,#?-&6&/I
Example: Lipoiu nephiosis - uoes that have type III. No
Example: Focal segmental glomeiulai scleiosis. No
Example: Biabetic glomeiuloscleiosis. No.
Example: IgA glomeiulonephiitis, uiffuse membianous glomeiulonephiitis. Yes
When we say 'uiffuse', this means that EvERY glomeiulus has something wiong
with it on ienal bx. What is 'focal'. not all glomeiuli involveu.
What if uz is focal anu uz in the glomeiulus is focal. Bave a pioblem - this is calleu
Focal Segmental ulomeiulus
What uoes piolifeiative mean. Bave lots of them. So, you have many nuclei. If all
the glomeiuli have a lot of nuclei, this is uiffuse piolifeiative glomeiulonephiitis
If you just see thick membianes, its membianous glomeiulonephiitis
If you see both incieaseu cell anu thickeneu membiane. Nembianopiolifeiative
glomeiulonephiitis
Auuio File Su: Renal 2
V) (4'6$."R/5?,.'6&5
The oiuei is: bloou, enuothelial cells of the capillaiies, unueineath theie is a BN,
anu then the visceial epithelial cells (looks like feet = pouocytes; which have spaces
in between them calleu slit poies) that line the bowman's capsule. Who .'P,/R
/"46?,/&],/ 6?, WVBe F&/5,-'; ,#&6?,;&'; 5,;;/ H#$A$5"6,/I. What keeps Albumin
out of the uiine noimally. Stiong negative chaige of the BN. Who is iesponsible foi
stiong "-"of the BN. A W(W 5';;,A ?,#'-'4 /<;='6,_ L?&5? ?'/ ' /6-$43 4,3
5?'-3,) If we immunologically uamage the visceial epithelial cell, what uo we
automatically also uamage. The BN, which means you'ie gonna spill a lot of piotein
in the uiine, which means you potentially can have nephiotic synuiome if you spill
>S.S giams in 24 his).
>) +,/6 $4 D,4'; V%
[6'&4/ - ioutine B & E hemotoxylin stains, silvei stains. @..<4$U;<$-,/5,46 stain
- pattein can be lineai oi gianulai (aka lumpy bumpy), which aie the only 2
patteins. These patteins aie immune complexes oi patteinsAb's that they aie
uetecting. Take bx, anu have Ab's with a fluoiescent tag on them. Ie want to see IgA
in the glomeiulus anu have anti IgA Ab's with a fluoiescent tag - if theie aie any, it
will attach to it anu make a fluoiescent tag. Theie aie also tags foi Igu, CS, fibiinogen
- so can get an iuea of what's in the glomeiulus anu an iuea of what pattein it is in (ie
lineai vs. lumpy bumpy gianulai pattein). It uoesn't tell us wheie these things aie, it
just tells us that they aie theie. What tells us wheie immune ueposits anu immune
complexes aie locateu aie ZB. So, we uo stains, fluoiescence, anu EN. Bow can we
tell that the pouocytes aie fuseu. Can only tell by EN bc its so small.
F@) G&==,-,45, E,6L,,4 (E -,5$34&6&$4 J/) &..<4, 5$.#;,%,/
Betect with Ab which have 2 Ag iecognition sites on the Ab. W$$A#'/6<-,
/"4A-$., &/ '4 @3W '46& VB (E8/) So, they get in the bloou they get into the
glomeiulai capillaiy anu aie uiiecteu against the BN. Wheievei theie was a spot on
the BN you will see an Igu Ab. Theie woulun't be one spot on the BN without Igu.
So, what if we uo a fluoiescent tag foi Igu oveilying the glomeiulus - what woulu you
see. Woulu see outlines of all the BN's of the entiie glomeiulus. It is lineai.
B>> ;&4,'- #'66,-4 $4 &..<4<U;<$-,/5,45, C W$$A#'/6<-,/)
@..<4, 5$.#;,%,/ - Ag with Ab attacheu anu is ciiculating in the blooustieam,
hence (3^(E 5$.#;,% - ie ;<#</ C &..<4, 5$.#;,% A]0 (3 C GQ(_ (E C '46&^GQ(
- they attach to eo anu float aiounu anu ueposit in ceitain places; in this case it will
ueposit in the glomeiulai capillaiy; 6"#, @@@ !:b HER5 &..<4, 5$.#;,%I) Bc they
aie immune complexes, they aie laigei than inuiviuual Ab's bc they aie Ag anu Ab
attacheu togethei - theiefoie they aie biggei, have uiff solubilities, have uiff chaiges
- they won't fit nice anu neat in the glomeiulus. So, uepenuing on the size anu chaige
will uepenu on wheie they locate themselves. Ie if too big, will locate unuei the
enuothelial nucleus. So, this woulu be calleu a subenuothelial membiane - they aie
so big that they fit unuei a pouocyte (they cannot get thiough the BN). Lupus is like
this, too - they cannot get passeu the BN anu hangout unuei the enuothelial cells.
:$/6 /6-,# WB \ E'56,-&'; (3 L&6? (E '3'&4/6 H&..<4, 5$.#;,%I_ L?&5? &/ J,-"
/.';;_ '4A J,-" /$;<E;,) +?," 5'4 3$ ';; 6?, L'" #'/6 6?, VB '4A A,#$/&6 <4A,-
6?, ,#&6?,;&'; /&A, \ 6?&/ &/ ' /<E,#&6?,;&'; A,#$/&6. So, how uo you finu out wheie
the ueposits aie. Cannot see with immunufluoiescence, but will be able to see with
EN bc they aie election uense (meaning that they inciease the uensity wheievei
they aie). So, immune complexes have uiff solubilities, uiff chaiges, anu ianuomly go
unueineath the enuothelium, unuei the subepithelial suiface; they will not have a
nice smooth lineai pattein like anti basement membiane Ab's. Example: A] 6?'6
&/486 ;&4,'- H/$ &6/ 4$6 W$$A#'/6<-,/I \ &6 5$<;A E, '4" &..<4, 5$.#;,% A] \
;<#</_ #$/6 /6-,#_ @3( 3;$.,-<;$4,#?-&6&/) Can get a hint of what the uz is,
uepenuing on what is in theie - ie what is the $4;" 3;$.,-<;'- 4,#?-&6&/ 6?'6 "$<
5'4 $4;" A% L&6? &..<4<U;<$-,/5,45,e @3( 3;$.,-<;$4,#?-&6&/. Bc if you aie
gonna call it glomeiulai nephiitis, this means that theie is no Igu in theie, but IgA.
So, the only way to accuiately ux IgA glomeiulonephiitis is to piove that it is IgA anu
nothing else. W-'4<;'-R;<.#" E<.#" #'66,-4 \ L?,4 "$< /,, 6?&/_ L?'6 A$,/ &6
.,'4e @..<4$5$.#;,% 6"#, @@@ A]i -,.,.E,- '46& VB8/ '4A '46& VB (E8/
'3'&4/6 6?, VB &/ 4$6 ' 6"#, @@@_ E<6 ' 6"#, @@) O?,-,'/_ &..<4, 5$.#;,%,/ '-,
6"#, @@@)
F@@) Q,#?-&6&5 J/) Q,#?-$6&5 W;$.,-<;$4,#?-&6&/
+?,-, '-, 7 6"#,/ $= 3;$.,-<;$4,#?-&6&/0 4,#?-&6&5 $- 4,#?-$6&5 (cannot be
both at same time; howevei, it can stait out nephiitic anu become nephiotic)
() Q,#?-&6&5 ["4A-$.,0
!'/ <4&Y<, 5'/6 that is ieu, anu looks like biconcave uisk - DV> 5'/6/ (unique to
nephiitic uz's); bc you have inflammation you will spill piotein, but not gieatei than
S.S giams in a 24 hi peiiou (bc if it uiu, it woulu be nephiotic) - so it is milu to
moueiate pioteinuiia. You aie spilling piotein, but not to the same level as
nephiotic, theiefoie L&;; 4$6 have pitting euema, ascites, etc. If aie inflaming the
glomeiulus, will you have oliguiia. Yes - all the glomeiulai capillaiies have swollen
up, uFR woulu ueciease, anu this woulu leau to oliguiia. Aie you uecieasing the
absoiption oi not filteiing Na. yes. So uoes the Na builu up. Yes - theiefoie iun the
iisk of BTN. [$_ 5;'//&5';;" L?'6 "$< /,, &4 4,#?-&6&5 A]8/ &/ ?,.'6<-&'_ DV>8/
5'/6/_ $;&3<-&'_ !+Q_ '4A .&;AR.$A,-'6, #-$6,&4<-&' H6?&/ &/ 6?, A,U&4&6&$4I
V) Q,#?-$6&5 ["4A-$.,0
Bas a uiffeient cast (='66" 5'/6), ?'J, 3-,'6,- 6?'4 9)N 3-'./ $= #-$6,&4 &4 ' 7K
?- <-&4, /'.#;,) O&;; ';/$ ?'J, #&66&43 ,A,.')
So, if you staiteu out nephiitic (RBC casts, milumoueiate pioteinuiia) anu all of a
suuuen you stait seeing pitting euema, stait seeing ovei S.S giams of piotein in the
uiine ovei 24 his, anu fatty casts - then nephiitic has become nephiotic.
F@@@) Q,#?-&6&5 ["4A-$.,/
() :-$;&=,-'6&J, W;$.,-<;$4,#?-&6&/
All the glomeiuli aie uiffuse, too many nuclei
V) :$/6 /6-,# WQ
Example: scailet fevei 2 weeks ago, piesents with hematuiia, RBC casts, milu to
moueiate pioteinuiia, BP, peiioibital puffiness. EN: lumen of capillaiy, bump on
lumen is enuothelial cell, unueineath is BN (giayish), anu epithelial cells unuei. Bas
boulueis that aie uensei than the noimal glomeiulai BN - these aie immune
complexes. In this case, it the bacteiia is the Ag-Ab immune complexes. Which siue
aie they closei to. Closei to epithelial siue, theiefoie they aie subepithelial ueposits
- hence post stiep uNN.
>) X<#</ WQ
Example: SS yo female with "+" seium ANA with a iim pattein (meaning you have
anti BNA Ab's piesent). X<#</ ';.$/6 ';L'"/ &4J$;J,/ 6?, P&A4,") Theie aie 6
types, anu the &.#$-6'46 $4, 6$ P4$L &/ 6"#, @F, which is a A&==</, #-$;&=,-'6&J,
3;$.,-<;$4,#?-&6&/_ which is the NC oveiall one seen in Lupus. Bas many nuclei,
theiefoie piolifeiative; has wiie loops. (oiient to EN) ueposits in BN aie anti BNA
ueposits. Woulu you agiee that they aie in the enuothelial cell. Yes. So what is this
location. Subenuothelial ueposits. Pouocytes with slit poies in btwn aie not fuseu b
c if they weie, it woulu be nephiotic synuiome. Also see lumen, enuothelial cells anu
ueposits. Immune complexes aie so big they can't get thiough the BN.
G) >-,/5,46&5 WQ
ulomeiulus suiiounueu by piolifeiating cells that aie paiietal cells bc not in the
glomeiulus, anu has ciescent shape, hence the name ciescentic glomeiulai nephiitis.
This is the O2D[+ 3;$.,-<;'- 4,#?-&6&/ 6$ ?'J, ER5 &4 9 .$46?/i #6/ L&;; 3$ &46$
'5<6, -,4'; ='&;<-, '4A A&, <4;,// #6 &/ $4 A&';"/&/. Nany uz's have a ciescentic
glomeiulonephiitis, but the only one I neeu to know is W$$A#'/6<-,/i 6?&/ &/ '
QZ:!D@+@> A]i 6?&/ A] ?'/ 5-,/5,46&5 3;$.,-<;$4,#?-&6&/ $4 E% H6?,-,=$-, '
V(G A%I)
@g) Q,#?-$6&5 ["4A-$.,/0
Pt with casts (fatty casts), polaiizeu specimen with maltese cioss - this is
cholesteiol in the uiine. When cholesteiol is polaiizeu, it looks like a maltese cioss.
+?,/, ='66" 5'/6/ '-, #'6?$4$34$.&5 =$- 4,#?-$6&5 /"4A-$.,) uieatei than S. S
giams piotein foi 24 his, fatty casts in the uiine, ascites, pitting euema, iisk of
spontaneous peiitonitis if you aie a chilu. 0iganism. Stiep pneumonia in kius, E coli
in auults.
() X&#$&A 4,#?-$/&/ 'P' B&4&.'; >?'43, G]0
Example: EN of 8 yo boy that hau an 0RI one week ago, anu now is all swollen, has
pitting euema thioughout bouy (anasaica) anu ascites, noimo-tensive, no BTN; saw
nothing on ienal bx; but then uiu a EN - see RBC in glomeiulai capillaiy lumen. So,
see enuothelial cells, see BN (without election uense ueposits), pouocytes (fuseu) -
=</&$4 $= #$A$5"6,/ &/ (XO(b[ /,,4 &4 '4" 5'</, $= 4,#?-$6&5 /"4A-$.,)
Naltese ciosses in uiine. Bx. X&#$&A 4,#?-$/&/) All pt with nephiotic synuiome
have hypeicholesteiemia. Since they have glomeiulai uz anu some of the cholesteiol
can get into the uiine, some can foim casts in the uiine. Aka minimal change uz.
Why is this happening. Bas lost neg chaige in uBN, theiefoie albumin can get
thiough. These pts have a select pioteinuiia - the only piotein in these pt's uiine is
albumin, anu it is gieatei than S.S giams pei 24 his. Rx - coiticosteioius (usually
goes away in 1 yeai nevei to come back again). The B>> 4,#?-$6&5 /"4A-$., &4
P&A/)
V) T$5'; [,3.,46'; W;$.,-<;$/5;,-$/&/
Example: #6 6?'6 &/ !@F cyd_ pitting euema - theiefoie look at uiine anu note that is
gieatei than S.S giams ovei 24 his. Bas fatty casts in uiine anu has BTN. Bo bx, anu
alieauy know what you aie gonna see bc it the B>> 4,#?-$6&5 /"4A-$., &4 (@G/
#6. 0n bx, some of the glomeiuli aie abnoimal anu otheis aie noimal, but only a pait
of the glomeiulus is messeu up. Theiefoie, it is focal segmental. Bc the ienal bx
with EN anu immunofluoience uiu N0T show ueposits, theiefoie it's
glomeiuloscleiosis. So, this is calleu focal segmental glomeiuloscleiosis. This is 6?,
B> ;,/&$4 &4 (@G/ #6/ '4A @FG(8/. Next to iapiuly piogiessive ciecentiic
glomeiulonephiitis, this is the next woise glomeiulai uz.
>) G&==</, .,.E-'4$</ 3;$.,-<;$4,#?-&6&/
Example: auult with pitting euema, ovei S.S giam pei 24 yis, fatty casts. Bo a bx
anu see not many 'uots' theiefoie not a piolifeiative uz. Bowevei the BN is thickei.
Bx. G&==</, .,.E-'4$</ 3;$.,-<;$4,#?-&6&/ C B>> 4,#?-$6&5 /"4A-$., &4
'A<;6/. This is subepithelial ueposit. Z#&.,.E-'4$</ /#&P,/ \ /#&P, ;&P, ;,/&$4
$4 6?, $<6/&A, $= WVB /,,4 L&6? /&;J,- /6'&4 = uiffuse membianous
glomeiulonephiitis (only one that looks like that).
Nany things can cause this (uiugs, cancei, nothing, infections); some the uiugs
incluue NSAIBs, Bep B, captopiil (king of tieatment of uiabetic nephiopathy anu
heait failuie), malaiia, syphilis, colon cancei (immune complex is anti-CEA Ab's).
Eventually leaus to ienal failuie anu can uie unless you get a ienal tiansplant
G) +"#, @ '4A @@ B,.E-'4$#-$;&=,-'6&J, W;$.,-<;$4,#?-&6&/
H,4A/ &4 c^&6&/d 6?,-,=$-, &6 &/ 6"#, @@@ !:b \ &..<4, 5$.#;,%jI
1. Type I has a ielationship with Bep C - how uo you iemembei. Nembianous =
Bep B (also iemembei the vasculitis - Polyaiteiitis Nouosa), Nembianopiolifeiative
= Bep C (also iemembei ciyoglobinemia).
So, 6"#, @ &/ ' /<E,4A$6?,;&'; A,#$/&6 6?'6 #-$A<5,/ 4,#?-$6&5 /"4A-$.,.
2. Type II is less common, anu has an Auto Ab against CS, calleu CS nephiitic factoi.
It causes CS conveitase to become oveiactive anu is constantly bieaking complement
uown. So, the lowest complement levels you will see is in type II glomeiulai
nephiitis - this is calleu uense ueposit uz bc the entiie BN an immune complex.
6-'. 6-'5P/ - mesangial cell (stiuctuial component of the glomeiulai capillaiy) -
the mesangial cell is extenuing itself between the BN anu the enuothelial cell, making
it look like a tiam tiack; so, it's a mesangial piocess btwn the BN anu enuothelial cell
- tiam tiack Nembianopiolifeiative uz
Z) G&'E,6&5 W;$.,-<;$/5;,-$/&/
Classic sign: big iounu balls on B anu E stain. When theie is excess ieu in the cell,
think ?"';&4, '-6,-&$;$/5;,-$/&/; this is a small vessel uz of uiabetes anu BTN. The
veiy fiist vessel that is hyalinizeu is the effeient aiteiiole. Let's say it is hyalinizeu.
So, bc the lumen is naiiow in the effeient aiteiiole, the uFR will inciease. So, what
is the Ci cleaiance. Incieaseu. So, in eaily uiabetic nephiopathy, theie is an
&45-,'/,A WTD '4A >- 5;,'-'45,. Why. Bc the effeient aiteiiole is hyalinizeu anu
obstiucteu. Is this bau. Yes - as a iesult the glomeiulus will take a pounuing foi the
next ten yeais - leauing injuiy calleu hypeifiltiation uamage. What is the piocess
wheie glucose attaches to an aa in a piotein). Nonenzymatic glycosylation. Lets say
this is also going on bc the pt is not watching himself too well, theiefoie L, '-,
4$4,4]".'6&5';;" 3;"5$/";'6&43 6?, WVB. What woulu happen when you
glycosylate a BN - what is it peimeable to. Piotein. So, have all this piessuie on the
glomeiulai capillaiy bc the effeient aiteiiole anu also nonenzymatically
glycosylating the uBN, so its peimeable to piotein. So, tons of piotein going into the
uiine. When you initially stait seeing it, is calleu .&5-$';E<.&4<-&') Will the
stanuaiu uipstick foi piotein uetect that. No. Theie aie special uipsticks that aie
available to uetect this - calleu micioalbuminuiia uipsticks. So, what uoes it mean
when youi uiabetic pt has a "+" uipstick foi micioalbuminuiia. !'J, 6$ 3&J, #6 (>Z
&4?&E&6$- bc you want to stop piogiession of this. Bow will it woik. Affeient
aiteiiole is contiolleu by PuE2; the effeient aiteiiole is contiolleu by AT II (which
constiicts it). So, when you give an ACE inhibitoi, what happens to AT II level. It
uecieases. So, bc AT II uecieaseu, you take off the vasoconstiictive element it has
on it. Even though it was hyalinizeu, it will open then lumen, taking piessuie off the
glomeiulus, anu ueciease the filtiation iate. So, the constant pounuing on the
glomeiulus is taken away. Neeu to get glycosylateu Bb (BbA1c) unuei 6%, but the
ACE inhibitoi cant uo it all, so must have peifect glycemic contiol, otheiwise will go
into chionic ienal uz. If they can uo this, the ACE &4?&E&6$- L&;; #-,J,46 6?, A])
+?, (>Z &4?&E&6$- ';/$ ?,;#/ !+Q. Pink stuff is type Iv collagen in the mesangium.
It builus up, ez to see big ciicle (big ballsgolf ballsChiistmas balls) aka Kimmelstiel-
Wilson nouules - this is nouulai glomeiulai scleiosis.
T) (.";$&A
Like to ueposit in the kiuneys. Its a special piotein. [6'&4 L&6? >$43$ -,A_ '4A
'=6,- "$< #$;'-&], &6_ &6 ?'/ ' H3-'44" /.&6?I '##;, 3-,,4 E&-,=-&43,45,. Light
gieen is what the amyloiu is supposeu to look like when you polaiize it with a Congo
Reu stain. Amyloiu anu uiabetic glomeiulai scleiosis aie nephiotic synuiomes.
W) [<..'-" 4,#?-$6&50
Lipoiu scleiosis = NCC nephiotic in kius
Focal segmental glomeiuloscleiosis = IvBA's, AIBs
Biffuse Nembianous glomeiulonephiitis = NC in auults
Type I anu II Nembianopiolifeiative glomeiulonephiitis = type I with hep C
ielationship, type II with autoAb against CS (lowest complement levels seen)
Biabetic nephiopathy
Amyloiu
g) >$.E$ $= Q,#?-&6&5 '4A Q,#?-$6&5 ["4A-$.,
() @3( W;$.,-<;$4,#?-&6&/ HE<-3,-8/ A]I
IgA glomeiulonephiitis is a vARIANT of Benoch Schonlein puipuia bc it is an
immune complex uz, anti IgA Abs (so is Benoch Schonlein - palpable puipuia in
buttocks of legs, polyaithiitis, uI bleeu, hematuiia (RBC casts))
0n immunofluoience, eveiything shows up in the mesangium. Example: in P&A/,
piesents with episoues of gioss hematuiia, goes away, comes back a few yeais latei;
in 'A<;6/, piesents with episouic bout of micioscopic hematuiia. So, have a lil
hematuiia, goes away, anu comes again. Lil pioteinuiia, no BTN. When it staits
getting woise (1u yeais latei), that's when it will be bau (so its not b9). @6 &/ 6?, B>
$= ';; 3;$.,-<;$4,#?-&6&/ '4A &/ 6"#, @@@ !:b)
Auuio File S1: Renal S
g@) VMQR>- \ :-,-,4'; (]$6,.&'
Can sepaiate pieienal azotemia vs. ienal failuie
VMQ = bloou uiea nitiogen anu >- = enu piouuct of cieatine metabolism. 0iea can
be filteieu anu ieabsoibeu in the piox tubule (so its not a peifect cleaiance
substance); Ci is only filteieu in the kiuney anu is ieabsoibeu oi secieteu. (lnulin
cleaiance is bettei). @= "$< 6'P, 6?, 4$-.'; VMQ ;,J,; H1fI_ '4A 4$-.'; >- ;,J,;
H1.3RAXI_ L&;; ?'J, 6?, 4$-.'; -'6&$ $= 1f01)
When you have #-,-,4'; ']$6,.&', theie is an inciease in B0N (this is what
azotemia means). Pie = befoie, theiefoie theie is something wiong 'befoie' the
kiuney - in othei woius, theie is nothing wiong with the kiuney, but the C0 is
uecieaseu (fiom any cause - ie CBF, NI, hypovolemia, caiuiomyopathy, etc).
(4"6?&43 6?'6 A,5-,'/,/ >2 L&;; ;,'A 6$ #-,-,4'; ']$6,.&' ER5 6?, WTD L&;;
A,5-,'/,) If you have less ienal bloou flow, you will filtei less anu the uFR will
ueciease. So, when it uecieases, it gives the piox tubule moie time to ieabsoib little
bit moie uiea than noimal. So, theie is inciease piox tubule ieabsoiption of uiea.
What about Ci. We know that it is not ieabsoibeu, but you uo have to get iiu of it
thiough the kiuneys. So, even though it is not ieabsoibeu, the uFR is uecieaseu,
theie is a back up of Ci anu will not be able to cleai it as fast. Theiefoie, theie will be
an inciease in seium Ci. Theie is little moie of an inciease is uiea bc it is being
ieabsoibeu than with Ci. So, theie is a uispiopoitionate inciease of B0NCi. All you
have to iemembei is 1S:1. So, 3-,'6,- 6?'4 ' 1N01 VMQR>- C #-,-,4'; ']$6,.&')
Example: the pt has CBF, B0N is 8u anu Ci is 2. So, both aie elevateu, but the B0N
Ci iatio is 4u:1, inuicating that it is pieienal azotemia, anu the pt uoes N0T have
ATN.
Lets say pt tiuly has -,4'; ='&;<-, - $;&3<-&'_ -,4'; 6<E<;'- 5'/6/_ '5<6, -,4';
='&;<-,. This L&;; '==,56 6?, VMQR>- ZwM(XXb bc something is wiong with the
kiuney, theiefoie the same effect on the B0N is the same on Ci. Foi both, uiea has to
be filteieu out of the kiuney anu it has faileu - both incieaseu piopoitionate to each
othei bc both have the same pioblem anu kiuney is scieweu up; cannot get iiu of
uiea, can't get iiu of cieatinine, so they inciease in piopoition to each othei bc the
uiea is not being ieabsoibeu anymoie bc the kiuney is in shock. Example: B0N = 8u,
Ci = 8, theiefoie the B0NCi iatio is 1u:1, anu pt is in ienal failuie. So, even though
the 1u:1 is maintaineu, still have ienal failuie bc it has incieaseu so much. @= 6?,
-'6&$ &/ 1N01_ &6 &/ #-,-,4'; ']$6,.&'i &= &6 &/ &45-,'/,A '4A /6&;; 1f01_ &6/ -,4';
='&;<-,)
g@@) (5<6, D,4'; T'&;<-,
() (5<6, +<E<;'- Q,5-$/&/0
B>> C @/5?,.&5 (5<6, +<E<;'- Q,5-$/&/ - this is what you woiiy about the most
when the >2 A,5-,'/,/_ #6 A,J,;$#/ $;&3<-&'. When a pt's C0 uecieases, anu have
pieienal azotemia, you have a ueciease in uFR, which is anothei cause of the
oliguiia. So, ueciease in C0 anu oliguiia is vERY BAB, anu stait to see B0NCi go up
- neeu to know if its pieienal azotemia, oi ienal azotemia - to uistinguish, get a
B0NCi. It its 1S:1, its still pieienal. But it can piogiess to ienal failuie - ischemic
acute tubulai neciosis. B>> &/5?,.&5 '5<6, 6<E<;'- 4,5-$/&/ C 4$6 6-,'6&43
#-,-,4'; ']$6,.&') [$_ &/5?,.&5 (+Q &/ 6?, L$-/6 6?, 3,6 '4A 6?, VMQR>- -'6&$
L&;; E, 4$-.';_ E<6 &45-,'/,A &4 J';<,/ H&, lfRlI
>$'3<;'6&$4 4,5-$/&/0 Sloughs off, blocks lumen anu contiibutes to oliguiia, anu
see casts in the uiine. The casts aie ienal tubule casts. So, 5$.E$ $= -,4'; 6<E<;'-
5'/6/_ $;&3<-&'_ VMQR>- $= 1f01 C (+Q.
Why uoes this have such a bau piognosis. When pt has ischemic neciosis, not only
aie you killing the tubulai cells, but the BN also gets uamageu, so the stiuctuial
integiity of the tubule is being taken away, which is not goou. When you have livei
uamage, anu uamage livei cells, anu the cells iegeneiate, the cells aie not
iegeneiating sinusoius anu tiiaus, but only themselves. If the BN isn't theie, anu the
patient has iecoveieu fiom ATN oi is in the piocess of uoing that, can you iegeneiate
a tubulai cell without a BN. No. So, the moie neciosis, the moie BN aie uestioyeu,
the woise the piognosis bc cannot iegeneiate anu cannot get back noimal function.
This is why it is such a bau uz. +?,-, '-, 7 #'-6/ $= 6?, 4,#?-$4 6?'6 '-, .$/6
/</5,#6&E;, 6$ &/5?,.&' \ L?'6 '-, 6?,"e [6-'&3?6 #$-6&$4 $= 6?, #-$% 6<E<;,
'4A 6?&5P '/5,4A&43 ;&.E $= 6?, .,A<;;'-" /,3.,46 HL?,-, 6?, Q'RSR7 >; 5$^
6-'4/#$-6 #<.# &/I) These two paits unueigo coagulation neciosis anu sloughing
off. So, will see these fall off in the pioximal tubule anu also in the thick ascenuing
limb of the meuullaiy segment.
V) Q,#?-$6$%&5 (+Q0
uentamycin, Au's. If they aie nephiotoxic, what is the fiist thing they will filteieu
fiom the glomeiulus. Pioximal tubule. So, 4,#?-$6$%&5 6<E<;'- 4,5-$/&/ -,;'6,A
6$ A-<3/ &4J$;J,/ 6?, #-$%&.'; 6<E<;,. Anu, the BN iemains intact; theiefoie the
piognosis of nephiotoxicity is way bettei foi 2 ieasons: only affecting the pioximal
tubules anu not affecting the BN. The B>> 4,#?-$6$%&5&6" C (W8/ H7
4A
B>> C
&46-'J,4$</ #",;$3-'./I. What is uFR in 8u yo. It is uecieaseu - the Ci is 4 mls
min; which is noimal in oluei people. Ci cleaiance uecieases along with uFR as they
get oluei; so, if you aie giving a uiug without nephiotoxicity the same uose as a
young peison, you will be killing the oluei peison. This is obviously occuiiing bc
Au's aie the NCC ATN anu uoctois aie not uecieasing the uose of the uiug to
ueciease nephiotoxicity.
g@F) +<E<;'- '4A @46,-/6&6&'; G&/$-A,-/ $= 6?, S&A4,"
() (5<6, :",;$4,#?-&6&/0
Bow uo you sepaiate it fiom a lowei 0TI. veiy easily. Pyelonephiitis is seen moie
in women bc of theii shoit uiethia. (5<6, #",;$4,#?-&6&/ &/ ' /"/6,.&5 &4=,56&$4
'4A &/ '4 &4=,56&$4 $= 6?, P&A4," #-$#,-) Bow uoes it get into the kiuney. At the
uietovesiculai junc, the muscle squeezes so theie is no ieflux of uiine fiom the
blauuei into the uietei. This is tiue in noimal people. Bowevei, not all people have a
noimal vesicouieteial junction. So, what happens in a pt with a blauuei infection
anu the junction is incompetent, it leaus to J,/&5$<-,6'; -,U;<%, anu the infecteu
uiine iefluxes up into uieteis, anu leaus to ascenuing infection that goes all the way
up to the kiuneys. So, they will ask you, cL?'6 &/ 6?, .,5? $= (XX
M+@8/ed H<-,6?-&6&/_ 5"/6&6&/_ #,;J&6&/_ $- #",;$4,#?-&6&/I \ A<, 6$ '/5,4A&43
&4=,56&$4 =-$. 6?, E,3&44&43 $= 6?, <-,6?-') Eveiy woman (has nothing to uo
with cleanliness) has the same E coli seiotype in hei stool at the intioutus of the
uiethia anu hei vagina. So, with tiauma oi ceitain seiotypes of E coli, it can ascenu
up the uiethia into the blauuei. If the pt has an incompetent uietovesiculai junc, up
the uieteis into the kiuneys. So, all 0TI's aie ascenuing fiom the beginning of the
uiethia on up.
With '5<6, 5?$;,5"/6&6&/_ ?'J, #'&4=<; <-&4'6&$4 HA"/<-&'I_ &45-,'/,A
=-,Y<,45"_ /<#-'#<E&5 #'&4_ Q2 =,J,-_ 4$ U;'4P #'&4_ Q2 OV> 5'/6/ HL&6?
4,<6-$#?&;/ &4 6?,.I \ L?"e VR5 6?, OV> 5'/6/ A,J,;$# &4 6?, -,4'; 6<E<;,/i
6?," A$ 4$6 A,J,;$# &4 6?, <-,6,- $- 6?, E;'AA,-i 6?," A,J,;$# &4 6?, P&A4," &4
6?, 6<E<;,)
[$_ =,J,-_ U;'4P #'&4_ '4A OV> 5'/6/ C (>M+Z :bZX2QZ:!D@+@[) So, its an
'/5,4A&43 &4=,56&$4 A<, 6$ &45$.#,6,46 J,/&5$<-,6'; u<45. This usually shows up
in newboin giils (anu will be a piob foi iest of lives).
Example: kiuney with white spots = abscesses seen in pyelonephiitis. If you have
constant acute attacks of pyelonephiitis, can become chionic. Theiefoie have
incieaseu iisk of BTN anu ienal failuie.
V) >?-$4&5 :",;$4,#?-&6&/
Example: scaiieu kiuney (on coitex), blunting of the calyces (occuis unuei the
scai), seen on intiavenous pyelogiams - ux. CBR0NIC pyelonephiitis. So, E;<46&43
$= 6?, 5';"5,/ C >!D2Q@> #",;$4,#?-&6&/)
>) (5<6, G-<3^&4A<5,A &46,-/6&6&'; 4,#?-&6&/
Can A-<3/ piouuce a nephiitis involving the inteistitium anu tubules. Yes - can be
acute anu chionic anu ez to uiagnose. Why. Bc will have fevei, anu uevelop a iash.
T,J,- y D'/? (obviously uue to uiug, bc staiteu aftei taking the uiug), $;&3<-&',
,$/&4$#?&;&<-&' (,$/&4$#?&;/ &4 6?, <-&4, \ #'6?$34$.$4&5). This is calleu '5<6,
A-<3 &4A<5,A &46,-/6&6&'; 4,#?-&6&/. This is moie anu moie common, anu is a veiy
common cause of chionic ienal failuie. So, put pt on uiug, get fevei, iash, oliguiia =
uiscaiustop uiug (nevei give again) - this is a combo of type I anu Iv BPY.
(4';3,/&5 4,#?-$#'6?"
Example: uiscoloiation in ienal meuulla, pale infaict, ienal papilla slougheu off -
iingeu signeu; anu on pyelogiams theie will be nothing theie just an empty space.
Bx. (4';3,/&5 4,#?-$#'6?". This =-$. 5$.E$ $= '5,6'.&4$#?,4 '4A '/#&-&4
$J,- ' ;$43 #,-&$A $= 6&.,) (5,6'.&4$#?,4 is piouucing fiee iauicals. Bc of the
pooi ciiculation in the meuulla, theie is fiee iauical uamage on the tubulai cells of
the meuulla. (/#&-&4 will block PuE2 (a vasouilatoi), theiefoie angiotensin II (a
vasoconstiictoi) is in chaige of the ienal bloou flow. vasoconstiictoi of the effeient
aiteiiole. The peiitubulai capillaiies aiise fiom the effeient aiteiiole. So, with
vasoconstiiction of the effeient aiteiiole, pt is affecting peiitubulai capillaiies going
aiounu collecting tubules anu ienal meuulla. So, is that piouucing ischemia. Yes. So,
pt ?'/ =-,, -'A&5'; A'.'3, '4A &/5?,.&' ;,'A&43 6$ '4';3,/&5 4,#?-$#'6?". This
is why the ienal papilla necioses, sloughs off, anu leaus to -,4'; #'#&;;'-" 4,5-$/&/.
So, '/#&-&4 '4A '5,6'.&4$#?,4 6$%&5&6") G&'E,6&5 4,#?-$#'6?" HER5 5'</,/
&/5?,.&'I_ '5<6, #",;$4,#?-&6&/ HER5 'E/5,// =$-.'6&$4I_ [>G] '4A 6-'&6_ 5'4 ';;
;,'A 6$ '4';3,/&5 4,#?-$#'6?")
gF) >?-$4&5 -,4'; T'&;<-,
G,U&4&6&$40 :6 ?'/ VMQR>- -'6&$ 1f01 =$- .$-, 6?'4 9 .$46?/. If both kiuneys
faileu: will not be able to exciete the things we noimally get iiu of (so those 6?&43/
L&;; E<&;A <# - ie salt); EP0 piouuction will ueciease, leauing to 4$-.$5"6&5
'4,.&' L&6? ' 5$--,56,A -,6&5<;$5"6, 56 $= ;,// 6?'4 7n. Will not be able to get
iiu of oiganic acius, leauing to .,6'E$;&5 '5&A$/&/, incieaseu anion gap. With
metabolic aciuosis, bones tiy to buffei all the aciu. Bc the bones aie buffeiing the
extia B ion, bone uz can uevelop, leauing to $/6,$#$-$/&/. The piox tubules aie
messeu up in the ienal tubules, anu 1-alpha hyuioxylase will ueciease (this
iesponsible is hyuioxylating vit B); so, with ienal failuie will also have
?"#$J&6'.&4$/&/ G (vit B uef). This means that theie will be ?"#$5';5,.&' anu
?"#$#?$/#?'6,.&', leauing to $/6,$.';'5&'. So, theie aie two bone uz's -
osteopoiosis (bc buffeiing anu weaiing away bone matiix) anu osteomalacia; also,
PTB i s ieacti ng to chioni c hypocal cemi a anu l eaus to /,5$4A'-"
?"#,-#'-'6?"-$&A&/. (also affects the bone). The bunCi iatio is 8u8. So, if you
know noimal ienal func you know what happens.
gF@) 26?,- :-$E;,./ -,;'6,A 6$ P&A4,"/0
Example: pt has essential BTN ovei 1u yis, anu pt is not compliant with meuication
- kiuney with cobblestone appeaiance = 4,#?-$/5;,-$/&/. 0nueilying uz causing it:
hyaline aiteiioloscleiosis bc theie is uecieaseu bloou flow, tubulai atiophy,
glomeiuli aie fibiosing off, ienal function is going uown, anu leaus to ienal failuie.
Example: lets say the pt wakes up with a big heauache anu bluiiy vision. Pt is
getting uizzy, goes to ui, anu piessuie is 24u14u, in the ietina, uuue has
papilloeuema with flame hemoiihages anu haiu anu soft exuuates, giaue 4
hypeitensive ietinopathy, B0NCi aie 8u8 - A%e B';&34'46 !+Q (aka flea bitten
kiuney - petechia visible on suiface of kiuney - see vessel changes ie hypeiplastic
aiteiioloscleiosis, anu the Bv's aie iuptuiing, leauing to petechial lesions on the
coitex - calleu flea bitten kiuney). This is all you have to know. They can also ask
D%0 @F 4&6-$#-<//&A, 6$ 3,6 6?, V: A$L4. So, they have CNS euema with
papilloeuema, anu if the BP isn't loweieu, they aie gonna uie.
Example: kiuney with abnoimal aieas that aie pale anu uepiesseu - so, if you take a
section thiough one of these, anu you see an iiiegulai iiiegulai pulse, will see pale
infaiction with coagulation neciosis bc what you aie looking at aie &4='-56/.
Iiiegulai iiiegulai pulse is fiom atiial fib, anu atiial fib is most uangeious foi
,.E$;&]'6&$4. So, these infaicts aie fiom .<;6&#;, ,.E$;&, leauing to multiple pale
infaicts of the kiuney. This is N0T pyelonephiitis bc has micioabcesses
Example: atiophy uue to uilatation of the ienal pelvis, leauing to ?"A-$4,#?-$/&/.
So, if you have hyuionephiosis anu incieaseu piessuie piessing on the coitex anu
meuulla, what happens to that. W,6 &/5?,.&' '4A '6-$#?" \ L?&5? &/ 5';;,A
5$.#-,//&$4 '6-$#?") This is veiy similai to cystic fibiosis uucts filleu with
mucous - the piessuie is impacteu back to the glanus, anu they unueigo
compiession atiophy. Coitex anu meuulla aie veiy thin, along with veiy uilateu
ienal pelvices. B>> C /6$4,
Example: /6'3?$-4 5';5<;</ \ <-&4, #! &/ ';P';&4, '4A /.,;;/ ;&P, '..$4&'i
6?,-,=$-,_ 6?,-, .</6 E, ' <-,'/, #-$A<5,-_ '4A 6?&/ &/ :-$6,</) VR5 &6 &/ '
<-,'/, #-$A<5,-_ they bieak uiea uown to ammonia, anu get an alkaline pB. This is
why a /6'3?$-4 5';5<;</ &/ B3 '..$4&<. #?$/#?'6,, anu only uevelops in
infections in pts that have uiease piouuceis. E coli aie not uiease piouucei anu
pioteus species aie anu they pieuispose to these stones. Bo not pass these stones
(too big), theiefoie neeu to extiact these (suigeiy). So, <-,'/, #-$A<5,-_ ';P';&4,
#!_ '..$4&' /.,;; 6$ 6?, <-&4,)
gF@@) +<.$-/ $= 6?, P&A4,"
If you see a mass in a kiuney, anu its an auult, it is a -,4'; 'A,4$5'-5&4$.'. If it's a
kiu, it's a Wilm's tumoi. So, if you see a mass in the kiuney, its piob not mets (bc not
many things go theie), its not b9, pick cancei.
[$_ 'A<;6 C -,4'; 'A,4$5'-5&4$.'_ P&A C O&;./ 6<.$-i 6?," A,-&J,A =-$. 6?,
#-$%&.'; 6<E<;, '4A 6?, B>> C /.$P&43i 6?," .'P, ;$6 $= ,56$#&5 ?$-.$4,/0
Z:2_ #'-'6?"-$&A ?$-.$4, H;,'A/ 6$ ?"#,-5';5,.&'I_ &4J'A, 6?, -,4'; J,&4)
>,;;/ '-, 5;,'-_ =<;; $= 3;"5$3,4)
Example: flank mass in chilu, BTN = Wilms tumoi; BTN occuis bc it's making
ienin; usually unilateial. Bistology: cancei wheie pt is uuplicating embiyogenesis of
a kiuney - eveiything is piimitive. Can see ihabuomyblasts; likes to mets to lung
If (G_ =-$. 58/$., 11_ '4A ?'J, 7 5;'//&5 U&4A&43/0 '4&-&A&' H'E/,46 &-&/I_ '4A
?,.&?"#,-6-$#?" $= '4 ,%6-,.&6" H$4, ,%6-,.&6" &/ E&33,- 6?'4 '4$6?,-I \ 6?&/
&/ ' /&34 6?'6 6?, L&;./ 6<.$- ?'/ ' 3,4,6&5 E'/&/)
Papillaiy lesion in the blauuei = tiansitional cell caicinoma (TCC)
What is the NCC tiansitional cell caicinoma of the blauuei. Smoking
Bye use to look. Aniline uye; what is chemotheiapy agent useu to Rx Wegenei's.
Cyclophosphamiue. What aie the complications of Cyclophosphamiue. Bemoiihagic
cystitis anu tiansitional cell caicinoma.
Bow uo you pievent this. Nesna.
gF@@@) M-&4'-" +-'56 @4=,56&$4
NC uiine abnoimality seen in the lab
Example: aiiow pointing to neutiophils in uiine; RBC's in it, too, bacteiia - E coli
(play ouus). So, /,, 4,<6-$#?&;/_ DV>8/ '4A E'56,-&') +?, A&#/6&5P L&;; #&5P <#
';; 6?-,, $= 6?,/, 6?&43/)
cyd A&#/6&5P =$- E;$$A A<, 6$ DV>/. Bematuiia is veiy fiequent anu sometimes a
lot of bloou comes out (?,.$--?'3&5 5"/6&6&/) anu most of the time its Z 5$;&, but
sometimes it can be fiom auenoviius.
Also, the A&#/6&5P ?'/ ;,<P$5"6, ,/6,-'/, anu it's measuiing the enzyme in the
leukocyte.
Nost uiinaiy pathogens aie nitiate ieuuceis, meaning that they conveit nitiate to
nitiite. 0n a A&#/6&5P_ 6?," ?'J, ' /,56&$4 =$- 4&6-&6,/. Bc E coli is a nitiate
ieuucei, theie shoulu be nitiites in the uiine, which aie uipstick "+" foi that.
So, you have a pt, woman oi man, who has uysuiia, incieaseu fiequency, supiapubic
pain anu have a uiine seuiment of neutiophils, RBC's, bacteiia oi uipstick finuings of
hematuiia, leukocyte esteiase pos, nitiate "+" C M+@
@/ &6 ;$L,- $- <##,-e @= 6?, #6 ?'/ =,J,-_ U;'4P #'&4_ OV> 5'/6/ &6/ <##,-_ &= 4$4,
$= 6?,/, 6?&43/ '-, #-,/,46_ &6/ ;$L,-)
Example0 pt with uysuiia, incieaseu fiequency, neutiophils in the uiine, few RBC's,
no bacteiia, "+" leukocyte esteiase, uiine cultuie is neg, anu sexually active peison,
ux. >?;'."A&' \ 4$-.'; <-&4, 5<;6<-,/ A$ 4$6 #&5P <# >?;'."A&' 6-'5?$.'6&/)
@6 &/ 6?, B> [+G) In men, calleu nonspecific uiethiitis, in woman its calleu acute
uiethial synuiome. We also use the teim calleu steiile pyuiia. We uon't have
bacteiia piesent, but uo have neutiophil piesent. 0n ioutine stool cultuie, its neg.
So, $4, 5'</, $= /6,-&;, #"<-&' &/ >?;'."A&' &4=,56&$4 '4A 6?, $6?,- $4, &/ +V)
B> $-3'4 6?'6 .&;&6'-" +V 3$,/ 6$ C P&A4,"_ 6?,-,=$-, L&;; ?'J, +V &4 6?,
<-&4,_ '4A &6 L&;; E, /6,-&;, ER5 <-&4, 5<;6<-,/ A$ 4$6 #&5P <#) [$_ -,.,.E,-
>?;'."A&' '4A +V '/ 5'</,/ $= /6,-&;, #"<-&')
:,4&/
Embiyo: what is the embiyology of ?"#$/#'A&'/. 0pening on the unueisuiface
(you pee anu it goes on youi shoes) - failuie of closuie of uiethial folu
Z#&/#'A&'/. 0pening on uppei suiface (pee anu goes in face); uefect in genital
tubeicle
:,"-$4&,8/ A]0 like Bupuytien's contiactuie
:-&'#&/. - peimanent eiection, seen commonly in SCBz bc of the RBC's anu sickle
cells tiappeu in the vasculai channels.
B> 5'45,- $= 6?, #,4&/ = /Y<'.$</ bc lack of ciicumcision. It is moie commonly
seen in an unciicumsciibeu pt - they usually uo not clean (pooi hygiene)
pieuisposes - the /.,3.' &/ 5'-5&4$3,4&5)
+,/6&5;,
Ciyptoichiu testis - testicle uoesn't want to come uown. Theie aie two phases in
the uecent of a testicle: tiansabuominal migiation uown to inguinal canal. NIF is
iesponsible foi this. The seconu pait of the tiip is anuiogen uepenuent. This
incluues testosteione anu uihyuiotestosteione. So, the fiist phase is fiom NIF anu
the seconu phase is anuiogen uepenuent. Neeu testicle uown by two yeais of age bc
if not, has a iisk of seminomas. Still at iisk if you get it uown. Lets say you went in,
anu it look atiophic anu othei testicle looks noimal, have to take noimal one out, too
bc it is also at iisk. So, must have testes examines to make suie you uon't have a
seminoma.
(4';$3": in tuineis, they aie infeitile anu have menopause befoie menaiche, bc by
two yeais of ages, they have no follicles in theii ovaiies, anu this is calleu a stieak
gonau. This is an ovaiy without any follicles. This is analagous to ciyptoichiu testes:
just like the ciyptoichiu testes pieuisposes to seminomas (which is a geim cell
tumoi), so uoes the stieak gonau pieuispose to a geim cell tumoi - howevei, uo not
call them seminomas in women, but A"/3,-.&4$.'/. So, in pts ux'u with Tuinei's
synuiome, they suigically iemove both ovaiies bc of the gieat iisk. They uon't keep
them in theie bc leau to cancei.
2-5?&6&/ - mumps
Z#&A&A".&6&/ - less than SS = N gonoiiheachlamyuia, gieatei than SS =
pseuuomonas
F'-&5$5,;, - on left siue bc speimatic vein connecteu to left ienal vein, wheias the
speimatic vein on the iight is connecteu to the IvC; bc of this, the piessuies inciease,
anu a vaiicocele on the left, leaus to incieaseu heat anu is one of the most common
causes of infeitility - ie what woulu happen if you blockeu the left ienal vein. Woulu
uevelop a vaiicocele. So, if you block the left ienal vein, you will inciease the
piessuie in the speimatic vein anu will leau to a vaiicocele.
+$-/&$4 - speimatic coiu twisting; when theie is a toision of the speimatic coiu, it
shoitens it. This means that the testicle will go up into the inguinal canal. This is
painful. You will lose youi ciemasteiic ieflex (in noimal male, if you scatch the
sciotum, it will contiact, which is lost in toision of the testicle).
!"A-$5,;, - peisistence of tunica vaginalis; when you have big sciotum, you uon't
know whethei its big bc theie is fluiu in it, oi its big bc theie is a testicle in it. So,
what uo you uo. Tiansilluminate. If it tiansilluminates, it is hyuiocele. If it uoesn't
its cancei. uu foi painless enlaigement of testicle : cancei, cancei, cancei!! (why
they uon't even uo bx, just iemove)
[,.&4$.' - NC (best piognosis); huge cells with lymphocyctic infiltiate. They aie
the counteipait of a woman's uysgeiminoma. These will melt with iauiation, ?'J,
;&66;, E,6' ?5W; met to paiaoitic lymph noues - why. Bc they came fiom the
abuomen, anu that's wheie they will go.
B> 6,/6&5<;'- 6<.$- &4 5?&;Ae b$;P /'5 6<.$-; tumoi maikei. Alpha feto piotein
O?'6 &/ L$-/6 6,/6&5<;'- 5'45,-e 5?$-&$5'-5&4$.' \ not the same piognosis of a
gestationally ueiiveu choiiocaicinma in a woman - you'ie ueau
Example:: 2S yo male with unilateial gynecomastia anu uyspnea. Chest xiay
ieveals multiple nouulai masses in the lung. So, gynecomastia anu mets uz, - what is
the piimaiy cancei. testicle - choiiocaicinoma. Souice of gynecomastia: V!>W &/
;&P, X!_ '4A 6?,-,=$-, &6 /6&.<;'6,/ #-$3,/6,-$4, &4 6?, .';,_ L?&5? &45-,'/,/
A<56 3-$L6? '4A E-,'/6 6&//<, '4A ;,'A/ 6$ 3"4,5$.'/6&'
Example:: same scenaiio, but oluei man - will leau to malignant lymphoma
So, oluei pts get malignant lymphoma (not as piimaiy uz, but fiom mets); the testes
mets a lot , esp in leukemia anu lymphomas
[<..'-"0
Woist = choiiocacinoma
NC = Seminoma
NC in kius = yolk sac tumoi
NC in olu = mets malignant lymphoma
:-$/6'6,
Bypeiplasia occuis in the peiiuiethial poition of the piostate glanu. This is why
you get uiibbling anu uiinaiy ietention as the most common symptom. Piostate
cancei is in the peiipheiy of the piostate glanu within the peiipheiy of youi fingei.
So, when you piess on it, you feel haiuness.
Example 7S yo man with uiinaiy ietention anu blauuei is up the umbilicus anu has
uiibbling - what is the most likely cause. N0T piostate cancei - why. Bc foi piostate
cancei to uo that, it has to invaue all the way thiough the piostate glanu to the
uiethiablauuei neck. This is piostate BYPERPLASIA bc it is alieauy aiounu the
uiethia, anu this is the NCC, not cancei. What male hoimone is totally iesponsible
foi piostate. Bihyuiotestosteione - in embiyogenesis, this hoimone fuses the labia
to foim a scotium, extenus the clitoiis to foim a penis anu makes a piostate glanu.
So, piostate BPY anu cancei aie N0T testosteione uep canceis, but uihyuiotesteione
uep canceis. If you use a S alpha ieuuctase inhibitoi, that will inciease testosteione.
This uiug will ueciease BIBYBR0TEST0STER0NE
NC cancei in men = piostate cancei
Piouuces osteoblastic mets.
CHAPTER 12: Gynae
Auuio File S2: uynaecology
!&-/<6&/. '4A F&-&;&]'6&$4
Biisutism = incieaseu haii in noimal haii beaiing aieas
viiilization = hiistuism, plus male seconuaiy sexual chaiacteiistics (zits, acne,
ueepei voice), clitoiomegaly (pathognomonic)
Testosteione is pieuominantly synthesizeu in the ovaiy. Nost testosteione in a
woman is fiom the ovaiy.
BBEA sulfate is 9S% fiom auienals, anu is an anuiogen. Theiefoie, if a pt has
hiistuism, have to get two tests - get a testosteione level - have to fiactionate it bc
sometimes the total can be noimal, but the fiee test can be incieaseu, anu you get a
BBEA sulfate test. So, if testeteione is pieuominantly elevateu, it is coming fiom the
ovaiy anu if BBEA is elevateu, it is coming fiom the auienals.
If it is auienal oigin, it consists of hyuioxylase uef (auiogenital synuiome),
Cushings, etc..
Biistuism fiom the ovaiies is a common phenomenon.
So, when you aie evaluating hiisutism, look at BBEA levels (auienal oiigin) anu
testosteione levels(ovaiian oiigin).
0ne of the common causes of ovaiian oiigin aie polycystic ovaiian synuiome.
:$;"5"/6&5 $J'-&'4 /"4A-$.,
B>> ?&-/6<&/. C #$;"5"/6&5 $J'-&'4 /"4A-$., H$- &A&$#'6?&5I
(Also uue to stiomal hypeiplasia - stioma of the ovaiy can make testosteione, oi
tumois otheis ovaiy)
This uz is a hypothalamic-pit abnoimality wheie FSB is suppiesseu anu LB is
incieaseu. If you know what LB uoes, it makes the pathophys easy. In a woman, LB
is iesponsible foi synthesis of theca inteina (which is aiounu the ueveloping follicle).
Buiing the piolifeiative phase of the cycle, what is pieuominantly being synthesizeu
is the 17 keto steioius BBEA anu anuiosteneuione. The anuiosteneuione is
conveiteu by oxyuoieuuctase into testosteione. Then, the test goes acioss the
membiane of the ueveloping follicle into the gianulosa cells, wheie theie is
aiomatase. FSB is put in theie. Then, the aiomatase in the gianulosa cell conveits
test into estiouiol anu this is wheie the woman gets hei estiauiol (fiom the
aiomatization piocess). LB is iesponsible foi synthesis of 17 keto steioius anu
testosteione in the ovaiies. This is why we will see hiistuism in a woman with
polycystic ovaiian synuiome (bc inciease of 17 ketosteioius, BBEA, anuiostenuione,
anu testosteione). 0besity is a common coiielation with this uz. This makes sense bc
excess auipose = moie aiomatase, so the sex hoimones test anu anuiosteneuione can
be conveiteu to estiogens in these pts. Anuiosteneuione is aiomatizeu into estione
(a weak estiogen). Testosteione is aiomatizeu into estiauiol, which is a stiong
estiogen. So, we have a paiauox - have a woman with signs of excess anuiogens
(hiisutism, acne - not signs of viiulization). At the same time, these aie being
conveiteu to estiogens so will have enuometiial hypeiplasia anu theiefoie have a
iisk of enuometiial caiicinoma. So, theie is a combo of incieaseu anuiogens anu
incieaseu estiogens. It is the incieaseu estiogens that causes suppiession of FSB via
negative feeuback, while theie is a P0SITIvE feeuback on LB. So, bc incieaseu
estiogens, pt is constantly suppiessing FSB anu constantly incieasing LB, so the
cycle iepeats itself. So, you can bieak the cycle with an 0CP bc the piogestin in it will
block LB. So, why uo they have cysts. Functions of FSB is to piepaie the follicle.
Also, they inciease the aiomatase activity. If the FSB is constantly suppiesseu, the
follicle uegeneiates anu leaves behinu a cystic spaces wheie the follicle useu to be.
So, pt has P0LYcytic ovaiian synuiome ielateu to chionic FSB suppiession. Can feel
these by pelvic exam anu seen with ultiasounu.
B,4/6-<'; A"/=<456&$4
G"/.,4$--?,' = painful menses (piimaiy anu seconuaiy - NCC piimaiy is too
much PuF - a Pu that incieases contiaction of the uteiine musculatuie. The NC
seconuaiy cause is enuometiiosis).
Theie aie also pioblems with uysfunctional uteiine bleeuing - this is N0T a
bleeuing abnoimality ielateu to a bleeuingoiganic cause. So, in othei woius, it is
not bleeuing fiom an enuometiial polyp, its not bleeuing fiom a cancei; this type of
bleeuing is a hoimone imbalance that causes abnoimality in bleeuing.
NCC abnoimal bleeuing in young lauy fiom menaiche to 2u yis of age =
anovulatoiy bleeuing. So, if a young lauy is bleeuing, that is the usual cause.
What is occuiiing. Theie is a peisistent estiogen stimulation that is occuiiing on
the mucosa, anu not enough piogesteione stimulation. So, they uevelop a lil
hypeiplasia, theie is a builu up of mucosa as the month piogiesses, anu then
eventually the stioma sloughs off anu leaus to significant bleeuing. So, its mainly an
estiogen piimeu uteius, without the effect of piogesteione anu they uo not ovulate
ielateu to this. This is the NCC.
(.,4$--?$,'
Piimaiy amenoiihea anu seconuaiy amenoiihea
When you think amenoiihea, it can be a piob with the hypothalamuspituitaiy. In
othei woius, is the hypothalamus putting out unRB oi not. Is the pit putting out
FSBLB oi not. So, is it a hypothalamic-pit abnoimality. Is it an ovaiian piob.
Naybe the ovaiy is not making enough estiogen. Is its an enu oigan piob.
This is anatomically ielateu - maybe she uoesn't have a vagina - D$P&6'4/P"^
S</6,-^!'</,- /"4A-$.,, oi maybe she has an impeifoiate hymen - she's been
having peiious all along, anu has bloou built up behinu it, oi ceivical stenosis (BES
exposuie) - these aie all anatomical ieasons foi the amenoiihea.

(/?,-.'48/ /"4A-$., - seconuaiy amenoiihea, woman has iepeateu uilatation
anu cuiotoshes(.), wheie the stiatum basalis is sciapeu away; have to leave
something behinu fiom which you can piolifeiate enuometiial mucosa - if you
sciape all the way uown the the muscle, will not be able to menstiuate again, anu will
scai eveiything off, leauing to an infeitile woman.
So, amenoiihea is piimaiy oi seconuaiy : hypothalamic-pit pioblem, ovaiian piob,
oi enu oigan piob. FSB anu LB levels help in uistinguishing those S.
If pt has hypothalamic-pit piob, what woulu FSB anu LB be. Low.
If hau a piimaiy ovaiian pioblem, what woulu they be. Bigh.
If you have an enu oigan uefect, what woulu FSB anu LB levels be. Noimal.
What is the fiist step in the woikup of any case of amenoiihea. Piegnancy test.
+<-4,-8/ /"4A-$.,0
Piimaiy cause of amenoiihea, webbeu neck, females
Najoiity aie X0, theiefoie uo not have a baii bouy. Befects in lymphatics. Can
make ux at biith via PE - see swelling of hanu anu feet (lympheuema) = tuineis
Webbeu neck is uue to lymphatic abnoimalities - get cystic hygiomas, which aie
uilateu lymphatics in the neck aiea anu fill with lymphatic fluiu anu stietch the skin -
bc they stietch the skin, looks like webbing. Bave pieuuctal coaictations. Bo not
have NR. some cases aie mosaics - X0XX anu theie is a iemote possibility that they
may be feitile. Theie aie also X0XY's that aie mosaic's. have menopause b4
menaiche. All of theie follicles aie gone by the age of 2, anu this is the stieak ovaiies
(gonau). Theiefoie, they aie susceptible to uysgeiminomas (seminomas aie in males
aie analogous).
M6,-&4, G&/$-A,-/
(A,4$."$/&/ - glanus anu stioma within the myometiium -veiy common cause of
uysmenoiiheal, uyspyiunia, menoiiagiah, hysteiectomy; uoes N0T pieuispose to
cancei.
Z4A$.,6-&$/&/ - functioning glanus anu stioma outsiue the uteius (myometiium is
INSIBE); NC location = ovaiy, causes bleeuing in the ovaiy - see chocolate cyst
(enuometioma's - not cancei, just enuometiiosis of the ovaiy), tube, in pouch of
Bouglas
Example: goou question to ask if pt has enuometiiosis: "Boes it huit when you
uefecate . Yes. Bow about when youi peiiou goes away." No, it goes away - this is
enuometiiosis bc theie is bleeuing in the iectal pouch of the pouch of Bouglas (theie
is enuometieosis theie). The iectum is filleu with stools, anu stieches the pouch of
Bouglas, leauing to pain. So, pain on uefecation uuiing the peiiou leaus to
enuometiiosis.
Z4A$.,6-&'; !"#,-#;'/&'
Fiom unopposeu estiogen. Always uangeious to have unopposeu estiogen,
meaning no piogesteione effect, bc then pt iuns iisk foi enuometiial cancei.
NCC enuometiial cancei = enuometiial BPY uue to unopposeu estiogen
Pouch of Bouglas can collect seeuing fiom ovaiian cancei, pus fiom PIB, unclotteu
bloou fiom iuptuieu ectopic piegnancy
(low pait of a woman's pelvis incluues: vagina, ceivical os, uteius, blauuei)
Z4A$.,6-&'; 5'45,-0
Eaily vs late menaiche - eaily is woise bc longei time foi estiogen to ciiculate
Eaily vs Late menopause - late is woise bc moie estiogen exposuie
0bese vs not obese - obese bc the estiogen factoi in auipose (moie aiomatase),
theiefoie, obese woman aie moie susceptible to canceis ielateu to estiogen - bieast
cancei, enuometiial cancei, ovaiian cancei
Type II uiabetics aie at incieaseu iisk bc 8u% of type II pts aie obese (so, the
obesity is the cause of incieaseu iisk of enuometiial cancei).
>'45,- '4A '3, E-'5P,6/
4S = ceivical
SS = enuometiial
6S = ovaiian
SS yo, postmenopausal is when you usually see enuometiial caicinoma. Any
woman that has been in menopause foi ovei 1 yi, anu then has iebleeuing has
enuometiial cancei until pioven otheiwise.
1
st
step in management. Enuometiial Bx
X,&$."$.' - NC b9 tumoi in a woman
Leiomyosaicoma - mitosis piob; NC saicoma of the uteius; big bulky tumois (as
aie all saicomas); leiomyoma is N0T a piecuisoi foi leiomyosaicoma.
Example: young woman suuuen onset of seveie lowei abuominal pain - .</6 A$ '
#-,34'45" H;$$P '6 E,6' \!>W ;,J,;I 6,/6 6$ -<;, $<6 ,56$#&5 #-,34'45")
2J'-&'4 .'//,/
Suiface ueiiveu - ueiiveu fiom the suiface of the ovaiy
ueim cell types - uysgeiminomas (men have these, too)
Sex choiu stiomal tumois - make estiogens (ie gianulosa cell tumois - theiefoie
can have hypeiestiinism which leaus to bleeuing anu enuo caicinomas), some make
anuiogens (seitoli leyuig cell tumois of the ovaiy - assoc with viiulization anu
hiistuism).
(males just have geim cell tumois)
T$;;&5<;'- 5"/6
B>> $= $J'-&'4 .'// &4 ' "$<43 L$.'4 C =$;;&5<;'- 5"/6
Follicle that iuptuieu, not neoplastic, accumulates fluiu anu leaus to peiitonitis. It
is bau if its on the iight siue bc it can be eithei iuptuieu folliculai cyst, appeuicitus,
ectopic piegnancy (iuptuieu), PIB; look at with ultiasounu
0nuei SS yo, most ovaiian masses aie b9
0vei SS yo, most ovaiian masses have a gieatei potential of being malignant.
[<-='5,A A,-&J,A (oveiall NC)
NC suifaceu ueiiveu = seious cystauenoma (B9); seious cystauenocaicinoma
(malignant)
(these aie the NC oveiall b9 anu malignant ovaiian tumois)
These aie also the NC that aie bilateial, anu the cystauenocaicinoma has
psommoma bouies (bluish coloieu - uue to apoptosis, uestiuction of the tumoi cell
anu ieplacement with uystiophic calcification). Also seen in papillaiy caicinoma of
the thyioiu anu in meningioma's
Example:: 6S yo, bilateial ovaiian enlaigement (iemem they tenu to aiise at this
age)
Any woman that is ovei SS anu has palpable ovaiies is cancei until pioven
otheiwise bc a postmenopausal woman shoulu be have ovaiies that aie atiophying.
Example:: 62 yo woman with ovaiian mass on the iight - alieauy know its bau bc
shoulun't have a palpable ovaiy.
>"/6&5 6,-'6$.'
Tooth, sebaceous glanus, caitilage, skin, thyioiu,,
NC oveiall geim cell tumoi, usually B9
If it is making thyioiu, it is calleu stiuma ovaiy
[,% 5?$-A /6-$.'; 6<.$-/
NC = fibiomas (B9)
Neigs synuiome: ovaiian fibioma, ascites, anu iight siue pleuial effusion - goes
away when you take the ovaiy out.
uianulosa cell tumoi of ovaiy: low giaue malignant tumoi; what uoes the gianulosa
cell noimally uo. It aiomatizes anuiogens anu estiogens, so a gianulosa cell tumoi is
moie than likely an estiogen piouucing tumoi.
Signet iing cells - is this a piimaiy cancei, oi mets fiom anothei site. Site is fiom
stomach - calleu a kiukenbuig tumoi; 6?,-, &/ Q2 #-&.'-" $J'-&'4 5'45,- 6?'6
?'/ /&34,6 -&43 5,;;/)
W,/6'6&$4'; G&/$-A,-/
:;'5,46'
Choiionic villus - outsiue layei = syncytiotiophoblast, cleai cells unuei the outsiue
layei = cytotiophoblast; which is making hoimones. Syncytiotiophoblast.
What hoimones is it making. B-hcu anu Buman Placental Lactogen (BPL) - giowth
hoimone of piegnancy. Bas myxomatous stioma. vessels coalesce into umbilical
vein, which has the highest o2 content.
Q,$#;'/./ $= 5?$-&$4&5 J&;;</0
!"A'6&A&=$-. .$;, - can be complete (46, XX, both X c'somes come fiom fathei -
calleu anuiogenesis) oi paitial (tiiploiu, 69 c'somes, can have a fetus piesent)
The complete moles have a gieatei piopensity to moving on to choiiocaicinoma.
>'</,/ $= 5?$-&$5'-5&4$.'0
Su% of choiiocaiicnomas aie fiom pieexisting hyauifoim mole (2% piogiess to
choiiocaicinoma; 1u% become moie aggiessive moles anu invaue myometiium
Qbank)
2S% fiom spontaneous aboition
2S% fiom noimal piegnancy
Byatiuifoim moles aie b9 tumois of the choiionic villus; choiiocaicinomas aie a
malignancy of the tiophoblastic tissue (uo not see choiionic villi). Loves to go to the
lungs anu iesponus well to chemotheiapy (can even go away in the piesence of
mets)
V-,'/6
Pictuie a schematic with nipple, lactifeious uuct, majoi uucts, teiminal lobules
(wheie milk is maue), anu the stioma
Nipple = Pagets uz of the bieast
Lactifeious uuct = Intiauuctal papilloma (NCC of bloouy nipple uischaige of woman
unuei Su) - b9 papillaiy tumoi, if you piess on it, bloou will come out of the aieola
Najoi uucts = wheie most of the canceis aiise fiom - invasive uuctal canceis,
meuullaiy caicinomas, mucinous caicinomas
Teiminal lobules (wheie milk is maue) - NC tumoi = lobulai cainicoma, is famous
be BILATERAL (so, lobulai tumois aie to the bieast as seious tumois aie to the
ovaiy in teims of theii bilatteiallity); .'..$3-'#?" A$,/486 #&5 <# ;$E<;'-
5'45,-/)
B>> $= .'// &4 E-,'/6 $= L$.'4 <4A,- Nf C U&E-$5"/6&5 5?'43,
B>> $= .'// &4 E-,'/6 $= L$.'4 $J,- Nf C 5'45,-0 infiltiating uuctal caicinoma
(not intiauuctal - this means that we aie not picking up the cancei eaily enough by
mammogiaphy anu picking up in the intiauuctal phase, anu oui techniques aie
insensitive - so we aie missing the uuctal stage anu we aie picking up the cancei
when it has invaueu - to pick up eaily, neeu to get at Smm oi less).
So, if they aie intiauuctal, has a goou piognosis
Example: SS yo woman with movable mass in bieast that gets biggei as the cycle
piogiesses = fibioauenoma
These aie the most commons in teims of age anu location
Sliue: U&E-$5"/6&5 5?'43, - cysts, lumpy bumpy in bieast, moie painful as the cycle
piogiesses bc they aie hoimone sensitive
Example:: uuctal hypeiplasia - cannot see; piecuisoi lesion foi cancei that aie
estiogen sensitive epithelial cells in the uucts (just like the enuometiial glanus aie
estiogen sensitive, the glanus lining the uucts aie estiogen sensitive).
[5;,-$/&43 'A,4$/&/ - in teiminal lobules, b9 pait of fibiocystic change (see cysts)
T&E-$'A,4$.'
B> 6<.$- 6?'6 .$J,/ '-$<4A &4 6?, E-,'/6 &4 ' L$.'4 <4A,- 9N C
U&E-$'A,4$.' - is the neoplastic components the glanus oi the stioma. It's the
stioma - as it giows, it compiesses the uuctstems, so they have slit like spaces; veiy
common. Even if you know it's a fibioauenoma, still get a bx
V-,'/6 >'45,-
Sliue: Bow uo you know its bieast cancei. nipple is haiu as a iock - when bieast
canceis invaue the stioma, they elicit a fibioblastic anu elastics tissue iesponse,
making it haiu - this is goou bc it makes it palpable. +?&/ &/ L?" ' L$.'4 $J,- Nf_
6?'6 ?'/ ' #'&4;,// #';#'E;, .'//_ &6/ 5'45,-)
@= &6/ #'&4=<; '4A <4A,- Nf_ &6/ -'-,;" 5'45,- H='6 4,5-$/&/_ U&E-$5"/6&5 5?'43,I)
So, the magic woiu is painless.
0utei quauiants of the bieast aie the NC sites bc this is wheie most of the bieast
tissue is. Theiefoie, this woulu be the NC site foi bieast cancei. The 2
nu
NC site is
aiounu the aieola.
Sliue: nipple being suckeu in, whitish mass, stellate (classic foi invasive cancei); on
mammogiaphy, see uensity with spicules coming out anu has calcifieu. This is highly
pieuictive foi cancei. What is the fiist step in management of a palpable mass. FNA
- bc can make a ux anu tell if its soliu oi cystic (this is also the fiist step in
management of colu nouule in thyioiu, not ultiasounu).
Sliue: intiauuctal cancei - netlike aiiangement, calleu comeuocaicinoma, junk that
comes out (like caseous neciosis); has eib-2 oncogene (aggiessive canceis).
Sliue: invasive cancei, see tumoi cells invauing stioma; see Inuian filing - sign of
invasive lobulai cancei; seen moie often in infiltiating uuctal caicinoma
Sliue: eczematous uz aiounu the nipple = pagets uz of the bieast - iash aiounu
nipple - cancei of the uuct that has spieau to the skin
Sliue: inflammatoiy caicinoma - woist, ieu, uimpleu skin bc the lymphatics aie
pluggeu with cancei unueineath anu the lymphatic fluiu leakeu out, but the
ligaments aie still attacheu, but incieasing the fluiu in the inteistium, anu as it
expanus out, it uimples - p'uoeu oiange - so, inflammatoiy caicinoma looks like that
bc its lymphatic filleu with tumoi, anu is the woist of the woist.
Sliue: lobulai caicinoma - NC cancei of the teiminal cancei (at the enu of the
uucts); it is famous foi bilateiality
Sliue: lympheuema is a woman that is postiauical masectectomy; when you aie
uoing a mouifieu iauical mastectomy, what aie you iemoving. The entiie bieast
incluuing a nipple, leaving behinu pec majoi, axillaiy iesection, anu taking pec minoi.
NC complication = wingeu scapula (bc cut the long thoiacic neive)
+?, ;<.#,56$." iemoves the unueilying tumoi with a goou boiuei of noimal
tissue aiounu it, take a few noues fiom the axilla (bc have to use foi staging bc they
go to lowei axillaiy fiist), anu then you uo iauiation of the bieast (goou foi bieast
conseivation - same piognosis as mastectomy)
Example:: ERA-PRA = estiogen ieceptoipiogesteione ieceptoi assay - what uoes
it mean. Relationship betwn estiogen anu its ieceptoi synthesis. So, if you aie in a
iepiouuctive peiiou of youi life when estiogen is abunuant, the ieceptois will be
uowniegulateu. This is why in women that aie young, in the iepiouuctive peiiou of
theii life, have bieast cancei anu aie ERPRA negative bc this is what we woulu expect
bc estiogen woulu uown iegulate ieceptoi synthesis. Wheieas, if you aie
postmenopausal, it leaus to up iegulation of the ieceptois anu those women aie
ERPRA positive. But what uoes this mean. It means that the tumoi is iesponuing to
estiogen anu neeu to take away that estiogen affect bc it is feeuing the tumoi. Bow
can you take it away. Tamoxifen - this is weak estiogen, so it hooks into the ieceptoi
of bieast tumois, so if theie is any left behinu, noimal estiogen in a woman can't get
into it anu won't be able to feeu the tumoi. So, it's a blockei of the ieceptoi.
Complications. Nenopausal type symptoms; also, it is an estiogen so you have the
iisk of enuometiial cancei. A benefit in the postmenopausal state with an ERA PRA
pos woman is that it uoes pievent osteopoiosis. So, cannot give estiogen to a woman
that is ERA PRA pos, but is a canuiuate foi tamox anu will piolong iecuiience.
CHAPTER 13: Endocrine
Auuio File SS: Enuociine 1
:-&.'-" J/ [,5$4A'-" J/ +,-6&'-"
Bashimotos = uestiuction of the thyioiu glanu = PRINARY hypothyioiuism (the
glanu sciews up the hoimone)
Bypopituitaiism anu hypothyioiuism = SEC0NBARY hypothyioiuism (no TSB to
stimulate)
Bypothalamic Bz = Saicoiuosis uestioying TRB: TERTIARY (no TRB)
Example: auenoma on paiathyioiu piouucing PTB leauing to hypeicalcemia =
piimaiy hypeipaiathyioiuism
Example: have hypocalcemiavit B uef, anu askeu the paiathyioiu to unueigo
hypeiplasia, that is calleu SEC0NBARY hypeipaiathyioiuism
Example: what if aftei a long time PTB keeps being maue = teitiaiy
hypeipaiathiyioiuism (iaie)
2J,-'56&J&6" J/ <4A,-'56&J&6" $= 3;'4A/
[6&.<;'6&$4 6,/6: if pt has unueiactive glanu, woulu use stimulation test to see if
the glanu is woiking.

[<#-,//&$4 6,/6: if pt has oveiactive glanu, woulu use suppiession test to see if
glanu will stop woiking.
Nost of the time, things that cause oveiactivity, we CANN0T suppiess them.
Theie aie 2 exceptions wheie we suppiess them, anu they ueal with oveiactivity in
the pituitaiy glanu
- 1)#-$;'56&4$.' can be suppiesseu bc it can pievent the tumoi fiom making
piolactin; biomociiptine suppiesses it (uopamine analog - noimally, women uo not
have galactoiihea bc they aie ieleasing uopamine, which is inhibiting piolactin
(theiefoie uopamine is an inhibitoiy substance - biomociiptine is also useu foi
tieating paikinson's bc biomociiptine is a uopamine analog (which is what is
missing in paikinsons uz)
2) :&6<&6'-" ></?&43/: b9 tumoi in the pitiuitaiy that is making ACTB - you CAN
suppiess it with a high uose of uexamethasone. These aie the only two exceptions
foi a tumoi making too much stuff.
(Theie is no way to suppiess a paiathyioiu auenoma making PTB, oi an auienal
auemona making coitisol, oi a an auienal tumoi fiom synthesizing aluosteione -
these aie A0T0N0N00S)
Example: pt with hypocoitisolism - lets uo an ACTB stimulation test - will hang up
an Iv uiip anu put in some ACTB; collecting uiine foi 17 hyuioxycoiticoius
(metabolic enu piouuct of coitisol) anu nothing happens - so what is the
hypocoitisol uue to. Auuison uz - glanu was uestioyeu - theiefoie, even if you keep
stimulating it, you will not be making coitisol.

Example: Let's say aftei a few uays you see in an inciease in 17 hyuioxycoiticoius,
then what is the cause of hypocoitisolism. Bypopituitaiism - in othei woius, it's
atiophic bc its not being stimulateu by ACTB, but when you gave it ACTB ovei a
peiiou of time, it was able to iegain its function. So, with that single test, you aie able
to finu cause of hypocoitisalism.
Can also look at hoimonal levels - ie Auuison's causing hypocoitisalism, what
woulu ACTB be. Bigh; if you have hypopituitaiism causing hypocoitisalism, what
woulu ACTB be. Low
!"#$#&6<&6'-&/.
B>> &4 'A<;6/ C 4$4=<456&$4&43 #&6<&6'-" 'A,4$.' (within sella tuicica - in the
sphenoiu bone, hence suigeiy is tiansphenoiual suigeiy, wheie the expanueu sella
tuicica is).
Pit Auenoma - usually nonfunctioning anu uestioys the noimal pituitaiy ovei time
as it giows, leauing to hypopituitaiism.
[?,,?'4/ H#$/6#'-6<. 4,5-$/&/I
Example:: have a piegnant woman, has abiuptio placenta anu goes in to
hypovolemic shock, but get out; uoing fine anu bieast feauing baby at home, but
suuuently stops bieast milk piouuction - ux. Postpaitum neciosis - theiefoie she
has infaicteu hei pituitaiy (coagulation neciosis), anu this is iesiuual pitiuataiy
H+?&/ &/ 4$6 ;&Y<,='56&J, 4,5-$/&/ E5 6?, #&6<&6'-" &/ 4$6 #'-6 $= 6?, E-'&4I)
Nech is ischemia anu coagulation neciosis. Piegnant woman have a pituitaiy glanu
two times the noimal size. Piolactin is being synthesizeu - but a piegnant woman
uoes not have galatoiihea bc the estiogen anu piogesteione inhibit ielease. So, the
moment you give biith, the inhibitoiy effect is ieleaseu anu stait having
galactoiihea. This is the 2
nu
NCC hypopit in auult.
B> &4 P&A/ C 5-'4&$#?'-4"3&$.'
Rathke's pouch oiigin - this is pait of the embiyological uevelopment of the
pituitaiy glanu - pieces of it iemain anu can become neoplastically tiansfoimeu into
a cianiophaiygioma. Its not a malignant tumoi, but a b9 tumoi in a bau place. It is
NC supia-sellai - (above the sella) - anu it goes uown anu uestioys the pituitaiy, but
likes to go foiwaiu anu bumps into optic chiasm, leauing to E&6,.#$-';
?,.&'4$#/&', leauing to visual fielu uefect.
Example:: chilu with heauaches anu visual fielu uefect - uo a schematic of it anu will
ask what the cause is - cianiophaiyngioma - tumoi of iathke's pouch oiigin.
W-$L6? !$-.$4,
When you have a tumoi that is expanuing in the sella tuicica, uiffeient ieleasing
factois (hoimones) ueciease in a ceitain succession. The fiist thing that is uestioyeu
is gonauotiopin. So, in a woman, what woulu happen. She woulu have amenoiihea
(seconuaiy amenoiihea). What if I weie a man (what is the analogous conuition).
Impotence; impotence is to a male as amenoiihea is to a female. Impotence = failuie
to sustain an eiection uuiing attempteu inteicouise. The next thing that goes is
giowth hoimone (which has 2 functions: 1) &45-,'/,/ '' <#6'P, anu 2) &4J$;J,A &4
3;<5$4,$3,4,/&/ (hoimone that piouuces bone anu tissue giowth is insulin like
giowth factoi-1, which is piesent in the livei - aka somatomeuins; so, uB ielease will
stimulate the livei to ielease IuF-1 to cause giowth of bones lineaily anu soft tissue);
an auult with the loss of giowth hoimone will not get smallei, but will have the
effects of lack of giowth hoimone: will stait to lose muscle mass anu will have fasting
hypoglycemia bc uB is noimally gluconeogenic. So, its not theie anu not
contiibuting is func to glucogngeogenesis, leauing to hypoglycemia. What woulu you
see in a chilu. Pituitaiy Bwaifism. Woulu see ?"#$#;'/&' (incomplete uevelopment
of something). So, pit uwaifisim is an incompletely uevelopeu chilu, but eveiything
looks noimal. What is the best stimulation test to see if you aie uB oi IuF-1
uefecient. Sleep. You giow when you sleep - exactly at S am (that's when uB comes
out). So, the best test is sleeping, then checking bloou at S am (if it isn't youi
uef).Why is histiuine anu aiginine ueficient. They aie essential to noimal giowth of
a chilu bc they stimulate giowth hoimone. These aie basic aa's. This is why wt
lifteis buy aighis supplements. So, best test is sleep, followeu by measuiing aig anu
his levels. The thiiu hoimone to go is TSB, which leaus to hypothyioiuism (theiefoie
low TSB anu low T4 - colu intoleiance, biittle haii, fatigue, uelayeu ieflexes). The
next thing that goes is ACTB , leauing to hypocoitisalism. Will be fatigue will a low
coitisol level. Will also leau to hypoglycemia bc coitisol is gluconeogenic. That last
thing to lose is piolactin.
G&'E,6,/ @4/&#&A</
Cential (lacking ABB) vs Nephiogenic (kiuney uoesn't iesponu to ABB)
Cential: one of the common causes is cai acciuent, leauing to heau tiauma. The
heau is shifteu anu stalk is seveieu. 0ne of the fiist things that goes is ABB bc it is
maue in the supiaopitic paiaventiiculai nucleus of the hypothalamus. In the same
neive it is maue in, it goes uown the stalk anu is stoieu in the P0STERI0R pituitaiy.
So, if you sevei that stalk, you sevei the connection anu leaus to ABB uef. Also uef in
all the ieleasing factois that aie maue in the hypothalamus that stimulate the
pituitaiy, leauing to hypopituitaiism (eventually - but initially will have ss of BI =
polyuiea anu thiist).
Nephiogenic: have ABB, but uoesn't woik on the collecting tubule to make it
peimeable to fiee watei. 0thei polyuiea's (BN - mech = osmotic uiuiesis,
polyuipisia - mech = uiink too much watei (psychological pioblem), hypeicalcemia
leaus to polyuiea).
Constantly uiluting, but will nevei be able to concentiate uiine; SIABB is the exact
opposite, wheie ABB is always theie, anu will constantly concentiating, anu will not
be able to uilute. In BI, constantly uiluting uiine, losing fiee watei, anu will nevei be
able to concentiate the uiine. So, you aie losing all the watei, anu seium Na will go
up, coiielating with an incieaseu plasma osmolality (bc most of plasma osmolality is
Na).

+$ 6,/60 -,/6-&56 L'6,- - in a noimal peison, if you iestiict watei, the plasma
osmolality will go up to 292 (the uppei limit of noimal foi the osmolality), 7Su uiine
osmolality - what uoes that mean. Pt is concentiating the uiine. So, if you aie
uepiiving a noimal pt of watei, it shoulu concentiate the uiine; watei is being
ietaineu get into the ECF to get the seium Na into noimal iange.
Example: pt iestiicteu watei anu have a S19 anu S12 plasma osmolality (which is
elevateu). So, they have hypeinatiemia. If you look at uiine osmolality, it is 11u anu
98. So you know that have BI. So, how uo you uistinguish cential fiom nephiogenic.
uive them ABB (aka vasopiessin). So, you give it to them anu see what happens to
uiine osmolality.
@= &6 &45-,'/,/ 3-,'6,- 6?'6 Nfn =-$. 6?, E'/,;&4,0 6?,4 &68/ 5,46-';)
@6 &6/ ;,// 6?'4 Nfn &68/ 4,#?-$3,4&5) So, gave ABB to fiist guy anu it uiine
osmolality change to SSu, inuicating that he has cential BI. Foi the seconu pt, ABB
was given, but only a lil inciease in uiine osmalality, inuicateu nephiogenic BI.
(5-$.,3';"
What is cheapest way foi scieening foi aciomegaly. Ask foi an olu pic of the pt 1u
yeais ago. uigantism in kiu bc epiphyses haven't fuseu, theiefoie an excess in uB
anu IuF-1 leau to an inciease in lineai giowth. Bau uz bc can uie fiom
caiuiomyopathy. So, they have excess uB anu excess IuF-1. So, what if you'ie an
auult with aciomegaly. Will not get tallei bc the epiphyses have fuseu, but bones will
giow wiuei. 0ne of the bones in the heau that uoes that is the fiontal bones, so they
stick out. So, get a goiilla like inciease in the fiontal lobe (bc it incieases size of the
sinuses), so the hat size will inciease. Youi hanus get biggei, feet get biggei, anu
eveiy oigan in the bouy gets biggei. Also, you piouuce a caiuiomyopathy, which
leaus to ueath.
W';'56$--?,'R:-$;'56&4$.'
Nen uo not get galactoiihea bc we uon't have enough teiminal lobules to make the
milk. So, if a male has a piolactinoma, uo not expect him to have galactoiihea. This
has many causes. When woman comes in with it, make suie you ask what uiug they
aie on - bc theie aie many uiugs that can stimulate piolactin synthesis.
Example:: 0CP's, hyuialazine, Ca channel blockeis, psychotiopic uiugs. Piimaiy
hypothyioiuism can also be a cause, theiefoie get a TSB level. Why. Bc if you have
hashimoto's, not only is TSB incieaseu, but you also have incieaseu TRB. TRB is
useu as a stimulation test foi piolactin. So, you must iule out hypothyioiuism in a
woman with galactoiihea (so in this case, theie is nothing wiong with the pituitaiy,
but the thyioiu, leauing to galactoiihea). [$_ .</6 -R$ ?"#$6?"-$&A&/..
If all this is iuleu out anu pt has high piolactin level, ux is piolactinoma (any time
theie is a piolactin level ovei 2uu it is always a piolactinoma). When pts have
piolactinoma, why uo they uevelop amenoiihea. Bc piolactin has a negative
feeuback on unRB. So, this is a cheap biith contiol pill foi the fiist thiee months
aftei piegnancy bc mom is bieast feeuing, anu the high piolactin levels aie feeuing
back on the pituitaiy on unRB.
+?"-$&A
Thyioiu stuuies - uo N0T have to know iesin TS uptake anu T4 inuexes; S things
neeu to know: T4, TSB, I 1S1 uptake
If TSB is noimal, the thyioiu is noimal. If TSB is uecieaseu, pt has hypeithyioiuism
oi hypopituitaiism. If TSB is incieaseu, have high piimaiy hypothyioiuism.
Thyioiu binuing globulin is the binuing piotein foi thyioiu hoimone
What is the binuing piotein foi
coitisol. Tianscoitin;
calcium. Albumin;
Fe. Tiansfeiiin;
Cu. Ceiuloplasmin; what % of binuing sites occupieu. Su%).
S of 9 binuing sites on TBu aie occupieu by thyioiu hoimone.
Fiee T4 level. When we measuie total T4 level, theie is fiee T4 anu bounu T4. The
fiee T4 is the pait that is metabolically active anu is conveiteu to TS. This pait is
uoing all the woik (that pait that is bounu is not).
What happens if you aie on an 0CP with an inciease of estiogen. TBu anu
tianscoitin inciease. So, incieaseu syn TBu, anu is immeuiately 1S occupieu (9 sites
on TBu, anu 1S occupieu by T4, so that is S T4's). Bc eveiything is in equilibiium,
the thyioiu senses that it lost S T4's anu ieplaces them immeuiatetly. So, has the
FREE T4 alteieu. No. So what is the TSB. Noimal. What is the T4. Incieaseu (but
the fiee hoimone level anu TSB not alteieu). So, an inciease T4 with a noimal TSB
means the pt is on estiogens. This is tiue foi any woman on estiogen oi any
piegnant women. So, the total T4 is elevateu bc incieaseu TBu (not be incieaseu fiee
hoimone level) anu it automatically has S sites occupieu by T4). Same is tiue foi
coitisol - if pt is piegnant oi on 0CP, coitisol is elevateu but uo not have signs of
cushings. Why. Bc tianscoitin is incieaseu bc estiogen incieasing the synthesis of it,
so theie is moie coitisol bounu to it, but the fiee coitisol levels aie still noimal.
Example:: if football playeiwt liftei, assume pt is on anabolics. They woik the
opposite. Anabolics bieak uown pioteins that you noimally woulu use foi othei
things to builu up anu put them into muscle. The pioteins it likes to go aftei is
binuing pioteins. So, when they aie on anabolics, thyioiu binuing globulin is
uecieaseu bc the aa's that you woulu have useu to make the binuing piotein aie
insteau utilizeu to make muscles stiongei. So, they won't woik if you aie not
woiking aa supplements.
Example: pt on anabolics, so less TBu being synthesize bc pioteins being useu
elsewheie (muscles). The same numbei of site aie occupieu, but missing TBu. So,
fiee T4 is the same, but missing TBu. So, if a peison has a low T4 with a TSB, they
aie on anabolic steioius. If a woman has a high T4 anu a noimal TSB, what is she on.
Estiogen. If a peison has high T4 anu low TSB, what uo they have. Bypeithyioiuism.
If pt has low T4 anu incieaseu TSB, what uo they have. :-&.'-" ?"#$6?"-$&A&/..
Bo not neeu iesin TS uptake to make these ux's.
@ 191 <#6'P, is a iauioactive test (iemembei that thyioiu hoimone is tyiosine with
iouine on it). (What aie othei things involveu with tyiosine. Nelanin, tyiosine
tyiosinase, uopamine - goes into the golgi appaiatus anu becomes melanin,
phenylalanine, uopamine, uopa, NE, epi (catecholamines), if you put iouiues on
tyiosine you have thyioiu hoimone). So, with hypeithyioiuism (ie giaves), thyioiu
glanu will be making moie thyioiu hoimone. Woulu we neeu moie iouiue to uo this.
Yes. So, if you gave a pt iauioactive iouiue, will theie be incieaseu uptake of
iauioactive iouiue in that oveiactive glanu. Yes. So, will have incieaseu I1S1 uptake.
What if I weie taking excess thyioiu hoimone to lose weight - what woulu that uo to
my TSB level. Suppiess it. So, when that pt is taking too much hoimone, the glanu
has atiophieu. So, if you have a iauioactive I 1S1, woulu theie be an incieaseu
uptake. No bc is has atiophieu. So, iauioactive I 1S1 is the main way to uistinguish
whethei a peison has tiue eviuence of hypeithyioiuism (uLANB is making too much
thyioiu hoimone) vs someone that is suiieptitiouslypuiposelyunknowingly taking
too much thyioiu hoimone anu piouucing hypeithyioiuism. I 1S1 is the best test to
uistinguish these two types of hypeithyioiuism. So, if its incieaseu, pt has giaves
(glanu is using it); if its uecieaseu, pt is taking thyioiu hoimone.
Example:: pt fiom wt loss clinic - they aie taking thyioiu hoimone, so they will lose
wt at the expense of hypeithyioiuism
Sliue: miuline cyst - ux. +?"-$3;$//'; 5"/6) Remembei that the thyioiu glanu was
oiiginally at the base of the tongue anu migiates uown the miuline to the cuiient
location.
Sliue: cyst in anolateial poition of neck - ux. Bianchiocleft cyst
(know all bianchiocleft ueiivatives - esp the one in the heau aiea).
+?"-$&A&6&/ (inflammation of the thyioiu)
The only imp one is hashimoto's
W-'J,8/ G] - exophalmos M4&Y<, 6$ W-'J,8/ G] - excess uAu's uepositeu in oibital
fat, anu pushing the eye out (pathonomognic foi giaves); apathetic giaves
0LB people with giaves uz have heait piob with atiial fib. They get heait
manifestations. So, any pt with atiial fib, must get a TSB level to iule out giaves.
/R/ ?"#,-6?"-$&A&/.0
heat intoleianc, sinus tachy, atiial fib, biisk ieflexes, uiaiihea, systolic BTN,
hypeicalcemia, incieaseu bone tuinovei (all symptoms aie auieneigic - they aie all
catecholamine things - why. T4 incieases the synthesis of beta ieceptois
(catecholamines aie cousins of Thyioiu hoimone anu they woik togethei. All the
symptoms aie auieneigic. What is the INITIAL Rx of giaves. Beta blockeis (blocking
auieneigic iesponse, then give PT0 to stop the glanu fiom making it - can stop all
the symptoms with beta blockei except one - sweating)
so, thyioiu stuuies on giaves pt: T4 is high, TSB is low, I 1S1 is BIuB
Auuio File S4: Enuociine 2
@4 ?"#,-6?"-$&A&/._ want to always look at the face anu will see peiioibital
puffiness, which is seen a lot bc of uAu's (also in vocal coius, leauing to hoaiseness,
tibial aiea leauing to nonpitting euema)
B&6-'; F';J, :-$;'#/, also has an inciease in uAus bc ueimatan sulfate is
iesponsible foi causing excess anu ieuuuency of the valve). Also seen in Bashimotos.
uiaves is uue to Igu Ab against TSB ieceptoi, causing it to synthesize too much.
What type of BPY ixn is this. Type II (Ab against the ieceptoi); Nu is also type II BPY
(have Ab against ieceptoi which is uestioying the ieceptoi). In hashimoto's
thyioiuitis, they also have an Igu against the ieceptoi, except insteau of activating
the glanu, it inhibits it. So, in Bashimoto's anu uiaves, these aie both autoimmune
uz's but at opposite enus of the spectium. 0ne as stimulatoiy Igu while the othei has
an inhibibitoiy one. So, an oveilying symptom that they both have is pietibial
myxeuema anu uAu ueposition. Wheie uo you see a ueciease in uAu's (ie
metabolism of uAu's). Lysosomal stoiage uzs - Buileis, Bunteis - neeu lysosomal
enzymes foi bieaking uown ueimatan sulfate, etc.
/R/ ?"#$6?"-$&A&/. \
weakness (NC) bc all pts with hypothyioiuism have pioximal muscle myopathy, so
they cannot get up out of chaiis , seium CK's aie elevateu. Also have biittle haii,
couise skin, slow mentation, peiioibital puffiness, uelayeu ieflex, uiastolic BTN
Sliue: bx of thyioiu glanu in Bashimotos's - no follicle, but uo see geiminal follicle
bc theie is autoimmune uestiuction of the glanu. Theie aie cytotoxic T cells that
uestioying it, anu aie synthesizing Ab's (Igu Abs, hence you see the geiminal
follicles), anu theiefoie looks like a lymph noue). Will see a low T4, high TSB, low I
1S1 (not necessaiy to uo this test).
Example: pt on estiogen - what will happen to T4. Inciease TSB. Noimal (no neeu
foi I 1S1 - this is bau bc babies thyioiu woulu take it up anu its thyioiu woulu take it
up anu leaus to cietinism)
thyioiu hoimone is iesponsible foi biain giowth in the fiist yeai, so it imp to uo
thyioiu hoimone scieens to avoiu cietinism (will be seveily NR bc biain uepenus on
thyioiu hoimone foi uevelopment).
Example: uiave's uz - T4 high, TSB, low, I 1S1 high
Example: pt on anabolic steioius - T4 low, TSB noimal
Example: Bashimotos - T4 low, TSB high, I 1S1 low
Example: factitious (taking too much thyioiu hoimone anu have hypeithyioiuism)
- T4 high, TSB low, I 1S1 low (main factoi that uistinguishes fiom giaves)
W$&6,-
Anytime thyioiu is big. Lots cysts.
B>> 3$&6,- C @$A&4, A,=
Nost often uue to low iouiue levels, so they have hypothyioiuism oi boiueiline
hypothyioiuism, so the glanus aie getting iev'u up, T4 goes up anu TSB goes uown
(so TSB will be stimulating it, then not, then it is, etc..).
Rx of choice - thyioxine
Sometimes have a nouule - nouules that uevelop in the thyioiu glanu get
hemoiihageu. Theie is suuuen inciease in hemoiihage uue to cyst. Bx with FNA.
Then, give thyioiu hoimone anu many times these things will get smallei.
In this countiy, we iouinize salt, so uon't see much. Bowevei, some places people
have iouine pooi uiets - ie uieat Lakes in Chicago aiea, Biitain; when they get giaves
uz, uue to inciease in TS bc they aie iouiue uef anu uo not have enough iouine.
>$;A 4$A<;, J/ !$6 Q$A<;,
Neans if nouule is taking up I 1S1 oi not. If it uoes not, theie is an aiea of lucency,
anu theiefoie colu. If it is hot, theie will be a black uot. Why. Bc if the nouule is
autonomously making thyioiu hoimone, what is the TSB. Becieaseu. If the TSB is
uecieaseu, woulu that suppiess the noimal poition of the thyioiu. Yes, so it unueigo
atiophy anu not take it up, leauing to black uot (woulun't see anything else). What is
chance that a colu nouule is malignant in a woman. 1S-2u%. Nost colu nouules in an
oluei woman aie benign. Nost aie cysts. A small % is folliculai auenoma. Any colu
nouule in a NAN is cancei until pioven otheiwise. Any colu nouule in a chilu is
cancei until pioven otheiwise. Any PERS0N that has been exposeu to iauiation anu
has a colu nouule has CANCER (papillaiy caicinoma of the thyioiu - iauiation
exposuie in heauneck aiea).
>'45,-/ $= 6?, 6?"-$&A
Neeu to bx (cannot tell if malignant just by looking at it) - this is tiue foi folliculai
auenoma, something b9, multinouulai goitei. Bone with FNA.
1. :'#&;;'-" 5'45,- woulu show up with a colu nouule, anu has :/'..$.'
E$A&,/) Papillaiy caicinomas mets to ceivical lymph noues next to them.
They commonly uo this, anu have a goou piognosis. This is the only assoc with
iauiation. Annie oiphan nuclei.
2. T$;;&5<;'- 5'45,- - 2
nu
NC type, invaues vessels. Bo not go to lymph noues.
Spieau hematogenously, theiefoie often go to lungs anu bone.
S. B,A<;;'-" 5'-5&4$.' - some cases aie spoiauic anu othei cases have AB
ielationship; assoc with NEN synuiomes (multiple enuociine neoplasia I, IIa,
IIb) Pink stain - stain with congo ieu anu see polaiizeu apple gieen
biiefiingence = amyloiu A (which came fiom calcitonin); what is the tumoi
maikei. Calcitonin (which is the scieening test of choice)
K) Example: wheie woulu the cancei be locateu in the bouy wheie the tumoi
maikei is conveiteu into amyloiu. B,A<;;'-" 5'-5&4$.' $= 6?, 6?"-$&A
BZQ @ - pit tumoi, paiathyioiu auenoma, pancieatic tumoi (usually Zolingei
Ellison, leauing to peptic ulcei).
BZQ @@' - meuullaiy caicinoma, pituitaiy , pheochiomocytoma
BZQ @@E - meuullaiy caicinoma, pheochiomocytoma, mucosal neuioma
Bow uo you scieen. Ret piotooncogene (unique to couing foi ieceptois in this
synuiome).
:-$34$/&/ HE,/6 6$ L$-/6I0 :'#&;;'-"mT$;;&5<;'-mB,A<;;'-"
:(D(+!bD2@G WX(QG
Pt can have tetany with a noimal total Ca. Ca is bounu anu fiee - it's the fiee Ca that
is metabolically active (which is tiue foi ANY hoimone - the pait that is bounu is
totally metabolically inactive). So, who uoes Ca inteiact with. PTB
So, if Ca is low, the PTB is high, anu if Ca is high, PTB is low. Roughly 1S of the
binuing sites in albumin aie occupieu by Ca. So, in othei woius, ioughly 4u% of the
total Ca is bounu to albumin. 47% is ionizeu Ca floating aiounu anu the iest is
phosphate anu sulfates. The ionizeu Ca is the metabollicaly active foim. NCC oveiall
of hypocalcemia = hypoalbuminemia. Bave low albumin level, theiefoie uecieaseu
level, anu less of albumin binus Ca. So, befoie you look at PTB levels, look at albumin
levels - if that is low, this is the cause of hypocalcemia. This is not affecting the fiee
hoimone level, just that albumin is uecieaseu. This the same as TBu being
uecieaseu, leauing to uecieaseu T4.
(;P';$/&/ H-,/# $- .,6'E$;&5I0 have uecieaseu B ions, anu pB is incieaseu. What
aie the aciuic aa's. ulutamate, Aspaitate. Why aie they aciuic. Bave C00B gioups
(as opposeu to basic aa's , which have moie basic NB gioups).
The ieason why albumin is such a gieat binuei of Ca is bc it has the most negative
chaiges in the bouy, bc it has the most aciuic aa's in it. So, if you have an alkalotic
state the C00B gioups become C00 "-" gioups. Bc if you have less B ions, its C00"-".
So, albumin has N0RE of a negative chaige in an alkalotic state, which means it can
binu moie Ca. So, wheie uoes it get it fiom. Ionizeu fiee Ca (so a bunch of ionizeu
fiee Ca binus to the the albumin). Bowevei, we have N0T alteieu the total, just took
it. It uoesn't affect the total, but it B0ES ueciease the ionizeu Ca level, leauing to
TETANY. So, total is the same, but the ionizeu level has uecieaseu. What is the mech
of tetany. Bave thiesholu foi the AP befoie the neive is stimulateu. Then you have a
iesting membiane potential. So, a uecieaseu ionizeu Ca level will lowei the
thiesholu foi activating the neive anu muscle. If its -6u foi noimal thiesholu. Pt is
paitially uepolaiizeu, theiefoie uoesn't take a lot to activate the muscle oi the neive
(which is the mech of tetany) - so you aie loweiing the thiesholu. In hypeicalcemia,
the opposite occuis anu you aie incieasing the thiesholu, so it takes moie ionizeu Ca
to activate the neive.
PTB on y axis anu Ca in x axis - ht of squaie = PTB anu wiuth = Ca
X$L /,-<. >'_ ;$L :+! C #-&.'-" ?"#$#'-'6?"-$&A&/.
B>> C #-,J&$</ 6?"-$&A /<-3,-"
Example: pt goes in to iemove thyioiu cancei (these uays they autotianplant it to
the aim)
Example: newboin with cyanosis, iiiitable anu xiay of chest shows not
anteiioimeuiastinum shauow - ux. Biueoige - hypopaiathyioiuism anu no thymus
Example: ;$L >'_ ?&3? :+! C /,5$4A'-" ?"#$#'-'6?"-$A&/. - so whatevei is
causing the hypocalcemia is causing a compensatoiy inciease in PTB (calleu
seconuaiy hypopaiathyiouism - the NCC of this is ienal failuie bc these pts have
hypovitaminosis B, which uecieases Ca anu incieases PTB). So, any ueciease in Ca
with cause a compensatoiy inciease in PTB.
Example: ?&3? >'_ ?&3? :+! C #-&.'-" ?"#,-#'-'6?"-$&A&/. = glanu is not
obeying negative feeuback. This is NCC hypeicalcemia is a community;
If pt is in a hospital, NCC hypeicalcemia = mets to bone (malignancy inuuceu). Nost
hypeicalcemia pts aie asmptomatic; if they ARE symptomatic, they have stones (Ca
stones, which is the NC symptomatic piesentation foi hypeicalcemia).
Labs: incieaseu Ca, incieaseu PTB, low phosphate (noimally PTB incieases Ca
ieabsoiption anu uecieaseu phophoius ieabsoiption). Almost always ovei Su yo
Example: ?&3? >'_ ;$L :+! C ';; $6?,- 5'</,/ ,%5,#6 #-&.'-"
?"#,-#'-'6?"-$&A&/.) NC uue to malignancy. Can PTB like peptiue cause
hypeiCa. Yes (so if you measuie PTB it will be noimal). Squamous cell of the lung,
ienal auenocacinoma, oi mets to bone (bieaking bone uown), saicoiusis (leauing to
hypeicalcemia), multiple myeloma (leauing to hypeicalcemia) all will have L0W
PTB. So, what is the ez'est way to ueteimine hypeiCa in a pt. PTB level
(if its high, its piimaiy hypeipaiathyioiuism; if its low, its all the causes - ie
malignancy).
(GDZQ(X WX(QG
></?&43 ["4A-$.,
P0RPLE stiiae, obesity, thin extiemities
NCC = pt on long teim steioiu theiapy (ie pts with ienal tiansplants, pt on
immunosuppiessant, Lupus)
If this is excluueu, neeu to think of S souices: pituitaiy Cushings, auienal Cushings,
ectopic Cushings. Which of the thiee will have the highest ACTB levels. Ectopic
(small cell caicinoma). Which woulu have the lowest ACTB levels. Auienal. Why.
Bc its making coitisol, which woulu suppiess the ACTB. Pit Cushings is usually a b9
tumoi making ACTB.
Theie aie 2 goou scieening tests foi Cushings (when you have excluueu the fact
that they aie not on steioius). The scieening tests aie: 24 hi uiine test foi fiee
coitisol. This is looking foi coitisol in the uiine, not attacheu to any piotein (so it's
fiee). It must mean that you have a lot of excess of it to have that much of it in youi
uiine. This is the BEST scieening test foi Cushings. This test uistinguishes Cushing's
synuiome fiom Cushingoiu obesity.
Example: see obese pt with Cushing's symptoms anu you think they have Cushings;
howevei, get a 24 hi uiine coitisol test anu it's noimal. If it's incieaseu, they tiuly
have Cushings - in othei woius, they have 99% sens anu specificity.
They will ask about A,%.,6? /<##-,//&$4 6,/6 (low vs high uose). What is
uexamethasone. It's a coitisol analog. If you give uexamethasone to a noimal
peison, it will suppiess ACTB. If you suppiess ACTB, the coitisol levels with be low,
inuicating the coitisol levels aie suppiessible. So, what happens when you give a
L0W uose of uexamethasone in a pt with Cushings - will you suppiess theii coitisol.
No. So, you see a lack of suppiession. Theiefoie pt has cushing's. Bowevei the L0W
uose just tells you pt has Cushings, not what kinu they have, so it just a scieening test
(if you uiu a 24 hi coitisol uiine level, it woulu be positive). Remembei that theie
aie two enuociine uz's that you CAN suppiess - PIT0ITARY Cushings anu
piolactinoma. So, if you give high uose of uexamethasone, you aie able to suppiess
the ACTB ielease by the pituitaiy anu coitisol goes uown. It will not be suppiesseu
in auienal anu ectopic Cushings (small cell).
|Reau last sentence if you get a long questionj
Example: foi one of these, they will uesciibe Cushings, anu ask about uexmeth
suppiession - fiist thing to uo is look at high uose suppiession - if its suppiesseu, its
automatically pituitaiy cushings (not a haiu question!)
So, why uo the pts look like this. Pt has hypeicoitisolism, which is gluconeogenic.
So, neeu substiates foi gluconeogenesis - main substiate is aa fiom muscles. Wheie
aie the muscles locateu. Aims anu legs - so pt will get a bieak uown of muscle in the
extiemities, which is why they have thin aims anu thin legs. Then will get alanine
tiansaminateu anu get pyiuvate. So, will always have thin aims anu extiemities. Bc
it is gluconeogenic, what will the glucose be. Bigh. What uoes that uo to insulin
ielease. Incieases it. What uoes insulin uo to fat. Incieases fat stoiage. What pait of
the bouy have the most auipose. Face anu tiunk. So, you aie getting an inciease in
ueposition of Tu in the face anu tiunk anu back. So, the thin extiemities is uue to
bieaking uown muscle foi aa's in gluconeogenesis. The moon facies, buffalo hump
anu tiuncal obesity is uue to inciease in insulin anu fat ueposition. The stietch
maiks aie uue to obesity, anu they aie puiple bc coitisol uecieases collagen
synthesis. Will get stiuctuially weakei collagen. Its like puipuia within the stietch
maik (like senile puipuia). Bieak uown the vessels bc inciease in coitisol.
Example: +-$<//,'<8/ /&34 - sign of tetany; this pt has BTN, hypeinatiemia,
hypokalemia, anu metabolic alkalosis - ux. Piimaiy aluosteionism. (have tetany bc
alkalosis - neg chaiges on albumin aie incieaseu, anu ioninzeu Ca level uecieases).
Aka Conn's synuiome
(A-,4'; B,A<;;' 6<.$-/
B> &4 'A<;6/ C #?,$5?-$.$5"6$.' Hb9, BTN) (so, auult, BTN, tumoi in auienal
meuulla = pheo); have unstable BTN - anxiety, sweat a lot; get a 24 hi uiine test foi
vNA anu metenephiine (these aie metabolic enupiouucts of NE an Epi (so, anxious,
sweating, BTN). Aie theie assoc with pheochiomocytoma. Yes - NEN IIa anu NEN
IIb, neuiofibiomatosis (ie pt with neuiofibiomatosis with BTN - what test you get.
vNA anu metanephiine 24 hi uiine, bc high assoc with pheo).
NC in kius = neuioblastoma (NALIuNANT)
Both of these aie fiom ienal meuulla, both aie neuial ciest oiigin, both piouuce
BTN. Pheo = auults ; neuio - kius
O'6,-?$</, T-&A,-&5?/,4 ["4A-$.,
N. menigitiuis
Example:: 12 yo, giam "-" uiploccocus, high fevei, nuchal iigiuity, spinal tap founu
neutiophils anu giam "-", kiu then 'ciasheu' - staiteu to get petechial lesions all ovei
the bouy, hypovolemic shock, uieu, on autopsy both auienal glanus aie hemoiihageu
- Bx. Wateihouse Fieiuiickson
B>> .,4&43&6&/ =-$. 1 .$46? 6$ 1l "-/ $= '3, C Q .,4&43&6&A&/) It is the 0NLY
meningitis with petechial lesions (anu they always mention this).

So, if they give meningitis anu petechia, know is N meningitis. If they aie
hypovolemic, they hemoiihageu theii auienals anu went into hypvolemic shock,
also, they have no coitisol oi mineialocoiticoius.
>'</, $= ?"#$5$-6&/$;&/. 6?'6 &/ 5?-$4&5 C (AA&/$48/ A]
NCC Auuisons = autoimmune uestiuction of the glanu (useu to be TB uue to
autoimmune uestiuction). The entiie auienal coitex is uestioyeu, theiefoie the
mineialocoiticoius anu glucocoiticoius aie low. So, theie is low coitisol with BIuB
ACTB. What uoes that uo to melanocytes. Incieases them, leauing to
hypigmentation in the mouth anu elsewheie. Theie is N0 aluosteione. Theie aie 2
pumps (NaK pump anu piotonK pump). Aie you gonna lose Na. Yes - which will
leau to hyponatiemia anu BYPERkalemia (peakeu T waves). Will you be able to get
iiu of the piotons in the uiine. No - theiefoie will have metabolic aciuosis. So, you
have hyponatiemia, hypeikalemia, metabolic aciuosis, hypeipigmentation.
Example: ambiguous genetalia - what is fiist step in management. C'some analysis
- have to finu out what the genetic sex is. It's XX. So, pt has ambiguous genetalia,
female, phenotypically cannot tell, /$ &68/ =,.';, #/,<A$?,-.'#?-$6&A, \ (play
ouus) - auienogenital synuiome uue to 71 ?"A-$%";'/, A,=)
17 hyuioxylase is iesponsible foi 17 ketosteiious (incluue BBEA, anuiosteneuione,
anu aie weak anuiogens). Anuiosteneuione can be conveiteu into testosteione anu
testosteione into uihyuiotestosteione.
17 hyuioxycoiticoius aie 11 ueoxycoitisol anu coitisol
[$_ &= "$< ?'J, '4 &45-,'/, &4 1h ?"A-$%"5$-6&5$&A/_ 6?&/ &/ '4 &45-,'/, &4 11
A,$%"5$-6&/$; '4A 5$-6&/$;
@= "$< ?'J, '4 &45-,'/, &4 1h P,6$/6,-$&A/_ H1h_ S[I &68/ '4 &45-,'/, &4 G!Z(
'4A '4A-$/6,4,A&$4,)
O?,4 "$< ?'J, '4 ,4]"., A,=_ 6?&43/ #-$% 6$ 6?, E;$5P &45-,'/, '4A 6?&43/
A&/6'; 6$ 6?, E;$5P A,5-,'/,
O&6? 71 ?"A-$%";'/, A,=_ ueciease mineialcoiticoius anu glucocoitiocoius anu
inciease anuiogens, leau to ambiguous genetalia (excess anuiogens), lose salt, high
ACTB, theiefoie hypeipigmenteu
O&6? 11 ?"A-$%";'/, A,= - uecieaseu coitisol, uecieaseu aluost, but incieaseu 11
ueoxycoiticosteione (weak mineialcoiicoiu), incieaseu 17 hyuioxy's anu 17 ketos -
lil giil will have ambiguous genitalia, lil boy will have piecocious pubeity (excess
anuiogens), BTN
1h ?"A-$%";'/, A,= - no anuiogens, incieaseu in mineialocoiticoius (BTN), so if
it's a lil boy he won't have test anu will look like a female bc no uevelopment (no
exteinal genitalia bc no 17 keto's, test, oi uihyuiotest). In a lil giil - she will be
unueiuevopeu.
@/;,6 5,;; 6<.$-/
0nly 2 to know: Insulinomas anu ZE synuiome
ZE: making too much gastiin, leaus to peptic ulceis
Insulinoma: is pt injecting oi uo they ieally have insulinoma.
When you bieak pioinsulin uown into insulin, you ielease C peptiue, so foi eveiy
insulin molecule that is ieleaseu, theie is C peptiue that is ieleaseu with it. So, if you
inject human insulin into youiself, anu piouuce a low glucose level anu C peptiue will
be S0PPRESSEB.
If you have a islet cell tumoi, glucose will be low, insulin will be high anu C peptiue
will be INCREASEB.
Example: pts that have access to insulin get this (Bis, nuises, phaimacists)
Auuio File SS: Enuociinology S - Nusculoskeletal 1
G&'E,6,/ B,;;&6</
+"#, 1
Absolute insulin ueficiency
Antibouies against islet cells
BKA
BLA ielationship
Insulin useu (always)
+"#, 7
Family histoiy of uiabetes
0besity
Amyloiu in islet cells
Bypeiosmolai non-ketotic coma
Insulin useu when eventually pt get iesistant to SF0
PATB0uENESIS: 2 mechanisms:
1) 2/.$6&5 G'.'3,
Tissue has to have aluose ieuuctase: only 2 have them:
i) Lens, glucose! soibitol, osmotic ieactive, absoibs watei into the lens
Retinal vessels in lens get weak, then uestioyeu uue to micioabsesses anu can
iuptuie anu leau to blinuness.
ii) Scwann Cells: NCC cause of peiipheial neuiopathy is Biabetes: NECB: osmotic
uamage
2) Q$4^,4]".'6&5 W;"5$/";'6&$4
Renueis the BN peimeable to pioteins: Byaline aiteiioloscloiosis, uiabetic
nephiophathy
BbA1c: long teim contiol of BN.
Sliue: Retina in a uiabetic-micioaneuiysms (ieu uots)
Sliue: Retina in a uiabetic-neovasculaiization
Example: Su yi olu, bluiiy vision; gets a piesciiption fiom a optometiist, new
glasses, one month latei, bluiiy vision again. uets new piesci, one mth latei, bluiiy
vision again. Bx: Biabetes.
ulucose is being conveiteu to soibitol-watei is going in anu changing the iefiactive
inuex. Classic question. BAvE to get a FASTINu BL00B uL0C0SE.
Lab: Fasting glucose >126 mgul on two sepaiate occasions.
Example: Beh Sc link: The FBS level has been uecieaseu fiom 14u mgul to 126 mg
ul. Is this incieasing the specificity oi the sensitivity of the test.
A: BIuB Sensitivity. By biinging it lowei ie closei to the noimal iange, you aie going
to be able to pick up moie people with uiabetes. When it was 14u, it was high sp: to
eliminate false positives. So it was unequivocally a uiabetic if it was > 14u.
ulucose toleiance test, uon't woiiy about it.
W,/6'6&$4'; G&'E,6,/
Bef: Woman who uiu not have uiabetes, but aftei becoming piegnant uevelops
uiabetes.
Risk factois foi baby:
RBS, piematuie ueliveiy
Women with uB, aie at a highei iisk foi ueveloping uiabetes latei on.
Amyloiu in Beta islets: Type 2
Antibouies against islets; inflammation: Type1
(Coxackie viius implicateu)
BLA coiielation: !X( GD9 '4A GDKC+"#, 1i piopensity foi ueveloping Type 1, if
ceitain enviionmental factoi comes in such as infection: Coxsackie, mumps, EBv
BLAB27: Ankylosing Sponuylitis
Env factois:
Chlamyueal Infection
0lceiative Colitis,
Shigellosis
Psoiiasis
CHAPTER 14: Musculoskeletal System
B</5<;$/P,;,6'; ["/6,.
Neeu to iuentify ciystals in synovial fluiu
W$<6
:/,<A$3$<6
Rhomboiu ciystals in synovial fluiu==pseuuogout
But Pseuuogout coulu also have neeule-shapeu ciystals (like those of mono-souium
uiate in uout) which makes BB uifficult. So you use a special filtei to make the whole
sliue ieu anu then the ciystals aie maue to look yellow oi blue.
When the coloi of the ciystals is yellow when the plane of filtei is paiallel to the
analyzei= Q,3'6&J,;" E&-,=-&43,46 CW2M+
East west uiiection: coloi is blue anu paiallel to analyzei=:$/&6&J,;" E&-,=-&43,46
C :[ZMG2W2M+ (calcium pyiophosphate)
(-6?-&6&/
2/6,$'-6?-&6&/
Piogiessive weaiing uown of aiticulai caitilage
Sometimes leaus to ieaction to injuiy: SP0R foimationat the maigin of the joint=
Bebeiuen's noue: osteophyte in the joint
Note the enlaigement of the BIP (Bebeiuens noues) anu PIP joints (Bouchaius
noues), enlaigements iepiesent osteophytes.
D?,<.'6$&A (-6?-&6&/
Inflammatoiy joint uz; enlaigeu NCP joints
Rh factoi sets up the inflammation: IgN Ab against Igu. Igu is in synovial fluiu. IgN-
Igu foim complexes, activate the complement system, uamage the joint, synovial
fluiu gets inflameu, staits giowing anu giowing, staits giowing ovei the aiticulai
caitilage= PANN0S; hypeiplastic synovial fluiu. (uiffeient fiom Tophus)
}oints can get fixeu, anu ankyloseu anu cannot move.
Bon't get fixing of the joint in 0A.
If iheumatoius uon't keep moving theii joints, anu if it is not contiolleu using anti-
inflammatoiy uiugs then eventually they cannot move it at all.
Sliue: Rheumatoiu nouules. Can be seen in Rheumatic fevei as well.
Example: oluei pt having tiouble eating anu swallowing ciackeis, feels like theie is
sanu in my eye all the time. 0n examination: eyes anu mouth aie uiy. Bx. [u$3-'48/
["4A-$.,) Pt with RA anu auto-immune uestiuction of laciimal glanus, salivaiy
glanus. Keiatoconjunctivitis sicca
Rheumatoiu nouules in lung + pneumoconiosis==Caplan Synuiome
Tieatment of RA= Nethotiexate
Example: Pt with RA, uevelops a maciocytic anemia with hypeisegmenteu
neutiophils, neuio exam is noimal, inteistitial fibiosis in lung. What is the uiug.
Nethotiexate
W$<6 C #$A'3-'
Big toe, usually fiist one to be involveu; usually at night.
Nonosouium uiate ciystals aie piecipitateu anu taken up by the neutiophils that
phagocytose it anu ielease chemicalsinflammatoiy ieaction.
Bon't uefine uout baseu on 0iic aciu level. Elevateu uiic aciu uoes not necessaiily
leau to gout. About 2S% of people might have elevateu uiic aciu.
Bx: BAS to be by piesence of uiic aciu ciystals in the joint.
Tieatment: Inuomethacin to contiol inflammation.
Cause: ovei piouuction (Rx=allopuiinol: blocks Xanthine oxiuase) oi unuei
excietion of uiic aciu (>9u% of cases) Rx=uiicosuiic uiugs like piobeneciu anu
Sulfinpyiazone
>?-$4&5 W$<6 C 6$#?</0 ueposition of monosouium uiate in soft tissuemalleolus
veiy uisabling as it eioues the joint.
Rx= allopuiinol
Sliue: Tophus that was polaiizeu showing NS0 ciystals
Sliue: X-iay of uigit showing eiosion by tophus
W,4,6&5/ $= W$<60
Nultifactoiial inheiitance
Av0IB ieu meats (full of puiines)
Av0IB Alcohol. Nechanism:
Netabolic aciuosis: uiic aciu has to compete with othei acius foi excietion in
pioximal tubule. Alcohol incieases all the lactic aciu, anu beta hyuioxyl butyiic acius.
So all these acius compete anu win against uiic aciu, anu get excieteu. 0iic aciu keeps
waiting anu waiting; anu builus up anu causes gout.
(4P";$/&43 /#$4A";&6&/ H([I
BLAB27 association
Sliue: Note anteiioi flexion which often iesults in iestiictive lung uisease. Buncheu
ovei, iestiicts movement of chest cavity, bloou gas abnoimalities,
2u yi olu, moining when he woke up, suuuen pain in sacio-lumbai iegion.
Inflammatoiy ieaction seen on X-iay, as the uay piogiesses pain uecieases.
Eventually, the inflammation spieaus to the veitebial column, anu it
fuses=="Bamboo spine"
Also uevelop: 0veitis, Aoititis, iiiuocyclitis, bluiiy vision, eventually go blinu.
Example: uenetic uz wheie uegeneiative aithiitis in veit col, on autopsy, black
caitilage; uiine on exposuie to aii tuins black. (;P$#6$4<-&'
Aut iec, homogentisic aciu oxiuase enzyme uef
Sliue: 2u yi olu, uysuiia, incieaseu fieq, uiinalysis= leucocyte esteiase positive,
steiile pyuiia--sexually active, hau non-specific uiethiitis, conjunctivitis, was tieateu.
It was Chlamyuia tiachomatis conjunctivitis, but one week latei, got steiile
conjunctivitis anu tenuonitis in Achilles tenuon.
So patient with non-infectious conjunctivitis, pieviously hau Chlamyuia tiachomatis
infection anu then uevelopeu conjunctivitis anu aithiitis (BLA B27 positive):
D,&6,-|/ /"4A-$.,
(4$6?,- Z4J 6-&33,- &4 !X(V7h #$/&6&J, #60 0lceiative Colitis
[,#6&5 '-6?-&6&/ A<, 6$ A&//,.&4'6,A 3$4$5$55,.&'
Note the hot knee anu the pustule on the wiist, on aspiiating: giam negative
uiplococci
STB= Sexually Tiansmitteu Bisease
S=Synovitis=joints
T= Tenosynovitis= joints in hanus anu feet
B= Beimatitis=pustules
NCC of septic aithiitis in 0S= uonoiihoea
Foi it to become uisseminateu, neeu to be ueficient in the final pathway of
Complement system: >N^>a (some say C6-C9)
Sliue: Note the Ixoues tick (vectoi of Boiielia buiguoifeii anu Babesia micioti), note
the eiythematous iash in the bottom scieen - the tick bite is in the centei of the iash
anu the iash extenus out in concentiic ciicles fiom that point, the iash is calleu
,-"6?,.' 5?-$4&5<. .&3-'4/ (pebble thiown in watei) Pathognomonic of X".,|/
A&/,'/,
Eaily foim Rx: tetiacycline
>?-$4&5 X".,8/ G&/,'/,0 Apait fiom uisabling joint uisease: myocaiuitis plus
bilateial Bell's palsy: CN vII involveu + pt will have Babesiosis
Iuiopathic: is usually 0nilateial Bell's Palsy= Beipes Simplex
Above Pt uevelops Bemolytic anemia, what uiu he see in his peiipheial bloou
smeai. Babesia micioti (iing foim similai to Plasmouium falcipaium)
D,.,.E,-0 6?, @%$A,/ 6&5P ?'/ 6?, -,/,-J$&- =$- V$--,;&' E<-3A$-=,-& HL?&6,
6'&;,A A,,- 6?'6 ?'/ V'E,/&' .&5-$6&I (QG V'E,/&' .&5-$6& intia-eiythiocytic
paiasite
Rx: Ceftiiaxone
V$4, G&/$-A,-/
2/6,$3,4,/&/ &.#,-=,56'
Sliue: Kiu with an eyeball, blue scleia: AB uisoiuei with uefect in synthesis of type I
collagen, note the blue scleia- loss of collagen in scleia allows bluish coloi of
choioiual vessels to shine thiough: 2/6,$3,4,/&/ &.#,-=,56' (N0T foieign bouy!)
"biittle bone uisease" cant bieak bone uown
Question: what's the uefect. Befective synthesis of type 1 collagen
Question: what's the mechanism of uevelopment of blue scleia.
Collagen in scleia, type 1 is uefective, so it is so thin, so you can see the unueilying
choioiual veins that gives the blue coloi.
2/6,$#,6-$/&/ C c.'-E;, E$4, A&/,'/,d
Befect in too much bone: uefect in osteoclasts
2/6,$#$-$/&/
Sliue: Becieaseu wiuth of intei veitebial caitilage. Note the collapse of the veitebia
uue to loss of bone mass: patients lose moie bone than is ieplaceu
Sliue: Bowagei's Bump
Nech: Postmenopausal osteopoiosis is uue to the loss of the inhibitoiy effect of
estiogen on the ielease of inteileukin 1 fiom osteoblasts; not enough estiogen to
stop the activity of Inteileukin-1 (osteoclast activating factoi) fiom bieaking youi
bone uown.
0steopoiosis: 0veiall ieuuction in bone mass. Both mineial ANB oiganic
component. WB0LE mass of bone is ieuuceu.
0steomalacia: Becieaseu mineialization of bone: oiganic pait of bone is noimal.
Caitilage is ok, osteoiu is ok; its not getting mineializeu
Bx of osteopoiosis: Bual beam Absoiptiometiy: uensity of the bone in whole bouy
is measuieu. Non invasive, veiy easy.
B> =-'56<-,0 5$.#-,//&$4 =-'56<-,: lose statuie,
7
4A
B> =-'56<-,: Colle's fiactuie of uistal iauius.
Question: Is swimming a goou exeicise foi pieventing osteopoiosis: N0. Because no
stiess on bones. It is gieat exeicise foi aeiobics. But it uoes not pievent osteopoiosis.
Walking is goou. Weight beaiing is even bettei than walking! Walk with Bumbells!
uet aeiobics anu inc in bone mass!
BAvE to stiess bone to builu it up.
Example: In space, lack of giavity anu astionauts aie given bisphosphonates, vit B
anu calcium to get bone uensity back: because seiious piob of osteopoiosis in space.
Tip: iepiouuctive women neeu to:
1) Exeicise
2) 1Suu mg of Ca eveiyuay
S) 4uu-8uu units of vit B
4) vit pill that contains Iion
V$4, +<.$-/
Z%$/6$/&/ H$/6,$5?$4A-$.'I
Note the caitilaginous cap on the suiface of the bone. This causes a piotubeiance of
the bone. This is the most common benign bone tumoi.
>?$4A-$/'-5$.' $= 6?, ?&#
B> .';&34'46 $4,
2/6,$3,4&5 /'-5$.'
Sliue: Note metaphyseal oiigin of the cancei anu extension into the muscle, note the
splintei of peiiosteum that is elevateu which woulu coiiesponu to Coumans tiiangle
Sliue: X-iay of pioximal humeius showing the sunbuist appeaiance of osteogenic
saicoma that is extenuing into the muscle, osteogenic implies that the cancei is
making bone
Auolescent, sun buist app, coumans tiiangle, knee aiea==0steogenic Saicome
[<##-,//$- W,4, -,;'6&$4/?&#0 Rb suppiessoi Chiomosome 1S
B</5<;'- G&/$-A,-/
G<5?,44,8/ B</5<;'- G"/6-$#?"
uowei's maneuvei
Elevateu Seium CK, Absence of uystiophin piotein
Sex linkeu iecessive, missing Bystiophin gene
vaiiant: Beckei's uystiophy: make uystiophin but it is uefective
Analogy: alfa 1 antitiypsin uef: NCC of BCC in chiluien
Auults get panacinai emphysema: many uiff sub types of alfa 1 anti-tiypsin:
1) Absent alfa 1 anti-tiypsin: get pan acinai emphysema.
2) Alfa 1 anti-tiypsin is piesent but it cannot get 00T of the hepatocytes: so get BCC
Auuio File S6: Nusculoskeletal 2 - Beimatology - CNS 1
B"$6$4&5 A"/6-$#?" ^ B> 'A<;6 A"/6-$#?"_ (G
Tiiplet iepeat uz - iepetition of tii-nt's (theie aie 4 uz's with this abnoimality - BB,
Fiagile X - have macioichiuism (big testes in auolescents), Fiieuiich's ataxia,
Nyotonic uystiophy).
In futuie geneiations, uz gets woise - anticipation. Theiefoie, can anticipate that in
futuie uz's it will get woise. Foi each geneiation, theie aie moie tiiplet iepeats
auueu on, leauing to a moie uefective piotein anu the uz gets woise anu woise.

Example: genetic counseloi telling couple that they have a uz, wheie if aie to have
chiluien, the uz will be fatal in theii chiluien. The couple uiun't listen to theii
counselei, hau a chilu anu the chilu uieu only aftei 1 month. What was it anu what is
this: an ie tiiplet iepeat uisoiuei (anticipation) Nuscle weakness in face (so mouth is
uioopeu open).

Example: pt with failuie to ielease giip on golf stick (oi when shaking hanu) - they
cannot ielax theii muscle giip, uiabetes, caiuiac abnoimality
B"'/6?,4&' W-'J&/
AutoAb against Ach ieceptoi - it's an Igu Ab, theiefoie is an Example: of type II
BPY, like uiave's, which is an Igu Ab against the ieceptoi (by uefinition, this makes it
type II). Whethei you uestioy the ieceptoi oi just block it is iiielevant. Ach cannot
hook into it anu theiefoie theie is muscle weekness. The fiist muscles aie the lius,
which leaus to liu lag. They also get uouble vision bc muscles of the eye aie messeu
up, leauing to uiplopia. Eventually, they get uysphagia foi solius anu liquius (gets
stuck in uppei esophagus, bc this is wheie theie is STRIATEB muscle). Eventually
muscle uz pievails thioughout.
Feel eneigizeu in the moining anu feel tiieu at night. Tensilon test positive. Can uie.
Rx is acetylcholinestiase inhibitois. By giving an inhibitoi, block the bieakuown of
Ach anu builu up Ach. With few ieceptois you have in theie, theie is a laigei chance
of hooking up to the ieceptois anu pt uoes well. Bowevei, eventually, no ieceptois
theie anu it uoesn't mattei how much Ach is theie, so pt is scieweu. Then, hei only
option is a thymectomy.
The thymus is in the anteiioi meuiastimun. Tiick question: they can ask, what is
the pathology. They can uesciibe Nu anu ask, what uo you expect to see in the
meuiastinum. Bo N0T put thymoma. This is a malignancy of the thymus anu uoes
occui in 1S-2u% of cases, but isn't the NC pathology seen in the thymus in a pt with
Nu. See geiminal follicles in the thymus (iemembei, this T cell countiy, not B cell
countiy, so its abnoimal to have geiminal follicles heie) - they aie the ones making
the Ab causing the Nu. So, by uoing a thymectomy foi Rx, you aie iemoving the Ab
piouucing tissue. 1S pts get a complete cuie. 1S get a paitial cuie, anu 1S uie bc
they waiteu too long foi thymectomy anu Rx anu uiun't have ieceptois, anyway. So,
B cell hypeiplasia is the NC thing you see, not thymoma. This wheie the Ab is being
maue.
X<#</
Butteifly uistiibution on the face (malai iash)
0f all the autoimmune uz's this one is the most likely one to have a "+" ANA (99%
sensitivity). The Ab's you want to oiuei to piove that its lupus aie anti-Smith Ab
(which has a 1uu% spec, theiefoie no false pos - theiefoie 1uu% PPv) foi lupus,
meaning that if you test "+" foi this Ab, you have Lupus. The othei Ab is anti -usBNA
- this not only inuicates that you have lupus, but also that you have KIBNEY uz. That
has a 98% spec, too. So, these aie two goou Ab's to confiim lupus. Noining stiffness
is piesent in lupus (simulates Rh aithiitisphotophobia), iash, peiicaiuitis; LE cell
piep - Anti - BNA Ab's aie phagocytoseu by neutiophils, anu they have alteieu BNA.
Not specific foi lupus (waste of time).
:-$3-,//&J, ["/6,.&5 [5;,-$/&/R>DZ[+
Tight face, telangiectasia, Raynauus, uysphagia (solius anu liquius), uystiophic
calcification, scleiouactly; if kiuneys involveu, it is piogiessive systemic scleiosis,
N0T CREST (uoesn't involveu kiuneys).
G,-.'6$."$/&6&/
Racoon eyes, elevateu seium CK, iash ovei the PIP (goutien' patches), highest assoc
with unueilying cancei.
[u$3-,4/ /"4A-$.,
Assoc with ih aithiitis, autoimmune - Ab's uestioy salivaiy glanus leauing to uiy
mouth, laciimal glanus leauing to uiy eyes.
Example: bx of lowei lip which is a confiimatoiy test - its looking to see if theie is
uestiuction of the minoi salivaiy glanus - see lymphocytes (which is confiimatoiy
ux). Ab's aie anti-SSa (aka anti-Ro) anu anti-SSb (aka anti-La) (SS = Sjogien's
synuiome).
Anti-io can also be in lupus pts, anu can cioss the placenta anu uisiupts the baby's
conuuction system (leaus to complete heait block).
CHAPTER 15: Dermatology
[P&4
V'/'; 5,;; 5'-5&4$.' (uppei lip)
[Y<'.$</ 5,;; 5'-5&4$.' (lowei lip)
:/$-&'/&/ - silveiy lesion that is ieu anu iaiseu. Can involve the hanus, scalp - pts
think they have uanuiuff (aka seboiieic ueimatitis - fiom malasezia fuifuia), but
they ieally have psoiiasis. 0n black peison won't see ieu lesion, will see silvei one.
Rash at piessuie points - esp the elbow.
(6$#&5 A,-.'6&6&/ - chilu with alleigic uiathesis staits uz; have eczema (aka atopic
ueimatitis); type I BPY.
>$46'56 A,-.'6&6&/ - ie to metal (nickel); type Iv BPY
Example: pathophys is equalant to what. "+" PPB, bc both aie type Iv BPY
[,E$--?,&5 G,-.'6&6&/
Bue to *(+(,,#-.( /0"/0" (a fungus)
IC pt (ie AIBs)
This is a pieAIBs lesion
+&4,' 5'#&6&/
Example: pt with balu spot on heau, fluouiesces anu seen with black light blacklight
(0v-A light)
Can cause Tinea capitis H4$L +-&5?$#?"6$4 6$4/<-'4/ &/ B>>I
Bc the fungus involves the innei poition of the shaft, theie aie no fluoiescent
metabolites, anu is O$$A ;&3?6 4,3'6&J,
All the othei supeificial ueimatophyte infections incluuing +&4,' 5$-#$-&/ (iing
woim)
Example: ieu outei euge anu cleai centei, what is fiist step in woikup. Sciape
outsiue anu uo K0B piep, anu see hyphae anu yeast foims. (;; $6?,- /<#,-U&5&';
A,-.'6$#?"6, &4=,56&$4/ H,%5,#6 +&4,' 5'#&6&/I '-, A<, 6$ 6-"5?$#?"6$4 -<E-')
What is the coloi aiounu Tinea capitis. Reu (= iubia) (how to iemembei it).
B$;;</5<. 5$46'3&$/<.
Sanuy like mateiial in ciatei, chiluien, self inoculate
Poxviius makes these (BNA viius)
volcano ciatei look, with sanuy stuff in it
:&6"-&'/&/ D$/,'
Example: iash on butt - non piuiitic iash, N0N INFECTI00S; oblong looking with
ieu on outsiue anu pale in miuule. You think this is T coipoiis, but its oblong (anu
not ciiculai). Bo a K0B piep, finu nothing; then put topical steioius anu uoesn't go
away; S uays latei comes back with iash in the line of langei in Chiistmas tiee like
uistiibution; not an infectious uz, ;&P, ' ?,-';A -'/?i 4$6 ' =<43</
G"/#;'/6&5 Q,J</ /"4A-$.,
Example: piecuisoi lesion foi malignant melanoma; if you have ovei 1uu nevi all
ovei bouy, you have uysplastic nevus synuiome
veiy common
Nust go to ueimatologist once a yeai bc neeu to look at uysplastic nevi.
Coulu be a piecuisoi lesion foi malignant melanoma.
K A&== 6"#,/ $= .';&34'46 .,;'4$.'
What is fiist step in management. Excision
Example: supeificial spieauing malignant melanoma (NC)
Example: on face of oluei pt - Lentigo maligna melanoma; iiiegulai boiuei, coin
coloieu, LEAST likely to met of all malignant melanomas.
Example: black pop'n uo not get malignant melanomas bc the black pigment in the
skin pievents 0v light uamage anu piopensity foi cancei. howevei, theie is one type
of cancei they malignant melanoma they CAN get:
black pt with uyspnea, on xiay finu multiple mets all ovei bouy. Bx is uone anu pt
has malignant melanoma, which pait of the bouy woulu you examine to finu the
piimaiy uz. 0nuei the nails, palms oi sole of the feet - this is Aciolentiginous
malignant melanoma ('acio' means euge oftip of) - this is the N0ST AuuRESSIvE of
all the melanomas. This has nothing to uo with iauiation. Pagets uz looks similai
Example: Nouulai malignant melanoma - also veiy aggiessive.
+?, .$/6 &.#$-6'46 6?&43 '==,56&43 #-$34$/&/ &/ A,#6? $= &4J'/&$4 (key to
piognosis - magic # is .76 mm). If its less than .76, its not gonna met.
+$%&4/
2 poisonous spiueis -
V;'5P L&A$L
Bas a neuiotoxin - causes spasm of the muscles in the uppei thighs anu abuomen
so stiong its almost like tetanus; pain muscle contiactions, esp in the abuomen.
Theie is an antivenom, painful bite
Example: peison went uown into theii cellai, lifteu boxes, felt shaip piick on fingei,
anu uevelopeu contiactuies ovei a peiiou of his - uue to black wiuow bite.
V-$L4 -,5;</, /#&A,- (aka violin spiuei)
Painless bite, has a neciotoxin, leauing to ulcei
So, neuiotoxin foi black wiuow, neciotoxin foi biown ieclous
O?,-, &/ -,5,#6$-/ 6$ '4A-$3,4/e [,E'5,$</ 3;'4A/ (this is why men get moie
zits than woman - testosteione will ielease lipiu iich mateiial which gets into the
haii follicle. Then, if you have piopiionum acnei (anaeiobe) it has lipases that
bieakuown fat fiom the sebaceous glanu anu piouuces FA's that iiiitate the follicle
anu enu up with acne. So, men moie likely to get it bc they have acne
It all occuis in the eiectoi pili muscle of the skin.
So, theie aie anuiogen ieceptois sebaceous glanus anu eiectoi pili muscle.
G-<3 </,A 6$ #-,J,46 ?&-/<6&/.e [#&-$4$;'56$4, (same uiug useu to block
aluosteione); this uiug is goou bc it blocks anuiogen ieceptois anu theiefoie
pievents hiisutism. Can also leau to gynecomastia.
CHAPTER 16: CNS
>Q[
Spinal fluiu - ueiives fiom choioiu plexus in the ventiicles. In the lateial, S
iu
anu 4
th

ventiicles. Its an ultiafiltiate of plasma. What is the uiffeience in seium anu spinal
fluiu. Way moie piotein in spinal fluiu bc it's an ultiafiltiate. Cell. Baiuly any cells
in spinal fluiu (none). ulucose. Lowei in spinal fluiu - about 6u% of what it is in
seium (if the spinal fluiu glucose level weie low, then something is in theie utilizing
it foi eneigy such as bacteiia oi fungus oi cancei cells). Is theie anything N0RE in
spinal fluiu than seium. Chloiiue (way highei in spinal fluiu than seium) - aiounu
12u. These aie imp bc theie aie injuiies to the heau.
Example: baseball that hits the eye in an oibital blowout fiactuie - can potentially
bieak ciibiifoim plate, leauing to uiipping fluiu out, which coulu be snot, seium, oi
spinal fluiu. So, its imp to know uiff's btwn the two.
Example: wackeu in the heau - fluiu out of eai (otoiihea), hemoiihage leaus to
battle sign. This is a fiactuie of the basilai plate anu theie is spinal fluiu theie.
Nost of the fluiu comes out the aqueuuct of sylvius - which is the NCC of
hyuiocephalus in chiluien bc it gets blockeu off until you get a builu up of spinal fluiu
in the S
iu
vent anu lateial vent, which is a naiiow aiea anu leaus to hyuiocephalus.
Then, it comes to the fouith vent anu neeus to get out bc it neeus to get into the
subaiachnoiu space. So, it goes thiough the foiamen of Luschka anu Nagenuie, so
fluiu goes out.
Buia means stiong - it's tightly auheient to the peiiosteum. So, when pt has
epiuuial hematoma (bloou clot betwn bone anu uuia). The only piessuie that can
split the peiiosteum away fiom uuia is aiteiial piessuie. So, 6?&/ &/ 6?, $4, L?,4
6?, .&AA;, .,43&'; '-6,-" -<#6<-,/, anu can be uone with aiteiial piessuie (not
venous).
It gets into the subaiachnoiu space (to piotect us - a cushion against uamage). uet
iiu of spinal fliuu in aiachonoiu gianulation. |A tumoi can aiise fiom the aiachnoiu
gianulations - meningioma.j It goes thiough the aiachnoiu gianulations, (theie aie
N0 LYNPBATICS IN BRAIN) anu the uuial sinuses anu conglomeiate into the jugulai
vein, which is emptieu into the iight siue of the heait.
So, when you uo a valsalva anu the neck veins uistenu, that piessuie tiansmits all
the way back to the uuial sinuses, to the aiachnoiu gianulations thiough the spinal
fluiu , anu iight uown the the neeule in the subaiachnoiu space at L4 anu the
piessuie goes up. This is calleu quakens step maneuvei. It is a gieat test foi when
you aie uoing a spinal tap to see if the entiie subaiachnoiu space is patent. If you
uon't see that manometei go up, theie is something blocking the spinal fluiu moie
pioximally.
Example: when you wt lift, you shoulun't holu youi bieath bc the piessuie aie huge
anu anu leau to a heiniateu uisk.
+,46$-&<. >,-,E,;;&
7u% of biain tumois in auults aie supiatentoiial (involve ceiebial coitex)
7u% of biain tumois in kius aie infiatentoiial (ceiebellai, cystic astiocytoma,
meuulloblastoma)
!"A-$5,#?';</
Communicating vs Noncommunicating
Communication of spinal fluiu in ventiicles with subaichnoiu space.
Q$45$..<4&5'6&43
NC
Something is pieventing spinal fluiu in the ventiicles fiom getting into the
subaiachnoiu space
B>> C /6,4$/,A (Y<,A<56 $= [";J&</
0i something going in the 4
th
vent, epenuymoma in kius will block it off, oi
meningitis in base of biain (TB), leaus to scai tissue bc blocks foiamen of magenuie
anu luschka.
>$..<4&5'6&43
Still communicating, but still a builu up of piessuie. 0ne cause coulu be tumoi of
choioiu plexus (papillaiy looking). So, if you have a tumoi theie, you have a gieatei
ultiafiltiate of plasma anu woulu be making moie plasma. Also, woulu be making
moie spinal fluiu. Theie woulu still be a communication with heie, but the piessuie
woulu builu up bc making moie than you commonly uo.
Noie commonly, what if you have a subaiachnoiu bleeu oi meningitis. Then pt has
scaiieu off aiachnoiu gianulations anu have no way of uiaining it out. So, still have a
communication, but cannot get iiu of it (NC).
(-4$;A >?&'-& B';=$-.'6&$4
Example: pull uown spinal coiu. This woulu biing the meuulla into the ceivical
iegion anu maybe a lil pait of the ceiebellum. Leaus to hyuiocephalus anu platybasia
(flattening of the base of the skull)
G'4A" L';P,- /"4A-$.,
Ceiebellai veimis is not uevelopeu
!,-4&'6&$4
Why woulu we heiniate in the biain. Bc theie is ceiebial euema anu no othei place
to go. The famous ones aie tonsillai heiniation thiough the foiamen magnum. (fiom
the ceiebellum) - ceiebellai heiniation - has been squeezeu into the foiamen
magnum, anu has constiiction. Can cause immeuiate ueath.
0ncal heiniation - meuial poition of the tempoial lobe heiniates thiough the
tentoiium ceiebelli anu piessing against miubiain, leaus to hemoiihage (uuiet's
hemoiihage). Also an oculomotoi neive that is gonna be compiesseu. So, this will
leau to opthalomoplegia (LR6S04, S), so eveiything inneivateu by CN III is paialyzeu.
With oculomotoi neive palsy, it is uown anu out. (uown anu in is CN 4 palsy - if CN 6
is paialyzeu, will look cioss eyeu). Look at pupil.
Example: NRI of oiibit, name muscles
Paiasympathetic constiict the pupil (noimally) , sympathetics uilate (noimally)
So, if you mess up the paiasympathetics, which noimally constiict, it will leau to
myuiiasis.
The fiist sign of uncal heiniation is myuiiasis of pupil on siue of heiniation (so it
uilates on that siue). Also, posteiioi ceiebial aiteiy can get blockeu with uncal
heiniation, leauing to post lobe infaiction.
S4$L E-'&4/6,. '4A >Q8/ '4A ?$L &6 -,;'6,A 6$ ?,-4&'6&$4
:'#&;;,A,.'
Any cause of incieaseu incianial piessuie
vit A tox
Leau poisoning - uelta-aminolevulinic aciu - leaus to incieaseu peimeability
Auuio File S7: CNS 2
!"A-$5,#?';</
NCC = stenosis of the aqueuuct of sylvius
Noncommunicating.
uet hyuiocephalus bc the sutuies have not fuseu
if you miss hyuiocephalus in auult anu sutuies have fuseu, will leau to uilatation of
the ventiicles anu eventually ovei yeais, the piessuie will tuin back to noimal bc the
incieaseu piessuies keep the choioiu plexus fiom making so much
Bementia, ataxia, uiinaiy incontinence.
Aka noimal piessuie hyuiocephalus (bc piessuies noimalize)
+<E,-$</ [5;,-$/&/
(G
Bamaitomas (noneoplastic piolifeiation of things)
ventiicles have bumps calleu tubeicles - which aie hamaitomas which have
piolifeiation of astiocytes. They piouuce hamaitomas that bulge into the ventiicle,
calleu canule stick uiipping. Bemaitomas of the kiuney calleu angiomyolipomas, NR,
caiuiac tumois (ihabuomyomas), shagieen patches, aieas of hypopigmentation,
woous light shine out
(4,45,#?';"
Woist of neuial tube uefects
Absent biain
F,-6,E-'; '-5? A,=,56/
[#&4' E&U&A' $55<;6' - tufts of haii come out, veit aiches uo not touch, no meninges
come
B,4&43$5,$;, - meninges come out
B,4&43$.";$5,;, - both meninges anu spinal coiu come out
Bigh alpha feto piotein levels in bloou of mothei; uecieaseu in uowns synuiome
Bave to be on folate to pievent neuial tube uefects (neuial tube finisheu foiming by
Su uays, so make suie she is on folate if she is tiying to get piegnant).
Q,<-$U&E-$.'6$/&/
Albiight synuiome (piecocious pubeity, caf au lait, bone zits)
Stuige webei
Caf au lait (coffee coloieu non iaiseu lesions) spot, plexifoim neuiofibiomas,
hypeipigmentation in the axilla (axillaiy fieckling), neuiofibiomas
AB , theiefoie late manifestations (esp foi neuiofibiomatosis), penetiance, vaiiable
expiessivity (you aie expiessing the uz, but uiff levels of how seveie the uz is)
Example: pt with !+Q anu pic, what test woulu you get. Relationship of
neuiofibioma with pheochiomocytoma, theiefoie get a 24 hi uiine foi vNA anu
metanephiine.
(5$</6&5 /5?L'44$.'
Example: pt with sensoiineiual heaiining loss - b9 tumoi of Schwann cells aiounu
CN 8
B,4&43&$.'/
0ptic neive gliomas
["-&43$.",;&'
Example: pt that woiks in factoiy anu one of woikeis says you aie buining youi
hanu anu pt uiun't notice this, on exam loss of musculatuie (loss of LNN) in intiinsic
muscles of the hanu, loss of pain anu temp in cape like uistiibution acioss back.
Can't feel pain (not ALS - in ALS, fiist place of uevelopment of loss of muscles is
heie, so uon't confuse; but ALS is 0NN anu LNN loss, P0RE N0T0R , so if pt has pain,
ie, this is sensoiy anu not ALS)
Big cystic cavity knocking off spinothalamic knocking off pain anu temp. can knock
off the coiticospinal tiact anu anteiioi hoin cells, so it will be a C0NB0 of sensoiy
ANB motoi loss foi syiingiomyelia.
@4=,56&$4/
B,4&43&6&/ J/ ,45,#?';&6&/
Neningitis - inflammation of meninges anu nuchal iigiuity; if you move youi heau
oi extenu youi knee, you will stietch the meniges, leauing to pain (stietching
inflameu meninges).
Encephalitis - sleeping sickness - they aie always sleeping anu uiowsy; they have
mental status abnoimalities (not nuchal iigiuity)
Pus at the base of the biain - can possibly block lushka anu majenuie, leauing to
obstiuctive hyuiocephaly anu noncommunicating
When you Rx meningitis, use steioius anu Abs. why. Steioius pievent scai tissue
foimation anu complications that aiise with it (ie hyuiocephalus).
This is stanuaiu TB meningitis Rx (TB in biain causes vasculitis anu scaiiing)
Beafness is a complication of meningitis.
D'E&,/
Example:: meningitis, ceiebial abcess, Rabies (NCC in States = skunks, uogs in S
iu

woilu)
Negii bouies (peikinje cell inclusion)
>BF
Peiiventiiculai calicifications
Example: section of kiu (biain) - see white stuff going aiounu ventiicles
NC congental infection = CNv
What bouy fluiu is best to cultuie fiom. 0iine
B,4&43&6&/
What is NC meningitissepis in fiist month of life. uioup B stiep - stiep agalactae -
bc many women have this oiganism in theii vagina, so they aie caiiieis. Piematuie
iuptuieu membianes lets the oiganism get up, get an choiioamnionitis anu into the
blooustieam.
2
nu
NCC is E coli
S
iu
NCC is listeiia monocytogenes (giam + iou with tumbling motility - as uoes
Tiichomonas vaginalis)
What foou shoulu piegnant women avoiu. Soft cheeses (ie feta cheese, but listeiia
is piesent).
NC in 1 month - 18 yo = N meningitiues
(not B influenza bc vaccination)
NC in 18+ = Stiep pn
Example: S2 yo man, nuchal iigiuity, tap shows incieaseu piotein, incieaseu
neutiophils anu uecieaseu glucose - ux. Stiep pn. what is the giam stain. uiam +
uiploccus
>-"#6$5$55</
Inuia ink - see naiiow baseu buu foi Ciyptococcus
Who uo you think this is in. IC'u pts
What is NC immunouef in 0SA. AIBs
NCC meningitis in AIBs pts. Ciyptococcus
B<5$-."5$/&/
In fiontal lobe, theiefoie fiom a uiabetic in ketoaciuosis
Example: special stain on AIBs pt with CB 4 ct of Su, CT showeu space occupying
lesion
Bx. +$%$#;'/.$/&/
Example: pig heiuei, anu long time pioblem with focal epileptic seizuies (uilating
theiapy) - multiple calcifieu anu cystic lesions in biain - ux. >"/6&5,-5$/&/
Example: }acob Ciuetzfeltus fiom piions (mau cow) - who is most likely to get.
Neuiopathologists, neuiosuigeons, beef, lettuce fiom Aiizona (cow manuie on it)
+-'<.'6&5 ;,/&$4/
Z#&A<-'; ?,.'6$.' (above uuia) - hit in heau miuule meningeal - have to
fiactuie bone (unuei aiteiial piessuies, can sepaiate uuia fiom peiiosteum). When
you get Su mls of bloou, you get uncal heiniation anu uie. Ie get him, say they aie ok,
6 his latei epiuuial hematoma anu ueath
[<EA<-'; ?,.'6$.' - iuptuie of biiuging veins betwn uuia anu aiachonoiu
membiane. If you have ceiebial atiophy, then the space bwtn the uuia anu
aiachnoiu membianes is biggei. Biiuging veins uangling, bieak anu get a hematoma.
Fluctuating levels of consciousness. Left untieateu leau to uementia. Bo CT to io
epi anu subuuial hematoma (also foi stiokes - if its a hemoiihagic stioke)
[6-$P,/
Sliue: Biain: one siue is biggei. Atheioscleiotic stioke; pale infaict of biain. At
bifuication, theie is an atheioscleiotic plaque anu thiombus. No bloou flow to biain
anu it infiacteu, staits bieaking uown, no iepeifusion, so it iemains a pale infaict. If
the thiombus uiu bieak apait, anu iepeifusse the biain, the bloou in the goes into the
aiea of infaiction anu is calleu a hemoiihagic infaict. Bowevei, this usually uoesn't
occui anu pale infaicts moie common. If no bloou, anu theie is infaiction, pt is a
canuiuate foi hepaiin theiapy. 0vei time, if pt suivives, enus up with cystic space
wheie theie was infaiction anu this is calleu liquefactive neciosis--pale infaict,
liquefactive neciosis.
Sliue: hemoiihagic infaict - bloou is to euge of biain - this is an embolic infaict,
usually fiom left siue of the heait. The vessel it always goes to is miuule ceiebial
aiteiy. It gets into the Ciicle of Willis anu into the miuule ceiebial. If you embolize
uown, will go into the supeiioi mesenteiic
The ieason it is hemoiihagic is bc pt will get bieakuown of fibiinolytic system of
the embolus anu leaus to iepeifusion. Insteau of being a pale infaict, it's a
hemoiihagic infaict. So, both a atheioscleiotic stioke anu hemoiihagic stioke aie
both infaicts - one is pale anu the othei is hemoiihagic.
Sliue: !+Q, piessuies cause lenticulostiiate vessels to come up anu supply this aiea
of the biain. Beiive fiom the miuule ceiebial aneuiysms, calleu Chaicot Bouchaiu
aneuiysm anu it iuptuies, leauing to giant hematoma anu bloou clot. Boiiible
piognosis.
So, embolic stioke goes to suiface of the biain anu if it's in the basal ganglia, &68/
';L'"/ '4 &46-'5,E-'; E;,,A =-$. !+Q)
Example: /<E'-'5?4$&A ?,.$--?'3, mostly uue to iuptuie congenital beiiy
aneuiysm. NC at the junction ant comm bianch of ant ceiebial aiteiy
Less common cause of SAB:
(F .';=$-.'6&$4
Stuige Webei - on same siue as skin lesion of the face, theie is an Av malfoimation
X'5<4'- &4='-56/ - small aieas on the biain; unusual bc they hit aieas of the biain.
Bepenuing on wheie in the inteinal capsule, can have a puie motoi stioke oi puie
sensoiy. NC uue to BTN
B<;6&#;, [5;,-$/&/ HB[I
B> A,.",;&4'6&43 G] H'<6$&..<4,I \ B[
[;&A,0uemylinateu: white mattei has myelin it, giey uoesn't. If you aie uestioying
white mattei, then you'll see giey unueineath. :;'Y<,/ $= B[.
2 ways to uemylinate
1) knock off cell that makes myelin in the biain (oligouenuiocytes in biain,
schwann cell in PNS) - viiuses uo this - subacute scleiosis, piogiessive multifocal
leukoencephalopathy, BPv - they affect the oligouenuiocyte;
2) can also have Ab's against myelin anu not the oligouenuiocyte, which is NS
paiesthesias
Nystagmus, ataxia, optic neuiitis with bluiiy vision (B>> $= 2#6&5 Q,<-&6&/C B[ bc
uemylination of optic neive)
@46,-4<5;,'- $#6?';.'#;,3&' (uemylination of NLF) - pathognomonic
[#&4'; 6'# L&;; /?$L &45-,'/,A #-$6,&4_ 4$-.'; 3;<5$/,_ &45-,'/, ;".#?/
!"A-$5,#?';</ Z% F'5<$
Seveie atiophy of biain anu ventiicles look biggei than they shoulu be
Bementia
(;]?,&.,-8/ G]
Classic lesion: senile plaque, neuiit's, amyloiu (Beta!!) - so beta amyloiu is toxic anu
the moie you have the moie toxic - pathognomonic of alzheimeis, on c'some 21,
theiefoie seen in uown's, neuiofib tangles (in any uementia anu BB)
Alz - piobs in higei levels - uementia
0nly way to ux is autopsy (confiimation) - see senile plaques
:'-P&4/$48/ G]
Resting tiemoi

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CBAPTER 1: Cell injuiy

Audio le 01: Cell Injury 1

Then look to see if theie is polychiomasia, if theie is polychiomasia (then uiviue

S% oi highei = BN iesponuing noimally, anu 2% oi lowei = not iesponuing

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