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I N F E C T I O N A N D I M M U N O C O M PR O M ISE D PA T I E N TS

**Immunodeficiencies should be considered in patients that LO O K chronically ill with infections that are unusually frequent, severe,
refractory to treatment or d/t rare/unusual microbes.
**3ULPDU\,'VDUH5$5(DQGVHFRQGDU\,'VVKRXOGEHFRQVLGHUHGILUVW

SE C O N D A R Y I M M U N O D E F I C I E N C I ES
x General&KURQLFGHELOLWDWLQJLOOQHVVSUHVHQFHRIIRUHLJQERGLHVLQYDVLYHSURFHGXUHVPDOQXWULWLRQ
x Neutropenia
usually d/t chemotherapy or hematological cancer; predisposes to infection when <1000/mm3
x Cellular Immune Dysfunction
! Prednisonecommon anti-inflam/corcicosteroid can be too potent w/doses greater than 10mg/day (2 pills)
! HIV
Initially there is macrophage infection and dissemination to dendritic cells of the lymph via blood
CD4 cells infected when they migrates thru the germinal centers of lymph nodes and contact follicular
dendritic cells
Several weeks post infection, get Mono-type syndrome then HIV-VSHFLILF&7/VDQGDQWL-+,9DEV
develop
Viremia declines and pt enters asymptomatic latent period and CD4 decreases over years
When CD4 drops below 200/mm3, anti-HIV-abs drop and viremia ensues and AIDS is present
x Without therapy it takes ~10yrs; with HAART it is much longer
Immunosupression is inversely related to CD4 count;
>500/mm3

200-499/mm 3

<200/mm 3

Normal

S. pneumoniae
Pulmonary TB
Kaposi (HHV8)
Shingles
Candida (vaginal and oral)

Pneumo. Carinii
Reactivated CMV
Candida esophagitis
Mycobacterium avium
disseminated/chronic herpes
miliary/extrapulm TB
disseminated fungi:
Cryptococcus neoformans, C. immitis, H.capsulatum
Toxoplasmosis
C hronic cryptosporidosis
PML

A cute Cryptosporidosis
Oral Hairy Leukoplakia

x
x

<50/mm 3

M etabolic DiseasesIncluing uremia and diabetes can cause immunodeficiencies

Splenectomy
! Predisposes to sepsis to encapsulated bacteria think sickle cell)
! H.influenzae, S.pneumoniae, N.meningitides, Group B Strep and Sal monella typhi
x Loss of G agPredisposes to aspiration, thus pneumonia
PR I M A R Y I M M U N O D E F I C I E N C I ES
7KHUHDUHRYHUSULPDU\,'VDQGDUHYHU\KDUGWRGLDJQRVH
Usually inherited or congenital, mostly manifesting before 20 y/o, commonly X-OLQNHGWKXVQHDUO\DOZD\V
Classification based on the deficient component
! 3<2*(1,&6%UXWRQV$JDPPDJORELQHPLD+\SHU,J(&KURQLF*UDQXORPDWRXVSKDJRF\WHV&&&Einactivator (Factor I) and Factor D (compliment control) deficiencies
! 3(5,2'217,7,6DIHDWXUHRI/HXNRF\WH$GKHVLRQ'HILFLHQF\SKDJRF\WLFFHOOGHIHFW
O T H E R I M M U N O L O G I C A L M O D U L A T O RS O F I N F E C T I O N
x /HSURV\+DQVHQV'LVHDVH
! Distal anesthesia caused by chronic infection of peripheral nerves w/ M.leprae
! Classic digit loss d/t abuse secondary to sensory loss, NOT from the infection
! Not very contagious, and easy to control its minimal spread potential
! Untreated:
T U B E R C U L O I D L eprosy: mild soft tissue &0,W-FHOOVSRRU+0,$E
x Th1 immuQHUHVSRQVH&'KHOS0DFVUHVXOWLQJLQYLJRURXVFHOO-mediated immunity
/(3520$7286/HSURV\23326,7( JURWHVTXHGHIRUPLWLHV&0,DQG+0,
x Th2 immune response (CD4 help B-cells) and minimal cell-mediated immunity results
x Subacute Bacterial E ndocarditis need four(4) things to happen
! Damage to endocardium: congenital, rheumatic fever, mitral valve regurg producing McCallums patch
! Platelet-Fibrin Thromubs: healing response to above damage
! Repetitive bacteremia: usually S.viridans from oral flora & trauma
! +LJKWLWHURIDJJOXWLQDWLQJ$EVWREDFWHULDWKH$EVVWLFNEDFWHULDWRJHWKHUUHVXOWLQJLQELRILOP

I N F E C T I V E E N D O C A R D I T IS

F requently of the valves, the most avascular body structures. Once fatal, is now totally curable with the advent of abx. IE is becoming
increasingly more common with IVDA and one of the most frequently missed serious infections where early Dx/Tx is critical

A C U T E B A C T E R I A L E N D O C A R D I T IS
x Usually a remote infection with S.aureus (75%), S.pneumoniae & pyogenes, N.meningitidies and H.influenzae
x Rapid destruction of valves w/o a chance for healing to occur w/50-80% of cases at previously normal valves
x Janeway OHVLRQVGWVHSWLFHPEROL
x Fever and heart failure force pt to seek medical care and often needs valve replacement
SU B A C U T E B A C T E R I A L E N D O C A R D I T IS
x Four mechanisms for Initiation
1. Bacteremia, often transient and frequent
2. Previous insult to valve (congenital, esp. MVP, prosthetic, rheumatic) or McCallums patch (jet effect)
3. Sterile platelet-fibrin thrombus covering the damaged area
4. High titer of agglutinatin Ab to the organism creating the critical inoculums
x Organism is usually low virulence (viridians grouS-hemolytic), enterococci, Coagulase-negative Staph and HACEK
( Hemophilius, Actinobacillus, Cardiobacterium, Eikenella and Kingella )
I N F E C T I V E E N D O C A R D I T IS
x Chronic infections d/t incomplete healing produces gradual non-specific illnesses (malaise, fatiute, weight loss)
LQFOXGLQJIHYHUZKLFKFDQEHDEVHQWLQHOGHUO\GHELOLWDWHGUHQDOSWV&+)HUVDQGWKRVHDOUHDG\RQ$E[
x Four more mechanisms for Development Of Infective E ndocarditis
1. Valve destruction leading to CHF
2. Embolization (esp in MCA)
3. Metastatic Infection (mycotic aneurysm, septal abscess, brain abscess, bacterial meningitis)
4. Immunologic Phenomenon (glomerulonephritis 80%, arthritis w/(+) RF
x Classical physical signs of IE
! &KDQJLQJKHDUWPXUPXUV2VOHUVQRGHVFOXEELQJVSOLQWHUKHPRUUKDJHVVSOHQomegaly and Roth Spots
! Headaches or CNS signs suggest mycotic aneurysm
! Echo shows valvular vegitations,
x Diagnosis w/organism identification via 3x/day blood cultures
x Bacteremia is often continuous, not intermittent
x 7UHDWPHQWVSHFLILFDQWLPLFURELDOVGDLOy EKG (P-R interval) and surg for severe CHF d/t valve failure

M E N I N G I T IS
A constellation of infections w/multiple etiologies but share clinically a headache, fever and nuchal rigidity meningismus.
E T I O L O G Y B ASE D O N A G E
Neonates
Strep. agalactiae
E. coli
Listeria monocytogenes

C hildren <10 Y ears of Age

Step. pneumoniae
Neisseria meningitides

A dolescents and A dults

Step. pneumoniae
Neisseria meningitides

E lderly
Strep. pneumonia
Gram neg bacilli, esp. enteric
Listeria monocytogenes

P A T H O G E N ESIS varies w/agent

x Streptococcus pneumonia
! The most common overall where ~50% of cases are 2o to ear/sinus/lung infections
x Neisseria meningitides
! ACUTE FULAMENTIDWDODWKUVGW',&ZKHUHKDYHSHWHFKLDOSXSUXULFUDVK
! CHRONICUHFXUUHQW fever, arthritis and morbiliform rash every 2/3days
! METASTATIC INFECTIONPHQLQJLHVPRVWFRPPRQ seeding point but the only site w/bacteremia
! IMMUNOLOGIC RXN-14d after completing therapy. Fever, arthritis and pericarditis. Abx are NOT required
x H emophilus influenzae
! Usually 2o to ear/sinus/lung infection spread to CNS via draining veins or bacteremia. This is now very
rare w/Hemophilus B vaccine
x M ycobacterium tuberculosis
! Cerebral or osseous Granulomata from pulmonary TB is often the source of spread to the meningies
! Once in the CNS, host defenses are pretty helpless at curbing infection w/CN6 palsy
! Rapidly fatal unless properly treated w/Rx that can enter CNS (mortality of 20-30%, persistent morbidity 50%)
! Persistent Sensorineural hearing loss in ~10% of children and up to 31% if the agent was S.pneumoniae
&RUWLFRVWHURLGVSULRUWR$E[VKRZQWRLQFLGHQFHRIKHDULQJORVV
D I A G N OSIS
x Suspected diagnosis is confirmed with LP showing
3013URWHLQDQG*OXFRVH
x Could also do gram stain to help early guidance
for abx therapy
PR E V E N T I O N
x Close contact ppl offered prophylactic Abx
(health care and family) as well as those recently
exposed (not really necessary unless mouth-mouth)
x Vaccinations for Haemophilius B (esp kids) and
N.meningitidis also available;
x Quadrivalent meningococcal vaccubatuib is
given to travlers going to endemic regions (SSA)

SE PSIS
x
x
x

x
x
x
x
x

InfectionFKDUDFWHUL]HGE\LQIODPPDWRU\UHVSRQVHWRDPLFURRUJDQLVPRUWKHLQYDVLRQRIQRUPDOO\VWHULOHKRVWWLVVXH
BacteremiaSUHVHQFHRIYLDEOHEDFWHULDLQWKHEORRGDQDORJRXVWRYLUHPLDIXQJHPLDRUSDUDVLWHPLD
Systemic Inflammatory Response Syndrome (SI RS) two or more of the following:
! Temp > 38 or < 30
! HR >90
! RR>20 or PaCO2 < 32mmHg
! WBC >12,000 or <4000/mm3 or >10% immature forms (bands)
SepsisEDVLFDOO\6,56FRQILUPHGWREHGWLQIHFWLRQPRUWDOLW\LV
Severe SepsisDVVRFZRUJDQG\VIXQFWLRQK\SRSHrfusion or hypOtension; may include lactic acidosis, oliguria and
AMS; mortality is up to 20%
Sepsis Induced H ypotensionV\VWROLFRUDUHGXFWLRQE\PRUHWKDQIURPEDVHOLQHZRRWKHUFDXVHV
Septic ShockSHUVLVWHQWK\S2WHQVLRQGHVSLWHK\GUDWLRQHIIorts) along w/abnormalities d/t hypoperfusion (mort: 46%)
M ultiple O rgan Dysfunction Syn (M O DS)DOWHUDWLRQLQRUJDQI[QZDFXWHSWVZKHUHKRPHRVWDVLVFDQWEH
maintained unless there is medical intervention; no specific treatment, case-basis.
Infection
Infection

&'()*+","-.-%*/%!"#"$%

Inflammation of tissues

E xogenous M ediators:
G(-) Lipid-A, Endotoxin
G(+) Peptidoglycan

PAF
Neutrophil Activation
T-FHOODFWLYDWLRQ,/-2, INF-
Release of O2 radicals & proteases

0DFVWKHQ7-cells

0)"%1"2-.-%
3'-4'5"%

E ndogenous M ediators:
IL-1,2,6, TNF-,)1-
etc

Hypothalamus
Reset Thermostat

Chills, Rigors, Shunting

of Blood from Skin &
Heat Seeking Behavior

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Arachadonic Acid Metabolism

LTE, TXA2 & PGE
causes
FEVER
Platelet Activation
Endothelial Damage
735 +\SHUPHWDEROLF5DWH
SEPSIS

PGE Synthesis
Myalgia &
Muscle Catabolism

D E A T H or
M O DS

Compliment Activation
Coagulation
Mac Activation 71),/-1,6

Widespreak Interstitial Edema

Mitochondrial Dysfunction
O2-transport Defecit
SEPTIC SHOCK

Hypotension and Capillary

Leakage
SEVERE SEPSIS

M anagement of Sepsis
! )LUVWO\SDWLHQWPXVWEHPHWLFXORXVO\H[DPLQHGIRUDVLWHRILQIHFWLRQEORRGXULQHFXOWXUH &;5PLQLPXP
! Two cultures from two different sites before choosing proper antimicrobial therapy
! Rapid broad spectrum Abx and drainage of abscesses ASAP is critical
! Should be in ICU w/arterial catheter to very carefully manage BP without inducing PE
! G O A LPDLQWDLQRUJDQFHOOSHUIXVLRQ WUHDWLQIHFWLRQWRinter rupt the Sepsis C ascade
! K E Y T H E R A PI ES$E[22, fluids and pressors to maintain BP
! C O R T I C OST E R O I DSORZGRVHVRQO\ZHYLGHQFHRIDGUHQRFRUWLFDOLQVXIILFLHQF\
! A C T I V A T E D PR O T E I N-CGURWUHFRJLQPD\EHKHOSIXOZVHSWLFVKRFN02'6DQG',&

ST AP H L O C O C C US A UR E US

G ENERA L INF O
x Gram (+) spherical and usually clustered and distinguishable by its ability to ferment glucose
x THREE human Staph SDWKRJHQVS.aureus, S.epidermidis & S.staphrophyticus
! 6DXUHXV distinguished by characteristic colonial morphology; coag (+) and mannitol fermentation
x 0DLQ+DELWDWDQWHULRUQDUHVDQGFDQspread easily to skin and mucous membrane
! normal shedding causes dissemination (shedding varies w/person)
x Cell wall virulence factors include:
! Protein-A : binds to IgG to inhibit phagocytosis
! M embrane damaging exotoxin and leukocidin
! Super-Ag exotoxins: high affinity for T-cells and MHC-II stimulating a massive T-cell response which causes
an outpouring of T-cell cytokines TNF-,/-2 and IFN- resulting in Toxin Associated Syndromes (below)
F O U R M A JO R D ISE ASES
1. Localized Abscess
a. Skin and soft tiVVXH, 'IRUWKHUDS\LQFLVLRQDQGGUDLQ
b. Bone osteomyelitis
2. Sepsis and Acute Endocarditis
3. Hospital-Acquired and Post-Influenzal Pneumonia
a. Remember S.aureus is part of flora in pharynx
4. Toxin Associated Syndromes
a. Food Poisioning (A-E & G)
i. Incubates b/w 10-45oc (hours only) so reheating improperly stored food is ineffective
ii. Binds to neural GI receptors (upper) to induce emesis and hypermobility via Vagus nerve
iii. 1-6hrs incubation, usually done w/in 24hrs and absent of fever
b. Scalded Skin
i. 5LWWHUV'LVHDVHVHYHUHGHHSGHVTXDPDWLRQLQQHRQDWHVWKH\KDYHQR$EVZZHDNUHQDOIXQFWLRQ
ii. &ODVVLF666PRUHVXSHUILFLDOVWLOOQR$EVEXWNLGQH\VFDQFOHDUWR[LQEHWWHU
iii. 6WDSKORFRFFDOVFDUOHWIHYHUPLVQRPHUVFDUOHWIHYHULVVWUHSDQGZLWK12SKDU\QJHDOK\SHUHPLD
and strawberry tongue seen in real strep scarlet fever; cleared by kidney and PO Abx is norm
iv. Bullous ImpetigoS.aureus-phage group-II; give PO Abx
c. Toxic Shock Syndrome (TSS)
i. Sepsis-like syndrome but Negative blood cultures
ii. High fever, hypOtension, diffuse erythema (sunburn-like), N/V/D and can progress to MSOF &death
iii. Also has late desquamation
iv. First outbreak with tampons which absorbed Mg ions needed to inhibit TSST-1 secretions
v. Remove source (drain abscess, remove tampon), give fluids, Iv-,JVDQG$E[WRSrevent recurrence
M E T H I C I L L I N-R ESIST A N T ST A P H A U R E US - M RSA
x Antibiotic Susceptibility of S.aureus
! most straiQVKDYHSODVPLG-lactamase that makes it resistant to PCN thus need for PRSP (penicillinase-resistant
semisynthetic penicillin methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin or nafcillin)or cephalosporin
! VVWUDQGVGHYHORSHGDFFHssory penicillin-binding protein (PBP-2a) making them PRSP-resistant
They are termed MRSA as methicillin is the prototype PRSP and the strains are mec-types I-I I I
Vancomycin is the D2&IRU056$DVLWLVUHVLVWDQWWR-lactams (clindamycin, macrolites, etc)
Quick spreading strands in some areas coined epidemic, thus EMRSA (class based on enterotoxin-A)
! VFRPPXQLW\DFTXLUHGHPHUJHQFH&$056$VHYHUHVNLQVRIWWLVVXHSURJUHVVLQJWRSQHXPRQLD VHSVLV
Are now very common, of the mec-type I V and are less resistant than hospital-MRSA
Hard to eradicate but usually sensitive to clindamycin, doxycycline, vancomycin)
! 9,6$UHVLVWDQWVWUDLQVWRYDQFRP\FLQEXWVHQVLWLYHWRTXLQXSULVWLQ-dalfospristin, linezolid & daptomycin

U R I N A R Y T R A C T I N F E C T I O NS
x Pathogenesis
1. Reservoir of organism in GIT or skin
2. Perineal Colonization (hygienic practices)
i. PremenarcheFRUQ\HIRUPV, strep, staph and lactobacilli
ii. Reproductive yearsODFWREDFLOOLLVSUHGRPLQDQW
iii. PostmenopausalPRUHDQDHUREHV3UHYRWHOODPHODQLQRJHQLFXV
3. U rethral Ascent QRWHLVFPORQJHUZDQWLPLFURELDOVLQSURVWDWH
4. Reflux (more common) or Bacteremia (neonates: S.aureus, mycobacteria or candida)
5. Pyelonephritis and Renal A bscess leading
6. SE PSIS
x Risk F actors
! Structural abnormality of UT
! Catheterization major advance w/closed drain system
! Pregnancy
! Tumors or Stones
x Syndromes
! &\VWLWLVG\VXULDIUHTXHQF\XUJHQF\SXUXLDEDFWHUHPLD+ hematuria and NO fever
! $FXWH8UHWKUDO6\QGURPHG\VXULDIUHTXHQF\XUJHQF\+ puruia, and NO fever, hematuria or bacteremia
Accounts for up to 40% of dysuria and may be a low bacterial count (ie: fungal, viral)
! $V\PSWRPDWLF%DFWHULXULDWUHDWFKLOGUHQDQGSUHJQDQWRQO\
! $FXWH3\HORQHSKULWLV)HYHUEDFWHULXULDG\VXULDIUHTXHQF\XUJHQF\S\UXLDKHPDWXULDDQG&9$WHQGHUQHVV
x L ab Diagnosis
! Significant bacteriuria means >108 &)8/EXWVPD\EHV\PSWRPDWLFDW5 %D\HVWKHRUHP
! Acceptable Specimens AM urine is best (ie: first void); must be refrigerated if it cant get to the lab w/in 2hrs
Clean Catch from Mid-Stream
Suprapubic $VSLUDWHDQ\JURZWKLVFRQVLGHUHGVLJQLILFDQW
&DWKHUL]HGSWVDVSLUDWHIURPSRUWDIWHUVZDEELQJZLWKDOFRKRO1(9(5IURPIROH\EDJ
x E tiology
! Enterobacteriaces the so-called uropathogenic strains of E.coli
! 6H[XDOO\$FWLYH6WDSKORFRFFXVVDSURSK\WLFXV

G AST R O E N T E R I T IS

G ENERA L INF O
x By definition: >300grams/day; up to 90% can be water so the main cause is excess water excretion & stool loosening
x Acute is less than two weeks and is often infectious; WITH vomiting is coined Acute Gastroenteritis
x 3-5Billion/year with up to 10-million deaths, mainly in preschoolers d/t dehydration (prevent with ORT)
x :HVWHUQQRUPDOO\VHOI-limiting w/in 24hrs (staph enterotoxin) but up to 10 days w/shigellosis
B A C T E R I A L G AST R O E N T E R I T IS
x

E N T E R O T O X I N PR O D U C I N G G R O UP

!
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produce exotoxin either before or after ingestion

Preformed toxins are usually of short incubation (<12hrs)
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Enterotoxins bind to receptor siWHVRIPXFRVDOFHOOVFDXVLQJIOXLGDQGHOHFWURO\WHVHFUHWLRQ
This overwhelms the absorptive capacity of colon causing watery diarrhea

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Passes thru gastric acid and colonizes bowels causing inflammation of colon with or w/o mucosal invasion
Results in small amts of diarrheal stool containing pus cells, mucus and often blood
Dx: isolate from stool (unless otherwise specified)

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V I R A L G AST R O E N T E R I T IS
x R O T A V I R US naked dsRNA
! Broken into seroGroups A, B, C and serotypes where group A is broken into type 1, 2, 3 and 4
! Very common b/w 6mos and 2yrs; 90% seropositive by 4 y/o
! Incubation of 1-GD\VIROORZHGE\DEUXSW19''-lasts for about a week, can cause dangerous dehydration
! Located in duodenum & proximal jejunum, destructing villous epitheliumPDODEVRUSWLRQXSWRZNUHFRYHU\
! Diagnose w/latex agglutination and T reat supportively, primarily ORT
x

N O R W A L K & N O R W A L K -L I K E V I R US (small RNA)

!
!
!
!

Four serotypes cause illness in humans 659*VPDOOURXQGYLUXVHVRIJDVWURHQWHULWLV

Usually older kids and adults, common w/community outbreaks and most ppl are seropositive by 5th decade
Incubation up to 2.5days with abrupt V/D lasting 1-2days but viral shedding can last up to 4days post-onset
Diagnose by EM, T reat supportively and Prevent with hygiene as T ransmission is fecal-oral

A D E N O V I R US

!
!

Fecal-oral, respiratory or even formites (towels) with a 5-10day incubation and sx lasting up to 10days
Aside from GI disturbances, it often causes respiratory illness ranging from conjunctivitis to pneumonia

PR O T O Z O A/P A R ASI T I C G AST R O E N T E R I T IS

x G I ARD I A L A M B L I A
! Fecal-oral by contaminated water and resistant to chlorination
! 3-25day incubation: w/ acute or chronic diarrhea, steatorrhea, bloating, fatigue, malabsorption & weight loss
! T reat w/metronidazole x3days
x E N T A M O E B A H IST O LYT I C A
! Fecal-oral by food/water or direct oral-anal contact with a 2-4 week incubation period (but can vary greatly)
! Most are asymptomatic but have wide variation
Mild abdominal discomfort and diarrhea; with or w/o blood and mucus
Fulminant dysentery w/fever, chills and +bloody mucoid diarrhea
! May have granulomata in colon wall in chronic pts and mistaken for colon cancer
! Perianal skin ulcers can cause dissemination into blood leading to liver abscesses (less commonly brain/lung)
! T reat acute with metronidazole and extraintestinal disesases follow w/iodoquinol, paromycin or diloxanide
x C RYPT OSPORI D I U M PARV U M
! Fecal-oral via food/water and can be person-person or from animals and is also resistant to chlorination
! Incubation up to 12days with diarrhea lasting 3weeks in healthy but can be fatal in IC pts (ie: AIDS)
! T reat by stopping immunosuppressive drugs if possible and Diagnose by locating cysts w/acid-fast stain
x C YC L OSPORA C AY E T A N E NSIS
! Food (fresh fruits/veg) and water borne, also via swimming
! Incubation of 7days w/diarrhea, nausea, anorexia, cramps and fatigue
! Health pts have Sx last >3weeks but ICs have it last for months
! T reat with trimethoprim-sulfamethoxazole x7days and Diagnose by locating cysts w/acid-fast stain

SUPPL I M E N T A L I N F O R M A T I O N F O R I N F E C T I O US D ISE ASES

I N F E C T I O NS C O M M O N T O D R U G USE RS
x Skin Infections
! cellulites, subcutaneous abscess, myositis, necrotizing fasciitis) d/t poor hygieneQRQVWHULOHVWDSK VWUHS
x Aspiration Pneumonia
! Due to altered consciousness; can cause lung abscesses, empyema nd brain abscesses
x Hepatitis
! $IHFDO-oral%&'SDUDHQWHUDOURXWHV
x Infective Endocarditis
! Right heart (venous) and commonly S.aureus (75%), candidia or strep; can cause pulmonary septic emboli
x STD/AIDS
! Exchange of sex for drugs
x Vascular Infections
! Mycotic aneurysms, infective thrombophlebitis (d/t infection following trauma); septic emboli or bacteremia
I M M U N O C O M PR O M ISE D
x Neutropenia
! With chemotherapy, BM-transplants, leukemia and the like
! risk by G(-) pseudomonas, G(+)S.aureus, epidermidis, S.viridans & Fungi candida, aspergillus, mucormycosis
x Impaired Humoral Immunity
! Congenital causes like MM, CLL or splenectomy which causes lack of opsonizing Abs
! ULVNE\HQFDSVXODWHGRUJV H.influenzae, S.pneumoniae, N.meningitides, Group B Strep and Sal monella typhi
x Impaired Cellular Immunity
! As in HIV, immunosuppressive therapy, Hodgkins lymphoma
! Uisk of intracellular organismas
BacteriaP\FREDFWHULXPOLVWHULDVDOPRQHOOD
9LUXVHV&09KHUSHV
)XQJL&U\SWRFRFFXVSQHXPRF\VWLVKLVWRSODVPDDQG3URWR]RDWR[RSODVPD
! 'LDEHWHVKDYH&0,WKXVmore susceptible to mucormycosis & foot infections
x CNS Dysfunction
! Risk of aspiration pneumonia
x HIV
! Toxoplasmosis causes ring enhancing lesions in the brain
! Cryptococcus can cause meningitis
! HIV-associated esophagitis (commonly candidia)
! HSV-SXQFKHGRXWOHVLRQV&RZGU\-type-A inclusions
! &09OLQHDUXOFHUV and can also have both intranuclear and intracytoplasmic inclusions

I N F E C T I O US D I A R R H E A L D ISE ASES
x Non-Inflammatory
! Watery, non-bloody diarrhea w/PERIUMBILICAL cramps, bloating or vomiting
! $JHQWV(7(&6DXUHXVYLUXVHVHWF
! Disrupts normal absorptive/secretory processes VRGLXPORVV water loss)
! &RPSOLFDWLRQVGHK\GUDWLRQPHWDEROLFDFLGRVLVK\SRNDOHPLD-)fecal leukocytes
x Inflammatory
! Fever and bloody diarrhea w/colonic tissue invasion and damage
! $JHQWVVKLJHOODVDOPRQHOODDPHELDVLV&MHMXQL<HUVLQLDand toxins (C.dificile/E.coli)
! Small volume, LEFT-LOWER cramps, tenesmus and urgency w/(+)leukocytes & lactoferrins in feces
&GLIILFLOH assoc w/Abx use and also gives rise to pseudomembranous colitis
SalmonellosisPRVWFRPPRQFDXVHRIRVWHRP\HOLWLVLQ6LFNOH&HOOSWV
! ,QIODPPDWRU\'LVHDVHV8&RU&'
SE C R E T O R Y or M A L A BSO RP T I V E SY N D R O M ES
x Endocrine tumors (VIPoma located in the pancreas and synthesizes vasoactive intestinal peptide; assoc w/MEN-1?)
x Malabsorptive can include things such as pancreatic insufficiencies
M O T I L I T Y D ISO R D E RS
x Chronic infections especially in IC pts, specifically things like CMV, mycobacterium avium and cryptosproidosis
x )DFWLWLRXVGLDUUKHD laxative abuse or stool dilution

U R I N A R Y T R A C T I N F E C T I O NS
x Common Sx/Sx
! 3DLQEXUQLQJGXULQJXULQDWLRQZLWKIUHTXHQF\DQGXUHWKUDOGLVFKDUJH
x Cystitis
! Strong, constant urge to urinate with sharp pain/burning during urination
! Inability to completely void and possible blood in urine
! Suprapubic pain and soreness in lower abdomen, back or flanks
x Pyelonephritis
! All symptoms of cystitis plus back pain, chills, fever and N/V
! Will also have tenderness at the CVA upon percussion
x Etiopathogenesis
! Mechanisms to maintain sterility include urine acidity, emptying of bladder, sphincters and immunomucosal
! Community Acquired(FRli (75%) and S.saprophyticus (~10%)
! Hospital
E.coli (50%);
Klebsiella, Proteus, Enterobacter & Serratia (40%);
E.fecalis & S.saprophyticus and S.aureus (10%)
! 1HRQDWHVusually hematologic but later in life is almost always d/t urethral ascent
x Risk Factors
! Any condition leading to urinary stasis (stones, obstruction, reflux and voiding disorders)
x Complications
! Renal parenchymal infections & scarring due to upper UTI
! This can lead to eventual renal insufficiency, HTN and RF (ESRD)
x Assessment and Diagnosis
!  XQFLUFXPFLVHG\U
!  LQJHQHUDOSDUWLFXODUO\\U
! Non-African American
! Fever >39oC -- note that absent fever/other risk factors GRHVQW preclude the presence of a UTI (asymptomatic)
! /$%68$DQGRUXULQHFXOWXUHQRWDOZD\VQHFHVVDU\WRFXOWXUH
x Urine Collection
! Must be mid-stream done by a clean-catch but older women who cant do this, a catheter is preferred
! If not, suprapubic aspiration is preferred
x Urine Testing
! Pyuria defined as >:%&/EXWUHDOO\LQIHFWHGSWVDUHXVXDOO\!
! Presence of bacteria w/o WBCs is likely d/t contamination of the specimen
! +HPDWXULDPLFURVFRSLFLVFRPPRQEXWJURVVLVUDUH
! WBC casts indicates pyelonephritis, glomerulonephritis and non-infective tubulointerstitial nephritis
! DIPSTICK
(+) nitrite is highly specific but not sensitive
Leukocyte esterase test is very specific DQGVRPHZKDWVHQVLWLYHIRUYDOXHV!:%&/
Clinical Sx/Sx and positive dipstick/micro tests is sufficient for diagnosis
! CULTURE
Done when Sx is suggestive but UA is negative
Also in complicated cases (IC, diabetics, recent hospitalizations, chronic/recurrent or w/instruments)
Patients older than 65 or pre-pubertal should have a culture done with a suspicion of a UTI
x Localization of Infection
! Upper vs. Lower is impossible in most cases (kidney vs. bladder)
! Base your thoughs on CVA pain, casts and such
! 6LPSO\ response from short course Abx (<3days) indicates lower, if not then suspect pyelonephritis
x Differentials
! 9DJLQLWLVZLOODOVRFDXVHG\VXULDZKHQXULQHSDVVHVLQIODPHGODELDGLVWLQJXLVKHGZYDJLQDOGLVFKDUJHRGRU
! 3URVWDWLWLVPXVWEHUXOHGRXWIRUPDOHV

!"#$%&'&()*
C O N G EST I V E H E A R T F A I L U R E C H F
x

Definition
! Inadequate pumping function of the heart leading to congestion & resulting in fluid accumulation in lungs and
peripheral tissues
! NOTE: symptoms will depend on onset, is it acute/chronic? Does it involve left, right or both ventricles?
Conventional Classification N Y H A

Note that 1-M E T is the energy expenditure at rest, thus the scale is based on multiples of energy needed at rest

1. No symptoms, even during exercise

A ble at < 7M E TS Carry 11kg up 8steps, shovel snow, play bball, jog/walk at 8km/hr
2. Decreased physical capacity during medium exercise
A ble at < 5M E TSgardening, roller skate, walk at 7km/hr
3. Severe reduction in physical capacity in light work (stairs) but asymptomatic at rest
A ble at < 2 M E TSshower/dress without stopping, make the bed, play golf and walk 4km/hr
4. Symptomatic at rest
Unable at > 2M E TScannot perform any of the above activities

L E F T V ENTRICUL A R F AILURE
x
x

C L I N I C A L PR ESE N T A T I O N
! Dyspnea, Orthopnea, PND, Hemoptysis, CP (occasional), Fatigue, Nocturia and Confusion
ETIOLOGY
! Inappropriate workload placed on the heart
Volume overload: mitral/aortic regurgitation
Pressure overload: systemic/pul monary hypertension
! Restricted Filling of the heart: constrictive pericarditis
! Loss of Myocardial Tissue/cells: infarction
! Decreased Contractility: poisoning and infections
H E M O D Y N A M I C C H A N G ES SYST O L I C
! C ausesFRURQDU\DUWHU\GLVHDVHYDOYXODUKHDUWGLVHDVH+71DJLQJDQGGLODWHGFDUGLRP\RSDWK\
! Pressure-Volume C hanges
Lower ejection, lower Stroke Volume and overall decreased Cardiac Output (CO = SV x HR)

NORM AL
note the curve & the various changes that are
represented by four major points
!

!"#

SYST E M I C H T N
causes increased afterload on the LV
causing !"#$%&''(%&, )" & *+"
!

Compensatory M echanisms
1. Increased Preload: heart will operate at larger
EDV
2. Increased release of C atecholamines can help
partially restore SV
x Blue curve is soon after heart failure
x Dashed-curve shows compensation
with catecholamines
3. H ypertrophy and ventricular volumes will
also increase in a futile effort to restore SV

ACUTE MI
loss of myocardium will cause a !"#
$%&''(%&, )" and *+"
!

&203(16$725<('9
In LV F , increasing the E DV will
slightly help restore S V
!

H E M O D Y N A M I C C H A N G ES D I AST O L I C
! This would encompass any diseases where filling is impaired causing a
('9RU (nd-Diastolic Pressure or both
'HFUHDVHG5HOD[DWLRQconstrictive pericarditis
,QFUHDVHG9HQWULFXODU6WLIIQHVVhypertrophic cardiomyopathies
! Entire curve is shifted to the left (dotted) with an overall
increase in end-diastolic pressure
! There is a marked decrease in L V filling DQG&2EXWWKHVWUHQJWKRIFRQWUDFWLOLW\
and ejection fraction are normal, its really just that there is not enough blood
being prepared for ejection
! NOTE: Ejection fraction is the fraction of EDV ejected after one beat and can be used
as an index for contractility (inotropic effects) so again, its N O T the contractility or E F, its simply )LOOLQJ
! ALSO: left atrial pressure increases can cause pulmonary congestion and edema
x N E U R O H U M O R A L C H A N G ES
! Increased Sympathetic Activity
2FFXUVLQHDUO\+)ZKHUH1(FDXVHVFRQWUDFWLOLW\DQG+5WKDWPD\LQLWLDOO\KHOSLPSURYH69
&RQWLQXWHGHIIHFWVZLOOSUHORDGDQGDIWHUORDGWKDWwill result in eventual exacerbation/worsening HF
! Activation of R A AS
There will be a release of renin dWUHQDOEORRGIORZFDXVLQJ1DUHWHQWLRQWKDWZLOOSUHORDG
7KLVYROXPHFRPELQHGZLWKYDVRFRQVWULFWLRQZLOOFDXVHSUHDIHUORDGFDXVLQJIXUWKHU&2
The decreased CO will cause more renin release and perpetuate this vicious cycle
! O ther C ytokines and Peptides
I L-1 can accelerate myocardial hypertrophy
T N F- can also accelerate hypertrophy AND apoptosis
E ndothelin ZLOOSXOPRQDU\YDVRFRQVWULFWLRQP\RF\WHK\SHUWURSK\DQGILEURVLV
A NP and B NP ZLOOFDXVHQDWULXUHVLV1DLQXULQHDQGYDVRGLODWLRQ
x NOTE: BNP is released by ventricular myocytes when stretched where its levels are increased
in CHF and measurement is important in differential diagnosis and evaluation of HF
x C E L L U L A R C H A N G ES
! Inefficient intracellular C a 2+ handing
!"#$%&'()*%+
! A drenergic desensitization
,"-./")&#0+
! Myocyte H ypertrophy, F ibrosis and A poptosis
x B ASIS F O R C L I N I C A L PR ESE N T A T I O N O F C H F
! Dyspnea
,QFUHDVHGSUHVVXUHLQSXOPRQDU\YDVFXODWXUHFDSLOODULHVGWOHIWDWULDOYHQWULFXODUSUHVVXUHV
This causes pulmonary congestion & edema that stimulates J-receptors to cause rapid/shallow breathing
There may be edema of bronchial walls that causes small airway obstruction, thus FDUGLDFDVWKPD
*HQHUDO(GHPDZLOODOVRFDXVHYLWDOFDSDFLW\DQGFORVXUHRIVPDOODLUZD\VZKHUHWKHZRUNUHTXLUHG
WREUHDWKZLOOPDUNHGO\LQFUHDVHFDXVLQJUHVSLUDWRU\PXVFOHIDWLJXHDQGG\VSQHD
94PLVPDWFKIURPHGHPDZLOO$-a JUDGLHQWFDXVLQJIXUWKHUK\SR[HPLDDQGDJDLQG\VSQHD
! O rthopnea
,QVXSLQHWKHUHZLOOEHYHQRXVUHWXUQFDXVLQJYHQWULFXODUSUHVVXUHDQGH[DFHUEDWLRQRISXOPHGHPD
! Paroxysmal Nocturnal Dyspnea PN D
'XULQJVOHHSWKHUHZLOOEHQDWXUDODGUHQHUJLFHIIHFWVYDJDODFWLYLW\DQGQRUPQRFWXUQDOGHFUHDVHLQ
the central respiratory center
x P H YSI C A L E X A M L V F
! 55+5SDOHFRROFODPP\DOWHUQDQVELEDVLODUUDOHVDSLFDOLPSXOVHGLVSODFHG66"may have RV F sx/sx
! Rales & Pleural Effusion
Rales due to the flXLGLQDOYHROLDQGFDSLOODU\SUHVVXUHFDQOHDNLQWRSOHXUDOVSDFHJLYLQJWKHHIIXVLRQ
! Displaced/Sustained A pical Impulse
Is considered VXVWDLQHG when it can be felt in late systole and in combination with displacement
(down and out) suggests an increase in LV volume or mass
! CXR
Characteristic EDWZLQJ density, cardiac enlargement and pulmonary edema
! Pale/Cold/C lammy
Pale/ColdSHULSKHUDOYDVRFRQVWULFWLRQGWVKXQWLQJRIEORRGWRZDUGYLWDORUJDQV
ClammyLQFUHDVHGVZHDWGWWKHUPRUHJXODWLRQZKHQERG\KHat cant get thru constricted skin vessels

T hird H eart Sound S3

Low pitched sound heard during rapid ventricular
filling in early diastole from dilation and is usually
best heard at the apex
! Fourth H eart Sound S4
Heard at the end of diastole with atrial contraction
and is caused by blood being forced into a stiff/failing/
hypertrophic ventricle; best heard laterally over apex
when pt is L-lateral recumbant
C O R PU L M O N A L E
x Characterized by RIGHT ventricular enlargement and failure as a result of pulmonary disease
! Pulmonary Vascular Disease and COPD
!

PR O G R ESSI V E L V F SU M M A R Y
A. Normal
B. ,PPHGLDWHHIIHFWRIFRQWUDFWLOLW\IROORZLQJ$0,QRFRPSHQVDWLRQ\HW
C. &RPSHQVDWHG/9)69LVSDUWLDOO\UHVWRUHGGXHWRSUHORDG
D. 'HFRPSHQVDWHG/9)GHVSLWHSUHORDG69UHPDLQVORZDQG
heart is overstretched

RIG H T V ENTRICUL AR F AILURE

x

C A USES
! Secondary to LVF which places an increased afterload on the right heart
! ,QFUHDVHGIORZIURPFRQJHQLWDOVKXQWFDQFDXVHUHDFWLYHSXOPRQDU\DUWHU\FRQVWULFWLRQDQGDIWHUORDGRQ59
! As a sequelae of pulmonary disease (cor pulmonale) causing pulmonary capillary destruction or hypoxic
vasoconstriction which increases RV afterload
! Right Ventricular Infarction of ischemia
P A T H O P H YSI O L O G Y O F R V F


!"#$%#

1(02*3#
4!5)#+"2!#
/%#

6")*77+-+("
2#/%#7+88+"9#

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"#

$=$>?#)(02*3#!4)2'*-2)#/%#
!*278!5#@#Z
#

%HUQKHLPV6\QGURPH(IIHFWDFRQGLWLRQZKHUHWKHVHSWXPEHFRPHVK\SHUWURSKLFRUDQHXU\VPDOto a point
where it encroaches into the RIGHT VENTRICLE and causes systemic congestion evident in hepatomegaly,
JVD and generalized edema but W I T H O U T pulmonary congestion
! M A J O R N O T E : if RVF is caused by a Left-sided defect like mitral stenosis, then the onset of RVF will lessen
the pulmonary edema because of the decreased blood flow INTO the lungs from the weak RV
C L I N I C A L PR ESE N T A T I O N O F R V F
! Shortness of B reath
LVF that has cuased pulmonary edema
Pre-existing pulmonary disease such as PE or COPD
Portal HTN causing ascites where the fluid restricts the diaphragm and causes dyspnea
Reduced RIGHT sided CO leading to acidosis, hypoxia and starvation for air
! Pedal E dema, A nasarca, Ascites
RVF will cause an increased right-sided pressure that will back up into the body and congest the venous
system causing dependent edema of the hands and legs, generalized edema (anasarca) & ascites (pitting)
! A bdominal Pain
Expansion of the liver due to congestion will stretch the capsule and cause RUQ pain
P H YSI C A L E X A M I N A T I O N
! E levated J VP and Hepato-jugular reflex but can also be caused by:
Pericardial Tamponade
Constrictive Pericarditis
Massive Pulmonary Embolus
! Sustained systolic heaves below sternum (RV-hypertrophy)
! S3 heard best at sterna border
! Because the most common cause of RVF is LVF, all that is found in L V F may also be found here
!

&'())*'(#+"#$%#
(,-((.)#/%#0'())*'(#

E K G & A R R Y T H M I AS
x

x
x

Definition
! Abnormal rhythm of the heart whos classification is based on the following
Rate (brady or tachy)
O rigin(ventricular or supraventricular)
M echanism (automatic, triggered or re-entry)
Clinical Presentation
! Palpation, Lightheadedness, Syncope and many non-spesifics like fatigue, dyspnea or exertional intolerance
! SYNCOPE
Due to organic heart condition like valvular stenosis, hypertrophy and ischemia
Sudden drop in C O caused by aortic dissection and tamponade
B radyar rhythmiasVLQXVQRGHGLVHDVHKHDUWEORFNo/3o) and pacemaker malfunctions
T achyar rhythmias9-tach/fib; torsades and SVT
EKG and Depolarization Fronts in the Heart

Normal Values for the Intervals

! PR 0.20s
! Q RS 0.10s
! Q T 0.43s
Heart Rate from the EKG
! 6LPSO\GLYLGHE\WKH5-R-interval in seconds (ie: 60/1.2s = 50 bpm)
Normal Sinus Rhythm
! 5K\WKPUHJXODU
! 5DWH-100 bpm
! 456QRUPDO
! P-ZDYHYLVLEOHDQGRQHEHIRUHHDFK456
! PR-LQWHUYDO< 0.20 (5boxes) note that prolonged may indicate 1st-degree block

B R A D Y A R R H Y T H M I AS
x

SA-Node Action Potential

! Has three phases (0, 3, 4) but note that Phase-4 is UNSTABLE
ZLWKDSUHSRWHQWLDODNDSDFHPDNHU-SRWHQWLDOZKLFKLVZKDW
gives the ultimate automaticity to the SA-node
Two Basic types of Bradyarrhythmias
! REDUCED AUTOMATICITY OF SA-NODE
Results in slow HR or pauses and if the SA-node stops, the next fastest locus of automaticity will take
over which is commonly the A V node
Reduction in SA-QRGHDXWRPDWLFLW\LVQDWXUDOO\VHHQZYDJDOWRQHDWQLJKWRUFDURWLGPDVVDJH
increasing age and of course, secondary to drugs like beta-blockers and CC-blockers
VAGAL STIMULATION: will cause (-)chronotropic via ACh on M2 receptors at the SAN causing a
decrease in Phase-K\SHUSRODUL]DWLRQRYHUDOO+5

!"#$%#&$'$%()%*%+*,)$%*#%#&$%-.!%)"%
$/$0#,*112%#&$%.3!%4(11%+(56%,+%
 %
CONDUCTION BLOCK
The AV node and Bundle of HIS are most vulnerable to a block in conduction b/w atria and ventricles
2FFXUVZLWKDJHYDJDOLQSXWFRQJHQLWDOGLVRUGHUV0'6/(etc), sarcoidosis, gout, lyme & CAD
Sinus B radycardia
!"#$%&'&%
! 5K\WKPUHJXODU
(#)*+,-.%
! 5DWHESP (long R-R)
! 456QRUPDO
! P-ZDYHYLVLEOHDQGRQHEHIRUHHDFK456
! PR-LQWHUYDOQRUPDO< 0.20 (5boxes)
/+"."#$*0%
1st Degree A V-Block
/&'(#)*+,-.%
! 5K\WKPUHJXODU
! 5DWHnormal
! 456QRUPDO
! P-ZDYH
! PR-LQWHUYDOProlonged; > 0.20 (more than 5boxes)
!

2nd Degree A V-Block Mobits T ype-I: W enckebach

! 5K\WKPUHJXODUO\LUUHJXODU
! 5DWHQRUPDO
! 456QRUPDO
! P-ZDYHZLOOEHIRUa-4 cycles then it will drop the Q RS making it 1:0
! PR-intervDOSURJUHVVLYHOHQJWKHQLQJXQWLO\RXdrop a Q RS
This is a block of SOM E but N O T A L L atrial beats

2nd Degree A V-Block Mobits T ype-I I: H ay

! 5K\WKPregular between dropped beats
! 5DWHQRUPDO or slow
! 456QRUPDO (may be wide infranodal)
! 3456 or 3:1
! P-wave ratenormal but faster than ventricular Q RS
! PR-LQWHUYDOnormal or wide BUT CONSTANT

3 rd Degree Complete A V-Block

! 5K\WKPUHJXODU
! 5DWHVORZ
! 456ZLGHYHQWULFXODU
! 3456FRPSOHWHGLVDVVRFLDWLRQIRURQHDQRWKHU
! P-ZDYHUDWHQRUPDOEXt faster than Q RS (atrial: always faster)
! PR-LQWHUYDOvery variable

!"#$%&'()!
"#$%##&!'()**#'!
"#+$,!

T A C H Y A R R H Y T H M I AS
x

!"#$%#&'#%#&$($%)*%+"($%
,"##$,%-"+./$0$*%,1$%
#"% .&'*$23%

Three Basic Principles:

! Increased SA N pacemaker automaticity
more rapid Phase-GHSRODUL]DWLRQFDXVHV+5DQGRIWHQLVSinus T achycardia
! Spontaneous Depolarizations
Usually due to long QT syndrome caused by decreased
function of the potassium channels slowing repolarization
,IUHSRODUL]DWLRQLVGHOD\HGSKDVH-2 plateau) then
spontaneous depolarizations can occur and will
repetitively reach threshold causing a tachycardic rhythm
The common tachycardic rhythm would be Torsade de Pointes
! Re-entrant Circuit most common

Common re-entrant rhythms include A-tach/fib/flutter, SVT (WPW) and V-tach

!"#$%&'('&
Sinus T achycardia
)*%+$,-.&
! 5K\WKPUHJXODU
! 5DWH> 100bpm (short R-R)
! 456QRUPDO
! P-ZDYHYLVLEOHDQGRQHEHIRUHHDFK456
! PR-LQWHUYDOQRUPDO< 0.20 (5boxes
Everything is N ORM A L except that it is much faster (exercise, stress, fright, fever)

Torsades de Pointes
! Twisting polymorphic V-tach that manifests when the QT-interval is prolonged ORQJ47V\QGURPH
! 47LVXVXDOO\SURORQJHGGW.-channels causing slow
repolarization where a spontaneous depolarization
occurs throwing the rhythm into tachycardia

Wolff-Par kinson-W hite Syndrome

! 7KH%XQGOHRI.HQWFDQFRPSOHWHWKHFLUFXLWDQDOORZDUH-entry tachycardia to manifest
! 7KHKHDUWZLOOEHSUH-H[FLWHGGRZQWKHVKRUWHUDFFHVVRU\SDWK
! The EKG will show a short PR-interval and wide QRS with a slurred upstroke known
As a D E L T A-W A V E
! IF enough times has elapsed, there can be re-entry into the atria
via accessory pathway and cause the atria to enter into an SVT rhythm

Supraventricular T achycardia
! 5K\WKPUHJXODU
! 5DWH140-220bpm
! 456QRUPDOQDUURZ
! P-ZDYHOLNHO\EXULHGLQSUHFHGLQJ7-wave
! PR-LQWHUYDOZLOOYDU\GHSHQGLQJRQWKHVLWHRIQHZLPSXOVH

A trial
!
!
!
!
!
!

F lutter VDZWRRWK
5K\WKPUHJXODU
5DWH~110bpm
456QRUPDOQDUURZ
P-ZDYHUHSODFHGZLWKEuried in multiple F (flutter) waves with 2:1 or 3:1 with QRS
P-ZDYHUDWHFDQEHXSWRESP
PR-LQWHUYDOLPPHDVXUDEOH

A trial
!
!
!
!
!
!

F ibrillation
5K\WKPirregularly irregular
5DWH100-160bpm
456QRUPDO (usually)
P-ZDYHnot distinguishable d/t fibrillation
P-ZDYHUDWHFDQEHXSWRESP
PR-LQWHUYDOLPPHDVXUDEOH

Many ectopic foci across atria causing very irregular conduction across the heart including ventricular irregularities

Ventricular T achycardia
! 5K\WKPregular
! 5DWHaESP
! 456ZLGHYHQWricular foci)
! P-ZDYHQRWVHHQ

Ectopic ventricular pacemaker foci generating irregular, rapid heart rhythm associated with poor C O

Ventricular F ibrillation
! 5K\WKPWRWDOO\LUUHJXODU
! 5DWHESP
! 456QRWUHFRJQL]DEOH
! P-ZDYHQRWVHHQ

Disorganized electrical signals from everywhere causing the ventricles to quiver and C O basically stops

C O R O N A R Y A R T E R Y D ISE ASE
x

C linical Presentation
! Silent ischemia, angina, unstable angina/MI and most extreme, sudden cardiac arrest/death
x E tiology of C A D
! A therosclerosis5)+\SHUWHQVLRQOLSLG'06PRNLQJDQGIDPLO\+[
! Coronary A rt. Spasm5)Japanese, and because its spasm, it can occur randomly, even w/o exertion
! E mboliUDUHO\FDXVHV&$'XVXDOO\IURPDYHJHWDWLRQZLWKHQGRFDUGLWLV
! Congenital-2% of pop; persistence of embryonic connections with medistinal vessels can cause CA-fistula
A T H E R OSC L E R OSIS
x Common Sites (in order)
1. Abdominal Aorta and Iliacs
2. Proximal Coronary Arteries
3. Thoracic, Femoral and Popliteal
4. Internal Carotid
5. Vertebral, Basilar and MCA
x Genesis of plaques
! LDL that has infiltrated into subendothelium (d/t shear
stress from flowing blood) will be oxidized and eventually
LQJHVWHGE\PDFURSKDJHVIRUPLQJWKHIRDPFHOOVDQG
build up to form fatty streaks
! The oxidized LDL that is not yet phagocytosed will also
cause release of cytokines and inhibit NO production
! Stimulation and migration of vascular SM from the media
to the intima, is followed by prolif & laying down collagen
! VSM will also take up the oxidized LDL and make more foam cells
! The actual formation of the plaque is characterized by fibrous thickening of arterial wall that may calcify
! $VWKHDWKHURVFOHURWLFSODTXHDJHVLWDWWUDFWV7VDQG0DFs and contain cell-damaging substances in the cap
which will fibrose to avoid rupture, but those thDWDUHZHDNDUHULVNIRUUXSWXUH
! If it were to rupture, it can distort the vessel and/or trigger thrombi formation both of which can obstruct flow
x L ipid M etabolism
! 'LHWDU\FKROHVWHURODQG7*VHQWHULQFK\ORPLFURQHQWHUFLUFXODWLRQDQGUHOHDVHWKH7*LQto lipid cells via LPL
! The remnants of the chylomicrons go to the liver where its synthesized/packaged VLDL
! 7KH9/'/VLPLODUO\GRQDWHVPRUH7*VWRWLVVXHYLD/3/DQGWKHQEHFRPHUHJXODU/'/V
! LDL is taken into peripheral tissue & liver to supply cholesterol for membranes and steroids
! It can then be oxidized and uptaken by Macs and VSM to make atherosclerotic lesions
! The Liver also releases HDL to go and collect excess peripheral cholesterol and bring it back to the liver for
metablolism in an effort to maintain low cholesterol levels in the plasma and peripheral tissue
x Nutritional Aspects
! Homocysteine
supplies H2O2 ZKLFKZLOOR[LGL]H/'/VWKXVK\SHUKRPRF\VWHLQHHPLDLVDVVRFZDWKHURVFOHURVLV
V-6, B-12 & Folic acid can help metabolize homocysteine so supplementing them can /'/R[LGDWLRQ
-carotene is an antioxidant (like the V6, B12, F A) and can also be used to help L D L oxidation
! Fat Intake
5HGXFLQJ08)$DQG38)$DQG2PHJD-)DWW\$FLGVFDQDOVRKHOSFKROHVWHURO/'/
x H ypertension
! (OHYDWHG%3ZLOOVKHDUVWUHVVRQHQGRWKHOLXPDQG/'/LQILOWUDWLRQLQWRVXEHQGRWKHOLXPWRIRUPDWKHUVFOHURVLV
x C linical M anifestation of A therosclerosis
! Angina, MI, thrombotic strokes, AAA, renal HTN
vascular insufficiency to legs and claudications
! Thrombi/clots can also completely stop blood supply
causing gangrene and ischemic sections of the bowel
C O R O N A R Y A R T E R I ES
x A natomy
! R C A and L C A arise at aortic roof just below the orifice
of the aortic valve
! L C A: quickly divides into L A D and L C X
! L A D: follows anterior interventricular groove and may
continue over the apex

Coronary Perfusion/ Supply

!"#$%&'()"*+*,-&&./012&
LAD
x A nterior free wall of L V
x A nterior part of septum
x A pex
LCX
x Most of lateral free wall of
LV
RCA
x Right ventricle
x L arge part of inferior wall
x Posterior wall of L V
x Posterior part of septum
x SA N O D E , A V N O D E

x
x

x
x
x

3-4%&'()"*+*,-&.5012&
LAD
x
x
LCX
x
x
x
x
RCA
x
x
x

Anterior free wall of LV

Anterior part of septum
Most of lateral free wall of
LV
M ajor part of inferior wall
Posterior wall of L V
A pex
Right ventricle
Posterior part of septum
SA NODE, AV NODE

Physiology of Coronary Circulation

! Mainly controlled by local metabolic autoregulation with very little sympathetic input or vasoconstriction
! During exercise, lactate is a vital substrate for myocardial metabolism
M yocardial Metabolism
! $FFRXQWVIRURIWKHERG\V22-consumption at rest
! $73IURP)$-oxidation & 30% from CHO-oxidation
! The myocardium cant store O 2 well and is very bad at anaerobic metabolism, thus needs constant O 2 supply
! ,6&+(0,$2FFXUVZ O2 demand and an DEVROXWH O2 supply (due to atherosclerosis or spasm)
A therosclerosis and C A D
! Is the most common cause of angina and MI and will build up at high shear sites like bifurcations
! Ruptured/Fissured plaques can cause platelet aggregation & transient occlusion for 10-20min = unstable angina
! Additionally, platelets will release TXA2 or Serotonin causing vasoconstriction to worsen blood flow
! A deep arterial insult can cause a fixed thrombus cutting off total blood supply, resulting in an A M I
! ,16+257SODWHOHWDggregation, cytokine mediated reactions that ultimately form an atheroma and occlusion
W hat happens when blood supply stops?
! Within 60s, myocardial O2 tension falls to zero causing rapid shift to anaerobic metab and lactic acid production
! This causes a dysfunction in contract/relaxation and will result in irreversible injury w/in 40-60 min w/o O2
I r reversible Injiry
! 8OWLPDWHO\GXHWRVHYHUH$73GHSOHWLRQ>&D2+], lactid acidosis and free radical damage
! There will be mitochondrial swelling, cell membrane damage and a marked depletion of glucose
C linical M anifestation of C A D
! CP, SOB, Shock , Tachy -or-Bradycardia, N/V and there will also be an audible S4 (fill noncompliant/stiff ventricle)
! CHEST PAIN
Mediated by sympathetic T1-5 and converge with other structures giving radiation to other body parts
Actual nerve trigger is adenosineWKXVEORFNLQJDGHQRVLQHUHFHSWRUDPLQRSK\OOLQH DQJLQDOSDLQ
! ISCHEMIA W/O PAIN
Lack of pain can be due to loss of afferents d/t peripheral neuropathy or a transplanted heart
7UDQVLHQWUHGXFWLRQLQSHUIXVLRQRUVLPSO\DYDULDWLRQLQWKHSDWLHQWVSDLQ threshold
! SHORTNESS OF BREATH
Systolic dysfunction will cause significant pulmonary congestion leading to SOB
! AUDIBLE S4
Diastolic dysfunction will result in myocardial stiffness where S4 is due to filling of stiff ventricle

A N G I N A P E C T O R IS in C A D
x Typically includes substernal CP, aggrevated by exertion/stress and relieved by nitro or rest
x Atypical Angina will lack one of these three primary characteristics
x Complaints of CP withOUT the other two is usually not cardiac, and is of lung, esophagus or chest wall
x ';V\PSWRPV(.*6WUHVV7HVW(FKRDQG$QJLRJUDP
x (.*'XULQJ$WWDFN67-GHSUHVVLRQ7ZDYHGLVFRUGDQWZ4565-height
x EKG Post-$WWDFNDUHQRUPDOUHPDLQGHU show old infarct, hypertrophy & ST and Twave abnormalities

STRESS TESTING
! done w/EKG; (-) usually rules out angina, (+) suggests coronary ischemia but may need more tests
x ANGIOGRAM
! is gold standard for CAD diagnosis but not always necessary; indicated to locate/assess lesion severity
! obstruction is physiologically significant when there is > 70% decrease in diameter
A C U T E C O R O N A R Y SY N D R O M ES A CS
x Unstable A ngina
! Chest Pain occurs at rest, lasting >20min with previous episode but different freq, severity or provocation
! Precipitating Factors
Inappropriate tachycardia: anemia, fever, hypoxia, tachyarrhythmias or thyrotoxicosis
Increased Afterload: Aortic stenosis or LVH
Increased Preload&2RUFKDPEHUGLODWDWLRQ
Inotropic States: sympathomimetic drugs and cocaine intoxication
! Pathogenesis
Plaque disruption leads to acute thrombosis
Vasoconstriction also manifests, caused by TXA2 and Serotonin released from platelets
! Diagnosis
C haracteristic CP and E K G shows ST-depression and symmetric T-inversion during episodes of CP
x V ariant A ngina 3ULQ]PHWDOV$QJLQD
! &DXVHGE\FRURQDU\DUWHU\VSDVPVRIWHQDIIHFWLQJ\RXQJVPRNHUVZRRWKHUVLJQLJLFDQW5)V
! There will be ST-elevation with intermittent, repetitive CP at REST in the AM and relieved with NO
! 3WVZLOODOVRKDYHRWKHUYDVRVSDVPLFV[V[OLNHPLJUDLQHDQG5H\QDXGV3KHQRPHQRQ
! Most attacks resolve WITHOUT infarctions and of course, angiogram should be (-) for a block
x Non-ST-E levation M I (NST E M I)
! Absent acute ST-elevation and Q-wave
! May also be non-spesific changes like ST-depression, T-inversion or both
! Without the elevation, means that it is SUB-ENDOCARDIAL infarction
! There will be myocardial necrosis noted by the biomarkers and the symptoms are the same as STEMI
x ST-E levation M I (ST E M I)
! W H O C riteria 2 of 3(1)Hx of CP for >20 min (2)changes in EKG (3) rise and fall of biomarkers
! C auses For Acute M I
Most common is atherosclerosis
Others include emboli from endocarditis, mural thrombi, inflammatory processes, radiation induced
coronary stenosis, cocaine abuse or neoplasms
5DUHO\FDXVHGE\5$6/(+XUOWHUV6\QGURPHDQGKRPRF\VWHLQXULD
! Physical E xam In ST E M I
5HVWOHVVDJLWDWHGFOHQFKHGZLWK+5DQG55
Low grade fever (nonspecific response to myocardial necrosis)
Sx/Sx of Hypoperfusion: cold, clammy, weak pulse, ashen,
Sx/Sx of Heart Failure: JVD, rales, LV-heave and may have S3 &S4 gallops/murmurs
B radycardia
x Inferior wall MI, AV node ischemia & conduction deficits
x Note that inferior wall MI can also cause Vagus nerve dysfunction
x SA-node dysfunction is rare d/t protective dual blood from RCA and LCA
T achycardia'XHWRHOHYDWHGFDWHFKRODPLQHVLQUHVSRQVHWRWKH&2
Nausea/VomitingActivation of vagus nerve (above) with inferior wall MI

E V I D E N C E F O R SU G G EST I N G A N M I
x E K G C hanges
! A normal, prior to MI
! B during acute stage with marked ST-elevation
! C several hours post MI, pathological Q-wave, decreasing ST-elevation and inverted T-wave
! D after several days post MI, only the pathological Q-wave persists, indicating an old infarct

x
x
x
x
x
x
x

Inferior (diaphragmatic) wall:

! Lead II, III & aVF !"#
A nterior wall of L V :
! Lead I, aVL, V4-V6 $#%
L ateral & Posterior wall of L V :
! V5, V6
Right V entricle:
! V1, V2 & sometimes V3
Septal wall :
! V3, V4 with or without reciprocal changes in II, III & aVF $#%
A nterioseptal (R V + Septum)
! V1, V2, V3, V4 !"#&'&$#%
Biomar kers in an Acute M I

U N D E R L Y I N G D ISO R D E RS/C O M P L I C A T I O NS I N P OST-A M I

x H ypertension and T achyUHSUHVHQWVV\PSDWKHWLFVZLWK$QWHULRU0,
x H ypO tension and B radyUHSUHVHQWVYDJDOWRQHZLWK3RVWHULRU0,
x Pericardial F riction RubPost MI Pericarditis 'UHVVOHUV6\QGURPHUHSUHVHQWV3RVWHULRU0,
x J V D, H yp O tension, S3, S4 and clear lungsRV failure thus RV Infarction
x H arsh Systolic M urmur, Palpable thrill at L-sternal borderVentricular Septal Rupture with Septal MI
x F ast, Slow or I r regular Pulse Atrial or Ventricular arrhythmias/Heart Block
x Systolic M V M urmurPapillary Muscle Rupture
x S4 G allopdecreased LV compliance/stiffening
x S3 G allop, Rales and Pulsus A lternanasLV Systolic dysfunction (C H F with >25% dysfunction)
x H ypO tension, cool, pale, clammy, A MS and O liguria Cardiogenic Shock
C O N D I T I O NS T H A T C A USE SH O C K I N A M I
x /$'2FFXOXVLRQVHYHUH/9G\VIXQFWLRQZ/&$QHFURVLVRIVHSWXPDQGLV anterior free wall rupture
x /&;2FFXOVLRQUXSWXUHRI/9ODWHUDOIUHHZDOORUUXSWXUHRISDSLOODU\PXVFOHVFDusing MR)
x Rupture of either Lateral or Anterior Free wall will cause pericardial effusion and tamponade
()*+,&-./0.-1&23&45267-897:&09;;.1&07<1;&/:761&=>?&875;&@2;0>#AB&

V A L V U L A R H E A R T D ISE ASE
H E A R T SO U N DS
x
x
x

S1
Signals the beginning of
ventricular systole
Mitral & tricuspid valve
closure
Loudest over apex

Loud S1
Mitral
Stenosis
Short PR
interval
Tachycardia
Hyperdynamic
state

Soft S1
Mitral
Regurg
Long PR
Interval
Poor
systolic
function
LBBB

S2
Closure of aortic & pulmonic
valve
x Best heart at the left upper sternal
border
x A2 is louder
x Normal Split 2 sounds during
inspiration, 1 sound during
expiration
Loud S2
Soft S2
Systemic
Aortic
HTN ($
stenosis
3+713 Pulmonic
ASD
stenosis
Hyperdynamic Aortic regurg
states
Aortic
Dilation
Normal Split 2 sounds during
inspiration, 1 sound during expiration
Wide splitting
- P2 is delayed RBBB
- Fixed splitting
- Respiration induced changes in
filling are similar in both
ventricles ASD
x

H E A R T M U R M U RS
x Classification
! Systolic b/w S1 and S2
! Diastolic b/w S2 and S1
! Continuous
! Pay attention to:
Timing & Duration
Intensity (I-VI)
Quality (blowing, harsh, rumble)
Radiation (neck, axilla or back)

x
x

S3
Early diastole
Corresponds to the
end of the rapid filling
phase of ventricular
diastole

Low frequency sound

Caused by interplay
b/t ventricular filling
& compliance

Pathological S3
x High LV filling
pressure
x &2
x Dilated poorly
contractile LV
x CHF

S4
Dull, low frequency

Precedes S1

Best heard over apex

Forceful atrial
contraction to fill a
non-compliant or stiff
ventricle

Coronary artery
disease

S4 disappears with
afib

A O R T I C ST E N OSIS
! C auses
&RQJHQLWDOXVXDOO\\RXQJHUWKDQ
5KHXPDWLFEZ-70and often accompanied AR, MS
'HJHQHUDWLYHROGHUWKDQDQGPRUHSUHYDOHQt with DM and hypercholesterolemia
! Pathogenesis
Abnormal flow thru the valve causes fibrosis and calcification eventually becoming stenosed
Normal opening is ~4cm 2 and stenosed it is often <0.8cm 2 causing the aortic-LV gradient to exceed
150mmHg at which point the pt will become symptomatic
Resistance from the narrowing ZLOODIWHUORDG/9SUHVVXUHDQGFDXVHHYHQWXDO
C O N C E N T R I C H Y P E R T R O P H Y RIWKH/9UHVXOWLQJLQFRPSOLDQFHDQGVLJQLILFDQW('3
! C hest Pain
Increased O2 demand from hypertrophy and decreased supply d/t coronary compression (and CAD)
May develop coronary obstruction from calcium emboli thrown from stenotic valve
! Syncope
&2GWIL[HGREVWUXFWLRQWRRXWIORZ
Transient atrial arrhythmias ZDWULDOILOOLQJDQGYHQWULFXODUDUUK\WKPLDVDULVLQJIURm ventricles)
! CHF
LVH backs into lungs, backs further into lungs and even further to right heart to cause RVF
Note the eventual LV dilation and contractile failure will also back all the way back to cause RVF
! Physical E xam
C arotid PulsesParvus et Tardus: they will both be decreased & late compared to apical impulse
M idsystolic murmur, loudest at apex, with radiation to sterna notch and neck
H igh pitched aortic ejection heard beginning just after S1 and S4 is often present as well

A O R T I C R E G U R G I T A T I O N/I NSU F F I C I E N C Y
! C auses
VALVULAR(QGRFDUGLWLV5KHXPDWLF'LVHDVH$QN6SRQGDQG&RQJHQLWDO
AORTIC
x Aortic aneurism or dissection
x Congenital CT disorders: Marfans, Ethler-Danlos & OI
x Inflammatory: aortitis (takayasu) syphilis, Ank Spond, RA, SLE
! Pathogenesis
A valvular cusp abnormality will progress to aortic dilatation, inflammation and eventual aortic tear
with loss of commissural support
5HJXUJZLOOYROXPHORDGRQWKH/9FDXVLQJ('9DQGSUHVVXUHHORQJDWLQJVDUFRPHUHWR/9YROXPH
The sarcomeres are added in SERIES E C C E N T R I C H Y P E R T R O P H Y, causing HUGE LV volumes
N O T E : OHDNZLOO('9WRV\VWROLFSUHVV %87(69WRGLDVWROLFSUHVV = Increased Pulse Pressure
! C linical
Pt will remain asymptomatic as long as compensation is still able
Upon failure of compensatory mechanisms there will be SOB and hypOtension with CV-collapse
! Physical E xam
+\SHUG\QDPLF3RXQGLQJ$UWHULDO3XOVHVVXGGHQULVHDQGVXGGHQIDOORISXOVHVGWZLGHSXOVHSUHVVXUH
x Upon palpation in most places; rhythmic pulseation of uvula, nail bed pulses and head bobbing
$SLFDO,PSXOVHODUJHO\GLVSODFHVGWUHPRGHOLQJDQGIRUFHIXOFRQWUDFWLRQ
6LVVRIWRUDEVHQWEFPLWUDOYDOYHFORVHVHDUO\IURPWKHUHJXUJDQG/93
! M urmurs (3)
Early diastolic due to regurg flow, best along left sterna border
Diastolic rumble from regurg flow on the mitral valve SURGXFLQJIXQFWLRQDOVWHQRVLV Austin Flint
Crecendo-decrecendo systolic murmur d/t increased SV across aortic valve (L-sternal border)

M I T R A L ST E N OSIS
! C auses
5KHXPDWLFPRVWFRPPRQnarrow from fusion and thick commussures, cusps and chordate tendineae
&DOFLILFXVXDOO\ZLOOFDXVHUHJXUJEXWFDQDOVRFDXVHVWHQRVLV
&RQJHQLWDOSUHVHQWLQLQIDQF\FKLOGKRRG
&ROODJHQYDVFXODUUDUHFDXVHVLQFOXGH6/( 5$
! Pathogenesis
Scarring and fusion of valve apparatus will decrease the opening from the normal 4-6cm2
Mild : < 2.5 cm2 and mild symptoms
Moderate: > 1.5 cm2 and usually NO symptoms at REST
Severe: < 1.0 cm2 FDXVLQJ/$3SXOPRQDU\YHQRXVSUHVVXUHUHVXOWLQJLQG\VSQHDGWSXOPFRQJHVWLRQ
! Pathophysiology
YROXPHDQGSUHVVXUHLQOHIWDWULDEDFNVLQWROXQJVDQGEDFNVIXUWKHUWR5-heart causing HF
! C linical
Dyspnea, Orthopnea, hemoptysis and fatigue
3DOSDWLRQVDQGWDFK\FDUGLD/$VL]HLQFUHDVHVFKDQFHRIDWULDODUUK\WKPLDV
Hoarsness of voice, because the /$JURZVDQGKLWV5HFXUUHQW/DU\QJHDO2UWKQHUV6\QGURPH
! Physical E xam
H E ART:
x Late diastolic, low pitched murmur
x Will also have diastolic rumble d/t turbulent flow thru stenotic valve
x may sometimes have an opening snap in early diastole; ONLY when pts leaflets are still mobile
L U N GS
x %LEDVLODUUDOHVEFRISXOPRQDU\FDSLOODU\SUHVVXUHFDXVLQJHGHPDLQDOYHROL
! A trial F ibrillation
A common arrhythmia w/increased atrial size, can form and throw clots (20% of pts)
7KHVHFDQFDXVHVWURNH7,$VDQGVXGGHQYLsion loss
M I TRA L RE GURGI T A TI O N
! E tiologyPRVWFRPPRQO\DSURODSVHRIWKHYDOYHIROORZHGE\FRURQDU\DUWHU\GLVHDVH
! C auses
Ruptured Chordae tendinae (infective endocarditis, Trauma and Acute rheumatic fever)
Ruptured/Dysfunctional papillary muscles (ischemia, MI and abscesses)
Perforated leaflets (infective endocarditis)
Inflammatory (rheumatic heart disease and collagen vascular disease)
Degenerative (myxomatous degeneration of leaflets or calcification of the annulus)
! Pathophysiology
MV fails to close alloZLQJILOOLQJDQGZLOOUHJXUJLQWRDWULDXSRQV\VWROH
Both atria and ventricle will enlarge to accommodate volume overloads
In acute MR, there has not yet been compensatory chamber expansion so it will quickly affect lungs
The developing loss of a pressure gradient b/w chambers causes a systolic murmur to manifest
! C linical
C hronic Symptoms will also develop gradually and include, dyspnea, fatigue and palpations
Acute,QFOXGHWKRVHFRQVLVWHQWZLWK/+)OLNH62%RUWKRSQHDDQGVKRFN
! Physical
Laterally displaced Hyperdynamic Apical Impulse
x Displaced due to the hypertrophy
x Hyperdynamic due to low pressure atria accepting ejection from ventricle
x NOTE: neither will happen in acute onset Mitral Regurg
Holosystolic/Pansystolic Murmur
x 7KURXJKRXWV\VWROHIURP66DQGZLWKHYHQLQWHQVLW\WKURXJKRXWEHVWDWDSH[D[LOOD
0XIIOHG6 6GXHWRPDUNHGPXUPXUWKDWREVFXUHVWKHPERWK
/RXG6LQVHYHUH05ZLWKKHDUWIDLOXUH
M I T R A L V A L V E PR O L A PSE M VP
! E tiologyFRQJHQLWDOPDUIDQV5+'RUVHTXHODHRI0, XVXDOO\
! PathYDOYHOHDIOHWKDVUHGXQGDQWWLVVXHDQGZLOOEDOORRQLQWR/$PDNLQJDFOLFNLQJVRXQG
! C linicalSDOSDWLRQVDUUK\WKPLDVDQGDW\SLFDO&3EXW0$<%(DV\PSWRPDWLF
! PhysicalWKLQ\RXQJIHPDOHPLG-systolic click and late systolic murmur; EKG may have ST-T changes

T E C H N I Q U ES I N D I F F E R E N T I A L D I A G N OSIS O F M U R M U RS
x Respiration
! Right sided murmurs tend to increase in intensity with inspiration and left murmurs are louder with expiration
! Remember the pneumonoic 5,/(
x V alsalva maneuver
! Most will decrease in length and intensity with valsalva EXCEPT FOR:
Systolic murmurs of hypertrophic cardiomyopathies (HCM)
Mitral Valve Prolapse
x H andgrip
! Mitral Regurg, Aortic Regurg and VSD will increase due to increased afterload on LV
x T ransient A rterial Occulsion
! Inflate cuffs oQERWKDUPVWRDIWHUORDGRQ/9WRLQFUHDVHLQWHQVLW\RI0LWUDO5HJXUJ$RUWLF5HJXUJDQG96'
x Positional C hanges
! 6WDQGLQJPRVWZLOOGLPLQLVKGXHWRSUHORDGUHWXUQ(;&(37+&0DQG093ZKLFKERWKEHFRPH/RXGHU
! 6TXDWWLQJPRVWZLOOJHWORXGHUGXHWRSUHORDG/return EXCEPT HCM and MVP which both become Softer

H Y PE R T E NSI O N
x

x
x
x

Definition
! Greater than 140/90 in adults on at least THREE CONSECUTIVE visits
! 8QNQRZQ(VVHQWLDO3ULPDU\a
! &DXVHLVNQRZQRWKHUGLVHDVH6Hcondary
Renin-A ngiotensin-A ldosterone System

Pathogenesis of H T N
! Remember that !"#$%$&#'$($)*
! 0HFKDQLVPVWR%3LQFOXGH
735&29ROXPH 9LVFRVLW\
Common C auses of H ypertension
! Coarctation
narrowing just distal to L-VXEFODYLDQFDXVLQJDQ%3RIDUPVDQGKHDGEXW%3LQORZHUERG\
there will be marked differences in radial and femoral pulses (diagnostic)
:LOOFDXVHUHQDOIORZDQG5$6VXUJLFDOUHPRYDORIFRQVWULFWLRQLVFXUDWLYH
! Salt Sensitivity
The majority of salt sensitive ppl (more % in $$ZLOOKDYH+71DGYLVHGLHWDU\VDOWV
! Renal C ause of H T N
Constriction of one/both renal arteries
Can be neoplasm of JG-cells
8UHWHUDOREVWUXFWLRQZLOOUHQDOLQWHUVWLWLDOSUHVVXUHDQGUHQLQUHOHDVH
$FXWH&KURQLFJORPHUXODRQHSKULWLVFDQQRWH[FUHWHVDOWWKXVLWVUHWDLQHGDORQJZZDWHUYROXPH%3
/LGGOHV6\QGURPH$'-JHQHWLFLQKHULWDQFHZKHUHWKHUHLV(1D&-FKDQQHOFDXVHV1D+-retention
! A drenal G land Disorders
-K\GUR[\ODVH'HILFLHQF\EORFNVZKROHULJKWVLGH21/<PDNHValdosterone
Cushings Syndrome
Pheochromocytoma
&RQQV6\QGURPHDGUHQDOWXPRU
! M etabolic Syndrome
&20%,1$7,212)'LDEHWHV+71&HQWUDO2EHVLW\'HFUHDVHG+'/DQG,QFUHDVHG7ULJO\FHULGHV
Possible HTN mechanism: LQVXOLQUHVLVWDQFHZLOOLQVXOLQUHOHDVHVWLPXODWLQJV\PSDWKHWLFV = HTN?
C linical Presentation
! Often asymptomatic; discovered with routine check-up/screening
! May present with: MI, CHF, Strokes, Hypertensive encephalopathy (confustion, seizures) and Renal Failure
Physical E xam
! Check for Hypertensive retinopathy (fundoscopy), LVH, Renal Artery Bruits and Orthostatics
C ardiac & V ascular F unction

SH O C K
x
x

Definition,QDGHTXDWHWLVVXHSHUIXVLRQGXHWRDUHODWLYHRUDEVROXWHGHFUHDVHLQ&2
Four T ypes+\SRYROHPLF'LVWULEXWLYH&DUGLRJHQLFDQG2EVWUXFWLYH

H Y P O V O L E M I C SH O C K
x Conditions+HPRUUKDJH7UDXPD6XUJHU\%XUQVDQGRWKHU0DVVLYH)OXLG/RVVHVVHYHUH9RPLWLQJRU'LDUUKHD
x Physical
! Cool, clammy pale skin, with weak, thread pulses and marked decrease in Urine output
! Lactic Acidosis (rises from 1mmol to >9mmol/L) depresses myocardium and vascular responsiveness to
catecholamines which may cause coma
x Compensatory Response to H ypovolemia
! 9DVRFRQVWULFWLRQ7DFK\FDUGLD7DFK\SQHDJOXFRFRUWLFRLGVFRUWLVROVWUHVVKRUPRQH$'+5$$6
! (32DQGV\QWKHVLVRI33VZLll increase as well as movement of interstitial fluid into capillaries.
! Baroresponse
Stretch in carotid sinus and arch will increase firing via CN IX & X to cardiovascular center in brain
H Y P O V O L E M AZLOOKDYH firing to the brain centers that will trigger the following response
x 6\PSDWKHWLF 3DUDV\PSDWKHWLFVWRKHDUW !" & #$%&'()&*+*&, = #- = ./0
x 6\PSDWKHWLFVWR9HLQVZLOO'1&2'% and #- to ./0
x 6\PSDWKHWLFVWRArteries will 3(4$)$%4&'*)& to 50" and ./0
! Neurohormonal
Use Angiotensin, Epi/NE, ADH, ACTH and Aldosterone
R A AS
x WULJJHUHGE\UHQDOSHUIXVLRQZLOO1D+ & H22UHWHQWLRQWRYROXPH
V ASO PR ESSI N/A D H
x WULJJHUHGE\%3EDURUHFHSWRU DQGRVPRODULW\RIEORRGZLOOK\SRWKDODPXVWR$'+UHOHDVH
from Posterior Pituitary
x ADH will cause vasocoQVWULFWLRQDVZHOODV1D+ & H2O retention
! V asoconstriction
Is generalized and spares brain and heart only
Renal vasoconstriction ZLOO*)5DQGFDXVHDFFXPXODWLRQRIQLWURJHQRXVZDVWHA zotemia)
Prolonged HTN will cause renal tubular damage and can lead to acute renal failure
! T achypnea
$%3ZLOO5%&FRXQWDQGVWLPXODWHFKHPRUHFHSWRUV WKDWVLJQDOUHVSLUDWRU\FHQWHUWR55
55ZLOOFDXVHWKRUDFLFSXPSLQJWRKHOSZLWKYHQRXVUHWXUQDQGLPSURYH&2
6WLPXODWLRQRIWKHUHVSLUDWRU\FHQWHUVZLOODOVRFDXVHYDVRconstrictor discharge
x C rush Syndrome
! Trauma pts with extensive skeletal muscle damage will release free radicals causing further tissue destruction
! Increased Ca2+ in damaged cells can reach toxic levels and large amts of K+ will also enter circulation
! M yoglobinuria will worsen renal failure
x Refractory Shock
! Persistent shock for hours where the vasculature loses its responsiveness to vasopressors
! Volume may return to normal but C O remains depressed
! Precapillary sphincters will relax but the postcapillary sphincters remain constricted so blood sits in the bed
! Cerebral ischemia depresses vasomotor and cardiogenic outflow causing %3WKXVPDNLQJVKRFNZRUVH
x Acute Respiratory Distress Syndrome
! Capillary endothelial cell damage and damage to alveolar epithelium will release cytokines
! This sequence may lead to ARDS and is a major contributing factor to the H I G H M O R T A L I T Y O F SH O C K

D IST R I B U T I V E SH O C K
x Commonly seen in anaphylaxis, sepsis and neurogenic syncope
x Although the major Sx/Sx are similar to hypovolemia, the major issue here is V ASO D I L A T I O N
! Vasodilation in contrast will cause warm & dry skin compared to the cool, clammy skin in hypovolemia
x Septic Shock
! Most common cause of death in ICU pts
! Hypoperfusion from loss of plasma into tissues WKLUGVSDFLQJ excess NO-synthesis and vasodilation
! C ardiac Depression due to toxins
! Eventual global cellular hypoxia, lactic acidosis and MOF
C A R D I O G E N I C SH O C K
x Will be seen in 10% of Myocardial Infarction, CHF and Arrhythmias
x Those who enter into C ardiogenic shock have up to 90% mortality
x Pathogenesis
! Impaired pumping to body and especially to myocardial cells
! :LOOFDXVHFRQJHVWLRQLQSHULSKHU\DQGOXQJVFRQJHVWLRQVKRFN
x Symptoms
! Identical to hypovolemia P L US pulmonary and peripheral edema/congestion
O BST R U C T I V E SH O C K
x Seen with PE, Tension Pneumo, Pericardial Tamponade and Cardiac Tumors
x Pericardial T amponade
! Sudden filling of pericardial space with fluid
! Causes sudden onset SOB and Becks T riad:
H ypotension
E levated J VP
M uffled H eart Sounds
! May also have Pulsus Paradoxusdrop in systolic BP >10mm Hg upon inspiration (normal is 5mmHg)
! SHULFDUGLDOSUHVVXUHZLOOQRWDOORZILOOLQJRIWKHKHDUWDQGDWULDZLOOFROODSVH
! J V PZLOORIFRXUVHLQFUHDVHDVWKHUHLVQRSODFHIRUWKHPWRGUDLQEXWWKH\GHVFHQWGXULQJYHntricular
contraction may be seen as the emptying of the ventricle can give SOME room for drainage
! E K Gwill have very low voltage evident by small amplitude in QRS-complex

!"#$%&'()&*+
COUGH 1
x

DefinitionIRUHFHIXOH[SXOVLRQRIDLUIURPOXQJVLQLWLDWHGE\LUULWDWLRQRIFRXJKUHFHSWRUVPRVWO\RIXSSHUORZHU57
but also in pericardium, esophagus, diaphragm and stomach
! Acute < 3wks
! Subacute 3-8 wks
! Chronic >8wks
DifferentialsLQFOXGHDVWKPD&23'7%SRVWQDVDOGULS*(5'%URQFKLWLV3QHXPRQLD&DQFHUDQGIRUHLJQREMHFW

LUNG C ANC ER
x

Definition
! uncontrolled growth of malignancy cells in one/both lungs & trachea-bronchial tree
! often arise from protective or ciliated cells of the bronchial epithelium d/t
! repeated carcinogenic insults FDXVHLQFUHDVHGUHSOLFDWLRQ+\SHUSODVLD'\VSODVLD&DUFLQRPDLQ6LWX
E PI
! .QHZ\UDQG.GHDWKV\UPRUHGHDWKVWKDQSURVWDWHEUHDVWFRORUHFWDOFRPELQHG
! DQG(many of which do NOT smoke!) -- and higher in AA vs. white
! \HDUVXUYLYDORIVPDOOFHOOVLVDQGDQGUHVSHFWLYH
Risk F actors
! Smoking (80% causative), Radiation, Env/Occupational (asbestos, radon, 2nd hand smoke
Second hand smoke causes 3000deaths/yr and has been classified as class A carcinogen
Tobacco works synergisticalO\H[$VEHVWRV55-5, w/RR-90)
! 2WKHU5)VLQFOXGHDUVHQLFnicke, mustard gas, chlorine and many others
C linical Presentation
! 90% are symptomatic at time of presentation
! Occasionally found on CXR as incidental when scanning for something unrelated
! '\VSQHD+HPRSW\VLV&3DQGDOVRUHPHPEHU9LUFKRZV1RGH
General Symptoms
! Pneumonia d/t obstruction
! Hiccups & Diaphragm paralysis (phrenic n)
! Pleural Effusion
! LOCAL GROWTH
Cough, Stridor, Local Wheezing, Dyspnea, Dysphagia, Hemoptysis
! LOCAL INVASIOIN
Hoarsness (recurrent laryngeal)
+RUQHUV6\QGURPH,QI&HUYLFDO*DQJSOXVORVVRIVZHDWLQJ
SVC Syndrome
Pancoast Tumor (apical tumor)
! INTRATHORACIC METASTASIS
Pericardial involvement causing effusion, tamponade or arrhythmias
Pleural involvement (~15%), dyspnea, cough, CP, effusion and paresis
Chest wall metastasis, ribs, vertebrae causing localized pain,
! DISTANT METASTASIS
A drenal and L ung (silent usually), Bone (pain & hypercalcemia) and B rain (seizures)
Paraneoplastic Syndromes
! SIADH will cause hyponatremia
! Cushing-Like Ectopic ACTH
! Lambert-Eaton Syndrome
! PTH-like Protein (squamous)
! Clubbing and Hypertrophic Osteoarthropathy
! Many other neurologic-based syndromes
Diagnosis
! H/P
! Diagnostic tests
CXR and Biopsy (bronchoscopy, FNA and rarely surgery for peripheral)
! Staging tests
CT, bone scan, BM-aspiration and PET scan all i mportant in guiding tretatment

x
x

Predicting M alignancy pulmonary nodules

! Radiologic &KDUDFWHULVWLFVVPDOOGLDPHWHU!FPZLWKVSLFXODWRLQDQGORFDWLRQEHLQJPRUHLQXSSHUOREH
! &OLQLFDO&KDUDFWHULVWLFVROGHUWKDQZLWKVPRNLQJKLVWRU\ZKLVWRU\RIRWKHUFDQFHUV
Predicting Benign pulmonary nodules
! Younger than 35, absent of risk factors (smoking/occupational) and a mass of small size (< 2cm)
! Doubling time being very slow (>400d) or very fast (<20d) is likely not cancer medium is often malignant
! Specific patterns of calcification like being diffuse, central, laminated or popcorn like all point to benign lesions
Diagnostic O ptions
! Firstly, find old films and evaluate any specific changes noted from older scans
! %URQFKRVFRS\EXWUHPHPEHULWVQRWJRRGIRUVPDOOQRGXOHVWKDWDUHYHU\ODWHUDOSDVWPLGFODYLFXODU
! )1$%[6XUJPXVWPHHt certain criteria before cutting and poking
! :DWFKIXOZDLWLQJLI\RXVXVSHFWLWVEHQLJQZDWFKIRU-years and if no growth then malignancy is unlikely
! STAGING RECCOMENDATINO
Solitary mass greater than 1cm with (+)PET go for surg but (-)PET monitory very close; surg w/growth

BRONC H O G ENIC C ARCINO M A

Most arise from bronchial epithelium or near the hilus with nearly all of them being associated with smoking. They are all ve ry aggressive and
widely metastasize to the liver (40%), brain (20%) and bone (20%).

C lassification
! Non-small cell carcinoma (70-75%)
Squamous cell carcinoma (30%)
x Usually central and often obstructing with the best survival of lung neoplasms
Adenocarcinoma (30%)
x Peripheral with local invasion and metastasis and not always associated with smoking
Large cell carcinoma (10-15%)
x Becoming les prevalent as new stains allow more cells to classify as squamous/adenocarcinoma
! Small Cell L ung C arcinoma (25%)
Tends to be fast growing and usually central (S & S is S) with a survival less than 1-yr WITH treatment
! Combined Patterns (10%)
Staging
! Critical for determining treatment
! Usually done w/CT and depends on LN, size and distant metastasis (TNM)
! SC L C
/LPLWHGGLVHDVHFRQILQHGWRRQHVLGHDQGUHJLRQDO/1
([WHQVLYHGLVHDVHDOORWKHUGLVHDVHHQFRPSDVVLng ~70% of pts
! NSC L C
Stage I single resectable mass with NO LN involvement
Stage I I single mass with ipsilateral LNs
Stage I I I invading important structures and/or contralateral LN involvement
Stage I V with metastasis

C OUG H II

Responsible for 30Million Dr visits/year and the most common symptom for which outpatient care is sought

x
x

Post-Nasal Drip
! Causes can be allergic/nonallergic, vasomotor rhinitis, acute pharyngitis and sinusitis
! Stimulation of cough receptor w/mucus
! Symptoms include frequent nasal discharge down back of throat and frequent throat clearing
! 3(FREEOHVWRQHDSSHDUDQFHWRQDVRSKDU\QJHDOPXFRVDDQGSUHVHQFHRIVHFUHWLRQV
! ';RQO\GHILQLWLYHZLWKUHVSRQVHWRWUHDWPHQW
G E R-Cough
! Stimulation of cough recetors in the URT or aspiration of gastric contents stimulating LRT
! ';XVXDOO\D-hr esophageal pH study being optimal for diagnosis
Normal Defense vs. Pulmonary Infections
! Gag/Cough Reflex, MC-HOHYDWRU&HOOXODUGHIHQVHVPDFVSPQVDQGO\PSKRDQG([WUDFHOOXODUPHGLDWRUV

PA T H O G E N ESIS O F PU L M O N A R Y I N F E C T I O N
x
x
x

Step-1: E ntry
! Aspiration, inhalation, inoculation (contamin equip), colonization (COPD), hematogenous or direct (adj abscess)
! Cellular & mechanical mechanisms overcome by evolving orgamisms, massive inoculation or IC pts
Step-2: Replication and Spread
! Have now escaped MC-defenses and their virulence factors will aid in replication (inoculation count is critical)
! 9LUXOHQFHIDFWRUVLQFOXGHWKHLUDGKHUHQFHIDFWRUVFHOOXODUWR[LQVDQG301NLOOLQJFDSDFLW\
Step-3: Establishing T issue Damage
! Direct damage (cytopathic effects)
! Self-'HIHQVHV\VWHPVDFXWHLQIODPPDWLRQEDFWHULDORU&HOOXODULPPXQHUHVSRQVHYLUDOIXQJDOP\FREDFWHULD

A C U T E B R O N C H I T IS
x
x
x

C auses
! 90% are caused by viruses but are treated w/Abx 70% of the time! Should give Abx w/Pertussis ONLY!
Diagnosis/C riteria
! Acute is < 3weeks and may/may not have purulent sputum affecting 5% of adults, 90% of which seek care
Bordetella Pertussis W hooping Cough
! Remarkably contagious PRVWO\LQNLGVZLWK0 0EXWQRZKDVYDFFLQHWRSUHYHQWWKRXJKLQFLGHQFHLQ\UV
! In adults, its is more mild with paroxysmal cough lasting ~10wks
! C L I N I C A L C O U RSE
&DWDUUKDOSKDVHHDUO\FOLQLFDOO\LQGLVWLQJXLVKDEOHIURPYLUDO857LQIHFWLRQ
3DUR[\VPDOSKDVH-6wks w/paroxysmal or bursts of numerous rapid whooping coughs
&RQYDOHVFHQWSKDVHFRXJKJUDGXDOO\GHFUHDVHVDQGUHVROYHVRYHUDQDGGO-3 weeks
! D XFXOWXUHDQG3&5IURPSRVWHULRUQDUHVIRU B.pertussis

A C U T E B A C T E R I A L PN E U M O N I A
x
x
x

x
x
x

Two forms%URQFKRSQHXPRQLD having a patchy distribution and Lobar having a much more confluent distribution
Most CommonFDXVHGE\S.pneumoniae (pneumococcus) classically presenting as lobar pneumonia
F O U R ST A G ES O F L O B A R
! Stage-1: CongestionERJJ\HQJRUJHGDOYHRODUYHVVHOV
! Stage-2: Red Hepatizationlobe is ILOOHGZ301V 5%&VUHVXOWLQJLQOLYHU-OLNHVWDWH
! Stage-3: Gray Hepatization3DOHFRORUGWLQJHVWLRQRI5%&E\301V
! Stage-4: ResolutionVORZUHWXUQWRQRUPDORUQHDUQRUPDO
P A T H O G E N ESIS
! Aspiration resulting in oropharyngeal colonization can be silent (microaspiration) or obvious (emesis)
! Most common pathogens include S.pneumoniae, H .influenzae and anaerobes from emesis aspiration
! Hospital acquired usually are due to Pseudomonas & S.aureus
R IS K F A C T O RS
! Age, smoking, altered LOC (cant protect airway), uremia, malnutrition, IC, obstruction, Diabetes, COPD, CHF
C O M M UNI T Y A C Q UIRED
! Mostly affecting >65y/o and is the most common cause of death by infectious disease
N OSO C O M I A L
! By definition, if pneumonia develops w/in 72hrs of admission
! Usually due to aspiration, line infection, direct inoculation or foley
! &DXVHVP.aeruginosa and S.aureus
PN E U M O C O C C A L V A C C I N A T I O N
! 5HFRPPHQGHGIRU!DQG!\UVLIWKH\KDYHVRPHFKURQLFGLVHDVHKHDUWOXQJOLYHUGLDEHWHV&$
! Avoid in pregnancy or w/current febrile illness
! 50% have mild side effects: pain/redness

LEIGONELLA
x
x
x

80% due to L eigonella pneumophilia

Will have (-JUDPVWDLQIORUXUHVFHQWVSXWXP$EV&XOWXUHRQ&KDUFRDOaLeigonella Urinary Ag (93%)
D X+3&;5:%&KLJKORZEDQGVVSXWXPFXOture and TAP THE FLUID

INF LUEN Z A
x
x
x
x

Commonly causes epidemics and commonly missed diagnosis (40% miss)

Seasonal influence with abrupt onset of Sx that include
! high-fever (+100), nonproductive cough, chills/sweats, myalgia, sore throat, persistent malaise & photophobia
R F!QXUVLQJKRPHVFKURQLFSXOPRQDU\GLVHDVH&9'PHWDEROLFGLVHDVHUHQDOHWF,&ORQJWHUPDVSLULQLQ18 month olds and those in 2nd/3rd trimester of pregnancy
V A C CINA TIO N
! made w/chicken eggs and supposed to protect against anticipated strain of the current season
! Efficacy varies w/age, IC and the match to the actual strain of the season
! Works great with kids/teens as it stimulates high HA-inhibition Ab titers (Elderly are not as good, but still good)
! Prevents up to 80% of nursing home deaths thus CDC recommends admin to any high-risk exposure person

T U B E R C U L OSIS

An airborne communicable disease caused by inhalation of Mycobacterium tuberculosis. Note that simply exposing/inhaling the bug is considered a
TB-infection but without symptoms will not be classified as Tuberculosis

x
x
x
x
x
x
x

x
x

x
x

Use BCG to vaccinate and PPD to test for exposure

TB is a type-4 T-cell mediated delayed type reaction with classic caseating granulomas
M ycobacterium
! Classic bacterial pneumonia and once infected there is a lifetime risk of developing TB (reactivation AIDS)
T ransmission
! M.tuberculosis spread in airborne particles (droplet nuclei) thus close contact is highest risk
! Without symptoms, the person is NOT infectious
Pathogenesis
! 10% of infections develop into 7%DWVRPHSRLQW FHUWDLQFRQGLWLRQVZLOOSURJUHVVLRQUHDFWLYDWLRQWRGLVHDVH
! ,QFUHDVHGULVN+,9VXEVWDQFHDEXVHUHFHQWLQIHFWLRQ'06LOLFRVLVERG\ZHLJKW,&DQG+HDG1HFNFDQFHU
Common Sited
! Lungs (85%), pleura, CNS, lymphatics, UG, bones/joints, disseminated/Miliary TB
PR I M A R Y VS SE C O N D A R Y
! Primary
first exposure usually with primary pulmonary focus (Ghon Focus) w/LN = called G hon Complex
! Secondary
Very simply a reactivation of the infection from previous incident
M iliary T B
! Infection gained access to the blood/lymph and has disseminated and will look like millets (pulm arteries/veins)
! This may be seen with BOTH primary and secondary TB infections
Diagnosis
! H/P
Hx includes history of exposure, infection or disease as well as symptoms and potential risk factors
Physical: ill appearing, fever, sweating, swollen nodes, rales and dullness to percussion (effusion)
! PPD, CXR and bacteriologic exam
CXR abnormalities often found in apical/posterior of upper, note w/AIDS can look abnormal
Cant be used to confirm Dx but can rule it out if they have a (+)PPD
6SHFLPHQ&ROOHFWLRQ-sputum smears (look for AFB w/in 24hrs)
Cultures should be done on all specimens even w/(-)smear and expect results in ~14days
Symptoms
! Cough, CP, hemoptysis, fever/chills/sweats, fatigability, anorexia and weight loss
Screening with PPD
! 'RQHRQKLJKULVNSHUVRQV+,9FORVHFRQWDFWV,9'$)2%ORQJ-term care, recent (occupational) exposure
! $GPLQRI33'FFRI-TU-PPD and read in 48-72hrs to check induration and record in mm
! > PP only in HIV, IVDA, transplant/IC and recent close contact with (+)CXR
! >PP in conditions other than HIV, high risk population, kids <4y/o, long term care and the like
! >PP in anyone
M ulti-Drug Resistant T B (M D R-T B)
! Usually due to incomplete/errors in therapy often due to non-FRPSOLDQFHLQWKHH[SHFWHGSRSXODWLRQ
! Spread from person to person just as normal TB does

WHEEZING - I
x Definition
! narrow/compressed airway making a whistling/musical sound during respiration
! Caused by: bronchial hyper-responsiveness, inflammation of airways or mucus hypersecretion
x Polyphonic (more than one airway) is most common, where monophonic suggests unilateral obstruction
x Differentials:
! Asthma, COPD, lung infection, CHF, bronchial tumors, foreign objects, PE or aspiration
AST H M A
vs.
C O PD
! Early (childhood) onset
 Onset in middle-ages
! Sx vary daily
Slowly progressive symptoms
! Usually at night and early morning
DOE often present
! Allergies, rhinitis and/or eczema also
often with long smoking Hx
! Often with family Hx
Irreversible airflow limitation
! Largely reversible airflow limitation

AST H M A

Reversible airway obstruction, inflammation, narrowing and increased responsiveness causing its associated symptoms
So na med reversible because its symptoms are spontaneously reversed with employment of treatment

x
x

x
x
x
x

Risk F actors
! Genetic Atopy, Environmental Exposures and Respiratory Infections
M ediators
! Mast, Mac, Eosin, Neutro, Lympho, Platelets & Epithelial cells release INFLAMMATORY MEDIATORS
! These will cause:
Bronchocontstriction
Microvascular leakage (Edema & Exudate)
Mucus Hypersecretion
Bronchial Hyper-responsiveness
A rachadonic A cid Products

Morphologic C hanges:
! Vascular Dilation
! Edema
! Epithelial damage
! Mucus gland hypertrophy and excessive secretions
! Inflammatory cell infiltration
! Smooth muscle hypertrophy
! Subendothelial fibrosis
K ey Asthmatic Symptoms
! Cough, Wheezing, Chest tightness and Dyspnea
Paterns of Asthma Symptoms
! Episodic, Nocutrnal, Seasonal and has specific triggers
Allergies, Viral infections, Chemicals, Environmental irritants and many more (ie: cold, exertion)
O ccupational Asthma
! Caused by chemicals, irritants, allergens but the percentage of cases actually caused by work env. is unknown
! Many asthmatic have work-associated exacerbation of their asthma at some point in their lives
E xercise-Induced Asthma
! 7UDQVLHQWEURQFKRVSDVPIROORZLQJaPLQRIVWUHQXRXVH[HUFLVH+5E\!RUDJH-based maximum)

V arying Severity of Asthma

! M I L D I N T E R M I T T E N T AST H M A
L ess than twice-weekly but normal/asymptomatic b/w attacks
Exacerbation is brief with varying intensities
Nighttime symptoms less than twice-monthly
FEV1 or PEFR is >80% also the PEFR should have <20% variation
! M I L D P E RSIST E N T AST H M A
More than twice-weekly but only once-daily at most
Exacerbation may affect activity
Nighttime symptoms are more than twice-monthly
FEV1 or PEFR is > 80% also the PEFR varies b/w 20-30%
! M O D E R A T E P E RSIST E N T AST H M A
Daily symptoms thus daily use of inhaler and affects pts activity
Exacerbation more than twice-weekly and can last up to several days
Nighttime symptoms occur more than once-weekly
FEV1 or PEFR is 60-80% also the PEFR should have >30% variation
! SE V E R E P E RSIST E N T AST H M A
Continued symptoms with marked limitations of physical activity
Frequent daily and nightly symptoms
FEV1 or PEFR is <60% also the PEFR should have >30% variation
Diagnosis
! P H YSI C A L E X A M
Character of breath sounds and check for non-wheezing signs including other allergic diseases
Remember typically it is an episodic condition so the PE can be perfectly normal
Upper A irwayHYLGHQFHRIUKLQLWLVVLQXVLWLVRUQDVDOSRO\SV
T horaxLQFUHDVHG$-P diameter and use of accessory muscles
L ungsDXGLEOHZKHH]HDQGVORZH[SLUDWLRQ
SkinIOH[XUDOHF]HPD
! P F T & SPI R O M E T R Y (with and without dilator)
Essential to initial eval to help assess severity of obstruction and aids in getting a differential
The degree of obstruction and response to therapy is also very important
3-important measurmentsF E V 1, F V C and of course their ratio: F E V 1/F V C
x This part of the test should specifically be done before and after bronchodilators
Natural Variables:
x Height, race, age (FEV1 decreases ~10cc/yr) and gender
Make sure to administer the test properly! (standing, noseclip, max force and 3x to ensure accuracy)
Normal V alues
x F V C >80% RISUHGLFWHGQRUPDOIRUWKHSHUVRQVGHPRJUDSKLFLQIR
x F E V 1 >80%
x F E F >65% (forced expiratory flow)
Pre & Post Bronchodilator
x FEV1 or FVC should increase by >12% after administration of dilators
P E F R Peak Expiratory Flow Rate
x Greatest flow velocity produced during forced expiration from fully inflated lungs
x Monitors response to therapy and denotes worstening asthma w/>20% daily variation
x Can also help identify asthma triggers; very easy and portable
! SP E C I A L T ESTS
Bronchoprovocation (histamine/methacholine)
Occupational aeroallergen challenge
GI Evaluation when GERD is suspected
CXR

O BST R U C T I V E PU L M O N A R Y D ISE ASES

Is the 4th leading cause of death in the United States with smoking being the primary cause

C H R O N I C O BST R U C T I V E PU L M O N A R Y D ISE ASE

! Preventable disease state characterized by airflow limitation usually progressive and not fully reversible
! Dynamic fixed airway narrowing /blockage due to:
,QIODPPDWLRQPXFXVGLVWRUWLRQGHVWUXFWLRQRIDOYHRODUWLVVXHDQGEURQFKRVSDVP
x Causes of Airflow Limitation
! Irreversible
fibrosis/narrowing, w/elastic recoil loss and destruction support needed for small airways/alveoli
! Reversible
accumulation of inflam cells, mucus, plasma exudates and SM contraction in central airways
Note there will be dynamic hyperinflation during exercise
x General Pathophysiology for COPD
! 6PRNLQJLQFLQIODPPDWLRQOHXNRF\WHV H[FHVVPXFXVZKLFKZLOOFDXVH94-mismatch)
! There will also be airway thickening and destruction/decrease in alveolar units
! Increased CO2 SURGXFWLRQGWYHQWLODWLRQFDXVHV&hronic Hypoxemia will cause pulmonary hypertension
! PI N K PU F F E R
Compensated COPD: non-hypoxic but is hyperventilating with early dyspnea and barrel chest
Note the
Tend to be predominately E mphysema (no bronchitic element)
major
will also have weight-loss
differences
!
B
L
U
E BLOATER
between
COPD with hypoxia and right sided failure
these two
diseases
C hronic B ronchitis with severe hypoxia and cyanosis, NO barrel chest
Tend to be Obese
x C H R O N I C B R O N C H I T IS
! Diagnosis is exclusively clinically based: Persistent productive cough for 3-consecutive months in at least 2consecutive years
Simple C hronicPXFRLGVSXWXPwith NO airway obstruction
C hronic Asthmatic B ronchitisK\SHU-responsive airway w/intermittent bronchospasm and wheezing
C hronic O bstructive B ronchitisFKURQLFRXWIORZEURQFKLWLVDVVRFZHPSK\VHPD
! H ypersecretion of mucus is the primary causative change
H ypertrophy and hyperplasia of mucus-secreting glands in submucosa as well as
! This condition is A L M OST A L W A YS complicated with emphysema
! F ibrosis is also present adding to luminal nar rowing UHVXOWLQJLQDLUZD\REVWUXFWLRQsmall-airway disease
x A C U T E B R O N C H I T IS
! Short term viral (can be bacterial) infection of airways that causes productive cough, dyspnea, CP and malaise
x E M P H YSE M A
! Loss of alveolar units due to two primary mechanisms/patterns
! PANA CINAR
KHUHGLWDU\1-antitrypsin (A T T) deficiency leading to trypsin-antitrypsin imbalance
This will affect the L O W E R lungs where the alveolus and alveolar ducts are enlarged
! C ENTRI A CIN AR
affects UPP E R lobes; expansion is ONLY seen in the respiratory bronchiole (alveoli/duct are spared)
Stronger association to smoking, and is the most common form
Upper lobes have decreased blood supply, hence less ATT, thus resulting in location of greatest damage
x B R O N C H I E C T ASIS
! Permanent dilation of bronchi usually associated with Hx of severe and chronic infections
! Bronchiolar destruction and dilation (ectasia) with fibrosis, emphysema atelactasis and vascular changes
! Commonly the LOWER lobes
! Causes
Tuberculosis & Cystic Fibrosis
B. pertussis and Rubeola
.DUWDJHQHUV6\QGURPHDEFECTIVE CILIA: a triad combination of sinusitis, bronchiectasis and situs
inversus
! Poor pulmonary drainage leads to recur rent infections
! Sputum is foul/rotten smelling (necrosis and infection) often causing pulmonary hemorrhage

D I A G N OSIS O F C O PD
x Pulmonary F unction Test - V alues
! (V T ) Tidal Volume
! (I R V) Inspiratory Reserve Volume
! (I C) Inspiratory Capacity
! (E R V) Expiratory Reserve Volume
! (R V) Residual Volume
! (F R C) Functional Residual Capacity
!
!

(V C) Vital Capacity
(T L C) Total Lung Capacity

normal inspiration/expiration; approx 500ml

air inspired above tidal volume; approx 3000ml
tidal volume plus inspiratory reserve volume (500+3000=3500ml)
air expired past tidal volume; approx 1200ml
gas remaining after full forced expiration; approx 1200ml
expiratory reserve volume plus residual volume (1200+1200=2400)
essentially the volume remaining in the lung after expiration of tidal volume

inspiratory capacity plus expiratory reserve volume (3500+1200=4700)

vital capacity plus residual volume (4700+1200 6L)

Pulmonary F unction Test Two M ethods

! H elium Methodfixed helium is given to breathe and full volume can be calculated based on concentration
change C 1 V 1 = C 2 (V 1 + V 2)
! Body Plethysmograph M ethod XVHV%R\OHV/DZ39 FRQVWDQWWRGHILQHYROXPHE\SODcing the pt in a
box. After breathing out a normal tidal volume, their mouth is closed and forced to inspire at which time lung
volume increases and box volume decreases which increases box pressure (expand and compress). This
pressure can be measured and used to calculate FRC.
L ung Diffusion C apacity (D L )
i. DL can be measured by using CO (based on its diffusion limited property); a small amount is given to the
patient and the time taken to be absorbed is known to be proportional to DL
ii. Transfer rate depends on area, alveolar/capillary thickness and Hemoglobin (thus anemia will mess results)
iii. DL will change predictably with certain diseases
1. E mphysema DL will decrease due to a decrease in alveolar surface area
2. F ibrosis/P E DL will decrease due to thickening of diffusion membrane (mucus/water)
3. A nemiaDL ZLOOGHFUHDVHGXHWRDGHFUHDVHLQFDSDEOH5%&VDQGVLQFH'L takes protein binding
into account, it will actually decrease.
O bstructive vs. Restrictive
! 2%6GHFUHDVHLQH[SLUDWory flow rates; dec in ratio but FVC can actually be normal; DCLO goes down
! 5(6GHFUHDVHLQTLC; ratio goes up but individually FEV and FVC will go down;
x QRWHWKDW'&/2ZLOOLQSDUHQFK\PDOGLVHDVHEXWLVXQFKDQJHGLQQHXURPXVFXODUGLVHDVHV

Smoking Cessation
! $6.LGHQWLI\DOOWREDFFRXVHUVDWHYHU\YLVLW
! $'9,6(VWURQJO\XUJHDOORIWKHPWRTXLW
! $66(66GHWHUPLQHZLOOLQJQHVVWRTXLW
! $66,67$LGLQFHVVDWLRQ
! $55$1*(VFKHGXOHIROORZ-ups to keep in contact/monitor
D rugs to H elp Cessation
! Nicotine Replacement, Bupropion/Nortryptyline
! Chantix (varenicline) ZRUNVRQ&16WRZLWKGUDZDOV\PSWRPVDQGEORFNQLFRWLQHHQWU\WR&16

D YSPN E A
x
x

Definition
! Describes a subjective experience of breathing discomfort (physiological, socio-env, beKDYLRUDODQGRWKHUV
Physiology
! Respiratory system is responsible for homeostasis respective to gasses and pH (via CO2)
! Defects in oxygenation and acidemia can cause tachypnea (can be considered a form of discomfort or dyspnea)
! Increased output from Resp Ctr
C hemoreceptors$UFKDQGFDURWLGERGLHVVWLPXODWHGE\K\SR[HPLDDFLGRVLVDQGK\SHUFDSQLD
M echanoreceptorsDLUZD\OXQJVDQGFKHVWZDOOPRQLWRUSUHVVXUHIORZDQGYROXPHFKDQJHV
! Oxygen Delivery/Utilization
Common w/anemia and cardiovascular disease where they can be a cause of exertional dyspnea
Mechanical loading may increase d/t changes in airway resistance or chest wall compliance
Acute Dyspnea
! Arising in minutes to hours and usually have classic sx/sx to help the diagnosis
Substernal CP with cardiac ischemia
Fever, cough and sputum with respiratory infection , urticaria or anaphylaxis
Wheezing with acute bronchospasms
! Dyspnea may be the sole complaint and a physical may reveal few abnormalities (PE, pneomothorax)
C hronic Dyspnea
! Asthma, COPD, ILD and Myocardial Dysfunction
! Work-up
Detailed H/P
L abs+EFULWEORRGJDV%13WRFKHFNIRUFDUGLDFVRXUFHDQG3)7
RadiographyODWHUDODQG$3&;5(FKRWRPRJUDSK\DQGFDUGLRSXOPRQDU\WHVWLQJ

I D I O P A T H I C L U N G D ISE ASES - I L D
x
x

x
x

E tiology
! Unknown (idiopathic) but detailed Hx is essential
Occupational/environmental exposures, medications and sx/sx consistent with connective tissue diseases
C linical Classifications
! Collagen Vascular Disease: Scleroderma, SLE, RA, Ankylosing Spondylitis
! Drug Induced: Nitrofurantoin, Amiodarone, Paraquat, Bleomycin, BCNU
! Primary/Unclassified: Sarcoidosis, ARDS, LAM (lymphagioleiomyomatosis) and BOOP
! Occupational/Env: Silicosis, Asbestosis, Farmers/Bird Breeders Lung, CWP
! Idiopathic: idiopathic pulmonary fibrosis and IBS
PathogenesisUp for debate; may be viral, genetic, unidentified bug, immune-mediated RF and ANA may be (+)
Symptoms
! 3URJUHVVLYHG\VSQHDPD\VWDUWDV'2(EXWZLOOJHWZRUVH
! Cough and fatigue are also common
! Pleuritic chest pain is rare and seen with sarcoidosis, 5$6/((*/$0SXOPVPDQGF\VWV
! Wheezing is seen with hypersensitivity pneumonitis and hemoptysis can be seen in DAD (diff alv dam) & LAM
Physical F indings
! %LEDVLODUUDOHVUHVWLQJWDFK\SQHDWDFK\FDUGLDFOXEELQJ6DQGSHULSKHUDOHGHPDIURP&RU3ulmonale
! 6SLURPHWU\UHVWULFWLYHGHIHFWGHFUHDVHGOXQJYROXPHDQGGHFUHDVHGFRPSOLDQFH

Pathogenesis of I L D
! Up for debate; may be viral, genetic, unidentified bug, immune-mediated RF and ANA may be (+)

SA R C O I D OSIS
! Chronic multiorgan inflammatory disorder spares no organ
! Again, unknown etiolotyPD\EHJHQHWLFHQYLURQPHQWDOLQIHFWLRXVRUDFRPELQDWLRQRIWKHDERYH
! Non-caseating granulomas and multinucleated giant cells
! Presentation
&;5XVXDOO\DEQRUPDOZLWKKLODUO\PSKDGHQRSDWK\ with or w/o infiltrates and extensive destruction,
fibrosis and volume loss
Respiratory V\PSWRPVG\VSQHDFKHVWGLVFRPIRUWFRXJKIHYHUPDODLVHZHLJKWORVVDQGOHWKDUJ\
May also have skin lesions, ocular symptoms, clubbing (rare) and crackles if fibrosis is present
8VXDOO\$$DURXQG-40y/o
! M anifestations
Skin(U\WKHPDQRGRVXPDQGOXSXVSHUQLR
Musculoskeletal DFXWHDQGFKURQLFDUWKULWLV
Neurosarcoidosis&16 meningitis, cranial nerves and peripheral neuropathy
Calcium MetabolismK\SHUFDOFHPLDDQGhypercaciurea
LymphFDQKDYHO\PSKDGHQRSDWK\DQGKHSDWR-splenomegaly
Cardiac6XGGHQGHDWKFRQGXFWLRQDEQRUPDOLWLHVDQGYHQWULFXODUDUUK\WKPLDV
G I KHSDWLWLVZLWKOLYHUHQ]\PHV
Renal LQWHUVWLWLDOQHSKULWLV*1QHSKURFDOFLQRVLV and urolithiasis
C O N N E C T I V E T ISSU E D ISE ASE
! Immune mediated inflammatory disease with direct association b/w ILD and CTD
! Very similar to IPF and seen in 50-\R
! Often associated with SLE and other chronic diffuse diseases
! May see Cutaneous lesions with Raynauds Phenomenon
! Up to 70% of cases with Connective Tissue Diseases will have associated Idiopathic L ung Disease

PL E U R A & C H EST P A I N

Chest pain can be caused by a plethora of conditions ranging from cardiovascular, pulmonary, musculoskeletal, neurologic and traumatic
a mong many others. One common cause of chest pain is PLE URITIS which again has many etiological factors, both emergent and nonemergent.

A natomy of the Pleura and Space

! Serous membrane with visceral and parietal surfaces with
<20mL of fluid just for lubrication
Note the parietal HAS somatic sensory fibers
where the visceral (as expected) does NOT
! It contains no air or gas and lymphatic vessels are directly
communicating with the space via stomas
! Pleural space is at negative pressure compared to intraalveolar and atmospheric pressures
! The net (-) press of -7 to -9 favors fluid movement into
pleura usually from parietal microvasculature and is mostly
removed by the parietal lymphatics

x
x
x
x

P L E U R A L E F F USI O N
! Excess fluid in the pleuUDOVSDFHWKDWPD\PHDV\PSWRPDWLFRUKDYHSDLQG\VSQHDFRXJKIHYHUDQGRWKHUV
! PHYSICAL EXAM
Decreased/absent tactile fremitus, dull percussion and diminished breath sounds over the effusion
Shifting dullness is virtually pathognomonic
! Thoracentesis
Unilateral effusion is more necessary than bilateral
! T ransudative Pleural Effusion
Occurs due to systemic alterations that influence movement ie: H[FHVVZDWHUDQGSODVPDSURWHLQV
&DXVHVLQFOXGH&+)FLUUKRVLV1HSKURWLF6\QGURPH3HULFDUGLDOGLVHDVHDQGPeritoneal dialysis
! E xudative Pleural Effusion
Must meet one of the following three criteria
x Pleural protein count/plasma protein count is greater than 0.5
x Pleural LDH/Plasma LDH greater than 0.6
x Pleural LDH is greater than 2/3rds of the upper limit of normal for plasma LDH
Occurs due to alteration of local factors that influence fluid movement across space
x Inflammation/infection widen gaps
x Tumors that obstruct flow
Causes vary greatly and include parapneumonic, neoplastic, TB, P E , GI, Drugs, Post-surg, HWF
Many conditions can be definitively diagnosed based on effusion labs (empyema, malignancy w/cyt)
Parapneumonic Effusion
x Associated with pneumonia and can vary from a few ml to several liters
x The character of the fluid can vary from being transparent, straw colored to frank pus
x Exudative StageLQFUHDVHGPLFURYDVFXODUH[WUDYLVDWLRQIURPIRFXVRISDUHQFK\PDOLQIHFWLRQ
x F ibropurulent Stage LQYDVLRQRISOHXUDOVSDFHZLWKEDFWHULD
x Organization StageILEUREODVWVPRYHLQWRH[XGDWHVDQGSURGXFHinelastic peel encasing lungs
x 75($70(17$E[IRUXSWRZNVDQGGUDLQDJH
Differentials Based on F luid A nalysis
! Low G lucose <40mg/dL
Complicated parapneumonic, malignancy, TB, RA, Paragonimias, Hemothorax and Churg-Strauss
! H igh Amylase
$FXWH&KURQLF3DQFUHDWLFGLVHDVHlook bad, hard to treat, massive effusion, trac from pancreas to lung
(VRSKDJHDO5XSWXUH(W2+HQGRVFRS\H[FUXFLDWLQJ&3thirst, pneumo w/effusion, must drain
Malignancy
! Low pH <7.2
Seen in malignancy, rheumatoid, TB, hemo, urinothorax, paragonimaisis and Churg-Strauss
pH must be measured with a blood-gas machine
T uberculous Pleuritis
! ADA>70 or IFN-LVKLJKor Granulomas on Bx all diagnostic
! Lymphocytic effusion DQG
(+)PPD with A D A >40 treat for TB pleuritis
(-)PPD retest in 5wks and treat if necessary
! D XQHHGOH%[WRWHVWIOXLG
F luid C ytology
! Excellent tool, give as much fluid as you can to make a nice sized pellet
! *UHDWIRUDGHQRFDUFLQRPDOHVVIRUO\PSKRPDVTXDPRXVFHOOPHVRWKHOLRPDRU+RGJNLQV
F low C ytometry
! Rapid quantification of nuclear DNA; remember that majority of malignancies have abnormal DNA
! Less sensitive than cytology but useful in demonstrating homogeneity of cells with lymphoma
Collagen V ascular Disease
! Rheumatoid PleuritisHOGHUO\ORZJOXFRVH high LDL and low pH
! L upus PleuritisPD\EHWKHLQLWLDOPDQLIHVWDWLRQRIWKHGLVHDVHDQGZLOOKDYH$1$LQIOXLG
C hylothorax vs. Pseudochylothorax
! Are your two suspected Dx when fluid is turbid after centerfuge and is usually differentiated by the history
PSE U D Oeffusion has been there for years and the pleura has marked thickening
C H Y L ODFXWHSURFHVVZLWKWULJO\FHULGHV!DQGIOXLGWULJ!RUIOXLGFKROHVWHURO
Asbestos Pleural Disease
! 1RWHWKDWLWVDFRPSOHWHO\SOHXUDOGLVHDVHVRSOHXUDOplaques are diagnostic but often benign

Neoplastic Disease
! Common in pts >50; must determine primary vs. secondary and should be ruled out in any exudative fluid
! If it is neoplastic, its almost always very bloody and diagnosis is done with T H R E E cytologic exams
! If the cytology is negative you may consider Bx in highly suspicious pts
PN E O M O T H O R A X
! Presence of air/gas in the pleural space giving sx/sx like effusion; eventually resuling in collapse
! P H YSI C A L E X A MDiminished tactile fremitus, hyperresonant, absent breath sounds and mediastinal shift
! ETIOLOGY
Can be spontaneous (primary) w/no associated lung disease or seconday with and associated disease
Can be a tension, traumatic or iatrogenic

A C U T E R ESPI R A T O R Y F A I L U R E - A R F
x

x
x
x
x

Definition
! Loss of the ability to ventilate adequately or oxygenate the blood and of course the organs
! Pa O 2 <50 and Pa C O 2 >50 and Pa O 2/F i O 2 ratio<300 (severe hypoxemic respiratory failure)
! 7\SLFDOO\FKDUDFWHUL]HGDVK\SR[LFRUK\SHUFDSQLF
H ypoxicOXQJIDLOVJLYLQJDEQRUPDOO\low P O 2 and P C O 2 is typically low as well
H ypercapnicUHVSLUDWRU\SXPSIDLOVDJDLQZLWKDEQRUPDOO\low P O 2 BUT P C O 2 is typically H I G H
Gas Exchage
! Ventilation, Minute Ventilation, Tidal Volume (all easy terms)
! A lveolar V entilationNQRZWKDWLWVHVWLPDWHGEDVHGon PaCO2
! H yperventilationZKHQ&22 is below 35
! H ypO ventilationZKHQ&22 is above 45
Oxygen Transport DO2
! +\SR[HPLFZKHQ3D22 drops thus decreasing DO2
! $QHPLFZKHQWKH+JEGURSVFDQWFDUU\22VWLOOFDXVLQJD'22
Causes of ARF
! B rain (CVA, medulla) Spinal (trauma, kyphosis), N M (GB, MG), T horax (pneumo) C ardiopulm (C H F, PE)
U R T (tumor or VC D) L R T (C OPD, pneumonia, Asthma or ILD)
Common Sx/Sx of ARF
! Increased rate & depth of breathing, restlessness, anxiety, agitation, confusion, tachycardia and arrhythmias
! 3DUDGR[LFDOEUHDWKLQJLVFRPPRQXVHRIDFFHVVRU\PXVFOHV6D22 (decompensation) and cyanosis (in severe)
!lveolar-"rterial Gradient
! The difference in partial gas pressures between the
Alveoli and the arteries which is calculated and
evaluated to help assess hypoxemia and define
what it is attributable to (ie: hypercapnia)

! !"#$%&%'(#$%)%*+,-./01-(2%%3,10-%4,5.-6%%*!"7#$89:;6%%
(note that F iO 2 is the fraction of inspired O 2 in a mix)

Normal @ 20 y/o = 4-17

Normal @ 80 y/o = 25-38
! ,16+257\RXneed the PACO2 to calculate PAO2
then simply subtract the known PaO2 to get the difference
! The gradient can be normal even with some underlying
condition like hypoventilation RUD)L22
! It can be increased due to a V/Q mismatch caused by a P E,
asthma, C O PD and man y others
! It can even be raised in NORMAL physiologic conditions seen when bronchial blood flow and a small portion
of coronary venous flow draining directly into the left ventricle rather than going to the lungs to be
oxygenated, thus non-perfused blood creates this minor discrepancy
V/Q M ismatch
! 6LPSO\ZKHUHYHQWLODWLRQDQGSHUIXVLRQDUHQRWEDODQFHGFDQEHGXHWRHLWKHUYHQWLODWLRQRUSHUIXVLRQ
! Normally its about 4L:5L giving about 0.8
! Causes
Non-perfusion of ventilated alveoli (PE), underSHUIXVHGDOYHROLZLWKQRUPYHQWLODWLRQEORRG+E
Non-ventilation of normally perfused alveoli seen in atelactasis, pneumonia and COPD
! NOTE: giving 100%-O2 to a person with Pulmonary Edema or ARDS MAY not help b/c there is a problem with
diffusion in which case, increasing the oxygen concentration will NOT help increase diffusion

A C U T E R ESPI R A T O R Y D IST R ESS SY N D R O M E - A R DS

x
x

x
x

Definition
! Acute respiratory failure characterized by non-cardiogenic pulmonary edema causing severe hypoxemia due to
5/VKXQWWKURXJKcollapsed or fluid filled alveoli
Acute L ung Injury
! ,VHVVHQWLDOO\WKHVDPHWKLQJMXVWWRDPRUHH[WUHPHGHJUHHFKDUDFWHUL]HGE\SHUPLDELOLW\DQGLQIODPPDWLRQ
! ';UHTXLUHVDFRPELQDWLRQRIC linical, Radiological and Physiologic abnormalities
C linicalSretty obvious respiratory distress
RadiologicELODWHUDOSXOPRQDU\LQILOWUDWHV
PhysiologicK\SR[HPLDQRWHGE\DPa O 2/F i O 2 ratio<300
E tiology
! Sepsis (40%), Pneumonia (30%), T rauma (20%) and Aspiration (10%)
T reatment
! Treat the UNDERLYING cause first if SRVVLEOHSHUKDSV$E[IRUVHSVLVSQHXPRQLDHWF
! Supportive care can include Ventilation, Dialysis, Pressors, Nutrition and providing time for recovery
! Many drug therapies have been attempted and failed with protective mechanical ventilation being the gold std
Complication of M echanical Ventilation
! ,QDGHTXDWH79DWHODFWDVLVK\SR[HPLDDQGK\SHUFDSQHD
! ([FHVVLYH7994PLVPDWFK$OYHRODU-Capillary injury, Inflammation, pulmonary HTN and Barotrauma
! LOWER tidal volumes of 6ml/kg (compared to the old 12ml/kg) DQG3ODWHDX3UHVVXUHRI<30 (old was <50)
has been shown to decrease mortality by 9%

H Y PE R C A PN I C R ESPI R A T O R Y F A I L U R E
x

x
x
x
x
x

A rterial C arbon Dioxide E quation

! V E = minute ventilation
! V D = dead space ventilation
! V T = tidal volume
C auses
! &22 Production
Increased activity, sepsis, thryotoxicosis and CHO metab
! $OYHRODU9HQWLODWLRQ
9E9D and overall V/Q mismatch
Central Control Disorders
! Central sleep apnea, drugs, medullary disorder, hypothyroidism and metabolic alkalosis
Spinal Injuries
! C3-5, Tetany
! Anterior Horn Injuries/Disorders such as ALS, Polio and Rabies (but not so much anymore)
Peripheral Nerve Disorders
! GB-Syndrome, Diptheria, Porphyria, Tick/Fish toxins and Critical Illness Polyneuropathy
N M J Disorders
! MG, Lambert-Eaton, Organophosphate poison, Bolulism, Drugs: aminoglycosides, antiarrhythmics & phenytoin
Respiratory M uscle W eakness/F atigue
! Causes:
Deinervation and Myopathy
(QGRFULQH+\SHUWK\URLGLVP+\SHUFRUWLVROLVP
0HWDEROLF3RWDVVLXP3KRVSKRUXV0DJQHVLXP0DOQXWULWLRQ
HyperinflDWLRQ&23'
! Fatigue
Skeletal Muscle (diaphragm) will fatigue when sustained at >40% of capacity for prolonged times
Exacerbated by obesity, ascites, lying down, scoliosis, Ank-Spond, Hypercarbia and certain ineffective
breathing conditions like asthma, COPD
! Treatment
Correct underlying disease condition and use ventilation to allow muscle to rest
Ventilation can be invasive or non (ie: bi-pap)

!""#$%&%'()
C O M PL I M E N T
x

x
x

Three Pathways
! &ODVVLFDOactivated by Ab bound to Ag
! $OWHUQDWHDFWLYDWHGE\PLFURELDOSDWKRJHQV
! /HFWLQDFWLYDWHGE\FDUERK\GUDWHV
Functions
! Defend against pygenic bacteria, clear immune complexes and bridge the gap b/w adaptive and innate
! Big target for immunopathological diseases
Compliment Regulation Disorders
! Factor-H Deficiency
Normally responsible for controlling C3-FRQYHUWDVHLQWKH$OWHUQDWLYHSDWKZD\WKXVD)DFWRU-H results
in continuous activation
MembranoproliIHUDWLYH*ORPHUXORQHSKULWLVPD\UHVXOWGWDFWLYDWLRQDW*0%FDXVLQJLQIODPPDWLRQ
and subsequent injury
! Paroxysmal Nocturnal Hemoglobinuria
A major regulatory protein of the MAC (at C8) is CD59 which will block the formation of the MAC
In PNH, CD59 is lowDEVHQWUHVXOWVLQIRUPDWLRQRI0$&RQ5%&OHDGVWRLQWUDYDVFXODUKHPRO\VLV
This happens at night b/c blood is more acidic at night (respiratory) where acid activates alternative path
! Compliment and Neisserial Infection
Inherited deficiency in formation RI0$&FDXVHV1HLVVHULDOLQIHFWLRQV
MAC is vital for lysis of N.meningitidisWKXVZLWKRXWD0$&WKHUHZLOOEHVXVFHSWLELOLW\
! Mannose Binding Lectin Deficiency
Mannose binding lectin normally binds to terminal mannose on bacteria to combat it
Children w/this deficiency (b/w 6mo-2yrs) have recurrent pyogenic infections and failure to thrive
! C3-Nephritic Factor
Normally stabilizes C3-convertase in the alternative path (C3bBb) to continually activate the cascade
7KLVLVDVVRFLDWHGZLWKGDPDJHLQWKHNLGQH\ M embranoproliferative G lomerulonephritis
MPGN is usually d/t immune complex deposition continually activation compliment causing damage
! C1-Inhibitor Deficiency
C1-INH normally inhibits C1 to prevent spontaneous activation of Classical Pathway
C1-INH also inactivates the protease: K allik rein which is part of the intrinsic coagulation pathway
Thus, a deficiency will cause Hereditary A ngioedema (usually AD inheritance)
x Excess anaphlatoxin (C3a, C5a) causes degranulation of masts and edema
x Uninhibited .DOOLNUHLQZLOODFWLYDWHEUDG\NLQLQZKLFKLVWKHPDLQFDXVHRIYDVRSHUPLDELOLW\
! Compliment and SLE
Immune complexes in SLE are thought to be a major contributor in compliment activation
Compliment binds to apoptitic cells and eliminates dead cells
If compliment fails, the complexes/dead cells will evoke an autoimmune response
! Screening for Compliment Disorders
Use an Assay to determine total compliment levels
8VXDOO\SHUIRUPD&ILUVWDQGLILWVORZWKHQ\RXFDQGRLQGLYLGXDOLH&&HWF

I M M U N O D E F I C I E C Y D ISO R D E RS
x

Primary Immunodeficiency (5)

! T-Cell Deficiency
! B-Cell Deficiency
! Combined B & T-Cell Deficiency
! Phagocytic Deficiency
! Compliment Deficiency
Secondary Immunodeficiency
! ,QIHFWLRXV'LVHDVHV$,'6&09005HWF
! 0HGLFDWLRQVVWHURLGVUDGLDWLRQFKHPRHWF
! 1HRSODVWLF+HPDWRORJLF'LVHDVHVOHXNHPLDP\HORPDDSODVWLFDQHPLD
! 0HWDEROLF'LVHDVHVGLDEHWHVPDOQXWULWLRQQHSKULWLFV\QGURPHV
! 7UDXPD 6XUJHU\DQHVWKHVLDEXUQVVSOHQHFWRP\

SE V E R E C O M B I N E D I M M U N O D E F I C I E N C Y SC I D
x Profound deficiency in B-cells and T-Cells thus are susceptible to virtually any type of microbial infection
x Without T-cells, live cannot be sustained
x SCID patients are subclassified at initial evaluation
! Absent T-cells and normal or increased number of nonfunctioning B-cells (T-,B+)
! Absence of both (T-,B-) and some are even (T+, B+)
x X-Linked SCID
! Include the (T-, B+) subgroup which is about 50% of all cases
! The cause is due to a mutated gamma chain on the I L-2 receptor
! [PRUHLQGXHWR[-link
x AUTOSOMAL RECESSIVE SCID
! Clinically indistinguishable from X-linked
! Mutation is on JA K3 tyrosine kinase responsible for transmitting signals from gamma chain of the receptors
x ADENOSINE DEAMINASE SCID
! Normally a purine degradation enzyme and a deficiency results in metabolites toxic to Lymphoid Stem Cells
! This will ultimately result in failure of both T and B cells to mature but gene therapy has been successful
! $'$FDQEHGLUHFWO\DGPLQLVWHUHGERXQGWRSRO\HWK\OHQHJO\FROP E G-A D A) to clear toxic metabolites
x CLINICAL FEATURES
! Early in life (4-6m)
! Interstitial pneumonia (pneumocystis carinii), protracted diarrhea, failure to thrive, (+)family Hx,
! Persistent skin rash with candidiasisYHU\FODVVLFDOIHDWXUH
! /\PSKRSHQLD/
! Decreased CD3+ Tcells
! 9HU\ORZ,JV and very low or absent response to mitogen
x THYMUS
! /DFNRIQRUPDOOREXODWLRQFRUWLFRPHGXOODU\GLIIHUHQWLDWLRQO\PSKRF\WHV DQGDEVHQW+DVVDOV&RUSXVFOHV
M H C-I I D E F I C I E N C I ES - Bare L ymphocyte Syndrome
x Cannot express MHC-II molecules due to genetic transcription defect which is inherited as AR
x T & B-cells may be normal in number but are unable to present foreign antigens
x Nocollaberation b/w immune cells (B-cells, Macs, Dendritics, etc)
x Pts will have deficient Th-FHOOVDQG$EVDVWKHLUGHYHORSPHQWLs dependent on (+)-selection by class-2 in the thymus
x Infants have recur rent infections, usually of the G I T
PR I M A R Y T-C E L L I M M U N O D E F I C I E N C Y D ISO R D E RS
x )UHTXHQWO\DVVRFLDWHGZLWKLQWUDFHOOXODUSDWKRJHQVYLUXVHVIXQJLDQGLQWUDFHOOXODUEDFWHULD
x Di-G E O R G E SY N D R O M E
! Defective migration of neural crest cells into 3rd and 4th SKDU\QJHDOSRXFKHVGWdeletion on chr-22q11
! Cardiac anomalies, thymic aplasia and parathyroid aplasia (causing hypocalcemia)
! Kids suffer from recurrent/chronic viral, bacterial, fungal and protozoal infections
! Little to no mature T-cells
! 1HRQDWDOWHWDQ\XVXDOO\REVHUYHGGXHWRFDOFLXP37+
x C H R O N I C M U C O C U T A N E O US C A N D I D I ASIS
! Defect in T-FHOOVGHILFLHQWZLWKVSHFLILFUHFHSWRUIRUFDQGLGDUHVXOWLQJLQFDQGLGLDVLVRIVNLQQDLOVDQG00V
PR I M A R Y B-C E L L I M M U N O D E F I C I E N C Y D ISO R D E RS
Most common i mmunodeficiency disorders accounting for 50% of all pri mary cases where pts exhibit recurrent pyogenic
infections like pneumonia, sinusitis and otitis media usually due to strep and staph infections
x B R87216;-L I N K E D A G A M M A G L O B U L I N E M I A (X L A)
! PRE-Bcells are plentiful but are unable to mature
! Defective BTK gene in tyrosine kinase which is essential for B-cell maturation
! %DVLFDOO\RQO\HIIHFWV[-linked) who will present at 6-PRQWKVZKHQPDWHUQDO,JVGisappear
! ,QIDQWVZLOOKDYHUHFXUUHQWEDFWHULDORWLWLVVHSWLFHPLDSQHXPRQLDDUWKULWLVPHQLQJLWLV
! 0267&20021 H . influenza & Strep pneumonia
! Infections do NOT respond to Abx, must give IV-,JV
x T R A NSI E N T H Y P O G A M M A G L O B U L I N E M I A O F I N F A N C Y
! Child is unable WRPDNH,J*VDWPRVWZKHQWKHPDWHUQDO,JVZHDQDQGSHUVLVWVIRUPRQWKV
! Deficiency in T-helper-FHOOVFDXVHVWKLVVORZSURGXFWLRQRI,J*VEXWWUHDWPHQWLVXVXDOO\XQQHFHVVDU\

x
x
x
x

C O M M O N V A R I A B L E I M M U N O D E F I C I E N C Y (C V I D)
! Failure of maturation of B-cells into antibody-producing cells, thus cant proliferate in response to an antigen
! There will be IgM but there will NOT be class switching to IgG or IgA
! Thus, patients will have markedly low IgG & IgA but IgM will be normal or slightly lower
! Can be familial or sporadic with Two peak age groups, 1-5 and again b/w 15-20 y/o
! Treatment of severe/chronics is IVIG where pts can maintain a normal life QRWHSUHJZRQWSDVV,J*VWREDE\
SE L E C T I V E IgA D E F I C I E N C Y
! 0RVWFRPPRQLQZHVWHUQZRUOGLQDVVRFLDWHGZLWK,J$release from B-cells
! Pts have recurrent Sinopulmonary infection and treatment is usually broad spectrum Abx
IgG SU B C L ASS D E F I C I E N C Y
! Numbered from IgG-1 thru IgG-4 based on abundance in serum, 1 is the most
! :LOOKDYHPRVWO\57,VXSSHUDQGORZHUDQGHVSZ,J*GHILFLHQF\WKHUHZLOOEHSQHXPRFRFFDOLQIHFWLRQV
SE L E C T I V E IgM D E F I C I E N C Y
! 9HU\UDUHFRQGLWLRQZKHUHSWVDUHUHFXUUHQWO\LQIHFWHGZHQFDSVXODWHGRUJDQLVPV H.influenza & S.pneumonia
! Encapsulated organisms are often T-LQGHSHQGHQW$JVZKLFKDFWLYDWH nave-%VWRPDNH,J0(here they cant!)
I M M U N O D E F I C I E N C Y W I T H I N CR E ASE D IgM
! Pts have an absence of CD40-ligand thus they cant switch from IgM to IgG, IgA or IgE
! They are susceptible to pyogenic infections (P.carinii is very common)

I M M U N O D E F I C I E N C I ES C A USE D B Y D E F E C TS I N P H A G O C Y T OSIS
x C O NG ENI T A L NEUTR OPENI A
! Neutrophil count less than 500/mm3 ZKLFKFDXVHVVXSSUHVVHGLQIODPPDWRU\UHVSRQVHDQGEDFWHULDOLQIHFWLRQV
x C Y C LI C NEUTROPENIA
! AR inheritance of a deficient Neutrophil elastase
! A condition where 3-6 days in every 21-day cycle exhibits severe neutropenia (<200/mm3)
! Thus there will be intervals of cyclic susceptibility to opportunistic infections
Apthous ulcers, gingivitis, stomatitis and cellulitis may occur
! Fatal in 10% due to overwhelming systemic infection and is often treated with admin of G-CSF
x SC H W A C H M A N-D I A M O N D SY N D R O M E
! AR inheritance; characterized by exocrine pancreas deficieny and bone marrow deficiency causing infections
! Neutropenia occurs in every patient with pancytopenia in up to 25% of SDS cases
! :LWK%0G\VIXQFWLRQSWVDUHDWULVNIRUOHXNHPLDVDQGP\HORG\VSODVLDV
x C H E D I A K -H I G ASH I SY N D R O M E
! AR inheritance characterized by abnormal giant granules and organelles in the cells
! Particularly defective lysosomes and melanosomes, resulting in defects in
neutrophils NK-cells, platelet dysfunction and neurologic abnormalitis
! There is defective degranulation and fusion of lysosome with phagosomes
! 29(5$//GLPLQLVKHGNLOOLQJRIRUJDQLVPVDQGHYHQWXDO
Lymphohistiocytic infiltration in liver, spleen & LN
! 35(6(17$7,21IDLUVNLQSDOH retina, light blonde hair known as
RFXORFXWDQHRXVDOELQLVP
! Most pts die in childhood w/overwhelming infection or hemorrhage (>50% die by 10)

C H R O N I C G R A N U L M A T O US D ISE ASE C G D
! Commonly X-linked though there are some AR forms
! Defect in NADPH-R[LGDVHV\QWKHVLVUHVXOWLQJLQVXSHUR[LGH
anions and hydrogen peroxide for phag killing
! Makes phagocytosed organisms hard to kill, especially Cat(+)
organisms as they can decompose what little peroxide there is
! Diagnosed by inability of phagocyte to digest NB T dye Purple is Perfect at killing
! Treat w/long term Abx like Trimethoprim-Sulfa and antifungal agents
! Bone marrow transplant is curative

L E U K O C Y T E A D H ESI O N D E F I C I E N C Y
! 1RUPDOO\OHXNRF\WHVVORZUROODQGLQWHUDct their Selectin
ligand with Selectins on the endo to stop & migrate
! ,Q/$'Oeukocyte interaction with endothelium is defective
due to AR disorder on Chr-21
! LAD-1
/DFNRI-integrin adhesion molecule on neutrophils
XVXDOO\WKHFKDLQFDOOHG&'
PWVKDYHUHFXUUHQWVRIWWLVVXHEDFWHULDOLQIHFWLRQVZ:%&EXW12SXV
Newborns have delayed separation of the umbilical cord
! LAD-2
Defects in Selectin ligand on the leukocyte and have milder symptoms compared to LAD-1

H Y PE RSE NSI T I V I T Y

FOUR CLASSIFICATIONS
x Type 1 Immediate
x Type 2 Antibody mediated
x Type 3 Immune complex mediated
x Type 4 T-Cell mediated
T Y P E-1: I M M E D I A T E
x Production of antibodies against
foreign proteins that are commonly found in the environment (pollutants, etc)
x These produced IgE antibodies bind to the histamine containing Masts and Basophils to release their histamine
x Sensitization Phase
! T-cytokines I L-4 and 13 will activate a B-cell to make IgE which seeks out the Mast cell
! IgE then attaches to Masts and Basophils where they wait to catch an Ag, which causes degranulation
x E ffector Phase
! Tissue damage is cused by inflammatory mediators such as histamine, LTE, PGE and PAF
! They induce vascular permeability, dilation and smooth muscle contraction (not vascular sm)
x T h1/T h2 Balance
! There may be an imbalance toward T h2 subset and its associated cytokines in allergic ppl
! IL-4 (and 13) which belong to Th2 is needed for isotype switching (to IgE)
! In contrast, IFN-which belongs to Th1 will block the effect of IL-WKXVimbalance may cause allergies!
x C linical M anifestation of Immediate H ypersensitivity
! Asthma, allergic rhinitis, hay fever, atopic dermatitis & anaphylaxis (among some others)
! A topic DermatitisAllergens are carried via blood to skin which can induce cytokines to attract lymphocytes,
eosinophils and macs to cause dermatitis
x T reatment
! Antihistamines, LTE-inhibitors, Sodium Cromlglycate and steroids to block arachadoic acid pathways
! E pinephrine will directly reverse histamine (vascular sm contraction, relax bronchial sm and SHUPLDELOLW\
! Desensitization
&RQWUROOHGH[SRVXUHRI$JWRSURGXFH,J*VEORFNLQJ$EV which should neutralize the antigen before
it causes an allergic reaction.

T Y P E I I: A N T B O D Y M E D I A T E D IgG & IgM

x &DXVHGE\$EVUHDFWLQJWRFHOOVXUIDFH$JV can be endogenous or exogenous
x Cell destruction usually d/t two main mechanisms
! compliment activation and MAC causing osmotic lysis
! ADCC NK-cells bind to IgG and secretes Perforin causing lysis
x TRANSFUSION REACTIONS
! Incompatible Blood Transfusion
PRVWSSOGHYHORS$EV,J0WRDOORJHQLFVSHFLILFLWLHVWRWKH$%2V\VWHPVRDWWDFNQRQ-self)
! Hemolytic Disease of the Newborn
Incompatibility b/w an Rh(-) mother and Rh(+) fetus
First preg: mother exposed to Rh-Ag and develops anti-Rh-$EVQRWHthat it is commonly RhD
Subsequent preg: anti-RhD-Ab will attack QHZIHWXVV5K'FDXVLQJhemolysis
! Autoimmune Hemolytic Anemia
$XWRLPPXQHDWWDFNRI5%&VZLWKXQNQRZQHWLRORJ\XVXDOO\DVVRFLDWHGZ6/(RUGUXJHYRNHG
$EVKDYHDEUHDNGRZQRIVHOI-tolerance DQGWDUJHW5%&VIRUO\VLV
x REACTIONS AGAINST TISSUE ANTIGENS
! *RRGSDVWXUHV6\QGURPH
Autoantibodies against collagen-IV in alveolar and glomerular basement membranes (anit-GBM-$EV
They will bind to cell surface receptors and cause compliment activation followed by lysis
! Myasthenia Gravis
Autoantibodies agains ACh-receptor at NMJ causing extreme muscle weakness
Mother w/MG can vertically transmit anti-AChR-Abs to fetus who will be born w/MG symptoms
'LDJQRVLVWHVWIRUDQWL-AChR-Ab; EMG; Edrophonium (IV- antiAChE)
Treatment
x antiAChE (Pyridiostigmine (3-4h) or Neostegmine (2-3h)
x JLYH$WURSLQHIRUSDUDV\PSDWKHWLFVLGHHIIHFWVDEGRPLQDOFUDPSVYRPLWLQJPLRVLV
MG CrisisSURJUHVVLYHZHDNQHVVGHVSLWHDQWL$&K(VWULJJHUVPXVFDULQLFVWKXVDQ0*-Crisis
! Pemphigus
Autoantibodies against desmoglein which attaches epidermal cells w/desmosomes
This will cause acanthyolysis where the epidermis separates resulting in blistering and shedding
T Y P E I I I: I M M U N E C O M P L E X M E D I A T E D
x Can be due to an autoimmune disease, persistent infections or the inhalation of antigenic material
x Sensitization Phase
! IgM/IgG bind to antigens and form immune complexes where persistent challenge to the immune system causes
excessive IC buildup that surpasses the capacity to clear them
x E ffector Phase
! 7KH,&VDUHGHSRVLWHGLQFDSLOODU\ZDOOVthat activate compliment and generate C3a/C5a
! 7KHDQDSKODWR[LQVZLOOUHFUXLWQHXWURSKLOVWRSKDJRF\WRVHWKH,&V
! C5a will bind to Mast and Basophils which release vasoactive amines
x Persistent Infection
! Leads to chronic immune complex formation and deposition in
tissues (Leprosy, Malaria, Hep & Infective Endocarditis)
x Inhalation of A ntigenic M aterial
! Seen in )DUPHUV/XQJ ZLWK,J*VDJDLQVW$FWLQRP\FHWHIXQJXV
ZKRV,&VGHSRVLWLQDOYHROLOHDGLQJWRinflammation and pulmonary fibrosis
x A rthus Reaction
! Subcutaneous injection of an antigen which in a person who has been previously
VHQVLWL]HGZLOOEHDWWDFNHGE\FLUFXODWLQJ$EVIRUP,&DQGGHSRVLWLQGHUPDO%9V
! It will cause local vasculitis, edema and sometimes hemorrhage
x Serum Sickness
! Reaction to proteins found in antiserum (ie: antivenom) that
IRUP,&VFDXVLQJIHYHUUDVKHQODUJHG/1DQGVZROOHQMRLQWV
! These symptoms usually take up to 2 weeks to manifest and can
vary depending on the route of administration
x O ther E xamples of T ype-I I I
! SLE, RA, PSGS and the above seen pneumonitis (farmers lung)

T YPE
x
x
x

I V : D E L A Y E D T Y P E T-C E L L M E D I A T E D
Mediated by immune cells (CD4/CD8) rather than antibodies
Sensitization QDwYH7-cells differentiate into either Th1 or Th2 cells providing immunosurveilance in blood/lymph
G ranulomatous H ypersensitivity
! The most important Type-4 which causes most of the pathological effects of diseases involving T-cell immunity
! Often due to intracellular organism persistence within the Macs that the cell is unable to destroy
! *UDQXORPD5[QHSLWKHOLRLGFHOOVGHULYHGIURPDFWLYDWHG0DFVZLOOIXVHWRIRUPJLDQWFHOOV
! 0RVW*+VDUHGXHWRDQLQIHFWLRXVDJHQWOLNH0\FREDFWHULD)XQJLDQG3URWR]RD (TB and Sarcoidosis)
x Sarcoidosis
! Multisystem disorder causing pulmonary fibrosis w/non-caseating granulomas
! 7DUJHWVKLODU/1H\HVVNLQERQHPDUURZDQGVSOHHQFDXVLQJDQHUJ\LPPXQHUHVSRQVH
! Activated T-cells elicit the pathologic mechanism by releasing mediators to attract Macs to form granuloma
! *UDQXORPDVFDQIHDWXUHasteroid bodies
x T uberculosis
! granulomatous infection caused most often by Mycobacterium tuberculosis
! Tissue damage due to T ype-I V delayed hypersensitivity and may result in cough and hemoptysis
! H armful/dangerous fever, night sweats, weakness, appetite and weight loss
! It uses the Macs to migrate via lymph (peribronchial) and will begin to develop granulomas by 2-4wks
! Healing is associated with fibrosis and calcification and the infection EHFRPHVFOLQLFDOO\VLOHQW
! Tuberculin Type Hypersensitivity
TB pts injected w/tuberculin will have fever and generalized sickness
7KHVHSUHYLRXVO\VHQVLWL]HGLQGLYLGXDOV7-cells will release IFN-WRDFWLYDWH0DFURSKDJHV
Endothelial cells are activated to express ICAM/VCAM-1 which binds receptors on Neutrophils and
Monocytes there is a peak at 48hrs w/area of hardening/swelling around injection site
x Contact H ypersensitivity
! Eczematous reaction and the point of contact with the antigen (nickel, chromate, poison ivy)
! 7KHLPPXQRORJLFDOO\DFWLYHSRUWLRQRIWKH$JLVD+DSWHQWRRVPDOODORQHPXVWEHERXQGWRFDUULHUSURWHLQ
! Sensitization Phase (10-14 days)
Langerhans cells is the principal APC to produce primarily CD4+ (and CD8)
! Effector Phase
As langerhans present to CD4 activated Th1 cells, they will secrete TNF-DQG,)1-WRDFWLYDWH0DFV
These cytokines are potent activators of cell adhesion molecules and help movement past dermoepidermal junction
! RHUS DERMATITIS Poison Ivy
The chemical in the leaf (hapten) binds to proteins in skin cells which are then ingested by langerhans
cells who present them to MHC-I and activate T-cells into Th1-cells

H I V/A I D
! Membrane SURWHLQVRQWKHYLUXVHQYHORSHbinds Tcells and when it enters, it loses the envelop and Copies its
WZRLGHQWLFDO51$VWUDQGVLQWR'1$WRPDNHYLUDOSDUWLFOHVXVLQJWKHKRVWVPDFKLQHU\
! Per-100,000$$+LVSDQLF:KLWH
! A D U L T R F060,9'$KHWHURVH[XDO, transfusion (1%)
! C H I L D R F3HULQDWDO, undefined (5%), transfusion (3%)
Perinatal T ransmission Assay for early Dx
x DNA-PCR and HIV culture (sens: 50% at birth and ~100% at 3mos)
x RNA-PCR better than DNA (more sensitive)
x Anti-HIV-,J$VHQVLWLYLW\DWELUWKDnd ~60% at 3mos
x HIV-Ab not definitive as it can be maternally passed via placenta
Diagnostic C riteria >18mos
x HIV-Ab w/western blot and/or HIV(+) on two different blood tests
! Immunopathogenesis
Constant high level of daily replication at about 1-billion thus high steady state of viral load
,PPXQHFOHDUDQFHLQLWLDOO\&'FDQPDWFKYLUDOUHSOLFDWLRQZLWKHYHQWXDOSURJUHVVLYHGHSOHWLRQDQG
immunologic dysfunction
! C haracteristic Immunologic Disturbances
Lab T-FHOOVQXPEHU I[QRI&'LPSDLUHG&'-&7/V$JUHVSRQVH &\WRNLQHV,)1,/-2)
&OLQLFDOO\LPSDLUHGW\SH-4 hypersensitivity, chronic active viral infections and opportunistic
Lab B-FHOOV+\SHU,JVZLWKLPSDLUHGVSHFLILF$EUHVSRQVH7-depend/independ) and recurrent
bacterial infections specifically encapsulated (S.pneumonia & H.influenza)
! Symptom Complex
Oral thrush, lymphadenopathy, hepatosplenomegaly, recurrent diarrhea and stunting
Lymphocytic Interstitial Pneumonitis
x Most common pulmonary process (seen w/parotitis & clubbing) likely assoc. w/EBV
x Insidious hypoxemia develops often and can be reversed w/corticosteroids
,QIHFWLRXV&RPSOLFDWLRQV chronic otitis & sinusitis (staph and strep)
Recurrent/chronic HSV/VZV may require prophylactic/continual acyclovir treatment
>500/mm3
200-499/mm 3
<200/mm 3
<50/mm 3
Normal

S. pneumoniae
Pulmonary TB
Kaposi (HHV8)
Shingles
Candida (vaginal and oral)
A cute Cryptosporidosis
Oral Hairy Leukoplakia

!
!

Pneumo. Carinii
Reactivated CMV
Candida esophagitis
Mycobacterium avium
disseminated/chronic herpes
miliary/extrapulm TB
disseminated fungi:
Cryptococcus neoformans, C. immitis, H.capsulatum
Toxoplasmosis
C hronic cryptosporidosis
PML

Neoplasms
B-cell and CNS Lymphomas
.DSRVLV6DUFRPDYHU\UDUH
Smooth Muscle tumors
O ther Conditions w/A I DS
Wasting, Cardiomyopathy, Nephropathy
+HPDWRORJLF$EQRUPDOLWLHVDQHPLDWKURPERF\WRSHQLDQHXWURSHQLDDEVROXWHO\PSKRSHQLD
'HUPDWRORJLF$EQRUPDOLWLHVGLVVHPLQDWHGPROOXFXPFRQWDJLRVXPIODWZDUWVVHERUUKHLFGHUPDWLWLV
T reatment
Protease Inhibitors
x Interrupts viral assembly making it noninfective; entering clinical trials in kids
x Has significant drug-drug interactions
Antiretroviral Drug Resistance
x Rapid development of resistance; high viral turnover promotes selects for drug resistant mutants
M easurment of V iral Load
RNA-PCR, Branched chain DNA (bDNA), Nucleic Acid Amplificaion Assay (NASBA)
3UHGLFWLRQRI3URJUHVVLRQLQGHSHQGHQWRI&'-Count
>100,000/mL = rapid deterioration
<10,000/mL = stable course

C O N N E C T I V E T ISSU E D ISO R D ES

R H E U M A T O I D A R T H RI T IS
x Chronic inflammatory disease with symmetric polyarthritis, progressive joint disease and deformity
x E PI!ZSHDNDWth-6th decade and the absence of identifiable disease
x P A T H O G E N ESIS(QGRWKHOLDODFWLYDWLRQDQGDGKHVLRQangiogenesis then fibrosis & formation of invasive pannus
! Early there is hypertrophy/hyperplasia of the synovium followed by extensive BV network formation
! T and B cells will infiltrate the synovium and the fluid along with a lot of neutrophils
! Eventually WKHFDUWLODJHLVLQYDGHGE\WKHV\QRYLXPZKHUHDIWHUEHFRPLQJLQIODPPDWRU\WLVVXH3$1186
x C lassic Associations
! 5KHXPDWRLG)DFWRUSUHVHQWLQRISDWLHQWV
! Subcutaneous nodules on extensor surfaces also very common (elbow area)
! 6FOHURPDODFLDGHJHQHUDWLYH thickening of the sclera, seen with RA patients
SYST E M I C L UPUS E E R Y T H E M A T OSUS SL E
x Usually women with onset b/w 15-45y/o and familial aggretations (SLE clusters)
x P A T H O G E N ESIS
! Anti-Nulear-$QWLERGLHV$1$LQRISDWLHQWVZKLFKELQGWR'1$51$DQG$JV present w//in the nuclei
! Anti-dsDNA may also be present
x Immune A bnormalities
! Hyperactive B and T-cells
! $EQRUPDOSKDJRF\WRVLVSKDJVDUHXQDEOHWRELQGWR,&VWKXVWKHUHPD\EHH[WHQVLYH,&GHSRVLWV
! Abnormal ImmunoregulationGHIHFWLYHFOHDULQJRI,&V
x C LINIC A L
! Malar rash across face/nose; may also have papulosquamous lesions resembling psoriasis
! *ORPHUXODU,*'HSRVLWLRQLQ*%0JLYLQJDQOXPS\-EXPS\DSSHDUDQFH
! Diffuse cerebral microinfarcts and vasculitis due to vessel occlusion by leukoaggregation
O T H E R R H E U M A T O L O G I C D ISE ASES
x Systemic Sclerosis - Scleroderma
! Hardening or Thickening of Skin, Blood Vessels, Joints, Muscles or Internal Organs
! Will see Raynaulds Phenomenon in hands/fingers
! MXOWLSOHWHODQJLHFWDVLDVDEQRUPDOFDSLOODU\GLODWLRQLQVNLQforming angioma-like bloches
! Dilated esophagus is also common due to hypOmobility
! 5HVSLUDWRU\GLIILFXOW\FDXVHGE\GLIIXVHSXOPRQDU\ILEURVLVRIWKHOXQJSDUHQFK\PD
x Inflammatory M yopathies
! Dermatomyositis
! Polymyositis
x 6MRHUJHQV6\QGURPH
! Development of autoimmune disease of exocrine glands 5R66-A) La(SS-%
! Decreased synthesis of secretions (eye, mouth)
! Test lacrimation w/Schrimer Test
x V asculitis
! Large vessel
T emporal A rtery A rteritis: tortuous, nodular and painful; flow inhibited by giant and mononuclear
cell infiltration in the blood vessel walls
T akayasu Pulseless Disease: granulomatous vasculitis of medium/large arteries with obliteration of
the lumen, commonly affecting the aortic arch & compromising great vessels w/intimal thickening
! Medium vessels PAN, Kawasakis disease,
P A N - Systemic: likely autoimmune post-Hep B/C infection causing transmural necrotizing
inflammation of small/medium vessels, typically seen in renal and visceral arteries but SPARES lungs
.DZDVDNLV: usually <4y/o; type-4 against endothelium and smc of vessels, specifically seen in
coronarys classically causing multiple aneurisms,
! Small vessels Wegener granulomatosis, HS purura (anaphylactoid) and microscopic polyangitis
x Polymyocitis/Dermatomyocitis
! ';V\PPHWULFSUR[LPDO PXVFOHZHDNQHVVPXVFOHHQ]\PHV(0*DEQRUP7\SLFDOUDVKDQGPXVFOHELRSV\
Biopsy will show diffuse mononuclear infiltration and degeneration of muscle fibers
*RWWURQVFKDQJHVRYHUH[WHQVRUVLGHRQKDQGMRLQWV

T R A NSP L A N T A T I O N

C L ASSI F I C A T I O N according to the source of the graft

x Iso/A utograft
! From same individual or identical twins thus NO genetic disparity, and NO need for immunosupression
! Used in rescue therapy w/bone marrow given supertoxic doses of chemo and then given back to the pt
x A llografts
! Graft from same speciesZKHUHLWVVXUYLYDOLVDIXQFWLRQRIJHQHWLFVLPLODULW\EZKRVW GRQRU
! There IS a need for immunosupression w/much research going toward establishing tolerance to avoid IS therapy
x Xenograft
! Across species such as pig heart valves with the complete immune system being a huge obstacle in full effect
H OST vs. G R A F T R E A C T I O N
x %RWWRPOLQHGRHVWKHJUDIWFDUU\$1<DQWLJHQVWKDWZLOOEHUHFRJQL]HGDVIRUHLJQLQWKHUHFLHSHQW
x H YPERA CUT E REJE C TI O N
! Occurs very rapidly LQSWVZKRDOUHDG\KDYH$EVDJDLQVWJUDIWXVXDOO\PXOWLSOHIDLOHGJUDIWVRUSRVW-SDUWXP
! Usually avoided with ABO matching and test in-vitro blood-blood rxn for presence of cytotoxic antibodies
! Xenografts always have hyperacute as it is natural IgM/IgG activating compliment to cause damage
! T R E A TFXUUHQWO\UHPRYDOLVWKHRQO\RSWLRQ future: try to create transgenic animals expressing human
compliment regulators
x A C U T E R E J E C T I O NS
! Most common type of rejectiondays to weeks and mediated by T-cells/MHC
! Needs close monitoring (ie: ALT for liver, and possible Bx of grafted organ to check for inflammation)
x C H RO NI C REJE C TI O N
! W eeks/months/years and is assoc w/TGF-UHOHDVHDORQJZORZ-grade CMI or IC deposition
! &DUGLQDO)HDWXUHVOXPLQDOREOLWHUDWLRQRIVXSSO\LQJ%9VDQG,QWHUVWLWLDO)LEURVLVVFDUIRUPDWLRQ
H IST O C O M P A T I B I L I T Y D I F F E R E N C ES
x MHC-I & MCH-,,LVPRVWUHVSRQVLEOHIRUUHMHFWLRQVZKHUHWKHUHDUHKLVWRFRPSDWLELOLW\JHQHVUHFRJQL]LQJ$JV
x 0+&([SUHVVLRQFRQWUROOHGE\F\WRNLQHV IFN-DQG71)-DUH very potent inducers
x H uman Leukocyte A ntigen
! HLA -1 are encoded by three loci A, B, C and HLA-2 is encoded only by DP, DQ and DR
! ([SUHVVLRQYDULHVEDVHGRQFHOO+/$-1 on nucleated cells and HLA-RQPDWXUH$3&VDQG%-cells
x M H C T yping
! Serologic 7HVWLQJ 8VLQJ$EVWRSRVVLEO\LPSO\FRPSDWLELOLW\
! 0L[HG/\SPSRF\WH5[Q0/5 used in attempt to mimic in-vivo graft rejection and takes ~72hrs in culture
x Genotyping
! PCR is used at the genomic level to provide high sensitivity, rapid and more accurate matches vs serology
T R E A T/A V O I D G v H D
x Deplete donor T-cells and infuse recipient pt w/IL-3 and GM-CSF to help restore lymphohematopoetic system
x 1RQVSHVLILF
! C yclosporin & F K -506 block IL-2 production and Rapamycin also inhibits IL-2 at a different stage
! Prednisone inhibits Mac activation and IFN-
! A zathioprine inhibits purine metabolism
! A nti-C D3 and A nit-C D4 are also used

!"#$%"&'"()*$%&+,-*"#&
PR E G N A N C Y
x
x

*UDYLGDSUHJQDQF\
3DUDRXWFRPHRISUHJQDQF\WZLQVFRXQWDV21(

PR E G N A N C Y O U T C O M ES
x F irst T rimester Bleeding
! Spontaneous A bortion
T hreatenedZKHQWKHFHUYL[LV&/26('DQGZLOODERUW
Complete
x Hemorrhage may continue, there is active labor with cervical dilation and full delivery of fetus
and placenta but fragments may remain
Incomplete
x H emor rhage is increased with uterine contractions and full dilation of the cervix
x The placenta is detached, PARTIALLY expelled with remaining fragments
M issed
x Cervix is closed, NOT dilated, NO delivery where placenta and fetus become necrotic
x The uterus will shrink with trapped decidual bleeding and minor cramps
H abitualUHFXUV2-3x and requires further evaluation
Septic A bortionQRWYHU\FRPPRQDVVSRQWDQHRXVPRUHcommon with improper termination
! Genetic/C hromosomal A bnormalities
Accts for 60% of 1st trimester abortions and 5% of stillbirths (affects 3% of couples)
Most frequent is T R ISO M Y 16, 18, 21
x E ctopic Pregnancy
! By definition: a pregnancy outside of the uterus, commonly the fallopian tube, ovary, cervix and abdomen
! Heterotopic pregnancy is one where there is simultaneous ectopic and intrauterine pregnancies
! SY M P T O MS
$PHQRUUKHDYDJLQDOEOHHGLQJSDLQ+&*SODWHDXDQG-)ultrasound for intrauterine pregnancy
F ailure to diagnose is the leading cause of maternal mortality
! TREATMENT
Stablize pt with fluids, blood, lab tests (CBC, Rh)
May require surgery if pt is in shock or hemorrhaging (may be able to do it laproscopically)
x Gestational T rophoblastic Neplasia
! H ydatiform Mole
Complete: no maternal genes, fertilized by two sperm (46, XX), distended villi and lack fetal vessels
Partial: maternal + 2-sperm = 69, XXY, fetal parts may be seen, NO MALIGNANCY (complete = 2%)
SYMPTOMS
x Vaginal bleeding (mimic abortion), enlarged uterus, +,*++&*, Hyperthyroid Sx w/HTN
x 86DEVHQWIHWXVZLWKVQRZVWRUPDSSHDUDQFH
TREATMENT
x UHVSRQGWRFXUHWWDJHPRQLWRUIDOORI+&*DQGLILWULVHVJLYH&KHPRUHVSRQVH
! C horiocarcinoma
Follows mole (50%), abortion (25%), normal pregnancy (23%) or ectopic (2%) and will have +&*
Friable hemorrhagic mass with NO CHORIONIC VILLI that can metastasize to Liver Lung and Brain
75($70(17FRPELQDWLRQFKHPRWKHUDS\
x T hird T rimester Bleeding
! Placental A bruption
Placenta prematurely separates and is assoc w/HTN, advanced age and trauma
Can do vaginal or cesarean depending on the pt
! Placenta Previa
Placenta implants over cervix; may be due to Nitabuch layer and leads to antepartum hemorrhage
Must to CESAREAN delivery
x H emolytic Disease of the F etus
! First pregnancy: Rh(+) fetus immunizes the Rh(-) mother against the Rh, so the second kid gets attacked
! Maternal anti-RhD-A ntibody (IgG) ZLOOFURVVWKHSODFHQWDDQGO\VHWKHIHWDO5%&V+<'5236)(7$/,6
! H ydrops F etalisVHYHUHDQHPLDGHFUHDVHGRQFRWLFSUHVVXUHFDXVHVDVFLWHVDQGKLJK-output cardiac failure
! D XDPQLRFHQWHVLVFKHFNELOLUXELQDQGJLYH5KR*$0WRSUHYHQWLWZKHQPRWKHUDQGNid differ in Rh

EST R O G E N
x T ypes
! -estradiol
! Estriol pregnancy
! Estrone menopause
x Biochemestry
! Secreted by ovary directly or circulating androstenedione is converted to estrone via aromatase from adipose
! Cholesterol is also converted to estradiol
!"#$%&'$( !"#)*+$(
,-+'(
x Estrogen Receptors E R
!"#$%&'
!())*'+#%%#(%'
,-$".'
! Is a transcription factor which when activated
/0-#"'
!)1#'
234'
will bind to DNA and produce its effects in the
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/617'
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given target tissue
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589&"$:&'
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x T arget Tissues
! B reastVWLPXODWHVJURZWKDQGGLIIHUHQWLDWLRQRIGXFWHSLWKHOLXP
! E ndometriumVWLPXODWHVSUROLIHUDWLRQJrowth and differentiation
! BoneLQKLELWVRVWHRFODVWDFWLYLW\
! V ascularYDVRGLODWDWLRQYLD12VDQGUHOD[HVWKHYDVFXODUVPRRWKPXVFOHWRQHYLDRSHQLQJ&D2+-channels
! B rainPD\KDYH&16DQGPHPRU\HIIHFWV""
D YSF U N C T I O N A L U T E R I N E B L E E D I N G
x Definitions
! MenorrKDJLDKHDY\DQGRUORQJSHULRGV
! 0HWRUUKDJLDEOHHGLQJEHWZHHQSHULRGV
! 0HQRPHWRUUKDJLDERWK
x Common Associations
! Irregularity of Menses especially in young & Perimenopausal
! Instability of Hypothalamic-Pituitary axis with imbalance of estrogen and progestin
x E tiology
! GYN(QGRPHWULDO &HUYLFDO3RO\SV/HLRP\RPD(QGRPHWULDO+\SHUSODVLD2YDULDQ7XPRUVSURGXFLQJ
hormones, Endometrial & Cervical Cancer,
! NON-GYN7K\URLGGLVHDVHEORRGG\VFUDVLDOHXNHPLDV,73PHGLFDWLRQV KHUEDOSURGXFWV
! LEIOMYOMA
Only 25% have symptoms that can include menorrhagia, pain and mass effects
Marked menorrhagia (w/anemia), progressive dysmenorrheal, pelvic/back/flank & leg pain are common
Pelvic pressure/heaviness and bloating, esp bladder pressure and possibly obstruction
Sometimes will have dyspareunia
Often has associated infertility, repeated miscarriages and premature labor
T R E A T16$,'2&7SURJHVWHURQH*nRH (agonist/antagonist), surgical removal or uterine artery
embolization (to atrophy uterine)
! ENDO M E TRI A L C ARC IN O M A
Most common GYN cancer c
Associated with bleeding that can be meno/meto or menometorrhagia (or spotting in post-menopause)
R FREHVLW\'0+71QXOOLSDUWL\ODWHPHQRSDXVHHQGRPHWULDOK\SHUSODVLD & unopposed estrogen
D XELRSV\DOVRH[DPLQHFHUYL[
T XK\VWHUHFWRP\GLODWDWLRQDQGFXUHWWDJHUDGLDWLRQDQGFKHPRLIDGYDQFHGHVSZ/1

A M ENORRH E A
Remember the M enstrual C ycle and the H-P A xis
1.
2.

3.

M enstrual Phase
a. Corpus luteum breaks down leads to progesterone and endometrial shedding
b. Lasts 4 days and blood loss should be >80mL
Proliferative Phase
a. Estrogen level proliferation of stromal and epithelial cells of the endometrium
b. Regeneration occurs from basal portion of endometrial glands left behind in stratum
basale
Secretory Phase
a. Progesterone levels, maturation of endometrium (prepared in proliferation phase)
making it suitable for implantation

PR I M A R Y v. SE C O N D A R Y
Primary
! Absence of period by age 16.5 and lack of ovarian estrogen secondary to endocrine, anatomic, genetics or drugs
x Secondary
! Absence of period for 6-12 months, usually d/t pregnancy, menopause, PCOD, ovarian failure and uterine scars
C O M M O N C A USES
x Most common cause of amenor rhea is pregnancy
x E ndocrine C auses
! H-P axis, hypothyroid, malnutrition, pituitary adenoma, PCOD, menopause, CAH, radiation/chemo
! Congenital A drenal H yperplasia
-hydroxylase deficiency
x pushes synthesis of ANDROGENS ONLY
x $JHQHWLFDOO\IHPDOHSHUVRQZLOOKDYHDPELJXRXVJHQLWDOLDEFRIWHVWRVWHURQH
-hydroxylase deficiency
x Genetcal males CANNOT produce androgens/steroids
x These pts will appear phenotypically female or ambiguous at birth
! Pituitary A denoma
Hypersecretion of prolactin leading to infertility and gonadal dysfunction by interrupting GnRH
$*Q5+ZLOOFDXVHLQKLELWLRQRI/+ )6+UHOHDVHWKXVVWRSSLQJVWHULRGRJHQHVLV
SXDPHQRUUKHDJDODFWRUUKHDQGLnfertility
D Xdefinitive with MRI of pituitary gland
T XLVWRJLYHdopamine receptor agonist (bromocriptine) to inhibit prolactin release
! Polycycytic O varian Disease
Excess androgens from ovary and adrenal glands (maybe faulty H-P axis)
SXROLJRPHQRUUKHD, secondary amenorrhea, hirsutism, obesity and infertility
L A B/+)6+$QGURJHQV
6WURQJDVVRFLDWLRQZLWK0HWDEROLF6\QGURPHLQVXOLQUHVLVWDQFHDQGWKHOLNH
T XSURJHVWHURQHSUHJQDQF\FDQEUHDNF\FOH
x A natomic C auses
! Imperforate hymen , Mullerian/UWHULQHDJQHVLVDQG$VKHUPDQV6\QGURPHREOLWHUDWLRQRIWKHFDYLW\
! Uterine Agenesis
Absent uterus, short or absent vagina but normal breasts, ovaries and pubic hair
x Genetic C auses
! 7XUQHUV6\QGURPH$QGURJHQ,QVHQVLWLYLW\DQG7UDQVJHQGHU0DOHV
! 7XUQHUV6\ndrome
Absene of all or part of the sex chromosome (45, X) and are often spontaneous abortions
Webbed neck, shield chest, spaced nipples and cubitus valgus FDUU\LQJDQJOHDWHOERZ
There may also be renal abnormalities, hypothyroidism and learning disabilities
T R E A THFKRUHQDOHYDOKRUPRQHUHSODFHPHQWDQGGRQRUHJJVWRLPSUHJQDWH
! A ndrogen Insensitivity
Genetically a male, but has testicular feminization GRQWSURGXFHPXOOHULDQ-inhibiting factor)
This causes, NO internal genitalia and normal female external, scant hair and short/absent vagina
Gonads are abnormal and must be removed as 20% can be malignant

M E N O P A USE
x Definition
! Last menstrual period precedHGE\perimenopauseZKLFKLVWKHWLPHRIZDQLQJRYDULDQIXQFWLRQ
! Associated with menstrual abnormalities and irregularities; but ovulation declines in late-V
! Mean age of onset is 51 and can hasten by ~2yrs w/smoking (8% will have it before age 40)
x Physiological C hanges
! Hot F lashes (80%)
9DVRPRWRULQVWDELOLW\VHFRQGDU\WRHVWURJHQFDXVLQJFKDQJHVLQK\SRWKDODPLFWHPSUHJVHWSRLQW
'';K\SHUWK\URLGLVPIHYHUDQGDQ[LHW\
! Menstrual disturbances, anxiety, depression, mood swings, sleep disturbances, vaginal (dry, itchy, painful)
OST E O P O R OSIS
x Definition
! Low bone mass and microarchitectural deterioration FDXVLQJIUDJLOLW\WKXVULVNRIIUDFWXUH
x Symptoms
! Shortening stature, back pain, fracture and kyphosis (though many pts are asymptomatic)
! '';UHQDORVWHRG\VWURSK\SDJHWVGLVHDVHDQGPHWDVWDWLFERQHOHVLRQV
x Risk F actors
! 0HQRSDXVHZKLWHDVLDQORZ%0,)DPLO\+[VPRNLQJVHGHQWDU\&D2+, hypothyroid, chemo, DepoProv
x Bone Remodeling Imbalance
! Postmenopausal women have more resorption than formation during remodeling that contributes to problem
x Osteoporotic F ractures
! Early-&ROOHVIUDFWXUHZULVWUDGLXV
! Lateral-Vertebral contributing to height loss
! Hip Fractures also very common, especially in elderly
x Bone Densitometry (B M D)
! T-ScoreUHSUHVHQWHGLQ67'(9compared to younger population
! Z-ScoreLQFRPSDULVRQWRPDWFKLQJDJHEUDFNHW
Osteopenia: -1 to 2.5SD below young adult mean
Osteoporosis: more than 2.5 SD below and considered severe osteoporosis with Hx of fractures
x Prevention
! Calcium w/Vit-D, Exercise, cessation of smoking and bisphonates
x T reatment
! Target A L L women w/osteoporosis RUWKRVHZLWKRVWHRSHQLDSOXVDGGO5)V
! Any woman over 70 y/o ZPXOWLSOH5)VHYHQZLWKRXW%0'WHVWLQJ
! R X(VWURJHQ6(50DQG%LVSKRVSKRQDWHVERWKZLOOUHVRUSWLRQ
H R T & C A R D I O V ASC U L A R D ISE ASE
x Risk/Benefit of Estrogen/Progesterone Replacement T herapy
! B E N E F I T:
KRWIODVKHV8*V\PSWRPV/'/+'/%0'DQGIUDFWXUHV
! R IS K :
3('97 and Stroke, EUHDVW&$GRHV127HQGRPHWULDOFDQFHUZKHQSURJHVWHURQHDOVRJLYHQ
New studies show that it may not be safe for women with Coronary artery disease
May also increase incidence of colorectal cancer
! CONTRA
Undiagnosed vaginal bleeding and estrogen dependant tumors
x C ur rent H R T Recommendations
! Should be used for SH O R T T E R M <5yrs
! Alternatives to consider:
Calcium, Bisphonates and PTH
E vista Raloxifene: SERM (selective ER modulator) is good b/c it does NOT stimulate breast

O V A R I A N T U M O RS
x Normal H istology
! Germ cells (oocytes) surrounded by hormonally active layer of granulosa & theca cells (stroma) covered by
epithelium
x M ajor O rigin of T umors
! E pithelial)ROOLFXODU&\VWV6HURXV0XFLQRXV&\VWDGHQRPD(QGRPHWUHRVLV
! Sex Cord/Stromal
! Germ Cell
%HQLJQPDWXUHWHUDWRPDGHUPRLGF\VWVDQGVWURPDRYDULL
0DOLJQDQWLPPDWXUHWHUDWRPDSDUWLDOdifferentiation) and dysgerminoma
E PI T H E L I A L T U M O RS
x E ndometriosis
! Occurrence of endometrial tissue at a site OTHER THAN the lining of the uterine cavity
! P A T HPHWDSODVLDRIFHORPLFHSLWKHOLD-or- (2) retrograde menstruation -or- (3) vascular dissemination
! SXRIWHQLVDV\PSWRPDWLFEXWFDQKDYHG\VPHQRUUKHDPHQRUUKDJLDLQIHUWLOLW\DQGGLVSDUHXQLD
x E pithelial O varian C ancer
! SXXVXDOO\YDJXHOLNHDEGRPLQDOSDLQGLVWHQWLRQIXOOQHVVFRQVWLSDWLRQXULQDU\IUHTPD\EHYDJLQDOEOHHGLQJ
! R FQXOOLSDULW\RYXlation, early menarche/late menopause, late 1st preg and fertility drugs
! G E N E T I CS%5&$-1 & 2, Lynch-II-Syndrome: colon, prostate, lung and uterus
! T X&LVSODWLQ&DUERSODWLQ$GULDP\FLQ&\WR[DQ7D[ROLQWUDSHULWRQHDOFKHPR
G E R M C E L L T U M O RS
x Benign Teratoma
! Most common arising in germ cells of ovary without fertilization where up to 20% can be bilateral
x M alignant
! Usually in adolescents presenting with rapid enlarging pelvic masses and are often fleshy and lobulated tumors
! Dysgerminoma
Arise in sexually abnormal females like gonadal dysgenesis and are often unilateral
They are sensitive to radiation and chemo and prevented by removing gonads before age 20
! E ndometrial Sinus T umors Yolk Sack
Originating from germ cells and differentiate into extraembryonic yolk sacks Schiller-Duval Bodies
There will be elevated -fetoprotein and -antitrypsin
T XVXUJLFDOVWDging, unilateral salphingo/oophorectomy and chemotherapy
! E mbryonal C arcinoma
Also originating from germ cells and will have high -fetoprotein and +C G
! C horiocarcinoma
Very rare (<1%) and more malignant than its uterine counterpart and often a metastatic from it
There will typically be excessive and early widespread metastasis, usually before clinical presentation
Very resistant to therapy and will also have +&* as the marker
T XRRSKRUHFWRP\
x C hemo for Germ Cell T umors
! Bleomycin, VP (16)
! Newer agents include: Navalbine and Oxalplatin
M E T AST ASIS T O O V A R Y
x Commonly from the G I, B reast or T hyroid where Krukenberg is a special type of metastasis
x K RU K ENB ERG
! from primary breast cancer; will have bilateral ovarian enlargement with signet ring cells forming mucin
! there will be diffuse infiltration of the stroma giving a sarcoma-like picture
! Initial presentation may be metastasis in ovary and primary lesion is very small
! Mechanism of spread can be direct, via peritoneal fluid, via fallopian tube, hematogenous or lymphatic
! SX$EGRPLQDOSDLQDEGRPLQDOSHOYLFPDVVYRPLWLQJDQRUH[LDUHFWDOV\PSWRPVDQGPHQVWUXDOLUUHJXODULW\
SU M M A R Y O F T U M O R M A R K E RS
x C A-125F\VWDGHQRFDUFLQRPD
x C A-1PXFXVDGHQRFDUFLQRPD
x A F PHQGRPHWULDODQGHPEU\RQDOWXPRUV
x +&*K\GDGLIRUPPROHFKRULRFDUFLnoma and embryonal carcinoma
x C E A*,FDQFHUPXFLQRXVDGHQRFDUFLQRPDRIWKHRYDU\

B R E AST C A N C E R
x Genetics
! B R C A-1
Located on 17q and has AD inheritance pattern
Breast cancer risk of 85% by age 70
Ovarian cancer risk of 65% by age 70
! B R C A-2
Located on 13q and is a tumor suppressor gene mutation
Breast cancer risk of almost 90% by age 80 and 10% in males
Ovarian cancer risk is up to 20%
x Gene T esting
! Done on women with breast cancer before age 50 or any woman with both ovarian and breast at any age
! Anyone who has a relative with a (+)BRCA or a family history of breast/ovarian cancer
x B reast C ancer Prevention
! ST A RT amoxifen and Raloxifene given to high risk women
! showed 50% reduction in DCIS and invasive breast cancer
! Prophylactic Oophorectoy for OVARIAN CANCER in BRCA (+) women

V A G I N I I T IS A N D SE X U A L L Y T R A NSM I T T E D D ISE ASES

V A G I N I T IS

H E RP ES SI M P L E X V I RUS
x D N A-virus with a 3-22 day incubation period
x Genital infections are commonly with Type-2 (90%)
x SXIHYHUPDODLVHDQRUH[LDJHQLWDOSDLQOHXFRUUKHDG\VXULDYDJLQDOEOHHGLQJEXWFDQEHFRPSOHWHO\DV\PSWRPDWLF
x L ESI O NPXOWLSOHYHVLFOHVSURJUHVVLQJWRVKDOORZXOFHUDWLRQVVXUURXQGHGE\SDLQIXOHU\WKHPDDQGZLQJXLQDO/1V
x T XDF\FORYLUYDOF\FORYLUFRPIRUWPHDVXUHV126(;
x PR E G N A N C YRIIHWXVZLOOEHDIIHFWHGLIDFWLYHOHVLRQGXULQJODERUF-section!)
SY P H I L L IS
x An STD caused by the spirochete Treponema pallidum and IS ABLE to cross placenta
x Incubation is ~90days
x Diagnosis
! using non-VSHFLILF$EVOLNH95'/DQG535RU7UHSRQHPDO6SHVLILFOLNH73,)7$-ABS and MHA
! Darkfield for spirochetes is the DEFINITIVE diagnosis (serologic tests can be false negatives)
x Primary - C linical
! PAINLESS chancre ulcerated lesions with raised border and indurated base and may have inguinal adenopathy
! Will disappear in 2-6 weeks
x Secondary C linical
! Maculopapular rash on palms and soles
! Mucus patches, condyloma lata (males and females) and generalized lymphadenopathy
! 50% are congenitally transmitted and will disappear in 2-6weeks
x Pregnancy
! Child can be unaffected but is often late stillborn or acquires congenital syphilis
! Congenital Syphillis
5DVKYHVLFOHVEXOODHVQXIIOHVRURSKDU\QJHDOPXFXVSDWFKHVKHSDWRVSOHQRZMDXQGLFH /1V
May also have pseudoparalysis d/t osteochondritis
! L ate Congenital Syphillis
+XWFKLQVRQVWHHWKPXOEHUU\PRODUVLQWHUVWLWLDONHUDWLWLVGHDI CN8, saddle nose, saber skin & CV
x T ertiary Syphillis
! CardioDRUWLWLV
! NeuroWDEHVGRUVDOLV
! Pupil$UJ\O-Robertson Pupils: Small, irregular pupils d/t dorsal midbrain lesion
! Skeletal &KDUFRW-RLQWV
x T reatment
! Benzathine penicillin G, IM
P E L V I C I N F L A M M A T O R Y D ISE ASE
x Diagnosis
! Based on pain, leukocytosis, fever and usually in a sexually active individual
! '';DSSHQGLFLWLVWRUVLRQGLYHUWLFXORVLV
x E tiology
! C hlamydia, Gonorrhea, Anaerobes but is usually polymicrobial infections
! Contributes to tubal infertility, ectopic pregnancies and chronic pelvic pain
x T reatment
! Without acute abdomen
ceftriaxone(250mg) and azithromycin (1mg) then re-evaluate in 24hrs
! Acute abdomen with high WBC count, temp or nulliparous
IV ampicillin, Gentamycin, Clindamycin do laproscopy with no response or uncleaer diagnosis

V I R A L I N F E C T I O NS
HIV
x
x

Transmitted sexually, via blood and vertically

3UHYHQWLRQFRQGRPVPDWHUQDODQWLYLUDOVGHFUHDVHWUDQVPLVVLRQIURP&HVDUHDQZYLUDOORDG

C ERVIC A L C ARCINO M A
x R FHDUO\VH[PXOWLSOHSDrtners, HPV infection
! HPV: 6, 11, 16, 18 with diseases ranging from condyloma to CIN
x SC R E E NDW\RRUZLWKLQ\UVRIVH[XDODFWLYLW\DQGZLWKLQWHUYDOEDVHGRQ3DSKLVWRU\DQGULVNIDFWRUV
x ';3DS-smear
! Pap-Smear C ategories
6DWLVIDFWRU\SUHVHQFHRUDEsence of transformational zone
8QVDWLVIDFWRU\XQDEOHWRDQDO\]HSRRUSUHVHUYDWLRQWRRIHZFHOOVREVFXUHGZLWKEORRG
1(*$7,9(IRULQWUDHSLWKHOLDOOHVLRQVRUPDOLJQDQF\
27+(5HQGRPHWULDOFHOOVLQZRPDQRYHU(needs eval for atypical endometrial cells)
! Pap-Smear Squamous Cell A bnormalities
Atypical squamous cells
LSIL (low grade squamous intraepithelial lesion)
HSIL (high grade squamous intraepithelial lesion)
Squamous Cell Carcinoma
! Pap-Smear Glandular Cell A bnormalities
Atypical Endocervical, Endometrial, Glandular
! Pap-Smear A denocarcinoma
Endocervical, Endometrial and NOS
x Cervical Dysplasia C I N
! M ild: C I N-IUHVROYHWRQRUPDO
! Moderate: C I N-I IULVNLV
! Severe: C I N-I I I carcinoma in situ 75% risk of cancer
x Cor relation between SI L and C I N
! SI LEDVHGRQF\WRORJ\DQGLVHLWKHUKLJKJUDGHRUORZJUDGH
! C I NEDVHGRQWLVVXHVDPSOHSDWKRORJ\DQGLVJUDGHGRQVFDOHIURP,WR,,,
x Colonoscopy
! Used for microscopic lesions where Bx is taken under colonoscopic guidance
! If woman has gross lesions then this is NOT indicated, just to regular biopsy of visible lesion
x T reatment of C I N
! Low grade: just watch/monitor
! H igh grade: II or III, cryosurgery laser, LEEP (loop electroexcision procedure) or cone biopsy
! C arcinoma in Situ: Cone biopsy or Hysterectomy
x Cervical C A N C E R
! Stage 1PLFURLQYDVLYH,-A) and localized to the cervix but with gross lesion (I-B)
Treat I-A with hysterectomy and treat I-B with radical hysterectomy w/L N dissection
! Stage 2H[WHQGHGLQWRXSSHUYDJLQD,,-A) or laterally into pelvis (II-B)
I I-A can be done with radical hysterectomy or radiation/chemo
Anything beyond I I-A it is no longer surgical and needs aggressive radiation and chemo
! Stage 3WRORZHUYDJLQD,,,-A) to lateral pelvic walls (III-B) or Hydroureter (III-B/hydronephrosis)
This also needs radiation/chemo and can cause renal failure
! Stage 4LQWRERZHORUEODGGHU,9-A) or distant spread (IV-B)
Very bad prognosis and only 10% respond to treatment
x V accination G A R D ASI L
! Against 9, 11, 16, 18 and is recommended for girls age 9-26 (and older) given in three vaccinations
! 99.8% will become seropositive for anti-+39$EV
! Note that this is N O T A T R E A T M E N T for pts who have already been infected with HPV

PR E G N A N C Y , G EST A T I O N A L-D I A B E T ES & H Y PE R T E NSI O N

P H YSI O L O G Y O F PR E G N A N C Y
x Presumptive Sx/Sx
! $PHQRUUKHD+HJDUV6LJQVRIWHQLQJRIWKHXWHUXVDQG&KDGZLFNVEOXHGLVFRORUDWLRQRIWKHFHUYL[
! $YJGXUDWLRQLVGD\VRUZNV1DJOHV5XOH!"#$!!%&'(!)!*+,-(!
x )RXU&RPSRQHQWV*DPHWRJHQHVLV)HUWLOL]DWLRQ2YXP %ODVWRF\VW7UDQVSRUW and finally, Implantation
! Oogenesis M eiosis: F irst Division
First division completed before birth and formation of two daughter cells with 23-chromosomes
One will receive all of the mother cell cytoplasm and is considered secondary oocytes
The other will be the polar body and is cast off while still in the ovary
! Oogenesis M eiosis: Second Division
Occurs upon sperm entering the secondary oocyte (haploid) and will divide w/o chromosome reduction
There will then be a second polar body and a mature ovum
ThHDQGQXFOHLIXVHDQGIRUPWKH]\JRWH fertilized egg
! F ertilization
7DNHVSODFHLQIDOORSLDQWXEHWKHQVSOLWVPRUXODVROLGEDOOE\aGD\V
! Blastocyst
When fluid accumulates inside the morula;
Inner cells will be the embryo and the outer will be that trophoblast
! Implantation
Will take place by day 6 and by ~7.5days there will be an embryonic disk
x Placenta
! Will develop at the site of the chorion and is of dual origin (fetal and maternal)
! Fetus will derive all of its nutrition & O2 from it via the umbilical vein to fetus and two umbilical arteries back
to the mother
x Placental Hormones
! H uman Plaental L actogen (H P L) LVGLDEHWRJHQLFDQGVXSSRUWVHDUO\RYDULDQIXQFWLRQ EUHDVWGHYHORSPHQW
! Progesterone from the placenta from maternal precursors whose principal metabolite is pregnanediol
,WZLOODOVRFDXVHVPRRWKPXVFOHUHOD[DWLRQDQG735WR%3
! Estriol is the main source of estrogen in pregnancy
x T rophoblast and Amnion
! The trophoblast will produce protein and steroid hormones
! +&*WKDWPDLQWDLQVVWeroidogenesis in the corpus luteum of pregnancy
! +&*FDQEHGHWHFWHGZLQGD\VRIFRQFHSWLRQ
C O M M O N C H A N G ES T O B O D Y SYST E MS
x Uterus
! Will increase in weight/size from 60g to 1000g at term and from the original 8cm to stretch up to subxyphoid
! Uterine blood flow will be ~600ml/min which is ~10% of CO where it is normally ~1%
x H ematologic C hanges
! &2E\+5E\ESP5%&PDVVE\:%&XSWRYROXPHE\
! Platelets are unchanged, Factor VII, VIII, IX, X will all increase and fibrinolytic activity will decrease
x Renal C hanges
! Dilation of ureter from progesterone
! *)5DQGUHQDOSODVPDIORZE\-50%
! Glycosuria is common but proteinuria is still ABNORMAL
x Pulmonary C hanges
! 7955DQG09ZLOODOO
! +\SHUYHQWLODWLRQFDQRFFXUGWVHQVLWLYLW\WR&22 by respiratory centers as a consequence of progesterone
x G I C hanges
! N/V in early pregnancy
! *(5'DQG+&/
! Cholestasis and upward displacement of the appendix
x E ndocrine C hanges
! (QODUJHGWK\URLGDQGDGUHQDOJODQGVZLWK7&RUWLVRODOGRVWHURQH$QJLRWHQVLQDQGRYHUDOO%05
x Skin C hanges
! 'HUPDWRVLVRI3UHJQDQF\Hyperpigmentation of areola, vulva, linea alba and sometimes the face

B R E ASTS I N PR E G N A N C Y
x L actation E ndocrinology
! Progesterone, estrogen, placental lactogen, prolactin, cortisol and insulin will all stimulate growth and
development of milk secreting apparatus of mammary glands
! :KHQSODFHQWDLVGHOLYHUHGWKHHVWURJHQDQGSURJHVWHURQHZLOOVWLPXODWHLQLWLDWLRQRIODFWDWLRQ
! Prolactin will tend to fall post-partum but VXFNOLQJZLOOSURODFWLQ levels
! O xytocin
IURPSRVWHULRUSLWXLWDU\ZLOOFDXVHFRQWUDFWLRQRIP\RHSLWKHOLDOFHOOVWRFDXVHOHWGRZQUHIOH[RIPLON
this is in a pulsatile fashion
! Colostrum
At 2-5 days post-partum and is full of IgA
! M ilk
,VWKHLGHDOIRRGZLWKSURWHLQODFWRVHZater and fat
Low in V it- K and not as much iron as in cow milk
$OVRFRQWDLQVORDGVRI$EVOLNHIgA and T & B lymphocytes
D I A B E T ES I N PR E G N A N C Y
x Commonly occur with known diabetics but may be a result of the pregnancy (gestational diabetes)
x Problems can manifest in both mother and fetus
x G O A LPD[LPL]HSUHFRQFHSWXDOEORRGVXJDUVRPLQLPL]HIHWDOPDOIRUPDWLRQVPDFURVRPLD VKRXOGHUG\VWRFLD
x C arbohydrate Metabolism
! There is a decrease tolerance in pregnancy and progressive resistance to hypoglycemic action of insulin
x E arly Pregnancy
! Insulin will transport glucose into fact cells with IDWV\QWKHVLVK\SHUWURSK\DQGLQKLELWLRQRIO\SRO\VLV
x L ate Pregnancy
! +&6KXPDQFKRULRQLFVRPDWRWURSKLQZLOOZRUNOLNHLQVXOLQWROLSRO\VLV
x F etal Complications
! IUGR (intrauterine growth restriction), ,malformations, diabetes, macrosomia (big baby), jaundice and death
! Spina bifida, renal agenesis or polycystic kidneys and situs inversus
x M aternal Complications
! Hypertension, edema, pyelonephritis, polyhydramnios and ketoacidosis
H Y P E R T E NSI O N I N PR E G N A N C Y
x C lassification
! Chronic HTN, Pre/Eclampsia (can be superimposed on chronic), Transient and unclassified
x Risk F actors
! Nulliparity, family history, multiple gestations, DM, chronic vascular or renal disease, mole & hydrops fetalis
x T reatment
! Bed rest, salt restriction, close monitoring (maternal and fetal), CC-blockers, anti-HTN meds
! NO DIURETICS should be used and if possible deliver the kid!
! M agnesium Sulphate
Prophylaxis in pre-eclampsia (to avoid seizures)
:LOODOVRVORZ10-WRVPFontraction but will N O T decrease BP
x !"#$%&'()*+,(! E T I O L O G YYDVRVSDVP$7-II sensitivity, immunologic, genetic, systemic renal disease and other theories
! Incidence is ~50%, higher in AA and primigravida
! Proteinuria - 300g/24hrs
! E dema weight gain of >2lb/week or 6lb/month with rapid pattern of gaining
! A dditional Sx can include, headache, visual changes, hyperreflexia, RUQ pain (hepatic edema)
! SI G NS
Oliguria <500ml/24hrs
IUGR
Convusions
H E L L P Syndrome .emolyisis, %leveated /iver function tests and /ow !latelets
x %&'()*+,(! Pregnancy related seizures that are induced by hypertension
! Complications include, pulmonary edema, HF, blindness, CVA/Strokes and death in extreme cases
! T R E A TFRQWUROFRQYXOVLRQVVWDELOL]H%3FRUUHFWK\SR[LDDQG'(/,9(5LISRVVLEOH